Refsgaardkirkeby3462

Although increasing evidence shows that the adipokine chemerin is involved in diabetic kidney disease (DKD), it is still unclear whether the chemerin acts as a critical element in renal function through the signaling pathways of transforming growth factor β1/Smads/connective tissue growth factor (TGF-β1/Smads/CTGF) in the context of DKD. Therefore, we sought to determine the role of chemerin and TGF-β1/Smads/CTGF signaling pathway in the development and/or progression of DKD.

We used rat renal mesangial cells (RMCs) and a DKD rat model as study subjects. RMCs and rats were randomly separated into different groups and transfected with the constructed chemerin expression vector pcDNA™ 3.1 (+)-chemerin. Rat renal function and inflammatory cytokines were assessed after treatment with chemerin or CCX832 (ChemR23 antagonist). Real time polymerase chain reverse transcription (RT-QPCR) was used to detect the mRNA expressions of TGF-β1, Smad2, Smad4, and CTGF. Cyclopamine in vivo Western blot was performed to determine protein expresgroup and the DKD chemerin group (all P<0.05). In contrast to those in the normal control group and blocked receptor group, tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1 showed higher concentrations in the DKD group and the normal chemerin group. This result was more pronounced in the DKD chemerin group (all P<0.05).

Chemerin may play a role in DKD by enhancing the signaling pathways of TGF-β1/Smads/CTGF transduction either in vitro or in vivo. Moreover, high glucose accelerates kidney injury by activating fibrotic pathways.

Chemerin may play a role in DKD by enhancing the signaling pathways of TGF-β1/Smads/CTGF transduction either in vitro or in vivo. Moreover, high glucose accelerates kidney injury by activating fibrotic pathways.Lung cancer is among the diseases with the highest rates of morbidity and mortality. Our previous study found that a novel biguanide derivative, 1-n-heptyl-5-(3, 4-difluorophenyl) biguanide (8e) shows excellent anti-proliferative activity in non-small cell lung cancer (NSCLC) cell line A549. However, the underlying mechanism remains elusive. In this research, we analyzed the effect of 8e on NSCLC cell lines and explored the cell death mechanism caused by 8e. From our data, we found that 8e significantly decreased the cell activity and inhibited the colony formation of A549 and H1299 cells in a dose-dependent manner. Interestingly, this inhibitory effect of 8e was significantly reduced after silencing EGFR with lentiviral vectors. In contrast, after overexpressing EGFR in A549 and H1299, the lethality of 8e to the tumor cells increased. Simultaneously, we observed that 8e inhibited the expression of EGFR and its two essential downstream signaling pathways, AKT/mTOR and c-Raf/ERK1/2, and significantly reduced the activation of the EGFR pathway induced by EGF. Therefore, the results showed that 8e inhibits the proliferation of NSCLC cells by down-regulating the expression of EGFR, thereby inhibiting the downstream signaling pathway AKT/mTOR and c-Raf/ERK1/2. In addition, 8e also markedly reduces migration and induces the apoptosis of A549 and H1299 cells. In vivo results based on a lung cancer cell transplanted xenograft mouse model have further shown that 8e blocks A549 tumor growth without any significant hepatotoxicity or nephrotoxicity. These results indicate the high potential value of 8e as a candidate for treating NSCLC.

Osteosarcoma is a malignant bone tumor consisting of mesenchymal cells. This study aimed to investigate the inhibitory effects of human bone marrow mesenchymal stem cell (hBMSC)-derived miR-1913 on osteosarcoma.

Cell viability was determined using CCK8 and colony formation assays. The cell migration and invasion abilities were assessed using wound healing and transwell assays. RT-qPCR and western blot were used to measure the miR-1913, Neurensin-2 (NRSN2), N-cadherin, and E-cadherin expression levels. Dual luciferase reporter assays were conducted to identify the target relationship between miR-1913 and NRSN2. The exosomes were extracted and identified using TEM and NTA assays.

In the osteosarcoma tumor tissues and cell lines, the NRSN2 expressions were up-regulated, which correlated with a poor osteosarcoma prognosis. MiR-1913 inhibited the cell viability, proliferation, migration, and invasion by negatively targeting NRSN2. Furthermore, the hBMSC-derived exosomes delivered miR-1913 to inhibit the NRSN2 expression in the osteosarcoma cells.

The inhibitory role of hBMSC-derived miR-1913 on osteosarcoma progression was achieved by targeting NRSN2, indicating the potential therapeutic value of hBMSC-derived miR-1913.

The inhibitory role of hBMSC-derived miR-1913 on osteosarcoma progression was achieved by targeting NRSN2, indicating the potential therapeutic value of hBMSC-derived miR-1913.FAM107A may have a dual role in regulating the biological functions of tumors; however, its role in prostate adenocarcinoma (PRAD) remains unknown. We analyzed FAM107A expression by employing databases to clarify its potential prognostic value for PRAD, as well as its role in the pathogenesis of PRAD. We observed that the FAM107A expression level is decreased in PRAD, and the reduced expression is considerably associated with poor overall survival and progression-free survival (PFS). To explore the mechanism of FAN107A in PRAD, we performed an immune cell infiltration analysis and a gene set enrichment analysis. The results showed that FAM107A expression is positively related to mast cells and natural killer cells. The Wnt signaling pathway, the MAPK signaling pathway, and the immune responses are differentially enriched in the FAM107A high-expression phenotype. The FAM107A low-expression phenotype is linked to apoptosis-induced DNA fragmentation and DNA methylation in PRAD. To assess the relationship between the clinical features and the FAM107A expression, we performed a logistic regression analysis and observed that a decreased FAM107A expression is associated with poor prognostic features, including the T stage, the N stage, the Gleason score, residual tumors, and the TP53 status. Our multivariate Cox regression results showed that the Gleason score, the primary therapy outcome, and the FAM107A expression are independent prognostic factors in PFS. In summary, we consider FAM107A an independent risk factor for PFS in PRAD. Moreover, several pathways may reveal the role of FAM107A in triggering carcinogenesis. These discoveries provide novel perspectives for future research to elucidate the pathogenic mechanism underlying PRAD.

This study was designed to investigate the association between the miR-29a/MMP9 axis expression levels and

(HP) infection in gastric cancer patients.

A total of 100 gastric cancer patients referred to our hospital from June 2017 to June 2019 were recruited as the study cohort. Among them, 50 HP-positive patients were included in the experimental group and 50 HP-negative patients were included in the control group. The changes in the patients' conditions were compared, the miR-29a/MMP9 axis expression levels were recorded, and the correlation between the miR-29a/MMP9 axis and the HP infections was analyzed. All the discharged patients were followed up for one year to analyze the correlation between the HP infections and the serum miR-29a and MMP9 expression levels with the disease progression.

The experimental group had higher miR-29a expression levels and higher MMP9 chromogenic scores than the control group (P<0.05). A negative correlation was found between the miR-29 expression level and the MMP relapse, and high miR-29a/MMP9 axis expression levels.This study explored the effects of coenzyme Q10 (CoQ10) on the testicular functions of male mice exposed to cigarette smoke. Eight-week-old BALB/c male mice were divided into the following groups the AV group (air with a vehicle), the AQ group (air with CoQ10), the SV group (smoke with a vehicle), and the SQ group (smoke with CoQ10). The results showed that the CoQ10 concentrations in the sera and testes were decreased in the groups subjected to smoke but they were improved after the administration of CoQ10. Neither smoke nor CoQ10 supplementation affected the serum or testis testosterone concentrations. Regarding the antioxidant system in the testis, the exposure to smoke induced malondialdehyde and hydrogen peroxide production and decreased the catalase and glutathione peroxidase activities. Oral CoQ10 administration reversed the oxidative damage. In apoptosis, the cytochrome c, c-caspase 9, and c-caspase 3 proteins were increased in the groups exposed to smoke but they were decreased after the CoQ10 administration. In mitochondrial biogenesis, smoke exposure led to decreases in the PGC1-α, NRF1, and NRF2 levels, but CoQ10 increased the expressions of these proteins. Additionally, oral CoQ10 administration improved the mitochondrial copy numbers that were reduced following the exposure to smoke. In summary, CoQ10 administration reduces smoke-induced testicular damage by regulating the antioxidant capacity, the cell apoptosis, the mitochondrial biogenesis, and the copy numbers in the testes.

Inflammation out of control may induce many diseases. Baicalin has certain anti-inflammatory effects, but its mechanism of action is not clear. Therefore, this study was designed to explore a potential mechanism of anti-inflammation.

In this study, RAW264.7 cells were induced by 1.0 g/mL lipopolysaccharide (LPS) and then exposed to baicalin at various concentrations (0.1-1.0 μmol/L). Then, we investigated the effect of baicalin in RAW264.7 inflammation models.

In this study, 0.1-1.0 μmol/L baicalin, especially baicalin at 1.0 μmol/L, effectively inhibited the expression of inflammatory factors (TNF-α, IL-1β, IL-6, Cox, and iNOS), decreased the activity of High Mobility Group Box 1 (HMGB1)/Toll-like Receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, and stimulated miR-181b expression. HMGB1 was proved to be negatively regulated by miR-181b. Here, up-regulation of miR-181b or down-regulation of HMGB1 exerted similar effects as baicalin and down-regulated miR-181b reversed the anti-inflammatory effect of baicalin in RAW264.7 inflammation models.

Baicalin can inhibit LPS-induced inflammation in RAW264.7 cells via the miR-181b/HMGB1/TRL4/NF-κB pathway.

Baicalin can inhibit LPS-induced inflammation in RAW264.7 cells via the miR-181b/HMGB1/TRL4/NF-κB pathway.

Acute myeloid leukemia (AML) is a hematological malignancy with an aberrant proliferation of immature myeloid cells. This study aimed at exploring the regulatory function of circMYC in AML progression.

Expression levels of CircMYC, miR-516a-5p, AKT3 and apoptosis-related proteins were determined by RT-qPCR and western blot. Cell viability and proliferation were examined by CCK8 assay and EdU assay. Annexin V/PI staining was used to assess cell apoptosis. Mitochondrial respiration function was confirmed by oxygen consumption rate (OCR). The relationships among circMYC, miR-516a-5p and AKT3 were detected by dual-luciferase reporter (DLR) assay, RNA-pull down assay and RNA immunoprecipitation (RIP) assay, respectively.

CircMYC was positively correlated with poor prognosis in AML patients (all P<0.05). Knockdown of circMYC decreased cell viability and OCR but increased cell apoptosis rates (all P<0.05), and miR-516a-5p overexpression displayed the similar trend. Mechanistically, the oncogenic effects of circMYC were achieved by sponging miR-516a-5p and increasing AKT3.