Asiatic acid attenuates malignancy of human metastatic ovarian cancer cells via inhibition of epithelial-tomesenchymal transition

Purpose: To investigate the anticancer effects of asiatic acid on human metastatic ovarian cancer cells.Methods: Human metastatic ovarian cancer cell line SKOV-3 was treated with various concentrations of asiatic acid for 24 and 48 h. Cell proliferation, migration, invasion and morphology were analyzed by CCK-8, Transwell and immunofluorescence assays, respectively. Epithelial-to-mesenchymal transitionrelated gene and protein expressions were analyzed by quantitative polymerase chain reaction (qPCR) and Western blotting.Results: Asiatic acid (10 μM) significantly suppressed SKOV-3 cell migration and invasion (both p < 0.01). Moreover, epithelial markers (E-cad and KRT-7/14/19) were elevated, while mesenchymal markers (vimetin, N-cad and ZEB1/2) were suppressed after asiatic acid treatment, at both mRNA and protein levels. Inhibition of epithelial-to-mesenchymal transition was further evidenced by immunofluorescence staining of pan-cytokeratin and F-actin.Conclusion: Asiatic acid attenuates the malignancy of human metastatic ovarian cancer cells via epithelial-to-mesenchymal transition inhibition, and thus, is a therapeutic agent for ovarian cancer management.Keywords: Asiatic acid, Ovarian cancer, Metastasis, Epithelial-to-mesenchymal transition, Vometi

The genetic contribution of CIDEA polymorphisms, haplotypes and loci interaction to obesity in a Han Chinese population

To investigate the association of tag-SNPs and haplotype structures of the CIDEA gene with obesity in a Han Chinese population. Five single nucleotide polymorphisms (SNPs) (rs1154588/V115F, rs4796955/SNP1, rs8092502/SNP2, rs12962340/SNP3 and rs7230480/SNP4) in the CIDEA gene were genotyped in a case-control study. Genotyping was performed using the sequenom matrixassisted laser desorption/ionization time-of-flight mass spectrometry iPLEX platform. There were significant differences between the obese and control groups in genotype distributions of V115F (P\u3e0.001), SNP1 (P = 0.006) and SNP2 (P = 0.005). Carriers of V115F-TT, SNP1-GG and SNP2-CC genotypes had a 2.84-fold (95 % CI 1.73-4.66), 2.19-fold (95 % CI 1.09-4.38) and 4.37-fold (95 % CI 1.21-15.08) increased risk for obesity, respectively. Haplotype analysis showed that GTTC (SNP1/ SNP2/V115F/SNP4) had 1.41-fold (95 % CI 1.02-1.95) increased risk for obesity; whereas, haplotype TTGC had 0.48-fold (95 % CI 0.24-0.96) decreased risk for obesity. Using the multifactor dimensionality reduction method, the best model including SNP1, SNP2, V115F and SNP4 polymorphisms was identified with a maximum testing accuracy to 59.32 % and a perfect cross-validation consistency of 10/10 (P = 0.011). Logistic analysis indicated that there was a significant interaction between SNP1 and V115F associated with obesity. Subjects having both genotypes of SNP1/GG and V115F/TT were more susceptible to obesity in the Han Chinese population (OR 2.66, 95 %: 1.22-5.80). Genotypes of V115F/TT, SNP1/ GG and SNP2/CC and haplotype GTTC of CIDEA gene were identified as risk factors for obesity in the Han Chinese population. The interaction between SNP1 and V115F could play a joint role in the development of obesity

Risk Factors of Subclinical Atherosclerosis and Plaque Burden in High Risk Individuals: Results From a Community-Based Study

China is going through major change and the incidence of first-ever stroke has increased dramatically. In this study, we aim to determine the ultrasound characteristics of carotid intima-media thickness (CIMT) and carotid plaques (CP) in the Chinese community-based population with high risk of stroke. 1009 stroke-free participants from Datun community were classified at high risk of stroke and included in this cross-sectional study. We performed B-mode carotid ultrasound imaging in all of the study subjects to measure the CIMT in the common carotid artery (CCA) far wall and CP in the CCA, bifurcation and internal carotid artery. Stepwise logistic regression analyses were used to determine factors associated with elevated CIMT and subclinical atherosclerosis, as well as plaque burden (≥2 plaques). Our results showed that traditional risk factors including aging, hypertension, current smoking and the level of high density lipoprotein cholesterol are associated with subclinical atherosclerosis and plaque burden in high-risk community residents. To improve primary prevention in this population, we may consider intense blood pressure and lipid management, and smoking cessation

Glutathione S-Transferase alpha 4 promotes proliferation and chemoresistance in colorectal cancer cells

Glutathion

Identification of Key Genes and Pathways in Post-traumatic Stress Disorder Using Microarray Analysis

Introduction: Post-traumatic stress disorder (PTSD) is characterized by impaired fear extinction, excessive anxiety, and depression. However, the potential pathogenesis and cause of PTSD are not fully understood. Hence, the purpose of this study was to identify key genes and pathway involved in PTSD and reveal underlying molecular mechanisms by using bioinformatics analysis.Methods: The mRNA microarray expression profile dataset was retrieved and downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened using GEO2R. Gene ontology (GO) was used for gene function annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was performed for enrichment analysis. Subsequently, protein–protein interaction (PPI) network and module analysis by the plugin MCODE were mapped by Cytoscape software. Finally, these key genes were verified in stress-exposed models by Real-Time quantitative (qRT-PCR). In addition, we performed text mining among the key genes and pathway with PTSD by using COREMINE.Results: A total of 1004 DEGs were identified. Gene functional annotations and enrichment analysis indicated that the most associated pathway was closely related to the Wnt signaling pathway. Using PPI network and module analysis, we identified a group of “seed” genes. These genes were further verified by qRT-PCR. In addition, text mining indicated that the altered CYP1A2, SYT1, and NLGN1 affecting PTSD might work via the Wnt signaling pathway.Conclusion: By using bioinformatics analysis, we identified a number of genes and relevant pathway which may represent key mechanisms associated with PTSD. However, these findings require verification in future experimental studies

Ultrasound Stimulation Modulates Voltage-Gated Potassium Currents Associated With Action Potential Shape in Hippocampal CA1 Pyramidal Neurons

Potassium channels (K+) play an important role in the regulation of cellular signaling. Dysfunction of potassium channels is associated with several severe ion channels diseases, such as long QT syndrome, episodic ataxia and epilepsy. Ultrasound stimulation has proven to be an effective non-invasive tool for the modulation of ion channels and neural activity. In this study, we demonstrate that ultrasound stimulation enables to modulate the potassium currents and has an impact on the shape modulation of action potentials (AP) in the hippocampal pyramidal neurons using whole-cell patch-clamp recordings in vitro. The results show that outward potassium currents in neurons increase significantly, approximately 13%, in response to 30 s ultrasound stimulation. Simultaneously, the increasing outward potassium currents directly decrease the resting membrane potential (RMP) from −64.67 ± 1.10 mV to −67.51 ± 1.35 mV. Moreover, the threshold current and AP fall rate increase while the reduction of AP half-width and after-hyperpolarization peak time is detected. During ultrasound stimulation, reduction of the membrane input resistance of pyramidal neurons can be found and shorter membrane time constant is achieved. Additionally, we verify that the regulation of potassium currents and shape of action potential is mainly due to the mechanical effects induced by ultrasound. Therefore, ultrasound stimulation may offer an alternative tool to treat some ion channels diseases related to potassium channels

Immunomodulatory effects of complex probiotics on the immuno-suppressed mice induced by cyclophosphamide

IntroductionPrevious studies have reported the beneficial effects of Bifidobacterium animalis subsp. lactis XLTG11, Lacticaseibacillus casei Zhang, and Lactiplantibacillus plantarum P8, respectively. However, studies on the immunomodulatory enhancing effects of three complex probiotics have not been conducted. The aim of our study is to investigate the immunomodulatory effects of complex probiotics effect on the immunosuppressed mice induced by cyclophosphamide (CTX).MethodsAn immunocompromised mouse model was established by intraperitoneal injection of cyclophosphamide, which was gavage of different doses of complex probiotics and levamisole hydrochloride. The splenic and thymic indices, intestinal barrier, leukocyte and lymphocyte counts, percentage of splenic lymphocyte subpopulations, cytokine levels, and gut microbiota were determined.ResultsResults showed that the complex probiotics significantly elevated the spleen and thymus indices, increased the villi and crypt depth and the goblet cells. The leukocyte and lymphocyte counts and the percentage of splenic lymphocyte subpopulations in the CTX-treated mice were significantly elevated by the complex probiotics. In addition, the cytokines (IL-6, IL-10, IL-1β, and IFN-γ) were significantly increased after complex probiotic treatment. The complex probiotics restored the gut microbiota structure to the pattern of the control group by reducing the ratio of Firmicutes/Bacteroidetes and enhancing the relative abundances of specific microbiota that produced short-chain fatty acids.DiscussionThis study provides theoretical support for the immunity-enhancing function of the complex probiotics as well as a pharmacological basis for its further development and utilization

Association between antibiotic use during early life and early-onset colorectal cancer risk overall and according to polygenic risk and FUT2 genotypes

Early-onset colorectal cancer (EOCRC) has been increasing worldwide. Potential risk factors may have occurred in childhood or adolescence. We investigated the associations between early-life factors and EOCRC risk, with a particular focus on long-term or recurrent antibiotic use (LRAU) and its interaction with genetic factors. Data on the UK Biobank participants recruited between 2006 and 2010 and followed up to February 2022 were used. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of the associations between LRAU during early life and EOCRC risk overall and by polygenic risk score (constructed by 127 CRC-related genetic variants) and Fucosyltransferase 2 (FUT2), a gut microbiota regulatory gene. We also assessed the associations for early-onset colorectal adenomas, as precursor lesion of CRC, to examine the effect of LRAU during early-life and genetic factors on colorectal carcinogenesis. A total of 113 256 participants were included in the analysis, with 165 EOCRC cases and 719 EOCRA cases. LRAU was nominally associated with increased risk of early-onset CRC (OR = 1.48, 95% CI = 1.01-2.17, P = .046) and adenomas (OR = 1.40, 95% CI = 1.17-1.68, P < .001). When stratified by genetic polymorphisms of FUT2, LRAU appeared to confer a comparatively greater risk for early-onset adenomas among participants with rs281377 TT genotype (OR = 1.10, 95% CI = 0.79-1.52, P = .587, for CC genotype; OR = 1.75, 95% CI = 1.16-2.64, P = .008, for TT genotype; Pinteraction  = .089). Our study suggested that LRAU during early life is associated with increased risk of early-onset CRC and adenomas, and the association for adenomas is predominant among individuals with rs281377 TT/CT genotype. Further studies investigating how LRAU contributes together with genetic factors to modify EOCRC risk, particularly concerning the microbiome-related pathway underlying colorectal carcinogenesis, are warranted