Efficacy of probiotics against dental caries in children: a systematic review and meta-analysis.

Dental caries causes serious consequences and the financial burden of society especially in children with high morbidity rate. Here we carried out a meta-analysis to systematically evaluate the efficacy of probiotics against dental caries in children. Forty-three RCTs were eligible for this meta-analysis after searching the PubMed, Cochrane and Web of Science from the inception through October 2021. Pooled estimates demonstrated that treatment with probiotics significantly reduced noncavitated (dicdas2-6mft) (SMD = -0.18, 95% CI: -0.3 to -0.06, p = 0.002) and cavitated (dicdas5-6mft) carious lesions in children (SMD = -0.32, 95% CI: -0.5 to 0.14, p = 0.0004). Probiotics also reduced prevalence of noncavitated (dicdas2-6mft) carious lesions (RR = 0.8, 95% CI: 0.67 to-0.97, p = 0.02). Salivary Streptococcus mutans was declined after intervention (SMD = -1.17, 95% CI: -1.85 to -0.5, p = 0.0007), while Lactobacillus counts were upregulated (SMD = 1.19, 95% CI: 0.46-1.92, p = 0.001). However, no significant effects in total bacteria counts and salivary pH were observed. Our findings suggest that probiotics especially Lactobacillus could be a promising therapeutic strategy for clinical applications in children dental caries.

Deciphering the molecular nexus of BTG2 in periodontitis and diabetic kidney disease.

OBJECTIVE: To investigate the role of BTG2 in periodontitis and diabetic kidney disease (DKD) and its potential underlying mechanism. METHODS: Gene expression data for periodontitis and DKD were acquired from the Gene Expression Omnibus (GEO) database. Differential expression analysis identified co-expressed genes between these conditions. The Nephroseq V5 online nephropathy database validated the role of these genes in DKD. Pearson correlation analysis identified genes associated with our target gene. We employed Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) networks to elucidate potential mechanisms. Expression levels of BTG2 mRNA were examined using quantitative polymerase Chain Reaction (qPCR) and immunofluorescence assays. Western blotting quantified proteins involved in epithelial-to-mesenchymal transition (EMT), apoptosis, mTORC1 signaling, and autophagy. Additionally, wound healing and flow cytometric apoptosis assays evaluated podocyte migration and apoptosis, respectively. RESULTS: Analysis of GEO database data revealed BTG2 as a commonly differentially expressed gene in both DKD and periodontitis. BTG2 expression was reduced in DKD compared to normal conditions and correlated with proteinuria. GSEA indicated enrichment of BTG2 in the EMT and mTORC1 signaling pathways. The PPI network highlighted BTG2's relevance to S100A9, S100A12, and FPR1. Immunofluorescence assays demonstrated significantly lower BTG2 expression in podocytes under high glucose (HG) conditions. Reduced BTG2 expression in HG-treated podocytes led to increased levels of EMT markers (α-SMA, vimentin) and the apoptotic protein Bim, alongside a decrease in nephrin. Lower BTG2 levels were associated with increased podocyte mobility and apoptosis, as well as elevated RPS6KB1 and mTOR levels, but reduced autophagy marker LC3. CONCLUSION: Our findings suggest that BTG2 is a crucial intermediary gene linking DKD and periodontitis. Modulating autophagy via inhibition of the mTORC1 signaling pathway, and consequently suppressing EMT, may be pivotal in the interplay between periodontitis and DKD.

Ischemia/reperfusion-activated ferroptosis in the early stage triggers excessive inflammation to aggregate lung injury in rats.

Objective: Lung ischemia/reperfusion injury (LIRI) is a clinical syndrome of acute lung injury that occurs after lung transplantation or remote organ ischemia. Ferroptosis and inflammation are involved in the pathogenesis of LIRI according to the results of several studies on animal models. However, the interactive mechanisms between ferroptosis and inflammation contributing to LIRI remain unclear. Methods: HE staining and indicators of oxidative stress were used to evaluated the lung injury. The reactive oxygen species (ROS) level was examined by DHE staining. The quantitative Real-time PCR (qRT-PCR) and western blot analysis were employed to detect the level of inflammation and ferroptosis, and deferoxamine (DFO) was used to assess the importance of ferroptosis in LIRI and its effect on inflammation. Results: In the present study, the link of ferroptosis with inflammation was evaluated at reperfusion 30-, 60- and 180-minute time points, respectively. As the results at reperfusion 30-minute point shown, the pro-ferroptotic indicators, especially cyclooxygenase (COX)-2 and acyl-CoA synthetase long-chain family member 4 (ACSL4), were upregulated while the anti-ferroptotic factors glutathione peroxidase 4 (GPX4), cystine-glumate antiporter (XCT) and ferritin heavy chain (FTH1) were downregulated. Meanwhile, the increased level of interleukin (IL)-6, tumor necrosis factor alpha (TNF-α) and IL-1ß were observed beginning at reperfusion 60-minute point but mostly activated at reperfusion 180-minute point. Furthermore, deferoxamine (DFO) was employed to block ferroptosis, which can alleviate lung injury. Expectedly, the survival rate of rats was increased and the lung injury was mitigated containing the improvement of type II alveolar cells ultrastructure and ROS production. In addition, at the reperfusion 180-minute point, the inflammation was observed to be dramatically inhibited after DFO administration as verified by IL-6, TNF-α and IL-1ß detection. Conclusion: These findings suggest that ischemia/reperfusion-activated ferroptosis plays an important role as the trigger for inflammation to further deteriorate lung damages. Inhibiting ferroptosis may have therapeutic potential for LIRI in clinical practice.

Detection of inflammatory bowel disease (IBD)-associated microRNAs by two color DNA-templated silver nanoclusters fluorescent probes.

Researches demonstrated that circulating miRNAs could be used as novel diagnostic and prognostic potential markers for patients with inflammatory bowel diseases (IBD). It is of great significance in clinical to develop rapid and specific detection methods for miRNAs. Herein, we established a fluorescent probe for ulcerative colitis (UC) activity-associated two serum biomarkers (miR-23a and miR-223) simultaneous detection, which used multi-color fluorescent DNA-stabilized silver nanoclusters (DNA-AgNC) illuminated by a close guanine (G)-rich sequence as a signal transducer and two split DNA probes as recognition units. In principle, the two DNA probe sequences containing AgNC nucleation sequence and G-rich sequence respectively, formed a ternary complex when in the presence of target miRNA through base pairing, so as to induce enhancement of fluorescence emission of AgNC by shortening the distance from G-rich sequence. The combined probes for miR-23a and miR-223 detection generated increased fluorescence signals at 460 nm ex/545 nm em and at 560 nm ex/630 nm em, respectively. With this technique, we successfully quantified the two target miRNAs with high selectivity. Furthermore, the potential clinic applicability of this method was verified by testing the spiked standard miRNAs in human serum. Thus, this one-step, low-cost, and homogenous method offers a great opportunity for disease-associated multiplex miRNAs simultaneous detection.

Effectiveness of Probiotics and Prebiotics Against Acute Liver Injury: A Meta-Analysis.

Background and Aims: Acute liver injury (ALI) is a clinical syndrome characterized by rapid loss of liver function, which may progress to life-threatening liver failure. We conducted this meta-analysis to examine the evidence on the effects of probiotics or prebiotics on ALI. Methods and Results: Several databases, including PubMed, EMBASE, and Cochrane Library, were scrutinized from the inception through February 2021 by combining key search terms, yielding 26 eligible studies, which concluded that modulation of gut microbiota significantly decreased aspartate transaminase [standardized mean difference (SMD): -1.51, 95% confidence interval (CI): -2.03 to -1.00], alanine aminotransferase (SMD: -1.42, 95% CI: -1.85 to -0.98), and bilirubin (SMD: -0.91, 95% CI: -1.33 to -0.49). In addition, administration of probiotics or prebiotics also promoted proliferation of Bifidobacterium (SMD: 1.21, 95% CI: -0.18 to 2.60) and inhibited Enterococcus (SMD: -1.00, 95% CI: -1.39 to -0.61), contributing to lower levels of endotoxin (SMD: -2.14, 95% CI: -2.91 to -1.37). Tight junction protein ZO-1 (SMD: 1.95, 95% CI: 0.14 to 3.76) was upregulated after intervention, thereby reducing bacterial translocation to the liver [odds ratio (OR) = 0.23, 95% CI: 0.13-0.44] and mesenteric lymph node (OR = 0.14, 95% CI: 0.08 to 0.26), with decreased tumor necrosis factor-α (SMD: -2.84, 95% CI: -3.76 to -1.93) and interleukin-6 (SMD: -2.62, 95% CI: -4.14 to -1.10). Oxidative stress was also relieved by reducing malondialdehyde (SMD: -1.83, 95% CI: -2.55 to -1.10) while elevating superoxide dismutase (SMD: 1.78, 95% CI: 1.00-2.55) and glutathione (SMD: 1.83, 95% CI: 0.76-2.91). Conclusion: Our findings suggest that probiotics and prebiotics could be a promising therapeutic strategy in ALI and possess a potential for clinical applications. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=255888, CRD42021255888.

A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials.

Background and aims: Metabolic syndrome (MetS), accompanied with significant intestinal dysbiosis, causes a great public health burden to human society. Here, we carried out a meta-analysis to qualify randomized controlled trials (RCTs) and to systematically evaluate the effect of microbial therapy on MetS. Methods and results: Forty-two RCTs were eligible for this meta-analysis after searching the PubMed, Cochrane, and Embase databases. Pooled estimates demonstrated that treatment with microbial therapy significantly reduced the waist circumference (WC) (SMD = -0.26, 95% CI -0.49, -0.03), fasting blood glucose (FBG) (SMD = -0.35, 95% CI -0.52, -0.18), total cholesterol (TC) (SMD = -0.36, 95% CI -0.55, -0.17), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.42, 95% CI -0.61, -0.22), and triacylglycerol (TG)(SMD = -0.38, 95% CI -0.55, -0.20), but increased the high-density lipoprotein cholesterol (HDL-C) (SMD = 0.28, 95% CI.03, 0.52). Sensitivity analysis indicated that after eliminating one study utilizing Bifidobacteriumlactis, results became statistically significant in diastolic blood pressure (DBP) (SMD = -0.24, 95% CI -0.41, -0.07) and in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (SMD = -0.28, 95% CI -0.54, -0.03), while the body mass index (BMI) showed significant difference after eliminating one study utilizing oat bran (SMD = -0.16, 95% CI -0.31, -0.01). There was still no significant effect in systolic blood pressure (SBP) and in hemoglobin A1c (HbA1c%). Conclusion: In patients with MetS, the conditioning with microbial therapy notably improves FBG, TC, TG, HDL-C, LDL-C, WC, BMI (except for the study using oat bran), HOMA-IR, and DBP (except for the Study using Bifidobacteriumlactis), however, with no effect in SBP and in HbA1c%.

A meta-analysis reveals the effectiveness of probiotics and prebiotics against respiratory viral infection.

Experimental experience suggests that microbial agents including probiotics and prebiotics (representative microbial agents) play a critical role in defending against respiratory virus infection. We aim to systematically examine these agents' effect on respiratory viral infection and encourage research into clinical applications. An electronic literature search was conducted from published data with a combination of a microbial agents search component containing synonyms for microbial agents-related terms and a customized search component for respiratory virus infection. Hazard ratio (HR), risk ratio (RR) and standard deviation (SD) were employed as effect estimates. In 45 preclinical studies, the mortality rates decreased in the respiratory viral infection models that included prebiotics or prebiotics as interventions (HR: 0.70; 95% confidence interval (CI): 0.56-0.87; P=0.002). There was a significant decrease in viral load due to improved gut microbiota (SD: -1.22; 95% CI: -1.50 to -0.94; P<0.001). Concentrations of interferon (IFN)-α (SD: 1.05; 95% CI: 0.33-1.77; P=0.004), IFN-γ (SD: 0.83; 95% CI: 0.01-1.65; P=0.05) and interleukin (IL)-12 (SD: 2.42; 95% CI: 0.32-4.52; P=0.02), IL-1ß (SD: 0.01; 95% CI: -0.37 to 0.40; P=0.94) increased, whereas those of TNF-α (SD: -0.58; 95% CI: -1.59 to 0.43; P=0.26) and IL-6 (SD: -0.59; 95% CI: -1.24 to 0.07; P=0.08) decreased. Six clinical studies had lower symptom scores (SD: -0.09; 95% CI: -0.44 to 0.26; P=0.61) and less incidence of infection (RR: 0.80; 95% CI: 0.64-1.01; P=0.06). Our research indicates that probiotics and prebiotics pose a defensive possibility on respiratory viral infection and may encourage the clinical application.

Hybrid Nanoparticles Modified by Hyaluronic Acid Loading an HSP90 Inhibitor as a Novel Delivery System for Subcutaneous and Orthotopic Colon Cancer Therapy.

BACKGROUND: As a therapeutic target for cancer treatment, HSP90 has been explored extensively. However, the significant side effects of the HSP90 inhibitor 17AAG have limited its clinical use. METHODS: In this study, we used hyaluronic acid (HA)-decorated DOTAP-PLGA hybrid nanoparticles (HA-DOTAP-PLGA NPs) as 17AAG-delivery carriers for targeted colon cancer therapy. RESULTS: Different methods were used to characterize the successful fabrication of these hybrid PLGA NPs. Our results demonstrated that internalization of HA-NPs in colon cancer cells was governed by CD44receptor-mediated endocytosis. Annexin V-propidium iodide staining experiments revealed that cell apoptosis induced by HA-NPs-17AAG in colon cancer cells was more efficient than free 17AAG. In two animal models used to screen anticancer efficacy (Luc-HT29 subcutaneous xenograft and AOM/DSS-induced orthotopic tumor model), HA-NPs-17AAG significantly inhibited xenograft and orthotopic tumor growth, demonstrating HA-NPs-17AAG had much better therapeutic efficiency than free 17AAG. It is worth noting that great biocompatibility of HA-DOTAP-PLGA NPs was observed both in vitro and in vivo. CONCLUSION: Our research offers a preclinical proof of concept for colon cancer therapy with DOTAP-PLGA NPs as a creative drug-delivery system.