The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

Objective To study the influence of different body serum iron levels on follicle stimulating hormone (FSH),luteinizing hormone (LH) and uterine ovarian index,and explore the body serum iron level effects on female mice sexual maturity further.Methods 36 three weeks C57BL/6J female mice were randomly divided into the normal control group,strengthen-iron 1 group and strengthen-iron 2 group,12 cases in each group.The normal control group with normal diet(310mgFe/kg),strengthen-iron 1 group and strengthen-iron 2 group were given high -iron diets(respectively with 465mgFe/kg and 620mgFe/kg) after born 3 weeks.each group body,uterus and ovary mass after 2 weeks were checked;colorimetric method was used to detect the serum iron level;the serum follicle stimulating hormone (FSH) and luteinizing hormone(LH) were detected by chemiluminescent immunoassay.Results The body of mice serum iron levels,uterine ovarian index (uterine ovarian wet mass/body mass) and follicle stimulating hormone(FSH) level of strengthen-iron 1 group and strengthen-iron 2 group were higher than those of normal control group (F =9.11,11.11,7.09,all P ＜ 0.01).Luteinizing hormone (LH) level of the strengthen-iron group was higher than those of normal control group (F =3.89,P ＜ 0.05).Conclusion Uterine ovarian index,follicle stimulating hormone level and luteinizing hormone level were affected with increased serum iron level;It suggests that the increasing serum iron level can cause female mice sexual maturity in advance.

Objective To investigate the potential of adult mesenchymal stem cells (MSCs) derived from human bone marrow to undergo cardiomyogenic differentiation after exposure to 5-azacytidine (5-aza) in vitro. Methods A small bone marrow aspirate was taken from the iliac crest of human volunteers, and hMSCs were isolated by 1.073g/mL Percoll and propagated in the right cell culturing medium as previously described. The phenotypes of hMSCs were characterized with the use of flow cytometry. The hMSCs were cultured in cell culture medium (as control) and medium mixed with 5-aza for cellular differentiation. We examined by immunohistochemistry at 21 days the inducement of desmin, cardiac-specific cardiac troponin I (cTnI), GATA 4 and connexin-43 respectively. Results The hMSCs are fibroblast-like morphology and express CD44+ CD29+ CD90+ / CD34- CD45- CD31- CD11a. After 5-aza treatment, 20-30% hMSCs connected with adjoining cells and coalesced into myotube structures after 14days. Twenty-one days after 5-aza treatment, immunofluorescence showed that some cells expressed desmin,GATA4, cTnI and connexin-43 in 5,10 μmol/L 5-aza groups, but no cardiac specific protein was found in neither 3μmol/L 5-aza group nor in the control group. The ratio of cTnI positively stained cells in 10 μmol/L group was higher than that in 5 μmol/L group (65.3 ± 4.7% vs 48.2 ± 5.4%, P ＜ 0.05). Electron microscopy revealed that myofilaments were formed. The induced cells expressed cardiac-myosin heavy chain (MyHC) gene by reverse transcription-polymerase chain reaction (RT-PCR). Conclusions Theses findings suggest that hMSCs from adult bone marrow can be differentiated into cardiac-like muscle cells with 5-aza inducement in vitro and the differentiation is in line with the 5-aza concentration. (J Geriatr Cardiol 2004;1(2) :101-107. )

Abstract?AIM: To assess the current situation of trachoma in Shaanxi Province and analyze its epidemiology and clinical features.?METHODS: The World Health Organization ( WHO ) simplified trachoma grading system was used for the recognition and registration of cases of trachoma. Trachoma rapid assessment ( TRA ) was conducted and 30.3687 million people from Shaanxi province were screened. Eyelids, eyelashes, conjunctiva and cornea were examined.The prevalence of trachoma trichiasis ( TT) in Shaanxi Province was estimated.?RESULTS: Totally 987 cases with TT were collected in Shaanxi province, in which 395 cases were male and 592 cases were female. The overall TT prevalence was 0.0325‰.The age of TT cases ranged from 25-86 years old, and concentrated in the 60-80 years old, only 58 cases were <50 years old.There were 12 cases of TT combined corneal opacity (CO) and the ratio was 1.2%. Sixty-four patients were cured by electrolysis trichiasis, the remaining 923 patients corrected by surgery interventions.?CONCLUSION: Based on the results of this study, trachoma blind is no longer estimated as a public health problem in Shaanxi province, as the detection rate of TT was less than 1‰ which is the goal of “elimination of trachoma” worldwide.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analgesics, Non-Narcotic ; adverse effects ; Anti-Bacterial Agents ; adverse effects ; Chemical and Drug Induced Liver Injury ; etiology ; Drugs, Chinese Herbal ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVESTo study the effectiveness of an artificial liver support system.

METHODSThirty-two patients with medicamentous liver insufficiency were treated with an artificial liver support system in addition to the routine medicinal therapy. Thirty patients treated with routine medicinal therapy only served as controls.

RESULTSThe clinical symptoms (e.g. hepatic encephalopathy) and the laboratory indices (serum total bilirubin and prothrombin time) of the treatment group patients were obviously improved compared with those of the control group patients (P < 0.05). The cure rate and hospitalization days were 90.6% (26/32) and 47 days respectively in the treatment group, and 43.3% (13/30) and 72 days in the control group (P < 0.05).

CONCLUSIONUsing an artificial liver support system combined with routine medicinal therapy is more effective than using medication alone.

Adult ; Aged ; Antineoplastic Agents ; adverse effects ; Antitubercular Agents ; adverse effects ; Female ; Hepatic Insufficiency ; chemically induced ; therapy ; Humans ; Liver, Artificial ; Male ; Middle Aged

Adolescent ; Adult ; Aged ; Chronic Disease ; Female ; Hepatitis, Viral, Human ; complications ; therapy ; Humans ; Liver Failure ; etiology ; therapy ; Liver, Artificial ; Male ; Middle Aged

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bile Acids and Salts ; metabolism ; Bilirubin ; blood ; Chemical and Drug Induced Liver Injury ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Fallopia multiflora ; chemistry ; HMGB1 Protein ; metabolism ; Hepatocytes ; drug effects ; Interleukin-1beta ; metabolism ; Liver ; drug effects ; pathology ; Plant Extracts ; pharmacology ; Rats ; Tumor Necrosis Factor-alpha ; metabolism

Disease recurrence is a main challenge in treatment of hepatocellular carcinoma (HCC). There is no generally accepted method for preventing recurrence of HCC after resection.

Objective To investigate the antibacterial molecular mechanism of Traditional Chinese Medicine Coptis rhizome against Yersinia pestis(Y.pestis).Methods The method based on whole genome DNA micrnarray of Y.pestis was used.The minimal inhibition concentration(MIC)of berberine to Y.pestis was determined with liquid dilution method.Then gene expression profile of Y.pestis was performed after exposed to berberine at the concentration of 10×MIC for 30 minutes.Total RNA extracted and purified from Y.pestis and reverse-transcribed to cDNA,then labeled by Cy-dye.Finally,the labeled probes were hybridized to the microarray and the results were obtained by a laser scanner and analyzed by the SAM software.Results The gene expression profile data revealed that the response of Y.pestis to berberine was a global phenomenon.A total of 360 genes changed significantly.Among them,333 genes were up-regulated,27 down-regulated.These differentially expressed genes were further classified into 24 different functional categories based on the genomie annotation of Y.pestis CO92,in which the number of mainly related genes were 83,75 and 48,including cell envelop,unkown,transport/binding proteins functions.The 40 genes related to the metabolism were upregulated,which was a remarkable change.Conclusion Our results have revealed the general gene expression changes of Y.pestis in response to berberine and demonstrated the antibacterial molecular mechanism of the Coptis rhizome.The major mechanism of Y.pestis in response to berberine is the upregulation of genes related to the metabolism.