Bipolar androgen therapy (BAT), as a new therapy, can effectively reduce the serum prostate specific antigen (PSA) level of a part of patients with castration resistant prostate cancer (CRPC), delay tumor progression, improve their quality of life and restore the sensitivity to drug therapy. This paper will review the background, possible mechanism, clinical research progress and development prospect of BAT.

Cardiomyopathy, Dilated/metabolism* ; Humans ; Microfilament Proteins/metabolism* ; Models, Cardiovascular ; Mutation ; Myocytes, Cardiac ; Pluripotent Stem Cells/metabolism* ; Transcription Factors/metabolism* ; Troponin T/metabolism*

AIM:Atherosclerosis primarily involved systemic arteries .Luminal surface , a monolayer of endothelial cells , of artery directly exposes to blood and is susceptible to active substances in the blood .Exosomes contain significantly amount of proteins and RNAs .Ex-osomes can be good and bad for cells , depending on their component .Thus, exosomes may contribute to atherosclerosis by affecting endothelial cells .This study analyzed the relationship of exosome proteins and atherosclerosis .METHODS: Fifty-six patients and healthy subjects were recruited and divided into two comparisons:healthy subjects vs atherosclerosis ( HS vs AS) , and hypertension vs hypertension plus atherosclerosis ( HT vs HT+AS) .Serum exosomes were decoded by protein mass spectrometry .The protein profile and function were analyzed by gene ontology ( GO) .RESULTS:It was found that five child terms repeatedly appeared in “response to stimulus” and “immune system process” of BP of the two categories ( HS vs AS and AS vs HT+AS):“positive regulation of innate immune response”,“immune response-activating signal transduction”,”activation of innate immune response”,“innate immune re-sponse-activating signal transduction” and “innate immune response activating cell surface receptor signaling pathway ”.Two child terms repeatedly showed in “binding” of MF of the two categories:“antigen binding” and “enzyme binding”.Two proteins, PSMA6 and PSMA7, were repeatedly shown in the two categories .CONCLUSION:GO analysis was utilized for structure hierarchy “tree” to illustrate these proteins involved in various terms in BP , CC and MF.The PPI analysis supplied proteins which may play potentially im-portant roles in AS process .Innate immune system and blood coagulation pathway contribute to AS formation .The proteins, PSMA6, PSMA7 and Annexin A2, may can be the new target proteins for prevention and treatment of AS .

Exosomes secreted by mesenchymal stem cells have shown great therapeutic potential in regenerative medicine .In this study, we performed meta-analysis to assess the clinical effectiveness of using exosomes in ischemia /reperfusion injury based on the reports pub-lished between January 2000 and September 2015 and indexed in the PubMed and Web of Science databases .The effect of exosomes on heart function was evaluated according to the following parameters:the area at risk as a percentage of the left ventricle , infarct size as a percentage of the area at risk , infarct size as a percentage of the left ventricle , left ventricular ejection fraction , left ventricular frac-tion shortening , end-diastolic volume , and end-systolic volume .Our analysis indicated that the currently available evidence confirmed the therapeutic potential of mesenchymal stem cell-secreted exosomes in the improvement of heart function .However , further mechanis-tic studies, therapeutic safety and clinical trials are required for optimization and validation of this approach to cardiac regeneration after ischemia/reperfusion injury .

AIM:To analyze the proteins included in exosomes derived from blood of patients with hypertension and seek the main pathologi -cal changes in hypertension .METHODS:Forty-seven patients and healthy subjects were recruited and divided into two comparisons :healthy subjects vs atherosclerosis ( HS vs AS) , and atherosclerosis vs hypertension plus atherosclerosis ( AS vs HT+AS) .We extrac-ted exosomes from blood and utilized LC-MS/MS to identify the protein expression .We used GO analysis to established the hierarchy programs of biological process and molecular function .PPI was used to find the proteins related to the terms .RESULTS:It was found that three final child terms repeatedly shown in BP of the two categories ( HS vs AS and AS vs HT+AS):“signal transduction in re-sponse to DNA damage”,“response to zinc ion”, and“platelet aggregation”.It was found that two final child terms in MF of the two categories:“interleukin 2 receptor binding” and“ploy(A) RNA binding”.The proteins, PSMA6, PSMA7 and CA2, were related to the terms in the two categories .CONCLUSION: We discovered that the exosome proteins may indicate the pathological changes in hypertension through the biological processes related with the specific proteins .These specific proteins, such as VCL, PSMA6, DP, AKAP, ATP5B and CA2, can be the new indicators for severity of hypertension and new therapeutic targets .

AIM:To investigate the effects of human induced pluripotent stem cell-derived exosomes (hiPSC-exo) on cell viability, capillary-like structure formation , and senescence in endothelial cells exposed to high glucose .METHODS: Exosomes were isolated from the conditional medium of hiPSCs and confirmed by transmission electron microscopy , nanoparticle tracking analysis , and Western blot analysis using Alix and CD63 as markers.hiPSC-exo were labeled with PKH26 for tracking.Cultured HUVECs were treated with high glucose (33 mmol/L) with or without hiPSC-exo (20 mg/L) for 48 h, and cell viability, capillary tube formation, and senescence were assessed .RESULTS:hiPSC-exo showed a typical cup shape and could be taken up by human umbilical vascular endothelial cells (HUVECs) in a concentration-dependent manner.When exposed to high glucose, viability and tube formation in HUVECs was signifi-cantly reduced, whereas the proportion of senescent cells was higher compared to that in control HUVECs (P<0.01).Furthermore, hiPSC-exo restored cell viability and capillary-like structure formation , and reduced senescence in HUVECs exposed to high glucose (P<0.01).However, hiPSC-exo had minimal effects on normal HUVECs.Therefore, stem cell-derived exosomes can promote cell proliferation, enhance capillary-like structure formation , and reduce senescence in endothelial cells exposed to high glucose . CONCLUSION:Our study highlights the role of exosomes derived from hiPSC and may provide a new strategy for maintaining vascular health, preventing vascular aging , and avoiding pathological vascular remodeling that occurs in many diseases .

Mesp family proteins comprise two members named mesodermal posterior 1 (Mesp1) and mesodermal posterior 2 (Mesp2). Both Mesp1 and Mesp2 are transcription factors and they share an almost identical basic helix-loop-helix motif. They have been shown to play critical regulating roles in mammalian heart and somite development. Mesp1 sits in the core of the complicated regulatory network for generation of cardiovascular progenitors while Mesp2 is central for somitogenesis. Here we summarize the similarities and differences in their molecular functions during mammalian early mesodermal development and discuss possible future research directions for further study of the functions of Mesp1 and Mesp2. A comprehensive knowledge of molecular functions of Mesp family proteins will eventually help us better understand mammalian heart development and somitogenesis as well as improve the production of specific cell types from pluripotent stem cells for future regenerative therapies.
Amino Acid Sequence ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Cell Differentiation ; genetics ; Gene Expression Regulation, Developmental ; Mesoderm ; embryology ; metabolism ; Mice, Knockout ; Molecular Sequence Data ; Pluripotent Stem Cells ; metabolism ; Sequence Homology, Amino Acid

[ ABSTRACT] AIM:To determine the role of transcription factor Bach1 in the functions of human microvascular en-dothelial cells ( HMVECs ) .METHODS: Bach1 siRNA was transfected into HMVECs to knock down the expression of Bach1.In vitro endothelial cell tube formation assay in Matrigel culture was used as a surrogate assay for angiogenic poten-tial.Migration of HMVECs was determined by using Transwell chambers.Cell proliferation was measured by CCK-8 assay. Real-time PCR, Western blotting, and ELISA were employed to determine mRNA expression and protein level.Reporter as-say was performed to determine vascular endothelial growth factor ( VEGF) transcriptional activity.RESULTS:Knockdown of Bach1 expression in HMVECs led to an increase in the tube formation and increased endothelial cell migration ability, whereas it has little effect on cell proliferation.Bach1 silencing increased the mRNA and protein expression of heme oxygen-ase-1 (HO-1), and enhanced VEGF transcriptional activation, and mRNA and protein expression.CONCLUSION:Bach1 silencing increases HO-1 and VEGF expression, thus promoting the cell migration and tube formation of HMVECs, indicating that Bach1 is a repressor for angiogenesis.

Objective To investigate the role and mechanism of low-dose aspirin concurrent with IFN-a in inducing hepatocellular carcinoma apoptosis in BEL-7402 cells. Methods BEL-7402 cells were cultured and treated with IFN-α,or low dose aspirin or both.MTT and flow cytometry were used to measure the cell proliferation and apoptosis after treatment with a singular drug or the combined regiment.The expressions of the apoptosis-related proteins were detected by Western blot.Results MTT assay revealed after IFN α administration alone or combined with aspirin treatment for 48 h,the proliferation ratio of the IFN-α or aspirin group were 82.45％ ± 1.71％ and 83.22％ ±2.26 ％,compared with the control group.The group which received the combined therapy had a proliferation ratio of 69.84 ％ ±1.18 ％,which was significantly lower than the single groups (P＜0.05).The flow cytometry revealed that the apoptosis ratio in IFN-α group and aspirin group were 14.78 ％ ±1.93％ and 14.00％±0.61％,respectively,while the IFN-α + aspirin group was 21.68％±1.28％,which was also significantly higher than that of the single groups (P＜0.05).Western blot detected that IFN-α and aspirin (1 mmol/L) could promote caspase-3 and caspase-9 protein expressions,and when the two drugs were combined,caspase-3 and caspase-9 were also significantly activated.IFN-α alone or combined with aspirin can promote the expression of pro-apoptotic protein Bax (P＜0.05),while the anti-apoptotic proteins expression of Bcl-2 and Bcl-xl did not change significantly (P＞0.05).Conclusions Low-dose aspirin can cooperate with IFN-α in inhibiting the BEL-7402 cell growth and inducing the cell apoptosis by activating and increasing caspase-3 and caspase-9 levels,which may be related to the increased expression of pro-apoptotic protein Bax.

OBJECTIVETo evaluate the quality of life in patients who underwent laparoscopic and open cholecystectomy for chronic cholecystolithiasis.

METHODSA prospective survey was made on 25 patients receiving laparoscopic cholecystectomy (LC group) and 26 patients receiving open cholecystectomy (OC group). The quality of life was measured with the gastrointestinal quality of life index (GLQI) preoperatively, and at 2, 5, 10 and 16 weeks after the operation.

RESULTSThe mean preoperative GLQI scores of all dimensions of the quality of life were 112.5 and 110.3 in the LC and OC groups respectively. In the LC group, the quality of life was not considerably reduced at 2 weeks after operation, with a mean GLQI score of 110. There was a significant improvement both in total mean score and in the aspects of symptomatology, emotional and physiological status from 5 to 16 weeks after LC operation. In the OC group, the GLQI score reduced to 102.0 at 2 weeks after surgery (P < 0.05). There were significant reductions in the aspects of symptomatology, physiological and social status as well. The GLQI scores reached to the preoperative level of 115.6 at 10 weeks after the operation (P > 0.05). The patients experienced significant improvements of GLQI at 16 weeks after OC operation (P < 0.01 or P < 0.05). The LC group showed better GLQI scores than did the OC group for up to 10 weeks postoperatively (P < 0.05).

CONCLUSIONSLC is betler or more rapidly than OC is improving the quality of life postoperatively. The assessment of the quality of life is valuable for measuring the outcome of surgical treatment.

Adult ; Cholecystectomy ; psychology ; Cholecystectomy, Laparoscopic ; psychology ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Quality of Life