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Abdominal aortic aneurysm (AAA) is a serious disorder with a high disability rates and mortality rates. Accumulating evidence has identified the vital functions of microRNAs (miRNAs) in the treatment of AAA. Hence, this study is aimed at exploring the modulatory role of miR-194 in the development of AAA.

After the establishment of mouse AAA models, the expression of miR-194 was determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR), while lysine demethylase 3A (KDM3A) was determined by Western blot analysis in vascular smooth muscle cells (VSMCs) from the abdominal aorta. Cell apoptosis, levels of inflammatory factors as well as expressions of matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9) were measured after altering the expression of miR-194 and KDM3A in VSMCs. Moreover, the interactions among miR-194, KDM3A, and BCL2 interacting protein 3 (BNIP3) were investigated by chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter gene assay.

miR-194 was poorly expressed while the expression of KDM3A was up-regulated in mice with AAA. miR-194 inhibited the expression of KDM3A while BNIP3 was positively mediated by KDM3A. More importantly, the number of macrophages was significantly reduced whereas the rate of apoptosis in VSMCs was enhanced. miR-194 reduced the inflammatory response and oxidative stress by repressing KDM3A-mediated BNIP3 expression.

miR-194 played a suppressive role in the progression of AAA by inhibiting the expression of BNIP3 via KDM3A, representing a promising target for AAA management.

miR-194 played a suppressive role in the progression of AAA by inhibiting the expression of BNIP3 via KDM3A, representing a promising target for AAA management.The current study examined the role of sex differences in the development of risk factors associated with obesity and its comorbidities using models that differ in their susceptibility to develop obesity, obesity-resistant S5B/Pl (S5B) and obesity-prone Osborne-Mendel (OM) rats. Male and female rats were fed a low fat or high fat diet (HFD) and markers of metabolic syndrome (MetSyn) and expression of inflammatory cytokines/chemokines in visceral and subcutaneous adipose depots were measured. We hypothesized that male and female OM and S5B rats would exhibit differential responses to the consumption of HFD and that females, regardless of susceptibility to develop obesity, would display decreased obesity-related risk factors. Results suggested that consumption of HFD increased adiposity and fasting glucose levels in male OM and S5B rats, decreased circulating adiponectin levels in male S5B rats, and increased body weight and triglyceride levels in male OM rats. The consumption of HFD increased body weight and adiposity in female OM rats, not female S5B rats. Overall, female rats did not meet criteria for MetSyn, while male rats consuming HFD met criteria for MetSyn. Visceral and subcutaneous adipose tissue inflammation was higher in male rats. In visceral adipose tissue, HFD consumption differentially altered expression of cytokines in male and female S5B and OM rats. These findings suggest that resistance to obesity in males may be overridden by chronic consumption of HFD and lead to increased risk for development of obesity-related comorbidities, while female rats appear to be protected from the adverse effects of HFD consumption.

Hepatic ischemia/reperfusion (I/R) injury is a critical factor affecting the prognosis of liver surgery. The aim of this study is to explore the effects of SET8 on hepatic I/R injury and the putative mechanisms.

The expression of SET8 and MARK4 in I/R group and sham group were detected both in vivo and in vitro. In addition, mouse and RAW 264.7 cells were transfected with MARK4 siRNA and SET8 siRNA knockdown of MARK4 and SET8, respectively. The expression of SET8, MARK4 and NLRP3-associated proteins were detected after different treatments. The pathology of liver and the serologic detection were detected after different treatments.

Our present study identified SET domain-containing protein 8 (SET8) as an efficient protein, which can negatively regulate hepatic I/R-mediated inflammatory response and ameliorate hepatic I/R injury by suppressing microtubule affinity-regulating kinase 4 (MARK4)/ NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway. The data showed that MARK4 deficiency inhibited hypoxia/reoxygenation (H/R)-induced NLRP3 inflammasome activation, while SET8 deficiency showed the opposite effect. We further demonstrated that SET8 restrained NLRP3 inflammasome activation by inhibiting MARK4. Moreover, we verified SET8 made protective effect on hepatic I/R injury.

SET8 plays an essential role in hepatic ischemia/reperfusion injury in mice by suppressing MARK4/NLRP3 inflammasome pathway. Our results may offer a new strategy to mitigate hepatic I/R injury.

SET8 plays an essential role in hepatic ischemia/reperfusion injury in mice by suppressing MARK4/NLRP3 inflammasome pathway. ABL001 cell line Our results may offer a new strategy to mitigate hepatic I/R injury.Type 2 diabetes mellitus is the most prevalent metabolic disorder characterized by hyperglycemia, hyperlipidemia as well as insulin resistance and is affecting the lives of a huge population across the globe. Genetic mutations, obesity and lack of physical activity constitute the possible factors that can lead to onset and progression of this disorder. However, there is another major factor that can be the root cause of type 2 diabetes mellitus and that is an imbalance in the microorganisms that inhabit the gut. The gut microbiome is a vital component that needs to be given significant attention because any “dysbiosis” in the colonic microorganisms can transform the host from a state of health to a state of disease. This transformation is quite obvious since the gut barrier integrity, host metabolism such as sensitivity to insulin and maintaining blood glucose level are carried out by the tiny organisms inhabiting our intestine. In fact, the normal functioning of the human body is accredited to the microbes, particularly the bacteria, because they generate their metabolites that communicate with host cells and maintain normal physiology.