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Aim To investigate the hepatotoxic effect of aqueous extract of fructus psoraleae (WEFP) on lipopolysaccharide (LPS)-induced hepatotoxicity in SD rats under immune stress and its mechanism. Methods SD rats were divided into control (CON), LPS, WEFP, LPS+WEFP group. The LPS and LPS+WEFP groups were injected with 4 mg·kg-1 LPS via tail vein; 2 h later, the rats in WEFP group and LPS+WEFP group received the WEFP (1.1 g·kg-1·d-1) by oral gavage for seven consecutive days. Different endpoints such as body weight, liver index, bile flow rate, serum biochemical, histopathological changes, inflammatory cytokines, protein and mRNA expression levels were determined to clarify the liver toxicity and mechanism of WEFP. Results Compared with the CON group, rats in the LPS group had no significant changes in body weight, liver coefficient, serum ALT, AST, and ALP liver injury indicators; mild steatosis in the liver of the rats in the WEFP group did not cause liver damage; for rats in the LPS+WEFP group, body weight and bile excretion decreased, liver coefficient, serum ALT, AST, ALP, TBA levels significantly increased, and IL-1 and TNF-α secretion in the liver increased; at the same time, the pathological changes such as inflammatory reaction, cholestasis, and steatosis appeared in liver, RhoA mRNA and protein expression increased, and TLR4 and ICAM-1 pro-inflammatory gene expression increased, leading to acute liver injury. Conclusions The non-hepatotoxic dose of LPS can cause the same dose of psoralen to show more obvious liver toxicity, leading to the body's immunospecific response. Psoralen can cause immune stress rats to activate the expression of RhoA and other pro-inflammatory genes, further aggravate the release of inflammatory factors,and promote inflammatory reaction damage to liver cells and intrahepatic bile duct tissues,leading to obstruction of bile acid efflux and causing special effects such as heterogeneous liver injury.
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Aim To investigate the protective effect of TFDM on doxorubicin-induced endothelial cell injury and its mechanism.Methods Cell viability was detected by CCK-8 assay.Cell morphology was observed by microscope.The changes of LDH, SOD and mitochondrial membrane potential were detected by kit method.Cell migration was detected by Transwell assay; Endothelial dysfunction and VEGF-B/AMPKa pathway related protein expression were detected by Western blot.Results Compared with model group, TFDM significantly increased cell viability, improved the morphologic changes of HUVEC induced by DOX, decreased LDH leakage, increased SOD activity, increased mitochondrial membrane potential, promoted endothelial cell migration, and inhibited endothelial cell injury.The results of Western blot showed that com pared with control group TFDM increased the expression levels of non-receptor tyrosine kinase ( Src) and focal adhesion kinase (FAK) .increased the phosphorylation level of eNOS, and decreased the expression level of ET-1 protein, thereby inhibiting endothelial dysfunction.The protein expression levels of VEGF-B, NRP1 , VEGFR1 and the ratio of p-AMPKa/AMPKa significantly increased in the administration group.Conclusion TFDM may inhibit doxorubicin-induced endothelial cell injury by activating VEGF-B/AMPKa pathway.
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Objective To investigate the molecular characteristics of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients receiving antiretroviral therapy (ART) in Guizhou Province. Methods Using a convenience sampling strategy, 8 583 samples were collected in Guizhou and an investigation was conducted including face-to-face questionnaire interview and HIV testing. Results 1 511 cases failed in HIV suppression (viral load, VL>1 000 copies/ml). 1 410 cases (93.31%) were successfully genotyped with HIV pol gene, among which 51.42% were genotyped as CRF01_AE, 26.67% as CRF07_BC and 16.1% as CRF08_BC. Conclusion The subtype changes caused by HIV gene mutation should precede the changes of main transmission routes of HIV through the analysis in recent years. Timely monitoring the changes of HIV subtypes can be one of the main bases for the prevention and control of AIDS.
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As one branch of epigenetics, the sirtuins family ( ClassⅢ histone deacetylase) receive much attention in recent years. SIRT1 as the most famous of the sirtuins family members has been verified involved in a variety of age-related diseases. While the SIRT1 formation is paid more and more attention in age-related cataract. Now, we briefly overviewed the research progress on the role of SIRT1 in age-related cataract.
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?Silent information regulator protein 1 ( SlRT1 ) is a kind of histone deacetylases class lll on which cell metabolism coenzyme NAD+ is dependent. By the transcriptional regulation, it participates in the regulation of gene transcription, energy metabolism and cell aging process, which can prolong the lifespan of organisms and delay the development of various age-related diseases and has attracted much attention in the field of anti - aging research. ln recent years, studies have shown that SlRT1 occupies an important position in the pathogenesis of many ophthalmic diseases, especially in ocular surface diseases, glaucoma, cataracts, uveitis, and ocular fundus diseases, etc. There is a possibility that the promotion of SlRT1 activity would be the new drug target of ophthalmic therapy. The paper will review studies on SlRT1 and ophthalmic diseases.
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This study is to investigate the effect of Euphorbia humifusa effective fraction (EHEF) on the CYP51 enzyme activity, the lanosterol content and the MEP, SUB gene expression of Trichophyton rubrum. Trichophyton rubrum was treated by EHEF for 7 days at 26 degrees C. The activity of CYP51 enzyme of Trichophyton rubrum in the cell membrane was determined by using ELISA kit, and the lanosterol content was investigated by using high performance liquid chromatography (HPLC), and the MEP, SUB gene expression of Trichophyton rubrum was detected with the reverse transcription polymerase chain reaction (RT-PCR) method. Results showed that EHEF can decrease the membrane CYP51 enzyme activity, and it also can accumulate the fungal lanosterol in a dose-dependent manner, and it also can decrease the gene expression of MEP and SUB. The antifungal mechanism of EHEF may be related to the inhibition on CYP51 enzyme activity, and to the effects on fungal cell membrane ergosterol biosynthesis. It may also play an antifungal effect by inhibiting the MEP, SUB gene expression of fungal proteases.
Subject(s)
Antifungal Agents , Pharmacology , Cell Membrane , Metabolism , Drugs, Chinese Herbal , Pharmacology , Enzyme Activation , Euphorbia , Chemistry , Gene Expression Regulation, Fungal , Lanosterol , Metabolism , Metalloproteases , Metabolism , Plants, Medicinal , Chemistry , Sterol 14-Demethylase , Metabolism , Subtilisins , Metabolism , Trichophyton , Genetics , Metabolism摘要
<p><b>OBJECTIVE</b>To investigate the expression of the Eag1 K( +) channel in the prostate cancer (PCa) tissue, its correlation with the development and progression of PCa, and whether it could be a target for the diagnosis and treatment of PCa.</p><p><b>METHODS</b>We used RT-PCR and immunohistochemistry to determine the mRNA and protein expressions of the Eag1 K(+) channel in the normal peritumoral tissue of androgen-dependent PCa (ADPCa) (group A) and androgen-independent PCa (AIPCa) (group B) as well as in the tumorous tissue of ADPCa (group C) and AIPCa (group D).</p><p><b>RESULTS</b>The relative coefficients of the mRNA expression of the Eag1 K(+) channel were 0.265 +/- 0.413, 0.167 +/- 0.511, 2.673 +/- 2.988 and 2.815 +/- 2.901 in groups A, B, C and D, respectively, increased significantly in the latter two groups (P < 0.05). The positive rates of the protein expression of the Eag1 K (+) channel were significantly higher in groups C (88.9%) and D (86.7%) than in A (7.4%) and B (6.7%) (P < 0.05).</p><p><b>CONCLUSION</b>The Eag1 K(+) channel might be involved in the pathophysiological processes of PCa, and is expected to be a valuable target for the diagnosis and treatment of PCa.</p>
Subject(s)
Humans , Male , Ether-A-Go-Go Potassium Channels , Metabolism , Immunohistochemistry , Prostate , Metabolism , Pathology , Prostatic Neoplasms , Metabolism , Pathology , RNA, Messenger , Genetics , Reverse Transcriptase Polymerase Chain Reaction摘要
<p><b>BACKGROUND</b>It remains a challenge to inhibit the local recurrence or distant metastasis of localized or locally advanced renal cell carcinoma (RCC) after surgical resection. We investigated the feasibility, safety and efficacy of immunotherapy using autologous tumor lysate (TL)-pulsed dendritic cells (DCs) and cytokine-induced killer (CIK) cells in patients with localized or locally advanced RCC.</p><p><b>METHODS</b>From January 2001 to July 2009, we collected 137 patients that met the selection criteria and randomly divided them into three groups. After surgery, immunotherapy with TL-pulsed DCs-CIK cells (DC-CIK group) and interferon (IFN)-α (IFN-α group) was performed in 46 patients, respectively. The other 45 patients received no postoperative adjuvant therapy (the control group). The changes in the numbers of T lymphocyte subsets, including CD4(+)CD25(high) regulatory T cells (Treg), were determined before the operation and after immunotherapy. The overall survival was compared among the three groups.</p><p><b>RESULTS</b>An increase of the CD4(+)/CD8(+) ratio and a decrease of CD4(+)CD25(high) cells were observed after TL-pulsed DC-CIK cells or IFN-a immunotherapy. All patients tolerated the TL-pulsed DC-CIK cells immunotherapy very well, and side effects in the DC-CIK group were less than in the IFN-α group. The metastasis and recurrence rates were significantly decreased after TL-pulsed DC-CIK cells or IFN-α immunotherapy compared with the control group (P < 0.01). The Log-rank test showed that the overall survival rates were significantly higher in the DC-CIK group and IFN-α group than that in the control group (P < 0.01), but there was no difference between the DC-CIK group and IFN-α group (P > 0.05).</p><p><b>CONCLUSION</b>Postoperative immunotherapy with TL-pulsed DC-CIK cells may prevent recurrence/metastasis and increase the overall survival rate after surgery in localized or locally advanced RCC.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Renal Cell , Allergy and Immunology , Mortality , Therapeutics , Cytokine-Induced Killer Cells , Allergy and Immunology , Dendritic Cells , Allergy and Immunology , Immunotherapy , Kidney Neoplasms , Allergy and Immunology , Mortality , Therapeutics , T-Lymphocyte Subsets , Allergy and Immunology摘要
Objective To study the HIV-1 diversity and how did it promot the rapid spread of AIDS,in Guizhou province.Methods A total of 190 HIV-1 positive subjects were collected in different years and regions from Guizhou province.The env and gag genes were amplified with nested PCR and their sequences were determined.The subtypes were identified by the MEGA 4.0 software and the relationships between subtypes and AIDS epidemic were analyzed.Results The number of HIV/AIDS reported cases was increased from 66 in 1998 up to 8435 in 2009,a 16.38 time increase in 7 years.Subtypes B(9),B'(4),C(2),CRF07_BC(75),CRF08_BC(17),CRF01_AE(64)were identified in Guizhou province among the samples collected in various periods of time.The genetic diversities in env gene of CRF07_BC and CRF08_BC increased along with the spreading of HIV (from 0.035±0.006 to 0.092±0.011).Subtype B'(4/11)appeared the main subtype prevailed in Guizhou in 1998 as well as CRF07_BC(26/41)in 2002 and CRF01_AE(62/119)in 2007.The HIV/AIDS epidemic in Guizhou province showed an rapidly upward trend,with the main risk factors of HIV transmission as 2610 cases through injecting drug users(IDUs).and 176 cases due to sexually transmitted infections(STIs),from year 2001 to 2006.However,STIs began to increase rapidly,after 2006,with 1713 cases of IDUs and 1833 cases of STIs.Data indicated that the change of composition of different HIV-1 subtypes was correlated with the mode of transmission in Guizhou province(x2=41.253,P=0.000).Conclusion The types of HIV strains changed over time as well the turnover of the main risk factors.Sexual transmission,including both hetero-and homo-sexual became the main risk factors,suggesting the development of related prevention and control programs,on HIV/AIDS should be considered accordingly in the future.
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OBJECTIVE@#To investigate the protective effect of isoflurane delayed preconditioning on myocardial ischemia reperfusion injury and the potential mechanism in rabbits.@*METHODS@#Thirty New Zealand male white rabbits were randomly assigned to 3 groups: Control group; I/R group; and 2.0% isoflurane group. Isoflurane group was exposed to 2.0% isoflurane-100% oxygen for 2 hours. Control group and I/R group were exposed to 100% oxygen for 2 hours and served as untreated controls. Twenty-four hours later I/R group and isoflurane group underwent 40 minutes of coronary occlusion followed by 2 hours of reperfusion. Blood samples were taken from the arterial line at 20 minutes before the occlusion(T1), 20 minutes after the occlusion(T2), 40 minutes after the occlusion(T3), 1 hours after the reperfusion(T4), and 2 hours after the reperfusion(T5) to determine the plasma level of TNF-alpha. At the end of the reperfusion, infarct size and area at risk were defined by Evans and TTC staining. The heart was harvested and levels of the p38MAPK activity were determined by Western blot, and ultrastructures were observed under the electron microscope.@*RESULTS@#The p38MAPK activity of isoflurane group was significantly lower than that of I/R group (P<0.05). Isoflurane significantly (P<0.05) reduced the infarct size(19.7%+/-2.8% in isoflurane group) of the left ventricular area at risk as compared with the controls (37.8%+/-1.7% in I/R group).The injury of I/R group was worse than that of isoflurane group under the light microscope. Isoflurane group had a lower level of TNF-alpha than I/R group.@*CONCLUSION@#Isoflurane can inhibit p38MAPK activity during myocardial ischemia reperfusion and modulate the cytokine expression, which may be one of the molecular mechanisms of isoflurane delayed preconditioning on cardioprotection.
Subject(s)
Animals , Male , Rabbits , Ischemic Preconditioning, Myocardial , Methods , Isoflurane , Pharmacology , Myocardial Reperfusion Injury , Pathology , Myocardium , Random Allocation , Tumor Necrosis Factor-alpha , Metabolism , p38 Mitogen-Activated Protein Kinases , Metabolism摘要
<p><b>OBJECTIVE</b>To observe the therapeutic effect of eye-needling combined with medication for treatment of ophthalmoplegia and explore the possible mechanism.</p><p><b>METHODS</b>One hundred and twenty cases were randomly divided into a treatment group and a control group. According to etiological factors, the control group were treated with medication and the treatment group with the medication plus eye-acupuncture at main point ocular muscles. Changes of the rima oculi, the range of ocular movement and the dialopia angle after treatment were recorded and statistically analyzed in the two groups.</p><p><b>RESULTS</b>The total effective rate was 93.4% and the cured rate was 54.1% in the treatment group, and 74.6% and 18.6% in the control group, with significant difference between the two groups (P < 0. 01).</p><p><b>CONCLUSION</b>Eye-needling combined with medication has an obvious therapeutic effect which is better than simple medication for ophthalmoplegia.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Acupuncture Therapy , Methods , Combined Modality Therapy , Ophthalmoplegia , Therapeutics摘要
@# Objective To observe the effect of “Shengbai Tablets” on increasing the numbers of leucocyte, enhancing lymphocyte proliferation and reducing the micronucleus rate of cells.Methods The leukopenia model of mouse was established with cyclophosphamide, and the changes of the leukocyte count, lymphocyte proliferation and micronucleus rate before and after Shengbai Tablets treatment were observed.Results After treatment, the leukocyte count, lymphocyte proliferation and micronucleus rate of the Shengbai Tablets group were ( 7.470 ±1.852)×109/L, (14768.23±8316.86) and (6.02±1.72)‰ respectively, all were significantly better than that of the group without Shengbai Tablets treatment ( P<0.05~0.01).Conclusion Shengbai Tablets is able to increase the numbers of leucocyte, enhance the lymphocyte proliferation and reduce the micronucleus rate.
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Objective To investigate whether mesenchymal stem cells can promote the recovery of acute renal tubular damage induced by mercuric chloride and to explore its possible mechanism.Methods Acute renal failure rat model was established by intraperitoneal injection of mercuric chloride.SD rats were randomly divided into three groups which were MSCs injection group, saline infusion group and normal control group.Seven days later,the changes of rat weight,survival,renal function and pathology were observed;PCNA,ED-1 and GFP were detected by immunohistochemistry; The expression of cytokines in kidney and the distribution of GFP plasmid-transfected MSCs in kidney were examined by RT-PCR.Results MSCs infusion ameliorated the decline of rat weight,survival, renal function,and pathological changes.PCNA and ED-1 positive cells in MSCs group were fewer than those in saline group.Expression of growth factors EGF,PDGF,HGF were obviously up- regulated and pre-inflammatory cytokines TNF-?was significantly reduced in MSCs-treated kidneys. GFP-labelled MSCs occurred occasionally in renal interstitium of MSCs-treated rats,but not in renal tubules.Conclusions Bone marrow mesenchymal stem cells can promote the recovery of acute renal tubular epithelial cells damage caused by mercuric chloride.The mechanism may partly depend on regulating the excretion of cytokines in renal microenvironment rather than completely depend on their differentiation to tubular cells.