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Abstracts Objective The oxidative balance score (OBS) reflects the overall burden of oxidative stress in an individual, with a higher OBS indicating greater antioxidant exposure. This study aimed to explore the association between constipation and OBS. Methods Variables were extracted from participants who completed a constipation questionnaire as part of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The OBS was developed based on dietary and lifestyle factors, encompassing 16 nutrients and 4 lifestyle variables. Weighted logistic regression and restricted cubic spline (RCS) analyses were employed to evaluate the association between OBS and constipation. Results After adjusting for all covariates, weighted multivariate logistic regression analysis revealed a 4% reduction in the incidence of constipation for each additional unit of OBS (OR: 0.96, 95% CI: 0.95–0.97, p

Background: Retinoblastoma (RB) is a rare primary malignant tumor primarily affecting children. Our study aims to compare the overall survival (OS) between pediatric and adult RB patients and establish a predictive model for adult RB patients' OS to assist clinical decision-making. Methods: This study retrospectively analyzed data from 1938 RB patients in the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2000 to 2015. Propensity score matching (PSM) ensured balanced characteristics between pediatric and adult groups. A Cox proportional hazards regression model was used to assess prognostic factors, and selected variables were utilized to construct a predictive survival model. The Nomogram model's performance was evaluated through the C-index, time-dependent ROC curves, calibration curves, and decision curve analysis (DCA). Results: Following PSM, adult RB patients had lower OS compared to pediatric RB patients. Independent prognostic factors for adult RB OS included age, gender, disease stage, radiation therapy, income, and diagnosis confirmation. In the training cohort, the Nomogram achieved a C-index for OS of 0.686 and accurately predicted 2-year, 3-year, and 5-year OS with AUC values of 0.672, 0.680, and 0.660, respectively. The C-index, time-dependent ROC curves, calibration curves, and DCA in both training and validation cohorts confirmed the Nomogram's excellent performance. Conclusion: In this study, adult RB patients have worse OS than pediatric RB patients. Consequently, we constructed a Nomogram to predict the risk for adult RB patients. The Nomogram demonstrated good accuracy and reliability, making it suitable for widespread application in clinical practice to assist healthcare professionals in assessing patients’ prognoses.

Abstract Background Invasive micropapillary carcinoma (IMPC) of the breast is known for its high propensity for lymph node (LN) invasion. Inadequate LN dissection may compromise the precision of prognostic assessments. This study introduces a log odds of positive lymph nodes (LODDS) method to address this issue and develops a novel LODDS-based nomogram to provide accurate prognostic information. Methods The study analyzed data from 1,901 patients with breast IMPC from the Surveillance, Epidemiology, and End Results database. It assessed the relationships between LODDS and the number of excised LN (eLN), positive LN (pLN), and the pLN ratio (pLNR), identifying an optimal threshold value using a restricted cubic spline method. Predictive factors were identified by the Cox least absolute shrinkage and selection operator (Cox-LASSO) regression and validated through multivariate Cox regression to construct a nomogram. The model's accuracy, discrimination, and utility were assessed. The study also explored the consequences of excluding LODDS from the nomogram and compared its effectiveness with the tumor-node-metastasis (TNM) staging system. Results LODDS improved N status classification by identifying heterogeneity in patients with pLN ratios of 0% (pLN =0) or 100% (pLN =eLN) and setting -1.08 as the ideal cutoff. Five independent prognostic factors for breast cancer-specific survival (BCSS) were identified: tumor size, N status, LODDS, progesterone receptor status, and histological grade. The LODDS-based nomogram achieved a strong concordance index of 0.802 (95% CI: 0.741-0.863), surpassing both the version without LODDS and the conventional TNM staging in all tests. Conclusions For breast IMPC, LODDS served as an independent prognostic factor, its effectiveness unaffected by the anatomical LN count, enhancing the accuracy of N staging. The LODDS-based nomogram showed promise in offering more personalized prognostic information.

BackgroundOxidative stress is acknowledged as a pivotal factor in the intricate pathophysiological processes and pathogenesis of constipation. Modifying dietary patterns can elevate in vivo antioxidant biomarker levels, consequently mitigating oxidative stress. The Composite Dietary Antioxidant Index (CDAI) provides a dependable scoring mechanism for quantifying the potential antioxidant capacity of diets. The association between CDAI levels and the risk of constipation remains uncertain.PurposeTo investigate the potential correlation between CDAI and constipation, aiming to improve constipation management through dietary guidance.MethodsA total of 11,165 adults aged ≥20 years, drawn from the 2005–2010 National Health and Nutrition Examination Survey, were enrolled in this cross-sectional study. We evaluated the correlation between CDAI levels and the risk of constipation through three weighted logistic regression models. Restricted cubic spline (RCS) analysis was employed to assess nonlinear trends, and stratified analyses were conducted.ResultsAfter adjusting for all confounding variables, the findings revealed an association between CDAI and constipation [OR = 0.937; 95% CI (0.892, 0.984), p = 0.012]. Moreover, individuals in the highest quartile of CDAI demonstrated a 40.1% lower likelihood of experiencing constipation compared to those in the lowest quartile [OR = 0.599; 95% CI (0.382, 0.939), p = 0.027]. The RCS analysis indicated a linear relationship between CDAI and constipation (P-non-linear =0.1016). Subgroup analysis by gender revealed a negative correlation in the male population [OR = 0.871; 95% CI (0.801, 0.947), p = 0.002], with men in the highest CDAI quartile exhibiting a 59.8% lower likelihood of experiencing constipation compared to those in the lowest quartile [OR = 0.402; 95% CI (0.206, 0.787), p = 0.010]. Furthermore, alterations in selenium [OR = 0.997; 95% CI (0.995, 1.000), p = 0.039] per milligram were independently linked to constipation. In a gender subgroup analysis of a single antioxidant, changes per milligram of vitamin E [OR = 0.904; 95% CI (0.838 to 0.975), p = 0.011] among males were independently associated with constipation.ConclusionThe fully adjusted model showed a correlation between CDAI and constipation and a significant correlation in quartiles. Meanwhile, subgroup analysis by gender showed that CDAI was negatively associated with constipation in the male population. Moreover, the findings of this study imply that investigations into antioxidant diets should be contextualized within dietary patterns.

BackgroundEvidence from observational studies and clinical trials has associated gut microbiota with infectious diseases. However, the causal relationship between gut microbiota and infectious diseases remains unclear.MethodsWe identified gut microbiota based on phylum, class, order, family, and genus classifications, and obtained infectious disease datasets from the IEU OpenGWAS database. The two-sample Mendelian Randomization (MR) analysis was then performed to determine whether the gut microbiota were causally associated with different infectious diseases. In addition, we performed reverse MR analysis to test for causality.ResultsHerein, we characterized causal relationships between genetic predispositions in the gut microbiota and nine infectious diseases. Eight strong associations were found between genetic predisposition in the gut microbiota and infectious diseases. Specifically, the abundance of class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae was found to be positively associated with the risk of lower respiratory tract infections (LRTIs). On the other hand, family Acidaminococcaceae, genus Clostridiumsensustricto1, and class Bacilli were positively associated with the risk of endocarditis, cellulitis, and osteomyelitis, respectively. We also discovered that the abundance of class Lentisphaeria and order Victivallales lowered the risk of sepsis.ConclusionThrough MR analysis, we found that gut microbiota were causally associated with infectious diseases. This finding offers new insights into the microbe-mediated infection mechanisms for further clinical research.

Background: Glioblastoma (GBM) is the most prevalent malignant brain tumor, significantly impacting the physical and mental wellbeing of patients. Several studies have demonstrated a close association between gut microbiota and the development of GBM. In this investigation, Mendelian randomization (MR) was employed to rigorously evaluate the potential causal relationship between gut microbiota and GBM.Methods: We utilized summary statistics derived from genome-wide association studies (GWAS) encompassing 211 gut microbiota and GBM. The causal association between gut microbiota and GBM was scrutinized using Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods. Cochrane’s Q statistic was employed to conduct a heterogeneity test. MR-Pleiotropic Residuals and Outliers (MR-PRESSO) were applied to identify and eliminate SNPs with horizontal pleiotropic outliers. Additionally, Reverse MR was employed to assess the causal relationship between GBM and pertinent gut microbiota.Results: The MR study estimates suggest that the nine gut microbiota remain stable, considering heterogeneity and sensitivity methods. Among these, the family.Peptostreptococcaceae and genus.Eubacterium brachy group were associated with an increased risk of GBM, whereas family.Ruminococcaceae, genus.Anaerostipes, genus.Faecalibacterium, genus.LachnospiraceaeUCG004, genus.Phascolarctobacterium, genus.Prevotella7, and genus.Streptococcus were associated with a reduced risk of GBM. Following Benjamini and Hochberg (BH) correction, family.Ruminococcaceae (OR = 0.04, 95% CI: 0.01–0.19, FDR = 0.003) was identified as playing a protective role against GBM.Conclusion: This groundbreaking study is the first to demonstrate that family.Ruminococcaceae is significantly associated with a reduced risk of GBM. The modulation of family_Ruminococcaceae for the treatment of GBM holds considerable potential clinical significance.

RhoGDIα knockout mice show low male fertility and compromised spermatogenesis, with an underlying defect in F-actin cytoskeleton depolymerisation, which can be alleviated by inhibiting Rac1.

Objective(s): The loss of enteric neurons has been shown to be a major cause of slow transit constipation (STC). Gut microbiota and muscularis macrophages (MMs) are associated with the enteric nervous system (ENS) development and gastrointestinal (GI) motility. This study aimed to investigate whether Dioscin (DIO) increased GI motility and inhibited neuron loss by modulating gut microbiota profile, improving inflammation in the ENS microenvironment.Materials and Methods: The STC model was established by loperamide. The alteration of the gut microbiota was analyzed by 16S rDNA sequencing. The longitudinal muscle and myenteric plexus (LMMP) from the colon were prepared for flow cytometry, immunofluorescence, western blot, and qRT-PCR. Results: DIO increased the stool number, stool water content and shortened whole gut transit time, helped to recover the gut microbial diversity and microbiota community structure, and increased the abundance of Muribaculaceae in STC mice. Compared with the STC group, the number of MMs and the level of the iNOS, IL-6, and TNFα genes were significantly decreased following DIO treatment. Moreover, DIO may increase the number of HuC/D+ neurons per ganglion by up-regulating the BMP2 secreted by MMs and activating the BMP2/p-Smad1/5/9 signaling pathway. Furthermore, the level of excitatory neurotransmitter AchE in colon tissues exhibited a substantial increase in the DIO group. However, the level of inhibitory neurotransmitter VIP was markedly decreased. Conclusion: Our results provide that DIO increases GI motility and inhibits neuron loss by modulating gut microbiota profile, improving inflammation in the ENS microenvironment and up-regulating the BMP2 secreted by MMs.

Steviol glycosides are ideal sweeteners that are widely used in food, medicine, and cosmetics. Rebaudioside C (RC) is considered to be the third most abundant steviol glycoside, which has a bitter aftertaste that limits its application. Hydrolysis of RC to generate other bioactive steviol glycosides is an effective way to promote its additional utilization. In our previous study, a bacterium Paenarthrobacter ilicis CR5301 was isolated and identified for hydrolyzing RC with high efficiency. Herein, the expression profiles of P. ilicis CR5301 in the deletion and presence of RC were investigated by RNA-seq. The RC metabolites were identified by high-performance liquid chromatography and ultra-performance liquid chromatography-triple-time of flight mass spectrometry. Novel results were discovered in four aspects of research. First, the identification of metabolites revealed that four metabolites, namely, dulcoside A, dulcoside B, dulcoside A1, and steviol, were produced during RC metabolism. Second, RNA-seq analyses unraveled that 105 genes of P. ilicis CR5301 were significantly differentially expressed, and 7 pathways were significantly enriched. Third, independent RT-qPCR verified the accuracy and reliability of the RNA-seq results. Finally, a complete catabolic model of RC in P. ilicis CR5301 was proposed, and key genes were indicated in the RC catabolic metabolism by combining them with literature and sequence alignments. This study comprehensively unraveled the genes and pathways of RC catabolism in P. ilicis CR5301 at the transcriptional and metabolic levels. It provided new insights and evidence for understanding the mechanism of RC catabolism in bacteria. Key candidate genes may potentially contribute to the RC hydrolysis and preparation of other functional steviol glycosides in the future.

BackgroundTo assess the effect of megarectum on postoperative defecation of female patients with congenital rectovestibular fistula or rectoperineal fistula.MethodsFrom March 2013 to February 2021, 74 female patients with congenital rectovestibular fistula or rectoperineal fistula were treated. The age of patients ranged from 3 months to 1 year. Barium enema and spinal cord MRI were performed in all children. 4 patients were removed from the study because of spinal cord and sacral agenesis. Finally, 70 patients underwent one-stage anterior sagittal anorectoplasty (ASARP). Anal endoscopy and anorectal pressure measurement were performed 1 year after surgery. All patients were divided into two groups depending on the presence of megarectum (+) and (−) and observed for constipation and anal sphincter function.Results16 patients (4 months to 1 year) were complicated with megarectum, and 5 patients (3 months to 9 months) were without megarectum. The incision infection was seen in 3 patients. All patients were followed up for 1 year to 5 years. Fecal soiling was seen in 2 patients and constipation in 14 patients. Among 16 patients with megarectum, soiling was seen in 1 patient and the constipation in 12 patients. Among 54 patients without megarectum, soiling was seen in 1 patient and constipation in 2 patients. There was a significant difference in the incidence of postoperative constipation between the two groups (megarectum (+) 75% vs. megarectum (−) 3.7% (P

Single nucleotide polymorphisms (SNPs) was associated with altering the secondary structure of long non-coding RNA (lncRNA). Increasing reports showed that lnc-LAMC2-1:1 SNP played an important role in cancer development and invasion. This study is to elucidate the molecular function of lnc-LAMC2-1:1 SNP rs2147578 promoting tumor progression in colon adenocarcinoma (COAD). In this study, we found that the lnc-LAMC2-1:1 SNP rs2147578 was upregulated in COAD cell lines. Furthermore, lnc-LAMC2-1:1 SNP rs2147578 promoted colon cancer migration, invasion, and proliferation. Interestingly, lnc-LAMC2-1:1 SNP rs2147578 positively regulated HMGB3 expression via miR-216a-3p in colon cancer cells. Functional enrichment analysis showed that targeting genes of miR-216a-3p were enriched in regulating the pluripotency of stem cells, MAPK signaling pathway, TNF signaling pathway, neurotrophin signaling pathway, relaxin signaling pathway, and FoxO signaling pathway. Tumor Immune Estimation Resource (TIMER) database revealed that there was a significantly positive correlation between HMGB3 expression and the infiltration of CD8+ T cells, B cells, neutrophils, macrophages, and CD4+ T cells. Finally, HMGB3 overexpression was validated in external data. In conclusions, lnc-LAMC2-1:1 SNP rs2147578 was involved in promoting COAD progression by targeting miR-216a-3p/HMGB3, and this study will provide a novel molecular target for COAD.

Abstract Background Autoimmune hepatitis (AIH) is a T cell-mediated immune disease that activates abnormally against hepatic antigens. We have previously reported that endometrial regenerative cells (ERCs) were a novel source of adult stem cells, which exhibiting with powerful immunomodulatory effects. Galectin-9 (Gal-9) is expressed in ERCs and plays an important role in regulating T cell response. This study aims to explore the role of ERCs in attenuation of AIH and to determine the potential mechanism of Gal-9 in ERC-mediated immune regulation. Methods ERCs were obtained from menstrual blood of healthy female volunteers. In vitro, ERCs were transfected with lentivirus vectors carrying LGALS9 gene and encoding green fluoresce protein (GFP-Gal-9-LVs) at a MOI 50, Gal-9 expression in ERCs was detected by ELISA and Q-PCR. CD4+ T cells isolated from C57BL/6 mouse spleen were co-cultured with ERCs. The proliferation of CD4+ T cells was detected by CCK-8 kit and the level of Lck/zap-70/LAT protein was measured by western blot. Furthermore, AIH was induced by ConA in C57BL/6 mice which were randomly assigned to untreated, unmodified ERC-treated and Gal-9 high-expressing ERC-treated groups. Histopathological score, liver function, CD4+/CD8+ cell infiltration in liver tissues, the proportion of immune cells in the spleen and liver, and ERC tracking were performed accordingly to assess the progression degree of AIH. Results After transfecting with GFP-Gal-9-LVs, Gal-9 expression in ERCs was significantly increased. Additionally, Gal-9 high-expressing ERCs effectively inhibited CD4+ T cell proliferation and downregulated CD4+ T cell active related proteins p-Lck/p-ZAP70/p-LAT in vitro. Furthermore, treatment with Gal-9 high-expressing ERCs restored liver function, ameliorated liver pathological damage, inhibit CD4+ and CD8+ T cell proliferation and suppress Th1 and Th17 cell response in the hepatitis mice. In addition, Gal-9 high-expressing ERCs further markedly enhanced the level of IL-10 but reduced the levels of IFN-γ, TNF-α, and IL-4 in mouse sera and liver. Cell tracking also showed that ERCs could migrate to the damaged liver organs. Conclusions The results suggested that Gal-9 was an essential modulator, which was required by ERCs in regulating T cell response and attenuating ConA-induced experimental hepatitis. And also, it provides a novel idea for the clinical treatment of AIH.

A cavernous hemangioma, well-known as vascular malformation, is present at birth, grows proportionately with the child, and does not undergo regression. Although a cavernous hemangioma has well-defined histopathological characteristics, its origin remains controversial. In the present study, we characterized the cellular heterogeneity of a cavernous hemangioma using single-cell RNA sequencing (scRNA-seq). The main contribution of the present study is that we discovered a large number of embryonic mesenchymal stem cells (MSCs) in a cavernous hemangioma and proposed that cavernous hemangiomas may originate from embryonic MSCs. Further analysis of the embryonic MSCs revealed that: 1) proinflammatory cytokines and related genes TNF, TNFSF13B, TNFRSF12A, TNFAIP6, and C1QTNF6 are significantly involved in the MSC-induced immune responses in cavernous hemangiomas; 2) UCHL1 is up-regulated in the embryonic MSC apoptosis induced by proinflammatory cytokines; 3) the UCHL1-induced apoptosis of MSCs may play an important role in the MSC-induced immune responses in cavernous hemangiomas; and 4) UCHL1 can be used as a marker gene to detect embryonic MSCs at different apoptosis stages. In addition to MSCs, ECs, macrophages, T lymphocytes and NKCs were intensively investigated, revealing the genes and pathways featured in cavernous hemangiomas. The present study revealed the origin of cavernous hemangiomas and reported the marker genes, cell types and molecular mechanisms, which are associated with the origin, formation, progression, diagnosis and therapy of cavernous hemangiomas. The better understanding of the MSC-induced immune responses in benign tumours helps to guide future investigation and treatment of embryonic MSC-caused tumours. Our findings initiated future research for the rediscovery of MSCs, cancers/tumours and the UCHL1-induced apoptosis.

Background: Pterostilbene (PTE) is a natural polyphenol compound that has been proven to improve intestinal inflammation, but its laxative effect on slow transit constipation (STC) has never been studied. This study aims to investigate the laxative effect of PTE on loperamide (LOP)-induced STC mice and its influence on intestinal microbes through a combination of network pharmacological analysis and experimental verification.Material and Methods: PTE was used to treat LOP-exposed mice, and the laxative effect of PTE was evaluated by the total intestinal transit time and stool parameters. The apoptosis of Cajal interstitial cells (ICCs) was detected by immunofluorescence. The mechanism of PTE’s laxative effect was predicted by network pharmacology analysis. We used western blot technology to verify the predicted hub genes and pathways. Malondialdehyde (MDA) and GSH-Px were tested to reflect oxidative stress levels and the changes of gut microbiota were detected by 16S rDNA high-throughput sequencing.Results: PTE treatment could significantly improve the intestinal motility disorder caused by LOP. Apoptosis of ICCs increased in the STC group, but decreased significantly in the PTE intervention group. Through network pharmacological analysis, PTE might reduce the apoptosis of ICCs by enhancing PI3K/AKT and Nrf2/HO-1 signaling, and improve constipation caused by LOP. In colon tissues, PTE improved the Nrf2/HO-1 pathway and upregulated the phosphorylation of AKT. The level of MDA increased and GSH-Px decreased in the STC group, while the level of oxidative stress was significantly reduced in the PTE treatment groups. PTE also promoted the secretion of intestinal hormone and restored the microbial diversity caused by LOP.Conclusion: Pterostilbene ameliorated the intestinal motility disorder induced by LOP, this effect might be achieved by inhibiting oxidative stress-induced apoptosis of ICCs through the PI3K/AKT/Nrf2 signaling pathway.

BackgroundHepatitis C virus-induced genes (HCVIGs) play a critical role in regulating tumor development in hepatic cancer. The role of HCVIGs in hepatic cancer remains unknown. This study aimed to construct a prognostic signature and assess the value of the risk model for predicting the prognosis of hepatic cancer.MethodsDifferentially expressed HCVIGs were identified in hepatic cancer data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases using the library (“limma”) package of R software. The protein–protein interaction (PPI) network was constructed using the Cytoscape software. Functional enrichment analysis was performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Univariate and multivariate Cox proportional hazard regression analyses were applied to screen for prognostic HCVIGs. The signature of HCVIGs was constructed. Gene Set Enrichment Analysis (GSEA) compared the low-risk and high-risk groups. Finally, the International Cancer Genome Consortium (ICGC) database was used to validate this prognostic signature. Polymerase chain reaction (PCR) was performed to validate the expression of nine HCVIGs in the hepatic cancer cell lines.ResultsA total of 143 differentially expressed HCVIGs were identified in TCGA hepatic cancer dataset. Functional enrichment analysis showed that DNA replication was associated with the development of hepatic cancer. The risk score signature was constructed based on the expression of ZIC2, SLC7A11, PSRC1, TMEM106C, TRAIP, DTYMK, FAM72D, TRIP13, and CENPM. In this study, the risk score was an independent prognostic factor in the multivariate Cox regression analysis [hazard ratio (HR) = 1.433, 95% CI = 1.280–1.605, P < 0.001]. The overall survival curve revealed that the high-risk group had a poor prognosis. The Kaplan–Meier Plotter online database showed that the survival time of hepatic cancer patients with overexpression of HCVIGs in this signature was significantly shorter. The prognostic signature-associated GO and KEGG pathways were significantly enriched in the risk group. This prognostic signature was validated using external data from the ICGC databases. The expression of nine prognostic genes was validated in HepG2 and LO-2.ConclusionThis study evaluates a potential prognostic signature and provides a way to explore the mechanism of HCVIGs in hepatic cancer.

Abstract Background Epithelial-mesenchymal transition (EMT) is an early event in tumour invasion and metastasis, and widespread and distant metastasis at early stages is the typical biological behaviour in small cell lung cancer (SCLC). Our previous reports showed that high expression of the transcription factor E2F1 was involved in the invasion and metastasis of SCLC, but the role of E2F1 in the process of EMT in SCLC is unknown. Methods Immunohistochemistry was performed to evaluate the expressions of EMT related markers. Immunofluorescence was used to detect the expressions of cytoskeletal proteins and EMT related markers when E2F1 was silenced in SCLC cell lines. Adenovirus containing shRNA against E2F1 was used to knock down the E2F1 expression, and the dual luciferase reporter system was employed to clarify the regulatory relationship between E2F1 and ZEB2. Results In this study, we observed the remodelling of cytoskeletal proteins when E2F1 was silenced in SCLC cell lines, indicating that E2F1 was involved in the EMT in SCLC. Depletion of E2F1 promoted the expression of epithelial markers (CDH1 and CTNNB1) and inhibited the expression of mesenchymal markers (VIM and CDH2) in SCLC cell lines, verifying that E2F1 promotes EMT occurrence. Next, the mechanism by which E2F1 promoted EMT was explored. Among the CDH1 related inhibitory transcriptional regulators ZEB1, ZEB2, SNAI1 and SNAI2, the expression of ZEB2 was the highest in SCLC tissue samples and was highly consistent with E2F1 expression. ChIP-seq data and dual luciferase reporter system analysis confirmed that E2F1 could regulate ZEB2 gene expression. Conclusion Our data supports that E2F1 promotes EMT by regulating ZEB2 gene expression in SCLC.

Oxidative stress induces bone loss and osteoporosis, and epigallocatechin-3-gallate (EGCG) may be used to combat these diseases due to its antioxidative property. Herein, oxidative stress in human bone marrow-derived mesenchymal stem cells (BM-MSCs) was induced by H2O2, resulting in an adverse effect on their osteogenic differentiation. However, this H2O2-induced adverse effect was nullified when the cells were treated with EGCG. In addition, treatment of BM-MSCs with EGCG alone also resulted in the enhancement of osteogenic differentiation of BM-MSCs. After EGCG treatment, expressions of β-catenin and cyclin D1 were upregulated, suggesting that the Wnt pathway was involved in the effects of EGCG on the osteogenic differentiation of BM-MSCs. This was also confirmed by the fact that the Wnt pathway inhibitor, Dickkopf-1 (DKK-1), can nullify the EGCG-induced enhancement effect on BM-MSC’s osteogenic differentiation. Hence, our results suggested that EGCG can reduce the effects of oxidative stress on Wnt pathway in osteogenic cells, which supported a potentially promising therapy of bone disorders induced by oxidative stress. Considering its positive effects on BM-MSCs, EGCG may also be beneficial for stem cell-based bone repair.

Background: Evidence from observational studies and clinical trials has associated gut microbiota with infectious diseases. However, the causal relationship between gut microbiota and infectious diseases remains unclear. Methods: We identified gut microbiota based on phylum, class, order, family, and genus classifications, and obtained infectious disease datasets from the IEU OpenGWAS database. The two-sample Mendelian Randomization (MR) analysis was then performed to determine whether the gut microbiota were causally associated with different infectious diseases. In addition, we performed reverse MR analysis to test for causality. Results: Herein, we characterized causal relationships between genetic predispositions in the gut microbiota and nine infectious diseases. Eight strong associations were found between genetic predisposition in the gut microbiota and infectious diseases. Specifically, the abundance of class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae was found to be positively associated with the risk of lower respiratory tract infections (LRTIs). On the other hand, family Acidaminococcaceae, genus Clostridiumsensustricto1, and class Bacilli were positively associated with the risk of endocarditis, cellulitis, and osteomyelitis, respectively. We also discovered that the abundance of class Lentisphaeria and order Victivallales lowered the risk of sepsis. Conclusion: Through MR analysis, we found that gut microbiota were causally associated with infectious diseases. This finding offers new insights into the microbe-mediated infection mechanisms for further clinical research. [ABSTRACT FROM AUTHOR]

Background: There is no standard management for small cell esophageal carcinoma (SCEC). The purpose of this multicenter, retrospective study (ChiSCER) was to investigate the treatment, outcomes, and risk factors impacting survival endpoints in patients with limited-stage SCEC (LS-SCEC). Materials and methods: Consecutive patients with LS-SCEC from 14 institutions between 2000 and 2020 in China were enrolled. Survival curves were constructed using the Kaplan-Meier method and compared using a log-rank test. Univariate and multivariate Cox regression models and propensity score matching (PSM) analysis were adopted in the prognostic analysis. Results were reported as hazard ratio (HR), 95% confidence interval (CI), and P value. Statistical significance was set as P value <0.05 in a two-tailed test. Results: Among 458 LS-SCEC patients, the median age was 63 [interquartile range (IQR), 57-68] years, and 318 (69%) were males. Eighty-four (18%), 167 (36%), and 207 (45%) patients received chemotherapy (CT) alone, CT plus definitive radiotherapy (CT+RT), and CT plus radical surgery (CT+S), respectively. With amedian follow-up time of 58.7 (95% CI 48.9-68.6) months, the median overall survival (OS) and 3-year OS rate for all patients 24.3 (95% CI 21.6-27) months and 37.3% (95% CI 32.8-42.5%), respectively. Multivariate analysis indicated that treatment modes, Karnofsky performance status (KPS), TNM stage, and CT cycle were independent prognostic factors for OS (P<0.05). Compared with CT alone, patients treated with CT+RT (HR 0.57, 95%CI 0.41-0.8, P=0.001) or CT+S (HR 0.59, 95% CI 0.42-0.82, P=0.002) had an improved OS, with no significant survival differences between CT+S and CT+RT groups after multivariate and PSM analyses (P>0.05). Subgroup analysis indicated that compared with CT+RT, patients with tumor location at lower 1/3 (HR 0.59, 95% CI 0.37-0.93, P=0.03) or tumor length >5 cm (HR 0.52, 95% CI 0.3-0.9, P=0.02) could obtain significant OS benefit fromCT+S. Patients with tumor location at middle 1/3 (HR 1.55, 95% CI 1.03-2.36, P=0.04) or tumor length =5 cm (HR 1.49, 95% CI 1.02-2.17, P=0.04) favored CT+RT. Distant metastasis accounted for 73.7% of all treatment failures after multidisciplinary treatments. Conclusion: Surgery and RT were equally effective local therapies for patients with LS-SCEC. The personalized decision of local therapy should be made after comprehensive considerations on tumor location, length, comorbidities, and organ preservation. [ABSTRACT FROM AUTHOR]

Current time obesity is the major challenges globally and the incidence of the obesity has raised dramatically in current years. The obesity enhanced the various metabolic diseases such as diabetes, cardiac, cancer and steatohepatitis. Natural drug having the long history to ameliorate the obesity and its related metabolic disorder. In this experimental study, we scrutinized the anti-obesity effect of nimbolide against high fat diet (HFD) induced obesity in rats. Wistar rats were divided into 5 groups and each group contains 10 rats. The body weight, tissue weight was estimated at regular time. Carbohydrate, lipid, hepatic, inflammatory cytokines, antioxidant and inflammatory parameters were estimated. The mRNA expression was also estimated. Nimbolide treated groups significantly (p < 0.001) suppressed the body weight at dose dependent manner. Nimbolide significantly (p < 0.001) reduced the hepatic parameters and altered the antioxidant parameters such as thiobarbituric acid reactive substances (TBARS), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx), superoxide mutase (SOD), glutathione S transferase (GST); decreased the level of inflammatory cytokines (IL-1β, IL-6, TNF-α). Nimbolide suppressed the mRNA expression of glucose-6-phosphatase HO-1 and nuclear factor erythroid-2 related factor-2 (Nrf2). Collectively, we can say that nimbolide having the capability to suppressed the HFD induced obesity via Nrf2/HO-1 pathway. [ABSTRACT FROM AUTHOR]