Effectiveness and Safety of Probiotics for Patients with Constipation-Predominant Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials.

To perform a systematic review and meta-analysis to evaluate the effectiveness and safety of probiotics in the treatment of constipation-predominant irritable bowel syndrome (IBS-C), we searched for randomized controlled trials (RCTs) comparing probiotic care versus placebos for patients with IBS-C in five comprehensive databases (March 2022). The risk of bias was assessed using the Cochrane Collaboration Risk of Bias Tool. RevMan 5.3 was used to perform a meta-analysis on stool consistency, abdominal pain, bloating, quality of life (QoL), fecal Bifidobacterium and Lactobacillus counts, and adverse events. The GRADE approach was used to evaluate the certainty of the evidence. Ten RCTs involving 757 patients were included. Only three studies were rated as having a low risk of bias. The meta-analysis results show that, compared to the placebo, probiotics significantly improved stool consistency (MD = 0.72, 95% CI (0.18, 1.26), p < 0.05, low quality) and increased the number of fecal Bifidobacteria (MD = 1.75, 95% CI (1.51, 2.00), p < 0.05, low quality) and Lactobacillus (MD = 1.69, 95% CI (1.48, 1.89), p < 0.05, low quality), while no significant differences were found in abdominal pain scores, bloating scores, QoL scores, or the incidence of adverse events (p > 0.05). The low-to-very low certainty evidence suggests that probiotics might improve the stool consistency of patients with IBS-C and increase the number of Bifidobacteria and Lactobacilli in feces with good safety. However, more high-quality studies with large samples are needed to verify the findings.

A New Chimeric Natriuretic Peptide, CNAAC, for the Treatment of Left Ventricular Dysfunction after Myocardial Infarction.

An innovative natriuretic peptide analog named CNAAC (structurally consisting of the C-terminus and ring of ANP and the N-terminus of CNP) that has been shown to exhibit potent vasodilatory, diuretic, and hypotensive effects in our previous study was evaluated for the treatment of left ventricular dysfunction following myocardial infarction. The temporal relaxation effect and metabolic status of CNAAC were determined. A myocardial ischemic model was established. Rats were randomly divided into Sham, MI, MI-ANP, MI-CNP, MI-VNP, and MI-CNAAC groups. Humoral factors were measured; echocardiography and hemodynamics methods were employed to assess the cardiac function at the fourth week after modeling. The results showed that CNAAC had a potent relaxant effect and longer duration of action than ANP, CNP, or VNP. The stability of CNAAC in blood was higher than other three NPs. Four weeks of NP administration ameliorated diastolic and systolic dysfunction, the hypertrophic index, myocardial fibrosis, and infarct size; it also restored the abnormal changes in humoral factors. These results demonstrate that CNAAC has a potent cardioprotective effect against left ventricular dysfunction after myocardial infarction. The results may lay the foundation for the clinical application of this newly designed NP chimera in the treatment and prevention of heart failure.

Integrated analysis of transcription factor, microRNA and LncRNA in an animal model of obliterative bronchiolitis.

Obliterative bronchiolitis (OB) is characterized by sub-epithelial inflammatory and fibrotic narrowing of the bronchioles, and it is the predominant factor limiting long-term survival after lung transplantation. To explore molecular mechanism of OB, we investigated the interaction of transcription factor (TF), microRNA, long noncoding RNA (lncRNA), and gene expression in the mice model of OB by integrated analysis of TF array, miRNA microarray, and lncRNA and mRNA microarray. After 28 days of orthotopic tracheal transplantation in mice, 42 TFs were significantly up-regulated in allogeneic graft compared to syngeneic graft; 62 miRNAs including miR-376-5p were up-regulated and 17 miRNAs including miR-338-3p were down-regulated over 2-fold; 137 mRNAs were down-regulated and 129 mRNAs were up-regulated over 2-fold; 234 lncRNAs were up-regulated and 212 lncRNAs were down-regulated over 2-fold in the allogeneic model compared to that in the syngeneic control group. We further analyzed potential interaction between TFs, miRNAs, lncRNAs and target genes by different algorithms. Four differentially expressed TFs (Myc/Max, FOXO1, FOXM1, and SMAD) were predicted to regulate 3 different miRNAs, 17 mRNAs, and 16 lncRNAs. These findings suggest that modulation of altered transcription factors such as Myc/Max and FOXO1, and miRNAs such as miR-376-5p and miR-338-3p may become a preventive or therapeutic targets in the chronic lung allograft dysfunction.

Protein-DNA array-based identification of transcription factor activities differentially regulated in obliterative bronchiolitis.

Lung transplantation has already become the preferred treatment option for a variety of end-stage pulmonary failure. However the long-term results of lung transplantation are still not compelling and the major death reason is commonly due to obliterative bronchiolitis (OB) which is considered as chronic rejection presenting manifests physiologically as a progressive decline in FEV1. Transcription factors (TFs) play a key role in regulating gene expression and in providing an interconnecting regulatory between related pathway elements. Although the transcription factors are required for expression of the proinflammatory cytokines and immune proteins which are involved in obliterative bronchiolitis following lung transplantation, the alterations of the transcription factors in OB have not yet been revealed. Therefore, to investigate the alteration pattern of the transcription factors in OB, we used protein/DNA arrays. Mice orthotopic tracheal transplantation model was used in this studying. In this study, we explored the activity profiles of TFs in Protein/DNA array data of tracheal tissue in 14 and 28 day after transplanted. From a total of 345 screened TFs, we identified 42 TFs that showed associated with OB progression. Our data indicate that TFs may be potentially involved in the pathogenesis of OB, and can prevent, diagnose and treat OB after lung transplantation. In development of OB, some of the TFs may have ability to modulate the transcription of inflammatory proteins such cytokines, inflammatory enzymes and so on.

Overview of fundamental study of pazopanib in cancer.

Angiogenesis is an indispensible process for tumor growth and metastasis. Anti-angiogenesis based therapy is one of the most promising treatments for inhibiting cancer progression. Through the exploration of inhibitors of vascular endothelial growth factor receptor (VEGFR)-2, deemed as the major angiogenesis pathway, pazopanib was found as a small molecular pan-VEGFR and pan-platelet-derived growth factor receptor (PDGFR) inhibitor, with suitable pharmacodynamic and pharmacokinetic parameters to be an oral drug. In an vitro study, pazopanib exerted anti-tumor effect through mechanisms including the Raf-MAPK/ERK (MEK)-extracellular signal-regulated kinase (ERK) pathway, and directly targeted on v-raf murine sarcoma viral oncogene homolog B (B-raf) as well. It inhibited the proliferation of cell lines, such as DU-145 and HRC-45 in hepatocellular carcinoma, through mechanisms like "cell cycle arrest." In vivo xenograft studies and phase I/II clinical trials revealed a series of plasma cytokine and angiogenic factors, such as interleukin (IL)-6, IL-12, hepatocyte growth factor (HGF), and soluble VEGFR2, which have significant association with clinical curative effect. Pazopanib has been shown to be effective in solid tumors and some hematological malignancies. Future studies should focus on the exploration of biomarkers to screen sensitive patients and concomitant or metronomic dosage with other kinds of medicines.

A comparison of the biological characteristics of EV71 C4 subtypes from different epidemic strains.

The comparative analysis of the biological characterization and the genetic background study of EV71 circulating strains is commonly recognized as basic work necessary for development of an effective EV71 vaccine. In this study, we sequenced five EV71 circulating strains, isolated from Fuyang, Hefei, Kunming and Shenzhen city of China and named them FY-23, FY-22, H44, K9 and S1 respectively. The sequence alignment demonstrated their genotypes be C4. The genetic distance of the VP1 gene from these isolates suggested that they were highly co-related with genetic identity similar to other previously reported EV71 strains in China. Additionally, these strains were identified to display some obvious proliferation dynamics and plaque morphology when propagated in Vero cells. However, a distinctive difference in pathogenic ability in neonatal mice was found. Some differences in cross neutralization test & immunogenic analysis were also found. All these results are related to the biological characterization of circulating EV71 strains in China and aid in the development of an EV71 vaccine in the future.