Physical activity enhances the effect of immune checkpoint blockade by inhibiting the intratumoral HIF1-α/CEACM1 axis.

Immune checkpoint blockade therapy has demonstrated significant therapeutic effects in certain types of cancers. However, there is limited reporting on the influence of physical activity on its efficacy. This study aimed to investigate the impact of physical activity on anti-PDL-1-mediated immune checkpoint therapy and the interplay of immune cells therein. HePa1-6 tumor-bearing mice were treated with anti-PDL-1 in conjunction with physical activity to assess tumor progression. Flow cytometry was utilized to analyze immune cell infiltration and differentiation levels within the tumor. The expression of HIF-a/CEACAM1 within the tumor due to physical activity was evaluated. HePa1-6 cells with high CEACAM1 expression were validated in mice to determine their inhibitory effects on immune cell proliferation and differentiation. A CD3/CEACAM1 chimeric antibody was developed for treating CEACAM1-overexpressing tumors, and flow cytometry was employed to assess T-cell response. Physical activity enhanced the efficacy of anti-PDL1 by suppressing the HIF-a/CEACAM1 axis within the tumor. In vivo experiments revealed that tumors with high CEACAM1 expression decreased infiltration and activation of CD8 + T cells within the tumor, suppressing T cell cytotoxicity without affecting Treg infiltration. In vitro, high CEACAM1 expression impacted the proliferation and activation of CD8 + T cells in a co-culture system. The constructed CD3/CEACAM1 chimeric antibody significantly activated the TCR within CEACAM1-overexpressing tumors and inhibited tumor progression. The findings suggest that physical activity augments the effectiveness of immune checkpoint blockade by inhibiting the intratumoral HIF1-α/CEACM1 axis.

Internal Ring Defect Closure Technique in Laparoscopic Mesh Hernioplasty for Indirect Inguinal Hernia.

PURPOSE: The best way to reduce seroma formation after laparoscopic indirect hernia repair is debated. We noticed that internal ring defect closure in laparoscopic mesh hernioplasty could provide promising outcomes with an effect on diminishing seroma formation. We introduce our closure technique and report our experience. METHODS: This prospective study was conducted from May 2019 to May 2021. Patients with European Hernia Society classification L3 indirect or scrotal hernia were recruited and underwent laparoscopic transabdominal patch plasty (TAPP). Hernia defect closure was performed before mesh deployment. The primary outcomes were seroma formation, postoperative pain, and hernia recurrence. Perioperative data and postoperative complications were also recorded. RESULTS: Consecutive 77 patients with 89 indirect hernias (including 51 scrotal hernias) were recruited in two regional tertiary hospitals. All operations were successful without open conversion. The mean size of the hernia defect was 3.7 ± 0.5 cm (range, 2.5-5.0 cm). The mean operative time for each hernia repair (peritoneum to peritoneum) was 48.3 ± 10.8 min (range, 33-72 min), and the mean time required for internal ring closure was 6.7 ± 2.2 min (range, 4-10 min). Intraoperative bleeding was minimal. The mean visual analog scale pain score at rest on the first postoperative day was 2.2 (range, 1-4). The average postoperative length of hospital stay was 18 h (range, 14-46 h). During a mean follow-up period of 9.4 months (range, 3-23 months), no hernia recurrence or chronic pain were noted. Seroma formation was detected on six sides of unilateral hernias (6.7%) on postoperative day 7, with a mean volume of 45.8 ml (range, 24-80 ml). All seromas were mild and resolved spontaneously within 3 months, with no need for evacuation or other treatment and without major impact on the final outcome. CONCLUSIONS: Defect closure in laparoscopic mesh hernioplasty for large indirect hernias is safe and feasible and can significantly reduce postoperative seroma formation and relative complications. This approach is recommended in large indirect or scrotal hernia repair.

Gold nano-particles (AuNPs) carrying miR-326 targets PDK1/AKT/c-myc axis in hepatocellular carcinoma.

Abnormal expression of microRNAs (miRNAs) contributes to tumour growth and invasion. MiR-326 expression often down-regulates in several kinds of cancer and low expression of miR-326 is linked with poor prognosis in cancer patients. In the present study, we aimed to explore the modulatory mechanism of miR-326 in hepatocellular carcinoma (HCC). miR-326 expression was significantly decreased in HCC cell lines and tissues. miR-326 decreased HCC cell growth by affecting cell-cycle progression and by promoting apoptosis. In addition, miR-326 inhibited HCC cell invasion by decreasing the EMT phenotype. We found that miR-326 functioned as a tumour suppressor by repressing its down-stream target PDK1. C-myc contributed to miR-326 down-regulation through binding at its promoter and inhibited its expression. Based on these results, we conducted a therapeutic experiment by using gold nano-particles (AuNPs) carrying miR-326. Restoration of miR-326 reduced tumour growth in vivo. Our findings suggest that miR-326 may be a candidate prognostic biomarker and a target for new therapies in HCC patients.

LINC01287 regulates tumorigenesis and invasion via miR-298/MYB in hepatocellular carcinoma.

Recently, it was reported that long non-coding RNAs (lncRNAs) participated in promoting hepatocellular carcinoma (HCC) initiation and progression. Herein, we reported that the expression level of LINC01287 was elevated in HCC cell lines and tissues. LINC01287 down-regulation inhibited HCC cells growth and invasion both in vitro and in vivo. LINC01287 exerted as a ceRNA and negatively regulated miR-298 expression. MYB was identified as a downstream target of miR-298. The miR-298/MYB axis mediated LINC01287's effect on HCC. To the best of our knowledge, our findings provided the first evidence that LINC01287 functioned as an oncogene in HCC. LINC01287 may be a candidate prognostic biomarker and a target for new therapies in HCC patients.

LINC01287/miR-298/STAT3 feedback loop regulates growth and the epithelial-to-mesenchymal transition phenotype in hepatocellular carcinoma cells.

BACKGROUND: The long non-coding RNAs (lncRNAs) have participated in the promotion of hepatocellular carcinoma (HCC) initiation and progression. Nevertheless, the biological role and underlying mechanism of LINC01287 in HCC has never been reported. METHODS: The TGCA database was used to explore the abnormal expression of lncRNAs in HCC. Real-time PCR and in situ hybridization assays were used to examine the expression of LINC01287 in HCC tissues. The clinicopathological characteristics of HCC patients in relation to LINC01287 expression were then analyzed. Infection of cells with the si-LINC01287 lentiviral vector was performed to down-regulate LINC01287 expression in HCC cells. MTT and colony formation assays were performed to examine cell growth ability, and FACS analysis was performed to examine the cell cycle and apoptosis. A Boyden assay was used to examine HCC cell invasion ability, and RNA immunoprecipitation tested the interaction between LINC01287 and miR-298. A luciferase reporter assay was used to examine whether STAT3 was a direct target of miR-298, and chromatin immunoprecipitation (ChIP) was used to examine the potential binding of c-jun to the miR-298 promoter. RESULTS: We revealed that the expression of LINC01287 was increased in HCC cell lines, as well as tissues. Knockdown of LINC01287 decreased HCC cell growth and invasion both in vitro and in vivo. LINC01287 can negatively regulate miR-298 expression by acting as a ceRNA. miR-298 directly targeted STAT3 and inhibited its expression. LINC01287 exerted its function via the miR-298/STAT3 axis in HCC. Interestingly, STAT3 elevated LINC01287 expression via c-jun, which bound to the LINC01287 promoter. A feedback loop was also discovered between LINC01287 and the miR-298/STAT3 axis. CONCLUSIONS: Our data indicated that LINC01287 played an oncogenic role in HCC growth and metastasis and that this lncRNA might serve as a novel molecular target for the treatment of HCC.