Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1

Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.

Effects of glucocorticoid use on survival of advanced non-small-cell lung cancer patients treated with immune checkpoint inhibitors

Background:Lung cancer is the second most common cancer worldwide,with non-small-cell lung cancer(NSCLC)accounting for the majority of cases.Patients with NSCLC have achieved great survival benefits from immunotherapies targeting immune checkpoints.Glucocorticoids(GCs)are frequently used for palliation of cancer-associated symptoms,as supportive care for noncancer-associated symptoms,and for management of immune-related adverse events(irAEs).The aim of this study was to clarify the safety and prognostic significance of glucocorticoid use in advanced patients with NSCLC treated with immune checkpoint inhibitors(ICIs).Methods:The study searched publications from PubMed,Embase,Cochrane Library,Web of Science,China Biology Medicine disc,Chinese National Knowledge Infrastructure,Wanfang Data,and Chinese Science and Technology Journal Database up to March 1st,2022,and conducted a meta-analysis to assess the effects of glucocorticoid use on overall survival(OS)and progressionfree survival(PFS)in NSCLC patients treated with ICIs through the available data.The study calculated the pooled hazard ratios(HRs)and 95%confidence intervals(CIs).Results:This study included data from 25 literatures that were mainly retrospective,with 8713 patients included.Patients taking GCs had a higher risk for tumor progression and death compared with those not taking GCs(PFS:HR=1.57,95%CI:1.33-1.86,P<0.001;OS:HR=1.63,95%CI:1.41-1.88,P<0.001).GCs used for cancer-associated symptoms caused an obviously negative effect on both PFS and OS(PFS:HR=1.74,95%CI:1.32-2.29,P<0.001;OS:HR=1.76,95%CI:1.52-2.04,P<0.001).However,GCs used for irAEs management did not negatively affect prognosis(PFS:HR=0.68,95%CI:0.46-1.00,P=0.050;OS:HR=0.53,95%CI:0.34-0.83,P=0.005),and GCs used for non-cancer-associated indications had no effect on prognosis(PFS:HR=0.92,95%CI:0.63-1.32,P=0.640;OS:HR=0.91,95%CI:0.59-1.41,P=0.680).Conclusions:In advanced NSCLC patients treated with ICIs,the use of GCs for palliation of cancer-associated symptoms may result in a worse PFS and OS,indicating that they increase the risk of tumor progression and death.But,in NSCLC patients treated with ICIs,the use of GCs for the management of irAEs may be safe,and the use of GCs for the treatment of non-cancer-associated symptoms may not affect the ICIs’survival benefits.Therefore,it is necessary to be careful and evaluate indications rationally before administering GCs in individualized clinical management.

Effect of externally applied Jidesheng anti-venom on skin and soft-tissue necrosis after Chinese cobra bite: a retrospective study

OBJECTIVE: To evaluate the effects of Jidesheng anti-venom used externally for skin and soft-tissue necrosis from Chinese cobra bite.METHODS: A retrospective review was performed according to the clinical data recorded from January 2002 to December 2012. A total of 126 patients(116 females and 10 males) with skin and soft-tissue necrosis due to Chinese cobra bite were divided into two groups. The control group was treated externally with 40% glyceride magnesium sulfate(n=52), and the treatment group was given Jidesheng anti-venom externally(n=74). The data collected included maximum local necrotic area of skin and soft tissues, de-tumescence time, healing time,and skin-grafting rate.RESULTS: There were no significant differences in gender, age, and disease condition between the control and treatment groups(P>0.05). No statistically significant difference was found in de-tumescence time between the two groups(P>0.05). The maximum local necrotic area of skin and soft tissues was(19.9 ± 7.3) cm2in the treatment group,while it was(23.3±6.4) cm2in the control group.The healing time of the treatment group was shorter than that of the control group [(32.1 ± 3.7) vs(34.4±4.5) days)] The skin-grafting rate in the treatment group was lower than that of the control group(10.81% vs 25.00%). There were statistically significant differences in maximum local necrotic area of skin and soft tissues, healing time, and skin-grafting rate between the control and treatment groups(all P<0.05).CONCLUSION: External application of Jidesheng anti-venom may help to promote wound healing and reduce the skin-grafting rate in cases of skin and soft-tissue necrosis due to Chinese cobra bite.