Source:Artificial Intelligence in Medicine, Volume 78
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Σάββατο 29 Ιουλίου 2017
Editorial Board
Source:Artificial Intelligence in Medicine, Volume 78
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Scholar : Journal of Oral and Maxillofacial Surgery, Year 2016, Issue 06 -New Issue Alert.
The C. elegans SET-2/SET1 histone H3 Lys4 (H3K4) methyltransferase preserves genome stability in the germline
Source:DNA Repair
Author(s): M. Herbette, M. Mercier, F. Michal, D. Cluet, C. Burny, G. Yvert, V. Robert, F. Palladino
Maintaining the integrity of genetic information across generations is essential for both cell survival and reproduction, and requires the timely repair of DNA damage. Histone-modifying enzymes play a central role in the DNA repair process through the deposition and removal of post-translational modifications on the histone tails. Specific histone modification act in the DNA repair process through the recruitment of proteins and complexes with specific enzymatic activities, or by altering the chromatin state at the site of DNA lesions. The conserved SET1/MLL family of histone methyltransferases (HMT) catalyzes methylation of histone H3 on Lysine 4 (H3K4), a histone modification universally associated with actively transcribed genes. Studies have focused on the role of SET1/MLL proteins in epigenetic regulation of gene expression. Much less is known on their role in the DNA repair process in a developmental context. Here we show that SET-2, the Caenorhabditis elegans orthologue of SET1, is required to preserve germline genome integrity over subsequent generations. Animals lacking the SET-2 catalytic subunit show a transgenerational increase in sensitivity to DNA damage-inducing agents that is accompanied by a defect in double-strand break (DSB) repair and chromosome fragmentation. These defects are not due to a failure to activate the DNA damage response (DDR) that allows detection, signaling and repair of DNA lesions, because cell cycle arrest and apoptosis, key components of this pathway, are efficiently induced in set-2 mutant animal. Rather, our results suggest that SET-2 plays a role in the transgenerational maintenance of genome stability by acting in DNA repair downstream of DDR signaling.
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Characterization of multifarious plant growth promoting traits of rhizobacterial strain AR6 under Chromium (VI) stress
Source:Microbiological Research
Author(s): Chinnannan Karthik, Namasivayam Elangovan, Thamilarasan Senthil Kumar, Subramani Govindharaju, Selvaraj Barathi, Mohammad Oves, Padikasan Indra Arulselvi
Plant growth promoting rhizobacteria (PGPR) can increase the host plant tolerance to cope up with heavy metal induced stress, which can be improve plant growth. Thus, the present study was designed to isolate Cr(VI) tolerant PGPR strain and evaluate its plant growth promoting (PGP) properties under Cr(VI) stress. Rhizobacterial strain AR6 was isolated from the rhizosphere of Phaseolus vulgaris L. and showed 99% homology with Cellulosimicrobium funkei (KM032184) in BLASTn analysis. Strain AR6 was specifically selected due to its high Cr(VI) tolerance (1200μg/ml) and substantial production of PGP substances. Strain AR6 produced 36.75μg/ml of indole acetic acid (IAA), 60.40μg/ml of ammonia and 14.23μg/ml of exopolysaccharide (EPS). Moreover, strain AR6 showed positive results for catalase, protease, amylase, lipase production and phosphate solubilization. A trend of Cr(VI) concentration dependent progressive decline for PGP traits of strain AR6 was observed excluding EPS which was regularly increased on increasing concentrations of Cr(VI). Among the four tested Cr(VI) concentrations, 250μg/ml showed the maximum toxicity to PGP activities of strain AR6. Inoculation of rhizobacterial strain AR6 significantly increased the root length of test crops in the presence of Cr(VI) and produced a considerable number of colonizes on the root of versatile dicot and monocot plants. Moreover, strain AR6 exhibited strong antagonistic activity against phytopathogen Aspergillus niger. Thus, the present study suggests that metal tolerant and PGP activities of the rhizobacterial strain AR6 could be exploited for environmental and agricultural issues.
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How type and number of training sessions influence the reliability of palpation
Publication date: Available online 29 July 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Carolina Lavazza, Valeria Milano, Alessandra Abenavoli, Alberto Maggiani
IntroductionAccurate and reliable palpation is needed to identify anatomical landmarks as well as to assess motion and dysfunctions. Although different trials suggested that training might increase reliability of palpation, the poor dependability of the examined tests may show the need to review the teaching methods to improve palpatory accuracy.The aims of this study were:Methods82 examiners with different years of experience were enrolled from AIMO institute. Two different type of training sessions were performed (individual and group training). A total of 5 training sessions were performed during 5 weeks and 5 different models with a similar BMI were used.A uni-variated statistical analysis was used to evaluate the main effect of type and number of trainings, a multi-variated analysis was used to verify cross-effects.ResultsOverall results show moderate reliability for the correct detection of the position of the heel lift (Random probability being 33%, GT = 58.6% and SIPS = 57.1%, both P-value < 0.001).No difference was shown between the types of training (p-value GT = 0.503, p-value PSIS = 1) and no overall improvement was shown after the first training (P-value(GT) = 0.25, P-value(PSIS) = 0.96). The professional group improved the reliability during the training sessions starting from substantial reliability and ended with an almost perfect reliability (P-value GT = 0.0029, P-Value PSIS<0.001). Whereas the 3rd 4th and 5th showed a decreased performance.ConclusionsType of training sessions seems not to influence reliability of palpations. The improvement of reliability during the training sessions seems to be related to the experience of examiners which plays an important role in reliability and the learning experience.
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Osteopathic manual therapy in heart failure patients: A randomized clinical trial
Publication date: Available online 29 July 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Sergio R. Thomaz, Felipe A. Teixeira, Alexandra C.G.B. de Lima, Gerson C. Junior, Magno F. Formiga, Lawrence Patrick Cahalin
BackgroundHeart Failure (HF) patients usually present with increased arterial resistance and reduced blood pressure (BP) leading to an impaired functional capacity. Osteopathic Manual Therapy (OMT) focused on myofascial release techniques (MRT) and in the balance of diaphragmatic tensions has been shown to improve blood flow in individuals using the resistive index (RI). However, its effects in HF patients have not been examined.PurposeTo evaluate the acute response of selected osteopathic techniques on RI, heart rate (HR), and BP in patients with HF.MethodsRandomized-controlled clinical trial of HF patients assigned to MRT (six different techniques with three aimed at the pelvis, two at the thorax, and one at the neck for 15 min) or Control group (subjects in supine position for 15 min without intervention). The RI of the femoral, brachial and carotid arteries was measured via doppler ultrasound while HR and BP were measured via sphygmomanometry before and after a single MRT or control intervention.ResultsTwenty-two HF patients equally distributed (50% male, mean age 53 years; range 32–69 years) (ejection fraction = 35.6%, VO2peak: 12.9 mL/kg−1 min−1) were evaluated. We found no intra or inter group differences in RI of the carotid (ΔMRT: 0.07% vs Δ Control:11.8%), brachial (ΔMRT:0.17% vs ΔControl: 2.9%), or femoral arteries (ΔMRT:1.65% vs ΔControl: 0.97%) (P > 0.05) and no difference in HR or BP (ΔMRT:0.6% vs ΔControl: 3%), (P > 0.05).ConclusionA single MRT session did not significantly change the RI, HR, or BP of HF patients.
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An ultra-effective method of generating extramultipotent cells from human fibroblasts by ultrasound
Source:Biomaterials, Volume 143
Author(s): Yong Seung Lee, Hyejung Heo, Jonghwan Lee, Sung Ung Moon, Woon Yong Jung, Yong Keun Park, Min Geun Park, Seung-Hun Oh, Soonhag Kim
Multipotent cells have similar basic features of all stem cells but limitation in ability of self-renewal and differentiation compared with pluripotent cells. Here, we have developed an ultra effective, gene- and chemical-free method of generating extra multipotent (xpotent) cells which have differentiation potential more than limited cell types, by the mechanism of ultrasound-directed permeation of environmental transition-guided cellular reprogramming (Entr). Ultrasound stimulus generated a massive number of Entr-mediated xpotent (x/Entr) spheroids from human dermal fibroblasts (HDFs) 6 days after treatment. The emergence of x/Entr was first initiated by the introduction of human embryonic stem cell (ESC) environments into the HDFs to start fast cellular reprogramming including activation of stress-related kinase signaling pathways, subsequent chromatin remodeling, and expression of pluripotent-related genes via transient membrane damage caused by ultrasound-induced cavitation. And then, pluripotent markers were transported into their adjacent HDFs via direct cell-to-cell connections in order to generate xpotent clusters. The features of x/Entr cells were intermediate between pluripotency and multipotency in terms of pluripotency with three germ layer markers, multi-lineage differentiation potential, and no teratoma formation. This physical stimulus-mediated reprogramming strategy was cost-effective, simple, quick, produced significant yields, and was safe, and can therefore provide a new paradigm for clinical application.
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Growth of hollow cell spheroids in microbead templated chambers
Source:Biomaterials, Volume 143
Author(s): Eddie Wang, Dong Wang, Andrew Geng, Richard Seo, Xiaohua Gong
Cells form hollow, spheroidal structures during the development of many tissues, including the ocular lens, inner ear, and many glands. Therefore, techniques for in vitro formation of hollow spheroids are valued for studying developmental and disease processes. Current in vitro methods require cells to self-organize into hollow morphologies; we explored an alternative strategy based on cell growth in predefined, spherical scaffolds. Our method uses sacrificial, gelatin microbeads to simultaneously template spherical chambers within a hydrogel and deliver cells into the chambers. We use mouse lens epithelial cells to demonstrate that cells can populate the internal surfaces of the chambers within a week to create numerous hollow spheroids. The platform supports manipulation of matrix mechanics, curvature, and biochemical composition to mimic in vivo microenvironments. It also provides a starting point for engineering organoids of tissues that develop from hollow spheroids.
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"Fat Grafting in the Hollow Upper Eyelids and Volumetric Upper Blepharoplasty".
BACKGROUND: Periorbital volume loss creates a shadow frame, where traditional excisional blepharoplasties may aggravate the situation. Divergence in filling treatments establishes a demand for simple and reproducible techniques to achieve consistent results. Here, the author's hollow upper eyelid evaluation and treatment approach are presented. METHODS: A retrospective photographic analysis was conducted for 32 women who underwent fat grafting on the hollow upper eyelids between 2012 and 2016. Pre- and postoperative evaluations of upper eyelid ratios at the medial and lateral corneal limbus, together with lateral contour modifications, were used to determine the efficacy of the technique to restore the youthful proportions and contours. RESULTS: Preoperative analysis showed 20 eyelids with an inner shadow or A-pattern and 44 eyelids with the complete extension of the hollow or C-pattern. Three patients presented mild blepharoptosis, and eight patients had undergone a previous upper blepharoplasty. Mean grafting volume was 0.4 cc in the deep plane and 2.8 cc in the superficial plane. Fat grafting exclusively was performed in six patients, improving all ratios and correcting the A-pattern deformity. Volumetric upper blepharoplasty combining fat grafting in two levels and orbicularis oculi muscle imbrication was performed in 26 patients, correcting every inverted ratio (p
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Methane-rich saline alleviates cerulein-induced acute pancreatitis by inhibiting inflammatory response, oxidative stress and pancreatic apoptosis in mice
Publication date: October 2017
Source:International Immunopharmacology, Volume 51
Author(s): Qun Xie, Miaomiao Fei, Zhenzong Fa, Liping Wang, Jun Wang, Yan Zhang, Jiafeng Wang, Xiaoming Deng
BackgroundAcute pancreatitis (AP) is a potentially life-threatening gastrointestinal disease involving intracellular activation of digestive enzymes and pancreatic acinar cell injury. The present study was performed to investigate whether methane-rich saline (MS) was involved in the regulation of AP.MethodsMS (16ml/kg) was administered at different dosing frequencies on mice with cerulein-induced AP. Serum amylase, lipase and histopathological changes in the pancreas tissue were measured. Serum cytokine TNFα, IL-6, IFNγ and IL-10 were detected by ELISA. The mRNA levels of these inflammatory cytokines in the pancreas were detected by real time-PCR. Myeloperoxidase (MPO) and superoxide dismutase (SOD) were determined using commercial kits. Apoptosis was assessed by immunohistochemistry and Western blot.ResultsMS treatment reversed the increased serum level of amylase and lipase, alleviated the pathological damage in the pancreas, and decreased the expression of TNFα, IL-6, IFNγ and IL-10 in cerulean-induced AP mice. In addition, MPO was down-regulated and SOD was up-regulated in the MS treated pancreas, indicating that MS had an anti-oxidant effect against AP. Furthermore, MS protected pancreatic cells against cerulean-induced apoptosis and abolished cleaved caspase-3.ConclusionMS exerted anti-inflammatory, anti-oxidant and anti-apoptotic effects on cerulein-induced AP in mice and may proved to be a promising therapeutic agent for the clinical treatment of pancreatitis.
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Cathelicidins display conserved direct antiviral activity towards rhinovirus
Source:Peptides
Author(s): Filipa Henderson Sousa, Victor Casanova, Fern Findlay, Craig Stevens, Pavel Svoboda, Jan Pohl, Lorna Proudfoot, Peter G. Barlow
Human rhinoviruses (HRVs) are the most common cause of viral respiratory tract infections, and are associated with significant morbidity and mortality in immunocompromised individuals and patients with pre-existing pulmonary conditions. The therapeutic options available are extremely limited and therefore novel therapeutics for HRV infections are of significant interest. Cathelicidins have been shown to have potent antiviral activity against a range of pathogens and are known to be key immunomodulatory mediators during infection. We therefore assessed the antiviral potential of cathelicidins from humans and other mammalian species against HRV, together with the potential for the human cathelicidin to modulate apoptotic pathways and alter cell viability during HRV infection. We demonstrate that LL-37, the porcine cathelicidin Protegrin-1, and the ovine cathelicidin SMAP-29 display potent antiviral activity towards HRV and that this activity is visible when either the virus is exposed to the peptides prior to cell infection or after cells have been infected. We further demonstrate that, in contrast to established findings with bacterial infection models, LL-37 does not induce apoptosis or necrosis in HRV-infected lung epithelial cells at physiological or superphysiological concentrations, but does reduce the metabolic activity of infected cells compared to uninfected cells treated with similar peptide concentrations. Collectively, the findings from this study demonstrate that the mechanism of action of cathelicidins against rhinovirus is by directly affecting the virus and we propose that the delivery of exogenous cathelicidins, or novel synthetic analogues, represent an exciting and novel therapeutic strategy for rhinovirus infection.
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Empirical research evaluating the effects of non-traditional approaches to enhancing sleep in typical and clinical children and young people
This paper examines the effects of non-traditional (non-behavioural and non-prescription pharmaceutical) approaches on sleep in children and young people (0-18 years). A systematic search identified 79 studies that met inclusion criteria. Seventeen percent of the studies were rated as having a conclusive level of evidence, forty-two percent with preponderant evidence and forty-one percent with only suggestive evidence. There were promising indications, with certain populations only, for aromatherapy, ketagenic diets, an elimination diet (few foods diet), elimination of cows milk, avoidance of caffeine, tryptophan with adenosine and uridine, omega-3 and omega-6, valerian, music, osteopathic manipulation and white noise.
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Investigating quality of life and self-stigma in Hong Kong children with specific learning disabilities
Source:Research in Developmental Disabilities, Volume 68
Author(s): Yi Chan, Yim Yuk Chan, Sui Lam Cheng, Yin Man Chow, Yau Wai Tsang, Clara Lee, Chung-Ying Lin
BackgroundChildren with specific learning disabilities (SpLD) are likely to develop self-stigma and have a poor quality of life (QoL) because of their poor academic performance. Although both self-stigma and poor QoL issues are likely to be found in low academic achievers without SpLD, children with SpLD have worse situation because their diagnosis of SpLD suggests that their learning struggles are biological and permanent. Specifically, students' perception of own capabilities may be affected more by the diagnosis of SpLD than their own actual performance.AimsWe examined the self-stigma and QoL of children with SpLD in Hong Kong, a region with an academics-focused culture.Methods and proceduresChildren with SpLD (n=49,Mage±SD=9.55±1.21; SpLD group) and typically developing children (n=32,Mage±SD=9.81±1.40; TD group) completed a Kid-KINDL to measure QoL and a Modified Self-Stigma Scale to measure self-stigma. All parents completed a parallel Kid-KINDL to measure QoL of their children.Outcomes and resultsCompared with the TD group, the SpLD group had a higher level of self-stigma (p=0.027) and lower QoL (child-reported Kid-KINDL: p=0.001; parent-reported Kid-KINDL: p<0.001).Conclusions and implicationsIn the academics-focused environment in Hong Kong, SpLD was associated with impaired QoL and higher self-stigma. Treatments targeting the learning process of children with SpLD may be designed to overcome self-stigma and to improve QoL. In addition, the program may involve parents of the children with SpLD or other people (e.g., the peer of the children with SpLD) for improving their understanding and perceptions of SpLD.
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Common and Uncommon Causes of Ventriculoperitoneal Shunt Malfunction Diagnosed on Plain Radiographs
Source:Current Problems in Diagnostic Radiology
Author(s): Phillip Bates, Dhanashree Rajderkar
Thousands of patients with hydrocephalus are treated successfully with ventriculoperitoneal shunts (VP shunts). VP shunts are known to have high malfunction rates, most of which are due to mechanical causes. When shunt malfunction is suspected, shunt series are often performed to evaluate the mechanical causes of malfunction. These initial radiographs have proven critical in guiding subsequent management. This article is designed to review the various causes of shunt malfunction that can be diagnosed with radiographs.
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Characteristics of the Most Recently Awarded MRI Patents in the United States
Source:Current Problems in Diagnostic Radiology
Author(s): Sushma Gaddam, Gregory Lemberskiy, Andrew B. Rosenkrantz
PurposeTo characterize recent MRI technical development and innovation based on data regarding MRI-related patents awarded in 2016.MethodsThe U.S. Patent and Trademark Office website was searched for patents awarded in 2016 and an abstract containing "magnetic resonance." Patent characteristics were summarized. An MRI physicist classified patents′ themes.Results423 MRI-related patents were awarded in 2016. 29% had one inventor, 24% two inventors, and 47% ≥2 inventors. Mean interval between patents being filed and awarded was 1,389±559 days (range, 167–4,029). Most common countries of patents′ first assignee were: USA (40%), Germany (24%), Netherlands (10%), and Japan (10%). 3% included assignees with different countries (most common collaborators USA and Germany). Patents′ first assignee had an industry affiliation in 76% vs. an academic affiliation in 21% (4% indeterminate). 3% had industry-academia collaboration. Patents′ most common themes were: coils (n=77), sequence design (n=65), and non-coil scanner hardware (n=41). These top themes were similar for USA, international, and industry based patents; however, for academic based patents, the most common themes were: sequence design, reconstruction, and exogenous agents. Less common themes included: image analysis, post-processing, spectroscopy, relaxometry, diffusion, motion correction, radiation therapy, implants, wireless devices, and PET/MRI.ConclusionThe majority of MRI-related patents were by non-U.S. inventors. A large majority had industry affiliation; minimal industry-academic collaboration was observed. Patents from industry and academic inventors had distinct top focuses: hardware and software, respectively. Awareness of the most recent years′ MRI patents may provide insights into forthcoming clinical translations and help guide ongoing research and entrepreneurism.
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Diffusion Tensor Imaging Of The Spinal Cord: Clinical Value, Investigational Applications, and Technical Limitations
Source:Current Problems in Diagnostic Radiology
Author(s): Aaron M. Rutman, Daniel Peterson, Wendy A. Cohen, Mahmud Mossa-Basha
While diffusion weighted imaging (DWI) has become a mainstay in modern brain imaging, it remains less utilized in the evaluation of the spinal cord. Many studies have shown promise in using DWI and diffusion tensor imaging (DTI) for evaluation of the spinal cord; however, application has been stalled by technical obstacles and artifacts, and questions remain regarding its clinical utility on an individual exam level. This review discusses the background, concepts, and technical aspects of DWI and DTI, specifically for imaging of the spinal cord. The clinical and investigational applications of spinal cord DTI, as well as the practical difficulties and limitations of DWI and DTI for the evaluation of the spinal cord are examined.
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Multimodality Imaging Spectrum of The Extranodal Lymphomas in The Head and Neck- A Pictorial Review
Source:Current Problems in Diagnostic Radiology
Author(s): Pankaj Watal, Girish Bathla, Siddharth Thaker, T Shawn Sato, Toshio Moritani, Wendy R.K. Smoker
Lymphoma is the second most common malignant neoplasm of the head and neck region, involving the nodal and/or extranodal sites in a variable fashion. Lymphoma may mimic a variety of tumors in this region depending on the subsite involved. The usual presentation of lymphomatous disease is presence of multiple enlarged, often conglomerate, lymph nodes without significant necrosis. Extranodal lymphomas demonstrate more complex radiologic features, but careful evaluation can identify distinct imaging patterns to suggest extranodal lymphomatous disease from other more common lesions. Knowledge of these imaging features can help raise suspicion for lymphoma as a differential consideration. This can be of critical importance since further work-up and management can be vastly different between lymphomatous disease and other disease entities. The authors present a pictorial review of the spectrum of imaging findings in extra-nodal head and neck lymphomas [EHNL].
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Accuracy and variability of high-dose-rate prostate brachytherapy needle tip localization using live two-dimensional and sagittally reconstructed three-dimensional ultrasound
Source:Brachytherapy
Author(s): William Thomas Hrinivich, Douglas A. Hoover, Kathleen Surry, Chandima Edirisinghe, Vikram Velker, Glenn Bauman, David D'Souza, Aaron Fenster, Eugene Wong
PurposeTo measure the accuracy and variability of manual high-dose-rate (HDR) prostate brachytherapy (BT) needle tip localization using sagittally reconstructed three-dimensional (3D) transrectal ultrasound (TRUS) augmented with live two-dimensional (2D) sagittal TRUS.Methods and MaterialsTen prostate cancer patients underwent HDR-BT during which the sagittally assisted sagittally reconstructed (SASR) segmentation technique was completed in parallel with commercially available sagittally assisted axially reconstructed (SAAR) TRUS for comparison. The SASR technique makes use of live 2D ultrasound intraoperatively and allows needle tip updates using the final 3D image in the absence of image artifacts. These updates were repeated offline twice by two separate users. Needle end-length measurements were used to calculate insertion depth errors (IDEs) for each technique.ResultsImages of 147 needles were analyzed. For the SASR technique, both users were confident in tip positions on the final 3D image within 3 mm for 52% of needles, so these tip positions were updated. For the remaining 48% of needles, the tip positions from the live 2D images were used. This SASR technique enabled the localization of all needles with IDEs within ±3 mm for 84% of needles and IDE range of [−6.2 mm, 5.9 mm], compared with 57% and [−8.1 mm, 7.7 mm] when using the commercially available SAAR technique.ConclusionsThe SASR technique mitigates the impact of 3D TRUS image artifacts on HDR-BT needle tip localization by incorporating live 2D sagittal TRUS intraoperatively and provides a statistically significant reduction in IDE variance compared with the routine SAAR technique.
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Lesion localization using the scroll bar on tomosynthesis: Why doesn't it always work?
Publication date: Available online 29 July 2017
Source:Clinical Imaging
Author(s): Sarah M. Friedewald, Victoria A. Young, Dipti Gupta
The scroll bar on digital breast tomosynthesis (DBT) is an important tool that facilitates localization of lesions on the orthogonal view. While this works well most of the time, occasionally the location of the lesion as directed by the scroll bar is seemingly inaccurate. There are five important reasons why the scroll bar indicator may suggest a contradictory lesion location. Understanding specific scenarios when this may occur will aid the reader in reconciling these differences.
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Disturbed Desmoglein-2 in the Intercalated Disc of Pediatric Patients with Dilated Cardiomyopathy
Publication date: Available online 29 July 2017
Source:Human Pathology
Author(s): Elise L Kessler, Peter GJ Nikkels, Toon AB van Veen
Dilated cardiomyopathy (DCM) leads to disturbed contraction and force transduction, and is associated with substantial mortality in all age groups. Involvement of a disrupted composition of the intercalated disc (ID) has been reported. However, in children, little is established about such subcellular changes during disease, because of the pathological mix-up with the ongoing cardiac maturation. This leaves maladaptive remodeling often undetected. We aimed at illustrating subcellular alterations in children diagnosed with DCM compared to age-matched controls, focusing on ID proteins known to be crucially stable under healthy conditions and destabilized during cardiac injury in adults. Left Ventricular or septal pediatric specimens were collected from 7 individuals diagnosed with DCM (age: 23weeks in utero - 8weeks postnatal) and age-matched controls that died of non-cardiovascular cause. We determined the amount of fibrosis and localization of ID proteins by immunohistochemistry. In pediatric DCM, most ID proteins follow similar spatio-temporal changes in localization as in controls. However, although no mutations were found, the signal of the desmosomal protein Desmoglein-2 was reduced in all pediatric DCM specimens, but not in controls or adult DCM patients. Endocardial and transmural fibrosis was increased in all pediatric DCM patients compared to age-matched controls. Composition of the ID in pediatric DCM patients is similar to controls, except for the localization of Desmoglein-2 and presence of severe fibrosis. This suggests that the architecture of desmosomes is already disturbed in the early stages of DCM. These findings contribute to the understanding of pediatric DCM.
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Status of Resident Attrition From Surgical Residency in the Past, Present, and Future Outlook
Publication date: Available online 29 July 2017
Source:Journal of Surgical Education
Author(s): Faris Shweikeh, Alexander C. Schwed, Chiu-Hsieh Hsu, Valentine N. Nfonsam
ObjectiveTo investigate the current rate of attrition in general surgery residency, assess the risk factors, and identify prevention strategies.DesignA literature review of the PubMed and MEDLINE databases, from January 1, 1980 to February 1, 2016, for relevant articles. The calculated attrition rate and the statistically significant influencing factors were the main measures and outcomes.SelectionAll English language articles that described attrition from a general surgery residency were included. Articles that performed an assessment of attrition rates, academic performance, reasons for resident loss, and demographics were identified and data from these studies were collected. Random-effect meta-analysis and meta-regression based on a generalized mixed-effects model was performed.ResultsA total of 26 studies were included. Reported attrition rates ranged from 2% to 30% over the course of residency training. Random-effect meta-analysis is indicative of a yearly attrition rate of 2.4% (95% CI: 1.3%-3.5%) and a cumulative 5-year attrition rate of 12.9% (95% CI: 7.9%-17.8%). Most of them leave residency during their first 2 years, and the rate significantly decreases with increasing postgraduate year (p < 0.0001). The Accreditation Council for Graduate Medical Education mandated 80-hour week is associated with a higher rate, though not significantly (3.2% [95% CI: 1.3%-5.1%] vs. 2.2% [0.9%-3.5%], p = 0.37). Pooled analysis demonstrates no statistically significant difference in the rate of attrition between males and females (2.1% [95% CI: 1.1%-3%] vs. 2.9% [95% CI: 1.6%-4.1%], p = 0.73). Most remain in graduate medical education and pursue residency training in other specialties.ConclusionAttrition in general surgery most commonly occurs within the first 2 years of training and, in contrast to previous findings, is not related to female sex. Restrictions on work hours seem to have increased the rate, whereas remediation practices can prevent it. Training programs should direct efforts towards attrition-prevention strategies.
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Physical Function after Total Knee Replacement: An observational study describing outcomes in a small group of women from China and the United States
Publication date: Available online 29 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Daniel K. White, Zhichang Li, Yuqing Zhang, Adam R. Marmon, Hiral Master, Joseph Zeni, Jingbo Niu, Long Jiang, Shu Zhang, Jianhao Lin
ObjectiveTo describe physical function before and six months after Total Knee Replacement (TKR) in a small sample of women from China and the United States (US).Participants60 women after TKR from China and the USDesign, Setting, Outcomes: Data was from an observational study of TKR outcomes in Newark, Delaware (US group) and a control group after TKR in Beijing (China group). Both groups followed the same Osteoarthritis Research Society International (OARSI) protocols for the six-minute walk and 30-second chair stand. We compared physical function prior to TKR and six months after using linear regression adjusted for covariates.ResultsAge and BMI were similar in the China group (n=30, 66 years and 27.0 kg/m2) as the US group (n=30, 65 years and 29.6 kg/m2). Before surgery, the China group walked 263 (95%CI [-309,-219]) less meters and had 10.2 (95%CI [-11.8, -8.5]) fewer chairs stands than the US group. At six months when compared to the US group, the China group walked 38 more meters, but this difference did not reach statistical significance (95%CI [-1.6, 77.4]), and had 3.1 (95%CI [-4.4, -1.7]) fewer chair stands. The China group had greater improvement in the six-minute walk compared with the US group, p< 0.001.ConclusionDespite having worse physical function prior to TKR, the China group had greater gains in walking endurance and similar gains in repeated chair stands compared with the US group after surgery.
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Work productivity loss after mild traumatic brain injury
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Noah D. Silverberg, William J. Panenka, Grant L. Iverson
ObjectiveTo examine the completeness of return to work (RTW) and the degree of productivity loss in individuals who do achieve a complete RTW after mild traumatic brain injury (MTBI).DesignMulti-site prospective cohort.SettingOutpatient concussion clinics.ParticipantsSeventy-nine patients (M=41.5 years old, 55.7% female) who sustained an MTBI and were employed at the time of the injury. Participants were enrolled at their first clinic visit and assessed by telephone 6-8 months post-injury.InterventionNone.MeasuresStructured interview of RTW status, British Columbia Postconcussion Symptom Inventory (BC-PSI), Lam Employment Absence and Productivity Scale (LEAPS), MINI Neuropsychiatric Interview, brief pain questionnaire. Participants who endorsed symptoms from three or more categories with at least moderate severity on the BC-PSI were considered to meet International Classification of Diseases-10 criteria for postconcussional syndrome. RTW status was classified as complete if participants returned to their pre-injury job with the same hours and responsibilities or to a new job that was at least as demanding.ResultsOf the 46 (58.2%) patients who achieved a RTW, 33 (71.7%) had a complete RTW. Participants with complete RTW had high rates of postconcussional syndrome (44.5%) and comorbid depression (18.2%), anxiety disorder (24.2%), and bodily pain (30.3%). They also reported productivity loss on the LEAPS, such as "getting less work done" (60.6%) and "making more mistakes" (42.4%). In a regression model, productivity loss was predicted by the presence of postconcussional syndrome and a comorbid psychiatric condition, but not bodily pain.ConclusionEven in patients who RTW after MTBI, detailed assessment revealed underemployment and productivity loss associated with residual symptoms and psychiatric complications.
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Kinesiophobia and its Association with Health Related Quality of Life Across Injury Locations
Publication date: Available online 29 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Penny Goldberg, Giorgio Zeppieri, Joel Bialosky, Charlotte Bocchino, Jon van den Boogaard, Susan Tillman, Terese L. Chmielewski
ObjectiveTo compare baseline kinesiophobia levels and their association with health-related quality of life across injury locations.DesignRetrospective cross-sectional study.SettingSingle, large outpatient physical therapy clinic within an academic medical center.Participants1233 patients who underwent an initial evaluation for a diagnosis related to musculoskeletal pain and completed the TSK-11 and SF-8™ questionnaires within 7 days of their first visit were eligible for inclusion. 380 patients were excluded for missing data or because they were under 18 years of age.InterventionsNot applicable.Main Outcome MeasuresComparison of baseline kinesiophobia levels and their association with health-related quality of life across injury locations in an outpatient physical therapy setting.ResultsA total of 853 patients (range: 18-94 years, mean age = 43.55 years) were included. Separate ANOVA models compared TSK-11 scores based on involved body region and Pearson correlation coefficients were used to examine the association between TSK-11 scores the SF-8™ sub-scales at each body region. TSK-11 scores did not differ by body region (range = 23.9 to 26.1). Weak to moderate negative correlations existed between kinesiophobia and the SF-8™ subscales.ConclusionKinesiophobia levels appear elevated and negatively associated with health-related quality of life at initial physical therapy evaluation regardless of injury location. These findings suggest physical therapists in outpatient orthopaedic settings should implement routine kinesiophobia assessment and provide stratified care based on kinesiophobia levels across musculoskeletal conditions.
http://ift.tt/2v9WvhI
A highly stable acetylcholinesterase biosensor based on chitosan-TiO2-graphene nanocomposites for detection of organophosphate pesticides
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Hui-Fang Cui, Wen-Wen Wu, Meng-Meng Li, Xiaojie Song, Yuanxu Lv, Ting-Ting Zhang
A highly stable electrochemical acetylcholinesterase (AChE) biosensor for detection of organophosphorus pesticides (OPs) was developed simply by adsorption of AChE on chitosan (CS), TiO2 sol-gel, and reduced graphene oxide (rGO) based multi-layered immobilization matrix (denoted as CS@TiO2-CS/rGO). The biosensor fabrication conditions were optimized, and the fabrication process was probed and confirmed by scanning electron microscopy and electrochemical techniques. The matrix has a mesoporous nanostructure. Incorporation of CS and electrodeposition of a CS layer into/on the TiO2 sol-gel makes the gel become mechanically strong. The catalytic activity of the AChE immobilized CS@TiO2-CS/rGO/glassy carbon electrode to acetylthiocholine is significantly higher than those missing any one of the component in the matrix. The detection linear range of the biosensor to dichlorvos, a model OP compound, is from 0.036μM (7.9 ppb) to 22.6μM, with a limit of detection of 29nM (6.4 ppb) and a total detection time of about 25min. The biosensor is very reproducibly and stable both in detection and in storage, and can accurately detect the dichlorvos levels in cabbage juice samples, providing an efficient platform for immobilization of AChE, and a promisingly applicable OPs biosensor with high reliability, simplicity, and rapidness.
http://ift.tt/2v9TKgi
Highly efficient electrochemical sensing platform for sensitive detection DNA methylation, and methyltransferase activity based on Ag NPs decorated carbon nanocubes
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Fenglei Gao, Taotao Fan, Shanshan Ou, Jing Wu, Xing Zhang, Jianjun Luo, Na Li, Yao Yao, Yingfeng Mou, Xianjiu Liao, Deqin Geng
In this paper, we reported a sensitive and selective electrochemical method for quantify DNA methylation, analyzing DNA MTase activity and screening of MTase inhibitor based on silver nanoparticles (Ag NPs) decorated carbon nanocubes (CNCs) as signal tag. The Ag NPs/CNCs was prepared by in situ growth of nanosilver on carboxylated CNCs and used as a tracing tag to label antibody. The sensor was prepared by immobilizing the double DNA helix structure on the surface of gold electrode. When DNA MTase was introduced, the probe was methylated. Successively, anti-5-methylcytosine antibody labeled Ag NPs/CNCs was specifically conjugated on the CpG methylation site. The electrochemical stripping signal of the Ag NPs was used to monitor the activity of MTase. The electrochemical signal has a linear relationship with M.SssI activities ranging from 0.05 to 120U/mL with a detection limit of 0.03U/mL. In addition, we also demonstrated the method could be used for rapid evaluation and screening of the inhibitors of MTase. The newly designed strategy avoid the requirement of deoxygenation for electrochemical assay, and thus provide a promising potential in clinical application.
http://ift.tt/2tMLqQ7
A high-sensitivity electrochemical aptasensor of carcinoembryonic antigen based on graphene quantum dots-ionic liquid-nafion nanomatrix and DNAzyme-assisted signal amplification strategy
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Jing-Yi Huang, Lang Zhao, Wan Lei, Wei Wen, Yi-Jia Wang, Ting Bao, Hua-Yu Xiong, Xiu-Hua Zhang, Sheng-Fu Wang
In this work, we have developed an electrochemical aptasensor for high-sensitivity determination of carcinoembryonic antigen (CEA) based on lead ion (Pb2+)-dependent DNAzyme-assisted signal amplification and graphene quantum dot-ionic liquid-nafion (GQDs-IL-NF) composite film. We designed hairpin DNA containing CEA-specific aptamers and DNAzyme chains. In the presence of CEA, hairpin DNA recognized the target and performed a DNAzyme-assisted signal amplification reaction to yield a large number of single-stranded DNA. The GQDs-IL-NF composite film was immobilized on the glassy carbon electrode for the interaction with single-stranded DNA through noncovalent π-π stacking interaction. Therefore, the methylene blue-labeled substrate DNA (MB-substrate) was fixed on the electrode and exhibited an initial electrochemical signal. Under optimal conditions, the response current change was proportional to the concentration of CEA, demonstrating a wide linear range from 0.5fgmL−1 to 0.5ngmL−1, with a low detection limit of 0.34fgmL−1. Furthermore, the proposed aptasensor was successfully applied in determining CEA in serum samples, showing its superior prospects in clinical diagnosis.
http://ift.tt/2v9WKJJ
Analytical, thermodynamical and kinetic characteristics of photoluminescence immunosensor for the determination of Ochratoxin A
Publication date: 15 January 2018
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Roman Viter, Maryna Savchuk, Igor Iatsunskyi, Zuzanna Pietralik, Nikolay Starodub, Nelya Shpyrka, Almira Ramanaviciene, Arunas Ramanavicius
Ochratoxin A (OTA) is one of the most widespread and dangerous food contaminants. Therefore, rapid, label-free and precise detection of low OTA concentrations requires novel sensing elements with advanced bio-analytical properties. In the present paper we report photoluminescence (PL) based immunosensor for the detection of OTA. During the development of immunosensor photoluminescent ZnO nanorods (ZnO-NRs) were deposited on glass substrate. Then the ZnO-NRs were silanized and covalently modified by Protein-A (Glass/ZnO-NRs/Protein-A). The latest structure was modified by antibodies against OTA (Anti-OTA) in order to form OTA-selective layer (Glass/ZnO-NRs/Protein-A/Anti-OTA). In order to improve immunosensors selectivity the surface of Glass/ZnO-NRs/Protein-A/Anti-OTA was additionally blocked by BSA. Formed Glass/ZnO-NRs/Protein-A/BSA&Anti-OTA structures were integrated within portable fiber optic detection system, what is important for the development of low cost and portable immunosensors. The immunosensor has been tested in a wide range of OTA concentrations from 10−4ng/ml until 20ng/ml. Interaction isotherms were derived from analytical signals of immunosensor. Association constant and Gibbs free energy for the interaction of Glass/ZnO-NRs/Protein-A/Anti-OTA with OTA were calculated, analyzed and compared with some other related results. Sensitivity range and limit of detection were determined as 0.1–1ng/ml and 10−2ng/ml, respectively. Interaction kinetics of ZnO-NRs with OTA was evaluated. Response time of the immunosensor toward OTA was in the range of 500–800s. Some insights related to the mechanism of PL-signal generation are proposed and discussed.
Graphical abstract
http://ift.tt/2tMZFEB
Fluorinated tripodal receptors for potentiometric chloride detection in biological fluids
Publication date: 15 January 2018
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Nadezda Pankratova, Maria Cuartero, Laura A. Jowett, Ethan N.W. Howe, Philip A. Gale, Eric Bakker, Gastón A. Crespo
Fluorinated tripodal compounds were recently reported to be efficient transmembrane transporters for a series of inorganic anions. In particular, this class of receptors has been shown to be suitable for the effective complexation of chloride, nitrate, bicarbonate and sulfate anions via hydrogen bonding. The potentiometric properties of urea and thiourea-based fluorinated tripodal receptors are explored here for the first time, in light of the need for reliable sensors for chloride monitoring in undiluted biological fluids. The ion selective electrode (ISE) membranes with tren-based tris-urea bis(CF3) tripodal compound (ionophore I) were found to exhibit the best selectivity for chloride over major lipophilic anions such as salicylate (logKCl−/Sal−pot=+1.0) and thiocyanate (logKCl−/SCN−pot=+0.1). Ionophore I-based ISEs were successfully applied for chloride determination in undiluted human serum as well as artificial serum sample, the slope of the linear calibration at the relevant background of interfering ions being close to Nernstian (49.8±1.7mV). The results of potentiometric measurements were confirmed by argentometric titration. Moreover, the ionophore I-based ISE membrane was shown to exhibit a very good long-term stability of potentiometric performance over the period of 10 weeks. Nuclear magnetic resonance (NMR) titrations, potentiometric sandwich membrane experiments and density functional theory (DFT) computational studies were performed to determine the binding constants and suggest 1:1 complexation stoichiometry for the ionophore I with chloride as well as salicylate.
http://ift.tt/2tMwn93
Sliding-strip microfluidic device enables ELISA on paper
Publication date: 15 January 2018
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Mohit S. Verma, Maria-Nefeli Tsaloglou, Tyler Sisley, Dionysios Christodouleas, Austin Chen, Jonathan Milette, George M. Whitesides
This article describes a 3D microfluidic paper-based analytical device that can be used to conduct an enzyme-linked immunosorbent assay (ELISA). The device comprises two parts: a sliding strip (which contains the active sensing area) and a structure surrounding the sliding strip (which holds stored reagents—buffers, antibodies, and enzymatic substrate—and distributes fluid). Running an ELISA involves adding sample (e.g. blood) and water, moving the sliding strip at scheduled times, and analyzing the resulting color in the sensing area visually or using a flatbed scanner. We demonstrate that this device can be used to detect C-reactive protein (CRP)—a biomarker for neonatal sepsis, pelvic inflammatory disease, and inflammatory bowel diseases—at a concentration range of 1–100ng/mL in 1000-fold diluted blood (1–100µg/mL in undiluted blood). The accuracy of the device (as characterized by the area under the receiver operator characteristics curve) is 89% and 83% for cut-offs of 10ng/mL (for neonatal sepsis and pelvic inflammatory disease) and 30ng/mL (for inflammatory bowel diseases) CRP in 1000-fold diluted blood respectively. In resource-limited settings, the device can be used as a part of a kit (containing the device, a fixed-volume capillary, a pre-filled tube, a syringe, and a dropper); this kit would cost ~ $0.50 when produced in large scale (>100,000 devices/week). This kit has the technical characteristics to be employed as a pre-screening tool, when combined with other data such as patient history and clinical signs.
http://ift.tt/2v4DnlA
Shell-encoded Au nanoparticles with tunable electroactivity for specific dual disease biomarkers detection
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Yuan Zhao, Yaxin Yang, Yali Sun, Linyan Cui, Fangjie Zheng, Jiru Zhang, Qijun Song, Chuanlai Xu
The exploration of electroactive labelling with tailorable and strong differential pulse voltammetry (DPV) responses is of great importance in accurate and sensitive screening of a panel of biomarkers related to cancer. Herein, shell-encoded gold nanoparticles (Au NPs) are fabricated and give rise to shell species-dominated DPV peak potentials. Two independent DPV peaks appear at −0.08V for Au@Cu2O core-shell NPs and 0.26V for Au@Ag core-shell NPs. Shell-encoded Au NPs drastically exhibit shell thickness-tunable amplified peak currents. The non-interfering and amplified DPV responses enable shell-encoded Au NPs to be an alternative electrochemical signal amplifier for dual screening of carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). The limits of detection (LODs) are calculated to be 1.8pg/mL for CEA and 0.3pg/mL for AFP. In comparison to the parallel single-analyte assays, shell-encoded Au NPs engineered electrochemical aptasensors offer multiplexing capability and show significant prospects in biomedical research and early diagnosis of diseases.
http://ift.tt/2vaeJiW
Hall effect biosensors with ultraclean graphene film for improved sensitivity of label-free DNA detection
Publication date: 15 January 2018
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Phan Thi Kim Loan, Dongqin Wu, Chen Ye, Xiaoqing Li, Vu Thanh Tra, Qiuping Wei, Li Fu, Aimin Yu, Lain-Jong Li, Cheng-Te Lin
The quality of graphene strongly affects the performance of graphene-based biosensors which are highly demanded for the sensitive and selective detection of biomolecules, such as DNA. This work reported a novel transfer process for preparing a residue-free graphene film using a thin gold supporting layer. A Hall effect device made of this gold-transferred graphene was demonstrated to significantly enhance the sensitivity (≈ 5 times) for hybridization detection, with a linear detection range of 1pM to 100nM for DNA target. Our findings provide an efficient method to boost the sensitivity of graphene-based biosensors for DNA recognition.
Graphical abstract
http://ift.tt/2tMwjpW
DNA origami nanorobot fiber optic genosensor to TMV
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Emanuela Torelli, Marisa Manzano, Sachin K. Srivastava, Robert S. Marks
In the quest of greater sensitivity and specificity of diagnostic systems, one continually searches for alternative DNA hybridization methods, enabling greater versatility and where possible field-enabled detection of target analytes. We present, herein, a hybrid molecular self-assembled scaffolded DNA origami entity, intimately immobilized via capture probes linked to aminopropyltriethoxysilane, onto a glass optical fiber end-face transducer, thus producing a novel biosensor. Immobilized DNA nanorobots with a switchable flap can then be actuated by a specific target DNA present in a sample, by exposing a hemin/G-quadruplex DNAzyme, which then catalyzes the generation of chemiluminescence, once the specific fiber probes are immersed in a luminol-based solution. Integrating organic nanorobots to inorganic fiber optics creates a hybrid system that we demonstrate as a proof-of-principle can be utilized in specific DNA sequence detection. This system has potential applications in a wide range of fields, including point-of-care diagnostics or cellular in vivo biosensing when using ultrathin fiber optic probes for research purposes.
http://ift.tt/2tMUGUg
Graphene oxide@gold nanorods-based multiple-assisted electrochemiluminescence signal amplification strategy for sensitive detection of prostate specific antigen
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Jun-Tao Cao, Jiu-Jun Yang, Li-Zhen Zhao, Yu-Ling Wang, Hui Wang, Yan-Ming Liu, Shu-Hui Ma
A novel and competitive electrochemiluminescence (ECL) aptasensor for prostate specific antigen (PSA) assay was constructed using gold nanorods functionalized graphene oxide (GO@AuNRs) multilabeled with glucose oxidase (GOD) and streptavidin (SA) toward luminol-based ECL system. A strong initial ECL signal was achieved by electrodeposited gold (DpAu) on the electrode because of gold nanoparticles (AuNPs) motivating the luminol ECL signal. The signal probes prepared by loading GOD and SA-biotin-DNA on GO@AuNRs were used for achieving multiple signal amplification. In the absence of PSA, the signal probes can be attached on the electrode by hybridization reaction between PSA aptamer and biotin-DNA. In this state, the GOD loaded on the probe could catalyze glucose to in situ produce H2O2 and then AuNRs catalyze H2O2 to generate abundant reactive oxygen species (ROSs) in luminol ECL reaction. Both the high-content GOD and AuNRs in the signal probe amplified the ECL signal in the ECL system. Moreover, the combination of SA with biotin-DNA further expands ECL intensity. The integration of such amplifying effects in this protocol endows the aptasensor with high sensitivity and good selectivity for PSA detection. This aptasensor exhibits a linear relation in the range of 0.5pgmL−1 to 5.0ngmL−1 with the detection limit of 0.17pgmL−1 (S/N = 3). Besides, the strategy was successfully applied in determination of human serum samples with recovery of 81.4–116.0%.
http://ift.tt/2v9DSKQ
Molecular imprinting coupled with electrochemical analysis for plasma samples classification in acute myocardial infarction diagnostic
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Victoria V. Shumyantseva, Tatiana V. Bulko, Larisa V. Sigolaeva, Alexey V. Kuzikov, Pavel V. Pogodin, Alexander I. Archakov
Electroanalysis of myoglobin (Mb) in 10 plasma samples of healthy donors (HDs) and 14 plasma samples of patients with acute myocardial infarction (AMI) was carried out with screen-printed electrodes modified first with multi-walled carbon nanotubes (MWCNT) and then with a molecularly imprinted polymer film (MIP), viz., myoglobin-imprinted electropolymerized poly(o-phenylenediamine). The differential pulse voltammetry (DPV) parameters, such as a maximum amplitude of reduction peak current (A, nA), a reduction peak area (S, nA × V), and a peak potential (P, V), were measured for the MWCNT/MIP-sensors after their incubation with non-diluted plasma. The relevance of the multi-parameter electrochemical data for accurate discrimination between HDs and patients with AMI was assessed on the basis of electrochemical threshold values (this requires the reference standard method (RAMP® immunoassay)) or alternatively on the basis of the computational cluster assay (this does not require any reference standard method). The multi-parameter electrochemical analysis of biosamples combined with computational cluster assay was found to provide better accuracy in classification of plasma samples to the groups of HDs or AMI patients.
http://ift.tt/2tMHiji
Liposome-amplified photoelectrochemical immunoassay for highly sensitive monitoring of disease biomarkers based on a split-type strategy
Source:Biosensors and Bioelectronics, Volume 99
Author(s): Junyang Zhuang, Bin Han, Wenchao Liu, Jinfei Zhou, Kewei Liu, Dapeng Yang, Dianping Tang
Liposomes are an excellent candidate component for biosensors to transduce and amplify detection signals due to their outstanding ability in encapsulating signal marker compounds. However, the use of liposomes for photoelectrochemical (PEC) signal transduction has not yet been achieved due the lack of appropriate sensing strategy. Herein, we report on a novel liposomes-amplified PEC immunoassay (LAPIA) method for sensitive HIV-p24 antigen (p24) detection based on a split-type strategy. Initially, liposomes were encapsulated with alkaline phosphatase (ALP) in their hydrophilic chamber and conjugated with secondary antibody on the surface to form the ALP-encapsulated liposomes (ALP-Ls) based PEC signal label. Sandwiched immunoassay based on the ALP-Ls label was then carried out in microwell plate. Upon addition of tween 20, the ALP molecules were released and catalyzed the hydrolysis of ascorbic acid 2-phosphate (AA-p) to produce ascorbic acid (AA). The latter then donated electron to the graphene/g-C3N4 nanohybrids based photoelectrode, arousing an increased photocurrent signal. The separation of immunoreaction step and PEC signal excitation (i.e. split-type) not only enabled the realization of liposomes based amplification strategy, but also could eliminate the PEC-caused biomolecules damage. The developed PEC method possessed a wide calibration range from 1.0pgmL−1 to 50ngmL−1 and a low detection limit of 0.63pgmL−1. Its practicability was demonstrated by assaying human serum samples. Moreover, the universality of the liposomes-amplified PEC sensing strategy was also demonstrated by developing it into a sensitive microRNA detection method.
http://ift.tt/2v9DQTe
Angiogenesis Inhibition in the Second-Line Treatment of Metastatic Colorectal Cancer. A Definite Conclusion?
Publication date: Available online 29 July 2017
Source:Seminars in Oncology
Author(s): M. Ducreux, P. Österlund, J.P. Pignon
http://ift.tt/2vh15eW
Dual-frequency ultrasonic treatment on microstructure and mechanical properties of ZK60 magnesium alloy
Publication date: January 2018
Source:Ultrasonics Sonochemistry, Volume 40, Part A
Author(s): Xingrui Chen, Fangkun Ning, Jian Hou, Qichi Le, Yan Tang
Compared with other dual-frequency acoustic applications, melt-treatment with dual-frequency ultrasound was less researched, especially in magnesium field. In this present work, traditional single-frequency ultrasonic field (SUF) treatment and dual-frequency ultrasonic field (DUF) treatment were used to refine the as-cast microstructure and improve the mechanical properties of the ZK60 (Mg–Zn–Zr) magnesium alloy. The influences of DUF on the microstructure evolution and mechanical properties were systematically investigated, and the cavitation bubble's dynamic behaviors were investigated by numerical simulation. α-Mg grains and second phases were dramatically refined by introduced ultrasound, and DUF showed higher refinement efficiency than SUF. The DUF treatment promoted the formation of small α-Mg globular grains and changed the distribution and morphology of MgZn2 phases. Mechanical properties of the as-cast alloy were much promoted with DUF. Yield strength, ultimate tensile strength and elongation increased to 153MPa, 239MPa and 13.9% respectively after 1400W DUF treatment, which were 30.8%, 42.3% and 58.0% higher than the values obtained from untreated samples and 20.5%, 20.7% and 30.0% higher than 1200W SUF treated samples. The DUF can generate more and larger cavitation bubbles, and make more bubbles into instantaneous bubbles, improving refinement efficiency.
http://ift.tt/2vgQ5y9
Hypothalamic mitochondrial abnormalities occur downstream of inflammation in diet-induced obesity
Source:Molecular and Cellular Endocrinology
Author(s): Rodrigo S. Carraro, Gabriela F. Souza, Carina Solon, Daniela S. Razolli, Bruno Chausse, Roberta Barbizan, Sheila C. Victorio, Licio A. Velloso
Hypothalamic dysfunction is a common feature of experimental obesity. Studies have identified at least three mechanisms involved in the development of hypothalamic neuronal defects in diet-induced obesity: i, inflammation; ii, endoplasmic reticulum stress; and iii, mitochondrial abnormalities. However, which of these mechanisms is activated earliest in response to the consumption of large portions of dietary fats is currently unknown. Here, we used immunoblot, real-time PCR, mitochondrial respiration assays and transmission electron microscopy to evaluate markers of inflammation, endoplasmic reticulum stress and mitochondrial abnormalities in the hypothalamus of Swiss mice fed a high-fat diet for up to seven days. In the present study we show that the expression of the inflammatory chemokine fractalkine was the earliest event detected in this study. Its hypothalamic expression increased as early as 3 h after the introduction of a high-fat diet and was followed by the increase of cytokines. GPR78, an endoplasmic reticulum chaperone, was increased 6 h after the introduction of a high-fat diet, however the actual triggering of endoplasmic reticulum stress was only detected three days later, when IRE-1α was increased. Mitofusin-2, a protein involved in mitochondrial fusion and tethering of mitochondria to the endoplasmic reticulum, underwent a transient reduction 24 h after the introduction of a high-fat diet and then increased after seven days. There were no changes in hypothalamic mitochondrial respiration during the experimental period, however there were reductions in mitochondria/endoplasmic reticulum contact sites, beginning three days after the introduction of a high-fat diet. The inhibition of TNF-α with infliximab resulted in the normalization of mitofusin-2 levels 24 h after the introduction of the diet. Thus, inflammation is the earliest mechanism activated in the hypothalamus after the introduction of a high-fat diet and may play a mechanistic role in the development of mitochondrial abnormalities in diet-induced obesity.
http://ift.tt/2tSCPiP
Gonadotropin-releasing hormone signaling: An information theoretic approach
Source:Molecular and Cellular Endocrinology
Author(s): Margaritis Voliotis, Kathryn L. Garner, Hussah Alobaid, Krasimira Tsaneva-Atanasova, Craig A. McArdle
Gonadotropin-releasing hormone (GnRH) is a peptide hormone that mediates central control of reproduction, acting via G-protein coupled receptors that are primarily Gq coupled and mediate GnRH effects on the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. A great deal is known about the GnRH receptor signaling network but GnRH is secreted in short pulses and much less is known about how gonadotropes decode this pulsatile signal. Similarly, single cell measures reveal considerable cell-cell heterogeneity in responses to GnRH but the impact of this variability on signaling is largely unknown. Ordinary differential equation-based mathematical models have been used to explore the decoding of pulse dynamics and information theory-derived statistical measures are increasingly used to address the influence of cell-cell variability on the amount of information transferred by signaling pathways. Here, we describe both approaches for GnRH signaling, with emphasis on novel insights gained from the information theoretic approach and on the fundamental question of why GnRH is secreted in pulses.
http://ift.tt/2u8pRZK
A functional drug re-purposing screening identifies carfilzomib as a drug preventing 17β-estradiol: ERα signaling and cell proliferation in breast cancer cells
Source:Molecular and Cellular Endocrinology
Author(s): Claudia Busonero, Stefano Leone, Cinzia Klemm, Filippo Acconcia
Most cases of breast cancer (BC) are estrogen receptor α-positive (ERα+) at diagnosis. The presence of ERα drives the therapeutic approach for this disease, which often consists of endocrine therapy (ET). 4OH-Tamoxifen and faslodex (i.e., fulvestrant - ICI182,780) are two ETs that render tumor cells insensitive to 17β-estradiol (E2)-dependent proliferative stimuli and prevent BC progression. However, ET has limitations and serious failures in different tissues and organs. Thus, there is an urgent need to identify novel drugs to fight BC in the clinic. Re-positioning of old drugs for new clinical purposes is an attractive alternative for drug discovery. For this analysis, we focused on the modulation of intracellular ERα levels in BC cells as target for the screening of about 900 Food and Drug Administration (FDA) approved compounds that would hinder E2:ERα signaling and inhibit BC cell proliferation. We found that carfilzomib induces ERα degradation and prevents E2 signaling and cell proliferation in two ERα+ BC cell lines. Remarkably, the analysis of carfilzomib effects on a cell model system with an acquired resistance to 4OH-tamoxifen revealed that this drug has an antiproliferative effect superior to faslodex in BC cells. Therefore, our results identify carfilzomib as a drug preventing E2:ERα signaling and cell proliferation in BC cells and suggest its possible re-position for the treatment of ERα+ BC as well as for those diseases that have acquired resistance to 4OH-tamoxifen.
http://ift.tt/2tSKv4M
A novel Brain Computer Interface for classification of social joint attention in Autism and comparison of 3 experimental setups: a feasibility study
Source:Journal of Neuroscience Methods
Author(s): Carlos P. Amaral, Marco A. Simões, Susana Mouga, João Andrade, Miguel Castelo-Branco
BackgroundWe present a novel virtual-reality P300-based Brain Computer Interface (BCI) paradigm using social cues to direct the focus of attention. We combined interactive immersive virtual-reality (VR) technology with the properties of P300 signals in a training tool which can be used in social attention disorders such as autism spectrum disorder (ASD).New methodWe tested the novel social attention training paradigm (P300-based BCI paradigm for rehabilitation of joint-attention skills) in 13 healthy participants, in 3 EEG systems. The more suitable setup was tested online with 4 ASD subjects. Statistical accuracy was assessed based on the detection of P300, using spatial filtering and a Naïve-Bayes classifier.ResultsWe compared: 1 − g.Mobilab+ (active dry-electrodes, wireless transmission); 2 − g.Nautilus (active electrodes, wireless transmission); 3 − V-Amp with actiCAP Xpress dry-electrodes. Significant statistical classification was achieved in all systems. g.Nautilus proved to be the best performing system in terms of accuracy in the detection of P300, preparation time, speed and reported comfort. Proof of concept tests in ASD participants proved that this setup is feasible for training joint attention skills in ASD.Comparison with Existing methodsThis work provides a unique combination of 'easy-to-use' BCI systems with new technologies such as VR to train joint-attention skills in autism.ConclusionsOur P300 BCI paradigm is feasible for future Phase I/II clinical trials to train joint-attention skills, with successful classification within few trials, online in ASD participants. The g.Nautilus system is the best performing one to use with the developed BCI setup.
http://ift.tt/2tSndft
Acute Ethanol Modulation of Neurocircuit Function in the Nucleus of the Tractus Solitarius
Source:Brain Research Bulletin
Author(s): Michael A. Aimino, Caitlin Coker, Yuval Silberman
The nucleus of the tractus solitarius (NTS) is a brain stem region critical to many physiologic processes and has been implicated in addiction to multiple classes of abused drugs, including alcohol (EtOH). That said, the mechanism by which EtOH modulates NTS neurocircuit activity is not well characterized and has yet to be examined utilizing electrophysiologic methods in mouse models of alcohol use disorders. To begin to address this gap in knowledge, we sought to use whole-cell and cell-attached recordings to determine the mechanism of acute EtOH action on GABAergic and glutamatergic neurotransmission, as well as on action potential firing in the NTS of adult male, EtOH naïve mice. Bath application of EtOH (50mM) significantly enhanced the frequency of spontaneous inhibitory postsynaptic current events, while increasing the amplitude of these events in half of the neurons tested. This finding suggests a presynaptic mechanism of EtOH action on GABAergic transmission in the NTS as well as a postsynaptic mechanism in subsets of NTS neurons. EtOH application was further associated with a significant decrease in action potential firing in most, but not all, NTS neurons tested. EtOH induced a small but significant decrease in spontaneous excitatory postsynaptic current frequency, indicating that EtOH may also inhibit NTS glutamatergic signaling to some degree. Intriguingly, in vivo EtOH exposure (4g/kg IP) enhanced c-FOS colocalization with tyrosine hydroxylase via immunohistochemical methods, indicating that NTS norepinephrine neurons may be activated by acute EtOH exposure. Although future work is needed, the current data indicate that acute EtOH may enhance GABAergic signaling in local NTS circuits resulting in disinhibition of NTS norepinephrine neurons. Such a finding has important implications in understanding the role of the NTS in the development of alcoholism.
http://ift.tt/2tSn2Ra
The roles of sodium-glucose cotransporter 2 inhibitors in preventing kidney injury in diabetes
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Krit Jaikumkao, Anchalee Pongchaidecha, Varanuj Chatsudthipong, Siriporn C. Chattipakorn, Nipon Chattipakorn, Anusorn Lungkaphin
Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD) worldwide. The early effective treatment of high plasma glucose could delay or prevent the onset of DN. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are new target treatments for ameliorating high plasma glucose and help to maintain glucose homeostasis in diabetic patients. Reduced renal glucose reabsorption by SGLT2 inhibition seems to have high potential to improve glycemic control in diabetes mellitus (DM) not only through glucose lowering but also through glucose-independent effects such as blood pressure-lowering and direct renal effects in diabetes. Of note, the important events in the pathogenesis of glucose-induced renal injury and DN including oxidative stress, inflammation, fibrosis and apoptosis conditions have shown to be ameliorate after the treatment with SGLT2 inhibitors. Interestingly, SGLT2 inhibitors have been reported to reduce albuminuria in DM via an activation of renal tubuloglomerular feedback by increased macula densa sodium and chloride delivery, leading to afferent vasoconstriction and attenuated diabetes-induced renal hyperfiltration. These effects also help to conserve glomerular integrity. Thus, the treatment of diabetes mellitus using SGLT2 inhibitors could be one of the effective approach for the management of diabetic-associated kidney disease like DN. This review summarizes the up to date information and discusses the bidirectional relationship between the SGLT2 inhibitor treatments and the renal functions that are available from both basic research and clinical reports. The details of renal outcomes of SGLT2 inhibitors in DN are also provide in this review.
http://ift.tt/2tMnD2T
Effects of long-term oral administration of methimazole on femur and tibia properties in male Wistar rats
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Marcin R. Tatara, Marcin Gołyński, Radosław P. Radzki, Marek Bieńko, Witold Krupski
Physiological concentrations of thyroid hormones are crucial for skeletal growth and development, physiological bone turnover and bone homeostasis maintenance. Methimazole (1-methyl-2-mercaptoimidazole) is an antithyroid drug used for the treatment of the hyperthyroidism in humans and animals. The aim of the study was to determine effects of long-term oral methimazole treatment in male Wistar rats on biochemical bone metabolism markers, as well as morphological, geometric, densitometric and mechanical properties of femur and tibia. Experimental rats were subjected to 90-day-long oral treatment with 0.05% water solution of methimazole and were kept under identical environmental conditions and received the same diet ad libitum as the control group. Serum concentration of osteocalcin (OC) and C-terminal telopeptides of type I collagen (CTX-I) was determined. Femur and tibia were evaluated using quantitative computed tomography (QCT), peripheral QCT (pQCT) and three-point bending test. Final body weight of the experimental group was significantly decreased by 30% (P=0.01). Methimazole treatment significantly decreased serum OC concentration by 21% (P=0.02) and increased CTX-I concentration by 17% (P=0.06). Methimazole decreased morphological, geometric and densitometric parameters of femur and tibia in rats. Mechanical evaluation of bones has shown significantly decreased maximum elastic strength and ultimate strength of femur in rats treated with methimazole by 36% and 40% when compared to the control group (P<0.05). In conclusion, this study has shown that long-term treatment with methimazole inhibits bone formation and accelerates bone resorption processes. The observed negative effects of methimazole treatment on body weight gain and skeletal properties may be considered as additional possible side effects in living organisms to those reported in the previous studies. It may be suggested that long-term antithyroid treatment should be combined with prevention of the negative effects of methimazole on bone tissue and whole body metabolism.
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Neuropharmacological and neuroprotective activities of some metabolites produced by cell suspension culture of Waltheria americana Linn.
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Jorge Mundo, Juana Villeda-Hernández, Maribel Herrera-Ruiz, María del Carmen Gutiérrez, Jesús Arellano-García, Ismael León-Rivera, Irene Perea-Arango
Waltheria americana is a plant used in Mexican traditional medicine to treat some nervous system disorders. The aims of the present study were to isolate and determine the neuropharmacological and neurprotective activities of metabolites produced by a cell suspension culture of Waltheria americana. Submerged cultivation of W. americana cells provided biomass. A methanol-soluble extract (WAsc) was obtained from biomass. WAsc was fractionated yielding the chromatographic fractions 4WAsc-H2O and WAsc-CH2Cl2. For the determination of anticonvulsant activity in vivo, seizures were induced in mice by pentylenetetrazol (PTZ). Neuropharmacological activities (release of gamma amino butyric acid (GABA) and neuroprotection) of chromatographic fractions were determined by in vitro histological analysis of brain sections of mice post mortem. Fraction 4WAsc-H2O (containing saccharides) did not produce neuronal damage, neurodegeneration, interstitial tissue edema, astrocytic activation, nor cell death. Pretreatment of animals with 4WAsc-H2O and WAsc-CH2Cl2 from W. americana cell suspensions induced an increase in: GABA release, seizure latency, survival time, neuroprotection, and a decrease in the degree of severity of tonic/tonic-clonic convulsions, preventing PTZ-induced death of up to 100% of animals of study. Bioactive compounds produced in suspension cell culture of W. americana produce neuroprotective and neuropharmacological activities associated with the GABAergic neurotransmission system.
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Rac2 deficiency attenuates CCl4-induced liver injury through suppressing inflammation and oxidative stress
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Yan Zou, Ji-bin Xiong, Ke Ma, Ai-Zhong Wang, Ke-Jian Qian
Oxidative stress is a leading cause to liver injury. Rac2 is a Ras-associated guanosine triphosphatase, an important molecule modulating a large number of cells and involved in the regulation of reactive oxygen species (ROS). For the study described here, we supposed that Rac2 knockout protects mice against CCl4-induced acute liver injury. We found that Rac2 expressed highly in CCl4-induced liver tissues. CCl4-treated Rac2 knockout (Rac2−/−) mice had reduced CD24 levels and steatosis. In addition, CCl4-induced high expression of pro-inflammatory cytokines and chemokine were reversed by Rac2 deficiency compared to CCl4-treated wild type (WT) mice. We also found that fibrosis-related signals of MMP-9, MMP-2 and TGF-β1 were also down-regulated in Rac2 knockout mice induced by CCl4. Significantly, oxidative stress induced by CCl4 was also suppressed owing to the lack of Rac2, evidenced by enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) levels, superoxide radical, H2O2, xanthine oxidase (XO), xanthine dehydrogenase (XDH) and XO/XDH ratio. Moreover, c-Jun N-terminal protein kinase mitogen-activated protein kinases (JNK MAPK) was activated by CCl4, which was reversed in the liver of Rac2−/− mice through western blot and immunohistochemical analysis. In vitro, endotoxin (LPS) was treated to hepatocytes isolated from WT mice and Rac2−/− mice. The data further confirmed the role of Rac2 deficiency suppressed pro-inflammatory cytokines and chemokine, as well as fibrosis-related signals. Of note, production of ROS induced by LPS was reduced in Rac2−/− cells, accompanied with enhanced SOD1, SOD2 and reduced XO and phosphorylated-JNK expressions. Our results indicated that Rac2 played an essential role in acute liver injury induced by CCl4, providing the compelling information of the effects of Rac2 on liver injury, and revealing a novel regulatory mechanism for acute liver injury.
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Efavirenz loaded nanostructured lipid carrier engineered for brain targeting through intranasal route: In-vivo pharmacokinetic and toxicity study
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Varsha Pokharkar, Arpana Patil-Gadhe, Prathyusha Palla
Intranasal delivery is a potential platform that can be employed in targeting the antiretrovirals (ARVs) to reach HIV that harbors in the central nervous system. The objective of the study was to develop an optimized efavirenz (EFV) loaded nanostructured lipid carrier (ENLC) and deliver it through intranasal route for brain targeting. Factorial design (23) was used to identify the key formulation variables influencing particle size and percent drug encapsulation of efavirenz in the NLC. Optimised ENLC-6 batch exhibited a spherical morphology with a mean particle size of 162nm, high drug encapsulation of 95.78±0.42% and in-vitro drug release of 92.45% at the end of 24h. Single dose in-vivo pharmacokinetic studies revealed significant therapeutic concentration of the drug in the CNS following IN administration with a Cmax value of 31.45±0.75 and T1/2 of 11.14h. A 10 fold increase (p<0.001) in% drug targeting efficiency (DTE) and 4.5 fold increase (p<0.001) in % drug targeting potential (DTP) for ENLC-6 was observed as compared to pure EFV. Sub-acute 28day IN toxicity in experimental animals indicated non-toxicity of encapsulated efavirenz over pure drug. Based on the findings we conclude that the intelligent choice of the lipdic carrier along with the strategic use of excipients can prove helpful for the efficient brain targeting of the encapsulated efavirenz which is devoid of toxicity. This may prove useful in the management of neuro-AIDS.
Graphical abstract
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Potential of the chlorogenic acid as multitarget agent: Insulin-secretagogue and PPAR α/γ dual agonist
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Maetzin Becerra Sanchez, Elizabeth Miranda-Perez, Juan Carlos Gomez Verjan, Maria de los Angeles Fortis Barrera, Julia Perez-Ramos, Francisco Javier Alarcon-Aguilar
The chlorogenic acid (CGA) is a natural product isolated from Cecropia obtusifolia, which possesses several pharmacological properties, such as: anti-carcinogenic, neuroprotective, antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic. In relation to its effects on the hyperglycemia and hypertriglyceridemia, few is known about the mechanisms in which this compound may be acting, therefore, the aim of the present study was to determine if CGA acts as an insulin secretagogue increasing intracellular calcium concentrations ([Ca2+]i) in RINm5F cells; or as an insulin sensitizer and lipid-lowering agent stimulating the expression of PPARγ and PPARα, respectively, in 3T3-L1 adipocytes. As results, RINm5F cells treated with 200μM of CGA showed an increase in [Ca2+]i of 9-times versus control and 4-times as compared to positive control; in addition, an increase in insulin secretion was observed similarly to those of positive control. CGA also significantly increased the mRNA expression of PPARγ (150%) and GLUT4 (220%), as well PPARα (40%) and FATP (25%) as it was appreciated by RT-PCR. Additionally, a chemoinformatic analysis suggested that CGA has suitable physicochemical properties to be considered as leader bioactive molecule for the development of novel agents with similar properties. Together, our results indicate that CGA possesses multiple mechanisms of action for the development of highly effective therapeutics in the treatment of metabolic diseases such as type 2 diabetes.
http://ift.tt/2tMeGGD
Neuroprotective properties of anthocyanidin glycosides against H2O2-induced glial cell death are modulated by their different stability and antioxidant activity in vitro
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Gedas Ereminas, Daiva Majiene, Kastytis Sidlauskas, Valdas Jakstas, Liudas Ivanauskas, Gintautas Vaitiekaitis, Julius Liobikas
The neuroprotective effect of several anthocyanins in combination with their stability and antioxidant/pro-oxidant activity has been investigated against H2O2–induced oxidative stress in C6 glial cells. First it was found that delphinidin (Dp) 3-O-glucoside and 3-O-rutinoside were degraded within an hour, and at the same time stimulated the production of H2O2 in the micromolar concentration range. The stability of peonidin, pelargonidin (Pg), malvidin (Mv) and cyanidin (Cy) 3-O-glucosides and Cy 3-O-rutinoside was significantly higher than that of Dp 3-O-glycosides, with Pg3G showing the highest percent recovery over time. Based on these findings and chemical difference (according to the set of functional groups on the B-ring) of tested anthocyanins Cy3G, Mv3G and Pg3G were selected as candidates for the protection of glial cells against H2O2-induced oxidative stress. It was revealed that Cy3G (5–20μM) and Mv3G (10–20μM) but not Pg3G protected glial cells against H2O2–induced necrotic cell death. Moreover, these anthocyanins sustained the glutathione antioxidant defence system. Finally, to the extent of our knowledge we were the first to demonstrate the protective effect of Cy3G on the resting mitochondrial respiration rate in H2O2-affected glial cells. The results suggest that Cy3G, as the most prominent antioxidant among tested anthocyanins, could be a potential adjuvant for the prevention or reduction of necrotic glial cell death during the oxidative stress conditions met in neurodegenerative diseases. However, further elucidation of other possible mechanisms for anthocyanins to protect the nervous system is encouraged.
http://ift.tt/2v9ANu3
Inhibition of Rad51 sensitizes breast cancer cells with wild-type PTEN to olaparib
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Qian Zhao, Jiawei Guan, Zhiwei Zhang, Jian Lv, Yulu Wang, Likun Liu, Qi Zhou, Weifeng Mao
PTEN is a tumor suppressor gene well characterized as a phosphatase. However, more evidences demonstrate PTEN functions in DNA repair independent of its phosphatase activity, which affects the efficacy of DNA damage anti-tumoral drugs in treating cancer cells with PTEN variations. Using BT549 breast cancer cells, we studied the roles of PTEN in DNA repair and in sensitization of breast cancer cells to olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor. Comet assay showed PTEN promoted DNA repair. PTEN-deficient BT549 cells are sensitive to olaparib, which shows the synthetic lethality between PTEN and PARP1. We expressed PTEN in BT549 cells and found PTEN-proficient BT549 cells resist to olaparib. Western blot showed that PTEN up-regulated Rad51 expression, suggesting PTEN promotes DNA repair through Rad51-dependnent homologous recombination. We used 5μM olaparib or 5μM RI-1, a Rad51 inhibitor, to treat PTEN-proficient BT549 cells respectively. The immunofluorescent analysis showed the combination of olaparib and RI-1 induced more than 4-fold of γH2AX foci than either of them. MTT assay showed 5μM RI-1 did not change the survival of PTEN-proficient BT549 cells, however, this dose of RI-1 sensitized PTEN-proficient BT549 cells to olaparib. Consequently, these results demonstrate that inhibition of Rad51 can sensitize BT549 cells with wild type PTEN to olaparib, which would contribute to using PARP inhibitors in individual treatment of breast cancer patients with PTEN variations.
Graphical abstract
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Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Osama M. Ahmed, Mohamed A. Hassan, Sanaa M. Abdel-Twab, Manal N. Abdel Azeem
The therapy of Type 2 Diabetes Mellitus (T2DM) stays a challenging issue. During the last decade, there has been an interest in the expansion of anti-diabetic drugs especially those of natural sources. Thus, the aim of this study was to assess the anti-hyperglycemic and the anti-hyperlipidemic effects as well as the anti-oxidant activities of navel orange hydroethanolic extract and its constituting flavonoids naringin and naringenin on nicotineamide (NA)/streptozotocin (STZ)-induced type 2 diabetic rats. To induce T2DM, 16h-fasted rats were intraperitoneally injected with STZ at dose of 50mg/kg body weight (b. w.), 15min after the intraperitoneal administration of NA (120mg/kg b. w.). The NA/STZ-induced type 2 diabetic rats were orally treated with navel orange peel hydroethanolic extract, naringin and narengenin at dose level of 100mg/kg b. w./day for 4 weeks. The treatments with navel orange peel hydroethanolic extract, naringin and narengenin potentially alleviated the lowered serum insulin and C-peptide levels, the depleted liver glycogen content, the elevated liver glucose-6-phosphatase and glycogen phosphorylase activities, the deteriorated serum lipid profile, and the suppressed liver antioxidant defense system of NA/STZ-induced type 2 diabetic rats. The treatments also enhanced the mRNA expression of insulin receptor β-subunit, GLUT4 and adiponectin in adipose tissue of STZ/NA-induced type 2 diabetic rats. In conclusion, the navel orange peel hydroethanolic extract, naringin and naringenin have potent anti-diabetic effects in NA/STZ-induced type 2 diabetic rats via their insulinotropic effects and insulin improving action which in turn may be mediated through enhancing insulin receptor, GLUT4 and adiponectin expression in adipose tissue.
http://ift.tt/2tMeE1t
Kiwi fruit (Actinidia deliciosa) ameliorates gentamicin-induced nephrotoxicity in albino mice via the activation of Nrf2 and the inhibition of NF-κB (Kiwi & gentamicin-induced nephrotoxicity)
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Yomna I. Mahmoud
Gentamicin is a potent aminoglycoside antibiotic, but the risk of nephrotoxicity limits its prolonged use. The toxicity of gentamicin is believed to result from oxidative stress, a condition that could be counteracted by dietary antioxidants. This study determines the possible renoprotective effects of kiwifruit against the pathophysiological and ultrastructural alterations induced by gentamicin. Mice were intraperitoneally injected with gentamicin (100mg/kg body weight) for eight consecutive days, and kiwi juice was administered for 8days, either concomitant to or after gentamicin injection. Gentamicin caused nephrotoxicity evidenced by the significant elevation of serum creatinine and blood urea nitrogen levels, along with significant reduction of serum sodium and potassium ions, compared to normal controls. This was associated with proximal tubular necrosis, lysosomal accumulation and mitochondrial alterations, together with glomerular atrophy, mesangial hypercellularity, and inflammatory cell infiltration. Moreover, immunohistochemical results pointed to the relevant role of Nrf2 and NF-κB in gentamicin-induced nephrotoxicity. Kiwi administration, especially when given after gentamicin injection, significantly ameliorated gentamicin-induced pathophysiological alterations, increased the nuclear immunoreactivity of Nrf2 and decreased that of NF-κB. In short, kiwi fruit shows a promising role as a nephroprotective agent against gentamicin-induced nephrotoxicity via attenuating oxidative stress, inflammation and cell death.
http://ift.tt/2v9yS95
Rhein ameliorates adenomyosis by inhibiting NF-κB and β-Catenin signaling pathway
Publication date: October 2017
Source:Biomedicine & Pharmacotherapy, Volume 94
Author(s): Tingting Feng, Shaobin Wei, Yan Wang, Xianyun Fu, Ling Shi, Liyuan Qu, Xiaoxue Fan
In the present study, we examined the effects of rhein on pituitary gland implantation-induced adenomyosis, an animal model which mimics human adenomyosis. Oral administration of rhein dose-dependently attenuated hyperplastic and hypertrophic myometrium and improved adenomyosis. The activation of NF-κB and β-catenin signaling pathway was observed in the ectopic endometria. While, rhein dose dependently inhibited the expressions of p-p65, p-AKT and actived Rac1. As Rac1 activation controlled nuclear localization of β-catenin during canonical Wnt signaling, we found that the degradation complex of β-catenin was improved by rhein. In addition, β-catenin nuclear translocation and its downstream genes were markedly suppressed by different doses of rhein. At the same time, decreased activation of epithelial–mesenchymal transition (EMT)-associated proteins including Snail and ZEB1 was detected in rhein-treated mice, indicating that the activation of Wnt signaling pathway was suppressed by rhein. The in vitro study verified a negative regulation of rhein on β-catenin in stromal cells. Stimulation of IL-1β significantly increased the nuclear translocation of β-catenin and improved its target genes expressions. While, rhein remarkably abolished the enhancement in a dose dependent manner. Taken together, our results demonstrated the ability of rhein to inhibit Wnt/β-catenin activation and its potential use in the treatment of adenomyosis and other abnormal activation of β-catenin −associated diseases.
http://ift.tt/2tMUG6K
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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