Quantitative reconstitution of yeast RNA processing bodies.

Many biomolecular condensates appear to form through liquid-liquid phase separation (LLPS). Individual condensate components can often undergo LLPS in vitro, capturing some features of the native structures. However, natural condensates contain dozens of components with different concentrations, dynamics, and contributions to compartment formation. Most biochemical reconstitutions of condensates have not benefited from quantitative knowledge of these cellular features nor attempted to capture natural complexity. Here, we build on prior quantitative cellular studies to reconstitute yeast RNA processing bodies (P bodies) from purified components. Individually, five of the seven highly concentrated P-body proteins form homotypic condensates at cellular protein and salt concentrations, using both structured domains and intrinsically disordered regions. Combining the seven proteins together at their cellular concentrations with RNA yields phase-separated droplets with partition coefficients and dynamics of most proteins in reasonable agreement with cellular values. RNA delays the maturation of proteins within and promotes the reversibility of, P bodies. Our ability to quantitatively recapitulate the composition and dynamics of a condensate from its most concentrated components suggests that simple interactions between these components carry much of the information that defines the physical properties of the cellular structure.

Dietary flavonoids intake contributes to delay biological aging process: analysis from NHANES dataset.

BACKGROUND: Diet may influence biological aging and the discrepancy (∆age) between a subject's biological age (BA) and chronological age (CA). We aimed to investigate the correlation of dietary flavonoids with the ∆age of organs (heart, kidney, liver) and the whole body. METHOD: A total of 3193 United States adults were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2007-2008 and 2017-2018. Dietary flavonoids intake was assessed using 24-h dietary recall method. Multiple linear regression analysis was performed to evaluate the association of dietary flavonoids intake with the ∆age of organs (heart, kidney, liver) and the whole body. BA was computed based on circulating biomarkers, and the resulting ∆age was tested as an outcome in linear regression analysis. RESULTS: The ∆age of the whole body, heart, and liver was inversely associated with higher flavonoids intake (the whole body ∆age ß = - 0.58, cardiovascular ∆age ß = - 0.96, liver ∆age ß = - 3.19) after adjustment for variables. However, higher flavonoids intake positively related to renal ∆age (ß = 0.40) in participants with chronic kidney disease (CKD). Associations were influenced by population characteristics, such as age, health behavior, or chronic diseases. Anthocyanidins, isoflavones and flavones had the strongest inverse associations between the whole body ∆age and cardiovascular ∆age among all the flavonoids subclasses. CONCLUSION: Flavonoids intake positively contributes to delaying the biological aging process, especially in the heart, and liver organ, which may be beneficial for reducing the long-term risk of cardiovascular or liver disease.

Long non-coding RNAs in aging organs and tissues.

The aging process directly impacts bodily functions on multiple levels, including a reduced ability to resist stress, damage and disease. Besides changes in metabolic control, the aging process coincides with the altered long non-coding RNAs (lncRNAs) expression, which are ≥200nt long class of non-protein coding RNAs. The majority of non-coding transcripts of mammalian organs and tissues are expressed in developmentally regulated and cell-type specific manners. Specific altered lncRNA level has been involved in induction and maintenance of the whole human body aging with highly specific spatial andtemporal expression patterns. Furthermore, many lncRNAs are transcribed in sense, antisense and bidirectional manners in the mammalian genome. They play a vital role in regulating organ or tissue differentiation during aging by binding with miRNA or proteins to act as a decoy. Recently, the correlation between lncRNAs and aging has been studied intensely. Here, we have summarized some examples of known and novel lncRNAs that have been implicated in the aging process in the whole mammalian body and we discuss these patterns, conservation and characters during aging. This may further promote the development of research on lncRNAs and the aging process.

Efficacy and safety of nanopaclitaxel formulation for cancer treatment: evidence from randomized clinical trials.

Aim: We aimed to analyze efficacy and adverse events for nano-bound paclitaxel in cancer treatment, which remain controversial. Method: We obtained relevant previously published studies and extracted data on the efficacy and adverse events of nano-bound paclitaxel. Fifteen randomized clinical trials were included. Results: Nanoparticle albumin-bound (Nab-) paclitaxel was beneficial in terms of objective response rate (odds ratio [OR]: 1.08, 95% CI: 0.72-1.62) and partial response (OR: 1.28, 95% CI: 0.89-1.83), while polymeric micellar (PM-) paclitaxel was beneficial in terms of objective response rate (OR: 1.76) and partial disease (hazard ratio [HR]: 0.65). Both Nab-paclitaxel and PM-paclitaxel resulted in slightly longer overall survival (HR: 0.93 and 0.94) and progression-free survival (HR: 0.93 and 0.87) when compared with solvent-based paclitaxel. Peripheral sensory neuropathy (OR: 3.47), neutropenia (OR: 1.79) and anemia (OR: 1.79) were more frequent after Nab-paclitaxel treatment. Conclusion: Nanopaclitaxel formulations have a better efficacy in cancer treatment; however, they increase the risk of hematological adverse events and peripheral sensory neuropathy. The PM-paclitaxel treatment had a high safety effect.

This was a pooled analysis of the efficacy and adverse events of nano-bound paclitaxel (polymeric micellar [PM] or nanoparticle-bound formulation) in cancer treatment. Relevant studies published since 2016 were retrieved from the PubMed, ISI Web of Science and Embase databases. Fifteen randomized clinical trials (4925 patients) were included in this meta-analysis. Compared with solvent-based paclitaxel, nanoparticle albumin-bound paclitaxel (Nab-paclitaxel) had beneficial effects in terms of objective response rate and partial response, while PM-paclitaxel exhibited beneficial effects in terms of objective response rate and partial disease. Both Nab-paclitaxel and PM-paclitaxel were associated with a slightly longer overall survival and better progression-free survival when compared with solvent-based paclitaxel. Peripheral sensory neuropathy, neutropenia and anemia adverse events were more frequent after Nab-paclitaxel treatment. The nanopaclitaxel formulation had an improved efficacy in treatment of solid-organ tumors, but it increased the risk of hematological adverse events and peripheral sensory neuropathy. This study provided evidence on the efficacy and safety of the nanocarriers of paclitaxel.

The association between dietary intake of flavonoids and its subclasses and the risk of metabolic syndrome.

Background: The healthiest way to prevent metabolic syndrome (MetS) is through behavioral and nutritional adjustments. We examined the relationship between total flavonoids intake, flavonoid subclasses, and clinically manifest MetS. Methods: A cross-sectional analysis was conducted among 28,719 individuals from the National Health and Nutrition Examination Survey (NHANES) and Food and Nutrient Database for Dietary Studies (FNDDS) 2007-2011 and 2017-2018. Two 24-h reviews were conducted to determine flavonoids intake and subclasses. The link between flavonoids intake and MetS was investigated using a multivariate logistic regression model. Results: Q2 and Q3 of total flavonoids intake were associated with 20 and 19% lower risk of incident MetS after adjusting age and sex. Anthocyanidins and flavanones intake in Q2 and Q3 substantially reduced the MetS risk compared to Q1. MetS risk decreased steadily as the total intake of flavonoids increased to 237.67 mg/d. Flavanones and anthocyanidins also displayed V-shaped relationship curves (34.37 and 23.13 mg/d). Conclusion: MetS was adversely linked with total flavonoids intake, flavanones, and anthocyanidins. Moreover, the most effective doses of total flavonoids, flavanones, and anthocyanidins were 237.67, 34.37, and 23.13 mg/d, respectively, potentially preventing MetS.

Artificial intelligence predicts lung cancer radiotherapy response: A meta-analysis.

BACKGROUND: Artificial intelligence (AI) technology has clustered patients based on clinical features into sub-clusters to stratify high-risk and low-risk groups to predict outcomes in lung cancer after radiotherapy and has gained much more attention in recent years. Given that the conclusions vary considerably, this meta-analysis was conducted to investigate the combined predictive effect of AI models on lung cancer. METHODS: This study was performed according to PRISMA guidelines. PubMed, ISI Web of Science, and Embase databases were searched for relevant literature. Outcomes, including overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and local control (LC), were predicted using AI models in patients with lung cancer after radiotherapy, and were used to calculate the pooled effect. Quality, heterogeneity, and publication bias of the included studies were also evaluated. RESULTS: Eighteen articles with 4719 patients were eligible for this meta-analysis. The combined hazard ratios (HRs) of the included studies for OS, LC, PFS, and DFS of lung cancer patients were 2.55 (95 % confidence interval (CI) = 1.73-3.76), 2.45 (95 % CI = 0.78-7.64), 3.84 (95 % CI = 2.20-6.68), and 2.66 (95 % CI = 0.96-7.34), respectively. The combined area under the receiver operating characteristics curve (AUC) of the included articles on OS and LC in patients with lung cancer was 0.75 (95 % CI = 0.67-0.84), and 0.80 (95%CI = 0.0.68-0.95), respectively. CONCLUSION: The clinical feasibility of predicting outcomes using AI models after radiotherapy in patients with lung cancer was demonstrated. Large-scale, prospective, multicenter studies should be conducted to more accurately predict the outcomes in patients with lung cancer.

LncRNAs as Theragnostic Biomarkers for Predicting Radioresistance in Cancer: A Systematic Review and Meta-Analysis.

Background: Radioresistance is the major obstacle after cancer radiotherapy. The dysregulation of long non-coding RNAs (lncRNAs) was closely related the radioresistance response. This meta-analysis was aimed to interpret the relationship between lncRNAs and radiotherapy responses in different cancers. Method: The studies were selected from databases including PubMed, ISI Web of Science, Embase, Google Scholar, PMC, and CNKI (China National Knowledge Infrastructure). The publication time was limited to before March 20, 2021. The hazard ratios (HRs) and 95% confidence interval were calculated with random-effects models. Subgroup analyses, sensitivity analyses, and publication bias were also conducted. Result: Twenty-seven lncRNAs in 14 cancer types were investigated, in which 23 lncRNAs were upregulated and four lncRNAs were downregulated. Dysregulation of these lncRNAs were found to be related to radioresistance response. The pooled HR and 95% confidence interval for the combined up-regulated lncRNAs was 1.73 (95% CI=1.50-2.00; P< 0.01) and down-regulated lncRNAs was 2.09 (95% CI= 1.60-2.72; P< 0.01). The HR values of the subgroup analysis for glioma (HR= 2.22, 95% CI= 1.79-2.74; p< 0.01), non-small cell lung cancer (HR=1.48, 95% CI=1.18-1.85; P<0.01), nasopharyngeal carcinoma (HR=4.26; 95% CI= 1.58-11.46; P< 0.01), and breast cancer (HR=1.29; 95% CI= 1.08-1.54; P< 0.01) were obtained. Moreover, the expression of lncRNAs was significantly related to overall survival of patients no matter if the sample size was >50 or not. In addition, the HR values of the subgroup analysis for lncRNA H19 (HR=2.68; 95% CI= 1.92-3.74; P <0.01), lncRNA FAM201A (HR=2.15; 95% CI= 1.15-3.99; P <0.01), and lncRNA HOTAIR (HR=1.22; 95% CI= 0.98-1.54; P =0.08) were also obtained. Conclusion: LncRNAs can induce cancer radioresistance by regulating cell death-related signaling pathways. Results indicated that lncRNAs, especially lncRNA H19, FAM201A, and HOTAIR, could be considered as a predictive theragnostic biomarker to evaluate radiotherapy response.

Gut microbiota-mitochondrial inter-talk in non-alcoholic fatty liver disease.

The increasing prevalence of non-alcoholic fatty liver disease (NAFLD), which is a progressive disease, has exerted huge a healthcare burden worldwide. New investigations have suggested that the gut microbiota closely participates in the progression of NAFLD through the gut-liver axis or gut-brain-liver axis. The composition of the microbiota can be altered by multiple factors, primarily dietary style, nutritional supplements, or exercise. Recent evidence has revealed that gut microbiota is involved in mitochondrial biogenesis and energy metabolism in the liver by regulating crucial transcription factors, enzymes, or genes. Moreover, microbiota metabolites can also affect mitochondrial oxidative stress function and swallow formation, subsequently controlling the inflammatory response and regulating the levels of inflammatory cytokines, which are the predominant regulators of NAFLD. This review focuses on the changes in the composition of the gut microbiota and metabolites as well as the cross-talk between gut microbiota and mitochondrial function. We thus aim to comprehensively explore the potential mechanisms of gut microbiota in NAFLD and potential therapeutic strategies targeting NAFLD management.

Telemedicine interventions to reduce blood pressure in a chronic disease population: A meta-analysis.

INTRODUCTION: Elevated blood pressure (BP) is a leading risk factor for many chronic diseases. Many investigations conducted using telemedicine (TM)-based interventions have the potential to control BP. The purpose of this study was to assess the efficacy of TM-based interventions in reducing BP. METHODS: Studies were selected from PubMed, PMC, Web of Science, Embase, Google Scholar, Cochrane Library, the Chinese National Knowledge Infrastructure (CNKI) and the Chinese Biomedical Literature Database (CBM) according to the inclusion and exclusion criteria. The mean and standard deviation changes in systolic BP (SBP) and diastolic BP (DBP) were analysed using standard mean difference (SMD) and 95% confidence intervals (CI) with a random-effects model or fixed-effects model to assess the efficiency of controlling BP. Subgroup analysis, influence analysis and publication bias analysis were also conducted. RESULTS: Sixteen randomised clinical trials were included in this meta-analysis. A TM-based lifestyle intervention significantly reduced daytime SBP (SMD = -0.18, 95% CI -0.27 to -0.10; p < 0.001) and DBP (SMD = -0.18, 95% CI -0.27 to -0.09; p < 0.001). The results of subgroup analysis indicated that this reduction in BP was reliable when BP interventions lasted for 6 months or longer in populations with cardiovascular disease and hypertension. Moreover, the detection data should be delivered by a device system to ensure accuracy. DISCUSSION: A TM-based intervention could reduce daytime SBP and DBP in populations with hypertension and cardiovascular disease. This review provides intuitive evidence of a reduction in BP using TM-based interventions.

The effects of supplementation of probiotics, prebiotics, or synbiotics on patients with non-alcoholic fatty liver disease: A meta-analysis of randomized controlled trials.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Research on the efficacy of probiotics, prebiotics, and synbiotics on NAFLD patients continues to be inconsistent. The purpose of this study is to evaluate the effectiveness of these microbial therapies on NAFLD. Methods: Eligible randomized-controlled trials reporting the effect of probiotics, prebiotics, or synbiotics in NAFLD were searched in PubMed, Web of Science, Embase, Google scholar, and CNKI databases from 2020 to Jul 2022. The changes in the outcomes were analyzed using standard mean difference (SMD) and 95% confidence intervals (CIs) with a random- or fixed-effects model to examine the effect of microbial therapies. Subgroup analysis, influence and publication bias analysis were also performed. The quality of the eligible studies was evaluated using the Cochrane Risk of Bias Tool. Results: Eleven studies met the inclusion criteria involving 741 individuals. Microbial therapies could improve liver steatosis, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-c), alanine aminotransferase (ALT), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), and homeostasis model assessment-insulin resistance (HOMAI-R) (all P < 0.05). But microbial therapies could not ameliorate body mass index (BMI), energy, carbohydrate, fat intake, fasting blood sugar, HbA1c, insulin, high-sensitivity C-reactive protein (hs-CRP), and hepatic fibrosis of patients with NAFLD. Conclusion: Probiotics, prebiotics, and synbiotics supplementation can potentially improve liver enzymes, lipid profiles, and liver steatosis in patients with NAFLD.

Association between probiotic, prebiotic, and yogurt consumption and chronic kidney disease: The NHANES 2010-2020.

Background: Previous studies suggested that gut dysbacteriosis may promote the occurrence of chronic kidney disease (CKD), and probiotic, prebiotic, or yogurt supplements may alleviate CKD progression. This study aims to examine the association between probiotic, prebiotic, or yogurt supplements and the risk of CKD using the data from NHANES. Methods: This study was designed to prospectively search data from the National Health and Nutrition Examination Survey (NHANES) (2011-2020). We examined dietary supplements and prescription medication labels to identify probiotic, or prebiotic product, and yogurt consumption during the dietary interview. The diagnosis of CKD was determined by the value of glomerular filtration rate (eGFR) and albumin creatinine ratio (ACR). Results: The study enrolled a total of 6,522 individuals. The prevalence of CKD was lower in the probiotic, prebiotic, or yogurt consumption group [age-adjusted odds ratio (OR): 0.77, 95% CI: 0.62-0.95, P = 0.02; multivariable-adjusted OR: 0.86, 95% CI: 0.69-1.07, P = 0.05]. Furthermore, 32% reduced risk was observed in the older group aged 55 years or older, and 32% reduced risk was also observed in the female population. Probiotic, or prebiotic, or yogurt supplements was associated a 12% reduction in moderate risk of CKD and an 11% reduction in very high risk of CKD. Conclusion: Our results suggest that probiotic, prebiotic, or yogurt supplements may contribute to the prevention of CKD and relieve its progression risk, especially in the female population and older population who were aged 55 years or older.

Develop a diagnostic tool for dementia using machine learning and non-imaging features.

Background: Early identification of Alzheimer's disease or mild cognitive impairment can help guide direct prevention and supportive treatments, improve outcomes, and reduce medical costs. Existing advanced diagnostic tools are mostly based on neuroimaging and suffer from certain problems in cost, reliability, repeatability, accessibility, ease of use, and clinical integration. To address these problems, we developed, evaluated, and implemented an early diagnostic tool using machine learning and non-imaging factors. Methods and results: A total of 654 participants aged 65 or older from the Nursing Home in Hangzhou, China were identified. Information collected from these patients includes dementia status and 70 demographic, cognitive, socioeconomic, and clinical features. Logistic regression, support vector machine (SVM), neural network, random forest, extreme gradient boosting (XGBoost), least absolute shrinkage and selection operator (LASSO), and best subset models were trained, tuned, and internally validated using a novel double cross validation algorithm and multiple evaluation metrics. The trained models were also compared and externally validated using a separate dataset with 1,100 participants from four communities in Zhejiang Province, China. The model with the best performance was then identified and implemented online with a friendly user interface. For the nursing dataset, the top three models are the neural network (AUROC = 0.9435), XGBoost (AUROC = 0.9398), and SVM with the polynomial kernel (AUROC = 0.9213). With the community dataset, the best three models are the random forest (AUROC = 0.9259), SVM with linear kernel (AUROC = 0.9282), and SVM with polynomial kernel (AUROC = 0.9213). The F1 scores and area under the precision-recall curve showed that the SVMs, neural network, and random forest were robust on the unbalanced community dataset. Overall the SVM with the polynomial kernel was found to be the best model. The LASSO and best subset models identified 17 features most relevant to dementia prediction, mostly from cognitive test results and socioeconomic characteristics. Conclusion: Our non-imaging-based diagnostic tool can effectively predict dementia outcomes. The tool can be conveniently incorporated into clinical practice. Its online implementation allows zero barriers to its use, which enhances the disease's diagnosis, improves the quality of care, and reduces costs.

The Diagnostic Value of Exosome-Derived Biomarkers in Alzheimer's Disease and Mild Cognitive Impairment: A Meta-Analysis.

Background: Alzheimer's disease (AD) diagnoses once depended on neuropathologic examination. Now, many widely used, validated biomarkers benefits for monitoring of AD neuropathologic changes. Exosome-derived biomarker studies have reported them to be significantly related to AD's early occurrence and development, although the findings are inconclusive. The aim of this meta-analysis was to identify exosome-derived biomarkers for the diagnosis of AD and mild cognitive impairment (MCI). Methods: PubMed, PubMed Central, Web of Science, Embase, Google Scholar, Cochrane Library, the Chinese National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM) were searched for studies assessing the diagnostic value of biomarkers, including data describing the pooled sensitivity (SEN), specificity (SPE), positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), diagnostic odds ratio (DOR), and area under the curve (AUC). The quality of the included studies was assessed using RevMan 5.3 software. Publication bias was analyzed. Results: In total, 19 eligible studies, including 3,742 patients, were selected for this meta-analysis. The SEN, SPE, DLR+, DLR-, DOR, and AUC (95% confidence intervals) of exosome-derived biomarkers in the diagnosis of AD or MCI were 0.83 (0.76-0.87), 0.82 (0.77-0.86), 4.53 (3.46-5.93), 0.21 (0.15-0.29), 17.27 (11.41-26.14), and 0.89 (0.86-0.92), respectively. Sub-group analyses revealed that studies based on serum or microRNA (miRNA) analysis, and those of Caucasian populations, AD patients, patient sample size >50, neuron-derived exosomes (NDE) from plasma and p-tau had higher sensitivity, specificity, and AUC values. Conclusion: Exosome-derived biomarkers have shown potential diagnostic value in AD and MCI, although further research is required for confirmation.

The effectiveness of balneotherapy and aquatic exercise on bone metabolism: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the effectiveness of balneotherapy and/or aquatic exercise on bone metabolism. DESIGN: A systematic literature search was conducted from inception to January 4, 2021. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a fixed-effect model according to study heterogeneity. RESULTS: Seven articles involving 467 participants were selected. Three balneotherapy studies were qualitatively integrated. The results showed that bone resorption slowed down with or without stimulation of bone formation. A pooled meta-analysis of four studies on aquatic exercise showed significant evidence for a reduction in parathyroid hormone (PTH; SMD = -0.71; 95% CI, -1.04 to -0.38; P < 0.001), and a significant increase in osteocalcin (OC; SMD = 0.60; 95% CI, 0.16 to 1.03; P = 0.007) after aquatic exercise. CONCLUSION: Balneotherapy and aquatic exercise had significant effects on bone metabolism, reducing bone resorption and/or increasing bone formation. This study highlights the importance of balneotherapy and aquatic exercise for bone health.

A quantitative inventory of yeast P body proteins reveals principles of composition and specificity.

P bodies are archetypal biomolecular condensates that concentrate proteins and RNA without a surrounding membrane. While dozens of P body proteins are known, the concentrations of components in the compartment have not been measured. We used live cell imaging to generate a quantitative inventory of the major proteins in yeast P bodies. Only seven proteins are highly concentrated in P bodies (5.1-15µM); the 24 others examined are appreciably lower (most ≤ 2.6µM). P body concentration correlates inversely with cytoplasmic exchange rate. Sequence elements driving Dcp2 concentration into P bodies are distributed across the protein and act synergistically. Our data indicate that P bodies, and probably other condensates, are compositionally simpler than suggested by proteomic analyses, with implications for specificity, reconstitution and evolution.

Neurofilament light chain level in traumatic brain injury: A system review and meta-analysis.

BACKGROUND: Neurofilament light (NfL) level was obviously increased in traumatic brain injury (TBI) individuals. But, no comprehensive meta-analysis has ever been conducted to assess the diagnostic performance of NfL. This study aims to evaluate the relationship between NfL level and TBI through a meta-analysis. METHODS: Studies were selected from Pubmed, Web of science, Embase, Google Scholar, PMC and Chinese National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM) through inclusion and exclusion criteria. The standard mean difference (SMD) and 95% confidence interval (CI) were calculated using the random-effect model or fixed-effect model to assess the association between NfL level and TBI. Subgroup analysis according to sample collection time, sample type and detection method was performed. The influence analysis and publication bias was also conducted. All analyses were performed using the RevMan 5.3 and Stata 12 software. RESULTS: A total of 9 studies were included. Results indicated that TBI individuals had a higher NfL expression level compared with the non-TBI individuals (SMD = 2.48, 95% CI = 1.52-3.43, I = 96%, P < .01). Similar NfL increasing was also observed in Caucasian population, 0-48 hour and 6-10 days sample collection time, as well as cerebrospinal fluid (CSF), serum, plasma sample subgroup analysis. Moreover, the NfL increasing still existed no matter the NfL expression level was detected by ELISA or Simoa assay. CONCLUSION: NfL expression level was increased in TBI individuals, which indicated that NfL could be a potential biomarker in the diagnosis of TBI and other neurodegenerative diseases.

Association between lncRNA GAS5, MEG3, and PCAT-1 Polymorphisms and Cancer Risk: A Meta-Analysis.

PURPOSE: Long noncoding RNAs (lncRNAs) have been widely studied, and single nucleotide polymorphisms (SNPs) in lncRNAs are considered to be genetic factors that influence cancer susceptibility. The lncRNA GAS5, MEG3, and PCAT-1 polymorphisms are shown to be possibly associated with cancer risk. The aim of this meta-analysis was to systematically evaluate this association. METHODS: Studies were selected from PubMed, Web of Science, Embase, Google Scholar, Cochrane Library, the Chinese National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM) through inclusion and exclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the random-effects model or fixed-effects model to assess the association between lncRNA polymorphisms and cancer susceptibility. Metaregression and publication bias analyses were also conducted. All analyses were performed using the Stata 12.0 software. RESULTS: Sixteen articles (covering 13750 cases and 17194 controls) were included in this meta-analysis. A significant association between SNP rs145204276 and gastric cancer risk was observed (del vs. ins: OR = 0.79, 95%CI = 0.72-0.86; del/del vs. ins/ins+del/ins: OR = 0.74, 95%CI = 0.59-0.91; del/ins vs. ins/ins: OR = 0.84, 95%CI = 0.67-1.05). For rs16901904, a decreased cancer risk was observed in three genetic models (C vs. T: OR = 0.79, 95%CI = 0.70-0.90; CC vs. CT+TT: OR = 0.49, 95%CI = 0.37-0.65; CC vs. TT: OR = 0.49, 95%CI = 0.37-0.66). No statistical significance was found in the metaregression analysis. For all of the included SNPs, no publication bias was found in all genotype models. CONCLUSIONS: The rs145204276 SNP in lncRNA GAS5 is likely to be associated with gastric cancer risk, whereas the rs16901904 SNP in lncRNA PCAT-1 bears association with a decreased cancer risk.

A network-based analysis of key pharmacological pathways of Andrographis paniculata acting on Alzheimer's disease and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Andrographis paniculata (AP) is a native plant with anti-inflammatory and antioxidant properties and used as an official herbal medicine. Recently more and more researches have indicated that AP shows pharmacological effects on Alzheimer's disease (AD) but its mechanism is unclear. AIMS OF THE STUDY: Network pharmacology approach combined with experimental validation was developed to reveal the underlying molecular mechanisms of AP in treating AD. MATERIALS AND METHODS: The compounds of AP from TCM database, the AD-related targets from disease database and the targets corresponding to compounds from swissTargetPrediction were collected. Then DAVID database was used for annotation and enrichment pathways, meanwhile the compound-target, protein-protein interaction from String database and compound-target-pathway network was constructed, molecular modeling was performed using Sybyl-x. Okadaic acid (OKA)-induced cytotoxicity model in PC12 cells was established to verify the mechanism of AP and the key proteins were detected by western blotting. RESULTS: 28 AP components were identified after ADME filter analysis and 52 targets were gained via mapping predicted targets into AD-related proteins. In addition, after multiple network analysis, the 22 hub target genes were enriched onto pathways involved in AD, such as neuroactive ligand-receptor interaction, serotonergic synapse, Alzheimer's disease, PI3K-Akt and NF-kB signaling pathway. Interestingly, molecular docking simulation revealed that the targets including PTGS2, BACE1, GSK3B and IKBKB had good ability to combine with AP components. Experimental validation in an in vitro system proved that AP treatment obviously increased in levels inactive of p-GSK3ß (P < 0.05) and decreased in levels of BACE (P < 0.05), PTGS2 (namely COX2, P < 0.05) and NF-kB protein (P < 0.05) compare with OKA treated group. CONCLUSION: Our data provided convincing evidence that the neuroprotective effects of AP might be partially related to their regulation of the APP-BACE1-GSK3B signal axis and inflammation, which should be the focus of study in this field in the future.

Inhibitory effects of piceatannol on human cytomegalovirus (hCMV) in vitro.

Human cytomegalovirus (hCMV) is a ubiquitous herpesvirus, which results in the establishment of a latent infection that persists throughout the life of the host and can be reactivated when the immunity is low. Currently, there is no vaccine for hCMV infection, and the licensed antiviral drugs mainly target the viral enzymes and have obvious adverse reactions. Thus, it is important to search for compounds with anti-hCMV properties. The present study aimed to investigate the suppressive effects of piceatannol on hCMV Towne strain infection and the putative underlying mechanisms using human diploid fibroblast WI-38 cells. Piceatannol supplementation prevented the lytic changes induced by hCMV infection in WI-38 cells. Furthermore, piceatannol suppressed the expression of hCMV immediate-early (IE) and early (E) proteins as well as the replication of hCMV DNA in a dose-dependent manner. Moreover, hCMV-induced cellular senescence was suppressed by piceatannol, as shown by a decline in the senescence-associated ß-galactosidase (SA-ß-Gal) activity and decreased production of intracellular reactive oxygen species (ROS). p16INK4a, a major senescence-associated molecule, was dramatically elevated by current hCMV infection that was attenuated by pre-incubation with piceatannol in a dose-dependent manner. These results demonstrated that piceatannol suppressed the hCMV infection via inhibition of the activation of p16INK4a and cellular senescence induced by hCMV. Together, these findings indicate piceatannol as a novel and potent anti-hCMV agent with the potential to be developed as an effective treatment for chronic hCMV infection.

Salidroside Delays Cellular Senescence by Stimulating Mitochondrial Biogenesis Partly through a miR-22/SIRT-1 Pathway.

Calorie restriction (CR) is a nongenetic intervention with a robust effect on delaying aging in mammals and other organisms. A mild stimulation on mitochondrial biogenesis induced by CR seems to be an important action mode for its benefits. Here, we reported that a component isolated from Rhodiola rosea L., salidroside, delays replicative senescence in human fibroblasts, which is related to its stimulation on mitochondrial biogenesis by activating SIRT1 partly resulted from inhibition on miR-22. Salidroside increased the mitochondrial mass that accompanied an increment of the key regulators of mitochondrial biogenesis including PGC-1α, NRF-1, and TFAM and reversed the mitochondrial dysfunction in presenescent 50PD cells, showing a comparable effect to that of resveratrol. SIRT1 is involved in the inducement of mitochondrial biogenesis by salidroside. The declined expression of SIRT1 in 50PD cells compared with the young 30PD cells was prevented upon salidroside treatment. In addition, pretreatment of EX-527, a selective SIRT1 inhibitor, could block the increased mitochondrial mass and decreased ROS production induced by salidroside in 50PD cells, resulting in an accelerated cellular senescence. We further found that salidroside reversed the elevated miR-22 expression in presenescent cells according to a miRNA array analysis and a subsequent qPCR validation. Enforced miR-22 expression by using a Pre-miR-22 lentiviral construct induced the young fibroblasts (30PD) into a senescence state, accompanied with increased senescence-related molecules including p53, p21, p16, and decreased SIRT1 expression, a known target of miR-22. However, salidroside could partly impede the senescence progression induced by lenti-Pre-miR-22. Taken together, our data suggest that salidroside delays replicative senescence by stimulating mitochondrial biogenesis partly through a miR22/SIRT1 pathway, which enriches our current knowledge of a salidroside-mediated postpone senility effect and provides a new perspective on the antidecrepitude function of this naturally occurring compound in animals and humans.