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

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 investigate the effect of Dectin-1 on the release of inflammatory factors interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in rat tracheal epithelial cells (RTECs) stimulated with heat-treated Candida glabrata (C.glabrata).Methods RTECs cultivated in vitro were randomly divided into three groups,including control group(RTECs + sterile normal saline),fungal stimulation group(RTECs + heat-treated C.glabrata),and inhibitor intervention group(RTECs + laminarin + heat-treated C.glabrata),cells were harvested after incubation for 0,2,4,6 hours respectively,cell survival rate was determined by MTT method,expression of Dectin-1 was analyzed by Western Blot,expression of IL-10 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA).Results Heat-treated C.glabrata destroyed cell structure and reduced cell survival rate.At the beginning of the culture (0 h),cell survival rate,expressions of Dectin-1,IL-10 and TNF-α among three groups were all not significantly different(all P＞0.05).After incubation for 2,4,6 hours,expressions of Dectin-1,IL-10 and TNF-α in fungal stimulation group and inhibitor intervention group were both significantly higher than control group;expressions of Dectin-1,IL-10,and TNF-α in inhibitor intervention group was lower than fungal stimulation group(all P＜0.05).The expressions of IL-10 in inhibitor intervention group at 0 h and 2 h was not significantly different,expressions of Dectin-1,IL-10,and TNF-α in fungal stimulation group and inhibitor intervention group at different incubation periods were significantly different(all P＜0.05).Conclusion Dectin-1 is an important receptor for RTECs to recognize the heat-treated C.glabrata,it induces the release of IL-10 and TNF-α,and mediate the occurrence of inflammation.

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.

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.