Quantitative assessment of the associations between DNA repair gene XRCC3 Thr241Met polymorphism and pancreatic cancer.

BACKGROUND: Prior research exploring the correlation between the XRCC3 Thr241Met polymorphism and the susceptibility to pancreatic cancer has yielded conflicting outcomes. To date, there has been a notable absence of studies examining this polymorphism. The primary aim of the current investigation is to elucidate the potential role of the XRCC3 Thr241Met polymorphism as a risk factor in the development of pancreatic cancer. METHODS: The comprehensive literature search was meticulously conducted across primary databases, including PubMed, Embase, and CNKI (China National Knowledge Infrastructure), spanning from the inception of each database through January 2024. To synthesize the data, a meta-analysis was performed using either a fixed or random-effects model, as appropriate, to calculate the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). RESULTS: The analysis revealed significant associations between the XRCC3 Thr241Met polymorphism and an increased risk of pancreatic cancer. This was evidenced through various genetic model comparisons: allele contrast (T vs. C: OR = 0.77, 95% CI = 0.70-0.86, P < 0.001), homozygote comparison (TT vs. CC: OR = 0.71, 95% CI = 0.58-0.88, P = 0.001), heterozygote comparison (TC vs. CC: OR = 0.67, 95% CI = 0.52-0.87, P = 0.003), and a dominant genetic model (TT/TC vs. CC: OR = 0.68, 95% CI = 0.57-0.81, P < 0.001). Additionally, subgroup analyses based on ethnicity disclosed that these associations were particularly pronounced in the Caucasian population, with all genetic models showing significance (P < 0.05). CONCLUSIONS: The XRCC3 Thr241Met polymorphism has been identified as contributing to a reduced risk of pancreatic cancer in the Caucasian population. This finding underscores the need for further research to validate and expand upon our conclusions, emphasizing the urgency for continued investigations in this domain.

The effects of scar in psychological disorder: A bibliometric analysis from 2003 to 2022.

Scars are fibrous tissues that replace normal tissue during the wound healing process. Scarring can lead to low self-esteem, social impairment, depression, anxiety, and other psychiatric and psychological distress, necessitating a comprehensive understanding of the latest perspectives, topical research, and directions in scarring-mental health. This is a biblioshiny and VOSviewer based bibliometric analysis study. All data were obtained from the Web of Science, and a total of 664 articles from 2003 to 2022 met the criteria. The last 7 years have been a period of rapid growth in the field, with 2022 having the highest number of articles. The United States is the core country with the highest production and citation rate. The most cited literature was written in 2003 by Van Loey NE et al. Van Loey NE is the most prolific and influential author in this field. The top five popular keywords include "quality of life", "depression", "management", "anxiety", and "prevalence". The paper concludes that the current focus of scholars in the field is on the treatment of scars and that multidisciplinary treatment of such patients is worth exploring. These findings provide relevant researchers with the current state of research and possible future directions in this field.

Urchin-Shaped Au-Ag@Pt Sensor Integrated Lateral Flow Immunoassay for Multimodal Detection and Specific Discrimination of Clinical Multiple Bacterial Infections.

A new lateral flow immunoassay strip (LFIA) combining sensitive detection and identification of multiple bacteria remains a huge challenge. In this study, we first developed multifunctional urchin-shaped Au-Ag@Pt nanoparticles (UAA@P NPs) with a unique combination of colorimetric-SERS-photothermal-catalytic (CM/SERS/PT/CL) properties and integrated them with LFIA for multiplexed detection and specific discrimination of pathogenic bacteria in blood samples. Unlike the conventional LFIA that relied on antibody (Ab), this novel LFIA introduced 4-mercaptophenylboronic acid (4-MPBA) as an ideal Ab replacer that was functionalized on UAA@P NPs (UAA@P/M NPs) with outstanding binding and enrichment capacities toward bacteria. Taking Staphylococcus aureus (S. aureus) as model bacteria, the limit of detection (LOD) was 3 CFU/mL for SERS-LFIA, 27 CFU/mL for PT-LFIA, and 18 CFU/mL for CL-LFIA, three of which were over 330-fold, 37-fold, and 55-fold more sensitive than ordinary visual CM-LFIA, respectively. Besides, this SERS-LFIA is capable of identifying three types of bacterial spiked blood samples (E. coli, S. aureus, and P. aeruginosa) effectively according to specific bacterial Raman "fingerprints" by partial least-squares-discriminant analysis (PLS-DA). More importantly, this LFIA was successfully applied to blood samples with satisfactory recoveries from 90.3% to 108.8% and capable of identifying the infected patients (N = 4) from healthy subjects (N = 2) with great accuracy. Overall, the multimodal LFIA incorporates bacteria discrimination and quantitative detection, offering an avenue for early warning and diagnosis of bacterial infection.

Comparative efficacy and safety of different combinations of three CDK4/6 inhibitors with endocrine therapies in HR+/HER-2 - metastatic or advanced breast cancer patients: a network meta-analysis.

BACKGROUND: This network meta-analysis aimed to assess the comparative efficacy and safety of combinations involving three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapies (ETs) in patients with metastatic or advanced breast cancer (BC) who are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-). METHODS: We initially identified relevant studies from previous meta-analyses and then conducted a comprehensive search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases to locate additional studies published between February 2020 and September 2021. Essential data were extracted, and a network meta-analysis was performed using R 4.1.1 software with a random-effects model. Furthermore, we assigned rankings to all available treatment combinations by calculating their cumulative probability. RESULTS: Data analysis included ten reports from nine studies. Pooled results demonstrated that each treatment combination significantly reduced the hazard risk of progression-free survival (PFS) compared to treatment with an aromatase inhibitor (AI) or fulvestrant alone. However, there were no differences observed in PFS or overall survival (OS) among the different treatment combinations. Additionally, patients receiving palbociclib plus AI and abemaciclib plus AI or fulvestrant experienced more severe adverse events (AEs), with hazard ratios (HRs) of 10.83 (95% confidence interval [CI] = 2.3 to 52.51) and 4.8 (95%CI = 1.41 to 16.21), respectively. The HR for ribociclib plus AI was 9.45 (95%CI = 2.02 to 43.61), and the HR for palbociclib plus fulvestrant was 6.33 (95%CI = 1.03 to 39.86). Based on the ranking probabilities, palbociclib plus fulvestrant had the highest probability of achieving superior PFS (37.65%), followed by abemaciclib plus fulvestrant (28.76%). For OS, ribociclib plus fulvestrant ranked first (34.11%), with abemaciclib plus fulvestrant in second place (25.75%). In terms of safety, palbociclib plus AI (53.98%) or fulvestrant (51.37%) had the highest probabilities of being associated with adverse events. CONCLUSIONS: Abemaciclib plus fulvestrant or ribociclib plus AI appear to be effective and relatively safe for the treatment of HR+/HER2- metastatic or advanced BC patients. However, given the reliance on limited evidence, our findings require further validation through additional studies.

Potential therapeutic target of EGF on bile duct ligation model and biliary atresia children.

BACKGROUND: The pathogenesis of liver fibrosis in biliary atresia (BA) is unclear. Epidermal growth factor (EGF) plays a vital role in liver fibrosis. This study aims to investigate the expression of EGF and the mechanisms of its pro-fibrotic effects in BA. METHODS: EGF levels in serum and liver samples of BA and non-BA children were detected. Marker proteins of EGF signaling and epithelial-mesenchymal transition (EMT) in liver sections were evaluated. Effects of EGF on intrahepatic cells and the underlying mechanisms were explored in vitro. Bile duct ligation (BDL) mice with/without EGF antibody injection were used to verify the effects of EGF on liver fibrosis. RESULTS: Serum levels and liver expression of EGF elevated in BA. Phosphorylated EGF receptor (p-EGFR) and extracellular regulated kinase 1/2 (p-ERK1/2) increased. In addition, EMT and proliferation of biliary epithelial cells were present in BA liver. In vitro, EGF induced EMT and proliferation of HIBEpic cells and promoted IL-8 expression in L-02 cells by phosphorylating ERK1/2. And EGF activated LX-2 cells. Furthermore, EGF antibody injection reduced p-ERK1/2 levels and alleviated liver fibrosis in BDL mice. CONCLUSION: EGF is overexpressed in BA. It aggravates liver fibrosis through EGF/EGFR-ERK1/2 pathway, which may be a therapeutic target for BA. IMPACT: The exact pathogenesis of liver fibrosis in BA is unknown, severely limiting the advancement of BA treatment strategies. This study revealed that serum and liver tissue levels of EGF were increased in BA, and its expression in liver tissues was correlated with the degree of liver fibrosis. EGF may promote EMT and proliferation of biliary epithelial cells and induce IL-8 overexpression in hepatocytes through EGF/EGFR-ERK1/2 signaling pathway. EGF can also activate HSCs in vitro. The EGF/EGFR-ERK1/2 pathway may be a potential therapeutic target for BA.

Association between dietary inflammatory index score and muscle mass and strength in older adults: a study from National Health and Nutrition Examination Survey (NHANES) 1999-2002.

PURPOSE: Chronic low-grade systemic inflammation affects muscle protein metabolism. The dietary inflammatory index (DII®) is a tool designed to assess the inflammatory potential of the diet. The available data on the association between DII and sarcopenia are limited. We aimed to investigate the association of the DII with components of sarcopenia in individuals over 50 years of age. METHODS: This cross-sectional study used the National Health and Nutrition Examination Survey (NHANES) 1999-2002 dataset. Body composition was measured, and isokinetic strength of the knee extensors (peak force) was evaluated. Low muscle mass and strength were defined using sex-specific thresholds. Energy-adjusted DII (E-DII™) scores were calculated using 24-h dietary recall data. Regression models were fit to evaluate the association between E-DII scores and low muscle mass and low muscle strength, alone and combined. RESULTS: Mean age of study participants was 62.1 ± 9.5 years, and 138 participants (7.4%) belonged to the combination group of low muscle mass and low muscle strength. In multivariable-adjusted regression models, higher E-DII score was associated with lower appendicular skeletal muscle index (ASMI) (ß = - 0.03, P  < 0.001, P trend <0.001), and lower peak force (ß = -2.15, P  = 0.04, P trend = 0.01) and higher likelihood for these components combined (OR = 1.12, 95% CI 1.01-1.25, P = 0.03). CONCLUSION: Higher E-DII score is associated with lower muscle mass and muscle strength, and increased likelihood for the combination of low muscle mass and low muscle strength in older adults. This has important implications for healthy aging.

Quantitative traits loci mapping and molecular marker development for total glutenin and glutenin fraction contents in wheat.

BACKGROUND: Glutenin contents and compositions are crucial factors influencing the end-use quality of wheat. Although the composition of glutenin fractions is well known, there has been relatively little research on the genetic basis of glutenin fractions in wheat. RESULTS: To elucidate the genetic basis for the contents of glutenin and its fractions, a population comprising 196 recombinant inbred lines (RILs) was constructed from two parents, Luozhen No.1 and Zhengyumai 9987, which differ regarding their total glutenin and its fraction contents (except for the By fraction). Forty-one additive Quantitative Trait Loci (QTL) were detected in four environments over two years. These QTL explained 1.3% - 53.4% of the phenotypic variation in the examined traits. Forty-three pairs of epistatic QTL (E-QTL) were detected in the RIL population across four environments. The QTL controlling the content of total glutenin and its seven fractions were detected in clusters. Seven clusters enriched with QTL for more than three traits were identified, including a QTL cluster 6AS-3, which was revealed as a novel genetic locus for glutenin and related traits. Kompetitive Allele-Specific PCR (KASP) markers developed from the main QTL cluster 1DL-2 and the previously developed KASP marker for the QTL cluster 6AS-3 were validated as significantly associated with the target traits in the RIL population and in natural varieties. CONCLUSIONS: This study identified novel genetic loci related to glutenin and its seven fractions. Additionally, the developed KASP markers may be useful for the marker-assisted selection of varieties with high glutenin fraction content and for identifying individuals in the early developmental stages without the need for phenotyping mature plants. On the basis of the results of this study and the KASP markers described herein, breeders will be able to efficiently select wheat lines with favorable glutenin properties and develop elite lines with high glutenin subunit contents.

Production and characterization of monoclonal antibodies against Toxoplasma gondii ROP18 with strain-specific reactivity.

The rhoptry kinase 18 of Toxoplasma gondii (TgROP18) has been identified as a key virulence factor that allows the parasite to escape from host immune defences and promotes its proliferation in host cells. Although much research is focused on the interaction between host cells and TgROP18, the development of monoclonal antibodies (mAbs) against TgROP18 has not been reported till date. To produce mAbs targeting TgROP18, two hybridomas secreting mAbs against TgROP18, designated as A1 and T2, were generated using cell fusion technology. The subtypes of the A1 and T2 mAbs were identified as IgG3 λ and IgM κ, and peptide scanning revealed that the core sequences of the antigenic epitopes were 180LRAQRRRSELVFE192 and 351NYFLLMMRAEADM363, respectively. The T2 mAb specifically reacted with both T. gondii type I and Chinese I, but not with T. gondii type II, Plasmodium falciparum or Schistosoma japonicum. Finally, the sequences of heavy chain and light chain complementarity-determining regions of T2 were amplified, cloned and characterized, making the modification of the mAb feasible in the future. The development of mAbs against TgROP18 would aid the investigation of the molecular mechanisms underlying the modulation of host cellular functions by TgROP18, and in the development of strategies to diagnose and treat Toxoplasmosis.

Expression of miR-93-5p in patients with esophageal carcinoma and its relationship with the curative effect and prognosis of radiotherapy.

This study aimed to investigate the expression of miR-93-5p in esophageal carcinoma-patients and its relationship with the curative effect and prognosis of radiotherapy. 102 patients with esophageal carcinoma treated in Yiwu Central Hospital from May 2013 to July 2015 were considered as the experimental group, and 89 healthy people for physical examination during the same period were selected as the control group. The expression of miR-93-5p in the serum of the two groups was compared. Based on the mean expression of miR-93-5p in serum, esophageal carcinoma patients were divided into high expression and low expression groups. Then the relationship between clinical-pathological characteristics and the expression of miR-93-5p was analyzed. The curative effect of radiotherapy in patients with esophageal carcinoma was evaluated, and the relationship between the expression of miR-93-5p, the curative effect of radiotherapy and the 3-year survival rate in patients with esophageal carcinoma was analyzed. The expression of miR-93-5p in the serum of the experimental group was significantly higher than that of the control group (P< 0.05); there was a significant correlation between the expression of miR-93-5p and pathological stage (P< 0.05). The expression of miR-93-5p in the effective radiotherapy group was significantly lower than that in the ineffective radiotherapy group (P< 0.05). ROC curve showed that the sensitivity and specificity of miR-93-5p in predicting radiotherapy response of esophageal carcinoma were 88.57 and 64.69% respectively, AUC was 0.864 (95%CI:0.791~0.936), P< 0.001; the 3-year survival rate of low expression group was significantly higher than that of high expression group (P< 0.05). In Conclusion, the expression of miR-93-5p was high in esophageal carcinoma patients, and the higher the expression, the worse the curative effect of radiotherapy and the worse the prognosis, which may be a new predictor of radiotherapy effect and prognosis in patients with esophageal carcinoma.

Inhibition of prostaglandin E2 receptor 4 by lnc000908 to promote the endothelial-mesenchymal transition participation in cardiac remodelling.

Long non-coding RNAs (lncRNAs) have emerged as potent regulators of cardiac disease; however, the role of lncRNA in cardiac fibrosis remains partially understood. In this study, we identified a cardiac endothelial-enriched lncRNA-lnc000908, which was markedly up-regulated in rats with cardiac fibrosis. In addition, the expression of prostaglandin E2 receptor 4 (EP4) was decreased in cardiac fibrosis. In vivo lnc000908 silencing by lentivirus increased the EP4 level, decreased endothelial-mesenchymal transition (EndMT) and improved cardiac fibrosis and cardiac function. Consistently, the lnc000908 knockdown also up-regulated EP4 and suppressed transforming growth factor-beta (TGF-ß)-induced EndMT in cardiac microvascular endothelial cells. In contrast, the lnc000908 overexpression by lentivirus decreased the EP4 level and induced EndMT. Of note, these pro- or anti-EndMT effects were reversed by the EP4 overexpression or the EP4 antagonist AH-23848, respectively. This study demonstrates that lnc000908 is a novel regulator of cardiac fibrosis by modulating the EP4 expression and EndMT.

Serum relaxin level predicts recurrence of atrial fibrillation after radiofrequency catheter ablation.

Relaxin, an emerging biomarker in heart failure, is involved in fibrosis and inflammation. The value of relaxin in predicting recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) is unknown and the subject of this study. We prospectively enrolled 248 consecutive patients with AF (paroxysmal in 127 and persistent in 121) who underwent RFCA at our center after measurement of circulating levels of relaxin by ELISA. Kaplan-Meier analysis with log-rank test and multivariate analysis were used to assess the association between pre-RFCA relaxin levels and post-RFCA AF recurrence at 18 months follow-up. At mean 16.3 ± 3.8 months post-RFCA, 195 (78.6%) patients maintained sinus rhythm, and their pre-RFCA relaxin level was lower than that in patients with AF recurrence (P < 0.001). From lowest to highest pre-RFCA relaxin level tertiles (T1; 82.10-< 234.36; T2; 234.36-< 342.26; and T3; 342.26-740.63 ng/L), AF recurrence rate increased significantly (8.5%, 20.5% and 34.9%, respectively; Kaplan-Meier analysis with log-rank test, χ2 = 18.44, P < 0.001). Using a cutoff of 285.4 ng/L, pre-RFCA relaxin level predicted AF recurrence during follow-up with sensitivity of 77.4% and specificity of 55.9% (area under the receiver operating characteristic curve = 0.71). On multivariate Cox proportional hazard model, relaxin level by tertile (T2, hazard ratio 2.678; 95% confidence interval 1.110-6.460; P = 0.028, and T3, hazard ratio 4.745; 95% confidence interval 2.075-10.854; P < 0.001, respectively compared with the T1) was the independent factor predicting recurrence. Elevated pre-RFCA relaxin level is associated with post-RFCA AF recurrence. A simple measurement of relaxin level therefore might help identify patients at high risk of AF recurrence after RFCA.Clinical Trial Registration chictr.org.cn identifier: ChiCTR-OOC-15006130.

Anti-Fibrosis Effect of Relaxin and Spironolactone Combined on Isoprenaline-Induced Myocardial Fibrosis in Rats via Inhibition of Endothelial-Mesenchymal Transition.

BACKGROUND: The effect of relaxin and spironolactone combined on myocardial fibrosis has not been reported. Thus, we investigated the effect of the combined therapy on isoprenaline-induced myocardial fibrosis and the mechanism. METHODS: Rats were injected subcutaneously with isoprenaline to induce myocardial fibrosis and underwent subcutaneous injection with relaxin (2 µg·kg-1·d-1) and given a gavage of spironolactone (30 mg·kg-1·d-1) alone or combined for 14 days. In vitro, the endothelial-mesenchymal transition was induced with transforming growth factor ß (TGF-ß) in human umbilical vein endothelial cells (HUVECs) pretreated with relaxin, 200 ng/ml, and/or spironolactone, 1uM. RESULTS: Relaxin and spironolactone used alone or combined improved cardiac function and decreased cardiac weight indices; reduced fibrous tissue proliferation; reduced levels of type I and III collagen; decreased the expression of α-smooth muscle actin (α-SMA) and transforming growth factor-ß1 (TGF-ß1), and increased the expression of cluster of differentiation-31 (CD31) in rats with isoprenaline-induced myocardial fibrosis. In vitro, compared with TGF-ß treatment, relaxin and spironolactone used alone or combined with TGF-ß decreased cell mobility, α-SMA and vimentin levels but increased vascular endothelial cadherin (VE-cadherin) and endothelial CD31levels. Especially, combined therapy had more remarkable effect than relaxin and spironolactone used alone both in vitro and in vivo. CONCLUSION: Relaxin and spironolactone combined affected isoprenaline-induced myocardial fibrosis in rats that the mechanism might be inhibition of the cardiac endothelial-mesenchymal transition.

Relaxin Ameliorates Renal Fibrosis and Expression of Endothelial Cell Transition Markers in Rats of Isoproterenol-Induced Heart Failure.

There may be cardio-renal interactions in rats of isoproterenol-induced heart failure, which may be associated with renal fibrosis and endothelial-to-mesenchymal transition (EndMT). Since its discovery, relaxin (RLX) which was regarded as a reproductive hormone for a long time, is recently considered an effective antifibrotic hormone in cardiac and renal fibrosis. We studied whether RLX diminished renal fibrosis in rats of isoproterenol (Iso)-induced heart failure and investigated the mechanism. Fifty male Sprague-Dawley rats were separated into five groups for treatment: control; Iso subcutaneously injection to induce heart failure, which led to renal fibrosis; RLX subcutaneously injection at low, medium and high dose (0.2, 2, 20 µg·kg-1·d-1 for 21 d). Indices of cardiac function and organ fibrosis were examined. Expression and changes in levels of collagen, cluster of differentiation 31 (CD31), α-smooth muscle actin (SMA), and transforming growth factor ß (TGF-ß) were measured in renal tissues. In rats with heart failure induced by Iso, treatment with RLX significantly ameliorated cardiac function and inhibited cardiac and renal fibrosis. RLX decreased renal collagen types I and III deposition, increased CD31 expression, and decreased the expression of α-SMA and TGF-ß, thereby possibly indicating inhibited renal EndMT in kidneys. Iso-induced heart and renal fibrosis was inhibited even greater with high-dose RLX, so the antifibrotic effect of RLX may be dose-related. In conclusion, RLX may ameliorate renal fibrosis in rats of Iso-induced heart failure, and it is infered that prevention of the EndMT may be one of the possible potential signaling pathways.

High molecular weight fibroblast growth factor-2 as a promising prognostic biomarker to predict the occurrence of heart failure in atrial fibrillation patients.

Heart failure (HF) has a significant effect on the prognosis of the patients with atrial fibrillation (AF), and also it is an important risk factor for overall mortality. High molecular weight fibroblast growth factor-2 (Hi-FGF-2) is emerging as a prognostic marker with HF and AF. The aim of this study was to prove that Hi-FGF-2 would predict occurrence of HF in the patients with AF. Subjects diagnosed with paroxysmal AF (Group paAF), persistent AF (Group peAF) and sinus rhythm (Group SR) were enrolled in the study. Serum Hi-FGF-2 concentration was measured by ELISA at baseline. Multivariable logistic models and receiver operating characteristic (ROC) curve analysis were established to predict the prognosis of AF subjects. 260 patients were enrolled in the study: 104 (40.0%) admitted for sinus rhythm (Group SR) and 156 (60.0%) with AF (Group paAF and Group peAF). The Hi-FGF-2 levels were much lower in the Group SR (58.2 ± 27.1 ng/L) than in the Group AF. Furthermore, the Group peAF (84.3 ± 34.1 ng/L) had higher Hi-FGF-2 levels than the Group paAF (72.9 ± 35.8 ng/L). Serum Hi-FGF-2 levels were classified into trisection in the multivariable logistic model (T1 < 57.3 ng/L, 57.3 < T2 < 86.5 ng/L, and T3 > 86.5 ng/L). Hi-FGF-2 showed good predictive ability for new-onset HF in the patients with AF. The occurrence of HF was associated significantly with increased tertile of serum Hi-FGF-2 levels (T2: OR 5.922, 95% CI 1.109-31.626, P = 0.037 and T3: OR 8.262, 95% CI 1.735-39.343, P = 0.008). ROC curve analysis showed that the area under curves for Hi-FGF-2 were 0.720 (P < 0.0001). Hi-FGF-2 has a significant meaning in AF subjects. Further to this, higher circulating Hi-FGF-2 was highly related to persistent AF, and Hi-FGF-2 may be an independent risk factor of occurrence HF in AF subjects.

Toxoplasma gondii inhibits differentiation of C17.2 neural stem cells through Wnt/ß-catenin signaling pathway.

Toxoplasma gondii is a major cause of congenital brain disease. T. gondii infection in the developing fetus frequently results in major neural developmental damage; however, the effects of the parasite infection on the neural stem cells, the key players in fetal brain development, still remain elusive. This study is aiming to explore the role of T. gondii infection on differentiation of neural stem cells (NSCs) and elucidate the underlying molecular mechanisms that regulate the inhibited differentiation of NSCs induced by the infection. Using a differentiation medium, i.e. , DMEM: F12 (1:1 mixture) supplemented with 2% N2, C17.2 neural stem cells (NSCs) were able to differentiate to neurons and astrocytes, respectively evidenced by immunofluorescence staining of differentiation markers including ßIII-tubulin and glial fibrillary acidic protein (GFAP). After 5-day culture in the differentiation medium, the excreted-secreted antigens of T. gondii (Tg-ESAs) significantly down-regulated the protein levels of ßIII-tubulin and GFAP in C17.2 NSCs in a dose-dependent manner. The protein level of ß-catenin in the nucleus of C17.2 cells treated with both wnt3a (a key activator for Wnt/ß-catenin signaling pathway) and Tg-ESAs was significantly lower than that in the cells treated with only wnt3a, but significantly higher than that in the cells treated with only Tg-ESAs. In conclusion, the ESAs of T. gondii RH blocked the differentiation of C17.2 NCSs and downregulated the expression of ß-catenin, an essential component of Wnt/ß-catenin signaling pathway. The findings suggest a new mechanism underlying the neuropathogenesis induced by T. gondii infection, i.e. inhibition of the differentiation of NSCs via blockade of Wnt/ß-catenin signaling pathway, such as downregulation of ß-catenin expression by the parasite ESAs.

Protective Effect of Spironolactone on Endothelial-to-Mesenchymal Transition in HUVECs via Notch Pathway.

BACKGROUND: Fibrosis results in excessive buildup of extracellular matrix proteins along with abnormalities in structure and is partly derived by a process involving transforming growth factor ß (TGF-ß) called endothelial-to-mesenchymal transition (EndMT). We investigated whether the aldosterone receptor-blocker spironolactone could abrogate TGF-ß-induced fibrosis in EndMT and the underlying mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into 5 groups for treatment: blank; vehicle control; TGF-ß (10 ng/ml); spironolactone (1 µM)+TGF-ß; and spironolactone+TGF-ß+DAPT (10 µM). Cell chemotaxis was assayed by transwell assay. The expression of CD31 and vimentin was determined by Immunofluorescence staining and western blot analysis. Notch1 protein level was detected by western blot analysis. RESULTS: Spironolactone significantly prevented TGF-ß-stimulated EndMT by down-regulate vimentin and up-regulate CD31 in HUVECs (p<0.01).It inhibited cell migration during EndMT (p<0.01). The protective effect of spironolactone against EndMT could be attenuated by blocking the Notch signal pathway with DAPT (p<0.01). Notch signaling was activated and cross-interacted with TGF-ß and spironolactone in regulating EndMT in HUVECs and reversed the spironolactone-related signaling by abrogating the antifibrotic actions with decreased Notch1 protein expression (p<0.01). CONCLUSION: Spironolactone may have a protective role in TGF-ß-induced EndMT in HUVECs mediated by the Notch signal pathway.

Photoguided Shape Deformation of Azobenzene-Containing Polymer Microparticles.

Here we present the generation of uniform microparticles with tunable diameters from azobenzene-based homopolymer by combining the microfluidics technique and emulsion-solvent evaporation route. In addition, the photoinduced deformation behavior of these microspheres, irradiated by a linearly polarized beam with different irradiation time and direction, are systemically studied. The deformation process through real time optical microscope observation can be investigated, benefiting from the uniform and microscaled size of the polymer particles. These results indicate that the deformation degree characterized by relative variation of the long axial for the particles can be controlled by the irradiation time. Moreover, elongated particles with tunable aspect ratio or tilted shape can be generated by manipulating the irradiation direction and/or time. Interestingly, the shape transformation kinetics displays a significant dependence on initial size of the polymer particle. In addition, the shape transformation of the polymer particle can lead to the variation of the orientation and distribution of the encapsulated anisotropic gold nanorods.

Toxoplasma gondii induce apoptosis of neural stem cells via endoplasmic reticulum stress pathway.

Toxoplasma gondii is a major cause of congenital brain disease; however, the underlying mechanism of neuropathogenesis in brain toxoplasmosis remains elusive. To explore the role of T. gondii in the development of neural stem cells (NSCs), NSCs were isolated from GD14 embryos of ICR mice and were co-cultured with tachyzoites of T. gondii RH strain. We found that apoptosis levels of the NSCs co-cultured with 1×106 RH tachyzoites for 24 and 48 h significantly increased in a dose-dependent manner, as compared with the control. Western blotting analysis displayed that the protein level of C/EBP homologous protein (CHOP) was up-regulated, and caspase-12 and c-Jun N-terminal kinase (JNK) were activated in the NSCs co-cultured with the parasites. Pretreatment with endoplasmic reticulum stress (ERS) inhibitor (TUDCA) and caspase-12 inhibitor (Z-ATAD-FMK) inhibited the expression or activation of the key molecules involved in the ERS-mediated apoptotic pathway, and subsequently decreased the apoptosis levels of the NSCs induced by the T. gondii. The findings here highlight that T. gondii induced apoptosis of the NSCs through the ERS signal pathway via activation of CHOP, caspase-12 and JNK, which may constitute a potential molecular mechanism responsible for the cognitive disturbance in neurological disorders of T. gondii.

Anti-fibrosis effect of scutellarin via inhibition of endothelial-mesenchymal transition on isoprenaline-induced myocardial fibrosis in rats.

Scutellarin (SCU) is the major active component of breviscapine and has been reported to be capable of decreasing myocardial fibrosis. The aim of the present study is to investigate whether SCU treatment attenuates isoprenaline-induced myocardial fibrosis and the mechanisms of its action. Rats were injected subcutaneously with isoprenaline (Iso) to induce myocardial fibrosis and rats in the SCU treatment groups were intraperitoneally infused with SCU (10 mg·kg-1·d-1 or 20 mg·kg-1·d-1, for 14 days). Post-treatment, cardiac functional measurements and the left and right ventricular weight indices (LVWI and RVWI, respectively) were analysed. Pathological alteration, expression of type I and III collagen, Von Willebrand factor, α-smooth muscle actin, cluster of differentiation-31 (CD31), and the Notch signalling proteins (Notch1, Jagged1 and Hes1) were examined. The administration of SCU resulted in a significant improvement in cardiac function and decrease in the cardiac weight indices; reduced fibrous tissue proliferation; reduced levels of type I and III collagen; increased microvascular density; and decreased expression of α-smooth muscle actin and increased expression of CD31, Notch1, Jagged1 and Hes1 in isoprenaline-induced myocardial fibrosis in rats. Our results suggest that SCU prevents isoprenaline-induced myocardial fibrosis via inhibition of cardiac endothelial-mesenchymal transition potentially, which may be associated with the Notch pathway.

Leadwise clustering multi-branch network for multi-label ECG classification.

The 12-lead electrocardiogram (ECG) is widely used for diagnosing cardiovascular diseases in clinical practice. Recently, deep learning methods have become increasingly effective for automatically classifying ECG signals. However, most current research simply combines the 12-lead ECG signals into a matrix without fully considering the intrinsic relationships between the leads and the heart's structure. To better utilize medical domain knowledge, we propose a multi-branch network for multi-label ECG classification and introduce an intuitive and effective lead grouping strategy. Correspondingly, we design multi-branch networks where each branch employs a multi-scale convolutional network structure to extract more comprehensive features, with each branch corresponding to a lead combination. To better integrate features from different leads, we propose a feature weighting fusion module. We evaluate our method on the PTB-XL dataset for classifying 4 arrhythmia types and normal rhythm, and on the China Physiological Signal Challenge 2018 (CPSC2018) database for classifying 8 arrhythmia types and normal rhythm. Experimental results on multiple multi-label datasets demonstrate that our proposed multi-branch network outperforms state-of-the-art networks in multi-label classification tasks.