Previously, we found that the miR-217 expression level was increased in hearts from chronic heart failure (CHF) patients by using miRNA profile analysis. This study aimed to explore the role of ...miR-217 in cardiac dysfunction. Heart tissue samples from CHF patients were used to detect miR-217 expression levels. A type 9 recombinant adeno-associated virus (rAAV9) was employed to manipulate miR-217 expression in mice with thoracic aortic constriction (TAC)-induced cardiac dysfunction. Cardiac structure and function were measured by echocardiography and invasive pressure-volume analysis. The expression levels of miR-217 were increased in hearts from both CHF patients and TAC mice. Overexpression of miR-217 in vivo aggravated pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction, whereas miR-217-TUD-mediated downregulation of miR-217 reversed these effects. PTEN was predicted and validated as a direct target of miR-217, and re-expression of PTEN attenuated miR-217-mediated cardiac hypertrophy and cardiac dysfunction. Importantly, cardiomyocyte-derived miR-217-containing exosomes enhanced proliferation of fibroblasts in vitro. All of these findings show that miR-217 participates in cardiac hypertrophy and cardiac fibrosis processes through regulating PTEN, which suggests a promising therapeutic target for CHF.
Irritable bowel syndrome (IBS) is a common gastrointestinal disease. The efficacy of different probiotics in treating IBS remains controversial. This network meta-analysis aimed to compare and rank ...the outcome-specific efficacy of different probiotic strains or combinations in adults with IBS. We searched the literature up to June 2023. Randomized controlled trials (RCTs) that evaluated the efficacy of probiotics in IBS were included. A frequentist framework was used to perform this study. In total, 9253 participants from 81 RCTs were included in the study. Four probiotic strains and five mixtures were significantly superior to placebo in improving IBS Symptom Severity Scale, among which Lactobacillus acidophilus DDS-1 ranked first (surface under the cumulative ranking, SUCRA, 92.9%). A mixture containing five probiotics (SUCRA, 100%) ranked first in improving the IBS-Quality of life. Bacillus coagulans MTCC 5856 (SUCRA, 96.9%) and Bacillus coagulans Unique IS2 (SUCRA, 92.6%) were among the most effective probiotics for improving abdominal pain. Three probiotic strains and two mixtures were effective in alleviating abdominal bloating. Four probiotic strains and a mixture were significantly superior to placebo in reducing the bowel movement frequency in diarrhea-predominant IBS (IBS-D). Bacillus coagulans MTCC 5856 (SUCRA, 99.6%) and Saccharomyces cerevisiae CNCM I-3856 (SUCRA, 89.7%) were among the most effective probiotics for improving the Bristol stool form scale of IBS-D. Only some probiotics are effective for particular outcomes in IBS patients. This study provided the first ranking of outcome-specific efficacy of different probiotic strains and combinations in IBS. Further studies are needed to confirm these results.
Background
The incidence and mortality of esophageal cancer are high, with 5.90 new cases and 5.48 deaths per 100 000 people worldwide in 2017. The prognosis of esophageal cancer is poor, with an ...overall 5‐year survival rate of less than 20%. Esophageal cancer in different geographical locations has different etiologies, and the incidence and mortality of esophageal cancer continue to rise in some regions.
Methods
We collected incidence and mortality data by age and gender for 195 countries and territories from 1990 to 2017 in the Global Burden of Disease (GBD) database. And we used these data to calculate the estimated annual percentage change (EAPC) to quantify trends in morbidity and mortality. Then we analyzed the gender‐ and age‐specific incidence and mortality in esophageal cancer to targeted high‐risk populations. Finally, we analyzed the correlation between the age‐standardized mortality rate (ASMR) and both the EAPC and social‐demographic index (SDI), and we calculated the Pearson correlation coefficient.
Results
We found that Malawi, East Asia, and high‐middle SDI regions had the highest age‐standardized incidence rate (ASIR) and ASMR, and the ASIR and ASMR in western Sub‐Saharan Africa showed an upward trend. Our study also showed that the incidence and mortality in esophageal cancer were highest in men and in the 70+ years age group, and they presented a decreasing trend in most regions, but the 15‐49 years age groups in Australasia, Caribbean, and Oceania and the 70+ years age group in High‐Income North America, Oceania and high‐SDI regions presented an increasing trend. There were significant negative associations between ASMR at baseline and EAPC and between ASMR and SDI in 2017.
Conclusion
By analyzing the global distribution of incidence and mortality in esophageal cancer, trends over time, and gender and age specificity, we can understand the heterogeneity of its global trends. This heterogeneity can help us to identify high‐risk groupsand to provide clues for the exploration of the etiology and early prevention of the disease.
Our study explores areas where morbidity and mortality continue to rise, and refines them into populations of different ages and genders. The heterogeneity of the incidence and mortality trends in esophageal cancer means that we can target high‐risk populations and provide clues for the exploration of the etiology and early prevention of the disease.
Structural changes in the gut microbiota are closely related to the development of functional constipation, and regulating the gut microbiota can improve constipation. Rifaximin is a poorly absorbed ...antibiotic beneficial for regulating gut microbiota, but few studies have reported its effects on constipation. The purpose of this study was to investigate the effect of rifaximin on loperamide-induced constipation in SD rats. The results showed that rifaximin improved constipation by increasing serum 5-HT, SP, and the mRNA expression of AQP3, AQP8, and reducing the mRNA expression of TLR2 and TLR4. In addition, rifaximin could regulate the gut microbiota of constipated rats, such as increasing the potentially beneficial bacteria Akkermansia muciniphila and Lactobacillus murinus, reducing the Bifidobacterium pseudolongum. According to metabolomics analysis, many serum metabolites, including bile acids and steroids, were changed in constipated rats and were recovered via rifaximin intervention. In conclusion, rifaximin might improve loperamide-induced constipation in rats by increasing serum excitatory neurotransmitters and neuropeptides, modulating water metabolism, and facilitating intestinal inflammation. Muti-Omics analysis results showed that rifaximin has beneficial regulatory effects on the gut microbiota and serum metabolites in constipated rats, which might play critical roles in alleviating constipation. This study suggests that rifaximin might be a potential strategy for treating constipation.
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The spread of antibiotic resistant pathogens and antibiotic resistance genes (ARGs) in the environment poses a serious threat to public health. However, existing methods are difficult ...to effectively remove antibiotic resistant pathogens and ARGs from the environment. In this study, we synthesized a new acridine-based photosensitizer, 2,7-dibromo-9-mesityl-10-methylacridinium perchlorate (YM-3), by the heavy atom effect, which could photodynamically inactivate antibiotic resistant pathogens and reduce ARGs by generating singlet oxygen (1O2) in an aqueous environment. The 1O2 yield of YM-3 was 4.9 times that of its modified precursor. YM-3 could reduce the culturable number and even the viable counts of methicillin-resistant Staphylococcus aureus and carbapenem-resistant Acinetobacter baumannii to 0 (inactivation rate > 99.99999%) after 2 and 8 h of low-intensity blue light (15 W/m2) irradiation, respectively. After 20 h of light exposure, the copy numbers of ARGs in both bacteria were reduced by 5.80 and 4.48 log, respectively, which might indicate that ARGs had been degraded. In addition, YM-3 still had an efficient bactericidal effect after five inactivation cycle. These characteristics of ultra-low light intensity requirement and efficient bactericidal ability make YM-3 have good application prospects for disinfection in indoor and sunlight environment.
During chronic heart failure, levels of circulating miRNAs endued with characteristics of diseased cells could be identified as biomarkers. In this study, we sought to identify cardiac-related ...circulating miRNAs as biomarkers of failing heart.
Total RNA of plasma and heart samples was extracted from 10 normal controls and 14 patients with chronic heart failure. Microarray was applied for miRNA profiles. Validation and organ/tissue distribution analysis was performed by qRT-PCR. In addition, bioinformatics analysis was performed to understand the critical roles of these cardiac-related circulating miRNAs in heart failure.
Results showed that levels of more than half of the miRNAs dysregulated in heart failed to show any differences in plasma. Meanwhile, more than 90% of the miRNAs dysregulated in plasma remained stable in heart. Four cardiac fibroblast-derived miRNAs (miR-660-3p, miR-665, miR-1285-3p and miR-4491) were found significantly upregulated in heart and plasma during heart failure. These 4 miRNAs strongly discriminated patients from controls, and 3 of them showed significant correlations with LVEF.
This study provides global profiles of miRNAs changes in plasma and failing heart, and using a circulation-tissue miRNA profiling comparison model, we successfully identify 3 cardiac-related circulating miRNAs as potential biomarkers for diagnosis of heart failure.
Diabetes is a leading cause of mortality and morbidity across the world. Over 50% of deaths among diabetic patients are caused by cardiovascular diseases. Cardiac diastolic dysfunction is one of the ...key early signs of diabetic cardiomyopathy, which often occurs before systolic dysfunction. However, no drug is currently licensed for its treatment.
Type 9 adeno-associated virus combined with cardiac Troponin T promoter were employed to manipulate miR-21 expression in the leptin receptor-deficient (db/db) mice. Cardiac structure and functions were measured by echocardiography and hemodynamic examinations. Primary cardiomyocytes and cardiomyocyte cell lines were used to perform gain/loss-of-function assays in vitro.
We observed a significant reduction of miR-21 in the diastolic dysfunctional heart of db/db mice. Remarkably, delivery of miR-21 efficiently protected against the early impairment in cardiac diastolic dysfunction, represented by decreased ROS production, increased bioavailable NO and relieved diabetes-induced cardiomyocyte hypertrophy in db/db mice. Through bioinformatic analysis and Ago2 co-immunoprecipitation, we identified that miR-21 directly targeted gelsolin, a member of the actin-binding proteins, which acted as a transcriptional cofactor in signal transduction. Moreover, down-regulation of gelsolin by siRNA also attenuated the early phase of diabetic cardiomyopathy.
Our findings reveal a new role of miR-21 in attenuating diabetic cardiomyopathy by targeting gelsolin, and provide a molecular basis for developing a miRNA-based therapy against diabetic cardiomyopathy.
Salt-alkali stress represents one of the most stressful events with deleterious consequences for plant growth and crop productivity. Despite studies focusing on the effects of salt-alkali stress on ...morphology and physiology, its molecular mechanisms remain unclear. Here, we employed RNA-sequencing (RNA-seq) to understand how Na
CO
stress inhibits rice seedling growth.
Na
CO
stress significantly inhibited the growth of rice seedlings. Through RNA-seq, many differentially expressed genes (DEGs) were shown to be potentially involved in the rice seedling response to salt-alkali stress. After 1-day and 5-day treatments, RNA-seq identified 1780 and 2315 DEGs in the Na
CO
-treated versus -untreated rice seedling shoots, respectively. According to the gene ontology enrichment and the Kyoto Encylopedia of Genes and Genomes annotation of DEGs, the growth-inhibition processes associated with salt-alkali stress involve a myriad of molecular events, including biosynthesis and metabolism, enzyme activity, and binding, etc. CONCLUSION: Collectively, the transcriptome analyses in the present work revealed several potential key regulators of plant response to salt-alkali stress, and might pave a way to improve salt-alkali stress tolerance in rice.
Vitamin A is a fat-soluble vitamin that is a crucial mediator of the immune system. In this study, we evaluated the effect of oral vitamin A supplementation on host immune responses to infectious ...bronchitis virus (IBV) infection in chickens. Forty 1-day-old specific pathogen-free (SPF) chickens were fed a basal diet and randomly divided into 2 groups (n = 20 birds per group). Chickens in the experimental group were treated orally with vitamin A (dissolved in 0.1 mL soybean oil, at a dose of 8,000 IU per kg diet) daily. Birds in the control group were orally administered 0.1 mL soybean oil without vitamin A until 21 d of age. On d 21 after birth, all chickens were infected with 0.1 mL of 106.5 50% median embryo infectious dose of a pathogenic IBV strain (CK/CH/LDL/091022) by intraocular and intranasal routes. The results demonstrated that oral vitamin A supplementation did not affect the clinical course of disease and growth performance of SPF chickens. However, vitamin A supplementation increased the IBV-specific IgG serum levels and decreased the viral load in some tissues of IBV-infected chickens. In addition, the results demonstrated that vitamin A supplementation decreased the expression levels of most immune-related molecules in some tissues of IBV-infected chickens. Vitamin A supplementation decreased the mRNA expression levels of some avian β-defensins (AvBD2, 3, 6, 7, 11, and 13) and increased the expression levels of AvBD9 and AvBD12 in some tissues of IBV-infected chickens. Similarly, vitamin A supplementation decreased the mRNA expression levels of some cytokines (interferon-γ, interleukin-1β IL-1β, and IL-6) and increased the mRNA expression levels of IL-2 in some tissues of IBV-infected chickens. Furthermore, vitamin A supplementation decreased the mRNA expression levels of myeloid differentiation primary response protein 88, nuclear factor-κB p65, toll-like receptor 3, toll-like receptor 7, and CD4. In summary, the present study suggests that vitamin A supplementation enhances the immune function of SPF chickens against IBV infection by inhibiting viral replication, increasing the IBV-specific antibody titer, and suppressing the excessive inflammatory responses to IBV infection.
Fowl adenovirus serotype 8b (FAdV-8b), as causative agent of inclusion body hepatitis (IBH), poses a great threat to the poultry industry. Considering the importance of innate immune response in host ...against viral infections, we investigated pathogenicity of a FAdV-8b strain HLJ/151129 in 1-mo-old specific pathogen-free (SPF) chickens and immune responses of host to FAdV-8b infection in this study. The results demonstrated that no obvious clinical signs were observed in infected birds. Neither mobility nor mortality was observed in both FAdV-8b infected and control chickens, as well. However, hepatic necrosis and a small amount of inflammatory cell infiltration were observed by pathological analysis. Viral load was detected in bursa of Fabricius, cecal tonsils, liver, heart, spleen, Harderian glands, and thymus. Virus shedding and viremia generated as early as 3 days postinfection (dpi) (9/10) and reached the peak at 7 dpi (10/10). In addition, the infected birds had developed FAdV-specific antibodies at 7 dpi, and the antibody titers reached the peak at 14 dpi. Furthermore, the results demonstrated that the mRNA expression levels of most of toll-like receptors (TLRs), most of avian β-defensins (AvBDs), and cytokines interleukin (IL)-2, IL-6, and interferon (IFN)-γ, were significantly upregulated in most tissues at early phases of FAdV-8b infection, especially in liver and spleen. In contrast, FAdV-8b infection results in downregulation of TLR4, TLR5, and TLR21 expressions in some tissues of infected chickens. In addition, FAdV-8b infection upregulated myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) p65, and TIR-domain-containing adapter inducing interferon-β (TRIF) expression in some tissues, while decreased NF-κBp65 and TRIF in spleen at both 72 hpi and 21 dpi. Taken together, these results confirmed that FAdV-8b could replicate in all investigated tissues of infected birds, and then, result in production of FAdV-specific antibody titers. Meanwhile, the FAdV-8b infection induces strong innate immune responses at early stage in chickens, which may associate with the viral pathogenesis.
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