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s of contact dermatitis are recommended.The balance between detoxification and toxicity is linked to enzymes of the drug metabolism Phase I (cytochrome P450 or oxidoreductases) and phase II conjugating enzymes (such as the UGTs). After the reduction of quinones, the product of the reaction, the quinols-if not conjugated-re-oxidizes spontaneously to form the substrate quinone with the concomitant production of the toxic reactive oxygen species (ROS). Herein, we documented the modulation of the toxicity of the quinone menadione on a genetically modified neuroblastoma model cell line that expresses both the quinone oxidoreductase 2 (NQO2, E.C. 1.10.5.1) alone or together with the conjugation enzyme UDP-glucuronosyltransferase (UGT1A6, E.C. 2.4.1.17), one of the two UGT isoenzymes capable to conjugate menadione. As previously shown, NQO2 enzymatic activity is concomitant to massive ROS production, as previously shown. The quantification of ROS produced by the menadione metabolism was probed by electron-paramagnetic resonance (EPR) on cell homogenates, ymes plays a fundamental role during the cells' detoxification process. The fluorescence measurements of the variation of redox homeostasis of each cell line and the detection of a glucuronide form of menadiol in the cells co-expressing NQO2 and UGT1A6 enzymes further confirmed our findings.Accumulation of β-amyloid (Aβ) causes oxidative stress, which is the major pathological mechanism in Alzheimer's disease (AD). β-asarone could reduce Aβ-induced oxidative stress and neuronal damage, but the molecular mechanism remains elusive. In this study, we used an Aβ-stimulated PC12 cell model to explore the neuroprotective effects and potential mechanisms of β-asarone. The results showed that β-asarone could improve cell viability and weaken cell damage and apoptosis. β-asarone could also decrease the level of ROS and MDA; increase the level of SOD, CAT, and GSH-PX; and ameliorate the mitochondrial membrane potential. Furthermore, β-asarone could promote the expression of Nrf2 and HO-1 by upregulating the level of PI3K/Akt phosphorylation. In conclusion, β-asarone could exert neuroprotective effects by modulating the P13K/Akt/Nrf2 signaling pathway. β-asarone might be a promising therapy for AD.Aim The FMS-related tyrosine kinase 3 ligand (FL) has an important role in regulating FMS-related tyrosine kinase 3 (Flt-3) activity. Serum FL levels are markedly increased among patients with hematopoietic disease. However, its role in radiation treatment remains unclear. In this study, we investigated the effects of FL on radiotherapy for esophageal squamous cell carcinoma (ESCC). Methods KYSE150 and KYSE450 cells were stimulated with FL (200 ng/ml). mRNA expression was analyzed using qRT-PCR. Cell viability was checked using CCK-8 assay kits. Proliferation was determined using the EdU assay. Radiosensitivity was detected through a colony-forming assay. Flow cytometry was used to evaluate cell apoptosis. The number of γH2AX foci was verified using an immunofluorescence assay. The change in relative proteins was determined by western blot analysis. The growth of transplanted tumors was demonstrated in nude mice. Results Our results showed that FL increased the radiation resistance of ESCC cells by promoting clone formation, increasing EdU incorporation, enhancing DNA damage repair, and inhibiting apoptosis. Moreover, the Flt-3 receptor expression significantly increased in ESCC cells after radiation, which may have been an important factor in their radioresistance. Conclusion Our results suggest that FL increases the radioresistance of esophageal cancer cells and that FL-Flt-3 could be a potential target for enhancing radiosensitivity in ESCC.Background We investigated the prevalence, demographic and clinical features, and risk factors associated with drug-induced liver injury (DILI) during the treatment of brucellosis inpatients in a retrospective study. Methods We collected the clinical data of 782 brucellosis inpatients admitted at the Shawan County People's Hospital, Xinjiang, from 2015-2019. All cases were re-evaluated using the international consensus of DILI criteria and RUCAM rating scale. 71 patients were confirmed as DILI cases and compared with 523 other patients with normal liver function. Results It was indicated that DILI occurred with a prevalence of about 9.08% among brucellosis inpatients receiving drug therapy. Hepatocellular injury was the most common type of DILI (61.97%, 95% confidence interval [CI] 50.34-72.37), followed by mixed (23.94%, 95% CI 15.52-35.04) and cholestatic types (14.08%, 95% CI 7.83-24.02). In addition, 13.64% of the hepatocellular DILI cases fulfilled Hy's law criteria and only two cases (2.82%) progressed to severe DILI. Most patients adopted the combination of rifampicin, antipyretic analgesics, anti-infective agents, and traditional Chinese medicine for the treatment of brucellosis, with all the 71 patients taking rifampicin as the drug of choice. Multivariable logistic regression analyses indicated that obesity, regular alcohol intake, and decreased serum albumin were the independent risk factors of DILI in patients with brucellosis after adjusting for gender, age, and ethnicity. Conclusion DILI occurred in a minority of inpatients diagnosed with brucellosis receiving rifampicin-based therapeutic regimen. In addition, obesity, alcohol abuse, and decreased serum albumin were valuable predictors of the risk of DILI in patients with brucellosis.Background Oral Chinese patent medicine (OCPM) combined with western medicine (WM) are believed to be effective for the therapy of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with sexual dysfunction (SD). These western medicines mainly involve antibiotics, phosphodiesterase type-5 inhibitor (PDE-5i), α-blockers. find more But there is no randomized controlled trial (RCT) that directly compares the efficacy of different OCPM. Hence, we operated a network meta-analysis (NMA) to contrast the efficacy of different OCPM for CP/CPPS with SD. Methods Relevant studies were searched in PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wanfang database. All of the RCTs concentrated on the use of OCPM to cure CP/CPPS with SD from the inception of the databases to November 2020. We appraised the risk of bias under the Cochrane Handbook and CONSORT statement. The data were statistically analyzed via STATA 13.0 and WinBUGS 1YGC + WM and QLBXC + WM. Conclusion Based on the NMA, QLSTC, CRYSG, SGYYC, LWDHP/YGC, QLBXC plus WM demonstrated the maximum probability of being the optimal therapies. Owing to the limitations of this research, these results should be confirmed by elaborate RCTs. Systematic Review Registration [https//www.crd.york.ac.uk/prospero/], identifier [CRD42021224060].Atrial fibrosis is a key contributor to atrial fibrillation (AF). Long non-coding ribonucleic acids (lncRNAs) were demonstrated to exhibit a key role in fibrotic remodeling; however, the function of nuclear-enriched abundant transcript 1 (NEAT1) in atrial fibrosis remains unclear. In the present study, we showed that NEAT1 was upregulated in atrial tissues of AF patients and was positively related to collagen I (coll I) and collagen III (coll III) expressions. Furthermore, the deletion of NEAT1 attenuated angiotensin II (Ang II)-caused atrial fibroblast proliferation, migration, and collagen production. We further observed that NEAT1 knockdown improved Ang II caused mouse atrial fibrosis in in vivo experiments. Moreover, we demonstrated that NEAT1 could negatively regulate miR-320 expression by acting as a competitive endogenous RNA (ceRNA). miR-320 directly targeted neuronal per arnt sim domain protein 2 (NPAS2) and suppressed its expression. We observed that NEAT1 exerted its function via the miR-320-NPAS2 axis in cardiac fibroblasts. These findings indicate that NEAT1 exerts a significant effect on atrial fibrosis and that this lncRNA is a new potential molecular target for AF treatment.It is known that the cell environment such as biomechanical properties and extracellular matrix (ECM) composition dictate cell behaviour including migration, proliferation, and differentiation. Important constituents of the microenvironment, including ECM molecules such as proteoglycans and glycosaminoglycans (GAGs), determine events in both embryogenesis and repair of the adult lung. Mesenchymal stromal/stem cells (MSC) have been shown to have immunomodulatory properties and may be potent actors regulating tissue remodelling and regenerative cell responses upon lung injury. Using MSC in cell-based therapy holds promise for treatment of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, so far clinical trials with MSCs in COPD have not had a significant impact on disease amelioration nor on IPF, where low cell survival rate and pulmonary retention time are major hurdles to overcome. Research shows that the microenvironment has a profound impact on transplanted MSCs. In our studies on acellular lung tissue slices (lung scaffolds) from IPF patients versus healthy individuals, we see a profound effect on cellular activity, where healthy cells cultured in diseased lung scaffolds adapt and produce proteins further promoting a diseased environment, whereas cells on healthy scaffolds sustain a healthy proteomic profile. Therefore, modulating the environmental context for cell-based therapy may be a potent way to improve treatment using MSCs. In this review, we will describe the importance of the microenvironment for cell-based therapy in chronic lung diseases, how MSC-ECM interactions can affect therapeutic output and describe current progress in the field of cell-based therapy.Background Haemonchus contortus is an important pathogenic nematode parasite and major economic constraint of small ruminants in tropics and subtropics regions. This review is an attempt to systematically address the; (a) efficacy of different plants against H. contortus by in vitro and in vivo proof; (b) toxicology, mechanism of action, and active phyto-compounds involve in anti-haemonchiasis activity; (c) and comparative analysis of plant species evaluated both in vitro and in vivo. Methods Online databases (Google Scholar, PubMed, Scopus, and ScienceDirect) were searched and published research articles (1980-2020) were gathered and reviewed. Results A total of 187 plant species were reported belonging to 59 families and 145 genera with Asteraceae and Fabaceae being frequently used. Out of the total plant species, 171 species were found to be evaluated in vitro and only 40 species in vivo. Twenty-four species were commonly evaluated for in vitro and in vivo anti-haemonchiasis activity. Among the reported asmpletely inhibited egg hatching in vitro and significantly reduced fecal egg count, decreased male length, and reproductive capacity of female in vivo. Conclusion This review summarized different medicinal plants owing to nematicidal activities against H. contortus eggs, larvae, and adult worms. Plants like L. viridiflorum, C. citriodora, C. procera, and A. herba-alba, while compounds anethole and carvone having promising nematicidal activities and could be an alternative source for developing novel drugs after further investigation.