Source:Trends in Cell Biology, Volume 27, Issue 8
http://ift.tt/2ugKowS
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Publication date: Available online 21 July 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Qingbin Guo, H. Douglas Goff, Steve W. Cui
A galacto-oligosaccharide product (VITAGOS™) was prepared by glycoside hydrolases (β-galactosidase from Aspergillus oryzae and Kluyveromyces lactis) using lactose as substrate. Monosaccharide composition analysis indicated that VITAGOS™ contained 40.3% (w/w, dry basis) glucose and 51.1% (w/w, dry basis) galactose. According to high performance size exclusion chromatography (HPSEC) analysis, VITAGOS™ was a sugar mixture with degree of polymerisation (DP) ranging from 1 to 7, with DP2 and DP3 as the dominant fractions (32% and 33%, w/w). In addition, more than three fractions were observed for each DP pool indicated by the oligosaccharides profiles obtained from high performance anion exchange chromatography (HPAEC) analysis. Six sub-fractions (F1-F6, corresponding to DP1 to DP6 rich fraction, respectively) were then collected using biogel P-2 column, followed by structural characterisation through methylation analysis combined with 1D & 2D NMR spectroscopy. The detailed molecular structures of VITAGOS™ with DP up to 4 are provided.
Endocrine disrupting compounds (EDCs) are a wide group of contaminants of emerging concern known to be harmful for organisms. The aim of the study was to assess the occurrence and distribution of six EDCs (estrone—E1, ß-estradiol—E2, 17α-ethinylestradiol—EE2, bisphenol A—BPA, perfluooctanoic acid—PFOA, perfluorooctane sulfonate—PFOS) in the Apenninic rivers and groundwaters of the Romagna area (North of Italy). Groundwaters were unaffected by EDC contamination, while all classes of compounds were detected at concentrations above the method quantification limit (MQL) in the majority of the river bodies. In detail, PFOA and PFOS concentrations varied between <MQL and 17.7 ng/l (PFOA) and between <MQL and 5.5 ng/l (PFOS), and their occurrence in the aquatic compartment was related to the discharge of wastewater treatment plant effluents. Concerning estrogens, EE2 was below the MQL in all samples, whereas E1 and E2 reached concentrations up to 39.7 ng/l (E2) and 28 ng/l (E1) in surface waters. The highest estrogen values were registered in those areas where livestock and farming are the main activities, indicating a close relation between these activities and estrogen release into the aquatic compartment. BPA (<MQL–171.3 ng/l) distribution in river waters did not show any correlation with a specific anthropic activity; a mixture of sources of contamination (e.g., industries of food packaging and plastic production) is rather responsible for its detection in river bodies. Overall, the northern part of the Romagna area showed a higher contamination by EDCs, in contrast with the southern part, which was almost unaffected by this kind of microcontamination.
Symmastia is a difficult surgical problem to correct. Symmastia has various etiologies and can occur following reduction mammoplasty. Techniques previously described have been criticized for their limited success due to temporary results, inadequate correction, or creation of secondary deformities. In this study, we present a novel approach to correct symmastia in a patient who developed the deformity following reduction mammoplasty. The technique described uses a buried dermal pennant suture, local advancement flaps, and liposuction to correct the symmastia and improve medial breast contour. We believe this technique provides adequate and long-term correction of symmastia in the breast reduction patient and avoids the shortcomings of previously described approaches.
Level of Evidence: Level V, therapeutic study
Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Yun-Yao Gu, Jian Chen, Zhu-Long Meng, Wan-Yu Ge, Yang-Yang Bian, Shao-Wen Cheng, Chen-Kun Xing, Jiang-Ling Yao, Jian Fu, Lei Peng
Osteoarthritis is a common disease and is frequently encountered in the older population; the incidence rises sharply with age. It is estimated that more than 360 million people suffer from OA. However, the pathogenesis of osteoarthritis remains unclear, and we cannot effectively prevent the progression of OA. The aim of this review was to explore the molecular markers and signaling pathways that induce chondrocyte apoptosis in OA. We searched, using the key words osteoarthritis, chondrocyte apoptosis, autophagy, endoplasmic reticulum stress, molecular targets, and biomarkers, in PubMed, Web of Science, and Google Scholar from 1994 to 2017. We also reviewed the signaling pathways and molecular markers associated with chondrocyte apoptosis and approaches aimed at inhibiting the apoptosis-inducing mechanism to at least delay the progression of cartilage degeneration in OA. This article provides an overview of targeted therapies and the related signaling pathways in OA.
http://ift.tt/2tvjJz6
Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): María Gabriela Montiel Schneider, Verónica Leticia Lassalle
Cardiovascular complications derivate from atherosclerosis are the main cause of death in western world. An early detection of vulnerable atherosclerotic plaques is primordial for a better care of patients suffering the pathology. In this context nanotechnology has emerged as a promising tool to achieve this goal. Nanoparticles based on magnetic iron oxide (MNPs) have been extensively studied in cardiovascular diseases diagnosis, as well as in the treatment and diagnostic of other pathologies. The present review aims to describe and analyze the most current literature regarding to this topic, offering the level of detail required to reproduce the experimental tasks providing a critical input of the latest available reports. The current diagnostic features are presented and compared, highlighting their advantages and disadvantages. Information on novel technology intended to this purpose is also recompiled and in deep analyzed. Special emphasis is placed in magnetic nanotechnology, remarking the possibility to assess selective and multifunctional systems to the early detection of artherosclerotic pathologies.Finally, in view of the state of the art, the future perspectives about the trends on MNPs in artherosclerorsis diagnostic and treatment have also been addressed.
Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Kevin Ita
Over the last number of years, a significant body of evidence has shown the benefit of using dissolving microneedles (DMNs) for transdermal drug delivery. These devices are prepared from a wide range of materials such as sugars and polymers. DMNs are mainly fabricated by micromolding, photopolymerization, drawing lithography and droplet-airborne blowing. In this review, we have focused on the advances made in the field in recent years using a representative set of studies. Although the list of studies is not exhaustive, they highlight the challenges encountered such as the need to increase mechanical strength as well as medication dose while ensuring fast release of the active ingredient. DMNs can be used to delivery low molecular drugs as well as peptides, proteins and other high molecular weight compounds.
Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Kunnathur Murugesan Sakthivel, Sreedharan Hariharan
DNA damaging agents are most common in chemotherapeutic molecules that act against cancer. However, cancer cells possess inherent biological features to overcome DNA damages by activating various distinct repair mechanisms and pathways. Importantly, various oncogenes, cancer stem cells (CSCs), hypoxic environment, transcription factors and bystander signaling that are activated in the cancer cells influence DNA repair, thereby effectively repairing the DNA damage. Repaired cancer cells often become more resistance to further therapy and results in disease recurrence. In this review, we summarize how the various signaling pathways in cancer cells regulates DNA repair and induce chemoresistance.
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
http://ift.tt/2ufrNRE
Little is known about biosecurity measures and toxic effects during pesticide application in the province of Jujuy, Argentina, particularly concerning the protective measures and mixture of pesticides used by rural workers. We carried out an observational study of agricultural workers from Jujuy (76 exposed subjects and 53 controls) to investigate the prevalence of chromosomal aberrations (CAs) in human lymphocytes as well as the activity level of acetylcholinesterase (AChE) in red blood cell erythrocytes. Whole blood samples (5 mL) were collected in heparinized Vacutainer tubes for cytogenetic analysis and erythrocyte cholinesterase activity determination according to Ellman's method. Cytogenetic results showed a significant CA increase in pesticide-exposed individuals as compared with controls (4.20 ± 0.15 vs. 1.00 ± 0.05, respectively; p < 0.001), suggesting that pesticides are clastogenic agents causing DNA damage. Erythrocyte cholinesterase activity was significantly lower in exposed individuals, evidencing the possible occurrence of perturbations in blood as well as neurotoxicity in pesticide sprayers. These results suggest the need for periodic biomonitoring of these biomarkers together with education and training of occupational workers for the safe application of potentially harmful pesticides.
J reconstr Microsurg
DOI: 10.1055/s-0037-1603735
Background When mobilizing free flaps, postoperative monitoring of perfusion is crucial to detect ischemia. Continuous monitoring may be feasible by applying a combination of tissue spectrophotometry and laser Doppler flowmetry (oxygen-2-see [O2C]). Material and Methods On 10 pigs, two symmetrical myocutaneous flaps were mobilized on each side of the abdomen based on the deep inferior epigastric vessels. Flaps were randomized to clamp either the artery or the vein and measurements using O2C were performed before, during, and after the intervention yielding information on blood flow, saturation (sat), and relative tissue hemoglobin (rHgb) concentration. Results Baseline values were similar in all groups. Introduction of ischemia caused a rapid decline in arterial ischemic flaps which all reached threshold levels in 3 minutes, whereas that was only the case for three of six venous ischemic flaps. Venous clamping resulted in a decline in sat, while the response to arterial clamping was an initial decline followed by an increase in sat. In all arterial ischemic flaps, rHgb concentration either decreased or remained at baseline levels but increased in all venous ischemic flaps. The median time to a 30% rise was 1 minute at an 8-mm depth. The rate of decreasing flow along with the rHgb measurements made it possible to distinguish the arterial ischemia (AI) from the venous ischemia (VI) within the first few minutes. Conclusion In this animal experimental model, O2C measurements of blood flow reliably detected ischemia. By adding information about rHgb, it was possible to distinguish between AI and VI.
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Although evidence of mosquito coils' impact on disease epidemiology is limited, they are popularized as mosquito-borne disease prevention devices. Their usage affects the environment, human and mosquito health. This study investigated the perception, usage pattern and efficacy of coils in a predominantly poor malaria-endemic Ghanaian peri-urban area. Information on protection methods, perception and usage pattern was garnered using questionnaires. The efficacy of commonly used coils in the area was then assessed on the malaria vector, Anopheles gambiae, in a glass chamber. Sole or co-application of mosquito control methods and risky usage practices were reported. Coils were deemed harmful to humans and mosquitoes, and their perceived effectiveness varied, with several factors influencing their purchase. High d-allethrin concentration coils induced quicker mosquito knockdown; however, mortality was less than 85%. The coil usage pattern compromises users' health and can enhance mosquito tolerance to d-allethrin. The coils were ineffective against the vector, outlining a dichotomy between the users' perception of efficacy and the observed efficacy. Hence, the usage of other safer and more effective vector control methods should be encouraged to protect households.
Publication date: Available online 20 July 2017
Source:Clinical Imaging
Author(s): Derek M. Biederman, Raghuram Posham, Raisa J. Durrani, Joseph J. Titano, Rahul S. Patel, Nora E. Tabori, Francis S. Nowakowski, Aaron M. Fischman, Robert A. Lookstein, Edward Kim
PurposeTo evaluate the outcomes of radioembolization (RE) as a therapy for unresectable hepatocellular carcinoma (HCC) in patients with marginal functional hepatic reserve.MethodsA retrospective review of 471 patients (1/2010–7/2015) treated with RE (Therasphere, BTG, UK) was performed. A total of 36 patients (mean age: 66.1±9.3, male: 86.1%) underwent therapy for HCC with a MELD≥15 (median: 16, range: 15–22). Baseline demographics of the study cohort were as follows: etiology (HCV: 26, 72.2%), cirrhosis (n=32, 88.9%), ECOG 0 (n=16, 44.4%), Child-Pugh class (A=15, B=19, C=2), unilobar distribution (n=27, 75%), AFP>200 (n=11, 30.6%), portal vein thrombosis (PVT, n=7, 19.4%), metastasis (n=3, 8.3%). Outcomes analyzed included CTCAEv4.03 laboratory toxicities (120-day), imaging response (mRECIST), progression-free survival (PFS), and overall survival (OS).ResultsA total of 42 treatments were performed with mean dose of 2.02±1.23GBq. The cumulative grade 3/4 toxicity was 28% overall and 21% for bilirubin at 120-days. The objective response and disease control rates were 48.3% (14/29) and 69% (20/29) respectively. The median (95% CI) PFS was 5.9 (4.4–7.7) months. Ten (27.8%) patients received additional locoregional therapy at a median (IQR) of 138 (102–243) days post RE. The mean (95% CI) OS was 21.9 (14.8–29.0) months. The absence of PVT was associated with improved OS (p=0.005) Disease control at 90-days was also associated with an OS benefit (p=0.037).ConclusionsPatients with unresectable HCC and marginal functional hepatic reserve treated with RE had favorable objective response and disease control rates, both predictive of overall survival.
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Biochar is a potential candidate for the remediation of metal(loid)-contaminated soils. However, the mechanisms of contaminant-biochar retention and release depend on the amount of soil contaminants and physicochemical characteristics, as well as the durability of the biochar contaminant complex, which may be related to the pyrolysis process parameters. The objective of the present study was to evaluate, in a former contaminated smelting site, the impact of two doses of wood biochar (2 and 5% w/w) on metal immobilization and/or phytoavailability and their effectiveness in promoting plant growth in mesocosm experiments. Different soil mixtures were investigated. The main physicochemical parameters and the Cd, Pb, and Zn contents were determined in soil and in soil pore water. Additionally, the growth, dry weight, and metal concentrations were analyzed in the different dwarf bean plant (Phaseolus vulgaris L.) organs tested. Results showed that the addition of biochar at two doses (2 and 5%) improved soil conditions by increasing soil pH, electrical conductivity, and water holding capacity. Furthermore, the application of biochar (5%) to metal-contaminated soil reduced Cd, Pb, and Zn mobility and availability, and hence their accumulation in the different P. vulgaris L. organs. In conclusion, the data clearly demonstrated that biochar application can be effectively used for Cd, Pb, and Zn immobilization, thereby reducing their bioavailability and phytotoxicity.
We evaluated the patterns of progression and determined clinical predictors of survival in patients with castration-resistant prostate cancer (CRPCa) who received sipuleucel-T.
We retrospectively analyzed 56 consecutive patients with asymptomatic or minimally symptomatic CRPCa treated with sipuleucel-T. Age, number of bone metastases, history of prior systemic treatment, and alkaline phosphatase level (ALP) were tested as predictors of survival in a multivariate Cox proportional hazards regression model. The Kaplan–Meier method was used to estimate event-free probabilities.
The 56 patients were a median age of 67 years (range 51–84 years). After sipuleucel-T treatment, 25 patients developed bone progression after a median of 22 months of follow-up (54% of patients were event free at 2 years) and 10% (6/56 patients) developed rapid progression. Eleven deaths were observed after a median of 28 months of follow-up. Forty-eight patients were included in the multivariate analysis for overall survival. The analysis showed that age >70 years (p = 0.012), number of bone metastases >20 (p = 0.018), prior systemic treatment (p = 0.018), and ALP level >90 IU/L (p = 0.010) significantly predicted worse overall survival. Two-year overall survival was 36% among the 16 patients with two or more of these factors and was 93% among the 32 patients with one or none of these factors (p = 0.0004).
CRPCa patients with age (>70 years), increased tumor burden in bone (>20 metastases and/or elevated ALP level), and/or prior systemic treatment are more likely to experience rapid deterioration after sipuleucel-T. These results need to be prospectively validated.
Publication date: Available online 20 July 2017
Source:Cell Stem Cell
Author(s): Martha S. Windrem, Mikhail Osipovitch, Zhengshan Liu, Janna Bates, Devin Chandler-Militello, Lisa Zou, Jared Munir, Steven Schanz, Katherine McCoy, Robert H. Miller, Su Wang, Maiken Nedergaard, Robert L. Findling, Paul J. Tesar, Steven A. Goldman
In this study, we investigated whether intrinsic glial dysfunction contributes to the pathogenesis of schizophrenia (SCZ). Our approach was to establish humanized glial chimeric mice using glial progenitor cells (GPCs) produced from induced pluripotent stem cells derived from patients with childhood-onset SCZ. After neonatal implantation into myelin-deficient shiverer mice, SCZ GPCs showed premature migration into the cortex, leading to reduced white matter expansion and hypomyelination relative to controls. The SCZ glial chimeras also showed delayed astrocytic differentiation and abnormal astrocytic morphologies. When established in myelin wild-type hosts, SCZ glial mice showed reduced prepulse inhibition and abnormal behavior, including excessive anxiety, antisocial traits, and disturbed sleep. RNA-seq of cultured SCZ human glial progenitor cells (hGPCs) revealed disrupted glial differentiation-associated and synaptic gene expression, indicating that glial pathology was cell autonomous. Our data therefore suggest a causal role for impaired glial maturation in the development of schizophrenia and provide a humanized model for its in vivo assessment.
Publication date: Available online 20 July 2017
Source:Cell Stem Cell
Author(s): Hitoshi Takizawa, Kristin Fritsch, Larisa V. Kovtonyuk, Yasuyuki Saito, Chakradhar Yakkala, Kurt Jacobs, Akshay K. Ahuja, Massimo Lopes, Annika Hausmann, Wolf-Dietrich Hardt, Álvaro Gomariz, César Nombela-Arrieta, Markus G. Manz
Bacterial infection leads to consumption of short-lived innate immune effector cells, which then need to be replenished from hematopoietic stem and progenitor cells (HSPCs). HSPCs express pattern recognition receptors, such as Toll-like receptors (TLRs), and ligation of these receptors induces HSPC mobilization, cytokine production, and myeloid differentiation. The underlying mechanisms involved in pathogen signal transduction in HSCs and the resulting biological consequences remain poorly defined. Here, we show that in vivo lipopolysaccharide (LPS) application induces proliferation of dormant HSCs directly via TLR4 and that sustained LPS exposure impairs HSC self-renewal and competitive repopulation activity. This process is mediated via TLR4-TRIF-ROS-p38, but not MyD88 signaling, and can be inhibited pharmacologically without preventing emergency granulopoiesis. Live Salmonella Typhimurium infection similarly induces proliferative stress in HSCs, in part via TLR4-TRIF signals. Thus, while direct TLR4 activation in HSCs might be beneficial for controlling systemic infection, prolonged TLR4 signaling has detrimental effects and may contribute to inflammation-associated HSPC dysfunction.
Publication date: Available online 20 July 2017
Source:Cell Stem Cell
Author(s): Ting Zhou, Lei Tan, Gustav Y. Cederquist, Yujie Fan, Brigham J. Hartley, Suranjit Mukherjee, Mark Tomishima, Kristen J. Brennand, Qisheng Zhang, Robert E. Schwartz, Todd Evans, Lorenz Studer, Shuibing Chen
Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally, HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly, HH suppresses viral propagation when administered to adult mice with active ZIKV infection, highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients.
Taxane monotherapy is widely used for advanced gastric cancer (AGC) after failure of standard first-line chemotherapy with fluoropyrimidine and cisplatin. Triplet chemotherapy with docetaxel, cisplatin, and S-1 (DCS) is a promising regimen for first-line chemotherapy of AGC. The aim of this study was to evaluate the efficacy of taxane monotherapy in patients refractory to DCS.
We retrospectively evaluated the efficacy and safety of taxane monotherapy in patients with AGC refractory to first-line therapy with DCS between January 2010 and April 2015. Selection criteria were as follows: ECOG PS of 0–2, treatment with taxane monotherapy in second-line or third-line therapy after failure of second-line irinotecan, absence of massive ascites, and adequate organ function.
A total of 30 patients were included in this study. Of these, 15 patients received paclitaxel while another 15 received nanoparticle albumin-bound paclitaxel in either second- or third-line treatment. Median age for the second/third-line group was 64.0/62.0 (range 27–75/42–75); 14/13 (93.3/86.7%) had ECOG PS of 0 or 1. No patients achieved complete or partial response and stable disease was observed in 37.5/35.7% of the patients in the second/third line. Median progression-free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line group, respectively. The incidences of any grade ≥3 adverse events in the second-line group and the third-line group were 60.0 and 33.3%, respectively. There was no treatment-related death.
Taxane monotherapy after DCS failure had acceptable toxicities but was ineffective in AGC patients.
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