Virus versus host: influenza A virus circumvents the immune responses

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ADSC Exosomes Mediate lncRNA-MIAT Alleviation of Endometrial Fibrosis by Regulating miR-150-5p

BackgroundSecondary infertility remains a major complication of endometrial fibrosis in women. The use of exosomes from adipose-derived mesenchymal stem cells (ADSCs) has shown promising results for the treatment of endometrial fibrosis. However, the mechanisms of action of ADSC-exosome (ADSC-Exo) therapy remain unclear.Materials and MethodsAn endometrial fibrosis model was established in mice treated with alcohol and endometrial epithelial cells (ESCs) treated with TGF-β1. ADSCs were isolated from Sprague Dawley (SD) rats, and exosomes were isolated from ADSCs using ExoQuick reagent. Exosomes were identified by transmission electron microscopy (TEM), NanoSight, and Western blot analysis. The expression level of lncRNA-MIAT was detected by qPCR analysis. Western blot analysis was carried out to determine the protein levels of fibrosis markers (TGFβR1, α-SMA, and CK19). A dual-luciferase reporter gene assay was used to verify the relationship between target genes. The endometrial tissues of the endometrial fibrosis model were stained with HE and Masson’s trichrome.ResultsADSCs and ADSC-Exos were successfully isolated, and the expression level of lncRNA-MIAT was significantly down-regulated in endometrial tissue and the TGF-β1-induced ESC injury model, whereas ADSC-Exos increased the expression of lncRNA-MIAT in the TGF-β1-induced ESC model. Functionally, ADSC-Exo treatment repressed endometrial fibrosis in vivo and in vitro by decreasing the expression of hepatic fibrosis markers (α-SMA and TGFβR1) and increasing the expression of CK19. Moreover, miR-150-5p expression was repressed by lncRNA-MIAT in the TGF-β1-induced ESC injury model. The miR-150-5p mimic promoted TGF-β1-induced ESC fibrosis.ConclusionADSC-Exos mediate lncRNA-MIAT alleviation of endometrial fibrosis by regulating miR-150-5p, which suggests that lncRNA-MIAT from ADSC-Exos may be a viable treatment for endometrial fibrosis

Meta-analysis of the effect of expression of MYB transcription factor genes on abiotic stress

Background MYB proteins are a large group of transcription factors. The overexpression of MYB genes has been reported to improve abiotic stress tolerance in plant. However, due to the variety of plant species studied and the types of gene donors/recipients, along with different experimental conditions, it is difficult to interpret the roles of MYB in abiotic stress tolerance from published data. Methods Using meta-analysis approach, we investigated the plant characteristics involved in cold, drought, and salt stress in MYB-overexpressing plants and analyzed the degrees of influence on plant performance by experimental variables. Results The results show that two of the four measured plant parameters in cold-stressed plants, two of the six in drought-stressed, and four of the 13 in salt-stressed were significantly impacted by MYB overexpression by 22% or more, and the treatment medium, donor/recipient species, and donor type significantly influence the effects of MYB-overexpression on drought stress tolerance. Also, the donor/recipient species, donor type, and stress duration all significantly affected the extent of MYB-mediated salt stress tolerance. In summary, this study compiles and analyzes the data across studies to help us understand the complex interactions that dictate the efficacy of heterologous MYB expression designed for improved abiotic stress tolerance in plants

Juvenile idiopathic arthritis and primary ovarian failure: a two-sample Mendelian randomization analysis in a mixed-gender cohort

BackgroundThe causal relationship between juvenile idiopathic arthritis (JIA) and primary ovarian failure (POF) remains uncertain. To elucidate this relationship, we employed a two-sample Mendelian randomization analysis.MethodsThe single nucleotide polymorphisms (SNPs) associated with JIA were obtained from a previously published genome-wide association study (GWAS), while the pooled data for POF originated from the FinnGen consortium. The study populations consisted exclusively of individuals of European descent. In our Mendelian randomization analysis, we performed inverse-variance weighted analysis, weighted-median analysis, weighted-mode analysis and Mendelian randomization-Egger regression analysis, supplemented by sensitivity analyses to validate the accuracy and robustness of the findings.ResultsThe IVW (OR = 1.23, 95% CI 1.06-1.43; P = 0.007) and weighted median (OR = 1.25, 95% CI 1.06-1.47; P = 0.009), along with sensitivity analysis validation, provide compelling evidence of a significant causal association between JIA and POF.ConclusionThe study revealed a significant causal association between genetically predicted JIA and POF, indicating that JIA significantly elevates the risk of developing POF. Therefore, it is recommended to implement screening for premature ovarian failure in women diagnosed with JIA

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Accumulation Characteristics and Safety Evaluation of Heavy Metals in Four Kinds of Aquatic Products from Lake Taihu

In order to investigate the current status of heavy metals pollution and food safety of aquatic products from Lake Taihu, atomic absorption spectrophotometry (AAS) was used to determine the contents of Pb, Cd, Cu, and Zn in the head, muscle and viscera of farmed and wild aquatic products. The results showed that the distribution patterns of heavy metals in different parts of aquatic products were quite different. Heavy metals were mainly distributed in the head and viscera of all investigated aquatic products except wild Carassius auratus. The contents of heavy metals in each part of aquatic products generally decreased in the following order: Zn > Cu > Pb > Cd. The levels of heavy metals pollution in the muscle tissue of farmed and wild aquatic products were different, with higher levels being found in the muscle tissue of wild aquatic products. Furthermore, the content of each heavy metal in muscle tissue were also different among different kinds of aquatic products, with both farmed and wild Metapenaeus ensishaving the strongest Cu accumulation capacity while wild C. auratus having the strongest Zn accumulation capacity. The heavy metals pollution in the muscle tissue of aquatic products from Lake Taihu was generally at slight level, and only a few of them were seriously polluted with heavy metals. The main pollution factors were Pb and Zn

Ubiquitination and Long Non-coding RNAs Regulate Actin Cytoskeleton Regulators in Cancer Progression

Actin filaments are a major component of the cytoskeleton in eukaryotic cells and play an important role in cancer metastasis. Dynamics and reorganization of actin filaments are regulated by numerous regulators, including Rho GTPases, PAKs (p21-activated kinases), ROCKs (Rho-associated coiled-coil containing kinases), LIMKs (LIM domain kinases), and SSH1 (slingshot family protein phosphate 1). Ubiquitination, as a ubiquitous post-transcriptional modification, deceases protein levels of actin cytoskeleton regulatory factors and thereby modulates the actin cytoskeleton. There is increasing evidence showing cytoskeleton regulation by long noncoding RNAs (lncRNAs) in cancer metastasis. However, which E3 ligases are activated for the ubiquitination of actin-cytoskeleton regulators involved in tumor metastasis remains to be fully elucidated. Moreover, it is not clear how lncRNAs influence the expression of actin cytoskeleton regulators. Here, we summarize physiological and pathological mechanisms of lncRNAs and ubiquitination control mediators of actin cytoskeleton regulators which that are involved in tumorigenesis and tumor progression. Finally, we briefly discuss crosstalk between ubiquitination and lncRNA control mediators of actin-cytoskeleton regulators in cancer

Cardiovascular and microvascular outcomes of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a meta-analysis of randomized controlled cardiovascular outcome trials with trial sequential analysis

Abstract Background Efficacy trials showed that glucagon-like peptide–1 receptor (GLP1R) agonists reduced metabolic risk factors in addition to glucose lowering, but the cardiovascular and microvascular efficacy of this drug class remains to be determined. We aimed to evaluate the overall cardiovascular and microvascular efficacy of GLP1R agonists by performing a meta-analysis with trial sequential analysis. Methods Randomized controlled, cardiovascular outcomes trials including at least 2000 patient-years’ follow-up and 100 composite cardiovascular events were included. Trial sequential analysis (TSA) was performed and the quality of evidence was graded. Results Thirty-three thousand four hundred fifty-seven patients and 4105 cardiovascular events from 4 large trials were included. GLP1R agonists were associated with a statistically significant reduction in risks for all-cause mortality (hazard ratio [HR]: 0.88, 95% CI: 0.81 to 0.95; number needed to treat [NNT]: 286 person-years), cardiovascular mortality (HR: 0.87, 95% CI: 0.79 to 0.96; NNT: 412 person-years), stroke (HR: 0.87, 95% CI: 0.76 to 0.98; NNT: 209 person-years) and the composite adverse cardiovascular outcome (MACE; HR: 0.91, 95% CI: 0.85 to 0.96; NNT: 241 person-years). The magnitude of benefit on MACE was attenuated in patients with a history of congestive heart failure (HR: 0.96, 95% CI: 0.85 to 1.08 with; HR: 0.87, 95% CI: 0.77 to 1.00 without). The risks for hospitalization for heart failure and myocardial infarction were not significantly different. The quality of the evidence was deemed as moderate to high based on GRADE approach. TSA provided firm evidence for a 10% reduction in all-cause mortality, a 15% reduction in MACE, and lack of a 15% reduction in hospitalization for heart failure, but evidence remains inconclusive for cardiovascular mortality and myocardial infarction. GLP1R agonists numerically reduced the rates for nephropathy but the risk for retinopathy was similar. Conclusions Meta-analysis with trial sequential analysis suggested that GLP1R agonists significantly reduced the risk for all-cause mortality and composite cardiovascular outcomes, but the reduction of cardiovascular mortality remains to be confirmed

Effects of supplementation with crystalline or coated methionine and lysine in low protein diet on growth performance, intestinal health and muscle quality of gibel carp, Carassius auratus gibelio

A 10-week feeding trial was conducted to elucidate the effects of coated amino acids on growth performance, intestinal health, and muscle quality of gibel carp (Carassius auratus gibelio) fed with low protein diet. A total of 450 carps (initial body weight of 15.67 g ± 0.04) were selected and randomly assigned into 6 groups, with each group consisting of three replicates and 25 fish per replicate. Six experimental diets were: control group (NP, 31.44% CP), low protein group (LP, 28.69% CP), low protein supplemented with crystalline methionine (CrM), crystalline methionine and crystalline lysine (CrML), coated methionine (CoM) or coated methionine and coated lysine (CoML). The results indicated that compared to the NP group, the LP group showed no significant difference in weight gain, specific growth rate, feed conversion ratio, viscerosomatic index, and condition factor (P > 0.05) but had a significant decrease in whole body crude fat content and increase in moisture content (P < 0.05). The hepatosomatic index in the CoML group was significantly lower than the LP group (P<0.05), and moisture content in the CrM and CoM groups was significantly lower than LP group (P<0.05). Serum alanine transaminase of the CrML group was significantly lower than the LP group. Methane dicarboxylic aldehyde content and superoxide dismutase activity in the CrML group were significantly lower than those in the LP group (P<0.05), and hardness, firmness, and chewiness in the CoM group were significantly lower (P<0.05) than the LP group. Compared to crystalline amino acids, coated amino acid groups showed a significant increase in crude fat content (P<0.05) and significant enhancements in the activities of superoxide dismutase and catalase (P<0.05). This results indicate that low protein feed supplemented coated amino acids can significantly improve the antioxidant capacity, fat deposition, intestinal health, and muscle quality of gibel carp

Transthyretin Exerts Pro-Apoptotic Effects in Human Retinal Microvascular Endothelial Cells Through a GRP78-Dependent Pathway in Diabetic Retinopathy

Background/Aims: Diabetic retinopathy (DR) is one of the main causes of blindness in the world. Our previous study showed that transthyretin (TTR) regulates key genes in the Tie2 pathway and inhibits the development of neovascularization in DR, but the mechanism is still unclear. Here, we investigated how TTR affects the progression of neovascularization in DR. Methods: Natural and simulated DR media (hyperglycemia and hypoxia) were used to culture human retinal microvascular endothelial cells (hRECs). Flow cytometry was employed to investigate the effect of TTR on apoptosis of hRECs. Fluorescent labeling and immunofluorescence staining were used to determine the TTR distribution in hRECs. The membrane proteins of hRECs were extracted and applied to a sepharose-TTR column, and the captured proteins were identified by Mass Spectrometric analysis. Gene knock-down and western blotting assays were used to study the key signal pathway of the most abundant identified protein. Results: TTR induced apoptosis of hRECs in an environment that simulated hypoxia. Immunofluorescent staining showed that TTR could enter the nuclei of hRECs. A total of 30 unique TTR-captured proteins were identified by Mass Spectrometry, and glucose-regulated protein 78 (GRP78) was one of the most abundant. Western blotting and gene knock-down indicated that TTR might upregulate GRP78 and facilitate apoptosis through the eIF2α/CHOP pathway. Conclusions: In the DR environment (hyperglycemia and hypoxia), TTR was shown to repress neovascularization by promoting apoptosis of hRECs through a GRP78-dependent pathway