Phosphatidylinositol 3-kinase (PI3K)/AKT signaling is a crucial pathway for cell survival and proliferation, which are regulated by several growth factors and activated receptors. Upregulated PI3K/AKT signaling molecules were reported in several cancers and they are associated with altered cellular functions, leading to oncogenesis. Here, we have examined the implications of elevated PI3K/AKT expression in the apoptosis resistance of human hepatocellular carcinoma (HCC) Huh7 cells. We showed that PI3K/AKT signaling is significantly upregulated in Huh7 cells by quantitative polymerase chain reaction and protein expression analysis. Also, perversely upregulated PI3K/AKT signaling Huh7 cells are highly resistant to treatment with chemotherapy drugs (docetaxel and sorafenib) and acquired apoptosis resistance through downregulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten). Hence, we have investigated the effect of PTEN overexpression on apoptosis induction in Huh7 cells. We showed that PTEN overexpressed Huh7 cells became more sensitive toward the aforesaid drugs and induced apoptotic cell death due to intracellular reactive oxygen species (ROS) generation. Concurrently, the overexpression of PTEN leads to the activation of mitochondria facilitated intrinsic apoptosis, evidenced by upregulated cytochrome C, caspase 3, and caspase 9. Collectively, our data suggest that the aberrant expression of PI3K/AKT signaling contributes to apoptosis resistance in HCC.

Background It remains controversial whether mesh should be fixed during laparoscopic inguinal hernia repair. A systematic review and meta-analysis of randomized-controlled trials (RCTs) was conducted to compare fixation and nonfixation in laparoscopic groin hernia repair. Methods A registration was listed with PROSPERO (International Prospective Register of Systematic Reviews; registration no. CRD42022350469). Databases including PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched to identify RCTs comparing fixation with nonfixation in laparoscopic groin hernia repair. The primary outcomes were postoperative pain at 24 hours and recurrence. Secondary outcomes were mean operative time, urinary retention, and postoperative pain at 6 months. Results A total of 18 trials, including 2617 patients with 2878 hernias, were included in this meta-analysis. In contrast to the fixation group, the nonfixation group was associated with lower postoperative pain scores at 24 hours and 6 months, a shorter mean operative time, and a lower incidence of urinary retention. There were no significant differences between the 2 types of procedures in terms of the rate of recurrence for patients with an inguinal hernia orifice smaller than 4 cm in size. Conclusions The nonfixation technique is an effective method to reduce urinary retention, mean operative time, and postoperative pain at 24 hours and at 6 months; however, the rate of recurrence was comparable to that of the fixation method.