Betulinic acid-mediating miRNA-365 inhibited the progression of pancreatic cancer

Background:The dilemma of pancreatic cancer treatment has become a global challenge.For this reason,effective,feasible,and new medical methods are currently much-needed.Betulinic acid(BA)has been valued as a potential therapy for pancreatic cancer.However,the mechanism by which BA exerts an inhibitory effect on the development of pancreatic cancer remains elusive.Methods:A rat model and two cell models of pancreatic cancer were established,and the effect of BA on pancreatic cancer was verified in vivo and in vitro by using MTT,Transwell,flow cytometry,RT-PCR,Elisa and immunohistochemistry.At the same time,miR-365 inhibitors were introduced to test whether BA played a role in mediating miR-365.Results:BA can significantly inhibit the proliferation and invasion of pancreatic cancer cells and promote apoptosis.In vivo experiments,BA can significantly lower the number of cancer cells and tumor volume in the rat model of pancreatic cancer.In vitro,it was found that BA inhibited the protein level and phosphorylation level of AKT/STAT3 by mediating the expression of miR365/BTG2/IL-6.Like BA,miR-365 inhibitors also significantly inhibited cell viability and invasion ability,and inhibited the protein level and phosphorylation level of AKT/STAT3 by changing the expression of BTG2/IL-6,and their combination had a synergistic effect.Conclusion:BA inhibits AKT/STAT3 expression and phosphorylation by modulating miR-365/BTG2/IL-6 expression,and BA inhibits the progression of pancreatic cancer through the aforementioned mechanism.

Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography:A single-blind,multicenter,randomized controlled trial

Background:Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography(ERCP),the benefits and safety of high-carbohydrate fluid diet(CFD)intake 2 h before ERCP remain unclear.This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’recovery.Methods:This prospective,multicenter,randomized controlled trial involved 15 tertiary ERCP centers.A total of 1330 patients were randomized into CFD group(n=665)and fasting group(n=665).The CFD group received 400 mL of maltodextrin orally 2 h before ERCP,while the control group abstained from food/water overnight(>6 h)before ERCP.All ERCP procedures were performed using deep sedation with intravenous propofol.The investigators were blinded but not the patients.The primary outcomes included postoperative fatigue and abdominal pain score,and the secondary outcomes included complications and changes in metabolic indicators.The outcomes were analyzed according to a modified intention-to-treat principle.Results:The post-ERCP fatigue scores were significantly lower at 4 h(4.1±2.6 vs.4.8±2.8,t=4.23,P<0.001)and 20 h(2.4±2.1 vs.3.4±2.4,t=7.94,P<0.001)in the CFD group,with least-squares mean differences of 0.48(95%confidence interval[CI]:0.26-0.71,P<0.001)and 0.76(95%CI:0.57-0.95,P<0.001),respectively.The 4-h pain scores(2.1±1.7 vs.2.2±1.7,t=2.60,P=0.009,with a least-squares mean difference of 0.21[95%CI:0.05-0.37])and positive urine ketone levels(7.7%[39/509]vs.15.4%[82/533],χ^(2)=15.13,P<0.001)were lower in the CFD group.The CFD group had significantly less cholangitis(2.1%[13/634]vs.4.0%[26/658],χ^(2)=3.99,P=0.046)but not pancreatitis(5.5%[35/634]vs.6.5%[43/658],χ^(2)=0.59,P=0.444).Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla(odds ratio[OR]:0.61,95%CI:0.39-0.95,P=0.028)in the multivariable models.Conclusion:Ingesting 400 mL of CFD 2 h before ERCP is safe,with a reduction in post-ERCP fatigue,abdominal pain,and cholangitis during recovery.Trail Registration:ClinicalTrials.gov,No.NCT03075280.

Hypoxic microenvironment in cancer:molecular mechanisms and therapeutic interventions

Having a hypoxic microenvironment is a common and salient feature of most solid tumors.Hypoxia has a profound effect on the biological behavior and malignant phenotype of cancer cells,mediates the effects of cancer chemotherapy,radiotherapy,and immunotherapy through complex mechanisms,and is closely associated with poor prognosis in various cancer patients.Accumulating studies have demonstrated that through normalization of the tumor vasculature,nanoparticle carriers and biocarriers can effectively increase the oxygen concentration in the tumor microenvironment,improve drug delivery and the efficacy of radiotherapy.They also increase infiltration of innate and adaptive anti-tumor immune cells to enhance the efficacy of immunotherapy.Furthermore,drugs targeting key genes associated with hypoxia,including hypoxia tracers,hypoxia-activated prodrugs,and drugs targeting hypoxia-inducible factors and downstream targets,can be used for visualization and quantitative analysis of tumor hypoxia and antitumor activity.However,the relationship between hypoxia and cancer is an area of research that requires further exploration.Here,we investigated the potential factors in the development of hypoxia in cancer,changes in signaling pathways that occur in cancer cells to adapt to hypoxic environments,the mechanisms of hypoxia-induced cancer immune tolerance,chemotherapeutic tolerance,and enhanced radiation tolerance,as well as the insights and applications of hypoxia in cancer therapy.