Abstract: TGF-β/Smad signaling pathway has a wide range of biological activities and plays an important roles in regulating cell growth, adhesion, differentiation, cell dynamic balance, and immune responses. The higher activity of TGF-β/Smad signaling pathway may promote scar formation, organ fibrosis, immunosuppression, and late-stage cancer progression, while low activity may lead to inflammation, dysplasia, poor healing and oncogenesis. The function of the TGF-β/Smad signaling pathway is extremely complex and can exhibit inhibitory or enhancing effects on immunity and inflammation under different circumstances, but immunosuppressive and anti-inflammatory effects are dominant. During HIV infection, the TGF-β/Smad signaling pathway interacts with HIV in a complex manner as HIV proteins tat and gp120 can induce TGF-β expression. Meanwhile, this signaling pathway may also play a role in HIV infection and replication, latent virus reservoir, host immune deficiency and HIV-related inflammation. It is worth noting that even though TGF-β, which mainly exhibits anti-inflammatory effects, is induced by HIV, high levels of TGF-β do not seem to inhibit HIV-related inflammation. So far, the relationship between TGF-β/Smad signaling pathway and HIV infection has not been elucidated, and its role and mechanism in HIV infection and related illnesses need further exploration and validation. This review summarizes the relevant research progress on the TGF-β/Smad signaling pathway and HIV infection, and provides a reference for further understanding of HIV pathogenesis and exploring strategies of AIDS treatment.

Aim To investigate the up-regulation of miR-22 through Wnt pathway inhibits the proliferation,migration and invasion in human gastric MGC803 cells induced by diallyl disulfide(DADS).Methods The effects of proliferation,migration,and invasion of gastric cancer cells were evaluated by MTT,wound-healing and invasion assays.Online prediction software was applied to search the target gene of miR-22.Luciferase report gene assay was used to assess the target genes Wnt-1 of miR-22.The expressions of Wnt-1,β-catenin and TCF-4 were tested by qRT-PCR and Western blot,respectively.Results MTT showed that DADS and miR-22 notably decreased the proliferation compared with control group(P<0.05).Wound-healing assay showed that DADS and miR-22 could significantly inhibit the migration of MGC803 cells compared with the control group, especially in miR-22+DADS(P<0.05). Invasion assay showed that DADS and miR-22 could markedly inhibit the invasion of MGC803 cells compared with the control group, especially in miR-22+DADS(P<0.05). Online prediction software to search the target gene exhibited that Wnt-1 may be a target gene of miR-22. Luciferase report gene assay disclosed that Wnt-1 was identified as a direct target of miR-22. Qrt-PCR showed that the expression of Wnt-1 Mrna was respectively down-regulated by DADS and miR-22 compared withcontrol group, especially in miR-22+DADS(P<0.05). Western blot exhibited that DADS and miR-22 obviously suppressed the expressions of Wnt-1, β-catenin and TCF-4 proteins, especially in miR-22+DADS(P<0.05).Conclusion Up-regulation of miR-22 through Wnt pathway can remarkably suppress the proliferation, migration and invasion in MGC803 cells by DADS.

Objective:This work aims to investigate diallyl disulfide (DADS) inhibition of cell migration and invasion in human colon cancer SW480 cells through the Rac1-ADF/cofilin1 pathway. Methods:The potential of cell migration and invasion was examined by scratch healing assay and transwell membrane assay. The expression of Rac1-ADF/cofilin1 pathway was detected by RT-PCR and Western blot. Results:After the SW480 cells were treated with 40 and 50 mg·L-1 of DADS for 24 h, the number of transmembrane cells through the Matrigel obviously decreased by 57.12%and 64.59%, respectively (P<0.05). After cell treatment for 48 h, the cell migration rates were 23.23%and 12.87%, which were significantly lower compared with the control group (75.86%;P<0.05). After the cells were treated with 45 mg·L-1 of DADS for 24 and 48 h, the expression of Rac1, Rock1, PAK1, LIMK1, and destrin mRNA respectively decreased compared with the control group (P<0.05). However, no significant difference was observed in the expression of cofilin1 mRNA (P>0.05). After the treatment with 45 mg·L-1 of DADS for 6, 12, 24, and 48 h, the expression of Rac1, Rock1, PAK1, LIMK1, and Destrin proteins respectively decreased in a time-dependent manner compared with the control group (P<0.05). However, no significant differences were observed in the expression of the cofilin1 protein (P>0.05). Moreover, the expression of p-LIMK1 and p-cofilin1 notably decreased in a time-dependent manner (P<0.05). Conclusion:DADS inhibits cell migration and invasion, which is related to the down-regulation of Rac1, Rock1, PAK1, LIMK1, p-LIMK1, p-cofilin1, and destrin through the Rac1-ADF/cofilin1 pathway.

Aim To explore the effects of DADS in the cell cycle of HT-29 cells. Methods HT-29 cells growth inhibition were measured by MTT assay and cell counting. Phase distribution of cell cycle was analyzed by flow cytometry. Expression of p21~(Waf1),C-myc,Cyclin E was determined by immunohisto- chemistry analysis. Results MTT assay showed that DADS significantly inhibited HT-29 cells and exhibited a time, dose- dependent model. Adding 60 ?mol?L~(-1) and 120 ?mol?L~(-1) DADS for 24 h suppressed HT-29 growth by 23.1%,45.6% respectively. Cell counting showed that average doubling time retarded from 22.58 h in normal cultured HT-29 cells to 31.2 h in 60umol?L~(-1) DADS experimented HT-29 cells(P

In order to investigate the anti-proliferative effects of triptolide (TP) on 4T1 mice breast cancer cell line in vitro and in mouse model, as well as the possible mechanisms, we detected the effect of TP on cell proliferation by MTT assay or Crystal Violet Staining in our research. Flowcytometry combined with FITC-Annexin V/PI staining were used for detecting TP induced 4T1 cell apoptosis. The protein expression of ERalpha, p-ERalpha, ERbeta, p-ERbeta, ERK, p-ERK, p38, p-p38, SAPK/JNK, and p-SAPK/JNK was tested by western blotting. We also compare TP with chemotherapy drug doxorubicin in 4T1 tumor bearing BLAB/c mice model, the Xenogen bioluminescence imaging, H&E, and IHC result indicated that TP exhibits an anticancer proliferation activity. As a result, TP in 100, 10, 1, 0.1 micromol x L(-1), all inhibited the proliferation of 4T1 cells by MTT assay and Crystal Violet Staining. TP which concentrations is 10, 1, 0.1 micromol x L(-1) could induce the apoptosis of 4T1 cells and reduce the cell proliferation. TP in 200 microg x kg(-1) could inhibit the tumor growth in vivo. The anticancer proliferation of TP was involved in its effect on reducing expression of ERalpha, p-ERalpha, ERbeta, and p-ERbeta, but nothing to do with the activation of MAPK signaling pathway.
Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; Diterpenes ; pharmacology ; therapeutic use ; Down-Regulation ; drug effects ; Epoxy Compounds ; pharmacology ; therapeutic use ; Female ; Lung Neoplasms ; secondary ; Mammary Neoplasms, Experimental ; drug therapy ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C ; Phenanthrenes ; pharmacology ; therapeutic use ; Phosphorylation ; drug effects ; Receptors, Estrogen ; metabolism ; Tumor Burden ; drug effects

Adult ; Cardiac Catheterization ; Female ; Heart Septal Defects, Ventricular ; surgery ; Humans ; Postoperative Complications

Objective To explore the clinical characteristics and therapy of brucellar meningitis in children.Method One case of brucellar meningitis was reported and relevant literatures were reviewed.A 10 years old boy was admitted to hospital with a history of half a month fever and cough and 3 days headache.His family raised sheep,but he denied contacting closely with sheep and eating raw goat's milk and mutton.Results The course of this reported child was subacute.Clinical manifestations included fever,headache and meningeal irritation sign positive.The cerebrospinal fluid(CSF)findings were similar to those of tuberculous meningitis,where WBC count was elevated with predominant lymphocytes,glucose and chloride decreased and protein increased.The serum bacterium burgeri antibody was positive,agglutination titer was 1160.After brucellar meningitis was diagnosed,three antibiotics including rifampin,minocycline and ceftriaxone sodium and other symptomatic treatment were used.The CSF findings were normal 2 weeks later.This child taked orally minocycline,rifampin and trimethoprim-sulfamethoxazole for 8 weeks post discharge,the recovery was good.The domestic and foreign documents showed that the incidence of the nervous system complications of brucellosis in children was lower than that in adult.The main clinical manifestations were acute meningitis /meningocephalitis.Brucellar meningitis could be misdiagnosed as tuberculous meningitis,because the course of disease,clinical manifestations and CSF findings were similar.Therapeutic alliance including 3 kinds of antibiotics,which could easily pass through blood-brain barrier,was used to treat brucellar meningitis.The total course of treatment shouldn't be shorter than 8 weeks.Conclusions Brucellar meningitis should be screened through epidemiological investigation,serum agglutination test and cerebrospinal fluid culture,in case the reason of meningitis of meningoencephalitis is unknown,especially its clinical manifestation resembles to tuberculous meningitis.

A reasonable and practicable quality standard was developed for mori liquid extract from different sources by TLC, HPLC and fingerprint technology. In TLC method, the compounds were separated on polyamide film using glacial acetic acid-water (1: 3) as mobile phase at a UV wavelength of 365 nm. All qualified samples had the spots of the same color as the control herb and substance. The RP-HPLC method was used to determine the content of mulberroside A with mobile phase of methanol-water (25: 75) at a wave-length of 326 nm. The mulberroside A was in good linear with a regression equation of Y = 46.965X (r = 0.999 6) in the range of 4.6 - 228 mg x L(-1). In 14 batches of samples, the mulberroside A in 4 batches of them was less than 0.5 g x L(-1), and was more than 2.0 g x L(-1) in the other batches. It was suggested that the content limit of mulberroside A should be no less than 1.5 g x L(-1). The HPLC fingerprints were evaluated by the similarities. It has found that the similarities of different mori liquid extracts were very low and the chemical diversity of mori cortex was the major factor of similarity. Moreover, the process impact was minimal. Thus the fingerprint was not included in this quality standard.
China ; Chromatography, High Pressure Liquid ; Disaccharides ; chemistry ; isolation & purification ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; standards ; Morus ; chemistry ; Quality Control ; Stilbenes ; chemistry ; isolation & purification

Aim Toresearchthemolecularmecha-nisms of DADS-induced apoptosis in human leukemia K562cells.Methods Cellviabilitywasmeasuredby MTT. Levels of DADS-induced ROS were measured by 2ˊ, 7ˊ-dichlorofluorescein diacetate ( DCFH-DA) fluo-rescence. DADS-induced mRNA levels of components of the NADPH oxidase were detected by Real-time PCR. The combination of protein Rac2 and p67phox was measured by immunoprecipitation assays. Flow cy-tometry methods were used to determine the percentage of apoptosis cells. DADS-induced Rac2 levels were measuredbyWesternblot.Results TheDADS-trea-ted K562 cells showed a dose-and time-dependent de-crease in cell viability and proliferation. There was sig-nificant up-regulation of the mRNA level of components of the NADPH oxidase complex in K562 cells after treatment with 6 mg·L-1 DADS for 6 h. Western blot results revealed that, compared with the control group, there was a significant up-regulation of Rac2 protein in K562 cells treated with 5. 0 and 10. 0 mg·L-1 DADS for 24h. And Rac2 combined with p67phox in DADS-induced apoptosis in K562 cells. PMA markedly in-creased the percentage of apoptotic cells, and DPI re-duced the percentage of apoptotic cells in DADS-in-duced K562 cells. Levels of DADS-induced ROS, also showed enhancement when exposed in PMA, but there was no DADS-induced ROS production evident when exposed in DPI in DADS induced K562 cells. Conclu-sions TheseresultsindicatethatNADPHoxidaseis the main source of DADS-induced ROS production. Diallyl disulfide induces apoptosis in human leukemia K562 cells through activation of NADPH oxidase.

OBJECTIVETo observe the effect of composite factors, like long-term high-salt & fat diet and alcohol abuse on blood viscosity and blood pressure in rats, and compare with a model induced by high molecular dextran, in order to build a chronic hyperviscosity aminal model which is similar to human hyperviscosity in clinic and lay a foundation for efficacy evaluation on traditional Chinese medicines.

METHODMale SD rats were randomly divided into the normal group, the high molecular dextran (HMD) group and the high salt & fat and alcohol (HSFA) group. The HMD group was given normal diet and water for 23 day and then 10% HMD through tail vein for 5 days. The HSFA group was fed with high salt and high fat diets every day and alcohol for 20 h x d(-1) for 13 weeks. After the modeling, whole blood viscosity and plasma viscosity were measured in the 5th, 8th and 11th week. Blood pressure was measured in the 5d, 7h, and 10th week. Red cell count (RBC) and hematocrit (HCT) were measured in the 11th week. PAgT, Fb, ET-1, NO, PGI, TXA2 contents of the normal group and the HSFA group were measured in the 13th week, and IECa21 content was measured with flow cytometry. Result: After the modeling, the HMD group was in good conditions with glossy hairs and active behaviors. The HSFA group was depressed with withered hairs and less activities. During the 5th-11th weeks, the HMD group and the HSFA group showed higher values in high and low shear whole blood viscosity (WBV) than the normal control group. The plasma viscosity (PV) of HMD rats was significantly increased only in the 5th week, and that of HSFA rats significantly increased in the 8"' and 11th week, particularly in the 11'h week. In the 111h week, the HSFA group showed significant increases in RBC and HCT. After the modeling, the blood pressure of HMD rats showed no significant changes, but the blood pressure of HSFA rats significantly increased during 7' and 101h weeks, particularly in the 10"' week. In the 13th week, PAgT, IECa2+, Fb, ET-1 of HSFA rats significantly increased, but with decreases in NO and PGI2.

CONCLUSIONLong-term high salt & fat and alcohol diets can cause abnormal blood viscosity in rats. WBV significantly increased since the 5th week in rats, and PV increased since the 8th week. The mechanism for increasing BV may be: (1) increases in RBC, HCT, and IECa2+, (2) PAgT increase, (3) Fb content increase, or (4) TXA2/PGI2, ET-1/NO imbalance. Although the modeling time with the method is longer than that with the HMD method, the model is more stable and moderate, and could lead to abnormal increases in WBV and PV; Whereas the HMD method only induced transient increase in plasma viscosity and abnormal increase in SBP. The model is more similar to traditional Chinese medicine syndromes and pathogenesis, with higher value for studies on efficacy of traditional Chinese medicines.

Alcoholism ; blood ; metabolism ; Animals ; Blood Pressure ; Blood Viscosity ; Diet, High-Fat ; adverse effects ; Disease Models, Animal ; Ethanol ; adverse effects ; metabolism ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride, Dietary ; adverse effects ; metabolism