Pathological significance of tRNA-derived small RNAs in neurological disorders

Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs(tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points:(1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes.(2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress.(3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma.(4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.

Transumbilical enterostomy for Hirschsprung’s disease with a two-stage laparoscopy-assisted pull-through procedure

BACKGROUND A one-stage laparoscopic operation has recently been considered a favorable option for the management of patients with Hirschsprung's disease(HD)due to its superior cosmetic results.One-stage transanal endorectal pull-through for the treatment of rectosigmoid HD has been widely used in newborns without complications.However,enterostomy is required in some HD cases for enterocolitis and dilated colon.Our transumbilical enterostomy(TUE)and twostage laparoscopy-assisted anorectoplasty were effective and achieved a similar cosmetic effect to one-stage laparoscopy on the abdominal wall in patients with anorectal malformation,but the effect in patients with HD is unclear.AIM To evaluate the safety,efficacy and cosmetic results of TUE in two-stage laparoscopy-assisted pull-through for HD.METHODS From June 2013 to June 2018,53 patients(40 boys,13 girls;mean age at enterostomy:5.5±2.2 mo)who underwent enterostomy and two-stage laparoscopy-assisted pull-through for HD with stoma closure were reviewed at our institution.Two enterostomy approaches were used:TUE in 24 patients,and conventional abdominal enterostomy(CAE)in 29 patients.Eleven patients with rectosigmoid HD had severe preoperative enterocolitis or a dilated colon.26 patients had long-segment HD,and 16 patients had total colonic aganglionosis(TCA).The patients with left-sided HD underwent the two-stage laparoscopic Soave procedure,and the patients with right-sided HD and TCA underwent the laparoscopic Duhamel procedure.Demographics,enterostomy operative time,complications and cosmetic results were respectively evaluated.RESULTS There were no differences between the groups with respect to gender,age at enterostomy,weight and clinical type(P>0.05).No conversion to open technique was required.Two patients experienced episodes of stomal mucosal prolapse in the TUE group and 1 patient in the CAE group(8.33%vs 3.45%,P>0.05).No parastomal hernia was observed in either of the two groups.Wound infection at the stoma was seen in 1 case in the TUE group,and 2 cases in the CAE group(4.17%vs 6.90%,P>0.05).No obstruction was noted in any of the patients in the TUE group,whereas obstruction was found in 1 patient in the CAE group.Enterocolitis was observed in 3 and 5 patients in the TUE and CAE group,respectively(12.50%vs 17.24%,P>0.05).There was no significant difference between the TUE group and CAE group in terms of the incidence of soiling and constipation(P>0.05).The cosmetic result using the scar score in the TUE group was better than that in the CAE group(6.83±0.96 vs 13.32±1.57,P<0.05).CONCLUSION TUE is a safe and feasible method for the treatment of HD,and the staged enterostomy and two-stage laparoscopy-assisted pull-through achieved a similar cosmetic effect to the one-stage laparoscopic procedure.

Apoptotic Mechanism of Human Leukemia K562/A02 Cells Induced by Magnetic Ferroferric Oxide Nanoparticles Loaded with Wogonin

Background： Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia. Recently, the application of drug-coated magnetic nanoparticles （MNPs） to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. Drugs coated with MNPs are becoming a promising way for better leukemia treatment. This study aimed to assess the possible molecular mechanisms of wogonin-coated MNP-Fe3O4 （Wog-MNPs-Fe3O4） as an antileukemia agent. Methods： After incubated for 48 h, the antiproliferative effects of MNPs, wogonin, or Wog-MNPs-Fe3O4on K562/A02 cells were determined by methyl thiazolyl tetrazolium （MTT） assay. The apoptotic rates of K562/A02 cells treated with either wogonin or Wog-MNPs-Fe3O4were determined by flow cytometer （FCM） assay. The cell cycle arrest in K562/A02 cells was determined by FCM assay. The elementary molecular mechanisms of these phenomena were explored by Western blot and reverse transcriptase polymerase chain reaction （RT-PCR）. Results： With cell viabilities ranging from 98.76% to 101.43%, MNP-Fe3O4was nontoxic to the cell line. Meanwhile, the wogonin and Wog-MNPs-Fe3O4had little effects on normal human embryonic lung fibroblast cells. The cell viabilities of the Wog-MNPs-Fe3O4group （28.64–68.36%） were significantly lower than those of the wogonin group （35.53–97.28%） in a dose-dependent manner in 48 h （P 〈 0.001）. The apoptotic rate of K562/A02 cells was significantly improved in 50 μmol/L Wog-MNPs-Fe3O4group （34.28%） compared with that in 50 μmol/L wogonin group （23.46%; P〈 0.001）. Compared with those of the 25 and 50 μmol/L wogonin groups, the ratios of G0/G1-phase K562/A02 cells were significantly higher in the 25 and 50 μmol/L Wog-MNPs-Fe3O4groups （all P〈 0.001）. The mRNA and protein expression levels of the p21 and p27 in the K562/A02 cells were also significantly higher in the Wog-MNPs-Fe3O4group compared with those of the wogonin group （all P〈 0.001）. Conclusions： This study demonstrated that MNPs were the effective drug delivery vehicles to deliver wogonin to the leukemia cells. Through increasing cells arrested at G0/G1-phase and inducing apoptosis of K562/A02 cells, MNPs could enhance the therapeutic effects of wogonin on leukemia cells. These findings indicated that MNPs loaded with wogonin could provide a promising way for better leukemia treatment.

Wogonin Inhibits Growth of Mantle Cell Lymphoma Cells through Nuclear Factor-κB Signaling Pathway

To the Editor： Mantle cell lymphoma （MCL） is a non-Hodgkin＇s lymphoma （NHL） subtype and considered one of the most aggressive lyrnphomas with worse prognosis than other subtypes ofN H L. Despite the great progress over the last several decades, treatment of MCL still has troubles in survival, relapse, and drug resistance.