ALKBH5 promotes hepatocellular carcinoma cell proliferation, migration and invasion by regulating TTI1 expression.

The objective of this research was to investigate the potential mechanisms of AlkB homolog 5, RNA demethylase (ALKBH5) in hepatocellular carcinoma (HCC). We used The Cancer Genome Atlas (TCGA), Kruskal-Wallis method and Kaplan-Meier (KM) survival analysis to study the expression of ALKBH5 and its correlation with clinical factors in HCC. In vitro experiments verified the expression of ALKBH5 and its effect on HCC cell phenotype. We screened differentially expressed genes (DEGs) from HCC patients associated with ALKBH5. Through this screening we identified the downstream gene TTI1 which is associated with ALKBH5 and investigated its function using Gene Expression Profiling Interaction Analysis (GEPIA) along with univariate Cox proportional hazards regression analysis. Finally, we analyzed the functions of ALKBH5 and TTI1 in HCC cells. Across numerous pan-cancer types, we observed significant overexpression of ALKBH5. In vitro experiments confirmed ALKBH5 as an oncogene in HCC, with its knockdown leading to suppressed cell proliferation, migration, and invasion. Bioinformatics analyses also demonstrated a significant positive correlation between ALKBH5 and TTI1. TTI1, highly expressed in cells, showed promising prognostic ability for patients. Further experiments confirmed that suppressing TTI1 impeded cell growth and movement, with this effect partially offset by increased ALKBH5 expression. Conversely, promoting these cellular processes was observed with TTI1 overexpression, but was dampened by decreased ALKBH5 expression. In conclusion, our findings suggest that ALKBH5 may influence proliferation, migration and invasion of HCC by modulating TTI1 expression, providing a new direction for treating HCC.

Comprehensive review on sexual dimorphism to improve scalp acupuncture in nervous system disease.

BACKGROUND: With the development of modern medicine, the Traditional Chinese Medicine (TCM) combined with western medicine began to be produced and applied. Scalp acupuncture (SA) as a Chinese medicine based on neurological theory, has a great advantage compared with TCM in the treatment of nervous system diseases. METHOD: In this paper, we analyze the physiological and pathological manifestations of sexual dimorphism (SD) to illustrate the necessity of SD treatment. In addition, we review the factors that can affect SD and analyze in physiological structure, function, and pathological neurons. Diseases (pathological basis, pathological manifestations, and incidence) and factors leading to gender differences, which to analyze the possibility of gender differences in SA. RESULT: Furthermore, we creatively a new insight of SD-SA and provide the complete SD treatment cases on the basis of the existing SA in different kinds of diseases including stroke, migraine, attention deficit hyperactivity disorder (ADHD), and depression. CONCLUSION: In summary, we believe that it is feasible to improve the clinical effectiveness of SA, which is able to promote the development of SA, and then provides an actionable evidence for the promotion of precision medicine in the future.

Factors contributing to exercise tolerance in patients with coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Exercise tolerance plays a vital role in the process of cardiac rehabilitation in patients undergoing percutaneous coronary intervention (PCI). The study sought to determine the characteristics, risks and correlates of post-PCI exercise tolerance in patients with coronary artery disease (CAD). METHODS: We analyzed clinical data of 299 CAD patients undergoing elective PCI and completing cardiopulmonary exercise testing (CPET). According to the Weber classification, post-PCI exercise tolerance was evaluated by peak oxygen uptake (VO2 peak). We assessed the impact of 34 predefined clinical features, cardiac functional parameters, and blood biochemistry data on exercise tolerance by univariate analysis and logistics regression analysis. RESULTS: Of 299 patients, 74.92% were men and average age was 60.90 ± 10.68 years. VO2 peak in the entire population was 17.54 ± 3.38 ml/kg/min, and 24.41% (n = 73) were less than 16 ml/kg/min, who were considered to have exercise intolerance. Multivariate logistics regression results showed that sex, diabetes mellitus, number of stents, left atrial diameter (LAD), end-diastolic volume (EDV), and hemoglobin influenced the peak oxygen uptake of CAD patients undergoing elective PCI. (All p < 0.05). CONCLUSIONS: Nearly one quarter of CAD patients have exercise intolerance in the early post-PCI period. Female, diabetes mellitus, number of stents, LAD, EDV might negatively impacted post-PCI exercise tolerance, which need further warrant by large scale cohort study.

Gut microbiota alteration after cholecystectomy contributes to post-cholecystectomy diarrhea via bile acids stimulating colonic serotonin.

Post-cholecystectomy diarrhea (PCD) is highly prevalent among outpatients with cholecystectomy, and gut microbiota alteration is correlated with it. However, how and to what extent changed fecal bacteria contributes to diarrhea are still unrevealed. Humanized gut microbiome mice model by fecal microbiota transplantation was established to explore the diarrhea-inducible effects of gut microbiota. The role of microbial bile acids (BAs) metabolites was identified by UPLC/MS and the underlying mechanisms were investigated with selective inhibitors and antagonists as probes. These mice transplanted with fecal microbiome of PCD patients (PCD mice) exhibited significantly enhanced gastrointestinal motility and elevated fecal water content, compared with these mice with fecal microbiome of NonPCD patients and HC. In analyzing gut microbiota, tryptophan metabolism was enriched in PCD microbiome. In addition, overabundant serotonin in serum and colon, along with elevated biosynthesis gene and reduced reuptake gene, and highly expressed 5-HT receptors (5-HTRs) in colon of PCD mice were found, but not in small intestine. Notably, diarrheal phenotypes in PCD mice were depleted by tryptophan hydroxylase 1 inhibitor (LX1606) and 5-HTRs selective antagonists (alosetron and GR113808). Furthermore, increased microbial secondary BAs metabolites of DCA, HDCA and LCA were revealed in feces of PCD mice and they were found responsible for stimulating 5-HT level in vitro and in vivo. Intriguingly, blocking BAs-conjugated TGR5/TRPA1 signaling pathway could significantly alleviate PCD. In conclusion, altered gut microbiota after cholecystectomy contributes to PCD by promoting secondary BAs in colon, which stimulates colonic 5-HT and increases colon motility.

Integration of pharmacodynamics, network pharmacology and metabolomics to elucidate effect and mechanism of Artemisia capillaris Thunb. in the treatment of jaundice.

ETHNOPHARMACOLOGICAL RELEVANCE: As one of the most commonly used herbs, Artemisia capillaris Thunb. (ACT) display favorable effect in the treatment of jaundice. However, mechanism of ACT in the treatment of jaundice remains unclear at present, which limits its development and application. AIM OF THE STUDY: To investigate effect and mechanism of Artemisia capillaris Thunb. (ACT) in the treatment of jaundice using pharmacodynamics, network pharmacology and metabolomics. METHODS: Effect of ACT in treating jaundice was evaluated by biochemical assays and pathological observation using the α-naphthyl isothiocyanate (ANIT)-induced mice. Jaundice-relieving mechanism of ACT was investigated by integration of network pharmacology and metabolomics. RESULTS: After the mice with jaundice were administrated ACT extract for 9 days, compared to that of the model group, serum D-BIL, T-BIL and ALP levels of the mice in the low, medium, high dose of ACT group decreased by 39.81%, 15.30% and 16.92%; 48.06%, 42.54% and 36.91%; 26.90%, 12.34% and 16.90%, respectively. The pathologic study indicated that ACT improved the symptoms of liver injury of the mice with jaundice. The network of herb (i.e., ACT)-components-targets-disease (i.e., jaundice) was established, which consisted of 17 components classified in flavonoids, chromones, organic acids, terpenoids, and 234 targets related to treatment of jaundice. Metabolomics analysis showed that, compared to that in the model group, level of 8 differential metabolites were upregulated and level of 29 differential metabolites were downregulated in the mice liver in the ACT group, respectively. The main metabolic pathways involved in treatment of jaundice by ACT were pantothenate and CoA biosynthesis, glutathione metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis in the liver, respectively. The integrated analysis of network pharmacology and metabolomics showed that 3α,7α,12α a-Trihydroxy-5ß-cholanate, glycocholate, taurocholate, pantetheine 4'-phosphate, and d-4'-phosphopantothenate were the potential biomarkers for treatment of jaundice, and AKR1C4, ALDH2 and HSD11B were the potential drug targets in the treatment of jaundice by ACT. CONCLUSION: The study based on metabolomics and network pharmacology indicated that ACT can display favorable jaundice-relieving effect by its multiple components regulating multiple biomarkers, multiple targets and multiple pathways, and may be a rational therapy for the treatment of jaundice.

Effect of Exercise on Carotid Artery Intima-Media Thickness in Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Carotid intima-media thickness (cIMT) is a validated surrogate marker of atherosclerosis that is independently associated with the risk for cardiovascular disease. Recent studies on the effect of exercise on cIMT have yielded conflicting results. METHODS: Studies that were available up until October 30, 2021 from the PubMed, Cochrane Library, Embase, and Web of Science databases were included in the analysis. Subgroup analyses were performed to determine the effects of the type, intensity, and duration of exercise on cIMT. RESULTS: This review included 26 studies with 1370 participants. Compared with control participants, those who engaged in exercise showed a decline in cIMT (weighted mean difference [WMD] -0.02; 95% confidence interval [CI], -0.03 to -0.01; I2 = 90.1%). Participants who engaged in aerobic (WMD -0.02; 95% CI, -0.04 to -0.01; I2 = 52.7%) or resistance (WMD -0.01; 95% CI, -0.02 to -0.00; I2 = 38.5%) exercise showed lower cIMT compared with control participants. An exercise duration of >6 months was associated with a 0.02 mm reduction in cIMT. In participants with low cIMT at baseline (<0.7 mm), exercise alone was not associated with a change in cIMT (WMD -0.01; 95% CI, -0.03 to 0.00; I2 = 93.9%). CONCLUSIONS: Exercise was associated with reduced cIMT in adults. Aerobic exercise is associated with a greater decline in cIMT than other forms of exercise. Large, multicenter, randomized controlled trials are required to establish optimal exercise protocols for improving the pathological process of atherosclerosis.

Health-Related Physical Fitness as a Risk Factor for Falls in Elderly People Living in the Community: A Prospective Study in China.

Objectives: Health-related physical-fitness (HRPF) involves multi-components of physical functional tests and is reported to be associated with the risk of fall. The study sought to determine whether specific physical fitness components were stronger predictors of falls among elderly people. Methods: This prospective cohort study involved 299 community residents age ≥60 years from Shanghai, China. The baseline data included comprehensive assessment of sociodemographic, clinical, and HRPF test. Subjects were followed for 1 year and were contacted by telephone to report falls. LASSO regression and Multivariate regression analysis were used to identify risk predictors of fall. In addition, we used receiver operating characteristic (ROC) curve analyses to determine whether the predictors have diagnostic. Results: During the 1-year prospective fall assessment, 11.7% of these subjects experienced one or frequent falls. LASSO models revealed that age (=0.01) and 8-ft up-and-go test score (=0.06) were positively associated with falls, while activity-specific balance confidence (ABC; = -0.007) and 2-min step test score (= -0.005) were inversely related. The Area Under roc Curve (AUC) for a linear combination of age, ABC scale score, 2-min step test and 8-ft up-and-go test was 0.778 (95% confidence interval: 0. 700-0.857), which was superior to any of the variables taken alone. Conclusion: Age, activity-specific balance confidence and fitness abnormalities were determined to contribute to the incident of falls. The value of 2-min step test score, and 8-ft up-and-go test score were the key HRPF components in predicting falls among elderly people.

Corrigendum: Analysis of time series gene expression and DNA methylation reveals the molecular features of myocardial infarction progression.

[This corrects the article DOI: 10.3389/fcvm.2022.912454.].

Effect of aging on acute pancreatitis through gut microbiota.

Background: Compared to younger people, older people have a higher risk and poorer prognosis of acute pancreatitis, but the effect of gut microbiota on acute pancreatitis is still unknown. We aim to investigate the effect of aging gut microbiota on acute pancreatitis and explore the potential mechanism of this phenomenon. Methods: Eighteen fecal samples from healthy adult participants, including nine older and nine younger adults were collected. C57BL/6 mice were treated with antibiotics for fecal microbiota transplantation from older and younger participants. Acute pancreatitis was induced by cerulein and lipopolysaccharide in these mice. The effect of the aged gut microbiota was further tested via antibiotic treatment before or after acute pancreatitis induction. Results: The gut microbiota of older and younger adults differed greatly. Aged gut microbiota exacerbated acute pancreatitis during both the early and recovery stages. At the same time, the mRNA expression of multiple antimicrobial peptides in the pancreas and ileum declined in the older group. Antibiotic treatment before acute pancreatitis could remove the effect of aging gut microbiota, but antibiotic treatment after acute pancreatitis could not. Conclusion: Aging can affect acute pancreatitis through gut microbiota which characterizes the deletion of multiple types of non-dominant species. This change in gut microbiota may potentially regulate antimicrobial peptides in the early and recovery stages. The level of antimicrobial peptides has negative correlations with a more severe phenotype.

Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression.

Myocardial infarction (MI) is one of the deadliest diseases in the world, and the changes at the molecular level after MI and the DNA methylation features are not clear. Understanding the molecular characteristics of the early stages of MI is of significance for the treatment of the disease. In this study, RNA-seq and MeDIP-seq were performed on heart tissue from mouse models at multiple time points (0 h, 10 min, 1, 6, 24, and 72 h) to explore genetic and epigenetic features that influence MI progression. Analysis based on a single point in time, the number of differentially expressed genes (DEGs) and differentially methylated regions (DMRs) increased with the time of myocardial infarction, using 0 h as a control group. Moreover, within 10 min of MI onset, the cells are mainly in immune response, and as the duration of MI increases, apoptosis begins to occur. Analysis based on time series data, the expression of 1012 genes was specifically downregulated, and these genes were associated with energy metabolism. The expression of 5806 genes was specifically upregulated, and these genes were associated with immune regulation, inflammation and apoptosis. Fourteen transcription factors were identified in the genes involved in apoptosis and inflammation, which may be potential drug targets. Analysis based on MeDIP-seq combined with RNA-seq methodology, focused on methylation at the promoter region. GO revealed that the downregulated genes with hypermethylation at 72 h were enriched in biological processes such as cardiac muscle contraction. In addition, the upregulated genes with hypomethylation at 72 h were enriched in biological processes, such as cell-cell adhesion, regulation of the apoptotic signaling pathway and regulation of angiogenesis. Among these genes, the Tnni3 gene was also present in the downregulated model. Hypermethylation of Tnni3 at 72 h after MI may be an important cause of exacerbation of MI.

Sleep behaviour and cardiorespiratory fitness in patients after percutaneous coronary intervention during cardiac rehabilitation: protocol for a longitudinal study.

INTRODUCTION: Most patients with coronary heart disease experience sleep disturbances and low cardiorespiratory fitness (CRF), but their relationship during cardiac rehabilitation (CR) is still unclear. This article details a protocol for the study of sleep trajectory in patients with coronary heart disease during CR and the relationship between sleep and CRF. A better understanding of the relationship between sleep and CRF on patient outcomes can improve sleep management strategies. METHODS AND ANALYSIS: This is a longitudinal study with a recruitment target of 101 patients after percutaneous cardiac intervention from the Seventh People's Hospital of Shanghai, China. Data collection will include demographic characteristics, medical history, physical examination, blood sampling, echocardiography and the results of cardiopulmonary exercise tests. The information provided by a 6-min walk test will be used to supplement the CPET. The Pittsburgh Sleep Quality Index will be used to understand the sleep conditions of the participants in the past month. The Patient Health Questionnaire and General Anxiety Disorder Scale will be used to assess depression and anxiety, respectively. All participants will be required to wear an actigraphy on their wrists for 72 hours to monitor objective sleep conditions. This information will be collected four times within 6 months of CR, and patients will be followed up for 1 year. The growth mixture model will be used to analyse the longitudinal sleep data. The generalised estimating equation will be used to examine the associations between sleep and CRF during CR. ETHICS AND DISSEMINATION: Ethical approval for this observational longitudinal study was granted by the Shanghai Seventh People's Hospital Ethics Committee on 23 April 2021 (2021-7th-HIRB-012). Study results will be disseminated in peer-reviewed journal articles.

Disordered Gut Microbiota Correlates With Altered Fecal Bile Acid Metabolism and Post-cholecystectomy Diarrhea.

Post-cholecystectomy diarrhea (PCD) is a common complication of gallbladder removal, and gut microbiota changes have been determined in PCD patients. Bile acid diarrhea (BAD) is supposed to be the main pathogenic factor for PCD due to the disrupted fecal bile acid metabolism in diarrheal patients. However, the profiling of bile acid metabolite alteration in PCD is unclear and whether changed gut microbiota and fecal bile acid metabolism are correlated is also underdetermined. The fecal bile acid metabolites from fecal samples were profiled by targeted UPLC/MS (ultra-high-performance liquid chromatography coupled with a triple-quadrupole mass spectrometer) and the composition of fecal bile acid metabolites in PCD patients was demonstrated to be distinct from those in Non-PCD and HC groups. In addition, the quantification of bile acid excretion in feces of diarrheal patients was significantly elevated. Furthermore, 16S rRNA sequencing results revealed that PCD patients had the lowest operational taxonomic units (OTU) and significant reduction in microbial richness and evenness. Bacterial composition was remarkably shifted in PCD patients, which mainly lay in dominated phyla Firmicutes and Bacteroidota. Besides, the co-abundance network among genus bacteria declined in PCD. Among the genera, Prevotella, Enterococcus, and Erysipelotrichaceae_UCG-003 were enriched, but Alistipes, Bacteroides, Ruminococcus, and Phascolarctobacterium were reduced. Moreover, these disease-linked genera were closely associated with several diarrheal phenotypes. Notably, changed bile acid metabolites exhibited strong correlations with gut microbiota as well. Conclusively, this study reveals associations between PCD-linked microbes and bile acid metabolites, which may synergistically correlate to postoperative diarrhea.

Inhibition of Human UDP-Glucuronosyltransferases1A1-Mediated Bilirubin Glucuronidation by the Popular Flavonoids Baicalein, Baicalin, and Hyperoside Is Responsible for Herb (Shuang-Huang-Lian)-Induced Jaundice.

Bilirubin-related adverse drug reactions (ADRs) or malady (e.g., jaundice) induced by some herbs rich in certain flavonoids have been widely reported. However, the causes and mechanisms of the ADRs are not well understood. The aim of this paper was to explore the mechanism of Shuang-huang-lian (SHL) injections and its major constituents-induced jaundice via inhibiting human UDP-glucuronosyltransferases1A1 (hUGT1A1)-mediated bilirubin glucuronidation. The inhibitory effects of SHL and its major constituents in the herbal medicine, including baicalein (BAI), baicalin (BA), and hyperoside (HYP), on bilirubin glucuroBBREVInidation were investigated. This study indicated that the average formation rates of bilirubin glucuronides [i.e., mono-glucuronide 1 (BMG1), BMG2, and bilirubin diglucuronide] displayed significant differences (P < 0.05). Specifically, the formation of BMGs was favored regardless of whether an inhibitor was absent or present. SHL, BAI, BA, and HYP dose-dependently inhibit bilirubin glucuronidation, showing the IC50 values against total bilirubin glucuronidation were in the range of (7.69 ± 0.94)-(37.09 ± 2.03) µg/ml, (4.51 ± 0.27)-(20.84 ± 1.99) µM, (22.36 ± 5.74)-(41.35 ± 2.40) µM, and (15.16 ± 1.12)-(42.80 ± 2.63) µM for SHL, BAI, BA, and HYP, respectively. Both inhibition kinetics assays and molecular docking simulations suggested that SHL, BAI, BA, and HYP significantly inhibited hUGT1A1-mediated bilirubin glucuronidation via a mixed-type inhibition. Collectively, some naturally occurring flavonoids (BAI, BA, and HYP) in SHL have been identified as the inhibitors against hUGT1A1-mediated bilirubin glucuronidation, which well explains the bilirubin-related ADRs or malady triggered by SHL in clinical settings. SIGNIFICANCE STATEMENT: Herbal products and their components (e.g., flavonoids), which been widely used across the entire world, may cause liver injury. As a commonly used herbal products rich in flavonoids, SHL injections easily lead to symptoms of liver injury (e.g., jaundice) owing to significant inhibition of hUGT1A1-mediated bilirubin glucuronidation by its flavonoid components (i.e., baicalein, baicalin, and hyperoside). Herb-induced bilirubin-related ADRs and the associated clinical significance should be seriously considered.

Anti-apoptotic effects of diosgenin on ovariectomized hearts.

BACKGROUND: The anti-apoptotic effects of diosgenin, a steroid saponin, on hearts in female with estrogen deficiency have been less studied. This study aimed to evaluate the anti-apoptotic effects of diosgenin on cardiac widely dispersed apoptosis in a bilateral ovariectomized animal model. METHODS: A total of 60 female Wistar rats, aged 6-7 months, were divided into the sham-operated group (Sham), bilateral ovariectomized rats for 2 months, and ovariectomized rats administered with 0, 10, 50, or 100 mg/kg diosgenin daily (OVX, OVX 10, OVX 50, and OVX 100, respectively) in the second month. The excised hearts were analyzed by H&E staining, TUNEL(+) assays and Western Blot. RESULT: Cardiac TUNEL(+) apoptotic cells, the levels of Fas ligand, Fas death receptors, Fas-associated death domain, active caspase-8, and active caspase-3 (FasL/Fas-mediated pathways) as well as the levels of Bax, Bad, Bax/Bcl2, Bad/p-Bad, cytosolic Cytochrome c, active caspase-9, and active caspase-3 (mitochondria-initiated pathway) were increased in OVX compared with Sham group but those were decreased in OVX 50 compared with OVX. CONCLUSION: Diosgenin appeared to prevent or suppress ovariectomy-induced cardiac FasL/Fas-mediated and mitochondria-initiated apoptosis. These findings might provide one of the possible therapeutic approaches of diosgenin for potentially preventing cardiac apoptosis in women after bilateral ovariectomy or women with estrogen deficiency.

Angiotensin II receptor blocker irbesartan attenuates sleep apnea-induced cardiac apoptosis and enhances cardiac survival and Sirtuin 1 upregulation.

BACKGROUND: The purpose of this study was to investigate whether or not angiotensin II type 1 receptor blocker irbesartan (ARB) with a partial agonist of PPAR-γ could protect against chronic nocturnal intermittent hypoxia (CIH)-induced cardiac Fas/FasL-mediated to mitochondria-mediated apoptosis. METHODS: Sprague-Dawley rats were in a normoxic control group (CON-G), or rats were in a chronic nocturnal intermittent hypoxia group (HP-G, from 3 to 7% oxygen versus 21% oxygen per forty seconds cycle, nocturnally 8 h per day for 1 month), or rats were in a chronic nocturnal intermittent hypoxia group pretreated with ARB (50 mg/kg/day, S.C.) (ARB-HP-G). Echocardiography, H&E staining, TUNEL staining, and Western blotting were measured in the left ventricle. RESULTS: Hypoxia-induced SIRT1 degradation, Fas receptors, FADD, active caspase-8 and caspase-3 (Fas/FasL apoptotic pathway) and Bax, tBid, active caspase-9 and -3 (mitochondrial apoptotic pathway) and TUNEL-positive apoptosis were reduced in ARB-HP-G when compared with HP-G. IGF-I, IGF1 receptor, p-PI3k, p-Akt, Bcl2, and Bcl-XL (IGF1/PI3K/AKT pro-survival pathway) were increased in ARB-HP-G compared to HP-G. CONCLUSIONS: Our findings suggest that the ARB may prevent cardiac Fas/FasL to mitochondrial apoptotic pathways and enhance cardiac IGF1/PI3K/AKT pro-survival pathway in the sleep apnea model associated with JNK de-activation and SIRT1 upregulation. ARB prevents chronic sleep apnea-enhanced cardiac apoptosis via enhancing survival pathways.

Relationship of Noninvasive Assessment of Arterial Stiffness with 10-Year Atherosclerotic Cardiovascular Disease (ASCVD) Risk in a General Middle-Age and Elderly Population.

PURPOSE: As a powerful indicator of arterial stiffening, the brachial-ankle pulse wave velocity (baPWV) has been extensively validated for predicting cardiovascular events. However, whether and how the brachial-ankle pulse wave velocity (baPWV) is correlated with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk is unclear. This study aimed to investigate the association between baPWV and 10-year ASCVD risk in Chinese population. METHODS: A total of 1768 subjects were enrolled from Shanghai, China. They were divided into two groups according to the Pooled Cohorts Equations model made by ACC/AHA as follows: low ASCVD risk (n = 992, 10-year ASCVD risk <7.5%) and high ASCVD risk (n = 776, 10-year ASCVD risk ≥7.5%). The baseline characteristics were obtained via the use of a questionnaire. Measurement of baPWV, laboratory tests, and echocardiography were conducted by trained physicians. The relationship between baPWV and 10-year ASCVD risk was evaluated using multiple logistic regression model and generalized additive model. RESULTS: The mean age of the subjects was 58.89±8.60 years, 32.69% of which were male. Non-linear relationship analysis revealed threshold effects between baPWV and 10-year ASCVD risk in which a baPWV of approximately 16 m/s might be the threshold effect of 10-year ASCVD risk. After multivariable adjustment, logistic-regression analysis demonstrated that ankle-brachial index (ABI) (OR 5.28, 95% CI 1.20-12.23) and baPWV (OR 9.09, 95% CI 6.84-12.07) were independently correlated with 10-year ASCVD risk. The AUC for baPWV for predicting 10-year ASCVD risk was 0.80 (95% CI 0.78-0.82). CONCLUSION: Increased baPWV as an indicator of arterial stiffness correlates strongly with 10-year ASCVD risk in general middle-aged and elderly populations. The association between baPWV and 10-year ASCVD risk is not purely linear but non-linear. Subjects with baPWV above 16 m/s are more likely to encounter a higher 10-year ASCVD risk.

SLC41A3 Exhibits as a Carcinoma Biomarker and Promoter in Liver Hepatocellular Carcinoma.

Liver Hepatocellular Carcinoma (LIHC) is the fifth widely occurred carcinoma, which is thought to be the second primary contributor of carcinoma-associated death. There are almost 788,000 death tolls worldwide. Solute carrier family 41 member 3 (SLC41A3) is a member of solute carrier family 41, and it is the key point of numerous researches. Our research attempted to explore the links between SLC41A3 and LIHC through public databases. Higher expression of SLC41A3 displayed an intimate association with higher pathological stages and poorer prognosis. GO and KEGG analysis revealed the possible regulatory pathways of SLC41A3. Additionally, we carried out cell functional experiments to determine the expression of SLC41A3 in the cell lines of LIHC, as well as the effects of its silence on cell proliferation, migration, and invasion. Our data showed that SLC41A3 was greatly increased in the cell lines of LIHC. Moreover, silencing SLC41A3 impeded LIHC cell proliferation, migration, and invasion in vitro. Collectively, our study demonstrated that highly expressed SLC41A3 was a probable indication of LIHC occurrence, and SLC41A3 could be regarded as a prospective target in the treatment of LIHC.

Cerebral Cortex Apoptosis in Early Aged Hypertension: Effects of Epigallocatechin-3-Gallate.

This study aimed to investigate cerebral cortex apoptosis on the early aged hypertension and the effects of green tea flavonoid epigallocatechin-3-gallate (EGCG). Twenty-four rats were divided into three groups: a control Wistar-Kyoto group (WKY, n = 8), a spontaneously early aged hypertensive group (SHR, n = 8), and an early aged hypertension with EGCG treatment group (SHR-EGCG, n = 8; daily oral EGCG 200 mg/kg-94%, 12 weeks). At 48 weeks old, blood pressures (BPs) were evaluated and cerebral cortexes were isolated for TUNEL assay and Western blotting. Systolic, diastolic, and mean blood pressure levels in the SHR-EGCG were reduced compared to the SHR. The percentage of neural cell deaths, the levels of cytosolic Endonuclease G, cytosolic AIF (Caspase-independent apoptotic pathway), Fas, Fas Ligand, FADD, Caspase-8 (Fas-mediated apoptotic pathway), t-Bid, Bax/Bcl-2, Bak/Bcl-xL, cytosolic Cytochrome C, Apaf-1, Caspase-9 (Mitochondrial-mediated apoptotic pathway), and Caspase-3 (Fas-mediated and Mitochondria-mediated apoptotic pathways) were increased in the SHR relative to WKY and reduced in SHR-EGCG relative to SHR. In contrast, the levels of Bcl-2, Bcl-xL, p-Bad, 14-3-3, Bcl-2/Bax, Bcl-xL/Bak, and p-Bad/Bad (Bcl-2 family-related pro-survival pathway), as well as Sirt1, p-PI3K/PI3K and p-AKT/AKT (Sirt1/PI3K/AKT-related pro-survival pathway), were reduced in SHR relative WKY and enhanced in SHR-EGCG relative to SHR. In conclusion, green tea flavonoid epigallocatechin-3-gallate (EGCG) might prevent neural apoptotic pathways and activate neural survival pathways, providing therapeutic effects on early aged hypertension-induced neural apoptosis.

RORγt inhibitor SR1001 alleviates acute pancreatitis by suppressing pancreatic IL-17-producing Th17 and γδ-T cells in mice with ceruletide-induced pancreatitis.

The management of acute pancreatitis (AP) remains a challenge to clinicians worldwide for limited effective interventions. Retinoid orphan receptor gamma t (RORγt) is a therapeutic target for several diseases; however, it is unclear whether inhibiting RORγt can ameliorate AP. The relative expression of RORγt, IL-17 and IL-23 in the peripheral blood mononuclear cells of AP patients was measured by RT-PCR. An AP mouse model was induced by ceruletide, and SR1001 was injected before ceruletide administration. RORγt+ cells, T helper 17 cells (Th17), regulatory T cells (Tregs) and γδ T cells were assessed in the pancreas and spleen by flow cytometry. Higher RORγt expression in patients indicated the potential role of RORγt in AP progression. Analyses of the IL-17/IL-23 axis confirmed its role. SR1001 significantly alleviated AP histologically in the mouse model. Serum levels of amylase, IL-6, TNFalpha, IL-17 and IL-23 decreased upon SR1001 treatment. SR1001 selectively decreased the number of RORγt+, Th17, Tregs and γδ T cells in the pancreas but not the spleen. Collectively, these results showed that SR1001 exerted therapeutic effects on AP by suppressing IL-17-secreting Th17 and γδ T cells in the pancreas. Thus, SR1001 may be a promising drug for the treatment of AP in the clinic.