Removing polycyclic aromatic hydrocarbons from water using granular activated carbon: kinetic and equilibrium adsorption studies

Abstract

Polycyclic aromatic hydrocarbons (PAHs) constitute a group of highly persistent, toxic and widespread environmental micropollutants that are increasingly found in water. A study was conducted in removing five PAHs, specifically naphthalene, acenaphthylene, acenaphthene, fluorene and phenanthrene, from water by adsorption onto granular activated carbon (GAC). The pseudo-first-order (PFO) model satisfactorily described the kinetics of adsorption of the PAHs. The Weber and Morris diffusion model's fit to the data showed that there were faster and slower rates of intra-particle diffusion probably into the mesopores and micropores of the GAC, respectively. These rates were negatively related to the molar volumes of the PAHs. Batch equilibrium adsorption data fitted well to the Langmuir, Freundlich and Dubinin–Radushkevich models, of which the Freundlich model exhibited the best fit. The adsorption affinities were related to the hydrophobicity of the PAHs as determined by the log K_ow values. Free energies of adsorption calculated from the Dubinin–Radushkevich model and the satisfactory kinetic data fitting to the PFO model suggested physical adsorption of the PAHs. Adsorption of naphthalene, acenaphthylene and acenaphthene in fixed-bed columns containing a mixture of GAC (0.5 g) + sand (24.5 g) was satisfactorily simulated by the Thomas model.

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Editorial Board

Publication date: February 2018
Source:Acta Oecologica, Volume 87





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Reply to: Comments on “Breast augmentation together with intraoperative glandular transposition flap for prevention and correction of lower pole deformities”

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Pathogenesis of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) or ‘idiopathic retinal arteriolar aneurysms (IRAA)’ with macular star

Publication date: March 2018
Source:Medical Hypotheses, Volume 112
Author(s): Koushik Tripathy




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Splenectomy may have more complications than currently proven

Publication date: March 2018
Source:Medical Hypotheses, Volume 112
Author(s): Somayeh Zakeri, Narjes Gorji, Marjan Akhtari, Reihaneh Moeini
The spleen has been one of the least understood major organs for centuries. Its significance is relatively well-known today but it seems that all aspects of its activities are not fully understood. Persian medicine (PM) has special views on the function of spleen; many side effects were reported in PM due to spleen dysfunction. On the other hand nowadays splenectomy as a treatment strategy is recommended for some disorders and increasing risk of infections is considered as the most important long term side effect of that. In this study, we hypothesize that splenectomy may have more side effects than currently proven.According to PM, spleen is in close connection with liver, cardiovascular system, stomach, bone, brain and skin, and that is why any kind of spleen dysfunction leads to change in blood viscosity, appetite and bone strength, liver dysfunction, mood and skin disorders, cancer formation and fever. Considering this viewpoint it can be hypothesized such side effects may also occur after splenectomy.Proven complications of splenectomy include hypercoagulated state, cardiovascular events and infectious diseases but there is also some evidence about increased risk of cancer, skin disease like systemic lupus erythematosus, mood disorder such as depression, defective bone formation and impairment of immunity which can be considered as different levels of evidence to confirm the hypothesis.But for some others such as changes in appetite, there are no studies let alone convincing evidence. Future research about theses possible complications may lead to novel results.



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Editorial Board

Publication date: March 2018
Source:Medical Hypotheses, Volume 112





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Editorial Board

Publication date: April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 178





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Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy

AbstractBackground.Several breast cancer (BC) trials have adopted pathological complete response (pCR) as a surrogate marker of long‐term treatment efficacy. In patients with luminal subtype, pCR seems less important for outcome prediction. BC is a heterogeneous disease, which is evident in residual tumors after neoadjuvant‐chemotherapy (NAC). This study evaluates changes in Ki67 in relation to disease‐free survival (DFS) and overall survival (OS) in patients without pCR.Subjects, Materials, and Methods.Four hundred thirty‐five patients with stage IIA–IIIC BC without pCR after standard NAC with anthracycline and paclitaxel were analyzed. We analyzed the decrease or lack of decrease in the percentage of Ki67‐positive cells between core biopsy samples and surgical specimens and correlated this value with outcome.Results.Twenty‐five percent of patients presented with luminal A‐like tumors, 45% had luminal B‐like tumors, 14% had triple‐negative BC, 5% had HER2‐positive BC, and 11% had triple‐positive BC. Patients were predominantly diagnosed with stage III disease (52%) and high‐grade tumors (46%). Median Ki67 level was 20% before NAC, which decreased to a median of 10% after NAC. Fifty‐seven percent of patients had a decrease in Ki67 percentage. Ki67 decrease significantly correlated with better DFS and OS compared with no decrease, particularly in the luminal B subgroup. Multivariate analysis showed that nonreduction of Ki67 significantly increased the hazard ratio of recurrence and death by 3.39 (95% confidence interval [CI] 1.8–6.37) and 7.03 (95% CI 2.6–18.7), respectively.Conclusion.Patients without a decrease in Ki67 in residual tumors after NAC have poor prognosis. This warrants the introduction of new therapeutic strategies in this setting.Implications for Practice.This study evaluates the change in Ki67 percentage before and after neoadjuvant chemotherapy (NAC) and its relationship with survival outcomes in patients with breast cancer who did not achieve complete pathological response (pCR). These patients, a heterogeneous group with diverse prognoses that cannot be treated using a single algorithm, pose a challenge to clinicians. This study identified a subgroup of these patients with a poor prognosis, those with luminal B‐like tumors without a Ki67 decrease after NAC, thus justifying the introduction of new therapeutic strategies for patients who already present a favorable prognosis (luminal B‐like with Ki67 decrease).

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Daily maternal separations during stress hyporesponsive period decrease the thresholds of panic-like behaviors to electrical stimulation of the dorsal periaqueductal gray of the adult rat

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): Ana Cristina Borges-Aguiar, Luana Zanoni Schauffer, Edo Ronald de Kloet, Luiz Carlos Schenberg
The present study examined whether early life maternal separation (MS), a model of childhood separation anxiety, predisposes to panic at adulthood. For this purpose, male pups were submitted to 3-h daily maternal separations along postnatal (PN) days of either the 'stress hyporesponsive period' (SHRP) from PN4 to PN14 (MS11) or throughout lactation from PN2 to PN21 (MS20). Pups were further reunited to conscious (CM) or anesthetized (AM) mothers to assess the effect of mother-pup interaction upon reunion. Controls were subjected to brief handling (15 s) once a day throughout lactation (BH20). As adults (PN60), rats were tested for the thresholds to evoke panic-like behaviors upon electrical stimulation of dorsal periaqueductal gray matter and exposed to an elevated plus-maze, an open-field, a forced swim and a sucrose preference test. A factor analysis was also performed to gain insight into the meaning of behavioral tests. MS11-CM rather than MS20-CM rats showed enhanced panic responses and reductions in both swimming and sucrose preference. Panic facilitations were less intense in mother-neglected rats. Although MS did not affect anxiety, MS11-AM showed robust reductions of defecation in an open-field. Factor analysis singled out anxiety, hedonia, exploration, coping and gut activity. Although sucrose preference and coping loaded on separate factors, appetite (adult weight) correlated with active coping in both forced swim and open-field (central area exploration). Concluding, whereas 3h-daily maternal separations during SHRP increased rat's susceptibility to experimental panic attacks, separations throughout lactation had no effects on panic and enhanced active coping.



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Molecular classification as prognostic factor and guide for treatment decision of pancreatic cancer

Publication date: Available online 28 February 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): David J. Birnbaum, François Bertucci, Pascal Finetti, Daniel Birnbaum, Emilie Mamessier
Clinico-pathological factors fail to consistently predict the outcome after pancreatic resection for oancreatic ductal adenocarcinoma (PDAC). PDACs show a high level of inter and intra tumor genetic heterogeneity. A molecular classification should help reduce heterogeneity among patients, with the consequences of better predicting evolution and better orienting the treatment. This review summarizes the information that should be retained in clinical practice from all the molecular analyses. PDAC can be classified based on mutational subtypes and gene alterations. Whole-genome sequencing identified mutational signatures, mutational burden and hyper-mutated tumors with specific DNA repair defects. Different molecular classifications have been established by using gene expression analyses to reduce PDAC heterogeneity. Their overlap/similarities allow the definition of molecular subtypes. DNA and RNA classifications can be used in prognosis assessment. They are useful in therapeutic choice for they allow the design of approaches that can predict the respective drug sensitivity of each molecular subtype. This review provides a comprehensive analysis of available molecular classifications in PDAC and how this can help guide clinical decisions.



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Protein Disaggregation in Multicellular Organisms

Publication date: Available online 28 February 2018
Source:Trends in Biochemical Sciences
Author(s): Nadinath B. Nillegoda, Anne S. Wentink, Bernd Bukau
Protein aggregates are formed in cells with profoundly perturbed proteostasis, where the generation of misfolded proteins exceeds the cellular refolding and degradative capacity. They are a hallmark of protein conformational disorders and aged and/or environmentally stressed cells. Protein aggregation is a reversible process in vivo, which counteracts proteotoxicities derived from aggregate persistence, but the chaperone machineries involved in protein disaggregation in Metazoa were uncovered only recently. Here we highlight recent advances in the mechanistic understanding of the major protein disaggregation machinery mediated by the Hsp70 chaperone system and discuss emerging alternative disaggregation activities in multicellular organisms.



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GR-regulating Serine/Threonine Kinases: New Physiologic and Pathologic Implications

Publication date: Available online 28 February 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Tomoshige Kino
Glucocorticoid hormones, end products of the hypothalamic–pituitary–adrenal axis, virtually influence all human functions both in a basal homeostatic condition and under stress. The glucocorticoid receptor (GR), a nuclear hormone receptor superfamily protein, mediates these actions of glucocorticoids by acting as a ligand-dependent transcription factor. Because glucocorticoid actions are diverse and strong, many biological pathways adjust them in local tissues by targeting the GR signaling pathway as part of the regulatory loop coordinating complex human functions. Phosphorylation of GR protein by serine/threonine kinases is one of the major regulatory mechanisms for this communication. In this review, recent progress in research investigating GR phosphorylation by these kinases is discussed, along with the possible physiologic and pathophysiologic implications.



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Mitochondria and Hypoxia: Metabolic Crosstalk in Cell-Fate Decisions

Publication date: Available online 28 February 2018
Source:Trends in Endocrinology & Metabolism
Author(s): David Bargiela, Stephen P. Burr, Patrick F. Chinnery
Alterations in mitochondrial metabolism influence cell differentiation and growth. This process is regulated by the activity of 2-oxoglutarate (2OG)-dependent dioxygenases (2OGDDs) – a diverse superfamily of oxygen-consuming enzymes – through modulation of the epigenetic landscape and transcriptional responses. Recent reports have described the role of mitochondrial metabolites in directing 2OGDD-driven cell-fate switches in stem cells (SCs), immune cells, and cancer cells. An understanding of the metabolic mechanisms underlying 2OGDD autoregulation is required for therapeutic targeting of this system. We propose a model dependent on oxygen and metabolite availability and discuss how this integrates 2OGDD metabolic signalling, the hypoxic transcriptional response, and fate-determining epigenetic changes.



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ABSTRACTS OF THE 5TH INTERNATIONAL CONFERENCE ON ADVANCES IN HEMATOLOGY AND ONCOLOGY (ICAHO2017)

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Clinical Burden of Modified Glasgow Prognostic Scale in Colorectal Cancer

Background/Aim: This study aimed to clarify the potential of modified Glasgow Prognostic Score (mGPS) as a prognostic biomarker and reveal the significance of fish oil (FO)-enriched nutrition in colorectal cancer (CRC). Patients and Methods: A total of 738 CRC patients from three different patient cohorts, including 670 patients in the biomarker study and 68 patients in the nutrition-intervention study, were analyzed. Results: High preoperative mGPS was significantly correlated with well-recognized disease progression factors and advanced UICC stage classification. In addition, high mGPS was an independent prognostic factor in both cohorts, especially in stage III and IV patients. These statuses were maintained in postoperative course and correlated with sarcopenia. Furthermore, FO-enriched nutrition suppressed systemic inflammatory reaction and improved skeletal muscle mass and prognosis, especially in CRC patients with mGPS 1 or 2. Conclusion: Assessment of mGPS could identify patients with high-risk CRC, who might be candidates for FO-enriched nutrition.

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Stereotactic Body Radiation Therapy for Patients with Early-stage Prostate Cancer

Aim: Stereotactic body radiation therapy (SBRT) is emerging as a new treatment option for early-stage prostate cancer, theoretically providing clinical and economic benefits compared to conventionally fractionated external-beam radiation therapy (CF-EBRT). This review aimed to evaluate available published data to determine if the proposed theoretical benefits translate clinically. Materials and Methods: A systematic search strategy was employed across three databases using predefined search terms, inclusion and exclusion criteria to identify relevant articles. Results: Sixteen articles were included. Biochemical progression-free survival rates of 77.1-100% were reported in SBRT studies compared to 55-98% in CF-EBRT studies. Incidence of acute grade 1, 2, and 3 genitourinary toxicities were reported in the range of 13.3-71%, 12-25% and 0-3%, respectively, in the SBRT cohort in comparison to 28.7-51.9%, 15.6-41.4%. and 1.1-8.1%, respectively, in the CF-EBRT cohort. Incidence of acute grade 1, 2, and 3 gastrointestinal toxicities were reported in the range of 13-67%, 1-27% and 0-9%, respectively, of the SBRT cohort compared to 16.1- 51.1%, 6.3-20.7% and 0-3%, respectively, of the CF-EBRT cohort. Mean treatment costs estimates associated with SBRT ranged from $22,152 to $24,873 and $33,068 to $35,431 for CF-EBRT. Conclusion: Available data support the hypothesis of lower rates of acute toxicity and reduced economic burden associated with SBRT compared to CF-EBRT, however, randomised data with longer follow-up are needed to determine whether SBRT is clinically more effective than CF-EBRT.

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Safety of Simultaneous Bilateral Pulmonary Resection for Metastatic Lung Tumors

Aim: We investigated the safety of simultaneous bilateral lung resection for lung metastases. Patients and Methods: We retrospectively analyzed 185 patients with pulmonary metastases who underwent unilateral or bilateral pulmonary resection from August 2009 to December 2016 at a single institution. Results: Single-stage bilateral lung resection was undertaken in 19 patients, and the other 166 patients underwent unilateral pulmonary resection, including 20 patients who underwent repeated resections for synchronous or metachronous metastases. Operative time and drainage days in the bilateral group were significantly longer than those in the unilateral group (220±20 vs. 152±6.9 min: p<0.01, and 2.79±0.3 vs. 2.08±0.1 days: p<0.01). Incidence of postoperative complications and postoperative in-hospital days did not differ between the two groups (p=0.33 and 0.66, respectively). The bilateral group was further divided into two groups, namely, those who underwent wedge resection on both sides (WW) and those who underwent wedge resection on one side and segmentectomy or lobectomy on an opposite side (WSL). Operative time in the WSL group was significantly longer than that in the WW group (260±19 vs. 201±18 min: p=0.03). However, there was no significant difference in duration of chest tube use and postoperative hospital days between the two groups (p=0.26 and p=0.89). No severe postoperative complications occurred in either group. Conclusion: One-stage bilateral pulmonary metastasectomy appears to be safe as long as only wedge resection is performed on at least one side.

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Centrosomal Abnormalities in Pancreatic Cancer: Molecular Mechanisms and Clinical Implications

The centrosome is the main microtubule-organizing center in human cells. It regulates normal cell-cycle progression and cell division. Aberrations in the number, structure and function of centrosomes have been found to drive genomic instability and tumorigenesis. Pancreatic cancer frequently displays centrosomal aberrations. Supernumerary and abnormal centrosomes are observed in the earliest stages of pancreatic tumor development, and the p53 pathway acts as an initial barrier to the proliferation of cells with extra centrosomes. In this review, we summarize recent advances in the understanding of centrosomal aberrations in pancreatic cancer, focusing on regulatory mechanisms and prospects for future anticancer treatment.

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Radiation Therapy for Angiosarcoma of the Scalp: Total Scalp Irradiation and Local Irradiation

Angiosarcoma, a rare cutaneous malignancy, frequently arises in the scalp of older individuals. Because it characteristically initially mimics benign disease, such as a bruise, definitive diagnosis in the early stages is difficult. Angiosarcoma of the scalp is highly malignant and often accompanied by lung metastases that cause hemopneumothorax. Although surgery has been the standard and most reliable curative treatment for angiosarcoma of the scalp, there is a high probability of local recurrence, even after wide surgical excision. Therefore, postoperative radiation therapy has been administered in an attempt to minimize local recurrence. However, surgery is contraindicated in many older patients because of severe comorbidities or age. Definitive radiation therapy has been administered to such patients and has achieved good local control. In particular, total scalp irradiation may be a promising option for curative treatment of angiosarcoma of the scalp. Recent reports suggest that chemotherapy, particularly with taxanes, can prolong survival by reducing the rate of distant failure after radiation therapy. Thus, radiation therapy along with chemotherapy is now recommended for curative treatment of patients with inoperable disease and even some patients with operable disease. Technological developments in radiation therapy, such as intensity-modulated radiation therapy, will contribute to enhanced efficacy and reduced toxicities in the treatment of patients with angiosarcoma of the scalp.

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Upper Abdominal Resection for Isolated Metastatic Lesions in Recurrent Cervical Cancer

Upper abdominal involvement in recurrent cervical cancer usually occurs as part of systemic disease and is most often amenable to palliative chemotherapy. However, in certain cases in which oligometastatic disease is proven, surgery might be considered. We present a case series of six patients submitted to surgery for upper abdominal oligometastases with cervical origin. The main surgical procedures performed included atypical hepatectomy (in five cases) and splenectomy (in one case). In all cases, the cervical origin of the lesions was revealed by histopathological studies. After a median follow-up period of 1 year, there was no evidence of recurrent disease in five cases, while the sixth case was diagnosed with disseminated lesions and is under palliative chemotherapy. In conclusion, upper abdominal resection for oligometastatic disease from cervical cancer can improve the long-term survival in selected cases.

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Gastric Cancer Cells in Peritoneal Lavage Fluid: A Systematic Review Comparing Cytological with Molecular Detection for Diagnosis of Peritoneal Metastases and Prediction of Peritoneal Recurrences

Background/Aim: Detecting free tumor cells in the peritoneal lavage fluid of gastric cancer patients permits to assess a more accurate prognosis, predict peritoneal recurrence and select cases for a more aggressive treatment. Currently, cytology and molecular biology comprise the two most popular methods of detection that are under constant study by researchers. Materials and Methods: We burrowed into the available literature comparing cytological with molecular detection of free intraperitoneal gastric cancer cells. PubMed, Science Direct, Scopus and Google Scholar were the search engines investigated. Results: As of 2017, 51 dedicated studies have been published. Messenger RNA of carcinoembryonic antigen was the genetic target most frequently described. The genetic technique is usually superior to cytology in sensitivity (38-100% vs. 12.3-67% respectively), whereas cytological examination tends to show a slight pre-eminence in specificity (approximately 100%). Conclusion: So far, given the imperfection of each method, employment of both cytology and molecular examination seem to be mandatory.

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Clinicopathological Characteristics of High-grade Squamous Intraepithelial Lesions Involving Condyloma Acuminatum

Background/Aim: Severe nuclear atypia can be associated with condyloma acuminatum. In this study, we investigated nine cases of perianal condyloma acuminatum with severe nuclear atypia and determined whether severe nuclear atypia is sufficient for the diagnosis of high-grade squamous intraepithelial lesion (HSIL). Materials and Methods: The clinical data and pathological features of the nine patients were collected. p16 Immunostaining and human papillomavirus genotyping were also performed. Results: The resected specimens of six men infected with human immunodeficiency virus showed features suggestive of HSIL, including the expansion of basaloid cells, severe nuclear pleomorphism in the lower one-third, bizarre nuclei, mitotic figure in the upper two-thirds, atypical mitosis, block positivity for p16, and high-risk human papillomavirus infection. In contrast, the resected specimens of the remaining three patients did not show any of those HSIL features, even though there were several microscopic foci showing severe nuclear atypia in the upper two-thirds of the papillomatous epithelium. Conclusion: Our observation regarding the occurrence of HSIL involving perianal condyloma acuminatum in human immunodeficiency virus-infected patients suggests that active, complete surgical excision of perianal condyloma acuminatum and a thorough histopathological examination are necessary. The diagnosis of severe nuclear atypia involving the upper two-thirds of the epithelium should be made with great caution.

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Is Adjuvant Endocrine Therapy Indicated for DCIS Patients After Complete Surgical Excision?

Data derived from pathological analysis, natural history, radiological characteristics, genomic profiling, and clinical outcome indicate that ductal carcinoma in situ (DCIS) is a heterogeneous disease; meaning that no single therapeutic strategy is best, but rather that treatment should be personalised and entail a rigorous multidisciplinary approach. The role of adjuvant endocrine therapy after surgical excision has been the subject of scientific debate in view of the in situ nature of this neoplasm. We reviewed the literature and summarised the evidence regarding the need for adjuvant endocrine therapy following complete surgical excision of DCIS through the identification of the most important outcomes, evaluation of quality of evidence, and assessment of the trade-offs involved. There is no scientific evidence that adjuvant endocrine therapy reduces the incidence of ipsilateral breast invasive recurrence or breast cancer mortality in the context of adequate local treatment of DCIS in the form of breast conserving surgery with clear surgical margins plus adjuvant radiotherapy or total mastectomy. Therefore, its routine use is not indicated. However, adjuvant endocrine therapy can be considered after a rigorous multidisciplinary discussion and patient counselling in a carefully selected subgroup of patients with high-risk estrogen receptor-positive DCIS.

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Number of Resected Lymph Nodes and Survival of Patients with Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Preoperative Chemoradiotherapy

Background: The association of extended lymph node (LN) dissection with improved outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received preoperative chemoradiotherapy (CRT) followed by surgery is debatable. Patients and Methods: We reviewed data from patients with esophageal cancer enrolled in three phase II clinical trials of preoperative paclitaxel and cisplatin-based CRT during 2000-2012. Patients with ESCC who underwent planned esophagectomy were enrolled. The number of resected LNs and other clinicopathological factors were analyzed regarding their impact on progression-free (PFS) and overall (OS) survival using Cox proportional hazards model. Results: In total, 139 patients were included. The median PFS and OS were 24.4 and 31.8 months, respectively. The median number of resected and positive LNs were 19 (range=2-96) and 0 (range=0-9), respectively. The mean number of positive LNs did not differ significantly among quartile groups of total resected LNs (quartile 1: 2-12, 2: 13-19, 3: 20-29, and 4: 30-96). The resected LN number analyzed as dichotomies divided by the median or as continuous variables was not associated with PFS or OS. However, in an exploratory analysis, patients of quartiles 2 and 3 had longer PFS and OS than those with quartiles of 1 and 4 in multivariate analysis (p=0.019 and 0.005, respectively). Conclusion: Although extensive LN dissection was not associated with improved survival, resection of 13-29 LNs was associated with improved survival in patients with locally advanced ESCC receiving preoperative paclitaxel and cisplatin-based CRT.

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Update on Surgical Management of Small Bowel Neuroendocrine Tumors

The widespread use of endoscopy and imaging in combination with the continuous update of the staging systems for neuroendocrine tumors has led to an increase in the incidence of small intestinal neuroendocrine tumors (si-NENs) globally. Despite high survival rates, severe complications may occur even in early stages due to the anatomic location of the primary site and the desmoplastic reaction. Surgery plays a central role in the management of patients with si-NENs. Excision of locoregional disease along with extensive lymph node dissection should be performed in fit patients, even in the presence of metastases. Multimodality treatment of liver metastases includes hepatectomy, ablative techniques and liver transplantation. Hormone therapy with somatostatine analogs is of high importance for symptomatic control; special caution should be exercised both pre- and intra-operatively. A multidisciplinary approach is essential in order to provide personalized therapeutics for patients with si-NENs. Clinical research and specialization in this field should be further encouraged.

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Expression of Class III Beta-tubulin Predicts Prognosis in Patients with Cisplatin-resistant Bladder Cancer Receiving Paclitaxel-based Second-line Chemotherapy

Background/Aim: Class III beta-tubulin (TUBB3) expression is recognized as a predictive marker for chemosensitivity to cisplatin- and taxane-based chemotherapies in various malignancies. The aim of this study was to clarify the predictive value of TUBB3 expression for the anticancer effects of first-line cisplatin-based chemotherapy and second-line paclitaxel-based chemotherapy in patients with urothelial cancer (UC). Patients and Methods: We reviewed 116 patients with UC (90 with bladder cancer and 27 with upper urinary tract cancer) treated with first-line cisplatin-based chemotherapy. Among them, 42 patients received a paclitaxel-based regimen as second-line chemotherapy for advanced cisplatin-resistant UC. TUBB3 expression was evaluated using immunohistochemistry, and survival analyses were performed using Kaplan–Meier survival curves and multivariate Cox proportional hazard analysis. Results: TUBB3 was mainly detected in the cytoplasm of cancer cells, and 64 patients (55.2%) were judged as having positive TUBB3 expression. TUBB3 expression was significantly associated with tumour grade (p<0.001). TUBB3 expression was not associated with time to progression after first-line cisplatin-based chemotherapy. However, positive expression of TUBB3 was significantly associated with unfavourable overall survival in patients receiving second-line paclitaxel-based chemotherapy (p=0.021). In addition, a multivariate analysis model including T-stage and metastasis at the beginning of second-line therapy and regimen showed that TUBB3 expression was an independent predictor of poorer survival (hazard ratio(HR)=3.44, 95% confidential interval(CI)=1.15-10.33, p=0.027). Conclusion: TUBB3 expression was identified as a useful predictive factor for survival after second-line paclitaxel-based therapy in patients with cisplatin-resistant UC. Our results are useful for determining treatment strategies for such patients

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Detection of Distinct Changes in Gene-expression Profiles in Specimens of Tumors and Transition Zones of Tenascin-positive/-negative Head and Neck Squamous Cell Carcinoma

Background/Aim: Having previously initiated genome-wide expression profiling in head and neck squamous cell carcinoma (HNSCC) for regions of the tumor, the margin of surgical resecate (MSR) and normal mucosa (NM), we here proceed with respective analysis of cases after stratification according to the expression status of tenascin (Ten). Materials and Methods: Tissue specimens of each anatomical site were analyzed by immunofluorescent detection of Ten, fibronectin (Fn) and galectin-1 (Gal-1) as well as by microarrays. Results: Histopathological examination demonstrated that Ten⁺Fn⁺Gal-1⁺ co-expression occurs more frequently in samples of HNSCC (55%) than in NM (9%; p<0.01). Contrary, the Ten^–Fn⁺Gal-1^– (45%) and Ten^–Fn^–Gal-1^– (39%) status occurred with significantly (p<0.01) higher frequency than in HNSCC (3% and 4%, respectively). In MSRs, different immunophenotypes were distributed rather equally (Ten⁺Fn⁺Gal-1⁺=24%; Ten^–Fn⁺Gal-1^–=36%; Ten^–Fn^–Gal-1^–=33%), differing to the results in tumors (p<0.05). Absence/presence of Ten was used for stratification of patients into cohorts without a difference in prognosis, to comparatively examine gene-activity signatures. Microarray analysis revealed i) expression of several tumor progression-associated genes in Ten⁺ HNSCC tumors and ii) a strong up-regulation of gene expression assigned to lipid metabolism in MSRs of Ten^– tumors, while NM profiles remained similar. Conclusion: The presented data reveal marked and specific changes in tumors and MSR specimens of HNSCC without a separation based on prognosis.

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Prognostic Significance of High EphA1-4 Expression Levels in Locally Advanced Gastric Cancer

Background/Aim: Erythropoietin-producing hepatocellular carcinoma receptor A (EphA) is associated with angiogenesis and invasive tumor progression. In this study, we evaluated the EphA1-4 expression levels in advanced gastric cancer. Patients and Methods: Tumor tissues obtained from 114 patients with advanced gastric adenocarcinoma who underwent gastrectomy were analyzed. In addition, the impact of EPHA 1-4 mRNA expression on survival was analyzed using the Kaplan-Meier plotter database on the website. Results: High EphA 1, 2, and 4 expression levels were significantly related to recurrence (p<0.01, p=0.04, and p<0.01). Both high EphA 1 and 4 expression levels were independent predictors of relapse-free interval (hazard ratio [HR]=2.0, p=0.03; HR=2.4, p=0.03) and disease-specific survival (HR=2.0, 95% p=0.03; HR=2.5, p=0.02) on multivariate analysis. In the Kaplan-Meier plotter database, high EPHA2 mRNA expression was significantly associated with poor survival in patients with gastric cancer (p=0.0098), and high expression levels of EPHA1 and 4 tended to be associated with poor survival (p=0.050, p=0.052). Conclusion: EphA 1, 2, and 4 may play key roles in recurrence and survival in patients with advanced gastric cancer.

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Modulation of Tumor Cell Metabolism by Laser Photochemotherapy with Cisplatin or Zoledronic Acid In Vitro

Background/Aim: Laser photochemotherapy is a new approach in cancer treatment using low-level laser therapy (LLLT) to enhance the effect of chemotherapy. Materials and Methods: In order to evaluate the effect of LLLT on tumor cells, HeLa cells were treated with cisplatin or zoledronic acid (ZA) followed by LLLT. Cell viability was evaluated with 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Oxidative phosphorylation and glycolysis were measured using extracellular flux analysis. Immunocytochemistry of heat-shock protein 70 (HSP70) and western blot analysis were performed. Results: LLLT alone increased viability and was associated with lower oxidative phosphorylation but higher glycolysis rates. Cisplatin and ZA alone lowered cell viability, glycolysis and oxidative phosphorylation. This effect was significantly enhanced in conjunction with LLLT and was accompanied by reduced oxidative phosphorylation and collapse of glycolysis. Conclusion: Our observations indicate that LLLT may raise the cytotoxicity of cisplatin and ZA by modulating cellular metabolism, pointing to a possible application in cancer treatment.

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A Feasibility Study of Capecitabine and Oxaliplatin for Patients with Stage II/III Colon Cancer -ACTOR Study-

Background/Aim: Past studies have suggested that adjuvant capecitabine and oxaliplatin (CAPOX) provides decreased tumor relapse and longer survival in patients with curatively resected colon cancer. We report the first evidence of the feasibility of adjuvant CAPOX in Japanese patients with early colon cancer. Patients and Methods: Eligible patients had histologically-confirmed stage II/III colon cancer and received curative resection. The primary endpoint was completion rate of treatment after 8 cycles of adjuvant CAPOX. Results: Thirty-six patients were enrolled in this study. The completion rate of CAPOX and oxaliplatin were 77.8% and 61.1%, respectively. The incidence of grade ≥3 adverse events was neutropenia (n=6), thrombocytopenia (n=3), nausea (n=5), hand-foot syndrome (n=1) and peripheral sensory neuropathy (n=1). Three-year disease-free survival for stage II patients and stage III patients were 100% and 79.3%, respectively. Conclusion: Adjuvant CAPOX can be safely administered to Japanese patients with stage II/III colon cancer.

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Combination Treatment of Polo-Like Kinase 1 and Tankyrase-1 Inhibitors Enhances Anticancer Effect in Triple-negative Breast Cancer Cells

Background/Aim: Breast cancer is the most common malignant cancer type in women, and triple-negative breast cancer (TNBC) is an extremely aggressive subtype of breast cancer with poor prognosis rates. The present study investigated the antitumor effect of polo-like kinase 1 (PLK1) inhibitor in combination with the tankyrase-1 (TNKS1) inhibitor on TNBC cells. Materials and Methods: We evaluated the antitumor effects of combination therapy with PLK1 and TNKS1 inhibitor using cell viability analysis, apoptosis assay and transwell assay for cell invasion and migration in TNBC cells. Results: Combination treatment with PLK1 and TNKS1 inhibitors not only inhibited the invasion and migration capacity of TNBC cells, but also increased the apoptosis and cell death of TNBC cells. The viability of TNBC cells with low expression of β-catenin and high expression of PLK1 was not affected by treatment with PLK1 inhibitor. However, the combination treatment with the TNKS1 inhibitor significantly decreased cell invasion and migration and increased apoptosis. Conclusion: Combination therapy of PLK1 and TNKS1 inhibitors may improve the therapeutic efficacy of the current treatment for TNBC.

http://ift.tt/2HUZ0II

Dental and skeletal changes associated with long-term oral appliance use for obstructive sleep apnea: A systematic review and meta-analysis

An oral appliance (OA) is an effective treatment option for patients with obstructive sleep apnea (OSA), but dental and skeletal changes have been detected by many studies after long-term OA use. Better understanding of the long-term side effects may decrease discontinuation of OA use and assist clinicians to make informed decisions. Accordingly, a systematic review and meta-analysis were performed to evaluate the dental and skeletal changes associated with OAs designed to advance the mandible. The quality of the studies was determined by using the risk of bias assessment tool for non-randomized studies (RoBANS), and 12 studies were included in the meta-analysis.

http://ift.tt/2ouIw1V

Pro-fibrotic phenotype of human skin fibroblasts induced by periostin via modulating TGF-β signaling

Publication date: Available online 6 February 2018
Source:Journal of Dermatological Science
Author(s): Miwa Kanaoka, Yukie Yamaguchi, Noriko Komitsu, Carol A. Feghali-Bostwick, Masahiro Ogawa, Kazuhiko Arima, Kenji Izuhara, Michiko Aihara
BackgroundPeriostin is a matricellular protein that belongs to a class of extracellular matrix (ECM)-related molecules defined by their ability to modulate cell–matrix interactions. We previously reported an elevated level of circulating periostin in patients with systemic sclerosis (SSc) and its association with the severity of skin sclerosis.ObjectiveTo examine the role of periostin in transforming growth factor (TGF)-β signaling involved in fibrosis.MethodsLevels of periostin were examined in skin and lung fibroblasts obtained from SSc patients. Levels of ECM proteins and pro-fibrotic factors were evaluated in periostin-expressing human skin fibroblasts in the presence or absence of TGF-β. Effects of periostin on the Smad proteins were also evaluated following stimulation with TGF-β by immunoblotting, immunofluorescence staining, and RNA interference.ResultsPeriostin was strongly expressed in skin and lung fibroblasts from SSc patients. Although recombinant periostin alone did not affect ECM protein levels, TGF-β and recombinant periostin treatment or periostin overexpression in skin fibroblasts significantly enhanced the production of ECM proteins. Overexpression of periostin in the presence of TGF-β also augmented expressions of α-smooth muscle actin and early growth response-1 but decreased the level and activity of matrix metalloproteinase 1. Interestingly, the level of Smad 7, a TGF-β-inducible inhibitor of TGF-β signaling, was reduced in periostin-expressing fibroblasts but increased in periostin-silenced fibroblasts. In addition, Smad 7 reduction induced by periostin was partially inhibited in integrin αV-silenced fibroblasts.ConclusionPeriostin contributes to fibrosis by enhancing TGF-β signaling via Smad 7 inhibition, which may lead to ECM deposition and periostin generation.



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The Editor's Choice

Publication date: March 2018
Source:Journal of Dermatological Science, Volume 89, Issue 3





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Lymph stasis promotes tumor growth

Publication date: Available online 15 February 2018
Source:Journal of Dermatological Science
Author(s): Valerio De Vita, Eleonora Ruocco




http://ift.tt/2oykfrB

Editor's Choice

Publication date: February 2018
Source:Journal of Dermatological Science, Volume 89, Issue 2





http://ift.tt/2GUhNmf

Editorial board

Publication date: March 2018
Source:Journal of Dermatological Science, Volume 89, Issue 3





http://ift.tt/2ovL0Ns

The role of the OVOL1–OVOL2 axis in normal and diseased human skin

Publication date: Available online 12 February 2018
Source:Journal of Dermatological Science
Author(s): Gaku Tsuji, Takamichi Ito, Takahito Chiba, Chikage Mitoma, Takeshi Nakahara, Hiroshi Uchi, Masutaka Furue
OVOLs (OVO-like proteins) are ubiquitously conserved genes encoding a C2H2 zinc finger transcription factor in mammals. Functional studies on OVOL1 and OVOL2 using knockout mice have suggested that these genes play a pivotal role in the development of epithelial tissues arising from germ cells; however, the role of the OVOL1–OVOL2 axis in normal and diseased tissues remains unclear. This review highlights recent advances in understanding how the OVOL1–OVOL2 axis modulates cell differentiation and proliferation in human keratinocytes, hair follicles, and benign or malignant skin tumors including squamous cell carcinoma and malignant melanoma. Furthermore, OVOL1 has been shown to be involved in the expression of skin barrier proteins including filaggrin (FLG), and its mutation or dysfunction leads to the development of atopic dermatitis (AD). OVOL1 has also been identified as a susceptibility gene for AD by genome-wide association studies, in addition to FLG. Therefore, we discuss the relationship between OVOL1 and FLG in the development of AD.



http://ift.tt/2t5CbP1

Heat shock protein 90 inhibitor enhances apoptosis by inhibiting the AKT pathway in thermal-stimulated SK-MEL-2 human melanoma cell line

Publication date: Available online 8 February 2018
Source:Journal of Dermatological Science
Author(s): Min Kyung Shin, Ki-Heon Jeong, Hyeongwon Choi, Hye-Jin Ahn, Mu-Hyoung Lee
BackgroundHeat shock proteins (Hsps) are chaperone proteins, which are upregulated after various stresses. Hsp90 inhibitors have been investigated as adjuvant therapies for the treatment of melanoma. Thermal ablation could be a treatment option for surgically unresectable melanoma or congenital nevomelanocytic nevi, however, there is a limitation such as the possibility of recurrence.ObjectiveWe evaluated apoptosis in a melanoma cell line treated with the Hsp90 inhibitor 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in hyperthermic conditions.MethodsSK-MEL-2 cells were stimulated at 43 °C for 1 h and treated with 0, 0.1 and 1 μM 17-DMAG. We evaluated the cell viability using MTT and apoptosis with HSP 90 inhibitor. We studied the protein expression of AKT, phospho-AKT, ERK, phospho-ERK, MAPK, and phospho-MAPK, caspase 3,7,9, and anti-poly (ADP-ribose) polymerase.Results17-DMAG significantly inhibited the proliferation of the SK-MEL-2 cells at 37 °C (0.1 μM: 44.47% and 1 μM: 61.23%) and 43 °C (0.1 μM: 49.21% and 1 μM: 63.60%), suggesting synergism between thermal stimulation and 17-DMAG. 17-DMAG treatment increased the frequency of apoptotic cell populations to 2.17% (0.1 μM) and 3.05% (1 μM) in 37 °C controls, and 4.40% (0.1 μM) and 4.97% (1 μM) in the group stimulated at 43 °C. AKT phosphorylation were activated by thermal stimulation and inhibited by 17-DMAG.ConclusionHsp90 inhibitor treatment may be clinically applicable to enhance the apoptosis of melanoma cells in hyperthermic condition.



http://ift.tt/2F2CRdT

Reduced-HMGB1 suppresses poly(I:C)-induced inflammation in keratinocytes

Publication date: Available online 2 February 2018
Source:Journal of Dermatological Science
Author(s): Hideki Mori, Masamoto Murakami, Teruko Tsuda, Kenji Kameda, Ryo Utsunomiya, Kana Masuda, Ken Shiraishi, Xiuju Dai, Mikiko Tohyama, Hiroki Nakaoka, Koji Sayama
BackgroundHigh mobility group box 1 (HMGB1) is a nuclear protein that stabilizes DNA and facilitates gene transcription. Additionally, cell stress or death induces the release of HMGB1 outside the cell membrane, where HMGB1 functions as an alarmin, causing an inflammatory response in combination with other cytokines, damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs).ObjectiveTo evaluate the effect of reduced-HMGB1 (previously termed chemoattractive-HMGB1) on polyinosine-polycytidylic acid [poly(I:C)]-induced inflammation in normal human keratinocytes (NHKs).MethodsWe focused on downstream components of the poly(I:C)-Toll-like receptor 3 (TLR3), retinoic acid-inducible gene-I (RIG-I), and melanoma differentiation-associated protein 5 (MDA5) pathways, including IκBα, nuclear factor (NF)-κB p65, mitogen-activated protein kinase (MAPK), and interferon regulatory factor 3 (IRF3), and assessed whether these pathways are involved in the suppression of poly(I:C)-induced inflammation in NHKs by HMGB1. An immunoprecipitation was performed to know whether HMGB1 could bind to poly(I:C), and immunofluorescence staining and flow cytometric analysis were performed to check whether reduced-HMGB interferes with cellular uptake of poly(I:C) translocation (possibly by endocytosis).ResultsApplication of exogenous HMGB1 before, but not after, exerted a suppressive effect on poly(I:C)-induced inflammation in NHKs. In addition, reduced-HMGB1, but not disulfide-HMGB1, exerted a suppressive effect on poly(I:C)-induced inflammation in NHKs, suggesting the importance of the redox status of exogenous HMGB1. Pre-treatment with reduced-HMGB1 inhibited the phosphorylation of IκBα, NF-κB p65, and IRF3 induced by poly(I:C) stimulation in NHKs; however, phosphorylation of p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) was unaffected. Disulfide-HMGB1 formed a complex with poly(I:C), as did reduced- and oxidized-HMGB1, albeit to a lesser extent. Immunofluorescence staining and flow cytometric analysis indicated that reduced-HMGB interferes with cellular uptake of poly(I:C) translocation (possibly by endocytosis).ConclusionThese findings suggest that pre-treatment with reduced-HMGB1 ameliorates poly(I:C)-mediated inflammation in NHKs.



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Localization of collagen type 5 in the papillary dermis and its role in maintaining stem cell functions

Publication date: February 2018
Source:Journal of Dermatological Science, Volume 89, Issue 2
Author(s): Yuichi Hasebe, Seiji Hasegawa, Yasushi Date, Satoru Nakata, Akiko Yagami, Yohei Iwata, Kazumitsu Sugiura, Hirohiko Akamatsu




http://ift.tt/2GRufTv

Proteins involved in the antioxidant and inflammatory response in rutin-treated human skin fibroblasts exposed to UVA or UVB irradiation

Publication date: Available online 15 February 2018
Source:Journal of Dermatological Science
Author(s): Agnieszka Gęgotek, Pedro Domingues, Elżbieta Skrzydlewska
BackgroundRutin, due to its polyphenolic structure, has antioxidant properties and can be used as a cytoprotective compound against UV-induced effects on skin cells.ObjectiveThe aim of this study was to examine the effect of rutin on proteomic profile in human skin fibroblasts irradiated with UV dose that induces apoptosis.MethodsProteome analysis based on the results obtained by the QExactive OrbiTrap mass spectrometer.ResultsResults show that rutin treatment more strongly protects against UVA-induced rather than UVB-induced increases in the total expression of proteins involved in antioxidant (such as SOD, TrxR, and Prxs 1/2) and inflammatory response (e.g., IL-17F, PAK2, and YWHAZ). However, in the case of UVB-irradiated cells, rutin additionally enhances the levels of disulfide-isomerase − an enzyme that is responsible for the formation and breakage of disulfide bonds. Moreover, UVB radiation promotes rutin-Keap1 adduct formation, which leads to the activation of Nrf2, a factor that is responsible for the synthesis of cytoprotective proteins. Furthermore, rutin partially prevents UV-induced apoptosis by restoring the physiological levels of p53, cytochrome c, and cell cycle and apoptosis regulator protein 2 that were increased following irradiation.ConclusionIn conclusion, our results show that rutin effectively prevents UV-induced damages associated with proinflammatory and prooxidative activity and protects cells against apoptosis.



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Reply: lymph stasis promotes tumor growth

Publication date: Available online 15 February 2018
Source:Journal of Dermatological Science
Author(s): Yoshiyuki Nakamura, Yasuhiro Fujisawa, Naoko Okiyama, Rei Watanabe, Ryota Tanaka, Yosuke Ishitsuka, Hideaki Tahara, Manabu Fujimoto




http://ift.tt/2t5BWDB

An infant with generalized pustular psoriasis and geographic tongue had a heterozygous IL36RN mutation and IgG2 deficiency

Publication date: Available online 6 February 2018
Source:Journal of Dermatological Science
Author(s): Risako Oi, Takuya Takeichi, Yusuke Okuno, Daiei Kojima, Kyoko Sugawara, Michihiro Kono, Hideki Muramatsu, Masashi Akiyama




http://ift.tt/2t5dh1V

Protective role of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous ligand for arylhydrocarbon receptor, in chronic mite-induced dermatitis

Publication date: Available online 21 February 2018
Source:Journal of Dermatological Science
Author(s): Mari Kiyomatsu-Oda, Hiroshi Uchi, Saori Morino-Koga, Masutaka Furue
BackgroundChronic eczema such as atopic dermatitis imposes significant socio-econo-psychologic burdens on the affected individuals. In addition to conventional topical treatments, phototherapy is recommended for patients with extensive lesions. Although immunosuppression is believed to explain its primary effectiveness, the underlying mechanisms of phototherapy remain unsolved. Ultraviolet irradiation generates various tryptophan photoproducts including 6-formylindolo[3,2-b]-carbazole (FICZ). FICZ is known to be a potent endogenous agonist for aryl hydrocarbon receptor (AHR); however, the biological role of FICZ in chronic eczema is unknown.ObjectiveTo investigate the effect of FICZ on chronic eczema such as atopic dermatitis.MethodsWe stimulated HaCaT cells and normal human epidermal keratinocytes (NHEKs) with or without FICZ and then performed quantitative reverse transcriptase polymerase chain reaction, immunofluorescence, and siRNA treatment. We used the atopic dermatitis-like NC/Nga murine model and treated the mice for 2 weeks with either Vaseline^® as a control, FICZ ointment, or betamethasone 17-valerate ointment. The dermatitis score, transepidermal water loss, histology, and expression of skin barrier genes and proteins were evaluated.ResultsFICZ significantly upregulated the gene expression of filaggrin in both HaCaT cells and NHEKs in an AHR-dependent manner, but did not affect the gene expression of other barrier-related proteins. In addition, FICZ improved the atopic dermatitis-like skin inflammation, clinical scores, and transepidermal water loss in NC/Nga mice compared with those of control mice. On histology, FICZ significantly reduced the epidermal and dermal thickness as well as the number of mast cells. Topical FICZ also significantly reduced the gene expression of Il22.ConclusionThese findings highlight the beneficial role of FICZ-AHR and provide a new strategic basis for developing new drugs for chronic eczema.



http://ift.tt/2oyjLBN

Editorial board

Publication date: February 2018
Source:Journal of Dermatological Science, Volume 89, Issue 2





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Introduction of the TERT and BMI1 Genes into Murine Dermal Papilla Cells Ameliorates Hair Inductive Activity

Publication date: Available online 21 February 2018
Source:Journal of Dermatological Science
Author(s): Masahiro Kiso, Shigeharu Yabe, Munenari Itoh, Hidemi Nakagawa, Hitoshi Okochi




http://ift.tt/2F2CAYp

The UVA-induced long non-coding RNA GS1-600G8.5 regulates the expression of IL-8

Publication date: Available online 21 February 2018
Source:Journal of Dermatological Science
Author(s): Kazuyuki Yo, Thomas M. Rünger




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Glyoxal-induced exacerbation of pruritus and dermatitis is associated with staphylococcus aureus colonization in the skin of a rat model of atopic dermatitis.

Publication date: Available online 21 February 2018
Source:Journal of Dermatological Science
Author(s): Rafael Taeho Han, Hye Young Kim, Hyun Ryu, Wooyoung Jang, Seung Ha Cha, Hyo Young Kim, JaeHee Lee, Seung Keun Back, Hee Jin Kim, Heung Sik Na
BackgroundAtopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease associated with hyperreactivity to environmental triggers. Among those, outdoor air pollutants such as particulate matter (PM) have been reported to aggravate pre-existing AD. However, underlying mechanisms of air pollution-induced aggravation of AD have hardly been studied.ObjectiveTo investigate the molecular mechanisms by which glyoxal, a PM-forming organic compound, exacerbates the symptoms of AD induced by neonatal capsaicin treatment.MethodsNaïve and AD rats had been exposed to either fresh air or vaporized glyoxal for 5 weeks (2 h/day and 5 days/week) since one week of age. Pruritus and dermatitis were measured every week. The skin and blood were collected and immunological traits such as Staphylococcus aureus skin colonization, production of antimicrobial peptides and immunoglobulin, and mRNA expression of inflammatory cytokines were analyzed.ResultsExposure to glyoxal aggravated pruritus and dermatitis in AD rats, but did not induce any symptoms in naïve rats. Staphylococcus aureus skin colonization was increased in the skin of both naïve and AD rats. Expression of antimicrobial peptides such as LL-37 and β-defensin-2 was also increased by exposure to glyoxal in the skin of both naïve and AD rats. The mRNA expression of Th1-related cytokines was elevated on exposure to glyoxal. However, serum immunoglobulin production was not significantly changed by exposure to glyoxal.ConclusionIn AD rats, exposure to glyoxal exacerbated pruritus and cutaneous inflammation, which was associated with increased colonization of S. aureus and subsequent immunological alterations in the skin.



http://ift.tt/2oAoS4z

A heterozygous mutation in the SAM domain of p63 underlies a mild form of ectodermal dysplasia

Publication date: Available online 21 February 2018
Source:Journal of Dermatological Science
Author(s): Toru Kawai, Ryota Hayashi, Hiroyuki Nakai, Yutaka Shimomura, Mazen Kurban, Lamiaa Hamie, Hiroki Fujikawa, Atsushi Fujimoto, Riichiro Abe




http://ift.tt/2GRtHgp

Dupilumab treatment in moderate-to-severe atopic dermatitis: A systematic review and meta-analysis

Publication date: Available online 20 February 2018
Source:Journal of Dermatological Science
Author(s): Fa-Ping Wang, Xiao-Ju Tang, Chuan-Qi Wei, Lin-Rui Xu, Hui Mao, Feng-Ming Luo
BackgroundDupilumab, a fully human monoclonal antibody against the interleukin-4-receptor α subunit, has been developed and used in clinical trials to treat atopic dermatitis (AD).ObjectiveWe aimed to assess the overall efficacy and safety of dupilumab treatment in AD.MethodsPubMed, Embase, Cochrane library databases, and the Chinese Biological Medicine (CBM) published up to September 2017 were searched. All randomized controlled trials (RCTs) of dupilumab treatment on adult patients with AD were included. Fixed- or random-effects models were used to calculate pooled standard mean differences or relative risks (SMD or RR, respectively).ResultsSix trials involving 2447 patients were identified. Pooled analysis revealed significant improvements in Eczema Area and Severity Index (EASI) score (SMD = −0.89, 95% CI: −1.0 to −0.78), percentage of body surface area (BSA) (SMD = −0.83, 95% CI: −0.90 to −0.75), pruritus numeric rating scale (NRS) scores (SMD = −0.81, 95% CI: −0.96 to −0.66), and Dermatology Life Quality Index (DLQI) scores (SMD = −0.78, 95% CI: −0.89 to −0.66). Dupilumab treatment was also associated with a significant increase in the proportion of patients achieving Investigator's Global Assessment (IGA) response (RR = 3.82; 95% CI: 3.23 to 4.51) and a similar incidence of adverse events (RR = 1.0; 95% CI: 0.96 to 1.04).ConclusionsOur analysis provided evidence that dupilumab had an acceptable safety profile and resulted in clinically relevant improvements in signs and symptoms of AD. Dose regimens of 300 mg qw and q2 w seemed to have similar benefits. Further long-term trials are required for confirmation.



http://ift.tt/2EY6ixz

Whole Exome Sequencing allows the identification of two novel groups of Xeroderma pigmentosum in Tunisia, XP-D and XP-E: Impact on molecular diagnosis

Publication date: February 2018
Source:Journal of Dermatological Science, Volume 89, Issue 2
Author(s): Mariem Ben Rekaya, Chokri Naouali, Olfa Messaoud, Meriem Jones, Yosra Bouyacoub, Majdi Nagara, Tommaso Pippucci, Haifa Jmel, Mariem Chargui, Manel Jerbi, Mohamed Alibi, Hamza Dallali, Anu Bashamboo, Kenneth McElreavey, Giovanni Romeo, Abdelhamid Barakat, Mohamed Zghal, Houda Yacoub-Youssef, Sonia Abdelhak
BackgroundSkin cancers (SC) are complex diseases that develop from complex combinations of genetic and environmental risk factors. One of the most severe and rare genetic diseases predisposing to SC is the Xeroderma pigmentosum (XP) syndrome.ObjectivesFirst, to identify the genetic etiology of XP and to better classify affected patients. Second, to provide early molecular diagnosis for pre-symptomatic patient and finally to offer genetic counseling for related individuals.MethodsWhole Exome Sequencing (WES) and Run Of Homozygosity (ROH) were performed for two patients belonging to two different multiplex consanguineous families. The identified mutations were confirmed by Sanger sequencing and researched in ten Tunisian families including a total of 25 affected individuals previously suspected as having XP group V (XP-V) form. All patients had mild dermatological manifestations, absence of neurological abnormalities and late onset of skin tumors.ResultsScreening for functional variations showed the presence of the ERCC2 p.Arg683Gln in XP14KA-2 patient and a novel mutation, DDB2 p. (Lys381Argfs*2), in XP51-MAH-1 patient. Sanger sequencing and familial segregation showed that the ERCC2 mutation is present at a homozygous state in 10 affected patients belonging to 3 families. The second mutation in DDB2, is present at a homozygous state in 5 affected cases belonging to the same family. These two mutations are absent in the remaining 10 affected patients. The ERCC2 c.2048G > A mutation is present in a medium ROH region (class B) suggesting that it mostly arises from ancient relatedness within individuals. However, the c.1138delG DDB2 mutation is present in a large ROH region (class C) suggesting that it arises from recent relatedness.ConclusionTo our knowledge, this is the first study that identifies XP-D and XP-E complementation groups in Tunisia. These two groups are very rare and under-diagnosed in the world and were not reported in North Africa.



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3 tesla MRI assisted detection of compression points in ulnar neuropathy at the elbow in correlation with intraoperative findings

Releasing the ulnar nerve from all entrapments is the primary objective of every surgical method in ulnar neuropathy at the elbow (UNE). The aim of this retrospective diagnostic study was to validate preoperative 3 Tesla MRI results by comparing the MRI findings with the intraoperative aspects during endoscopic-assisted or open surgery.

http://ift.tt/2FEtjm6

‘Investigation of the activation of temporalis and masseter muscles in voluntary and spontaneous smile production.’

Masticatory muscles or their nerve supply are options for facial reanimation surgery but their ability to create spontaneous smile has been questioned. This study assessed the percentage of healthy adults who activate temporalis and masseter during voluntary and spontaneous smile.

http://ift.tt/2F1Ygzy

Orthotopic transfer of vascularized groin lymph node flap in the treatment of breast cancer-related lymphedema: clinical results, lymphoscintigraphy findings and proposed mechanism

Vascularized lymph node transfer (VLNT) has become more popular in treating secondary lymphedema. However, the mechanism has not been clearly elucidated.The purpose of this study were (1) to evaluate the outcome of vascularized groin lymph node (VGLN) transfer using axilla as a recipient site in patients with breast cancer-related lymphedema (BCRL) and (2) to provide radiological evidence of lymphangiogenesis in VLNT.

http://ift.tt/2FCzhnv

Assessment and identification of nitrogen pollution sources in the Cheongmi River with intensive livestock farming areas, Korea

Abstract

This study aimed to develop methods for assessing and identifying nitrogen sources in the Cheongmi River, Korea, that has intensive livestock farming areas (ILFA) in its watershed. The assessment focused on the feasibility of the simultaneous use of stable isotopic compositions of ammonium (δ¹⁵N_NH4) and nitrate (δ¹⁵N_NO3) for identifying the main nitrogen pollution sources in the Cheongmi River watershed. Our results suggested that the organic nitrogen (Org-N) to total nitrogen (T-N) ratio could be used as an indicator for assessing the effect of livestock excreta on waterways in ILFA. We observed that the T-N concentration was much more strongly affected by livestock excreta than the T-P concentration in the mainstream of the Cheongmi River. The positive correlation was more significant between δ¹⁵N_NH4 and NH₄-N than that between δ¹⁵N_NO3 and NO₃-N for river water samples. Furthermore, the use of δ¹⁵N_NH4 was more effective than that of δ¹⁵N_NO3 in evaluating nitrogen variations between May and August in the Cheongmi River because the differences in δ¹⁵N_NH4 between May and August were more remarkable compared to those in δ¹⁵N_NO3. Finally, the simultaneous use of δ¹⁵N_NH4 and δ¹⁵N_NO3 showed that the dominant nitrogen source at sites M3, M4, M5, and M6, specifically in May, was livestock excreta in the Cheongmi River. The results of this study could be used for sustainable water quality management in the Cheongmi River watershed.

http://ift.tt/2t1wQsf

Gradient nano-engineered in situ forming composite hydrogel for osteochondral regeneration

Publication date: April 2018
Source:Biomaterials, Volume 162
Author(s): Janani Radhakrishnan, Amrutha Manigandan, Prabu Chinnaswamy, Anuradha Subramanian, Swaminathan Sethuraman
Fabrication of anisotropic osteochondral-mimetic scaffold with mineralized subchondral zone and gradient interface remains challenging. We have developed an injectable semi-interpenetrating network hydrogel construct with chondroitin sulfate nanoparticles (ChS-NPs) and nanohydroxyapatite (nHA) (∼30–90 nm) in chondral and subchondral hydrogel zones respectively. Mineralized subchondral hydrogel exhibited significantly higher osteoblast proliferation and alkaline phosphatase activity (p < 0.05). Osteochondral hydrogel exhibited interconnected porous structure and spatial variation with gradient interface of nHA and ChS–NPs. Microcomputed tomography (μCT) demonstrated nHA gradation while rheology showed predominant elastic modulus (∼930 Pa) at the interface. Co–culture of osteoblasts and chondrocytes in gradient hydrogels showed layer–specific retention of cells and cell-cell interaction at the interface. In vivo osteochondral regeneration by biphasic (nHA or ChS) and gradient (nHA + ChS) hydrogels was compared with control using rabbit osteochondral defect after 3 and 8 weeks. Complete closure of defect was observed in gradient (8 weeks) while defect remained in other groups. Histology demonstrated collagen and glycosaminoglycan deposition in neo–matrix and presence of hyaline cartilage–characteristic matrix, chondrocytes and osteoblasts. μCT showed mineralized neo–tissue formation, which was confined within the defect with higher bone mineral density in gradient (chondral: 0.42 ± 0.07 g/cc, osteal: 0.64 ± 0.08 g/cc) group. Further, biomechanical push-out studies showed significantly higher load for gradient group (378 ± 56 N) compared to others. Thus, the developed nano-engineered gradient hydrogel enhanced hyaline cartilage regeneration with subchondral bone formation and lateral host-tissue integration.



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Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation

Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Hong Ji Yan, Tommaso Casalini, Gry Hulsart-Billström, Shujiang Wang, Oommen P. Oommen, Matteo Salvalaglio, Sune Larsson, Jöns Hilborn, Oommen P. Varghese
Synthetic scaffolds that possess an intrinsic capability to protect and sequester sensitive growth factors is a primary requisite for developing successful tissue engineering strategies. Growth factors such as recombinant human bone morphogenetic protein-2 (rhBMP-2) is highly susceptible to premature degradation and to provide a meaningful clinical outcome require high doses that can cause serious side effects. We discovered a unique strategy to stabilize and sequester rhBMP-2 by enhancing its molecular interactions with hyaluronic acid (HA), an extracellular matrix (ECM) component. We found that by tuning the initial protonation state of carboxylic acid residues of HA in a covalently crosslinked hydrogel modulate BMP-2 release at physiological pH by minimizing the electrostatic repulsion and maximizing the Van der Waals interactions. At neutral pH, BMP-2 release is primarily governed by Fickian diffusion, whereas at acidic pH both diffusion and electrostatic interactions between HA and BMP-2 become important as confirmed by molecular dynamics simulations. Our results were also validated in an in vivo rat ectopic model with rhBMP-2 loaded hydrogels, which demonstrated superior bone formation with acidic hydrogel as compared to the neutral counterpart. We believe this study provides new insight on growth factor stabilization and highlights the therapeutic potential of engineered matrices for rhBMP-2 delivery and may help to curtail the adverse side effects associated with the high dose of the growth factor.



http://ift.tt/2BKCIJR

Blood brain barrier (BBB)-disruption in intracortical silicon microelectrode implants

Publication date: May 2018
Source:Biomaterials, Volume 164
Author(s): Cassie Bennett, Malaroviyam Samikkannu, Farrah Mohammed, W. Dalton Dietrich, Suhrud M. Rajguru, Abhishek Prasad
Chronically implanted microelectrodes in the neural tissue elicit inflammatory responses that are time varying and have been shown to depend on multiple factors. Among these factors, blood brain barrier (BBB)-disruption has been hypothesized as one of the dominant factors resulting in electrode failure. A series of events that includes BBB and cell-membrane disruption occurs during electrode implantation that triggers multiple biochemical cascades responsible for microglial and astroglial activation, hemorrhage, edema, and release of pro-inflammatory neurotoxic cytokines that causes neuronal degeneration and dysfunction. Typically, microwire arrays and silicon probes are inserted slowly into the neural tissue whereas the silicon Utah MEAs (UMEA) are inserted at a high speed using a pneumatic inserter. In this work, we report the sequelae of electrode-implant induced cortical injury at various acute time points in UMEAs implanted in the brain tissue by quantifying the expression profile for key genes mediating the inflammatory response and tight junction (TJ) and adherens junction (AJ) proteins that form the BBB and are critical to the functioning of the BBB. Our results indicated upregulation of most pro-inflammatory genes relative to naïve controls for all time points. Expression levels for the genes that form the TJ and AJ were downregulated suggestive of BBB-dysfunction. Moreover, there was no significant difference between stab and implant groups suggesting the effects of UMEA insertion-related trauma in the brain tissue. Our results provide an insight into the physiological events related to neuroinflammation and BBB-disruption occurring at acute time-points following insertion of UMEAs.



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Comparative evaluation of cell- and serum-derived exosomes to deliver immune stimulators to lymph nodes

Publication date: April 2018
Source:Biomaterials, Volume 162
Author(s): Gyeonghui Yu, Heesun Jung, Yoon Young Kang, Hyejung Mok
To determine whether exosomes are efficient carriers for immune stimulating molecules into lymph nodes, comparative studies of exosomes (EXOs) derived from different origins (cells and serums) in terms of physicochemical properties and delivery efficiency were performed. Serum-derived EXOs were of a preferable size and generated higher yields than RAW264.7 cell-derived exosomes (RAW-EXO). In particular, fetal bovine serum-derived exosomes (bo-EXO), with a size below 50 nm, were delivered not only to surface zones (subcapsular sinus (SCS) macrophage zone) but also to inner paracortex zones (T cell zone) of lymph nodes, which allowed an efficient delivery of immune stimulating molecules to antigen presenting cells and T cells. The encapsulation of immune stimulating biomolecules (monophosphoryl lipid A (MPLA) and CpG oligodeoxynucleotides (CpG ODN)) within EXOs greatly increased intracellular delivery to macrophages via phagocytic pathways, which induced higher TNF-α and IL-6 secretion than free MPLA and free CpG ODN. MPLA-incorporated exosomes activated and differentiated T cells after subcutaneous injection, which elevated cytokine IFN-γ and TNF-α induction for CD3⁺ T cells. Taken together, bo-EXOs might serve as efficient carrier systems of immune stimulators to lymph nodes for desired immune responses.



http://ift.tt/2BGryF5

Biodegradable near-infrared-photoresponsive shape memory implants based on black phosphorus nanofillers

Publication date: May 2018
Source:Biomaterials, Volume 164
Author(s): Hanhan Xie, Jundong Shao, Yufei Ma, Jiahong Wang, Hao Huang, Na Yang, Huaiyu Wang, Changshun Ruan, Yanfeng Luo, Qu-Quan Wang, Paul K. Chu, Xue-Feng Yu
In this paper, we propose a new shape memory polymer (SMP) composite with excellent near-infrared (NIR)-photoresponsive shape memory performance and biodegradability. The composite is fabricated by using piperazine-based polyurethane (PU) as thermo-responsive SMP incorporated with black-phosphorus (BP) sheets as NIR photothermal nanofillers. Under 808 nm light irradiation, the incorporated BP sheets with concentration of only 0.08 wt% enable rapid temperature increase over the glass temperature of PU and trigger the shape change of the composite with shape recovery rate of ∼100%. The in vitro and in vivo toxicity examinations demonstrate the good biocompatibility of the PU/BP composite, and it degrades naturally into non-toxic carbon dioxide and water from PU and non-toxic phosphate from BP. By implanting PU/BP columns into back subcutis and vagina of mice, they exhibit excellent shape memory activity to change their shape quickly under moderate 808 nm light irradiaiton. Such SMP composite enable the development of intelligent implantable devices, which can be easily controlled by the remote NIR light and degrade gradually after performing the designed functions in the body.



http://ift.tt/2HHvKVK

Adsorption force of fibronectin controls transmission of cell traction force and subsequent stem cell fate

Publication date: April 2018
Source:Biomaterials, Volume 162
Author(s): Manping Lin, Shilong Mao, Jinfeng Wang, Juan Xing, Yuanliang Wang, Kaiyong Cai, Yanfeng Luo
The transmission of cell traction force (CTF) to underlying biomaterials is essential for adhered cells to measure and respond to their mechanical microenvironment. Given that the protein layer adsorbed on materials lies between the cells and materials, we hypothesize that the interfacial strength of protein-material interfaces (i.e., the adsorption force of proteins, Fad) should have an important role in regulating the transmission of CTF. To test this hypothesis, rat mesenchymal stem cells (rMSCs) were cultured on poly(dimethyl siloxane) (PDMS) substrates with different Fad of fibronectin (FN), and the transmission of CTF was observed by immunofluorescence staining of FN and deformation of PDMS. As revealed, FN on substrates with low Fad is more liable to be desorbed by CTF, which prevents the transmission of CTF to substrates. In contrast, high Fad facilitates the transmission of CTF from rMSCs to the FN layer and PDMS substrates so that rMSCs can perceive the mechanical properties of substrates. We further demonstrated that the divergent transmission of CTF on low and high Fad substrates regulates the lineage specifications of rMSCs. Our study confirms the important role of Fad in CTF transmission and provides a new perspective to gain insights into cell-material interactions and cell fates, which may help to guide the design of better biomaterials.

Graphical abstract

http://ift.tt/2okX9UA

Surface modification of nanofibrous matrices via layer-by-layer functionalized silk assembly for mitigating the foreign body reaction

Publication date: May 2018
Source:Biomaterials, Volume 164
Author(s): Yuna Qian, Linhao Li, Yang Song, Lili Dong, Peixing Chen, Xiaoming Li, Kaiyong Cai, Oliver Germershaus, Li Yang, Yubo Fan
The inherent hydrophobicity and large surface area of electrospun synthetic polymeric scaffolds often cause non-specific protein adsorption, thereby influencing macrophage functions and eventually leading to fibrosis at the tissue-scaffold interface. This work reports fabrication of silk fibroin (SF)-functionalized electrospun polycaprolactone (PCL) fibers by single-component layer-by-layer assembly and decorate the SF with heparin disaccharide (HD), resulting in the non-covalent binding of interleukin-4 (IL-4) with the capacity to modulate macrophage polarization. A modified SF derivative was obtained by diazonium coupling and then covalently bonded with HD via click chemistry to eventually bind IL-4 efficiently and maintain its bioactivity. In vitro studies showed that IL-4 surface-functionalized nanofibrous scaffolds promoted polarization to M2 macrophages in the short-term. Importantly, in a murine subcutaneous implantation model, we found that promoting transient shifts in macrophage polarization at early stage can significantly inhibit the extent of the late foreign body reactions. Furthermore, the results of a transcriptomic profiling showed that MARK, PI3K, JNK and NF-κB signaling pathways played an important role in regulating the macrophage phenotypes in the SF/HD/IL-4-functionalized fibers. Our results suggest that such a strategy offers a new approach for utilizing biological agent surface functionalization to modulate the foreign body reaction to nanofibrous scaffolds.



http://ift.tt/2GE5YQS

Metabolomics facilitates the discrimination of the specific anti-cancer effects of free- and polymer-conjugated doxorubicin in breast cancer models

Publication date: April 2018
Source:Biomaterials, Volume 162
Author(s): Ana Armiñán, Martina Palomino-Schätzlein, Coralie Deladriere, Juan J. Arroyo-Crespo, Sonia Vicente-Ruiz, María J. Vicent, Antonio Pineda-Lucena
Metabolomics is becoming a relevant tool for understanding the molecular mechanisms involved in the response to new drug delivery systems. The applicability of this experimental approach to cell cultures and animal models makes metabolomics a useful tool for establishing direct connections between in vitro and in vivo data, thus providing a reliable platform for the characterization of chemotherapeutic agents. Herein, we used metabolomic profiles based on nuclear magnetic resonance (NMR) spectroscopy to evaluate the biochemical pathways involved in the response to a chemotherapeutic anthracycline drug (Doxorubicin, Dox) and an N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-conjugated form (HPMA-Dox) in an in vitro cell culture model and an in vivo orthotopic breast cancer model. We also used protein expression and flow cytometry studies to obtain a better coverage of the biochemical alterations associated with the administration of these compounds. The overall analysis revealed that polymer conjugation leads to increased apoptosis, reduced glycolysis, and reduced levels of phospholipids when compared to the free chemotherapeutic drug. Our results represent a first step in the application of integrated in vitro and in vivo metabolomic studies to the evaluation of drug delivery systems.



http://ift.tt/2CcxDdD

A TRACER 3D Co-Culture tumour model for head and neck cancer

Publication date: May 2018
Source:Biomaterials, Volume 164
Author(s): Miki Young, Darren Rodenhizer, Teresa Dean, Elisa D'Arcangelo, Bin Xu, Laurie Ailles, Alison P. McGuigan
Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment and have been shown to play an important role in the progression of cancer. To probe these tumour-stroma interactions, we incorporated CAFs derived from head and neck cancer patients and squamous carcinoma cells of the hypopharynx (FaDu) into the Tissue Roll for the Analysis of Cellular Environment and Response (TRACER) platform to establish a co-culture platform that simulates the CAF-tumour microenvironmental interactions in head and neck tumours. TRACER culture involves infiltrating cells into a thin fibrous scaffold and then rolling the resulting biocomposite around a mandrel to generate a 3D and layered structure. Patterning the fibrous scaffold biocomposite during fabrication enables control over the specific location of different cell populations in the rolled configuration. Here, we optimized the seeding densities and configurations of the CAF and FaDu cell tissue sections to enable a robust 3D co-culture system under normoxic conditions. Co-culture of CAFs with FaDu cells produced negligible effects on radiation resistance, but did produce increases in proliferation rate and invasive cell migration at 24 and 48 h of culture. Our study provides the basis for use of our in vitro co-culture TRACER model to investigate the tumour-stroma interactions, and to bridge the translational gap between preclinical and clinical studies.



http://ift.tt/2GJ5UiI

Unique electrophysiological and impedance signatures between encapsulation types: An analysis of biological Utah array failure and benefit of a biomimetic coating in a rat model

Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Patrick A. Cody, James R. Eles, Carl F. Lagenaur, Takashi D.Y. Kozai, X.Tracy Cui
Intracortical microelectrode arrays, especially the Utah array, remain the most common choice for obtaining high dimensional recordings of spiking neural activity for brain computer interface and basic neuroscience research. Despite the widespread use and established design, mechanical, material and biological challenges persist that contribute to a steady decline in recording performance (as evidenced by both diminished signal amplitude and recorded cell population over time) or outright array failure. Device implantation injury causes acute cell death and activation of inflammatory microglia and astrocytes that leads to a chronic neurodegeneration and inflammatory glial aggregation around the electrode shanks and often times fibrous tissue growth above the pia along the bed of the array within the meninges. This multifaceted deleterious cascade can result in substantial variability in performance even under the same experimental conditions. We track both impedance signatures and electrophysiological performance of 4 × 4 floating microelectrode Utah arrays implanted in the primary monocular visual cortex (V1m) of Long-Evans rats over a 12-week period. We employ a repeatable visual stimulation method to compare signal-to-noise ratio as well as single- and multi-unit yield from weekly recordings. To explain signal variability with biological response, we compare arrays categorized as either Type 1, partial fibrous encapsulation, or Type 2, complete fibrous encapsulation and demonstrate performance and impedance signatures unique to encapsulation type. We additionally assess benefits of a biomolecule coating intended to minimize distance to recordable units and observe a temporary improvement on multi-unit recording yield and single-unit amplitude.



http://ift.tt/2BLpOLu

Targeting CD14 on blood derived cells improves intracortical microelectrode performance

Publication date: May 2018
Source:Biomaterials, Volume 163
Author(s): Hillary W. Bedell, John K. Hermann, Madhumitha Ravikumar, Shushen Lin, Ashley Rein, Xujia Li, Emily Molinich, Patrick D. Smith, Stephen M. Selkirk, Robert H. Miller, Steven Sidik, Dawn M. Taylor, Jeffrey R. Capadona
Intracortical microelectrodes afford researchers an effective tool to precisely monitor neural spiking activity. Additionally, intracortical microelectrodes have the ability to return function to individuals with paralysis as part of a brain computer interface. Unfortunately, the neural signals recorded by these electrodes degrade over time. Many strategies which target the biological and/or materials mediating failure modes of this decline of function are currently under investigation. The goal of this study is to identify a precise cellular target for future intervention to sustain chronic intracortical microelectrode performance. Previous work from our lab has indicated that the Cluster of Differentiation 14/Toll-like receptor pathway (CD14/TLR) is a viable target to improve chronic laminar, silicon intracortical microelectrode recordings. Here, we use a mouse bone marrow chimera model to selectively knockout CD14, an innate immune receptor, from either brain resident microglia or blood-derived macrophages, in order to understand the most effective targets for future therapeutic options. Using single-unit recordings we demonstrate that inhibiting CD14 from the blood-derived macrophages improves recording quality over the 16 week long study. We conclude that targeting CD14 in blood-derived cells should be part of the strategy to improve the performance of intracortical microelectrodes, and that the daunting task of delivering therapeutics across the blood-brain barrier may not be needed to increase intracortical microelectrode performance.



http://ift.tt/2sIThSR

Time-responsive osteogenic niche of stem cells: A sequentially triggered, dual-peptide loaded, alginate hybrid system for promoting cell activity and osteo-differentiation

Publication date: May 2018
Source:Biomaterials, Volume 163
Author(s): Zuyuan Luo, Siqi Zhang, Jijia Pan, Rui Shi, Hao Liu, Yalin Lyu, Xiao Han, Yan Li, Yue Yang, Zhixiu Xu, Yi Sui, En Luo, Yuanyuan Zhang, Shicheng Wei
The efficacy of stem cell-based bone tissue engineering has been hampered by cell death and limited fate control. A smart cell culture system with the capability of sequentially delivering multiple factors in specific growth stages, like the mechanism of the natural extracellular matrix modulating tissue formation, is attractive for enhancing cell activity and controlling cell fate. Here, a bone forming peptide-1 (BFP-1)-laden mesoporous silica nanoparticles (pep@MSNs) incorporated adhesion peptide, containing the arginine-glycine-aspartic acid (RGD) domain, modified alginate hydrogel (RA) system (pep@MSNs-RA) was developed to promote the activity and stimulate osteo-differentiation of human mesenchymal stem cells (hMSCs) in sequence. The survivability and proliferation of hMSCs were enhanced in the adhesion peptide modified hydrogel. Next, BFP-1 released from pep@MSNs induced hMSCs osteo-differentiation after the proliferation stage. Moreover, BFP-1 near the cells was self-captured by the additional cell-peptide cross-linked networks formed by the ligands (RGD) binding to receptors on the cell surface, leading to long-term sustained osteo-stimulation of hMSCs. The results suggest that independent and sequential stimulation in proliferation and osteo-differentiation stages could synergistically enhance the survivability, expansion, and osteogenesis of hMSCs, as compared to stimulating alone or simultaneously. Overall, this study provided a new and valid strategy for stem cell expansion and osteo-differentiation in 2D or 3D culture systems, possessing potential applications in 3D bio-printing and tissue regeneration.

Graphical abstract

http://ift.tt/2BuYbp5

Controlled release of collagen-binding SDF-1α from the collagen scaffold promoted tendon regeneration in a rat Achilles tendon defect model

Publication date: April 2018
Source:Biomaterials, Volume 162
Author(s): Jie Sun, Chenchen Mou, Qin Shi, Bing Chen, Xianglin Hou, Wen Zhang, Xiaoran Li, Yan Zhuang, Jiajia Shi, Yanyan Chen, Jianwu Dai
It had been demonstrated that stromal cell-derived factor-1α (SDF-1α) could promote in situ tendon regeneration by recruiting endogenous cells. However, native SDF-1α diffuses too fast in vivo, reducing its local concentration and efficacy. In this study, we prepared a recombinant SDF-1α containing a collagen-binding domain (CBD-SDF-1α) and developed a functional collagen scaffold by tethering CBD-SDF-1α on the collagen scaffold for in situ tendon regeneration. CBD-SDF-1α could induce the migration of mesenchymal stem cells, dermal fibroblasts and Achilles tendon fibroblasts in vitro, and achieve controlled release from the collagen scaffold. In a rat Achilles tendon defect model, the functional scaffold could increase the recruitment of CXCR4 positive fibroblast-like cells and the deposition of Tenascin-C at 7 days after implantation. After 4 and 12 weeks, the functional collagen scaffold could promote the expression of type I collagen, increase the diameters of collagen fibrils and improve the mechanical properties of regenerated tendons. Hence, the functional scaffold increased the efficacy of tendon regeneration by controlling release of SDF-1α, enhancing the recruitment of fibroblast-like cells and providing instructive microenvironment and mechanical support for tendon regeneration. Therefore, CBD-SDF-1α-modified collagen scaffold could serve as a practical application for tendon regeneration.



http://ift.tt/2nX34Px

Iron-engineered mesoporous silica nanocatalyst with biodegradable and catalytic framework for tumor-specific therapy

Publication date: May 2018
Source:Biomaterials, Volume 163
Author(s): Liying Wang, Minfeng Huo, Yu Chen, Jianlin Shi
Inorganic mesoporous silica-based nanovehicles are highly promising for drug delivery but still suffer from the disadvantages of lacking functionality and poor biodegradability on account of the inert silica framework. Moreover, conventional cancer therapeutics typically employ toxic anticancer drugs or invasive external irradiations, which will inevitably give rise to severe adverse effects and diminished therapeutic outcome. In this work, we report on the iron engineered framework of mesoporous silica nanoparticles (MSNs) to fabricate a nanocatalyst with biodegradable and catalytic framework via a "dissolution-regeneration" strategy (designated as rFeOx-HMSN). Based on the abundant overexpressed hydrogen peroxide (H2O2) and mild acidic nature in tumor microenvironment (TME), rFeOx-HMSN nanocatalyst could trigger in-situ Fenton-like reactions to produce highly toxic hydroxyl radicals (·OH), causing remarkable oxidative damages against tumor cells/xenografts. Additionally, the iron-engineered rFeOx-HMSN nanocatalyst could readily collapse via an iron-extraction strategy under protein-rich environment, thereby improving the biodegradability of rFeOx-HMSN nanocatalyst. This work paves a promising way to engineer the inert framework of MSN into functional, biodegradable and catalytic nanoplatform, featuring effective tumor-therapeutic outcome and stimuli-responsive biodegradation concurrently.

Graphical abstract

http://ift.tt/2svaUpb

Effect of hyaluronic acid hydrogels containing astrocyte-derived extracellular matrix and/or V2a interneurons on histologic outcomes following spinal cord injury

Publication date: April 2018
Source:Biomaterials, Volume 162
Author(s): Russell E. Thompson, Jennifer Pardieck, Laura Smith, Peter Kenny, Lindsay Crawford, Molly Shoichet, Shelly Sakiyama-Elbert
One reason for the lack of regeneration, and poor clinical outcomes, following central nervous system (CNS) injury is the formation of a glial scar that inhibits new axon growth. In addition to forming the glial scar, astrocytes have been shown to be important for spontaneous SCI recovery in rodents, suggesting some astrocyte populations are pro-regenerative, while others are inhibitory following injury. In this work, the effect of implanting hyaluronic acid (HA) hydrogels containing extracellular matrix (ECM) harvested from mouse embryonic stem cell (mESC)-derived astrocytes on histologic outcomes following SCI in rats was explored. In addition, the ability of HA hydrogels with and without ECM to support the transplantation of mESC-derived V2a interneurons was tested. The incorporation of ECM harvested from protoplasmic (grey matter) astrocytes, but not ECM harvested from fibrous (white matter) astrocytes, into hydrogels was found to reduce the size of the glial scar, increase axon penetration into the lesion, and reduce macrophage/microglia staining two weeks after implantation. HA hydrogels were also found to support transplantation of V2a interneurons and the presence of these cells caused an increase in neuronal processes both within the lesion and in the 500 μm surrounding the lesion. Overall, protoplasmic mESC-derived astrocyte ECM showed potential to treat CNS injury. In addition, ECM:HA hydrogels represent a novel scaffold with beneficial effects on histologic outcomes after SCI both with and without cells.



http://ift.tt/2BGN3FM

Photo-crosslinkable, injectable sericin hydrogel as 3D biomimetic extracellular matrix for minimally invasive repairing cartilage

Publication date: May 2018
Source:Biomaterials, Volume 163
Author(s): Chao Qi, Jia Liu, Yang Jin, Luming Xu, Guobin Wang, Zheng Wang, Lin Wang
Millions of patients worldwide suffer from cartilage injury and age/disease-related cartilage degeneration. However, cartilage, such as articular cartilage, is poor at self-regeneration. Current treatments are often invasive with limited efficacy. Developing minimal invasive strategies for effective cartilage repair is highly desired. Here, we report an injectable, photo-crosslinkable sericin hydrogel as a biomimetic extracellular matrix for minimal invasively repairing cartilage. Sericin was functionalized to be sericin methacryloyl (SerMA), which formed an in situ hydrogel upon UV light irradiation via photo-crosslinking. Possessing excellent biocompatibility, SerMA hydrogels were adhesive to chondrocytes, and promoted the proliferation of attached chondrocytes even in a nutrition-lacking condition. SerMA hydrogels exhibited photoluminescent property allowing real-time monitoring hydrogels' status. The mechanical properties and degradation rates (73% for SMH-1, 47% for SMH-2 and 37% for SMH-3 after 45 days) of SerMA hydrogels were readily tunable by varying methacryloyl modification degrees to meet various repair requirements. Notably, the in vivo implantation of chondrocyte-laden SerMA hydrogels effectively formed artificial cartilages after 8 weeks. Most importantly, the artificial cartilages molecularly resembled native cartilage as evidenced by high accumulation of cartilage-specific ECM components and upregulated expression of cartilage-critical genes. Together, this sericin hydrogel is a promising tissue engineering scaffold for generating artificial cartilage in vivo towards effective, minimal invasive cartilage repair.



http://ift.tt/2F3EAfr

Dual-responsive polyplexes with enhanced disassembly and endosomal escape for efficient delivery of siRNA

Publication date: April 2018
Source:Biomaterials, Volume 162
Author(s): Jia Zhu, Mingxi Qiao, Qi Wang, Yuqing Ye, Shuang Ba, Jingjing Ma, Haiyang Hu, Xiuli Zhao, Dawei Chen
Despite the extracellular barriers for siRNA delivery have been overcome by utilizing advanced nanoparticle delivery systems, the key intracellular barriers after internalization including efficient disassembly of siRNA and endosomal escape still remains challenging. To address the issues, we developed a unique pH- and redox potential-responsive polyplex delivery system based on the copolymer of mPEG-b-PLA-PHis-ssPEI1.8 k, which is composed of a pH-responsive copolymer of PEG-b-PLA-PHis (Mw 5 k) and a branched PEI (Mw1.8 k) linked with redox cleavable disulfide bond. The copolymer showed excellent siRNA complexation and protection abilities against endogenous substances at the relatively low N/P ratio of 6. The siRNA release from the polyplexes (N/P 6) was markedly increased from 13.62% to 58.67% under conditions simulating the endosomal microenvironment. Fluorescence resonance energy transfer (FRET) test also indicated a higher disassembly extent of siRNA from the copolymer. The accelerated siRNA release from the polyplexes was markedly restrained when the N/P ratio was raised above 10 due to the increasing of electrostatic interactions. The efficient endosomal escape of siRNA after internalization was confirmed by confocal microscopy, which was attributed to the cleavaged PEI chains inducing membrane destabilization, the "proton sponge effect" of PHis and PEI as well as the relative small size of after disassembly. The enhanced disassembly and endosomal escape were elucidated as the leading cause for polyplexes (N/P 6) showed more efficient Bcl-2 silencing (85.45%) than those polyplexes with higher N/P ratios (N/P 10 and 15). In vivo results further demonstrated that polyplexes (N/P 6) delivery of siBcl-2 significantly inhibited the MCF-7 breast tumor growth as compared to its counterparts. The incorporation of convertible non-electrical interactions at a balance with electrostatic interactions in complexation siRNA has been demonstrated as an effective strategy to achieve efficient disassembly from stable polyplexes. Moreover, polyplexes equipped with the enhanced disassembly and endosomal escape provides a new potential way to tackle the intracellular delivery bottleneck for siRNA delivery.



http://ift.tt/2ExGAik

Reduction-sensitive fluorescence enhanced polymeric prodrug nanoparticles for combinational photothermal-chemotherapy

Publication date: May 2018
Source:Biomaterials, Volume 163
Author(s): Yuanyuan Zhang, Dan Yang, Hongzhong Chen, Wei Qi Lim, Fiona Soo Zeng Phua, Guanghui An, Piaoping Yang, Yanli Zhao
In this study, a reduction-sensitive supramolecular polymeric drug delivery system was developed for combinational photothermal-chemotherapy of cancer. The multifunctional system was self-assembled by specific host–guest interactions between hydrophilic β-cyclodextrin functionalized hyaluronic acid and adamantane linked camptothecin/dye conjugate, where a near-infrared (NIR) absorbing dye IR825 was loaded. The hydrophilic hyaluronic acid shell endows the assembly with excellent colloidal stability and biocompatibility. The embedded disulfide bond in the camptothecin/dye conjugate was cleaved under reducing environment, leading to the release of the conjugated drug and the recovery of fluorescence emission. Meanwhile, the dye IR825 could efficiently transfer the absorbed light into local heat, making the nanoplatform an effective system for photothermal therapy. As evident by confocal microscopy images, the nanoplatform was quickly internalized by HeLa, MCF-7, and U14 cancer cells and released drug molecules inside the cells. In vitro cell viability assays confirmed that the cancer cells were efficiently killed by the treatment of the nanoplatform under NIR light irradiation. Significant tumor regression was also observed in the tumor-bearing mice upon the administration of the nanoplatform through combinational photothermal-chemotherapy therapy. Hence, this nanoplatform presented a great potential in site-specific combined photothermal-chemotherapy of tumor.

Graphical abstract

http://ift.tt/2o0mrI9

Editorial Board

Publication date: April 2018
Source:Biomaterials, Volume 161





http://ift.tt/2svO4NZ

In vitro outlook of gold nanoparticles in photo-thermal therapy: a literature review

Abstract

Hyperthermia is an anti-cancer treatment in which the temperature of the malignant tumor is increased more than other adjacent normal tissues. Microwave, ultrasound, laser, and radiofrequency sources have been used for hyperthermia of cancerous tissues. In the past decade, near-infrared (NIR) laser for cancer therapy, known as photo-thermal therapy (PTT), was expanded in which the photo-sensitizer agent converts the light photon energy to heat. The heat following PTT can destroy cancer cells. There are some photo-sensitizer agents which have been used for PTT; however, owing to recent advances in nanotechnology, noble metal nanoparticles like gold (Au) nanoparticles (GNPs) have been used successfully in PTT. GNPs have some desirable specifications, including simple and controlled synthesis, small size, high level of biocompatibility, and surface plasmon resonance (SPR). The SPR effect of the GNPs increases the radiative properties like absorption and scattering; therefore, they can be used in PTT. In this article, we reviewed recent in vitro studies of PTT using GNPs in literature. At first, we focus on the physical properties of GNPs, their interaction with infrared radiation, and physical parameters governing the interaction of infrared radiation with the GNPs. Then, we review the passive and active targeting of GNPs using the different coating to induce the thermal damage in cancer cells using low-level laser PPT. The GNPs' cellular internalization into cancer cells is a challenge which is consequently considered. In this review, we also summarize the results of synergistic cancer therapy studies on the combination of radiation therapy as a routine cancer treatment and PTT: in which significant improvement occurs in treatment efficacy.

http://ift.tt/2F0rvXL

Commentary on “Post-carotid Endarterectomy Hypertension. Part 2: Association with Peri-operative Clinical, Anaesthetic, and Transcranial Doppler Derived Parameters”

Publication date: Available online 28 February 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Leonie M.M. Fassaert, Gert J. de Borst




http://ift.tt/2F49ML3

Response to the Commentary on “Post-Carotid Hypertension Part 2: Association with Peri-operative Clinical, Anaesthetic, and Transcranial Doppler Derived Parameters”

Publication date: Available online 28 February 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Jeremy Edward Newman, A. Ross Naylor




http://ift.tt/2FF7V0e

The role of digital communication in patient–clinician communication for NHS providers of specialist clinical services for young people [the Long-term conditions Young people Networked Communication (LYNC) study]: a mixed-methods study.

Young people with long-term conditions and health professionals value digital consulting for improved health-care access and engagement, but express concerns about cost, ethics and patient safety.

http://ift.tt/2EZqQWq