Identification of potential candidate proteins for reprogramming spinal cord-derived astrocytes into neurons:a proteomic analysis

Our previous study has confirmed that astrocytes overexpressing neurogenic differentiation factor 1(NEUROD1)in the spinal cord can be reprogrammed into neurons under in vivo conditions.However,whether they can also be reprogrammed into neurons under in vitro conditions remains unclear,and the mechanisms of programmed conversion from astrocytes to neurons have not yet been clarified.In the present study,we prepared reactive astrocytes from newborn rat spinal cord astrocytes using the scratch method and infected them with lentivirus carrying NEUROD1.The results showed that NEUROD1 overexpression reprogrammed the cultured reactive astrocytes into neurons in vitro with an efficiency of 13.4%.Using proteomic and bioinformatic analyses,1952 proteins were identified,of which 92 were differentially expressed.Among these proteins,11 were identified as candidate proteins in the process of reprogramming based on their biological functions and fold-changes in the bioinformatic analysis.Furthermore,western blot assay revealed that casein kinase II subunit alpha(CSNK2A2)and pinin(PNN)expression in NEUROD1-overexpressing reactive astrocytes was significantly increased,suggesting that NEUROD1 can directly reprogram spinal cord-derived reactive astrocytes into neurons in vitro,and that the NEUROD1-CSNK2A2-PNN pathway is involved in this process.This study was approved by the Animal Ethics Committee of Fujian Medical University,China(approval No.2016-05)on April 18,2016.

Surgical outcomes of subtotal colectomy with antiperistaltic caecorectal anastomosis vs total colectomy with ileorectal anastomosis for intractable slow-transit constipation

Background:Few studies have compared the surgical outcomes of different surgical procedures currently used to treat refractory colonic slow-transit constipation(STC),despite the increase in the number of cases.This study aimed to analyse the long-termsurgical outcomes of subtotal colectomy with antiperistaltic caecorectal anastomosis(SC-ACRA)vs total colectomy with ileorectal anastomosis(TC-IRA)for severe STC.Methods:Between January 2005 and January 2015,we retrospectively collected clinical data of 55 patients who underwent TC-IRA(n=35)or SC-ACRA(n=20)for severe STC at our institution.The post-operative functional outcomes between the two groups were compared.Results:There were no significant differences in age(P=0.655),sex(P=0.234),period of constipation(P=0.105)and defecation frequency(P=0.698)between the TC-IRA and SC-ACRA groups.During a median follow-up period of 72 months(range,12–120 months),there were no significant differences between the TC-IRA and SC-ACRA groups regarding the median number of bowel movements per day[3(1/6–7)vs 3(1/6–5),P=0.578],Cleveland Clinic Florida Constipation Score[2(0–20)vs 2(0–19),P=0.454],Cleveland Clinic Incontinence Score[0(0–5)vs 0(0–2),P=0.333]and Gastrointestinal Quality of Life Index[122(81–132)vs 120(80–132),P=0.661].Moreover,there was no significant difference in the incidence of postoperative complications between the two groups(37.1%vs 25.0%,P=0.285).Conclusions:Our findings indicate that both TC-IRA and SC-ACRA are effective treatments for severe STC,with similar long-termoutcomes.

Antifungal Activity of Aspidin BB from Dryopteris fragrans against Trichophyton rubrum Involved Inhibition of Ergosterol Biosynthesis

Objectives Aspidin BB, a typical phloroglucinol derivative from Dryopteris fragrans, possesses significant antifungal property. This study aimed to investigate potential mechanism of antifungal activity of Aspidin BB against Trichophyton rubrum which is the most common pathogens responsible for chronic dermatophytosis. Methods The minimum inhibitory concentration （MIC） ofAspidin BB against strains was determined by broth microdilution. The effects of Aspidin BB on ergosterol biosynthesis were investigated by content determination based on UPLC method. Besides, the effects of drugs on squalene epoxidase （SE） in T. rubrum cell membrane were analyzed. Results MIC value of Aspidin BB against T. rubrum was 25.0 IJg/mL. Aspidin BB reduced ergosterol content significantly, but no notable effect on squalene epoxidase activity. Conclusion The results suggested that Aspidin BB inhibited ergosterol biosynthesis. However, it was not squalene epoxidase but other components may sever as possible targets in ergosterol biosynthesis pathway.

Altered Retinal Dopamine Levels in a Melatonin-proficient Mouse Model of Form-deprivation Myopia

Reduced levels of retinal dopamine,a key regulator of eye development,are associated with experimental myopia in various species,but are not seen in the myopic eyes of C57BL/6 mice,which are deficient in melatonin,a neurohormone having extensive interactions with dopamine.Here,we examined the relationship between form-deprivation myopia(FDM)and retinal dopamine levels in melatonin-proficient CBA/CaJ mice.We found that these mice exhibited a myopic refractive shift in form-deprived eyes,which was accompanied by altered retinal dopamine levels.When melatonin receptors were pharmacologically blocked,FDM could still be induced,but its magnitude was reduced,and retinal dopamine levels were no longer altered in FDM animals,indicating that melatonin-related changes in retinal dopamine levels contribute to FDM.Thus,FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice.The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.

Transanal total mesorectal excision for rectal cancer: a multicentric cohort study

In the original version of this manuscript,the following line in the abstract read:‘among the 211 patients,175(82.9%)had complete TME and 33(15.6%)had incomplete TME’.This has now been corrected to:‘among the 211 patients,175(82.9%)had complete TME and 33(15.6%)had near complete TME’.The author apologises for the error.

Transanal total mesorectal excision for rectal cancer:a multicentric cohort study

Background:Transanal total mesorectal excision(taTME)has recently emerged as a promising novel surgical procedure for rectal cancer.It is believed to hold the potential advantage of providing better access to mobilize the distal rectum and achieving better pathologic results.This study aimed to evaluate the feasibility of taTME for rectal cancer and summarize the preliminary experience in 10 Chinese hospitals.Methods:A total of 211 patients were enrolled in this study.Variables for evaluation of safety,feasibility,and oncologic outcomes were retrospectively collected and analysed.Results:The median distance between the tumor and the anal verge was 5.9cm(range,1.5–12 cm).The median operating time was 280 min(range,70–600 min)and the median estimated intra-operative blood loss was 50mL(range,10–1,500 mL).The overall rate of complication was 27.9%.Among the 211 patients,175(82.9%)had complete TME and 33(15.6%)had near complete TME.The circumferential resection margin was negative in 97.7%of patients.The patients were followed for a median of 35months(range,2–86months).There was 7.6%(16)mortality,6.2%(13)had local recurrence,and 12.8%(27)had systemic recurrence.Kaplan–Meier survival analysis showed that 1-,2-,and 3-year disease-free survival rates were 94.8%,89.3%,and 80.2%,respectively,and 1-,2-,and 3-year OS rates were 97.4%,95.7%,and 92.9%,respectively.Conclusions:Although limited by its retrospective nature,taTME was safe and feasible in selected patients.Future work with rigorous data recording is warranted.