Endothelial nitric oxide synthase deficiency influences normal cell cycle progression and apoptosis in trabecular meshwork cells

AIM： To clarify how the endothelial nitric oxide synthase （eNOS, NOS3） make effect on outflow facility through the trabecular meshwork （TM）. METHODS： Inhibition of NOS3 gene expression in human TM cells were conducted by three siRNAs. Then the mRNA and protein levels of NOS3 in siRNA-treated and negative control （NC） cells were determined, still were the collagen, type IV, alpha 1 （COL4A1） and fibronectin 1 by real-time PCR and Western blot analysis. In addition, NOS3 concentrations in culture supernatant fluids of TM cells were measured. Cell cycle and cell apoptosis analysis were performed using flow cytometry. RESULTS： The mRNA level of NOS3 was decreased by three different siRNA interference, similar results were obtained not only of the relative levels of NOS3 protein, but also the expression levels of COL4A1 and fibronectin 1. The number of cells in S phase was decreased, while contrary result was obtained in G2 phase. The number of apoptotic cells in siRNA-treated groups were significant increased compared to the NC samples. CONCLUSION： Abnormal NOS3 expression can make effects on the proteins levels of extracellular matrix component （e.g. fibronectin 1 and COL4A1）. Reduced NOS3 restrains the TM cell cycle progression at the G2/ M-phase transition and induced cell apoptosis.

Fish oil-containing lipid emulsions prevention on parenteral nutrition-associated cholestasis in very low birth weight infants:a meta-analysis

Background The effect of fish oil-containing lipid emulsions on preventing parenteral nutrition-associated cholestasis(PNAC)in very low birth weight(VLBW)infants is not known.Thus,we conducted a meta-analysis to identify any preven-tion effect.Methods PubMed,EMBASE,and CENTRAL were searched up to 26 January 2021 for studies related to the preventive effect of fish oil-containing lipid emulsions and fish oil-free lipid emulsions on cholestasis in VLBW infants.Revman 5.3 was used to synthesize the results.A fixed-effect model was used to summarize the data when the heterogeneity was non-significant(I2<50%),and a random-effects model was used when the heterogeneity was significant(I2>50%).Results Of 728 articles,11 randomized controlled trials met the inclusion criteria.The meta-analysis indicated that fish oil-containing lipid emulsion reduced the occurrence of PNAC significantly with risk ratio(RR)=0.53,95%confidence interval(CI)0.36-0.80,P=0.002.The heterogeneity was non-significant with I2=23%.Subgroup analysis based on par-enteral nutrition duration and median birth weight was performed.The synthesis results for patients with parenteral nutri-tion duration exceeding 14 days revealed I2=35%(P=0.15)and pooled RR=0.47,95%CI 0.30-0.73,P=0.0008;and for patients with duration less than 14 days revealed I2=0%(P=0.72)and pooled RR=1.14,95%CI 0.39-3.35,P=0.81.The synthesis for patients with birth weight more than 1000 g revealed I2=0%(P=0.41)and pooled RR=0.55,95%CI 0.26-1.18,P=0.12;and for patients with birth weight below 1000 g revealed I2=44%(P=0.11)and pooled RR=0.53,95%CI 0.33-0.85,P=0.009.Conclusions The fish oil-containing lipid emulsion can reduce the occurrence of PNAC in VLBW infants based on the avail-able original randomized controlled trial studies,especially for patients with parenteral nutrition duration exceeding 14 days and extremely low birth weight infants.Future studies should be performed before a definitive conclusion can be established.