Analysis of functional hub genes indicates DLGAP5 is linked to lung adenocarcinoma prognosis

Introduction:The difficulty in treating lung adenocarcinoma(LUAD)is caused by a shortage of knowledge about the biological mechanisms and a lack of treatment choices.Objectives:The aim of this study was to identify a valuable molecular target for the treatment of LUAD.Methods:Using multiple databases,we screened for hub genes in LUAD using Cytoscape and explored the expression and prognosis of DLG associated protein 5(DLGAP5)in LUAD.We investigated the genetic variation,functional enrichment,and epigenetic activity of DLGAP5.Furthermore,we evaluated the relationship between the tumor microenvironment(TME)and DLGAP5.Results:Our study identified 10 hub genes in LUAD:CDC45,KIAA0101,DLGAP5,CDT1,NCAPG,CCNB1,CDCA5,CDC20,KIF11,and AURKA.We discovered that DLGAP5 was overexpressed and associated with poor prognosis in LUAD.DLGAP5 exhibited an overall genetic variation frequency of 2%,and its DNA promoter was hypomethylated in LUAD(p<0.05).The expression of DLGAP5 in LUAD showed a positive correlation with the majority of N6-methyladenosine(m6A)-methylation genes.Additionally,DLGAP5 was primarily associated with the cell cycle in LUAD.Notably,there was a significant favorable association between DLGAP5 and CD274,CTLA4,HAVCR2,and LAG3 in LUAD.Conclusion:DLGAP5 may be a therapeutic target for LUAD,as it affects cancer cells proliferation and development through the regulation of cell-cycle checkpoints and modulation of immune cell infiltration and immune checkpoints in the TME.

Non-coding RNA: a key regulator of the pathogenicity and immunity of Flaviviridae viruses infection

Flaviviridae is a family of viruses that mainly spread through arthropod vectors,such as mosquitoes.Major members of the Flaviviridae family include dengue virus(DENV),yellow fever virus,Zika virus(ZIKV),West Nile virus and hepatitis C virus(HCV).As Flaviviridae viruses remain a major global public health threat,elucidation of the exact mechanisms of pathogenesis during infection is required for the successful control of these deadly viruses.

Suppressed expression of miR-378 targeting gzmb in N cells is required to control dengue virus infection

Dengue virus （DENV） remains a major public health threat because no vaccine or drugs are available for the prevention and treatment of DENV infection, and the immunopathogenesis mechanisms of DENV infection are not fully understood. Cytotoxic molecules, such as granzyme B （GrzB）, may be necessary to control viral infections. However, the exact role of GrzB during DENV infection and the mechanisms regulating GrzB expression during DENV infection are not clear. This study found that miR-27a~, miR-3Oe, and miR-378 were down-regulated in DENV-infected patients, and DENV infection in humans induced a significant up-regulation of GrzB in natural killer （NK） cells and CD8＋ T cells. Further investigation indicated that NK cells, but not CD8＋ T cells, were the major sources of GrzB, and miR-378, but not miR-27a~ or miR-3Oe, suppressed GrzB expression in NK cells. Notably, we found that overexpression of miR-378 using a miR-378 agomir in DENV-infected mice inhibited GrzB expression and promoted DENV replication. These results suggest the critical importance of miR-378 in the regulation of GrzB expression and a protective role for GrzB in controlling DENV replication in vivo. Therefore, this study provides a new insight into the immunopathogenesis mechanism of DENV infection and a biological basis for the development of new therapeutic strategies to control DENV infection.

Th1 cytokines, true functional signatures for protective immunity against TB?

The lack of an effective preventative vaccine against tuberculosis(TB)presents a great challenge to TB control.Since it takes an extremely long time to accurately determine the protective efficacy of TB vaccines,there is a great need to identify the surrogate signatures of protection to facilitate vaccine development.Unfortunately,antigen-specific Th1 cytokines that are currently used to evaluate the protective efficacy of the TB vaccine,do not align with the protection and failure of TB vaccine candidates in clinical trials.In this review,we discuss the limitation of current Th1 cytokines as surrogates of protection and address the potential elements that should be considered to finalize the true functional signatures of protective immunity against TB.

External rectal prolapse:abdominal or perineal repair for men?A retrospective cohort study

Background:External rectal prolapse is a relatively rare disease,in which male patients account for a minority.The selection of abdominal repair or perineal repair for male patients has rarely been investigated.Methods:Fifty-one male patients receiving abdominal repair(laparoscopic ventral rectopexy)or perineal repair(Delorme or Altemeier procedures)at the Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between March 2013 and September 2019 were retrospectively analysed.We compared the recurrence,complication rate,post-operative defecation disorder,length of stay,and quality of life between the abdominal and perineal groups.Results:Of the 51 patients,45 had a complete follow-up,with a median of 48.5 months(range,22.8–101.8 months).A total of 35 patients were under age 40 years.The complication rate associated with abdominal repair was less than that associated with perineal repair(0%vs 20.7%,P=0.031)and the recurrence rate was also lower(9.5%vs 41.7%,P=0.018).Multivariate analysis showed that perineal repair(odds ratio,9.827;95%confidence interval,1.296–74.50;P=0.027)might be a risk factor for recurrence.Moreover,only perineal repair significantly improved post-operative constipation status(preoperative vs post-operative,72.4%vs 25.0%,P=0.001).There was no reported mortality in either of the groups.No patient’s sexual function was affected by the surgery.Conclusions:Both surgical approaches were safe in men.Compared with perineal repair,the complication rate and recurrence rate for abdominal repair were lower.However,perineal repair was better able to correct constipation.

Nutrition Metabolism and Infections

Infection and nutrition are intricately interacted and further influence human health.Infections are a worldwide health problem and malnutrition plays a significant role in the emergence of infection.Growing evidence suggests that the optimization of dietary nutrients intake is crucial in maintaining systemic immunity and may help improve resistance to infections.In this review,we explore a wide range of topics including interactions between nutrients and various infectious diseases.We also discuss the role of diet-induced gut microbiota in the infection-nutrition cycle and review how dietary-microbiome crosstalk may affect disease development and progression,which may provide an attractive option to the design of a diet leading to favorable outcomes in the future.We will also present evidence and propose mechanisms of nutrients that may specifically modulate host immunity and metabolism to infectious pathogens and also cover its influence on nutrition,focusing on immuno-nutrients.We provide representative nutrients in the present review based on their intensive studies and wide acceptance of their immuno-modulating properties.Moreover,the efficacy and translational cost of their plausible utility to be anti-infective nutrients are also reviewed.Finally,we highlight the current progress and challenges to gain a better understanding of the research into microbiota,infectious diseases,and nutrition with an emphasis on future research directions.