Carbon-based photoelectrochemical sensors: recent developments and future prospects.

Owing to the considerable potential of photoelectrochemical (PEC) sensors, they have gained significant attention in the analysis of biological, environmental, and food markers. However, the limited charge mass transfer efficiency and rapid recombination of electron hole pairs have become obstacles in the development of PEC sensors. In this case, considering the unique advantages of carbon-based materials, they can be used as photosensitizers, supporting materials and conductive substrates and coupled with semiconductors to prepare composite materials, solving the above problems. In addition, there are many types of carbon materials, which can have semiconductor properties and form heterojunctions after coupling with semiconductors, effectively promoting the separation of electron hole pairs. Herein, we aimed to provide a comprehensive analysis of reports on carbon-based PEC sensors by introducing their research and application status and discussing future development trends in this field. In particular, the types and performance improvement strategies of carbon-based electrodes and the working principles of carbon-based PEC sensors are explained. Furthermore, the applications of carbon-based photoelectric sensors in environmental monitoring, biomedicine, and food detection are highlighted. Finally, the current limitations in the research on carbon-based PEC sensors are emphasized and the need to enhance the sensitivity and selectivity through material modification, structural design, improved device performance, and other strategies are emphasized.

The predictive value of the hs-CRP/HDL-C ratio, an inflammation-lipid composite marker, for cardiovascular disease in middle-aged and elderly people: evidence from a large national cohort study.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is associated with inflammation and abnormal lipid metabolism. However, a single inflammatory index or a single lipid index cannot accurately predict the prognosis of CVD independently because it is prone to be affected by various confounding factors. METHODS: This population-based cohort study included 6,554 participants from the China Health and Retirement Longitudinal Study (CHARLS) to investigate correlations. In the present study, the occurrence of CVD events such as stroke and heart disease was evaluated by considering self-reported diagnoses at the beginning of the study and during wave 4, and a restricted cubic spline model was used to investigate potential nonlinear relationships in addition to multivariate logistic regression models. Stratified analyses were performed to examine how sociodemographic characteristics may influence the results. RESULTS: Seven years of follow-up (2011-2018) revealed that 786 people (11.99%) developed CVD. According to the adjusted model, the high-sensitivity C-reactive protein (hs-CRP)-to-high-density lipoprotein cholesterol (HDL-C) ratio is a contributing factor to CVD risk (OR 1.31, 95% CI 1.05-1.64). In addition, a nonlinear relationship was observed between the hs-CRP/HDL-C ratio and the occurrence of new CVD, stroke, or cardiac issues (Poverall <0.05, Pnonlinear <0.05). Moreover, noteworthy associations between the hs-CRP/HDL-C ratio and age were detected in the stratified analysis (P = 0.048), indicating that younger participants had more negative effects of a high hs-CRP/HDL-C ratio. CONCLUSIONS: According to the present cohort study, a high hs-CRP/HDL-C ratio is a significant risk factor for CVD, new stroke, and heart problems. Early intervention in patients with increased hs-CRP/HDL-C ratios may further reduce the incidence of CVD, in addition to focusing on independent lipid markers or independent inflammatory markers.

Aucubin alleviates doxorubicin-induced cardiotoxicity through crosstalk between NRF2 and HIPK2 mediating autophagy and apoptosis.

BACKGROUND: Doxorubicin (DOX) is widely used for the treatment of a variety of cancers. However, its clinical application is limited by dose-dependent cardiotoxicity. Recent findings demonstrated that autophagy inhibition and apoptosis of cardiomyocytes induced by oxidative stress dominate the pathophysiology of DOX-induced cardiotoxicity (DIC), however, there are no potential molecules targeting on these. PURPOSE: This study aimed to explore whether aucubin (AU) acting on inimitable crosstalk between NRF2 and HIPK2 mediated the autophagy, oxidative stress, and apoptosis in DIC, and provide a new and alternative strategy for the treatment of DIC. METHODS AND RESULTS: We first demonstrated the protection of AU on cardiac structure and function in DIC mice manifested by increased EF and FS values, decreased serum CK-MB and LDH contents and well-aligned cardiac tissue in HE staining. Furthermore, AU alleviated DOX-induced myocardial oxidative stress, mitochondrial damage, apoptosis, and autophagy flux dysregulation in mice, as measured by decreased ROS, 8-OHdG, and TUNEL-positive cells in myocardial tissue, increased SOD and decreased MDA in serum, aligned mitochondria with reduced vacuoles, and increased autophagosomes. In vitro, AU alleviated DOX-induced oxidative stress, autophagy inhibition, and apoptosis by promoting NRF2 and HIPK2 expression. We also identified crosstalk between NRF2 and HIPK2 in DIC as documented by overexpression of NRF2 or HIPK2 reversed cellular oxidative stress, autophagy blocking, and apoptosis aggravated by HIPK2 or NRF2 siRNA, respectively. Simultaneously, AU promoted the expression and nuclear localization of NRF2 protein, which was reversed by HIPK2 siRNA, and AU raised the expression of HIPK2 protein as well, which was reversed by NRF2 siRNA. Crucially, AU did not affect the antitumor activity of DOX against MCF-7 and HepG2 cells, which made up for the shortcomings of previous anti-DIC drugs. CONCLUSION: These collective results innovatively documented that AU regulated the unique crosstalk between NRF2 and HIPK2 to coordinate oxidative stress, autophagy, and apoptosis against DIC without compromising the anti-tumor effect of DOX in vitro.

ACEI/ARB and beta-blocker therapies for preventing cardiotoxicity of antineoplastic agents in breast cancer: a systematic review and meta-analysis.

Anthracyclines and trastuzumab are widely used to treat breast cancer but increase the risk of cardiomyopathy and heart failure. With the use of trastuzumab and anthracycline-containing medications, this study intends to evaluate the effectiveness and security of current treatments against cardiotoxicity. We conducted a systematic review of randomized controlled trials (RCTs), which used at least one angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or beta-blocker (BB) to prevent cardiotoxicity of antineoplastic agents for breast cancer, in 4 databases (PubMed, Cochrane Library, EMBASE, Web of Science) from inception to 11 May 2022, without language restrictions. The outcome of interest was left ventricular ejection fraction (LVEF) and adverse events. Stata 15 and R software 4.2.1 were used to perform all statistical analyses. The Cochrane version 2 of the risk of bias tool was used to assess the risk of bias, and the grading of recommendations assessment, development, and evaluation (GRADE) assessment was used to appraise the quality of the evidence. Fifteen randomized clinical studies with a total of 1977 patients were included in the analysis. The included studies demonstrated statistically significant LVEF in the ACEI/ARB and BB treatment groups (χ2 = 184.75, I2 = 88.6%, p = 0.000; SMD 0.556, 95% CI 0.299 to 0.813). In an exploratory subgroup analysis, the benefit of experimental agents on LVEF, whether anthracyclines or trastuzumab, was prominent in patients treated with ACEIs, ARBs, and BBs. Compared to placebo, ACEI/ARB and BB treatments in breast cancer patients protect against cardiotoxicity after trastuzumab and anthracycline-containing medication treatment, indicating a benefit for both.

Neocryptotanshinone ameliorates insufficient energy production in heart failure by targeting retinoid X receptor alpha.

Retinoid X receptor alpha (RXRα) is a nuclear transcription factor that extensively regulates energy metabolism in cardiovascular diseases. Identification of targeted RXRα drugs for heart failure (HF) therapy is urgently needed. Neocryptotanshinone (NCTS) is a component derived from Salvia miltiorrhiza Bunge, the effect and mechanism of which for treating HF have not been reported. The goal of this study was to explore the pharmacological effects of NCTS on energy metabolism to protect against HF post-acute myocardial infarction (AMI) via RXRα. We established a left anterior descending artery ligation-induced HF post-AMI model in mice and an oxygen-glucose deprivation-reperfusion-induced H9c2 cell model to investigate the cardioprotective effect of NCTS. Component-target binding techniques, surface plasmon resonance (SPR), microscale thermophoresis (MST) and small interfering RNA (siRNA) transfection were applied to explore the potential mechanism by which NCTS targets RXRα. The results showed that NCTS protects the heart against ischaemic damage, evidenced by improvement of cardiac dysfunction and attenuation of cellular hypoxic injury. Importantly, the SPR and MST results showed that NCTS has a high binding affinity for RXRα. Meanwhile, the critical downstream target genes of RXRα/PPARα, which are involved in fatty acid metabolism, including Cd36 and Cpt1a, were upregulated under NCTS treatment. Moreover, NCTS enhanced TFAM levels, promoted mitochondrial biogenesis and increased myocardial adenosine triphosphate levels by activating RXRα. In conclusion, we confirmed that NCTS improves myocardial energy metabolism, including fatty acid oxidation and mitochondrial biogenesis, by regulating the RXRα/PPARα pathway in mice with HF post-AMI.

Mechanisms and Drug Intervention for Doxorubicin-Induced Cardiotoxicity Based on Mitochondrial Bioenergetics.

Doxorubicin (DOX) is an anthracycline chemotherapy drug, which is indispensable in antitumor therapy. However, its subsequent induction of cardiovascular disease (CVD) has become the primary cause of mortality in cancer survivors. Accumulating evidence has demonstrated that cardiac mitochondrial bioenergetics changes have become a significant marker for doxorubicin-induced cardiotoxicity (DIC). Here, we mainly summarize the related mechanisms of DOX-induced cardiac mitochondrial bioenergetics disorders reported in recent years, including mitochondrial substrate metabolism, the mitochondrial respiratory chain, myocardial ATP storage and utilization, and other mechanisms affecting mitochondrial bioenergetics. In addition, intervention for DOX-induced cardiac mitochondrial bioenergetics disorders using chemical drugs and traditional herbal medicine is also summarized, which will provide a comprehensive process to study and develop more appropriate therapeutic strategies for DIC.

Effects and Safety of Oral Iron for Heart Failure with Iron Deficiency: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Background: Oral iron supplement is commonly prescribed to heart failure patients with iron deficiency. However, the effects of oral iron for heart failure remain controversial. This study included randomized controlled trials (RCTs) for meta-analysis to evaluate the effects of oral iron for heart failure patients. Methods: Nine databases (The Cochrane Library, Embase, PubMed, CINAHL, Web of science, CNKI, SinoMed, VIP, and Wanfang) were searched for RCTs of oral iron for heart failure from inception to October 2021. The effects were assessed with a meta-analysis using Revman 5.3 software. The trial sequential analysis was performed by TSA 0.9.5.10 beta software. The risk of bias of trials was evaluated via Risk of Bias tool. The evidence quality was assessed through GRADE tool. Results: Four studies including 582 patients with heart failure and iron deficiency were enrolled. The results indicated that oral iron treatment could improve left ventricular ejection fraction (LVEF, MD = 1.52%, 95% CI: 0.69 to 2.36, P = 0.0003) and serum ferritin (MD = 1.64, 95% CI: 0.26 to 3.02, P = 0.02). However, there was no between-group difference in the 6-minute walk distances (6MWT), N terminal pro B type natriuretic peptide (NT-proBNP) or hemoglobin level when compared with control group. Subgroup analyses revealed that the effects of oral iron on 6 MWT and serum ferritin could not be affected by duration and frequency of oral iron uptakes. In trial sequential analysis of LVEF and serum ferritin, the Z-curves crossed the traditional boundary and trail sequential monitoring boundary but did not reach the required information size. Conclusion: This analysis showed that oral iron could improve cardiac function measured by LVEF, and iron stores measured serum ferritin, but lack of effect on exercise capacity measured by 6 MWT, and iron stores measured by hemoglobin. Given the overall poor methodological quality and evidence quality, these findings should be treated cautiously.

Qishen Granule Protects against Doxorubicin-Induced Cardiotoxicity by Coordinating MDM2-p53-Mediated Mitophagy and Mitochondrial Biogenesis.

Doxorubicin (DOX), the anthracycline chemotherapeutic agent, is widely used for the treatment of various cancers. However, its clinical application is compromised by dose-dependent and fatal cardiotoxicity. This study is aimed at investigating the cardioprotective effects of Qishen granule (QSG) and the specific mechanism by which QSG alleviates DOX-induced cardiotoxicity (DIC) and providing an alternative for the treatment of DIC. We first evaluated the cardioprotective effects of QSG in a DIC mouse model, and the obtained results showed that QSG significantly protected against DOX-induced myocardial structural and functional damage, mitochondrial oxidative damage, and apoptosis. Subsequently, after a comprehensive understanding of the specific roles and recent developments of p53-mediated mitochondrial quality control mechanisms in DIC, we investigated whether QSG acted on MDM2 to regulate the activity of p53 and downstream mitophagy and mitochondrial biogenesis. The in vivo results showed that DOX inhibited mitochondrial biogenesis and blocked mitophagy in the mouse myocardium, while QSG reversed these effects. Mechanistically, we combined nutlin-3, which inhibits the binding of p53 and MDM2, with DOX and QSG and evaluated their influence on mitophagy and mitochondrial biogenesis in H9C2 cardiomyocytes. The obtained results showed that both DOX and nutlin-3 substantially inhibited mitophagy and mitochondrial biogenesis and induced mitochondrial oxidative damage and apoptosis, which could be partially recovered by QSG. Importantly, the immunoprecipitation results showed that QSG promoted the binding of MDM2 to p53, thus decreasing the level of p53 protein and the binding of p53 to Parkin. Collectively, QSG could promote the degradation of p53 by enhancing the binding of MDM2 to the p53 protein, resulting in the reduced binding of p53 to the Parkin protein, thus improving Parkin-mediated mitophagy. Increased degradation of p53 protein by QSG simultaneously enhanced mitochondrial biogenesis mediated by PGC-1α. Ultimately, QSG relieved DOX-induced mitochondrial oxidative damage and apoptosis by coordinating mitophagy and mitochondrial biogenesis.

The multi-faced role of FUNDC1 in mitochondrial events and human diseases.

Mitophagy plays a vital role in the selective elimination of dysfunctional and unwanted mitochondria. As a receptor of mitophagy, FUN14 domain containing 1 (FUNDC1) is attracting considerably critical attention. FUNDC1 is involved in the mitochondria fission, the clearance of unfolded protein, iron metabolism in mitochondria, and the crosstalk between mitochondria and endoplasmic reticulum besides mitophagy. Studies have demonstrated that FUNDC1 is associated with the progression of ischemic disease, cancer, and metabolic disease. In this review, we systematically examine the recent advancements in FUNDC1 and the implications of this protein in health and disease.

The roles of the mitophagy inducer Danqi pill in heart failure: A new therapeutic target to preserve energy metabolism.

BACKGROUND: Mitophagy can regulate mitochondrial homeostasis, preserve energy metabolism and cardiomyocytes survival effectively to restrain the development of heart failure (HF). Danqi Pill (DQP), composed of the dry roots of Salvia miltiorrhiza Bunge and Panax notoginseng, is included in the 2015 national pharmacopeia and effective in the clinical treatment of coronary heart diseases. Our previous studies have approved that DQP exerted remarkable cardioprotective effects on HF. However, the effect and mechanism of DQP on mitophagy have not been proved yet. HYPOTHESIS/PURPOSE: We aim to explore whether DQP regulates mitophagy to protect against HF and to elucidate the in-depth mechanism. STUDY DESIGN: The HF rat model for evaluating DQP's efficacy was established with left anterior descending coronary artery ligation. The oxygen-glucose deprivation-reperfusion-induced cardiomyocyte model was conducted to clarify the potential mechanism of DQP. METHODS: The mitochondria-targeted fluorescent protein Keima (mt-Keima) was applied for detecting mitophagy flux. Co-immunofluorescence and co-immunoprecipitation were performed to detect protein co-localization. Flow cytometry for JC-1 and Annexin-FITC/PI staining was utilized for assessing mitochondrial activity and function. RESULTS: In vivo, medium dose of DQP (1.5 g/kg) notably improved cardiac function and inhibited cardiac apoptosis in HF rats. Co-immunofluorescent staining of LC3B and TOM20 showed that DQP restored mitophagy. Further co-immunoprecipitation demonstrated that DQP increased the co-localization of FUNDC1 with either ULK1 or PGAM5. In vitro, DQP markedly protected mitochondrial membrane potential damage, reduced cardiomyocytes apoptosis, decreased the level of mitochondrial ROS, and increased the ATP level. Parallel with the in vitro results, DQP increased the interaction of FUNDC1 and LC3B, while knockdown of FUNDC1 diminished the interaction. Besides, Mt-Keima signaling detection further confirmed that DQP significantly promoted mitophagy. Intriguingly, knockdown of ULK1 or PGAM5 separately weakened rather than eliminated these effects of DQP on FUNDC1-mediated mitophagy, mitochondrial homeostasis and energy metabolism. CONCLUSION: Our results demonstrated that DQP protected against HF by improving FUNDC1-mediated mitophagy to perverse energy metabolism through the coordinated regulation of ULK1 and PGAM5.

Meta-analysis of randomized controlled trials of the effects of probiotics on type 2 diabetes in adults.

BACKGROUND & AIMS: Despite advancements in preventive medicine and pharmacotherapy, diabetes remains an overwhelming health problem. Evidence from randomized controlled trials (RCTs) suggests that probiotics may offer beneficial effects on glycemic control. Our objective was to perform a systematic review and meta-analysis of RCTs to quantify the effect of probiotic administration on glycemic homeostasis in type 2 diabetes. METHODS: Medline, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for relevant trials published until October 12, 2021. RCTs that lasted ≥3 weeks and assessed the effects of probiotics on the markers of glycemic homeostasis in type 2 diabetes were included. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran's Q statistic and quantified using the I2 statistic. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. RESULTS: A total of 33 eligible trial comparisons (n = 1927) were included in this meta-analysis. Our results revealed that compared with placebo, a median probiotic dose of ∼109 cfu/day significantly reduced the glycated hemoglobin (HbA1c) levels (MD: -0.19% [95% CI: -0.32, -0.07]; P = 0.003), fasting blood glucose levels (MD: -1.00 mmol/L [95% CI: -1.45, -0.56]; P < 0.0001), fasting insulin levels (MD: -5.73 pmol/L [95% CI: -12.17, 0.72]; P = 0.08), and HOMA-insulin resistance (IR) (MD: -1.00 [95% CI: -1.32, -0.68]; P < 0.00001). The certainty of evidence was graded low for HbA1c and fasting glucose, moderate for fasting insulin, and high for HOMA-IR. Probiotic supplements do not induce clinically significant reductions in HbA1c levels, but lead to marginally clinically significant reductions in fasting glucose and fasting insulin levels in patients with type 2 diabetes. Compared with single-strain and low-dose probiotics, multi-strain and high-dose probiotics have a greater beneficial effect on glycemic homeostasis. In addition, probiotic treatment may be more effective in patients with a high baseline body mass index and age.

Hsa_circ_0004712 downregulation attenuates ovarian cancer malignant development by targeting the miR-331-3p/FZD4 pathway.

BACKGROUND: Circular RNAs (circRNAs) are gradually reported to be implicated in the development of malignant tumors, including ovarian cancer (OC). This paper intended to explore the function and action mechanism of hsa_circ_0004712 in OC. RESULTS: In our results, hsa_circ_0004712 was aberrantly overexpressed in OC tissues and cells. Downregulation of hsa_circ_0004712 impaired OC cell proliferation, colony formation, invasion and migration, and accelerated apoptosis. Hsa_circ_0004712 directly targeted miR-331-3p whose inhibitors reversed the effects of hsa_circ_0004712 downregulation. FZD4 was targeted by miR-331-3p, and hsa_circ_0004712 could positively regulated FZD4 expression by targeting miR-331-3p. The anti-tumor effects of miR-331-3p restoration were reversed by FZD4 overexpression. Downregulation of hsa_circ_0004712 also impaired tumor development in vivo by regulating miR-331-3p and FZD4. CONCLUSION: In conclusion, hsa_circ_0004712 deficiency repressed OC development by mediating the miR-331-3p/FZD4 pathway, predicting that hsa_circ_0004712 was a promising biomarker for OC diagnosis and therapy.

Identification of the key characteristics of Bifidobacterium longum strains for the alleviation of ulcerative colitis.

Bifidobacterium longum (B. longum) species are widely used to prevent and treat ulcerative colitis (UC). In this study, phylogenetic and pan-genomic characterization of 122 B. longum strains was performed on the basis of 936 core genes; among these, four strains from different branches of the phylogenetic tree were selected for an evaluation of anti-inflammatory and immune modulatory activities in a DSS-induced colitis mouse model. Among the tested B. longum strains (B. longum FBJ20M1, B. longum FGDLZ8M1, B. longum FGSZY16M3, and B. longum FJSWXJ2M1), B. longum FGDLZ8M1 was found to most effectively alleviate colitis by reducing the expression of pro-inflammatory cytokines, restoring the colon length, and maintaining the mucosal integrity. The anti-inflammatory mechanisms of B. longum FGDLZ8M1 were related to the inhibition of NF-κB signaling. Genomic analysis indicated that these protective effects of B. longum FGDLZ8M1 may be related to specific genes associated with carbohydrate transport and metabolism and defense mechanisms (e.g., tolerance to bile salts and acids). Correlation analysis indicated that gastrointestinal transit tolerance was the most strongly associated factor. Our findings may contribute to the rapid screening of lactic acid bacterial strains with UC-alleviating effects.

Strain-Specific Effects of Bifidobacterium longum on Hypercholesterolemic Rats and Potential Mechanisms.

Hypercholesterolemia is an independent risk factor of cardiovascular disease, which is among the major causes of death worldwide. The aim of this study was to explore whether Bifidobacterium longum strains exerted intra-species differences in cholesterol-lowering effects in hypercholesterolemic rats and to investigate the potential mechanisms. SD rats underwent gavage with each B. longum strain (CCFM 1077, I3, J3 and B3) daily for 28 days. B. longum CCFM 1077 exerted the most potent cholesterol-lowering effect, followed by B. longum I3 and B3, whereas B. longum B3 had no effect in alleviating hypercholesterolemia. Divergent alleviation of different B. longum strains on hypercholesterolemia can be attributed to the differences in bile salt deconjugation ability and cholesterol assimilation ability in vitro. By 16S rRNA metagenomics analysis, the relative abundance of beneficial genus increased in the B. longum CCFM 1077 treatment group. The expression of key genes involved in cholesterol metabolism were also altered after the B. longum CCFM 1077 treatment. In conclusion, B. longum exhibits strain-specific effects in the alleviation of hypercholesterolemia, mainly due to differences in bacterial characteristics, bile salt deconjugation ability, cholesterol assimilation ability, expressions of key genes involved in cholesterol metabolism and alterations of gut microbiota.

Efficacy of probiotics in multiple sclerosis: a systematic review of preclinical trials and meta-analysis of randomized controlled trials.

Preliminary evidence shows the potential role of probiotics in ameliorating multiple sclerosis (MS); however, the effects of probiotics on MS remain unclear. Therefore, the aim of this study was to evaluate the efficacy of probiotics on multiple sclerosis by systematically reviewing the preclinical trials (animal trials) and performing meta-analysis of randomized controlled trials. PubMed, Web of Science, Cochrane central of randomized clinical trials, EMBASE, Clinical Trials, and a search engine Google Scholar were systematically searched and manually screened updated to November 2020, resulting in eligible 3 randomized controlled trials (RCTs) and 22 preclinical studies. Meta-analysis of RCTs enrolling 173 patients with MS receiving probiotics revealed significant beneficial effects of probiotic supplementation on mental health (expanded disability status scale scores: standardized mean difference [SMD] = -1.22; I2 = 92%; 95% CI, -2.40 to -0.03, P = 0.04; Beck depression inventory total scores: SMD = -1.58; I2 = 94%; 95% CI, -3.03 to -0.12; P = 0.03; general health questionnaire scores: SMD = -0.71; I2 = 0%; 95% CI, -1.02 to -0.40; P < 0.00001; depression anxiety and stress scale scores: SMD = -0.72; I2 = 0%; 95% CI, -1.12 to -0.33; P = 0.0003), with very low certainty of evidence. In addition, probiotic intake markedly improved insulin resistance and inflammatory and oxidative stress markers. Preclinical studies have shown that probiotic consumption reduces the incidence and severity of MS, delays MS progression (15 studies), and improves motor impairment (3 studies) with favorable alterations of immune and inflammatory markers (20 studies) and intestinal microbiome compositions (4 studies) in MS. These results indicated that probiotics may have beneficial effects on the prevention and treatment of multiple sclerosis.

Meta-analysis of randomized controlled trials of the effects of probiotics on functional constipation in adults.

BACKGROUND & AIMS: Clinical trials have reported controversial results regarding the effectiveness of probiotics in alleviating functional constipation in adults. We reviewed relevant randomized controlled trials to elucidate the effectiveness of probiotics on constipation symptoms in adults with functional constipation. METHODS: We searched Medline, the Cochrane Library, Web of Science, and Google Scholar for relevant articles published up to April 2019. The primary outcomes of interest were stool frequency, gut transit time (GTT), stool consistency, and bloating. Two authors independently performed the study selection, risk-of-bias assessment, and data extraction. The outcome data were extracted from each included study and synthesized using weighted mean differences (WMDs) or standardized mean differences (SMDs). Pooled data synthesis was performed using a random-effects model. RESULTS: In total, 2327 relevant studies were identified, 15 of which were found to be eligible randomized controlled trials and were included in the meta-analysis. Pooling of the extracted data demonstrated that probiotic consumption significantly reduced the whole GTT by 13.75 h [95% confidence interval (CI): -21.93 to -5.56 h] and increased the stool frequency by 0.98 (95% CI: 0.36 to 1.60) bowel movements per week. This increase was significant with the consumption of multispecies probiotics [at least two bacteria; WMD: 1.22 (95% CI: 0.50 to 1.94) bowel movements per week] but not with the consumption of Bifidobacterium lactis [WMD: 1.34 (95% CI: -0.27 to 2.94) bowel movements per week] or B. longum [WMD: -0.02 (95% CI: -0.56 to 0.53) bowel movements per week] alone. Multispecies probiotics (WMD: 1.37; 95% CI: 0.72 to 2.01), but not single-species probiotics (WMD: 1.18; 95% CI: -0.59 to 2.96), improved stool consistency (WMD: 1.30; 95% CI: 0.22 to 2.38). Similarly, multispecies probiotics (at least two bacteria; WMD: -0.49; 95% CI: -0.85 to -0.13), but not single-species probiotics (WMD: -0.24; 95% CI: -0.55 to 0.07), significantly decreased bloating. Performance bias were high, whereas detection bias was unclear because of inadequate reporting. CONCLUSION: Consumption of probiotics, in particular, multispecies probiotics, may substantially reduce the GTT, increase the stool frequency, and improve the stool consistency. Thus, probiotics can be regarded as safe and natural agents for alleviation of functional constipation in adults.

Lactobacillus reuteri A9 and Lactobacillus mucosae A13 isolated from Chinese superlongevity people modulate lipid metabolism in a hypercholesterolemia rat model.

While there is strong evidence showing that many food-borne probiotics regulate cholesterol metabolism, few studies have examined how probiotics of human origin affect cholesterol metabolism. Because people living in so-called 'longevity villages' are unlikely to have hypercholesterolemia, we hypothesized that probiotics isolated from the residents would have cholesterol-reducing effects on rats with hypercholesterolemia. We isolated 16 strains of Lactobacillus from four longevity populations in China. The strains were tested in vitro for bile salt hydrolase (BSH) activity and two isolates, Lactobacillus reuteri A9 and Lactobacillus mucosae A13, were screened out. These two strains were then administered daily for 28 d to rats fed a cholesterol-rich diet. The serum total cholesterol levels in the L. reuteri A9 and L. mucosae A13 groups decreased by 24.3% and 21.6%, respectively. The serum low density lipoprotein cholesterol levels decreased by 23.8% and 25.2%, respectively. The L. reuteri A9 and L. mucosae A13 groups also exhibited upregulated hepatic mRNA expression of Sterol regulatory element-binding protein 2 (Srebp2) by 2.71-fold and 2.54-fold, respectively. The mRNA expression levels of hepatic low-density lipoprotein receptor (Ldlr) in the two groups were significantly up-regulated by 1.28-fold and 2.17-fold, respectively. The composition of gut microbiota was recovered by oral gavage in both experimental groups, and the destroyed diversity of gut microbiota was relieved.

Disturbance of trace element and gut microbiota profiles as indicators of autism spectrum disorder: A pilot study of Chinese children.

Autism spectrum disorder (ASD) is a neuro-developmental disorder that is characterized by impairments of reciprocal social interaction and restricted stereotyped repetitive behavior. The goal of the present study was to investigate the trace element and gut microbiota profiles of Chinese autistic children and screen out potential metallic or microbial indicators of the disease. One hundred and thirty-six children (78 with ASD and 58 healthy controls) aged from 3 to 7 years were enrolled. The levels of lead, cadmium, arsenic, copper, zinc, iron, mercury, calcium and magnesium in hair samples from the children were analyzed. Fecal samples were also collected and the children's gut microbiota profiles were characterized by 16s rRNA sequencing. Concentrations of lead, arsenic, copper, zinc, mercury, calcium and magnesium were significantly higher in the ASD group than in the control group. Linear discriminant analysis effect size analysis indicated that the relative abundance of nine genera was increased in the autistic children. Redundancy analysis showed that arsenic and mercury were significantly associated with Parabacteroides and Oscillospira in the gut. A random forest model was trained with high accuracy (84.00%) and the metallic and microbial biomarkers of ASD were established. Our results indicate significant alterations in the trace element and gut microbiota profiles of Chinese children with ASD and reveal the potential pathogenesis of this disease in terms of metal metabolism and gut microecology.

The therapeutic protection of a living and dead Lactobacillus strain against aluminum-induced brain and liver injuries in C57BL/6 mice.

Our previous study found that Lactobacillus plantarum CCFM639 had the ability to alleviate acute aluminum (Al) toxicity when the strain was introduced simultaneously with Al exposure. This research was designed to elucidate the therapeutic effects of living and dead L. plantarum CCFM639 against chronic Al toxicity and to gain insight into the protection modes of this strain. Animals were assigned into control, Al only, Al + living CCFM639, and Al + dead CCFM639 groups. The Al exposure model was established by drinking water for the first 4 weeks. The strain was given after Al exposure by oral gavage at 109 colony-forming units once per day for 12 weeks. The results show that the Al binding ability of dead CCFM639 was similar to that of living CCFM639 in vitro. The ingestion of living or dead CCFM639 has similar effects on levels of Al and trace element in tissues, but living strains led to more significant amelioration of oxidative stress and improvement of memory deficits in Al-exposed mice. In conclusion, in addition to intestinal Al sequestration, CCFM639 treatment offers direct protection against chronic Al toxicity by alleviation of oxidative stress. Therefore, L. plantarum CCFM639 has a potential as dietary supplement ingredient that provides protection against Al-induced injury.