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.

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

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

Objective To explore the reason of colon cancer with appendicitis and reduce the rate of misdiagnosis. Methods We car-ried out analysis retrospectively to analyze 1 094 hospitalized patients with colon cancer in the First Affiliated Hospital of Harbin Medical Uni-versity from January 2006 to March 2013. Results Among 1 094 colon cancer patients,31 patients who firstly diagnosed with acute appendi-citis received appendectomy,1 patient with appendiceal abscess received non-surgical treatment. Among 31 patients with acute appendicitis,6 patients were found to be with ileocecal tumors during surgeries;24 patients were diagnosed with colon cancer within one year;incision of 1 patient did not heal, with continuous drainage of brown liquid;the appendicitis of 1 patient who received non-surgical treatment was recur-rent. Conclusion As lack of typical symptoms,colon cancer is prone to misdiagnose and diagnose incorrectly when the cancer co-exists with appendicitis and symptoms of appendicitis were showed firstly. Therefore,clinicians should be vigilant for patients with appendicitis. In order to induce the rate of misdiagnosis,it is essential that requesting disease history carefully,timely and relevant inspection and appropriate ex-ploratory surgery for the patients with appendicitis.

Caenorhabditis elegans is a very important model organism in life sciences. C. elegans has been widely used in research on life sciences, especially in drug screening and the mechanism of drugs, thanks to some of their prominent characteristics, including a short life,short generation cycle, and easy culture and observation. Aging is a complex process, which is the result of multiple factors. There are mainly three types of anti-aging signal pathways in C. elegans, including insulin-insulin-like growth factor-1 signal pathway, diet-restricted signaling pathway and mitochondrial respiratory chain/ATP synthesis pathway. In this paper, we reviewed the aging models based on the above three signaling pathways and the progress in anti-aging drugs based on the above aging models. In addition, a number of C. elegans models of aging-related neurodegenerative diseases can be obtained by using transgenic or chemical mutagenesis. Thus, this paper reviewed the transgenic models of C. elegans associated with neurodegenerative diseases, including theα-synuclein transgenic model of Parkinson disease, theβ-amyloid deposition model of Alzheimer disease, and the polyQ of Huntington disease, and summa?rized the effective drugs based on the above disease models. This review will provide reference for the study of C. elegans in the future screening of anti-aging drugs and drug screening for the prevention and treatment of neurodegenerative diseases.

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.

Objective: To observe the therapeutic effects of needle warming moxibustion for chronic diarrhea. Methods: Two-hundred cases with chronic diarrhea were divided randomly into a treatment group and a control group. 100 cases in the treatment group were treated with needle warming moxibustion on specific acupoints. 100 cases in the control group were treated by oral administration of Smecta. Results: The therapeutic results showed cure in 52 cases, remarkable effect in 34 cases, improvement in 14 cases and the total effective rate in 100.0% in the treatment group, and cure in 5 cases, remarkable effect in 23 cases, improvement in 33 cases, failure in 39 cases and the total effective rate in 61.0% in the control group. The comparison of the total effective rate between the two groups was statistically significant (P<0.05). Conclusion: The needle warming moxibustion on specific acupoints is better than oral administration of Smecta in the therapeutic effects.