BACKGROUND:Forskolin,a diterpenoid natural compound extracted from Coleus forskohlii,has a crucial regulatory role in skeletal muscle repair.However,the regulatory role of forskolin on myogenic differentiation of C2C12 skeletal muscle cells has not been fully explored.OBJECTIVE:To explore the effects of forskolin on the differentiation of C2C12 myoblast cell line and probe into the underlying molecular mechanisms.METHODS:C2C12 cells were treated with 0,0.1,0.25,0.5,1,5,10 and 20 μmol/L forskolin during growth,and cell proliferation was detected by cell counting kit-8 and qRT-PCR.C2C12 cells were treated with 0,0.25,0.5 and 1 μmol/L forskolin during the induction of myogenic differentiation.Immunofluorescence staining and qRT-PCR were used to detect C2C12 cells differentiation.Western blot was used to detect the expression level of myogenic differentiation-related signaling pathway proteins.RESULTS AND CONCLUSION:(1)The viability of C2C12 cells was decreased and cell proliferation was inhibited after treatment with high concentrations(＞1 μmol/L)of forskolin.(2)The qRT-PCR results showed that forskolin up-regulated the expression of Myh2,Myh4,Myomaker,but down-regulated the expression of Myh7 compared with the 0 μmol/L group,when C2C12 cells were differentiated for 4 days.Immunofluorescence staining results showed that the fusion index and myotube diameter of C2C12 cells were increased after forskolin treatment,and the number of myotubes was also increased.(3)Western blot results showed that the phosphorylated extracellular signal-regulated kinase 1/2 expression was inhibited;however,the phosphorylated protein kinase B was promoted after treatment with forskolin.The protein expression level of the myogenic differentiation transcription factor Myogenin was significantly up-regulated after treatment with forskolin.The above results demonstrate that forskolin may promote myogenic differentiation of C2C12 skeletal muscle cells through the extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathway.

BACKGROUND:Forskolin,a diterpenoid natural compound extracted from Coleus forskohlii,has a crucial regulatory role in skeletal muscle repair.However,the regulatory role of forskolin on myogenic differentiation of C2C12 skeletal muscle cells has not been fully explored.OBJECTIVE:To explore the effects of forskolin on the differentiation of C2C12 myoblast cell line and probe into the underlying molecular mechanisms.METHODS:C2C12 cells were treated with 0,0.1,0.25,0.5,1,5,10 and 20 μmol/L forskolin during growth,and cell proliferation was detected by cell counting kit-8 and qRT-PCR.C2C12 cells were treated with 0,0.25,0.5 and 1 μmol/L forskolin during the induction of myogenic differentiation.Immunofluorescence staining and qRT-PCR were used to detect C2C12 cells differentiation.Western blot was used to detect the expression level of myogenic differentiation-related signaling pathway proteins.RESULTS AND CONCLUSION:(1)The viability of C2C12 cells was decreased and cell proliferation was inhibited after treatment with high concentrations(＞1 μmol/L)of forskolin.(2)The qRT-PCR results showed that forskolin up-regulated the expression of Myh2,Myh4,Myomaker,but down-regulated the expression of Myh7 compared with the 0 μmol/L group,when C2C12 cells were differentiated for 4 days.Immunofluorescence staining results showed that the fusion index and myotube diameter of C2C12 cells were increased after forskolin treatment,and the number of myotubes was also increased.(3)Western blot results showed that the phosphorylated extracellular signal-regulated kinase 1/2 expression was inhibited;however,the phosphorylated protein kinase B was promoted after treatment with forskolin.The protein expression level of the myogenic differentiation transcription factor Myogenin was significantly up-regulated after treatment with forskolin.The above results demonstrate that forskolin may promote myogenic differentiation of C2C12 skeletal muscle cells through the extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathway.

Background: Hypertension is a major risk factor for cardiovascular diseases, including AF, which is one of the most common cardiac arrhythmias globally. AF is strongly associated with an increased risk of stroke, heart failure (HF), and cardiovascular mortality. Although intensive blood pressure lowering has been shown to reduce adverse cardiovascular events, its effect on the risk of AF remains debated. Some studies suggest a beneficial effect, whereas others are inconclusive. Therefore, a comprehensive review and meta-analysis are needed to clarify these effects. Objective: This study aims to evaluate the impact of intensive blood pressure lowering on the incidence of atrial fibrillation (AF) in hypertensive patients. Methods: We performed a systematic review and meta-analysis by searching PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library up to September 2, 2024, for randomized controlled trials comparing intensive blood pressure lowering with standard treatment in hypertensive patients. Studies were included if participants were 40 year or older with systolic blood pressure between 130 and 180 mm Hg (1 mm Hg≈0.133 kPa). Data extraction was conducted by 2 independent researchers, and statistical analysis was performed using Review Manager (RevMan) 5.4. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A random-effects model was applied if heterogeneity was detected (I > 50%). Results: A total of 6 randomized controlled trials involving 34,824 participants were included in the analysis. Intensive blood pressure lowering significantly reduced the risk of new-onset AF compared with standard treatment (RR = 0.76, 95% CI = 0.62-0.93, p < 0.01, I = 0%). Reductions were also observed in stroke (RR = 0.71, 95% CI = 0.58-0.87, p < 0.005, I = 7%), HF (RR = 0.67, 95% CI = 0.45-0.99, p = 0.05, I = 53%), and nonfatal coronary events (RR = 0.80, 95% CI = 0.70-0.92, p < 0.005, I = 39%). However, intensive blood pressure lowering had no significant effect on cardiovascular mortality or all-cause mortality compared with standard treatment. Discussion: Intensive blood pressure lowering significantly reduces the risk of AF and other cardiovascular events, such as stroke, HF, and nonfatal coronary events, particularly among high-risk hypertensive patients. These findings support the potential benefits of intensive blood pressure management in reducing AF incidence and improving overall cardiovascular outcomes, but the evidence is limited.

BACKGROUND:The osteogenic differentiation of mesenchymal stem cells is regulated by a variety of molecules.Long non-coding RNA(lncRNA)has attracted much attention because they can participate in regulating a variety of biological processes,but the regulatory role of lncRNA on osteogenic differentiation of mesenchymal stem cells has not been fully explored. OBJECTIVE:To explore the effect of lncRNA Gm16104 on osteogenic differentiation of C3H10T1/2 mesenchymal stem cells. METHODS:The C3H10T1/2 mesenchymal stem cells were induced into osteogenic differentiation by bone morphogenetic protein-2.Alkaline phosphatase staining was performed to identify the osteogenic differentiation of the cells 5 days after osteogenic induction.Expression levels of alkaline phosphatase and lncRNA Gm16104 were detected by qRT-PCR after 0,1,3,and 5 days of osteogenic differentiation.After transfection of the overexpression plasmid of pcDNA-Gm16104,the osteogenic differentiation was identified by alkaline phosphatase staining and qRT-PCR 4 days after osteogenic induction.The expression levels of osteogenesis-related signalling pathway proteins were detected by western blot assay. RESULTS AND CONCLUSION:(1)After 5 days of osteogenic induction,alkaline phosphatase activity was significantly increased.(2)Compared with 0 days,expression levels of the osteogenic marker gene alkaline phosphatase increased and expression levels of Gm16104 decreased after 1,3,and 5 days of osteogenic induction.(3)Transfection of C3H10T1/2 cells with pcDNA-Gm16104 plasmid significantly increased the expression level of Gm16104.(4)Overexpression of Gm16104 inhibited alkaline phosphatase activity,the expression levels of the osteogenic marker gene alkaline phosphatase and the osteogenesis-related transcription factor Osterix.(5)Overexpression of Gm16104 inhibited phosphorylated protein expression of PI3K and Akt.(6)The above results suggest that overexpression of Gm16104 may inhibit osteogenic differentiation of C3H10T1/2 mesenchymal stem cells through the PI3K/Akt signaling pathway.