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Will paraquat trigger Parkinson's ailment? An assessment reviews.
The ability of tSMS to modulate neuronal activities in the remote cortex could expand the possibility of its clinical use. Although tolerance serves as a major limitation in the long-term clinical use of opioids in patients with chronic severe pain, mechanisms of opioid tolerance are poorly understood. In this study, a morphine tolerance model was established by subcutaneously injecting male rats with morphine (10 mg/kg) twice a day for 10 consecutive days. In addition, a subset of morphine-tolerant rats underwent testosterone replacement therapy. The levels of mu-opioid receptor (MOR) mRNA and protein in the trigeminal ganglia (TGs) of morphine-tolerant versus control rats and of morphine-tolerant rats with vs. without testosterone replacement therapy were measured. We found that testosterone levels were significantly lower in morphine-tolerant rats than in the controls (1.248 ± 0.231 ng/ml vs. 2.223 ± 0.153 ng/ ml, respectively; p = 0.008). Furthermore, chronic morphine exposure led to a downregulation in the levels of MOR mRNA to 79.3%, and of MOR protein to 68.9%. Testosterone replacement therapy restored MOR mRNA and protein levels specifically in rats who had developed a tolerance to morphine, thereby suggesting a potential role of testosterone in the opioid-receptor response to chronic morphine exposure. In summary, our study provides evidence for the involvement of testosterone in the proper regulation of the peripheral MOR system in rats following prolonged morphine exposure. We also suggest that analgesic therapeutic measures should take into account the testosterone levels of patients who have built up a tolerance to morphine. Medical named entity recognition (NER) in Chinese electronic medical records (CEMRs) has drawn much research attention, and plays a vital prerequisite role for extracting high-value medical information. In 2018, China Health Information Processing Conference (CHIP2018) organized a medical NER academic competition aiming to extract three types of malignant tumor entity from CEMRs. Since the three types of entity are highly domain-specific and interdependency, extraction of them cannot be achieved with a single neural network model. selleck chemical Based on comprehensive study of the three types of entity and the entity interdependencies, we propose a collaborative cooperation of multiple neural network models based approach, which consists of two BiLSTM-CRF models and a CNN model. In order to tackle the problem that target scene dataset is small and entity distributions are sparse, we introduce non-target scene datasets and propose sentence-level neural network model transfer learning. Based on 30,000 real-world CEMRs, we pre-train medical domain-specific Chinese character embeddings with word2vec, GloVe and ELMo, and apply them to our approach respectively to validate effects of pre-trained language models in Chinese medical NER. Also, as control experiments, we apply Gated Recurrent Unit to our approach. Finally, our approach achieves an overall F1-score of 87.60%, which is the state-of-the-art performance to the best of our knowledge. In addition, our approach has won the champion of the medical NER academic competition organized by 2019 China Conference on Knowledge Graph and Semantic Computing, which proves the outstanding generalization ability of our approach. Fas-ligand/CD178 belongs to the TNF family proteins and is the well-characterized inducer of cell death. We showed previously that the interaction of Fas-ligand and caveolin-1 is necessary for Fas-ligand translocation to rafts, and the subsequent induction of Fas-ligand-dependent cell death. Both molecules can undergo phosphorylation, however the role of the phosphorylation state of Fas-ligand and caveolin-1 in their physical association, and consequently in of Fas - mediated cell death induction is currently unknown. In this study, we show that in control cells Fas-ligand interaction with caveolin-1 is not observed, and both molecules are phosphorylated. The intracellular part of Fas-ligand was shown to form a complex with p59Fyn-kinase. Upon cell death activation, the expression and activity of p59Fyn-kinase decreases substantially, leading to the disruption of Fas-ligand - p59Fyn-kinase association, dephosphorylation of Fas-ligand and caveolin-1, and formation of a complex between them (Fas-ligand - caveolin-1). The analysis of the effects of kinase and phosphatase inhibitors revealed that phosphorylation of Fas-ligand and caveolin-1 at tyrosine residues suppressed Fas-mediated cell death. Thus, dephosphorylation of Fas-ligand and caveolin-1 is critical for triggering Fas-ligand-mediated apoptotic pathway and cell death execution. The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic lung diseases, such as Idiopathic Pulmonary Fibrosis (IPF). Cellular senescence is a major hallmark of aging and has a higher occurrence in IPF. The lung epithelium represents a major site of tissue injury, cellular senescence and aberrant activity of developmental pathways such as the WNT/β-catenin pathway in IPF. The potential impact of WNT/β-catenin signaling on alveolar epithelial senescence in general as well as in IPF, however, remains elusive. Here, we characterized alveolar epithelial cells of aged mice and assessed the contribution of chronic WNT/β-catenin signaling on alveolar epithelial type (AT) II cell senescence. Whole lungs from old (16-24 months) versus young (3 months) mice had relatively less epithelial (EpCAM+) but more inflammatory (CD45+) cells, as assessed by flow cytometry. Compared to young ATII cells, old ATII cells showed decreas dysfunction and impaired lung repair. Schizophrenia (SCZ) is a severe mental disorder with a high heritability. Although its pathophysiology is mainly unknown, dysregulated immune activation and inflammation have recently emerged as possible candidates in the underlying mechanisms of SCZ. Previous studies suggest that aberrant inflammasome activation, glia dysregulation, and brain inflammation may be involved in the pathophysiology of the disorder. Here, we studied the effects of inflammatory modulation on human induced pluripotent stem cell (iPSC)-derived astrocytes generated from SCZ patients and healthy controls (CTRL). Inflammasome activation was mimicked by short-term IL-1β exposure, and gene expression were measured with high-coverage RNA-Seq to ensure a global characterization of the transcriptional effects of the treatment. IL-1β exposure modulated several pathways involved in innate immune responses, cell cycle regulation, and metabolism in both SCZ and CTRL astrocytes. Significant differences were found in the expression of HILPDA and CCL20 genes, both of which had reduced up-regulation upon IL-1β treatment in SCZ astrocytes compared to CTRL astrocytes. CCL20 data were further validated and confirmed using qPCR, ELISA, and regulatory T lymphocyte (Treg) migration assays. Additionally, we found significantly decreased mRNA expression of the Treg-specific marker FOXP3 in the blood of a large cohort of SCZ patients (n = 484) compared to CTRL (n = 472). Since CCL20 is a specific chemoattractant for CD4+CD25+CCR6+ Tregs, which are crucially involved in anti-inflammatory responses during brain (auto)inflammation, our results imply a plausible role for an altered astroglia-CCL20-CCR6-Treg axis in SCZ pathophysiology. ETHNOPHARMACOLOGICAL RELEVANCE Capparis spinose (C. spinosa) belonging to Capparaeae, originates from dry areas in the west or central Asia and Mediterranean basin. For thousands of years, C. spinosa has been reported to be used as a therapeutic traditional medicine to relieve various ailments including rheumatism, pain and inflammatory diseases. AIM OF THE STUDY There are several studies mentioning that systemic inflammation results in learning and memory impairments through the activation of microglia. The objective of this study was to investigate the effect of C. spinosa on both in vivo and in vitro models of neuroinflammation and cognitive impairment using lipopolysaccharide (LPS). MATERIALS AND METHODS In vivo 40 male rats were used in the present study. Cognitive impairment was induced using LPS (1 mg/kg/d; i.p.) for 4 weeks. Treatment with C. spinosa (100 and 300 mg/kg/d; p.o.) was performed 1 h before LPS administration. At the end of the experiment, rats were undergone for behavioral and biochemicalnosa has a neuroprotective effect, and might be considered as an effective therapeutic agent for the treatment of neurodegenerative diseases that are accompanied by microglial activation, such as AD. V.ETHNOPHARMACOLOGICAL RELEVANCE Gastrodiae Rhizoma (GR), a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating headache, dizziness, tetanus, epilepsy, and etc., has been proven to relieve chronic atrophic gastritis (CAG). Due to its complex ingredients, the active fractions responsible for the treatment of CAG remain largely unknown. AIM OF THE STUDY To explore the underlying material and interpret its underlying mechanism, the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG was studied based on the 1H NMR metabolomics. MATERIALS AND METHODS The rat model of CAG was established by autoimmune method. The modeled CAG rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of Gastrodiae Rhizoma for 21 consecutive days. The stomach and serum samples were collected and then subjected to histopathology observation, biochemical measurement (MDA, SOD, GSH, NO, XOD and pepsin), 1H NMR metabolic profiling and multivariate/univariate statistical analysis. RESULTS The results showed that T1 had the best therapeutic effect, T2 the second, and T3 and T4 the poorest with no obvious therapeutic effect, demonstrating that the effective components of Gastrodiae Rhizoma should be compounds of high polarity. T1 achieved good therapeutic effects due to the anti-inflammatory and anti-oxidant activities, and by rectifying the disturbed energy and amino acid metabolism in CAG model. CONCLUSION This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means. ETHNOPHARMACOLOGICAL RELEVANCE Zoujin pill (ZJP), a medication used to treat gastrointestinal disorders since the 15th Century in China, have been reported to exert anti-depressant effects in various models. STUDY AIM To assess the effects of ZJP on gastrointestinal function and depressive behavior in rats under chronic unpredictable mild stress (CUMS), and to examine the underlying mechanisms related to brain-gut axis. METHODS The rats suffered the stressor once daily for 5 weeks. ZJP (0.6 and 1.2 g/kg) and fluoxetine (15 mg/kg) as positive control were administered to the rats through gastric intubation once daily for 5 consecutive weeks. The anti-depression effects were compared by performing sucrose preference tests and open field tests. Gastrointestinal motility was investigated by determining the gastrointestinal transit rate and by electrogastrogram. The serum levels of the gastrointestinal hormone (GAS, MOT, VIP, SP), inflammatory cytokine (IL-1β, IL-6; , TNFα) and glucagon-like peptide-1 (GLP-1) were assayed by enzyme-linked immunosorbent assay.
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