Modulation of adipose tissue metabolism by microbial-derived metabolites

Obesity and its complications, including type 2 diabetes, cardiovascular disease, and certain cancers, have posed a significant burden on health and healthcare systems over the years due to their high prevalence and incidence. Gut microbial derivatives are necessary for the regulation of energy metabolism and host immunity, as well as for maintaining homeostasis of the intestinal environment. Gut flora metabolites may be a link between gut microbes and diseases, such as obesity, and help understand why alterations in the microbiota can influence the pathophysiology of human disease. This is supported by emerging evidence that microbial-derived metabolites, such as short-chain fatty acids, bile acids, tryptophan, trimethylamine-N-oxide, and lipopolysaccharides, can be beneficial or detrimental to the host by affecting organs outside the gut, including adipose tissue. Adipose tissue is the largest lipid storage organ in the body and an essential endocrine organ that plays an indispensable role in the regulation of lipid storage, metabolism, and energy balance. Adipose tissue metabolism includes adipocyte metabolism (lipogenesis and lipolysis), thermogenesis, and adipose tissue metabolic maladaptation. Adipose tissue dysfunction causes the development of metabolic diseases, such as obesity. Here, we review the current understanding of how these microbial metabolites are produced and discuss both established mechanisms and the most recent effects of microbial products on host adipose tissue metabolism. We aimed to identify novel therapeutic targets or strategies for the prevention and treatment of obesity and its complications

MiRNA-145 increases therapeutic sensibility to gemcitabine treatment of pancreatic adenocarcinoma cells.

Pancreatic adenocarcinoma is one of the most leading causes of cancer-related deaths worldwide. Although recent advances provide various treatment options, pancreatic adenocarcinoma has poor prognosis due to its late diagnosis and ineffective therapeutic multimodality. Gemcitabine is the effective first-line drug in pancreatic adenocarcinoma treatment. However, gemcitabine chemoresistance of pancreatic adenocarcinoma cells has been a major obstacle for limiting its treatment effect. Our study found that p70S6K1 plays an important role in gemcitabine chemoresistence. MiR-145 is a tumor suppressor which directly targets p70S6K1 for inhibiting its expression in pancreatic adenocarcinoma, providing new therapeutic scheme. Our findings revealed a new mechanism underlying gemcitabine chemoresistance in pancreatic adenocarcinoma cells

Effect of Baicalin on inflammatory mediator levels and microcirculation disturbance in rats with severe acute pancreatitis

Objective: To investigate the effect of Bacailin on inflammatory mediator levels and microcirculation disturbance in severe acute pancreatitis (SAP) rats and explore its therapeutic mechanism on this disease. Methods: SAP model rats were randomly divided into model control group and Baicalin treated group, 45 rats in each group. The same number of normal rats were included in sham-operated group. These groups were further subdivided into 3 h, 6 h and 12 h subgroups, respectively (15 rats in each subgroup). At 3, 6 and 12 hours after operation, rats were killed to conduct the following experiments: (1) to examine the mortality rates of rats, the ascites volume and pancreatic pathological changes in each group; (2) to determine the contents of amylase, PLA~2~, TXB~2~, PGE~2~, PAF and IL-1[beta]; in blood as well as the changes in blood viscosity.Results: (1) Compared to model control group, treatment with Baicalin is able to improve the pathological damage of the pancreas, lower the contents of amylase and multiple inflammatory mediators in blood, decrease the amount of ascitic fluid and reduce the mortality rates of SAP rats; (2) at 3 hours after operation, the low-shear whole blood viscosity in Baicalin treated group was significantly lower than that in model control group;at 12 hours after operation, both the high-shear and low-shear whole blood viscosity in Baicalin treated group were also significantly lower than those in model control group.Conclusion: Baicalin, as a new drug, has good prospects in the treatment of SAP since it can exert therapeutic effects on this disease through inhibiting the production of inflammatory mediators, lowering blood viscosity, improving microcirculation and mitigating the pathological damage of the pancreas

The hygroscopicity of moso bamboo (Phyllostachys edulis) with a gradient fiber structure

This article studies the hygroscopicity of moso bamboo (Phyllostachys edulis) with a gradient fiber structure assessed by a dynamic vapor sorption (DVS) apparatus and fitted with a Haillwood–Horrobin (H–H) model. The effects of the chemical composition, gradient fiber structure, and mesopore structure of the bamboo were also investigated. The results demonstrate that the hygroscopicity of bamboo gradually increases from the outer to the inner layer along the thickness of the culm wall, which is related to the gradient distribution of the fibers. The structure–function relationships between the chemical composition, multi-scale structure, and hygroscopicity identified in this study provide a theoretical basis for bamboo drying and storage technology, as well as the processing and application of bamboo fiber-based composites

Corticosteroids for the prevention of bronchopulmonary dysplasia in preterm infants: a network meta-analysis

Objective: To determine the comparative efficacy and safety of corticosteroids in the prevention of bronchopulmonary dysplasia (BPD) in preterm infants.  Study design: We systematically searched PubMed, EMBASE and the Cochrane Library. Two reviewers independently selected randomised controlled trials (RCTs) of postnatal corticosteroids in preterm infants. A Bayesian network meta-analysis and subgroup analyses were performed.  Results: We included 47 RCTs with 6747 participants. The use of dexamethasone at either high dose or low dose decreased the risk of BPD (OR 0.29, 95% credible interval (CrI) 0.14 to 0.52; OR 0.58, 95% CrI 0.39 to 0.76, respectively). High-dose dexamethasone was more effective than hydrocortisone, beclomethasone and low-dose dexamethasone. Early and long-term dexamethasone at either high dose or low dose decreased the risk of BPD (OR 0.11, 95% CrI 0.02 to 0.4; OR 0.37, 95% CrI 0.16 to 0.67, respectively). There were no statistically significant differences in the risk of cerebral palsy (CP) between different corticosteroids. However, high-dose and long-term dexamethasone ranked lower than placebo and other regimens in terms of CP. Subgroup analyses indicated budesonide was associated with a decreased risk of BPD in extremely preterm and extremely low birthweight infants (OR 0.60, 95% CrI 0.36 to 0.93).  Conclusions: Dexamethasone can reduce the risk of BPD in preterm infants. Of the different dexamethasone regimens, aggressive initiation seems beneficial, while a combination of high-dose and long-term use should be avoided because of the possible adverse neurodevelopmental outcome. Dexamethasone and inhaled corticosteroids need to be further evaluated in large-scale RCTs with long-term follow-ups

Effect of p21Waf1 and p27Kip1 on centrosome replication and proliferation of breast cancer cell

Aberrant centrosome numbers are detected in virtually all cancers，increasing the risk for cell division errors and chromosomal instability. Deregulation of the centrosome duplication cycle is considered as the major contributing factor for abnormal amplification of centrosomes. p21Waf1 and p27Kip1, general CDK inhibitors by inhibiting cyclin-dependent kinase 2 (CDK2)/cyclin E and cyclin A complexes, controlled the initiation and progress of centrosome duplication . We transfected p21 Waf1, p27 Kip1 or p21 Waf1- p27 Kip1 genes into MCF-7 cells by lipofection to explore the effect of the genes on centrosome duplication and proliferation of breast cancer cell. The result shows that the cell growth was obviously inhibited after being transfected, resulting in an accumulation of cells in G1 and the proportion of cells which contained abnormal centrosomes was obviously decreased. Comparing with p21 Waf1or p27 Kip1, the effects of p21Waf1- p27 Kip1 genes are more significative. These results suggest that p21Waf1 and p27Kip1 genes could inhibit the growth of human breast cancer cells and reverse abnormal duplication of centrosomes. p21Waf1 and p27Kip1 cooperate to regulate centrosome duplication and cell cycle progress, indicating p21 Waf1- p27 Kip1 combined gene might be potential therapeutic agents of breast cancer which reveals suppressed p21Waf1 and p27Kip1 expression

Deficiency of Mkrn2 causes abnormal spermiogenesis and spermiation, and impairs male fertility.

Although recent studies have shed insights on some of the potential causes of male infertility, new underlining molecular mechanisms still remain to be elucidated. Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. We developed an Mrkn2 knockout mouse model to study the role of this gene, and found that deletion of Mkrn2 in mice led to male infertility. Mkrn2 knockout mice produced abnormal sperms characterized by low number, poor motility, and aberrant morphology. Disruption of Mkrn2 also caused failure of sperm release (spermiation failure) and misarrangement of ectoplasmic specialization (ES) in testes, thus impairing spermiogenesis and spermiation. To understand the molecular mechanism, we found that expression of Odf2, a vital protein in spermatogenesis, was significantly decreased. In addition, we found that expression levels of Odf2 were decreased in Mkrn2 knockout mice. We also found that MKRN2 was prominently expressed in the sperm of normal men, but was significantly reduced in infertile men. This result indicates that our finding is clinically relevant. The results of our study provided insights into a new mechanism of male infertility caused by the MKRN2 downregulation