Sheep Model for Uterine Transplantation: The Best Option Before Starting a Human Program

OBJECTIVE: This study reports the first four cases of a uterine transplant procedure conducted in sheep in Latin America. The aim of this study was to evaluate the success of uterine transplantation in sheep. METHOD: The study was conducted at Laboratory of Medical Investigation 37 (LIM 37) at the University of São Paulo School of Medicine. Four healthy mature ewes weighing 40-60 kg were used as both the donor and recipient for a transplant within the same animal (auto-transplant). Institutional guidelines for the care of experimental animals were followed. RESULTS: The first two cases of auto-transplant were performed to standardize the technique. After complete uterine mobilization and isolation of the blood supply, the unilateral vascular pedicle was sectioned and anastomosed on the external iliac vessels. After standardization, the protocol was implemented. Procurement surgery was performed without complications or bleeding. After isolation of uterine arteries and veins as well as full mobilization of the uterus, ligation of the distal portion of the internal iliac vessels was performed with subsequent division and end-to-side anastomosis of the external iliac vessels. After vaginal anastomosis, the final case presented with arterial thrombosis in the left uterine artery. The left uterine artery anastomosis was re-opened and flushed with saline solution to remove the clot from the artery lumen. Anastomosis was repeated with restoration of blood flow for a few minutes before another uterine artery thrombosis appeared on the same side. All four animals were alive after the surgical procedure and were euthanized after the experimental period. CONCLUSION: We describe the success of four uterine auto-transplants in sheep models.

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The acceptability of vaginal smear self-collection for screening for cervical cancer: a systematic review

Cervical cancer is a major cause of death in adult women. However, many women do not undergo cervical cancer screening for the following reasons: fear, shame, physical limitations, cultural or religious considerations and lack of access to health care services. Self-collected vaginal smears maybe an alternative means of including more women in cervical cancer screening programs. The objective of this systematic review was to evaluate the acceptability of vaginal smear self-collection for cervical cancer screening. We selected articles from PubMed, the Cochrane Library and Embase that were published between January 1995 and April 2016. Studies written in English, French, Italian, Portuguese or Spanish that involved women between 18 and 69 years of age who had engaged in sexual intercourse were included in this review. The review was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Nineteen studies were ultimately evaluated in this review. Most of the included studies (n=17) demonstrated that the self-collection method exhibited outstanding acceptability among women with respect to cervical cancer screening, and only two studies indicated that self-collection exhibited low acceptability among women in this context. The acceptability of self-collection was determined subjectively (without standardized questionnaires) in 10 studies (53%) and via structured and validated questionnaires in the remaining studies. The results of our review suggest that the self-collection method is well-accepted and may therefore encourage greater participation in cervical cancer screening programs. However, additional studies are required to verify these results.

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Diagnostic models of the pre-test probability of stable coronary artery disease: A systematic review

A comprehensive search of PubMed and Embase was performed in January 2015 to examine the available literature on validated diagnostic models of the pre-test probability of stable coronary artery disease and to describe the characteristics of the models. Studies that were designed to develop and validate diagnostic models of pre-test probability for stable coronary artery disease were included. Data regarding baseline patient characteristics, procedural characteristics, modeling methods, metrics of model performance, risk of bias, and clinical usefulness were extracted. Ten studies involving the development of 12 models and two studies focusing on external validation were identified. Seven models were validated internally, and seven models were validated externally. Discrimination varied between studies that were validated internally (C statistic 0.66-0.81) and externally (0.49-0.87). Only one study presented reclassification indices. The majority of better performing models included sex, age, symptoms, diabetes, smoking, and hyperlipidemia as variables. Only two diagnostic models evaluated the effects on clinical decision making processes or patient outcomes. Most diagnostic models of the pre-test probability of stable coronary artery disease have had modest success, and very few present data regarding the effects of these models on clinical decision making processes or patient outcomes.

http://ift.tt/2nIwOl5

Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer

Publication date: Available online 23 March 2017
Source:Cancer Cell
Author(s): Xiaoju Wang, Yuanyuan Qiao, Irfan A. Asangani, Bushra Ateeq, Anton Poliakov, Marcin Cieślik, Sethuramasundaram Pitchiaya, Balabhadrapatruni V.S.K. Chakravarthi, Xuhong Cao, Xiaojun Jing, Cynthia X. Wang, Ingrid J. Apel, Rui Wang, Jean Ching-Yi Tien, Kristin M. Juckette, Wei Yan, Hui Jiang, Shaomeng Wang, Sooryanarayana Varambally, Arul M. Chinnaiyan
Transcription factors play a key role in the development of diverse cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the gene encoding the transcription factor ERG is recurrently rearranged and plays a critical role in prostate oncogenesis. Here, we identified a series of peptides that interact specifically with the DNA binding domain of ERG. ERG inhibitory peptides (EIPs) and derived peptidomimetics bound ERG with high affinity and specificity, leading to proteolytic degradation of the ERG protein. The EIPs attenuated ERG-mediated transcription, chromatin recruitment, protein-protein interactions, cell invasion and proliferation, and tumor growth. Thus, peptidomimetic targeting of transcription factor fusion products may provide a promising therapeutic strategy for prostate cancer as well as other malignancies.

Teaser

Wang et al. identify peptides that interact with the DNA binding domain of ERG, thereby attenuating protein-protein interactions and chromatin recruitment of ERG and inducing ERG degradation. These peptides reduce proliferation, invasion, and tumor growth of prostate cancer cells with the TMPRSS2:ERG gene fusion.


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m6A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program

Publication date: Available online 23 March 2017
Source:Cancer Cell
Author(s): Sicong Zhang, Boxuan Simen Zhao, Aidong Zhou, Kangyu Lin, Shaoping Zheng, Zhike Lu, Yaohui Chen, Erik P. Sulman, Keping Xie, Oliver Bögler, Sadhan Majumder, Chuan He, Suyun Huang
The dynamic and reversible N⁶-methyladenosine (m⁶A) RNA modification installed and erased by N⁶-methyltransferases and demethylases regulates gene expression and cell fate. We show that the m⁶A demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs. Integrated transcriptome and m⁶A-seq analyses revealed altered expression of certain ALKBH5 target genes, including the transcription factor FOXM1. ALKBH5 demethylates FOXM1 nascent transcripts, leading to enhanced FOXM1 expression. Furthermore, a long non-coding RNA antisense to FOXM1 (FOXM1-AS) promotes the interaction of ALKBH5 with FOXM1 nascent transcripts. Depleting ALKBH5 and FOXM1-AS disrupted GSC tumorigenesis through the FOXM1 axis. Our work uncovers a critical function for ALKBH5 and provides insight into critical roles of m⁶A methylation in glioblastoma.

Graphical abstract

Teaser

Zhang et al. reveal that elevated RNA m⁶A demethylase ALKBH5 in glioblastoma stem-like cells enhances self-renewal and tumorigenesis through regulation of FOXM1. The lncRNA antisense to FOXM1 promotes the interaction of ALKBH5 with FOXM1 nascent RNA, leading to demethylation and elevated expression of FOXM1.


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PDL-1 Targeting in Resectable Oesophageal Cancer: a Phase II Feasibility Study of Atezolizumab and Chemoradiation

Conditions:   Esophageal Cancer, Stage II;   Esophageal Cancer Stage III
Interventions:   Drug: Atezolizumab;   Drug: Carboplatin;   Drug: Paclitaxel;   Radiation: Radiotherapy 23 x 1.8 Gy
Sponsors:   Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA);   UMC Utrecht
Not yet recruiting - verified March 2017

http://ift.tt/2nInde6

Biomarker-based Study in R/M SCCHN

Condition:   Carcinoma, Squamous Cell of Head and Neck
Interventions:   Drug: Afatinib;   Drug: Palbociclib;   Drug: IPH2201;   Drug: standard of care
Sponsor:   European Organisation for Research and Treatment of Cancer - EORTC
Not yet recruiting - verified March 2017

http://ift.tt/2mVxUp6

Hypovitaminosis D in patients with heart failure: effects on functional capacity and patients’ survival

Abstract

Chronic heart failure is a major cause of morbidity and mortality, but its prognosis remains poor. Vitamin D hormone has many extra-skeletal functions including a positive impact on the cardiovascular system, and has been proposed for mortality risk evaluation in heart failure patients. The aim of the present study was to evaluate vitamin D status in heart failure patients, measured by high performance liquid chromatography coupled with mass spectrometry and to correlate serum 25 hydroxy-vitamin D (25OHD) levels with functional (peak VO₂%) and mortality (Metabolic Exercise Cardiac Kidney Index) heart failure parameters. We enrolled 261 consecutive patients diagnosed with heart failure; all patients underwent a comprehensive clinical and biochemical characterization, and serum 25OHD levels were measured by high performance liquid chromatography coupled with mass spectrometry. Cardiopulmonary test parameters and Metabolic Exercise Cardiac Kidney Index of mortality risk were measured in all patients. Serum 25OHD levels ranged between 2 and 45 ng/ml (mean 17 ± 9 ng/ml); most patients (87%) showed hypovitaminosis D, and 25% showed severe vitamin D deficiency (serum 25OHD < 10 ng/ml). Patients with 25OHD < 10 ng/ml had significantly lower cardiopulmonary test VO₂/kg, peak VO₂% and significantly higher N-terminalproBrain natriuretic peptide and Metabolic Exercise Cardiac Kidney Index, than patients with 25OHD > 10 ng/ml. Patients with peak VO₂% < 50% showed significantly lower 25OHD compared to those with peak VO₂% > 50%. There was a significant, positive correlation (r = 0.16, p = 0.008) between 25OHD levels and peak VO₂%, and an inverse correlation with Metabolic Exercise Cardiac Kidney Index (r = −0.21, p < 0.001), even when adjusted for age, Body Mass Index, MDRD, N-terminalproBrain natriuretic peptide. In conclusion, our findings show that vitamin D levels are associated with functional and mortality heart failure prognosis parameters.

http://ift.tt/2nc8dSU

Effects of a sustained release formulation of 1,25-dihydroxyvitamin D3-glycosides for milk fever prevention on serum 1,25-dihydroxyvitamin D3, calcium and phosphorus in dairy cows

Publication date: Available online 23 March 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Heinrich Bachmann, Michael Lanz, Susanne Kehrle, Wolfgang Bittner, Annick Toggenburger, Georg A. Mathis, Walter Rambeck
Milk fever (MF) is a metabolic disease in dairy cows around parturition. The clinical lead sign is muscular paresis leading in severe cases to paralysis of the affected animal. Multiparturient animals of high performing dairy breeds are most likely to be affected and have a high probability of recurrence. An acute drop in blood calcium levels causes the disease when the demand for calcium at the onset of lactation exceeds the ability to replete blood calcium levels through mobilization from bone and intestinal uptake. With the understanding of the underlying mechanism, calcium supply management and vitamin D supplementation became prime candidates for MF prevention and therapy. Several strategies have been developed for MF prevention. Application of the active form of Vitamin D, 1,25(OH)2D3, was found to prevent MF effectively. In order to prevent a delayed hypocalcemia, which was occasionally seen after stopping the treatment with 1,25(OH)2D3, a new approach was chosen by applying Solanum glaucophyllum extract (SGE), which contains 1,25(OH)2D3-glycosides, as instant-release (irSGE) in combination with slow-release (srSGE) tablets.In a first study, non-lactating cows were treated with a single bolus of either synthetic 1,25(OH)2D3, irSGE, or srSGE and the results were compared to a control group without treatment. Blood serum levels of 1,25(OH)2D3 (1,25D), calcium (Ca), phosphate (P) and magnesium (Mg) were followed for 11days and the area under the curve (AUC) was calculated. Calcium and phosphate excretion in urine were determined during 15 days. While serum concentration of 1,25(OH)2D3 was back to pre-treatment level in the irSGE, srSGE and 1,25(OH)2D3 treated group within 3 days, calcium and phosphate levels remained elevated for up to 9 days. AUC of serum 1,25(OH)2D3 was 2.89 (1,25D), 3.13 (irSGE) and 4.21 (srSGE) times higher than control. Serum calcium levels were 1.07^* (for 1.25D); 1.08^* (for irSGE) and 1.12^* (for srSGE) times higher than control. Serum phosphate levels were 1.20^* (for 1,25D); 1.30^* (for irSGE) and 1.41^* (for srSGE) times higher than control, with ^* p<0.05. In a second field study calving cows treated with one bolus containing ir- and sr- tablets of SGE were compared to an untreated control group and to a group treated with 4 boli of commercial calcium salts. As a result, calcium serum levels increased (+19% compared to baseline) around calving after treatment with the single bolus of SGE. The single bolus of SGE lead also to an increase of serum phosphate (+31% compared to baseline). These calcium and phosphate increases were statistically significant (p<0.001) 0–24hours after calving compared to the control group and to the group treated with calcium salts. The sample size of the study was too small to draw a conclusion on the effect on MF prevention.In conclusion, application of a single bolus of a SGE extract lead to an increase of serum calcium and phosphate for up to 9days and may thus have the potential to prevent a hypocalcemia and −phosphatemia, an important cause for clinical milk fever.



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Ovarian cancer with metastatic inguinal lymphadenopathy: A case series and literature review

Publication date: Available online 20 March 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Islam H. Metwally, Mohammad Zuhdy, Amr Hassan, Reham Alghandour, Nirmeen Megahed
Background: Ovarian cancer is the 4th commonest cancer among Egyptian women. It can spread through 3 different lymphatic pathways to para-aortic/paracaval lymph nodes, to pelvic lymph nodes and only occasionally through the round ligament of the uterus to the inguinal nodes. These rare cases are staged IVb on FIGO system. Presentation: We present a series of 4 cases of ovarian cancer metastasizing to inguinal nodes. The literature review revealed only 17 published similar cases. Management controversies as well as prognosis are discussed in our study. Conclusion: Inguinal metastasis from ovarian cancer seems more frequent than previously thought. Examination of inguinal region should be mandatory in all cases diagnosed with ovarian cancer.



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Accelerated hypofractionated adjuvant whole breast radiation with simultaneous integrated boost using volumetric modulated arc therapy for early breast cancer: A phase I/II dosimetric and clinical feasibility study from a tertiary cancer care centre of India

Publication date: March 2017
Source:Journal of the Egyptian National Cancer Institute, Volume 29, Issue 1
Author(s): Dodul Mondal, Pramod Kumar Julka, Daya Nand Sharma, Manisha Jana, Macharla Anjaneyelu Laviraj, Suryanarayan VS Deo, Soumyajit Roy, Randeep Guleria, Goura K. Rath
BackgroundHypofractionation has become standard of care after Breast Conserving Therapy (BCT) in many European and few others western countries. Though still debatable, tumor cavity boost is routinely practised in our centre. Hypofractionation is not yet the current standard of practice in Asian countries. Employing hypofractionation and simultaneous integrated boost to lumpectomy cavity with conformal technique is not the current practice in this region. Hence the study was performed to see whether accelerated hypofractionation and simultaneous boost can be combined using volumetric modulated arc therapy (VMAT) in treating early breast cancer (EBC) patients.Patients and methodsFemale patients with EBC treated by whole breast radiation and boost were treated simultaneously to a dose of 40.5Gy and 48Gy in fifteen fractions over three weeks to entire breast and tumor cavity respectively with VMAT. Dosimetry including target coverage, OAR (organ at risk) sparing and acute radiation toxicity were evaluated.ResultsTen consecutive patients were treated. Planning target volume (PTV) coverage and OAR sparing were mostly satisfactory. Mean volume of PTVWB and PTVBoost were 786.18cm³ and 228.9cm³ respectively. Mean Dmean to PTVWB and PTVBOOST were 41.9Gy and 49.1Gy respectively. Dmax to PTVWB and PTVBOOST were 127.56% and 110.67% respectively. Ipsilateral lung mean dose and V20 were 13.92Gy and 21.53% respectively. V40 and V25 of heart were 0.17% and 2.25% respectively. All patients are disease free after a median follow up of two years. Most acute toxicities were Grade1. Only two patients out of ten developed Grade 2 skin reaction during radiation. Early cosmesis using Harvard cosmesis scale is good to excellent.ConclusionsAccelerated hypofractionated RT using SIB-VMAT is a clinically feasible technique with acceptable initial result. Initial results are encouraging.Mini abstractSimultaneous integrated boost with accelerated hypofractionated whole breast radiotherapy using Volumetric Modulated Arc Therapy is a novel approach. Patient selection and technical considerations are of paramount importance. The present study describes successful implementation of this approach.



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Risk stratification and pattern of cardiotoxicity in pediatric Ewing sarcoma

Publication date: March 2017
Source:Journal of the Egyptian National Cancer Institute, Volume 29, Issue 1
Author(s): Emad Moussa, Manal Zamzam, Ahmed Kamel, Zeinab Salah, Iman Attia, Lina Gaber, Ranin Soliman, Sameera Ezzat
IntroductionAnthracycline chemotherapy contributes to improved outcomes in Ewing sarcoma; however, the most feared complication is cardiotoxicity. Echocardiograms were routinely used to monitor cardiac function after anthracycline treatment. Nevertheless, indices chosen to assess cardiac toxicity vary significantly among different centers, and no uniform protocol has been accepted as ideal.MethodsThis retrospective study included children with Ewing sarcoma treated at Children's Cancer Hospital Egypt over 4years. All echocardiograms and related clinical assessments were reviewed.ResultsIn total, 149 patients (median age 11years; range 1–18years) were included. Although all patients had a reduced ejection fraction compared with their baseline echocardiogram, only 39 patients developed cardiotoxicity (26%): 43% acute-onset, 36% chronic early-onset, and 21% chronic late-onset. There were no statistically significant association between the frequency of myocardial dysfunction and risk factors, including age, sex, follow-up duration, cumulative doxorubicin dose, and mediastinal irradiation. Over one-third (39%) of the patients with cardiac toxicity regained normal cardiac parameters, whereas seven patients died of acute cardiac toxicity.ConclusionThe routine use of echocardiography to screen for anthracycline-induced cardiac toxicity before and during chemotherapy identified myocardial dysfunction. Early medical intervention can improve cardiac parameters. Improved screening techniques with better sensitivity and predictability are needed.



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2016 Reviewer Acknowledgements

Publication date: March 2017
Source:Journal of the Egyptian National Cancer Institute, Volume 29, Issue 1





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Mechanical and Biological Effects of Ultrasound: A Review of Present Knowledge

Publication date: Available online 23 March 2017
Source:Ultrasound in Medicine & Biology
Author(s): Zahra Izadifar, Paul Babyn, Dean Chapman
Ultrasound is widely used for medical diagnosis and increasingly for therapeutic purposes. An understanding of the bio-effects of sonography is important for clinicians and scientists working in the field because permanent damage to biological tissues can occur at high levels of exposure. Here the underlying principles of thermal mechanisms and the physical interactions of ultrasound with biological tissues are reviewed. Adverse health effects derived from cellular studies, animal studies and clinical reports are reviewed to provide insight into the in vitro and in vivo bio-effects of ultrasound.



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Efficacy and safety of omalizumab in Japanese and Korean patients with refractory chronic spontaneous urticaria

Publication date: Available online 21 March 2017
Source:Journal of Dermatological Science
Author(s): Hide Michihiro, Park Hae-Sim, Igarashi Atsuyuki, Ye Young-Min, Kim Tae-Bum, Yagami Akiko, Roh Jooyoung, Lee Jae-Hyun, Chinuki Yuko, Youn Sang Woong, Lee Soo-Keol, Inomata Naoko, Choi Jeong-Hee, Fukunaga Atsushi, Wang Junyi, Matsushima Soichiro, Greenberg Steve, Khalil Sam
BackgroundMany patients with chronic spontaneous/idiopathic urticaria (CSU/CIU) do not respond adequately to treatment with non-sedating H1 antihistamines (H1AH). There are limited studies on use of omalizumab as add-on therapy for treatment of CSU in an Asian population.ObjectiveThe POLARIS study (NCT02329223), representing the first randomized, double-blind, placebo-controlled phase III trial of omalizumab for CSU in an Eastern Asian population, evaluated efficacy and safety of omalizumab as add-on therapy for treatment of CSU.MethodsThis 26-week multicenter (41 Japanese/Korean sites) study enrolled patients (12–75 years) who were symptomatic despite H1AH treatment. Eligible participants (N=218) were randomized 1:1:1 to receive three subcutaneous injections of omalizumab 300mg, 150mg, or placebo every 4 weeks, followed by 12 weeks of follow-up. Primary outcome was change from baseline to Week 12 (Wk12) in weekly itch severity score (ISS7). Safety was assessed through the summary of adverse events (AEs).ResultsBaseline demographics and disease characteristics were generally well balanced across treatment groups. At Wk12, statistically significant decreases from baseline were observed in ISS7 with omalizumab vs placebo (mean changes −10.22, −8.80, and −6.51 for omalizumab 300mg, 150mg and placebo; p <0.001 and p=0.006 vs placebo, respectively). Overall AE incidence was similar across treatment groups (54.8%, 57.7%, and 55.4% in omalizumab 300mg, 150mg, and placebo groups, respectively); nasopharyngitis was the most frequently reported AE in all treatment arms.ConclusionThe POLARIS study demonstrates that omalizumab is an efficacious and well-tolerated add-on therapy in Japanese and Korean H1AH-refractory patients with CSU.



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Vascular Psoriasis Area Severity Index: a dermoscopic standard technique for assessing severity psoriasis and therapeutic management

Publication date: Available online 21 March 2017
Source:Journal of Dermatological Science
Author(s): M. Carlesimoa, V. Garelli, M.C. Fortuna, G. De Vita, L. Sorriso-Valvo, F. Buccolini, A. Melini, D. Di Nunno, G. Pranteda, A. Rossi




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A similar local immune and oxidative stress phenotype in vitiligo and halo nevus

Publication date: Available online 19 March 2017
Source:Journal of Dermatological Science
Author(s): Yuqi Yang, Shuli Li, Guannan Zhu, Qian Zhang, Gang Wang, Tianwen Gao, Chunying Li, Lin Wang, Zhe Jian
BackgroundVitiligo and halo nevus are two common T-cell-mediated skin disorders. Although autoimmunity has been suggested to be involved in both diseases, the relationship between vitiligo and halo nevus is not fully understood.ObjectiveThe aim of the current study was to investigate whether vitiligo and halo nevus share the same immunological and oxidative stress response.MethodsInfiltrations of T cells, and expressions of chemokine receptors (CXCR3, CCR4, CCR5) and cytotoxic markers (Granzyme B, Perforin) in the lesions of vitiligo and halo nevus were examined by immunohistochemistry. Enzyme-linked immunosorbent assay was performed to analyze the expressions of chemokines in the serum samples and cytotoxic markers secreted by CD8⁺ T cells which were sorted from the peripheral blood mononuclear cells in healthy donors, vitiligo and halo nevus patients. Tissue levels of chemokine receptors and CXCR3 ligands in healthy controls, vitiligo patients and halo nevus patients were determined by qRT-PCR analysis. The percentages of CXCR3⁺ CD4⁺ T and CXCR3⁺ CD8⁺ T cells from the peripheral blood samples were examined by flow cytometry. Tissue and serum hydrogen peroxide (H2O2) concentrations were measured using H2O2 assay kit.ResultsImmunohistochemistry revealed a significant T-cell response, with pronounced dermal infiltrates of CD8⁺ T cells in vitiligo and halo nevus. The inflammatory cytotoxic markers such as Granzyme B and Perforin were also elevated in vitiligo and halo nevus, suggesting inflammatory responses in situ. By qRT-PCR and ELISA assay, we found significantly increased expressions of the chemokine receptor CXCR3 and its ligands, especially the accumulated CXCL10 in the skin lesions of vitiligo and halo nevus. Moreover, the level of H2O2, a key player involved in regulation of the immune response was significantly upregulated in the skin lesions of vitiligo and halo nevus. In addition, the increased H2O2 concentration correlated positively with CXCL10 level in skin lesions of vitiligo and halo nevus.ConclusionsThese results demonstrate a H2O2-involved autoimmune phenotype in vitiligo and halo nevus, characterized by increased level of IFN-γ-inducible chemokine pair CXCL10-CXCR3, as well as a dense CD8⁺ T infiltration in the skin lesions, thus suggesting a similar pathogenesis of the two diseases.



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Novel interferon-γ enzyme-linked immunoSpot assay using activated cells for identifying hypersensitivity-inducing drug culprits

Publication date: Available online 14 March 2017
Source:Journal of Dermatological Science
Author(s): Kenichi Kato, Asami Kawase, Hiroaki Azukizawa, Takaaki Hanafusa, Yukinobu Nakagawa, Hiroyuki Murota, Shimon Sakaguchi, Hideo Asada, Ichiro Katayama
BackgroundThe drug-induced lymphocyte stimulation test (DLST), also referred to as lymphocyte transformation test (LTT), is used to identify the culprit drug in cases of cutaneous adverse drug reactions (cADR). Although DLST is a widely used in vitro test, its sensitivity and specificity are unsatisfactory. Recent reports suggest that the detection of drug-induced interferon (IFN)-γ production using enzyme-linked immunoSpot (ELISpot) assay (conventional IFN-γ ELISpot) is useful for identifying culprit drugs in cADR cases.ObjectiveThe aim of this study was to establish a novel method for identifying culprit drugs in patients with cADR by efficiently detecting drug-specific IFN-γ production using activated cells.MethodsSixteen patients with cADR, including drug-induced hypersensitivity syndrome, erythema multiforme-like eruption, maculopapular exanthema, Stevens-Johnson syndrome, and toxic epidermal necrolysis, caused by clinically convincing culprit drugs were enrolled in this study. In some cases, the blood samples were obtained at two or three different time points. Peripheral blood mononuclear cells (PBMCs) from total 20 samples were analyzed using both the DLST and drug-induced conventional IFN-γ ELISpot. In addition, drug-induced IFN-γ ELISpot was performed using PBMCs, which were stimulated with anti-cluster of differentiation (CD)-3/CD28 antibody-coated microbeads and interleukin (IL)-2 for 7 days before exposure to the culprit drugs (modified IFN-γ ELISpot).ResultsAmong the culprit drugs tested in each patient, the modified IFN-γ ELISpot was positive in 17 samples (13 patients) while DLST and conventional IFN-γ ELISpot were positive in eight and four samples (six and three patients), respectively.ConclusionThe modified IFN-γ ELISpot using activated PBMCs was more sensitive than the conventional IFN-γ ELISpot was for detecting drug-induced IFN-γ production, which could be a useful in vitro tool for identifying culprit drugs in cADR cases.



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Central nervous system gliomas

Publication date: Available online 22 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Michele Reni, Elena Mazza, Silvia Zanon, Gemma Gatta, Charles J. Vecht
Evidence-based practical guidelines on diagnosis, prognosis, and treatment on the most frequent adult brain tumours are delineated. In Europe, 27,000 new cases of malignant glial tumours and 1,000 new cases of malignant ependymal tumours are diagnosed every year. The most common glial tumours are glioblastoma multiforme and anaplastic glioma, comprising more than 50% and 10%, respectively, of the total gliomas.Prognosis of gliomas is generally poor. Environmental and genetic factors have been correlated with an increased risk of developing brain tumours.Surgical resection represents the first treatment option for all histotypes.Role and timing of radiotherapy and chemotherapy as well as treatment for recurrent/progressive disease should be based on age, performance status, histopathological diagnosis, molecular markers, and previous therapy. Impaired neurocognitive and neuropsychological function is common in long-term survivors, regardless of the histology and grade of the tumour and should be taken into account in treatment planning.



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Review of current evidence available for guiding optimal Enoxaparin prophylactic dosing strategies in obese patients—Actual Weight-based vs Fixed

Publication date: Available online 22 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Zikai He, Hana Morrissey, Patrick Ball
BackgroundThe current debate over the optimal Enoxaparin prophylactic dosing strategies in obese patients centre around whether it should be based on the actual weight of the patient (i.e. weight-based), or at an artificially fixed amount, as it is the case in Australia (40mg daily). The vast majority of the evidence available today is laboratory-based, measuring serum Antifactor-Xa activities as a marker for physiological response.AimThe aim of the parent study is to compare the clinical outcomes for obese patients who received fixed doses of enoxaparin compared to those who received weight-based doses within the licensed dosage recommendations. This review was conducted to examine whether a gap in knowledge exists in relation to dosing obese patients with enoxaparin as VTE prophylaxis after hospital admission to aid in development of the parent study concept.MethodDatabases such as Medline, EBSCOhost, ProQuest were interrogated using combinations of words such as "enoxaparin", AND "dosing strategy", AND "obese/obesity" AND "prophylaxis". Only eleven out of 14 primary studies which were considered to be sufficiently similar in methodology and anticipated outcomes were reviewed and analysed.ResultsPooled data from the eleven studies suggested that weight-based or higher-than-fixed dosing had a 36.2% higher success rate than fixed dosing, and was more likely to achieve the desired serum Anti-Xa activity levels (52.2% and 16% respectively). The rate of failure to achieve this is significantly lower in the weight-based groups (13.3%) than in fixed-dose groups (18.5%). These eleven studies reviewed included 601 patients in total.ConclusionThere is insufficient evidence to support or negate the current enoxaparin health outcomes in obese and very obese patients due to the lack of post-discharge follow-up from hospitals. Further research is required to compare long-term outcomes after fixed and weight-based dosing of enoxaparin. The optimal dose of enoxaparin per kilogram of body weight for prophylaxis remains to be determined.



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Increase in sensory sensitivity around, but not in the central part of, the hyperkeratotic papule in lichen amyloidosis

Abstract

Lichen amyloidosis (LA) is an itchy skin disorder characterized by amyloid deposits in the superficial dermis. Pruritus is the presenting symptom in 90% of LA patients.¹ However, the underlying mechanisms and mediators of pruritus in LA remain unclear.

One LA patient complained of severe pruritus in the hyperkeratotic papules, especially around the papule.

This article is protected by copyright. All rights reserved.

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Burden of respiratory comorbidities in patients with atopic dermatitis and psoriasis

Abstract

Atopic dermatitis (AD), a skin disease with an estimated lifetime prevalence of up to 20%, represents a major global healthcare burden.¹ Patients with AD have a propensity to develop asthma due to a combination of genetic, immunological and environmental factors, yet descriptive studies on the impact of respiratory diseases in adults with AD are scarce.² In contrast, psoriasis, another chronic inflammatory skin disease, has been associated with respiratory comorbidities such as chronic obstructive pulmonary disease (COPD)³, asthma⁴ and obstructive sleep apnea (OSA).

This article is protected by copyright. All rights reserved.

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Developing Cognitive Task Analysis–based Educational Videos for Basic Surgical Skills in Plastic Surgery

Publication date: Available online 23 March 2017
Source:Journal of Surgical Education
Author(s): Celine Yeung, Catherine McMillan, Tomas J. Saun, Kimberly Sun, Veerle D'hondt, Herbert P. von Schroeder, Glykeria Martou, Matthew Lee, Elizabeth Liao, Paul Binhammer
ObjectiveTo describe the development of cognitive task analysis (CTA)-based multimedia educational videos for surgical trainees in plastic surgery.DesignA needs assessment survey was used to identify 5 plastic surgery skills on which to focus the educational videos. Three plastic surgeons were video-recorded performing each skill while describing the procedure, and were interviewed with probing questions. Three medical student reviewers coded transcripts and categorized each step into "action," "decision," or "assessment," and created a cognitive demands table (CDT) for each skill. The CDTs were combined into 1 table that was reviewed by the surgeons performing each skill to ensure accuracy. The final CDTs were compared against each surgeon's original transcripts. The total number of steps identified, percentage of steps shared, and the average percentage of steps omitted were calculated.SettingSunnybrook Health Sciences Centre, Toronto, Ontario, Canada, an urban tertiary care teaching center.ParticipantsCanadian junior plastic surgery residents (n = 78) were sent a needs assessment survey. Four plastic surgeons and 1 orthopedic surgeon performed the skills.ResultsTwenty-eight residents responded to the survey (36%). Subcuticular suturing, horizontal and vertical mattress suturing, hand splinting, digital nerve block, and excisional biopsy had the most number of residents (>80%) rank the skills as being skills that students should be able to perform before entering residency. The number of steps identified through CTA ranged from 12 to 29. Percentage of steps shared by all 3 surgeons for each skill ranged from 30% to 48%, while the average percentage of steps that were omitted by each surgeon ranged from 27% to 40%.ConclusionsInstructional videos for basic surgical skills may be generated using CTA to help experts provide comprehensive descriptions of a procedure. A CTA-based educational tool may give trainees access to a broader, objective body of knowledge, allowing them to learn decision-making processes before entering the operating room.



http://ift.tt/2mUSl5A

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for rapid identification of Mycobacterium abscessus

Publication date: Available online 23 March 2017
Source:Medical Journal Armed Forces India
Author(s): Raghu Sriram, A.K. Sahni, Vaibhav L. Dudhat, A.K. Pujahari
BackgroundNontuberculous mycobacteria are increasingly being implicated in infections and have become an important cause of health care associated infections. Mycobacterium abscessus, a rapidly growing mycobacteria, is of particular concern as it tends to be resistant to commonly used therapeutic options. Conventional phenotypic methods for speciation of mycobacteria are time consuming, labor intensive and not always reliable. Molecular methods require expertise and are expensive. The study was used to evaluate the use of matrix associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) as a means of rapid identification of M. abscessus.Methods35 isolates of rapidly growing Mycobacterium from an outbreak of surgical site infections at a tertiary care hospital were identified using phenotypic methods. The mycobacterial isolates were inactivated and an extraction protocol was followed. These isolates were then analyzed by MALDI biotyper (Bruker Daltonics) using biotyper software 4.0 and the mycobacterial reference database v 2.0.ResultsAll 35 isolates were identified as M. abscessus by MALDI biotyper but the scores obtained according to guidelines of the company were lower than previous studies with only 23 out of the 35 isolates having scores of greater 1.8 which was described as the minimum score to be achieved for reliable identification.ConclusionMALDI-TOF MS offers a rapid and inexpensive method for identification of Mycobacteria; however, the scores obtained in our study were lower than reported in other studies.



http://ift.tt/2nHqw5j

Ultraviolet A-induced oxidation in cornea: Characterization of the early oxidation-related events

Publication date: Available online 22 March 2017
Source:Free Radical Biology and Medicine
Author(s): Corinne Zinflou, Patrick J. Rochette
Exposure to sunlight ultraviolet-A (UVA), the main component of solar UV reaching the eyes, is suspected to play an important part in the onset of ocular pathologies. UVA primary biological deleterious effects arise from the photo-induction of oxidative stress in cells. However, the molecular bases linking UVA-induced oxidation to UVA toxicity in eyes remain poorly understood, especially with regards to the cornea. To shed some light on this issue, we have investigated the susceptibility and response potential of the different corneal cellular layers (epithelium, stroma and endothelium) to UVA-induced oxidation. We have monitored UVA-induced immediate effects on cellular redox balance, on mitochondrial membrane potential, on 8-Hydroxy-2'-deoxyguanosine (8-OHdG) accumulation in cellular DNA and on S-glutathionylated proteins (PSSG) levels along whole rabbit corneas. Higher redox imbalance was observed in the posterior part of the cornea following irradiation. Conversely, UVA-altered mitochondrial membrane potentials were observed only in anterior portions of the cornea. UVA-induced 8-OHdG were found in nuclear DNA of epithelia, while they were found in both nuclear and mitochondrial DNA in stromal and endothelial cells. Finally, significantly higher levels of cytosolic PSSG were measured in epithelia and endothelia immediately after UVA exposure, but not in stromas. Taken together, our findings indicate that while corneal epithelial cells are subjected to important modifications in response to UVA exposure, they efficiently limit the early manifestations of UVA-induced toxicity. On the other hand, the corneal endothelium is more susceptible to UVA-induced oxidation-related toxicity.

Graphical abstract

http://ift.tt/2nMUHZ2

Comparative effects of EtOH consumption and thiamine deficiency on cognitive impairment, oxidative damage, and β-amyloid peptide overproduction in the brain

Publication date: Available online 22 March 2017
Source:Free Radical Biology and Medicine
Author(s): Yu-Shi Gong, Kun Hu, Lu-Qi Yang, Juan Guo, Yong-Qing Gao, Feng-Lin Song, Fang-Li Hou, Cui-Yi Liang
The effects of chronic EtOH consumption, associated or not with thiamine deficiency (TD), on cognitive impairment, oxidative damage, and β-amyloid (Aβ) peptide accumulation in the brain were investigated in male C57BL/6 mice. We established an alcoholic mouse model by feeding an EtOH liquid diet, a TD mouse model by feeding a thiamine-depleted liquid diet, and an EtOH treatment associated with TD mouse model by feeding a thiamine-depleted EtOH liquid diet for 7 weeks. The learning and memory functions of the mice were detected through the Y-maze test. Biochemical parameters were measured using corresponding commercial kits. The Aβ expression in the hippocampus was observed by immunohistochemical staining. Several results were obtained. First, EtOH significantly reduced cognitive function by significantly decreasing the Glu content in the hippocampus; increasing the AChE activity in the cortex; and reducing the thiamine level, and superoxide dismutase (SOD), glutathione peroxidase (GPx), and choline acetyltransferase (ChAT) activities in both the hippocampus and cortex. The treatment also increased the levels of malondialdehyde (MDA), protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), and nitric oxide (NO) and the activities of total nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS), and monoamine oxidase B (MAO-B). Furthermore, EtOH enhanced the expression levels of Aβ1–42 and Aβ1–40 in the hippocampus. Second, TD induced the same dysfunctions caused by EtOH in the biochemical parameters, except for learning ability, 8-OHdG content, and GPx, tNOS, and AChE activities in the cortex. Third, the modification of MDA, protein carbonyl and NO levels, and GPx, iNOS, ChAT, and MAO-B activities in the brain induced by chronic EtOH treatment associated with TD was greater than that induced by EtOH or TD alone. The synergistic effects of EtOH and TD on Aβ1–40 and Glu release, as well as on SOD activity, depended on their actions on the hippocampus or cortex. These findings suggest that chronic EtOH consumption can induce TD, cognitive impairment, Aβ accumulation, oxidative stress injury, and neurotransmitter metabolic abnormalities. Furthermore, the association of chronic EtOH consumption with TD causes dramatic brain dysfunctions with a severe effect on the brain.

Graphical abstract

http://ift.tt/2nMISCe

Na+/K+-ATPase Interaction with Methylglyoxal as Reactive Metabolic Side Product

Publication date: Available online 22 March 2017
Source:Free Radical Biology and Medicine
Author(s): Marika Svrckova, Martina Zatloukalova, Petra Dvorakova, Dominika Coufalova, David Novak, Lenka Hernychova, Jan Vacek
Proteins are subject to oxidative modification and the formation of adducts with a broad spectrum of reactive species via enzymatic and non-enzymatic mechanisms. Here we report that in vitro non-enzymatic methylglyoxal (MGO) binding causes the inhibition and formation of MGO advanced glycation end-products (MAGEs) in Na⁺/K⁺-ATPase (NKA). Concretely, MGO adducts with NKA amino acid residues (mainly Arg) and N^ε-(carboxymethyl)lysine (CML) formation were found. MGO is not only an inhibitor for solubilized NKA (IC50 = 91±16 μM), but also for reconstituted NKA in the lipid bilayer environment, which was clearly demonstrated using a DPPC/DPPE liposome model in the presence or absence of the NKA-selective inhibitor ouabain. High-resolution mass spectrometric analysis of a tryptic digest of NKA isolated from pig (Sus scrofa) kidney indicates that the intracellular α-subunit is naturally (post-translationally) modified by MGO in vivo. In contrast to this, the β-subunit could only be modified by MGO artificially, and the transmembrane part of the protein did not undergo MGO binding under the experimental setup used. As with bovine serum albumin, serving as the water-soluble model, we also demonstrated a high binding capacity of MGO to water-poorly soluble NKA using a multi-spectral methodology based on electroanalytical, immunochemical and fluorimetric tools. In addition, a partial suppression of the MGO-mediated inhibitory effect could be observed in the presence of aminoguanidine (pimagedine), a glycation suppressor and MGO-scavenger. All the results here were obtained with the X-ray structure of NKA in the E1 conformation (3WGV) and could be used in the further interpretation of the functionality of this key enzyme in the presence of highly-reactive metabolic side-products, glycation agents and generally under oxidative stress conditions.

Graphical abstract

http://ift.tt/2nMXwcN

The Genetic Landscape of Small Cell Carcinoma of the Urinary Bladder

This review investigates recent advances in the understanding of the genetics of small cell carcinoma of the urinary bladder and the potential implications in diagnosis, prognosis, and treatment.

http://ift.tt/2nh0zbw

Missing Author Initial in Byline

In the Original Investigation titled "Correlation of Long-term Results of Imatinib in Advanced Gastrointestinal Stromal Tumors With Next-Generation Sequencing Results: Analysis of Phase 3 SWOG Intergroup Trial S0033," published February 9, 2017, in JAMA Oncology,¹ the middle initial of one of the authors was inadvertently omitted from the byline. The first author's full name should have appeared as "Michael C. Heinrich, MD." This article was corrected online.

http://ift.tt/2nbmQpt

Association of HIV Status With Local Immune Response to Anal Squamous Cell Carcinoma

This study compares the local tumor immune microenvironment in anal squamous cell carcinomas from HIV-positive and HIV-negative patients.

http://ift.tt/2ngWeFe

Adjuvant Therapy in Subsets of Gastrointestinal Stromal Tumor

In 1998, the modern era of recognizing gastrointestinal stromal tumor (GIST) as a unique entity began, with a report linking KIT protein expression and gene mutations to the putative cell of origin for GIST. Immunohistochemical detection of the KIT protein provided a tool to distinguish GIST from other types of cancer (particularly leiomyosarcoma). With accurate diagnosis, it became clear that while some cases of metastatic leiomyosarcoma responded to chemotherapy, the response rate of GIST was essentially 0%. Therefore, KIT expression could be used to identify patients with GIST who would not benefit from conventional chemotherapy.

http://ift.tt/2nbm8ZF

Risk of Bias and Heterogeneity—Reply

In Reply We appreciate the interest and comments by Matsumoto et al regarding our article, which assessed the incidence of programmed cell death 1 (PD-1) inhibitor–related pneumonitis in a systematic review and meta-analysis of published trial reports. Risk of bias is certainly an important concept. Indeed, we have assessed publication bias using Begg's and Egger's tests with funnel plots, heterogeneity using Cochrane's Q statistics, and inconsistency by I² statistics, as presented in the Results section. In terms of the risk of bias for individual studies, it should be noted that we have included the original articles that have published the results of the prospective trials of PD-1 inhibitors, to date. These trial studies were conducted according to the detailed trial protocols that were approved by the institutional review boards and were designed to address the important domains of risk of bias assessment described in the established tool. In addition, the trials used National Cancer Institute Common Terminology Criteria for Adverse Events as a unified guideline to assess and grade pneumonitis during therapy. However, we also recognize that trials with small sample sizes may be less trustworthy sources compared with large observational studies with broad eligibility criteria involving typical patient populations. Although inclusion of such observational studies may contribute to evaluation of the incidence of pneumonitis in the real-world setting, such data were not available at the time of the study because PD-1 inhibitors are a novel group of agents that have only recently been approved for treatment of patients with cancer in the clinical setting. The systematic review part of the article was intended to provide the summary of the data of PD-1 inhibitor–related pneumonitis that were available in the early trial publications, to meet the increasing needs in the immuno-oncology community in a timely manner.

http://ift.tt/2nh1Pvi

Risk of Bias and Heterogeneity

To the Editor We read the article by Nishino et al with great interest, and we appreciate the authors' efforts to summarize the incidence of programmed cell death 1 inhibitor–related pneumonitis. However, we would like to express 2 concerns.

http://ift.tt/2nbwbxT

Birth Outcomes Among Adolescent and Young Adult Cancer Survivors

This case-control cohort study compares the birth outcomes of adolescent and young adult cancer survivors with those of women without a cancer diagnosis.

http://ift.tt/2nh2GfK

KIT and PDGFRA Mutations in Patients With Gastrointestinal Stromal Tumor

This exploratory analysis of a randomized clinical trial investigates the effect of KIT and PDGFRA mutations on recurrence-free survival in a population of patients with gastrointestinal stromal tumors treated with surgery and adjuvant imatinib.

http://ift.tt/2nbtP1O

Toxicity detection in water containing heavy metal ions with a self-powered microbial fuel cell-based biosensor

Publication date: 1 June 2017
Source:Talanta, Volume 168
Author(s): Dengbin Yu, Lu Bai, Junfeng Zhai, Yizhe Wang, Shaojun Dong
In this work, a self-powered microbial fuel cell (MFC)-based biosensor was developed for detecting toxicity in water containing heavy metal ions. Experimental conditions containing concentration of potassium ferricyanide, load resistor and glucose concentration were optimized. Six heavy metal ions (2mg/L, Cu²⁺, Hg²⁺, Zn²⁺, Cd²⁺, Pb²⁺ and Cr³⁺) were tested by this biosensor and the inhibition ratios obtained were 12.56%, 13.99%, 8.81%, 9.29%, 5.59% and 1.95%, respectively. The inhibition ratios of 28.13% was also obtained for detecting the laboratory wastewater containing several heavy metal ions. The experimental results exhibited the feasibility and potential of the self-powered biosensor in detecting toxicities in water containing heavy metal ions.

Graphical abstract

http://ift.tt/2mwucHb

An electrochemical bisphenol A sensor based on one step electrochemical reduction of cuprous oxide wrapped graphene oxide nanoparticles modified electrode

Publication date: 1 July 2017
Source:Talanta, Volume 169
Author(s): Rongguang Shi, Jing Liang, Zongshan Zhao, Aifeng Liu, Yong Tian
Bisphenol A (BPA), as an important industrial material, has been widespread concerned in recent years as its endocrine disrupting effect. This study reported a novel bisphenol A sensor via a facile one step electrochemical reduction of graphene oxide (rGO) and cuprous oxide (Cu2O) nanocomposite modified glassy carbon electrodes. The characterization of the fabricated sensor was performed by scanning electron microscopy and X-ray spectroscopy. The prepared Cu2O-rGO electrode presented fast response, high sensitivity and low background current. The response of BPA on prepared electrode was 2.15 times higher than reduced graphene modified electrode. Under the optimized experimental parameters, the detection range of the modified electrode was from 1×10⁻⁷ to 8×10⁻⁵ M and the limit of detection was 5.3×10⁻⁸ M (S/N =3). The prepared Cu2O-rGO modified electrode has been successfully used for detecting BPA in environmental water samples.

Graphical abstract

http://ift.tt/2mwqeOM

Thrombin aptasensor enabled by Pt nanoparticles-functionalized Co-based metal organic frameworks assisted electrochemical signal amplification

Publication date: 1 July 2017
Source:Talanta, Volume 169
Author(s): Yang Yang, Zhehan Yang, Jiajia Lv, Ruo Yuan, Yaqin Chai
In this work, a Pt nanoparticles-functionalized Co-based metal organic frameworks (PtNPs@Co(II)MOFs@PtNPs) was synthesized and applied in electrochemical aptasensor for thrombin (TB) detection. First, the Co(II)MOFs@PtNPs were prepared via the mixed solvothermal method, which consists of inner Pt nanoparticles (PtNPs) encapsulated by aminofunctionalized Co(II)MOFs materials. Following that, additional PtNPs were adsorbed on the surface of Co(II)MOFs@PtNPs, resulting in the formation of PtNPs@Co(II)MOFs@PtNPs nanocomposite. The PtNPs@Co(II)MOFs@PtNPs nanocomposites with a large surface area were implimented as nanocarriers to immobilize a mass of TBA II for the formation of the TBA II bioconjugates that could be captured onto the electrode surface by sandwich-type format. Moreover, the PtNPs@Co(II)MOFs@PtNPs nanocomposites could directly use as redox tags for charge-generating and electron-transporting with the electron transfer from Co(II) to Co(III). Furthermore, in the presence of H2O2, the PtNPs@Co(II)MOF@PtNPs could effectively catalyze H2O2 oxidation with improvement electron transfer of redox probe, resulting in electrochemical signal amplification. Based on the above superior advantages, TB was determined in the concentration range from 0.1pM to 50nM with a detection limit of 0.33fM. Furthermore, the excellent sensitivity and selectivity can be easily established for quantitative analysis of other analytes.

Graphical abstract

http://ift.tt/2mwvhPn

Simultaneously fabrication of free and solidified N, S-doped graphene quantum dots via a facile solvent-free synthesis route for fluorescent detection

Publication date: 1 June 2017
Source:Talanta, Volume 168
Author(s): Chang Xia, Xin Hai, Xu-Wei Chen, Jian-Hua Wang
A facile one-step solvent-free synthesis approach is proposed for the simultaneous fabrication of free and solidified N, S-doped graphene quantum dots (N, S-GQDs) by using citric acid as precursor and L-cysteine as dopant. Graphene nucleus is firstly formed via the intermolecular dehydration of citric acid. N and S are then incorporated into the graphene structure by attacking the margin of graphene nucleus. The cross-linking among the graphene nucleus via the intermolecular condensation leads to the generation of free N, S-GQDs, while the intermolecular amidation between L-cysteine molecules and graphene nucleuses contributes to the solid-state fluorescence graphene quantum dots (SSF-GQDs). The free N, S-GQDs exhibit favorable photoluminescence behaviors such as high fluorescent quantum yield of 74.5%, stable photoluminescence within a wide range of pH and high tolerance to external ionic strength of up to 1.0molL⁻¹ NaCl, making it excellent fluorescence probe for the sensitive detection of Fe³⁺ with a linear range of 0.01–3μM and a detection limit of 3.3nM. The solidification of GQDs prevents the aggregation of GQDs efficiently and offers the solidified N, S-GQDs yellow-green fluorescence, with a fluorescence quantum yield of 10.6%. This proposed protocol provides a novel avenue to fabricate diverse fluorescent graphene materials for different practical applications.

Graphical abstract

http://ift.tt/2mwFfA3

Editorial board members

Publication date: January–March 2017
Source:Mutation Research/Reviews in Mutation Research, Volume 771





http://ift.tt/2mYfzso

Drug repositioning based on triangularly balanced structure for tissue-specific diseases in incomplete interactome

Publication date: Available online 22 March 2017
Source:Artificial Intelligence in Medicine
Author(s): Liang Yu, Jin Zhao, Lin Gao
Finding new uses for existing drugs has become a new strategy for decades to treat more patients. Few traditional approaches consider the tissue specificities of diseases. Moreover, disease genes, drug targets and protein interaction (PPI) networks remain largely incomplete and the relationships between drugs and diseases conform to the triangularly balanced structure. Therefore, based on tissue specificities of diseases, we apply the triangularly balanced theory and the module distance defined for incomplete interaction networks to build drug-disease associations. Our method is named as TTMD (Tissue specificity, Triangle balance theory and Module Distance). Firstly, we combine three different drug similarity networks. Then, in the tissue-specific PPI network of a disease, we calculate its similarities with drugs using module distance. Finally, breast cancer and hepatocellular carcinoma (HCC) are taken as case studies. In the top-5% of predicted associations, 96.9% and 90.3% results match with known associations in Comparative Toxicogenomics Database (CTD) for breast cancer and hepatocellular carcinoma respectively. Clinical verification, literature mining and KEGG pathways enrichment analysis are further conducted for the top-5% newly predicted associations. Overall, TTMD is an effective approach for predicting new drug indications for tissue-specific diseases and provides potential values for the treatments of complex diseases.



http://ift.tt/2nVuN27

The effect of G3 PAMAM dendrimer conjugated with B-group vitamins on cell morphology, motility and ATP level in normal and cancer cells

Publication date: 1 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 102
Author(s): Łukasz Uram, Magdalena Szuster, Maria Misiorek, Aleksandra Filipowicz, Stanisław Wołowiec, Elżbieta Wałajtys-Rode
In a search for the safe vitamin carrier the PAMAM G3 dendrimer covalently substituted with 9 and 10 molecules of vitamin B7 (biotin) and B6 (pyridoxal), respectively (BC-PAMAM) was investigated. Dendrimer substitution with B-group vitamins significantly alters its biological properties as compared to native form. Observed effects on investigated cell parameters including morphology, adhesion, migration and ATP level were different for normal human fibroblasts (BJ) and squamous cell carcinoma (SCC-15) cell lines. BC-PAMAM revealed significantly less pronounced effects on investigated parameters, particularly at higher concentrations (5–50μM), which is relevant with its lower positive surface charge, as compared with native form. The bioconjugate, up to 50μM concentration, appeared to be a safe vitamin carrier to normal fibroblasts, without significant effect on their adhesion, shape and migration as well as on intracellular ATP level. In SCC-15 cells BC-PAMAM, at low concentrations (0.1–0.5μM), altered the cell shape and increase adhesion, whereas at higher concentrations opposite effects were seen. Measurements of cellular level of ATP showed that higher resistance of cancer cells to toxic effects of native PAMAM dendrimers may be due to higher energy supply of cancer cells.

Graphical abstract

http://ift.tt/2o9675z

Early preclinical evaluation of dihydropyrimidin(thi)ones as potential anticonvulsant drug candidates

Publication date: 1 May 2017
Source:European Journal of Pharmaceutical Sciences, Volume 102
Author(s): Mariana Matias, Gonçalo Campos, Samuel Silvestre, Amílcar Falcão, Gilberto Alves
Although significant advances are occurring in epilepsy research, about 30% of epileptic patients are still inadequately controlled by standard drug therapy. For this reason, it continues to be important to develop new chemical entities through which epilepsy could be effectively controlled. In this study, the anticonvulsant activity of forty-two dihydropyrimidin(thi)ones was explored and their efficacy was evaluated in rodents against the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole tests. The results of preliminary pharmacological screening after intraperitoneal injection in mice revealed that twenty-four compounds showed protection in half or more of the animals tested in the MES seizure model, being nine of them active at the lowest dose tested (30mg/kg). Structurally, the most promising compounds (both urea and thiourea derivatives) presented smaller lateral chains and unsubstituted or para-substituted phenyl ring with a methyl group. Compounds 4, 5 and 11 also protected against MES-induced seizures in 50–75% of rats after oral administration at 30mg/kg. Moreover, the minimal motor and/or neurological impairment evaluated through the rotarod assay showed that around 52% of the compounds presented lower toxicity than the antiepileptic drugs lamotrigine, carbamazepine and phenytoin. In addition, the most active compounds did not show notable cytotoxicity in in vitro experiments conducted in several cell lines (relative cell proliferation higher than 50% at 30μM), which can be relevant due to the fact that the toxicity is a common problem of the available antiepileptic drugs. Furthermore, additional computational studies indicated that all compounds respected the Lipinski's rule of five, which, together with the data of efficacy and toxicity, make them attractive compounds to be developed in the future as potential anticonvulsant agents.

Graphical abstract

http://ift.tt/2ngULyV

Geochemical behavior of ultramafic waste rocks with carbon sequestration potential: a case study of the Dumont Nickel Project, Amos, Québec

Abstract

The geochemical behavior of ultramafic waste rocks and the effect of carbon sequestration by these waste rocks on the water drainage quality were investigated using laboratory-scale kinetic column tests on samples from the Dumont Nickel Project (RNC Minerals, QC, Canada). The test results demonstrated that atmospheric CO₂ dissolution induced the weathering of serpentine and brucite within the ultramafic rocks, generating high concentrations of Mg and HCO₃⁻ with pH values ranging between 9 and 10 in the leachates that promote the precipitation of secondary Mg carbonates. These alkaline pH values appear to have prevented the mobilization of many metals; Fe, Ni, Cu, and Zn were found at negligible concentrations in the leachates. Posttesting characterization using chemical analyses, diffuse reflectance infrared Fourier transform (DRIFT), and scanning electron microscope (SEM) observations confirmed the precipitation of secondary hydrated Mg carbonates as predicted by thermodynamic calculations. The formation of secondary Mg carbonates induced cementation of the waste particles, resulting in the development of a hardpan.

http://ift.tt/2nrxSsX

Using fluorescent dyes as proxies to study herbicide removal by sorption in buffer zones

Abstract

The performance of buffer zones for removing pesticides from runoff water varies greatly according to landscape settings, hydraulic regime, and system design. Evaluating the performance of buffers for a range of pesticides and environmental conditions can be very expensive. Recent studies suggested that the fluorescent dyes uranine and sulforhodamine B could be used as cost-effective surrogates of herbicides to evaluate buffer performance. However, while transformation mechanisms in buffers have been extensively documented, sorption processes of both dyes have rarely been investigated. In this study, we measured the adsorption, desorption, and kinetic sorption coefficients of uranine and sulforhodamine B for a diverse range of buffer zone materials (soils, litters, plants) and compared the adsorption coefficients (Kd) to those of selected herbicides. We also compared the global sorption capacity of 6 ditches, characterized by varying proportions of the aforementioned materials, between both dyes and a set of four herbicides using the sorption-induced pesticide retention indicator (SPRI). We found that both the individual Kd of uranine for the diverse buffer materials and the global sorption capacity of the ditches are equivalent to those of the herbicides diuron, isoproturon, and metolachlor. The Kd of sulforhodamine B on plants and soils are equivalent to those of glyphosate, and the global sorption capacities of the ditches are equivalent for both molecules. Hence, we demonstrate for the first time that uranine can be used as a proxy of moderately hydrophobic herbicides to evaluate the performance of buffer systems, whereas sulforhodamine B can serve as a proxy for more strongly sorbing herbicides.

http://ift.tt/2o92s7P

Application of a novel magnetic carbon nanotube adsorbent for removal of mercury from aqueous solutions

Abstract

In this research, multiwall carbon nanotube was magnetized and subsequently functionalized by thiosemicarbazide. After characterization by FTIR, BET, SEM, EDAX, and VSM techniques, the magnetized adsorbent (multi-walled carbon nanotubes (MWCNTs)/Fe₃O₄) was used for removal of Hg²⁺ from aqueous solutions and the experimental conditions were optimized. The adsorption capacity of 172.83 mg g⁻¹ was obtained at 25 °C and pH = 3 which was superior to the value obtained for initial multiwall carbon nanotube, magnetized sample, and many previously reported values. In the presence of Pb⁺² and Cd⁺², the adsorbent was selective towards mercury when their concentration was respectively below 50 and 100 mg L⁻¹. The adsorption process was kinetically fast and the equilibration was attained within 60 min with 69.5% of the capacity obtained within 10 min. The used adsorbent was regenerated by HNO₃ solution, and the regenerated adsorbent retained 92% of its initial capacity. The magnetic sensitivity of the adsorbent allowed the simple separation of the used adsorbent from the solution by implying an appropriate external magnetic field. The adsorption data was well fitted to the Langmuir isotherm model, indicating homogeneous and monolayer adsorption of mercury by the adsorbent.

http://ift.tt/2mUEkET

Use of nanofractional radiofrequency for the treatment of acne scars in Indian skin

Summary

Background

Pitted acne scars of all types remain notoriously challenging to treat with no satisfactory treatment modality, particularly true for darker Fitzpatrick skin types such as Indian skin.

Aim

Nanofractional radiofrequency has been shown to be an effective treatment modality for the cosmetic improvement of acne scars.

Methods

Twenty healthy male and female Indian patients aged 16–60 years with Fitzpatrick skin types IV-V and moderate-to-severe acne scar lesions received 1–3 treatments with a nanofractional radiofrequency device (Venus Viva) at baseline and at 3- to 6 week intervals and were evaluated with photographs at each treatment visit and up to 6 months after the final treatment session. Patients reported on their satisfaction with the treatment. The safety of treatments was evaluated by the frequency, severity, and type of adverse events.

Results

The majority of study patients achieved improvement in the appearance of their acne scar lesions. There was less improvement on ice pick scar compared to box and rolling type scars, with less impact on ice pick scar type. Overall patient satisfaction from treatment at the 6-month follow-up visit was very high. Adverse events were mild but transient in nature.

Conclusion

The data and results presented here support the efficacy of nanofractional radiofrequency used for the cosmetic improvement of acne scar lesions in facial skin. Moreover, the favorable adverse event profile witnessed in this trial underscores the safety of this technology for cosmetic facial treatments such as facial acne scar lesion therapy in darker Fitzpatrick skin types.

http://ift.tt/2ngMCKT

Functional changes in the reward circuit in response to gaming-related cues after training with a commercial video game

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Tobias Gleich, Robert C. Lorenz, Jürgen Gallinat, Simone Kühn
In the present longitudinal study, we aimed to investigate video game training associated neuronal changes in reward processing using functional magnetic resonance imaging (fMRI). We recruited 48 healthy young participants which were assigned to one of 2 groups: A group in which participants were instructed to play a commercial video game ("Super Mario 64 DS") on a portable Nintendo DS handheld console at least 30minutes a day over a period of two months (video gaming group; VG) or to a matched passive control group (CG). Before and after the training phase, in both groups, fMRI imaging was conducted during passively viewing reward and punishment-related videos sequences recorded from the trained video game. The results show that video game training may lead to reward related decrease in neuronal activation in the dorsolateral prefrontal cortex (DLPFC) and increase in the hippocampus. Additionally, the decrease in DLPFC activation was associated with gaming related parameters experienced during playing. Specifically, we found that in the VG, gaming related parameters like performance, experienced fun and frustration (assessed during the training period) were correlated to decrease in reward related DLPFC activity. Thus, neuronal changes in terms of video game training seem to be highly related to the appetitive character and reinforcement schedule of the game. Those neuronal changes may also be related to the often reported video game associated improvements in cognitive functions.



http://ift.tt/2ngZErJ

BrainRuler- a free, open-access tool for calculating scalp to cortex distance

Publication date: Available online 23 March 2017
Source:Brain Stimulation
Author(s): Philipp M. Summers, Colleen A. Hanlon




http://ift.tt/2mw8jYD

The American Journal of Rhinology & Allergy

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New insights into upper airway innate immunity  
Hariri, Benjamin M.; Cohen, Noam A. 
The innate immune system and its role in development of CRS [ read more >>> ]

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Decreased interaction between ZO-1 and occludin is involved in alteration of tight junctions in transplanted epiphora submandibular glands

Abstract

Tight junctions (TJs) in salivary epithelium play an important role in regulating saliva secretion. Autologous transplantation of submandibular glands (SMGs) is an effective method to treat severe dry eye syndrome. However, epiphora occurs in some patients 6 months after transplantation. We previously found that the acinar TJs are enlarged in rabbit SMGs after long-term transplantation, but the exact TJ components involved in the epiphora are still unknown. Here, we found that the mRNA and protein expression of ZO-1 and occludin were increased in the transplanted SMGs obtained from epiphora patients, while other TJs were unchanged. The intensity of ZO-1 and occludin at the apicolateral membranes as well as occludin in the cytoplasm were increased in epiphora SMGs, but the interaction between ZO-1 and occludin was decreased as evidenced by both co-immunoprecipitation assay and co-immunofluorescence staining. Mechanically, the expression of casein kinase 2α (CK2α) and CK2β, which was reported to affect occludin modification and the interaction of occludin with ZO-1 in previous literatures, were increased in epiphora glands. Moreover, activation of muscarinic acetylcholine receptor (mAChR) by carbachol directly decreased the interaction between ZO-1 and occludin and increased the acinar TJ width in the freshly isolated human SMGs, whereas these effects were abolished by pretreatment with CK2 inhibitor. Taken together, our findings suggest that decreased interaction between ZO-1 and occludin might contribute to the epiphora occurred in the transplanted SMGs, and mAChR together with the intracellular molecule CK2 might be responsible for the alteration of TJs in epiphora glands.

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Bioassay-guided isolation of active principles from Nigerian medicinal plants identifies new trypanocides with low toxicity and no cross-resistance to diamidines and arsenicals

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): Godwin Unekwuojo Ebiloma, John Ogbaji Igoli, Evangelos Katsoulis, Anne-Marie Donachie, Anthonius Eze, Alexander Ian Gray, Harry P. de Koning
Ethnopharmacological relevanceLeaves from the plant species studied herein are traditionally used in northern Nigeria against various protozoan infections. However, none of these herbal preparations have been standardized, nor have their toxicity to mammalian cells been investigated. In search of improved and non-toxic active antiprotozoal principles that are not cross-resistant with current anti-parasitics, we here report the results of the in vitro screening of extracts from seven selected medicinal plant species (Centrosema pubescens, Moringa oleifera, Tridax procumbens, Polyalthia longifolia, Newbouldia laevis, Eucalyptus maculate, Jathropha tanjorensis), used traditionally to treat kinetoplastid infections in Nigeria, and the isolation of their bioactive principles.Aim of the studyTo investigate the efficacies of medicinal plant extracts, and of compounds isolated therefrom, against kinetoplastid parasites, assess cross-resistance to existing chemotherapy, and assay their toxicity against mammalian cells in vitro.Material and methodsPlants were extracted with hexane, ethyl acetate and methanol. Active principles were isolated by bioassay-led fractionation, testing for trypanocidal activity, and identified using NMR and mass spectrometry. EC50 values for their activity against wild-type and multi-drug resistant Trypanosoma brucei were obtained using the viability indicator dye resazurin.ResultsSeven medicinal plants were evaluated for activity against selected kinetoplastid parasites. The result shows that crude extracts and isolated active compounds from Polyalthia longifolia and Eucalyptus maculata, in particular, display promising activity against drug-sensitive and multi-drug resistant Trypanosoma brucei. The EC50 value of a clerodane (16α-hydroxy-cleroda-3,13(14)-Z-dien-15,16-olide) isolated from Polyalthia longifolia was as low as 0.38µg/mL, while a triterpenoid (3β,13β-dihydroxy-urs-11-en-28-oic acid) isolated from Eucalyptus maculata displayed an EC50 of 1.58µg/mL. None of the isolated compounds displayed toxicity towards Human Embryonic Kidney cells at concentrations up to 400µg/mL. In addition, the isolated compounds were active against Leishmania mexicana, as well as against T. congolense.ConclusionWe have isolated a clerodane compound from Polyalthia longifolia that shows low toxicity, no cross-resistance with current treatments, and promising activity against both human-infective and veterinary Trypanosoma species.

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Antinociceptive and anti-inflammatory effects of the methanolic stem bark extract of Antrocaryon klaineanum Pierre (Anacardiaceae) in mice and rat

Publication date: 5 May 2017
Source:Journal of Ethnopharmacology, Volume 203
Author(s): Annie Laure Magne Fongang, Edwige Laure Nguemfo, Yolande Djouatsa Nangue, Calvin Bogning Zangueu, Yannick Fouokeng, Anatole Guy Blaise Azebaze, Eulogio José Llorent-Martínez, Maria Luisa Fernández-de Córdova, Alain Bertrand Dongmo, Wolfgang Vierling
Ethnopharmacological relevanceAntrocaryon klaineanum is used by traditional healers to treat many disorders including pain and inflammatory diseases. This study aimed to evaluate the analgesic and antiinflammatory activities of methanol extract of A. klaineanum in mice and rats.Materials and methodsReverse phase high-performance liquid chromatography (RP-HPLC) was performed to establish the chromatographic fingerprint and to identify various chemical components of the plant extract. The anti-nociceptive activity of methanol extract of A. klaineanum was assessed using the acetic acid-induced abdominal constriction model, formalin test, capsaicin and cinnamaldehyde induced-neurogenic pain and hot plate test. Anti-inflammatory activity was assessed on carrageenan-induced inflammation. Extract was administrated orally at 200, 400 and 600mg/kg.ResultsPhytochemical analysis indicated the presence of proanthocyanidins, phenolic acids and flavonoids. The results of anti-nociceptive and anti-inflammatory activities showed that methanol extract significantly (p<0.01) reduced the pain induced by acetic acid with an inhibition percentage of 45.49% (600mg/kg). In the formalin test, the extract also significantly (p<0.01) reduced linking time in both phase (neurogenic and inflammatory) of the test with inhibition percentage of 56.28% and 60.73% respectively at the dose of 600mg/kg. The methanol extract of A. klaineanum significantly (P<0.001) reduced neurogenic pain linking time induced by capsaicin and cinnamaldehyde by 82.54% and 75.94% at the highest dose (600mg/kg) respectively. More over the extract significantly increase the reaction time in hot plate test. In the inflammatory test, the plant extract significantly reduced the carrageen induced rat paw oedema from 30min to 6h with a maximum percentage inhibition of 89.88% (6h) at the dose of 600mg/kg.ConclusionThese results demonstrate that the methanol extract of A. klaineanum may possess analgesic and anti-inflammatory effects and provide support of the traditional use of this plant in the treatment of different pain and inflammatory conditions. Further investigation could reveal metabolites of the extract responsible for the observed effects.

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Comparison of Lamiaceae medicinal uses in eastern Morocco and eastern Andalusia and in Ibn al-Baytar's Compendium of Simple Medicaments (13th century CE)

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): Asmae El-Gharbaoui, Guillermo Benítez, M. Reyes González-Tejero, Joaquín Molero-Mesa, Abderrahmane Merzouki
Ethnopharmacological relevanceTransmission of traditional knowledge over time and across culturally and historically related territories is an important topic in ethnopharmacology. Here, we contribute to this knowledge by analysing data on medicinal uses in two neighbouring areas of the Western Mediterranean in relation to a historical text that has been scarcely mentioned in historical studies despite its interest.Aim of the studyThis paper discusses the sharing of popular knowledge on the medicinal uses of plants between eastern Morocco and eastern Andalusia (Spain), focusing on one of the most useful plant families in the Mediterranean area: Lamiaceae. Moreover, we used the classical work of Ibn al-Baytar (13th century CE) The Compendium of Simple Medicaments and Foods as a basis to contrast the possible link of this information, analysing the influence of this historical text on current popular tradition of medicinal plant use in both territories.Materials and methodsFor data collection, we performed ethnobotanical field research in the eastern part of Morocco, recording current medicinal uses for the Lamiaceae. In addition, we systematically reviewed the ethnobotanical literature from eastern Andalusia, developing a database. We investigated the possible historical link of the shared uses and included in this database the information from Ibn al-Baytar's Compendium. To compare the similarity and diversity of the data, we used Jaccard's similarity index.ResultsOur field work provided ethnobotanical information for 14 Lamiaceae species with 95 medicinal uses, serving to treat 13 different pathological groups. Of the total uses recorded in Morocco, 30.5% were shared by eastern Andalusia and found in Ibn al-Baytar's work. There was a higher similarity when comparing current uses of the geographically close territories of eastern Morocco and eastern Andalucía (64%) than for eastern Morocco and this historical text (43%). On the other hand, coincidences between current uses in eastern Andalusia and the ones related in the Compendium are lower, 28%.ConclusionsThe coincidence of the current ethnobotanical knowledge in the two territories is high for the Lamiaceae. Probably the shared historical background, recent exchanges, information flow, and the influence of the historical herbal texts have influenced this coincidence. In this sense, there is a high plant-use overlap between Ibn al-Baytar's text and both territories: nearly half of the uses currently shared by eastern Morocco and eastern Andalusia were included in the Compendium and are related to this period of Islamic medicine, indicating a high level of preservation in the knowledge of plant usage. The study of 14 species of Lamiaceae suggests that this classical codex, which includes a high number of medicinal plants and uses, constitutes a valuable bibliographical source for comparing ancient and modern applications of plants.

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Anticancer and anti-angiogenic activities of extract from Actinidia eriantha Benth root

Publication date: 5 May 2017
Source:Journal of Ethnopharmacology, Volume 203
Author(s): Jian-guo Wu, Li Ma, Shui-hua Lin, Yan-bin Wu, Jun Yi, Bin-jun Yang, Jin-zhong Wu, Ka-hing Wong
Ethnopharmacological relevanceThe roots of Actinidia eriantha Benth (AER) are commonly used traditional folk medicine for the treatment of gastric carcinoma, nasopharyngeal carcinoma, and breast carcinoma. Besides, the anti-proliferative and immunomodulatory effects of AER polysaccharides on tumor-bearing mice have been reported previously.Aim of the studyThis work was carried out to investigate the anticancer and anti-angiogenic activities of AER.Materials and methodsThe growth inhibitory effects of ethanol extracts from the leaves (EEL), stems (EES) and roots (EER) of A. eriantha on human gastric carcinoma SGC7901 cells, human nasopharyngeal carcinoma CNE2 cells, human breast carcinoma MCF7 cells and human umbilical vein endothelial cells (HUVECs) were evaluated by MTT assay. The ethyl acetate fraction from EER (EA-EER) was further investigated for the anticancer activity against SGC7901 cells and the anti-angiogenic activity in HUVECs in vitro. The apoptosis in SGC7901 cells and HUVECs was confirmed by DAPI nuclear staining and flow cytometry analysis, the effect on cellular DNA fragmentation was detected in SGC7901 cells. And the cell cycle-arresting activity in HUVECs was determined by flow cytometry. Moreover, the inhibitory effect of EA-EER on cell migration in HUVECs was observed by both wound-healing and Transwell migration assays. RT-PCR and Western-blotting were performed to determine the mRNA and protein expression levels, respectively, including Bax, Bcl-2 and caspase-3 in SGC7901 cells, as well as VEGF-A and VEGFR-2 in HUVECs. Furthermore, the in vivo anti-angiogenic activity of EA-EER was evaluated by using chick embryo chorioallantoic membrane (CAM) assay. Ultimately, the chemical components in EA-EER were isolated and purified by repeated column chromatography followed by structure characterization using ¹H and ¹³C nuclear magnetic resonance and mass spectroscopy.ResultsCompared with EEL and EES, EER displayed the strongest growth inhibitory effect on SGC7901 cells, CNE2 cells and HUVECs. Among the EER fractions, EA-EER exhibited the most potent growth inhibitory activity against SGC7901 cells, CNE2 cells and HUVECs. Moreover, EA-EER induced obvious apoptosis in SGC7901 and HUVECs, and significantly inhibited the proliferation of HUVECs via blockade of cell cycle G1 to S progression. Furthermore, EA-EER suppressed the expression of Bcl-2 and improved the expression Bax and caspase-3 in SGC7901 cells. EA-EER not only inhibited migration of HUVECs, but also down-regulated the expression of VEGF-A and VEGFR-2 in HUVECs. In vivo, EA-EER exposure reduced the formation of blood vessels in chick embryos. A bio-guided isolation of EA-EER led to the isolation of three compounds for the first time, namely (6R, 7E, 9S)-6, 9-hydroxy-megastigman-4, 7-dien-3-one-9-O-β-D-glucopyranoside, Oleanolic acid-23-O-β-D-glucopyranoside, 3β, 23, 24-trihydroxyl-12-oleanen-28-oic acid.ConclusionThe present research demonstrated that the significant anticancer and anti-angiogenic effects of AER, providing the supportive evidence for its traditional use in the treatment for cancer. It was suggested that AER could be use as a potential source of cancer therapeutic drug.

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Standardization and anti-inflammatory activity of aqueous extract of Psittacanthus plagiophyllus Eichl. (Loranthaceae)

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): Adrielle Nara Serra Bezerra, Laís Tatiele Massing, Ricardo Bezerra de Oliveira, Rosa Helena Veras Mourão
Ethnopharmacological importanceThe hemiparasitic species Psittacanthus plagiophyllus Eichl. (Loranthaceae), also known as erva de passarinho, is used in folk medicine in the Santarém region in the state of Pará, Brazil, to treat gastritis and a variety of inflammatory disorders. In view of the lack of pharmacological studies on this species in the literature and the fact that it is used constantly by the local population, this study sought to standardize the extract of the leaves of P. plagiophyllus (AEPp) and to assess its anti-inflammatory potential in in vivo tests.Material and methodsQuality control and standardization of AEPp were performed following the 5th edition of the Brazilian Pharmacopeia. To assess the in vivo anti-inflammatory activity of AEPp, the carrageenan-induced and dextran-induced rat paw edema models were initially used. To investigate the effect of AEPp on carrageenan-induced leukocyte recruitment and exudate production, the air pouch inflammation model was used. In addition, the antioxidant activity of AEPp was assessed in vitro by the DPPH radical scavenging method.ResultsThe chromatographic profile of AEPp indicated the presence of flavonoids, coumarins and hydrolyzable and condensed tannins. Measurement of phenolics revealed the following percentages in the extract: 12.62±0.18% total phenolics, 5.39±0.01% total tannins, 12.54±0.24% hydrolyzable tannins, 8.37±0.32% condensed tannins and 1.23±0.02% total flavonoids. In 500 and 1000mg/kg doses (p.o.) AEPp had significant edema-inhibiting activity (p<0.01) in both the models used, suggesting that the extract may act in vascular and cell events in the inflammatory response and exert an inhibitory effect on mediators responsible for edema. In all the doses tested [250, 500 and 1000mg/kg (p.o.)], AEPp inhibited total leukocyte and neutrophil migration and reduced the amount of exudate in the air pouch in a dose-dependent manner. Both effects were statistically significant (p<0.01). The extract also reduced the DPPH radical (maximum reduction 93.13±1.71% at a concentration of 75µg/mL), indicating that it has antioxidant activity. AEPp, therefore, exhibited considerable in vivo anti-inflammatory activity and in vitro antioxidant activity. This may be due to its high phenolics content.ConclusionThese findings provide evidence to support the use of P. plagiophyllus in folk medicine to treat inflammatory disorders.

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Effects of antrosterol from Antrodia camphorata submerged whole broth on lipid homeostasis, antioxidation, alcohol clearance, and anti-inflammation in livers of chronic-alcohol fed mice

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): Yuan-Yen Chang, Yi-Chen Liu, Yueh-Hsiung Kuo, Yi-Ling Lin, Yi-Hsieng Samuel Wu, Jr-Wei Chen, Yi-Chen Chen
Ethnopharmacological relevanceAntrodia camphorata is a functional fungus in Taiwan and owns several pharmacological functions. Antrosterol, a bioactive constitute of sterols in edible Antrodia camphorata submerged whole broth, can protect liver from CCl4 damage via enhancing antioxidant and anti-inflammatory capacities.Aim of the studyThe aim of this study was to investigate the hepatoprotection of antrosterol (named as EK100) against alcohol consumption.Materials and methodsA Lieber-DeCarli regular EtOH diet (EtOH liquid diet, 5% (v/v) alcohol) was applied to induce alcoholic liver damage. Mice were randomly divided into 5 groups: (1) Control: control liquid diet; (2) EtOH: EtOH liquid diet; (3) EK100_1X: EtOH liquid diet and 1mg EK100 (Antrosterol)/Kg body weight (bw); (4) EK100_5X: EtOH liquid diet and 5mg EK100/Kg bw; (5) EK100_10X: EtOH liquid diet and 10mg EK100/Kg bw. At the end of experiment, the livers were collected for histo-pathological analyses, RNA and protein extraction, and enzymatic activities.ResultsAntrosterol reduced serum/liver lipids of alcohol-diet fed mice which highly related to upregulated fatty acid β-oxidation and downregulated lipogenesis, and increased fecal lipid/bile-acid outputs. Antrosterol enhanced hepatic antioxidant capabilities in alcohol-diet fed mice while it also lowered serum alcohol level, as well as increased alcohol dehydrogenase (ADH) and catalase (CAT) activities and decreased CYP2E1 protein expression in livers of alcohol-diet fed mice. Besides, antrosterol lowered hepatic inflammation and fibrosis related gene expressions, as well as serum AST/ALT values and TNF-α/IL-1β contents in alcohol-diet fed mice.ConclusionBased on the results, hepatoprotection of antrosterol is mostly attributed to its regulations of lipid homeostasis, antioxidant capability, alcohol metabolism, and anti-inflammation.

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The use of Chinese herbal medicine as an adjuvant therapy to reduce incidence of chronic hepatitis in colon cancer patients: A Taiwanese population-based cohort study

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): Tsai-Hui Lin, Hung-Rong Yen, Jen-Huai Chiang, Mao-Feng Sun, Hen-Hong Chang, Sheng-Teng Huang
Ethnopharmacological relevanceThere is a decided lack of in-depth studies to evaluate the effectiveness of Chinese Herbal Medicine (CHM) as an adjuvant therapy on the incidence of chronic hepatitis in patients with colon cancer.Aim of the studyThe aim of this study is to assess whether CHM treatment decreased the incidence of chronic hepatitis in colon cancer patients who received conventional Western medical treatment.Materials and methodsA Taiwanese nationwide population-based study of colon cancer patients receiving Western medicine treatment in conjunction with CHM treatment, using data provided by the National Health Insurance (NHI) Research Database, was conducted. A total of 61676 patients were diagnosed with colon cancer in Taiwan within the defined study period, from 1997 to 2010. After randomly equal matching for age, sex, excluding patients younger than 18 years of age, chronic hepatitis before colon cancer diagnosis date, receiving acupuncture and/or moxibustion and taking CHM for less than 30 days, data from 155 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence of CHM and the therapeutic potential of herbal products in treating patients with colon cancer.ResultsCHM used for patients with colon cancer exhibited significantly decreased incidence rates of chronic hepatitis [hazard ratio (HR)=0.53; 95% confidence interval (CI):0.38–0.74], with multivariate adjustment, compared to those without CHM use. The protective effect of CHM treatment with statistical significance across the stratification of age, gender, co-morbidity and treatment modality was noted. The cumulative incidence of chronic hepatitis was also reduced in patients with colon cancer receiving CHM treatment during a five-year period. In this study, we provide the ten most used single herbs and herbal formulas that were prescribed for patients with colon cancer; moreover, we identify the eight single herbs and five formulas used in CHM treatment which significantly decreased incidence of chronic hepatitis among colon cancer patients.ConclusionsThis nationwide retrospective cohort study determined that therapy using CHM as an adjuvant modality may have a significant impact on liver protection in patients with colon cancer.

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A review of the ethnopharmacology, phytochemistry and pharmacology of Notopterygium incisum

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): John Teye Azietaku, Huifen Ma, Xie-an Yu, Jin Li, Mahmood Brobbey Oppong, Jun Cao, Mingrui An, Yan-xu Chang
Ethnopharmacological relevanceNotopterygium incisum Ting ex H.T. Chang, known in Chinese as 'Qianghuo' is a traditional Chinese medicinal herb with the rhizome and roots associated with meridians of the kidney and urinary bladder. It is pungent, bitter and warm in nature. It has been used over the years to disperse cold, prevent painful obstructions from wind, damp and warm pain. It has also been used with other herbs to treat wind-cold exterior syndrome and wind-cold-damp bi-syndromes and has been known to grow well in regions of high altitude such as Gansu, Tibet etc.The aim of the reviewThis systematic review focuses on the ethnopharmacological uses of this herb, including recent advances on the phytochemical and pharmacological study of N. incisum. Recent analytical methods developed for the quantitative and qualitative determination of constituents in this herb have also been reviewed. Additionally, future trends and prospects in the study of this herb have been proposed.Materials and methodVarious literature and electronic databases such as Pubmed, Science Direct, Springer, Wiley etc were searched and data obtained. Other online academic libraries such as Google Scholar and ethnopharmacological literature were searched systematically for more information on the herb.ResultsThis review focuses on the ethnopharmacological uses of N. incisum and also the various chemical constituents present in the herb and their various therapeutic effects such as analgesic, anti-inflammatory, anti-cancer and antioxidants effects. Analytical methods developed for the quantitative and qualitative determination of various compounds in this herb were further reviewed.ConclusionIn this paper, we have reviewed various researches conducted on N. incisum especially in areas of its ethnopharmacological use, phytochemicals, pharmacology and developed analytical methods. This herb has been used over the years in treating headache, rheumatoid arthritis, cold, diaphoretic etc, prompting many types of research into identifying which compounds are responsible for these activities and their mechanism of action. More research is needed in the area of pharmacokinetics and toxicology to give further information on the clinical use and control the quality of the herb.



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