Zachohart4665

or the treatment of NAFLD in offspring caused by maternal obesity.Cardiac fibrosis is a primary event during myocardial infarction (MI) progression, which impairs cardiac function. The present study aimed to investigate the effect of SGLT2 on cardiac fibrosis following MI. To validate the role of SGLT2 in the regulation of cardiac fibrosis in vivo, an MI rat model was established. Echocardiography was performed to determine cardiac function at 4 weeks post-MI. Acalabrutinib price MI model rats were transfected with short hairpin RNA (sh)-SGLT2 or sh-negative control lentiviruses to investigate the effect of SGLT2 on rat heart function post-MI. Subsequently, the effects of SGLT2 on the cardiac fibrosis of infarcted hearts were assessed by performing Masson's trichrome staining. To further clarify the effect of SGLT2 on cardiac fibroblast proliferation, TGFβ was used to stimulate primary cardiac fibroblasts in vitro. The results demonstrated that SGLT2 served a key role in cardiac fibrosis. SGLT2 expression levels in infarct tissues were significantly increased at week 1 post-MI compared with the sham group. Compared with the control group, SGLT2 knockdown attenuated cardiac fibrosis by inhibiting the expression of collagen I and collagen III in cardiac fibroblasts in vitro and in vivo. Furthermore, the results indicated that SGLT2 expression was modulated by miR-141 in cardiac fibroblasts. In summary, the present study indicated that upregulated SGLT2 expression in cardiac fibrosis following MI was regulated by miR-141 and SGLT2 that knockdown reduced cardiac fibrosis and improved cardiac function after MI.Morphine has been widely used for the treatment of pain and extensive studies have revealed a regulatory role for morphine in cell apoptosis. However, the molecular mechanisms underlying morphine-mediated apoptosis remain to be fully elucidated. The present study aimed to investigate the effects of morphine on lipopolysaccharide (LPS)-induced bone marrow-derived macrophage (BMDM) apoptosis and to determine the role of the peroxisome proliferator-activated receptor (PPAR)γ signaling pathway in this process. BMDMs were isolated from BALB/c mice and stimulated with LPS. Hoechst 33342 staining and flow cytometric analysis were performed to evaluate the effects of morphine on LPS-induced apoptosis of BMDMs. Caspase activity assays were used to determine the involvement of the apoptosis pathway. The expression levels of caspase-3, caspase-8, caspase-9 and PPARγ were analyzed using western blotting. Finally, GW9662, a specific PPARγ antagonist, was used to determine whether the regulatory effects of morphine on LPS-induced BMDM apoptosis were PPARγ-dependent. The results of the present study revealed that morphine increased the apoptosis of LPS-stimulated BMDMs. Morphine upregulated the expression levels and activity of caspase-3 in LPS-stimulated BMDMs, but downregulated the expression levels and activity of caspase-8. Morphine treatment also upregulated LPS-induced PPARγ expression levels in BMDMs. Finally, the stimulatory effects of morphine on LPS-induced apoptosis and caspase-3/9 activation were markedly reduced by GW9662. In conclusion, the findings of the present study indicated that morphine significantly promoted LPS-induced BMDM apoptosis and caspase-3/9 activation. These results suggested that the intrinsic pathway of apoptosis may be involved in the proapoptotic effects of morphine on LPS-stimulated BMDMs, which may be dependent, at least partially, on PPARγ activation.A novel tri-layer membrane consisting of polycaprolactone (PCL) fibrous sheets and structured nanofibers with a gelatin (Gt) shell and a simvastatin-containing PCL core (PCL-Gt/PCL-simvastatin membrane) was prepared. The soft external layer comprised of Gt/PCL-simvastatin, the external layer of PCL and the middle layer of both microfilaments, interwoven together. The membrane was designed to promote osteoinduction and act as a barrier against cells but not against water and molecules in order to promote guided bone regeneration. The structure of the membrane was characterized by scanning electronic microscopy. The in vitro release rates of simvastatin over 32 days were determined by high-performance liquid chromatography. For in vitro biological assays, bone marrow mesenchymal stem cells and human fibroblasts were cultured on the different surfaces of the membrane. Cell adhesion, proliferation, distribution, and differentiation were examined. For in vivo testing, cranial defects were created in rabbits to assess the amount of new bone formed for each membrane. The results revealed that membranes with multi-layered structures showed good cell viability and effective osteoinductive and barrier properties. These results suggest that the novel multi-layered PCL-Gt/PCL-simvastatin membranes have great potential for bone tissue engineering.Aseptic loosening is a major complication of prosthetic joint surgery. The leading cause of arthroplasty failure is particulate wear debris such as titanium particles. Dendritic cells (DCs) are one type of immune cells that play an important role in the initiation and progression of inflammatory processes. DCs can develop into tolerogenic DCs (tolDCs), which present an alternative therapeutic strategy for inflammatory disorders. Previously, antigen-specific tolDCs were generated, which showed a promising effect in treating inflammatory arthritis and immune thrombocytopenia. The present study reports that tolDCs effectively inhibited titanium particle-induced inflammation in an air-pouch mouse model by decreasing pro-inflammatory cytokines. In addition, a mechanistic study demonstrated that tolDCs significantly protected against titanium particle-induced inflammatory processes in vitro by releasing anti-inflammatory cytokines, such as interleukin-10. Collectively, these findings not only demonstrate that tolDCs play an important role in inhibiting titanium particle-induced inflammation but also provide a potential alternative for the prevention or treatment of titanium particle-induced inflammation.STAT3 is expressed in neural stem cells (NSCs), where a number of studies have previously shown that STAT3 is involved in regulating NSC differentiation. However, the possible molecular mechanism and role of STAT3 in spinal cord injury (SCI) remain unclear. In the present study, the potential effect of STAT3 in NSCs was first investigated by using short hairpin RNA (shRNA)-mediated STAT3 knockdown in rat NSCs in vitro. Immunofluorescence of β3-tubulin and glial fibrillary acidic protein staining and western blotting showed that knocking down STAT3 expression promoted NSC neuronal differentiation, where the activity of mTOR was upregulated. Subsequently, rats underwent laminectomy and complete spinal cord transection followed by transplantation of NSCs transfected with control-shRNA or STAT3-shRNA at the injured site in vivo. Spinal cord-evoked potentials and the Basso-Beattie-Bresnahan scores were used to examine functional recovery. In addition, axonal regeneration and tissue repair were assessed using retrograde tracing with FluoroGold, hematoxylin and eosin, Nissl and immunofluorescence staining of β3-tubulin, glial fibrillary acidic protein and microtubule-associated protein 2 following SCI. The results showed that transplantation with NSCs transfected with STAT3-RNA enhanced functional recovery following SCI and promoted tissue repair in rats, in addition to improving neuronal differentiation of the transplanted NSCs in the injury site. Taken together, in vitro and in vivo evidence that inhibiting STAT3 could promote NSC neuronal differentiation was demonstrated in the present study. Therefore, transplantation with NSCs with STAT3 expression knocked down appears to hold promising potential for enhancing the benefit of NSC-mediated regenerative cell therapy for SCI.Autophagy is a self-digestion process in cells that can maintain energy homeostasis under normal circumstances. However, misfolded proteins, damaged mitochondria and other unwanted components in cells can be decomposed and reused via autophagy in some specific cases (including hypoxic stress, low energy states or nutrient deprivation). Therefore, autophagy serves a positive role in cell survival and growth. However, excessive autophagy may lead to apoptosis. Furthermore, abnormal autophagy may lead to carcinogenesis and promote tumorigenesis in normal cells. In tumor cells, autophagy may provide the energy required for excessive proliferation, promote the growth of cancer cells, and evade apoptosis caused by certain treatments, including radiotherapy and chemotherapy, resulting in increased treatment resistance and drug resistance. On the other hand, autophagy leads to an insufficient nutrient supply in cancer cells and the destruction of energy homeostasis, thereby inducing cancer cell apoptosis. Therefore, understanding the mechanism of the double-edged sword of autophagy is crucial for the treatment of cancer. The present review summarizes the signaling pathways and key factors involved in autophagy and cancer to provide possible strategies for treating tumors.Anti-angiogenesis therapy is a novel treatment method for malignant tumors. Endothelial cell (EC) migration is an important part of angiogenesis. Dihydroartemisinin (DHA) exhibits strong anti-angiogenic and anti-EC migration effects; however, the underlying molecular mechanisms are yet to be elucidated. The TGF-β1/activin receptor-like kinase 5 (ALK5)/SMAD2 signaling pathway serves an important role in the regulation of migration. The present study aimed to explore the effects of DHA treatment on EC migration and the TGF-β1/ALK5/SMAD2 signaling pathway. The effects of DHA on human umbilical vein EC migration were assessed using wound healing and Transwell assays. The effects of DHA on the TGF-β1/ALK5/SMAD2 signaling pathway were detected using western blotting. DHA exhibited an inhibitory effect on EC migration in the wound healing and Transwell assays. DHA treatment upregulated the expression levels of ALK5 and increased the phosphorylation of SMAD2 in ECs. SB431542 rescued the inhibitory effect of DHA during EC migration. DHA inhibited EC migration via the TGF-β1/ALK5/SMAD2-dependent signaling pathway, and DHA may be a novel drug for the treatment of patients with malignant tumors.Chronic intermittent hypoxia (CIH) has been shown to induce cell apoptosis in multiple organs of the human body. The present study aimed to assess the effects of exogenous klotho on CIH-induced genioglossus muscle injury, as well as the involvement of endoplasmic reticulum stress (ERS) in this process. A total of 36 adult C57BL/6 male mice were assigned to normoxia control (NC), CIH and CIH + klotho groups (n=12 mice/group). ELISA was performed to detect the level of klotho protein in the serum and in the genioglossus muscle tissue samples. Apoptosis was evaluated using the TUNEL assay. Reactive oxygen species (ROS) levels were quantified using a dihydroethidium assay kit, and the protein and mRNA levels of ERS-associated proteins (namely, glucoseregulated protein 78, C/EBP homologous protein, cleaved caspase-12 and cleaved caspase-3) in genioglossus samples were assessed using immunoblot assay and reverse transcription-quantitative PCR, respectively. Compared with the NC group, the quantities of klotho protein in the serum and genioglossus muscle tissue samples in the CIH group were significantly decreased, whereas the apoptotic rate, ROS levels and protein and mRNA levels of the ERS-associated proteins in the genioglossus muscle were significantly increased.