Experimental Biology and Medicine最新文献

The influences of TRIM28 on the gastric tumorigenesis together with potential molecular mechanisms remain to be studied. We aimed at exploring the important effects of TRIM28 on gastric cancer (GC) and uncovering underling molecular mechanisms. Through immunohistochemistry analysis of 20 pairs of GC and the peritumoral tissues, the expression level of TRIM28 was determined. A variety of assays were applied to explore the important roles of TRIM28 in GC. Western blotting and qRT-PCR analyses were used to analyze the association between TRIM28 and the Wnt/β-catenin signaling pathway. TRIM28 was highly expressed in GC tissues than peritumoral tissues. And high expression level of TRIM28 in GC was associated with good prognostic effects. In vitro functional assays suggested TRIM28 knockdown enhanced the proliferation and clone formation of GC cell. Moreover, TRIM28 knockdown enhanced the expression level of stemness markers, strengthened sphere-forming and drug-resistance properties of GC cells, suggesting important effect on GC cell stemness. Besides, our analysis showed that the Wnt/β-catenin signaling was involved in the effect of TRIM28 on GC cell stemness property, and blocking Wnt/β-catenin signaling pathway obviously rescued the promotion influence of TRIM28 knockdown. Overall, TRIM28 has an important influence on regulating the stem-like property of GC cell via Wnt/β-catenin signaling, suggesting TRIM28 a promising drug target and a potential predictor of prognosis.

Chemokines critically orchestrate the tumorigenesis, metastasis, and stemness features of cancer cells that lead to poor outcomes. High plasma levels of transforming growth factor-β1 (TGFβ1) correlate with poor prognostic features in advanced lung cancer patients, thus suggesting the importance of TGFβ1 in the lung tumor microenvironment. However, the role of chemokines in TGFβ1-induced tumor stemness features remains unclear. Here, we clarify the previously undocumented role of CXCL1 in TGFβ1-induced lung cancer stemness features. CXCL1 and its receptor CXCR2 were significantly upregulated in TGFβ1-induced lung cancer stem cells (CSCs). CXCL1 silencing (shCXCL1) suppressed stemness gene expression, tumorsphere formation, colony formation, drug resistance, and in vivo tumorigenicity in TGFβ1-induced lung tumorspheres. Immunohistochemistry staining showed that patients with stage II/III lung cancer had higher expression levels of CXCL1. The levels of CXCL1 were positively associated with lymph node metastasis and correlated with the expression of the CSC transcription factor Oct-4. Furthermore, online database analysis revealed that CXCL1 expression was negatively correlated with lung cancer survival in patients. Patients with high TGFβ1/CXCL1/CD44 co-expression had a worse survival rate. We suggest that CXCL1 serves as a crucial factor in TGFβ1-induced stemness features of lung cancer.

In clinical trials, rhubarb extract (Rb) was demonstrated to efficiently alleviate constipation. We would like to find out the underlying mechanism of rhubarb relieving constipation. However, there are few studies on the effects of rhubarb on colonic mucus secretion and constipation. The aim of this study was to investigate the effects of rhubarb on colonic mucus secretion and its underlying mechanism. The mice were randomly divided into four groups. Group I was the control group and Group II was the rhubarb control group, with Rb (24 g/kg body weight [b.w.]) administered through intragastric administration for three days. Group III mice were given diphenoxylate (20 mg/kg b.w.) for five days via gavage to induce constipation. Group IV received diphenoxylate lasting five days before undergoing Rb administration for three days. The condition of the colon was evaluated using an endoscope. Particularly, the diameter of blood vessels in the colonic mucosa expanded considerably in constipation mice along with diminishing mucus output, which was in line with the observation via scanning electron microscope (SEM) and transmission electron microscope (TEM). We also performed metagenomic analysis to reveal the microbiome related to mucin gene expression level referring to mucin secretion. In conclusion, Rb relieves constipation by rebuilding mucus homeostasis and regulating the microbiome.

Bayesian networks are increasingly used to quantify the uncertainty of subjective and stochastic concepts such as trust. In this article, we propose a data-driven approach to estimate Bayesian parameters in the domain of wearable medical devices. Our approach extracts the probability of a trust factor being in a specific state directly from the devices (e.g. sensor quality). The strength of the relationship between related factors is defined by expert knowledge and incorporated into the model. We use propagation rules from requirements engineering to estimate how much each trust factor contributes to the related intermediate nodes in the network and ultimately compute the trust score. The trust score is a relative measure of trustworthiness when different devices are evaluated in the same test conditions and using the same Bayesian structure. To evaluate our approach, we developed Bayesian networks for the trust quantification of similar wearable devices from two manufacturers under identical test conditions and noise levels. The results demonstrated the learnability and generalizability of our approach.

Acute lung injury (ALI) caused by endotoxin represents one of the common clinical emergencies. Mitochondria-associated endoplasmic reticulum membranes (MAM) serve as a critical link between mitochondria and endoplasmic reticulum (ER), which has an essential effect on maintaining intracellular homeostasis. As an important component of MAM, type-1 inositol-1,4,5-trisphosphate receptor (IP3R-1) mediates the ER-to-mitochondrial transport of Ca²⁺. This study explored the role of IP3R-1 and MAM in ALI. Besides the levels of inflammasome-associated components interleukin (IL)-6, tumor necrosis factor (TNF)-α, and malonyldialdehyde (MDA) were increased in both bronchoalveolar lavage fluid (BALF) and serum, increased cross-sectional area of mitochondria, elevated MAM formation, and decreased respiratory control ratio (RCR) were observed within lung tissues collected in lipopolysaccharide (LPS)-treated mice, accompanied by upregulation of IP3R-1 in total lung lysates and MAM. Ca²⁺ uptake level in the mitochondria, production of reactive oxygen species (ROS) in the mitochondria, and the formation of MAM were elevated within LPS-treated MLE-12 cells, and all those changes in response to LPS were partly inhibited by knocking down of IP3R-1 expression in MLE-12 cells. Collectively, IP3R-1 has a critical effect on MAM formation and mitochondrial dysfunction, which could be innovative therapeutic targets for ALI caused by endotoxin.

This study was conducted to compare the impact of cinnamon silver nanoparticles (C-Ag-NPs) and cinnamon aqueous extract (CAE) on the total body weight (TBW), body weight gain (BWG), blood count (BC), fasting blood glucose (FBG), triglycerides (TGs), total cholesterol (TC), low-density (LDL-C) and high-density (HDL-C) lipoprotein cholesterol, liver function enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) of normal and streptozotocin (STZ) diabetic rats. The CAE was administered to rats at different doses (50.0 and 100.0 mg/kg bw), whereas the C-Ag-NPs were ingested at doses of 25.0 and 50.0 mg/kg bw for 30 days. At the end of the experiment, the administration of high or low dosages of CAE or C-Ag-NPs to diabetic rats significantly reduced the FBG, TC, TG, and LDL-C and significantly increased the HDL-C compared with the diabetic control rats. The highest dose (50.0 mg/kg bw) of the C-Ag-NPs was the most efficient at significantly reducing (P < 0.05) the levels of all the analyzed parameters compared with the CAE. However, the treated and normal rats did not show any hypoglycemic activity after ingesting the CAE or C-Ag-NPs. Such effects were associated with considerable increases in their BWG. The diabetic rats that ingested the CAE or C-Ag-NPs showed a gradual decrease in their FBG, TC, LDL, and TG levels, but they were still higher than those in the normal rats. Furthermore, the C-Ag-NPs and CAE considerably enhanced the hepatic (GPT, GOT, ALP, and GGT) and antioxidant biomarker enzyme activities (SOD, CAT, and GPx) in diabetic rats. Relative to the untreated diabetic control, the C-Ag-NPs were more effective than the CAE in the diabetic rats. The C-Ag-NPs exhibited a protective role against hyperglycemia and hyperlipidemia in the diabetic rats and modulated their liver function enzyme biomarkers and antioxidant enzyme activities more than the CAE.

This study tested whether combined dapagliflozin and entresto would be superior to mere one therapy on protecting the residual renal function and integrity of kidney parenchyma in hypertensive kidney disease (HKD) rat. In vitro results showed that the protein expressions of oxidative-stress/mitochondrial-damaged (NOX-1/NOX-2/oxidized-protein/cytosolic-cytochrome-C)/apoptotic (mitochondrial-Bax/cleaved caspeases 3, 9)/cell-stress (p-ERK/p-JNK/p-p38) biomarkers were significantly increased in H₂O₂-treated NRK-52E cells than those of controls that were reversed by dapagliflozin or entresto treatment. Adult-male SD rats (n = 50) were equally categorized into group 1 (sham-operated-control), group 2 (HKD by 5/6 nephrectomy + DOCA-salt/25 mg/kg/subcutaneous injection/twice weekly), group 3 (HKD + dapagliflozin/orally, 20 mg/kg/day for 4 weeks since day 7 after HKD induction), group 4 (HKD + entresto/orally, 100 mg/kg/day for 4 weeks since day 7 after HKD induction), and group 5 (HKD + dapagliflozin + entresto/the procedure and treatment strategy were identical to groups 2/3/4). By day 35, circulatory levels of blood-urine-nitrogen (BUN)/creatinine and urine protein/creatinine ratio were lowest in group 1, highest in group 2, and significantly lower in group 5 than in groups 3/4, but no difference between groups 3/4. Histopathological findings showed the kidney injury score/fibrotic area/cellular expressions of oxidative-stress/kidney-injury-molecule (8-OHdG+/KIM-1+) exhibited an identical trend, whereas the cellular expressions of podocyte components (synaptopodin/ZO-1/E-cadherin) exhibited an opposite pattern of BUN level among the groups. The protein expressions of oxidative stress/mitochondrial-damaged (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D)/apoptotic (mitochondrial-Bax/cleaved-caspase 3)/mitochondrial-fission (PINK1/Parkin/p-DRP1)/autophagic (LC3BII/LC3BI ratio, Atg5/beclin-1)/MAPK-family (p-ERK/p-JNK/p-p38) biomarkers displayed a similar pattern, whereas the protein expression of mitochondria-biogenesis signaling (SIRT1/PGC-1α-Mfn2/complex I-V) displayed an opposite pattern of BUN among the groups. In conclusion, combined dapagliflozin-entresto therapy offered additional benefits on protecting the residual kidney function and architectural integrity in HKD rat.