Garcinol, a benzenetriol compound extracted from Garcinia cambogia, has antitumor activity, however, its antitumor mechanism remains unclear. The aim of this study was to investigate the role and mechanism of garcinol as a novel potential proteasome inhibitor. We applied the drug affinity responsive target stability (DARTS) method coupled to mass spectrometry to determine the binding protein of garcinol; the proteasome activity assay was used to determine the effect of garcinol on its hydrolase activity; immunofluorescence and proximity ligation assay (PLA) were used to detect the effects of garcinol on ubiquitin and RPN6; and flow cytometry were used to determine the effects of garcinol on cell apoptosis; and the anti-cancer effect was studied in organoid models. The results showed that RPN6 was a direct binding protein of garcinol; garcinol inhibited the hydrolase activity of proteasome, and induced the accumulation and aggregation of ubiquitin protein, and its proteasomal inhibitory effect was dependent on RPN6; further studies showed that garcinol induced oligomerization of RPN6 and formation of granules in the nucleus; finally, it was verified that garcinol induced apoptosis of tumor cells, and inhibited the growth of organoids of Apc^min/+ small intestine mice. These results suggest that garcinol is a potential proteasome inhibitor, which inhibits proteasome activity by directly targeting RPN6 on proteasome 19S, which in turn induces cell apoptosis and inhibits tumor growth.

Child ; Ectodermal Dysplasia ; diagnosis ; genetics ; Family Health ; Genes, Recessive ; genetics ; Humans ; Male ; Sex Factors

Aged ; Anthracosis ; complications ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Humans ; Lung ; metabolism ; pathology ; Lung Neoplasms ; complications ; metabolism ; pathology ; Male ; Middle Aged ; Retinoblastoma Protein ; metabolism

ObjectiveTo investigate the mechanism and the protective effect of heat shock protein 27 (HSP27) on rat cardiomyocytes when ischemic preconditioning performed.MethodsCultured rat cardiomyocytes were divided into four groups: control group, ischemic group,ischemic preconditioning group and cyclohexamide group. Cell viabilities were analyzed by MTT. The apoptosis was evaluated with DNA ladder and flow cytometry Annexin V Flous staining. Western Blot was used to determine the expression of HSP27 and caspase-3 in cardiomyocytes.ResultsIschemic preconditioning could improve cell viability. The apoptosis ratio in ischemic preconditioning group was significantly less than that in ischemic group. These were accompanied by an increase in the expression of HSP27 and a decrease in caspase-3. The expression of the increased HSP27 and the protective effect induced by ischemic preconditioning were completely abolished by the presence of cycloheximide, a translation inhibitor.ConclusionThe expression of HSP27 induced by ischemic preconditioning plays an important role in protecting cardiomyocytes, and the mechanism is possibly related to the inhibition of cell apoptosis.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Diarrhea ; therapy ; Female ; Humans ; Irritable Bowel Syndrome ; therapy ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Moxibustion ; methods

Animals ; Cochlea ; growth & development ; metabolism ; Female ; Guinea Pigs ; Male ; Nerve Growth Factor ; metabolism

Objective:To study the feasibility of using the bionic technology to construct small-caliber vascular prostheses with modified SIS.Methods: The vascular endothelial cells and smooth muscle cells were separated from canine saphenous artery,the cells blended with collagen gel,which were planted respectively on the SIS films,these films were rolled into the biologic three-layer prostheses around a 3mm diameter polyethylene tube;one-layer prostheses without these cells and collagen gel served as control.These 2 types of prostheses were implanted into the defect of bilateral canine femoral by anastomosis in 15 dogs.doppler colour ultrasonic,histology detection and electron microscope examination were done postoperatively.Results: By 12 weeks postoperatively,14 biologic vascular prostheses had kept well patency,the patency rate being 93.3%,the biologic structure like blood vessels had formed,the inner surface of the vessels had been covered with full endothelial cells,a lot of smooth muscle cells had been found in the media of vascular walls in regular line;the patency rate in control group was 60.0%,the endothelial cell coverage was incomplete.Conclusions: The bionic vascular prostheses showed potent blood compatibility,which could keep long-term patency in vivo.Curative effect of repairing the small-caliber vessel defect was well satisfactory.

BACKGROUND:Kinesin II family member 3A (KIF3A), as an important member of the kinesin-2 family, not only holds some general characters of kinesin including the regulation of intracel ular transport and mediation of microtubule movement, but also possesses its own specific features.
OBJECTIVE:To review the research progress of the function of KIF3A recently.
METHODS:A computer-based online research for relative literatures published from January 1996 to July 2016 was performed in PubMed and CJFD databases using the English retrieval words of“KIF3A;kinesin;molecular motor”and Chinese keywords of“kinesin;microtubule;function;molecular motor;spinal cord injury”, respectively. A total of 92 articles were retrieved, and 62 eligible articles were included according to the inclusion criteria.
RESULTS AND CONCLUSION:KIF3A is involved in new bone formation regulation, in the control of nephron number, cell survival and gene expression, in sperm formation and in the inhibition of prostate cancer and glioblastoma process:In the meanwhile, whether KIF3A is involved in spinal nerve injuries is discussed. All provide valuable new information and new ideas for further in-depth study on the KIF3A.

Objective To explore the strategy of repairing penile defect after necrosis caused by shortwave diathermy.Methods Between January 2004 and June 2012,18 cases with penile defect after necrosis caused by shortwave diathermy were admitted in our hospital.The age of those patients ranged from 18 to 55 years old (mean 34 years old).Among them,15 cases have been married.All patients have the history of penile shortwave diathermy therapy after surgery.After debridement,penile complete defect was found in 6 cases,incomplete defect was found in 10 cases and corpus cavernosum and corpus spongiosum partly defect was found in 2 cases.Under general anesthesia,we applied penis extent in 10 cases with incomplete defect,forearm free flap in 2 cases with penile complete defect,abdominal artery perforators flap in other 4 cases with penile complete defect.In 2 cases with corpus cavernosum and corpus spongiosum partly defect,the scrotal septal skin flap and fascia pedicle flap was used for 1-stage urethral reconstruction and costicartilage was implanted for 2-stage cavernosum reconstruction.Results 18 patients were followed up for 0.5-10.0 years (mean 2.3 years).16 cases with penile complete defect or incomplete defect had normal length after operation,ranged from 6.3 to 9.2cm.During erectile phase,the length of their penis ranged from 8.7 to 11.5 cm.No feeling abnormality or erectile dysfunction was complained.All patients exhibited the excellent morphology and felling of penis with minor scar in donor site.Early (half a month) complications included distant flap necrosis in 1 case and disruption of the wound in 1 case,which were cured after debridement and conventional treatment.After one year,we did not see the flap atrophy.One case had tumid which influenced penile beautiful and sexual intercourse.It was improved by local liposuction.One month after surgery,two patients with corpora cavernosa and corpus spongiosum partial defect had normal voiding.No feeling and erectile dysfunction were complained during the following-up.Conclusions According to the characteristics of the penile defect due to the shortwave diathermy,selecting the optimal skin flap and individual repair strategy are the keys to successful treatment.

The Expert Consensus on the Diagnosis and Therapy of myelodysplastic syndrome (MDS) (2014) will be interpreted in this paper focusing on whether it is scientific and reasonable.Some advises and views will be put forward,hoping that it will be useful to improve the diagnostic and therapeutic ability on MDS for clinicians in our country.