Animals ; Bone Marrow Cells ; cytology ; metabolism ; Cell Proliferation ; Interleukin-10 ; genetics ; metabolism ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Organisms, Genetically Modified ; Rats ; Rats, Sprague-Dawley ; Transfection

OBJECTIVETo investigate the potential curative effects of bone marrow mesenchymal stem cells (BMSCs) overexpressing IL-10 for treating liver fibrosis by using a CCl4-induced rat model.

METHODSBMSCs were cultured and marked by DAPI staining of the cells' nuclei. Meanwhile, 60 Wistar rats were treated with CCl4 to induce liver fibrosis and randomly divided into three groups: A: injected with DAPI-marked BMSCs transfected with pcDNA3.0-IL-10; B: injected with DAPI-marked BMSCs; C: injected with phosphate-buffered saline. Histological analysis of excised livers was conducted to observe BMSCs (by DAPI marker) and fibrosis (by Masson's stain). Western blotting was used to detect IL-10 expression in BMSCs. Effects on expression of tumor necrosis factor-alpha (TNFa) were analyzed by enzyme-linked immunosorbent assay, and on hydroxyproline (HYP) levels were analyzed by the acid hydrolysis method.

RESULTSFollowing CCl4-inducement, rat livers showed the characteristic pathological changes of fibrosis and DAPI-marked cells (BMSCs) were observed. Compared with group C (pulmonary fibrosis score: 3.15+/-0.96; HYP level: 1.89+/-1.03 mug/mg), the extent of liver fibrosis was significantly lower in group A (pulmonary fibrosis score: 1.01+/-0.35; HYP level: 0.73+/-0.29 mug/mg) and group B (pulmonary fibrosis score: 1.34+/-0.65; HYP level: 1.21+/-0.78 mug/mg). The therapeutic effects were significantly greater in group A than group B (q=-4.73, P less than 0.05). TNFa protein expression was significantly lower in group A (275.21+/-86.35) and group B (321.76+/-98.49) than in group C (476.23+/-126.43). The TNFa expression was significantly lower in group A than group B (q=-7.43, P less than 0.05).

CONCLUSIONIL-10 gene-modified BMSCs are effective for treating liver fibrosis in a CCl4-induced rat model.

Animals ; Bone Marrow Cells ; Interleukin-10 ; genetics ; Liver Cirrhosis, Experimental ; therapy ; Male ; Mesenchymal Stromal Cells ; Rats ; Rats, Wistar ; Transfection

OBJECTIVETo study the effects of kaixinsan on behavior and expression of p-CREB in hippocampus of the chronic stress rats.

METHODThe male Wistar rats which gained the similar scores by Open-field test were selected, then the depression model rat was produced by separation and chronic unpredictable mild stress. Open-field test was performed to detect the behavior of rats and immunohistochemistry was used to observe the changes of p-CREB expression in hippocampus.

RESULTOn the 22nd day, the body weight and sacchar-intake of the depression model rats were all lower than those of the normal rats and the body weight and sacchar-intake of the rats treated by drugs were higher compared with model rats (P < 0.01). The depressive behavior in kaixinsan 4 g x kg(-1) group was significantly improved compared with the model group, the crossing scores and rearing scores were all increased (P < 0.01) and the expression of p-CREB in CA1, CA3 and DG in hippocampus was higher than that in the model group (P < 0.05 and P < 0.01).

CONCLUSIONKaixinsan might improve depressive behavior by increasing expression of p-CREB in CA1, CA3 and DG in hippocampus of the chronic stress rats.

Animals ; Antidepressive Agents ; pharmacology ; Behavior, Animal ; drug effects ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Depression ; etiology ; physiopathology ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Hippocampus ; metabolism ; Male ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Stress, Psychological ; complications

Objective To investigate the significance of genomic amplification of the telomerase RNA component (TERC) gene to serve as a genetic biomarker in the screening of cervicallesions.Methods A total of 715 cases were recruited,with liquid-based cytology diagnosis as normal (n=347),atypical squamous cells of undetermined significance (ASCUS,n=180),atypical squamous cells cannot exclude a high-grade lesion (ASC-H,n=13),low-grade squamous intraepithelial lesions (LSIL,n=115),high-grade squamous intraepithelial lesions(HSIL,n=59)and atypical glandular cells(AGC,n=1).The remaining cervical cells in the cytological preserving fluid were analyzed using a two-color fluorescence in situ hybridization (FISH) probe targeted to chromosome 3q26 containing TERC gene.The TERC gene findings were compared to the cytological and histological detected results,as well as high-risk human papillomavirus (HPV) detected results.Results Genomic amplification of TERC gene was found in 5.8% of normal specimens,22.2% of ASCUS.30.8% of ASC-H,27.8% of LSIL,86.4% of HSIL and 1/1 of AGC.The positive rate was significantly lower in normal,ASCUS,ASC-H and ISIL.compared with HSIL(all P<0.01).Significantly more cells with genomic amplification of TERC gene were found in cervical intraepithelial lesion(CIN) Ⅱ-Ⅲ than CIN Ⅰ (77.8% vs.9.3%),as well as invasive cervical cancer (96.7% vs.9.3%).both P < 0.01.The rate of TERC gene amplification was higher in HPV positive patients (33.5%) than in HPV negative patients(5.2%,P<0.01).The sensitivity of TERC gene amplification was significantly higher than that of cytological screening (81.88% vs.36.96%,P<0.01) in the differentiation of CIN Ⅱ or higher and CIN Ⅰ or lower diseases,its specificity Was hisher than high-risk HPV test (93.32% vs.33.93%,P<0.01) and positive prediction value (81.29%) was similar with cytological method (86.44%,P>0.05);but its negative prediction value (93.56%) was lower than HPV test (97.06%,P<0.05).Conclusions The positive rates of TERC gene amplification increased as cervical diseases worsened.TERC gene amplification is related to HPV infection.The gain of chromosome 3q26 in cytological specimens is an effective molecular genetic biomarker in screening of CIN Ⅱ or higher and invasive cervical cancer.

OBJECTIVETo explore the effect of compound qizhu granule (CQG) on cellular immunity of chronic hepatitis B (CHB) patients.

METHODSTotally 103 CHB patients treated with lamivudin (LAM) for 6 months, who had partial virological response (HBeAg positive) were randomly assigned to two groups, 50 in the treatment group and 53 in the control group. All patients took LAM 100 mg (once a day) plus ADV 10 mg (once a day). Patients in the treatment group additionally took CQG, one dose per day. After one-year treatment hepatitis B virus (HBV) DNA negative rates, HBeAg seroconversion, levels of HBV specific cytotoxic T lymphocyte (CTL), non-specific CTL and natural killing (NK) cells were compared between the two groups.

RESULTSAfter 1-year treatment, HBV DNA negative rate of the treatment group was 88: 0% in 44 cases, slightly higher than that of the control group (41 cases, 77.4%), but with no statistical difference (P >0.05). HBeAg seroconversion of the treatment group was 32.0% in 16 cases, higher than that of the control group (8 cases, 15.1%), with statistical difference (P <0.05). Levels of HBV specific CTL (0.79%±0. 07%), non-specific CTL (19.4%±1.8%) and NK cells (14. 1%± 1.5%) of the treatment group were higher than those of the control group (0.58% ± 0.08%, 17.5% ± 1.7%, and 11.1%±1.5%, respectively; allP <0.01).

CONCLUSIONTreating CHB patients with partial virological response by ADV plus CQG could improve specific and non-specific cellular immunity, thereby elevating HBeAg seroconversion rate.

Drugs, Chinese Herbal ; therapeutic use ; Hepatitis B e Antigens ; immunology ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Immunity, Cellular ; immunology ; T-Lymphocytes, Cytotoxic ; drug effects

Adult ; Amphotericin B ; administration & dosage ; therapeutic use ; Antifungal Agents ; administration & dosage ; therapeutic use ; Fluconazole ; administration & dosage ; therapeutic use ; Glucocorticoids ; adverse effects ; Hepatitis B, Chronic ; complications ; Humans ; Male ; Pulmonary Aspergillosis ; complications ; diagnosis ; drug therapy ; Tomography, X-Ray Computed

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

The research of anti-hepatocellular carcinoma(HCC) drug has attracted more and more attention. Natural products are the important source of active compounds for cancer treatment. A biflavonoid HIS-4 was isolated from Resina draconis in our previous study. MTT assay, hoechst staining, and flow cytometry analysis were used to investigate the effects of HIS-4 on the proliferation and apoptosis of human hepatoma HepG2 and SK-HEP-1 cells. Moreover, the effects of HIS-4 on the migration and invasion ability of HepG2 and SK-HEP-1 cells were evaluated by wound healing assay and Transwell assay. In addition, MTT assay, flow cytometry analyses, Hoechst staining, wound healing assay, Transwell assay, and tube formation assay were used to explore the anti-angiogenic activity of HIS-4 in human umbilical vein endothelial cells(HUVECs). Mechanistically, the HIS-4 regulatory of signal pathways in H9 epG2 and SK-HEP-1 cells were analyzed by Western blot. This results showed that HIS-4 suppressed the proliferation of human hepatoma HepG2 and SK-HEP-1 cells. Moreover HIS-4 induced their apoptosis of HepG2 and SK-HEP-1 cells. HIS-4 inhibited the migration and invasion of HepG2 and SK-HEP-1 cells. Additionally, HIS-4 exhibited angiogenesis effects. Mechanistically, up-regulation of MAPK signaling pathway and down-regulation of mTOR signaling pathway may be responsible for anti-hepatoma activity of HIS-4. Therefore, HIS-4 may be a promising candidate drug for HCC treatment.
Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Biflavonoids ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Cell Movement ; Cell Proliferation ; Dracaena ; chemistry ; Hep G2 Cells ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; Phytochemicals ; pharmacology