Alcoholism ; drug therapy ; metabolism ; physiopathology ; Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hippocampus ; metabolism ; Learning ; drug effects ; physiology ; Male ; Memory ; drug effects ; physiology ; Phytotherapy ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; genetics ; metabolism ; Superoxide Dismutase ; metabolism

Objective To further clarify the pathogenesis of different types of Kaposi′s sarcoma (KS) by measuring the protein expressions of caspase-3 and E-cad in tumor tissues of Xinjiang Uygur patients with acqured immunodeficiency syndrome (AIDS)-Kaposi′s sarcoma (KS) and classical KS.Methods From July 2011 to October 2014, 38 patients with KS at the First Affiliated Hospital of Xinjiang Medical University and Urumqi Infectious Disease Hospital were enrolled, among whom 28 were male and 10 were female, and all of them were uygur.Immunohistochemical and Western blot methods were used to detect the expressions of caspase-3 and E-cad proteins in 22 cases of AIDS-KS patients and 16 cases of classic KS.The quantitative data of normal distribution were analyzed by t test, while count data were compared with χ2 test with R × C table.Results KS lesions in patients with classic KS were confined to the skin, without mucosal, lymph node or visceral involvement.Lesions in AIDS-KS patients were not only confined to the skin and superficial lymph nodes, but also oral mucosa involved in 12 cases and internal organs involved in 7 cases.Liver and lung involvement was more common.The CD4+T lymphocyte count in patients with AIDS-KS was (200.8±166)/μL.All 15 AIDS cases with CD4+ T cell count less than 200/μL developed opportunistic infections.CD4+ T lymphocyte count of patients with classic KS was (562.52±222.66)/μL and the 16 patients with CD4+T lymphocyte count greater than 350/μL had no opportunistic infections.The results of immunohistochemistry showed that the positive expression rate of caspase-3 protein in KS tissues in patients with AIDS-KS was 68.2%, in patients with classic KS was 100.0%, with significant difference between two groups (χ2=7.37, P=0.01).The positive expression rate of E-cad protein in KS tissues in patients with AIDS-KS was 72.7%, in patients with classic KS was 100.0%, with significant difference between two groups (χ2=5.18, P=0.03).Western blotting showed that the gray value of caspase-3 in the KS tissue of patients with AIDS-KS was 0.55±0.36, and that in patients with classic KS was 0.86±0.56, with significant difference between two groups (t=-2.070, P<0.05).The gray value of E-cad in the KS tissue of patients with AIDS-KS was 0.54±0.41, and that in patients with classic KS was 0.85±0.45, with significant difference between two groups (t=-2.060,P<0.05).Conclusions There are differences in the protein expressions of caspase-3 and E-cad in tumor tissues of patients with AIDS-KS and classical KS in Xinjiang Uygur patients with Kaposi's sarcoma, which may correlate with a faster progression and a higher mortality rate for AIDS-KS.

AIM:To explore the potentially beneficial clinical effects of traditional Chinese medicine(TCM) combined with photocoagulation for diabetic retinopathy(DR).METHODS:Chinese patients with DR were divided into two groups. A joint treatment group received both the TCM ziyinliangxuesanyutang and photocoagulation, while a control group received only photocoagulation laser treatment. Visual acuity tests, visual field retinal sensitivity tests, and fundus fluorescein angiography (to measure neovascular regression) were performed. Vision was compared between the two groups 1 month, 6, and 12 months after treatment.RESULTS:Twelve months after treatment, the recovery of visual acuity (62.3% vs 43.1%, P=0.037) and retinal sensitivity \[17.0±3.7 decibels (dB) vs 14.9±3.7dB, P=0.002\] as well as neovascular regression (67.2% vs 48.3%, P=0.036) in the joint treatment group were all significantly greater than that of the control group.CONCLUSION:Compared with laser treatment alone, the joint application of TCM and photocoagulation is shown to be more effective than DR treatment method.

The cyp51 primers and two pairs of mutant primers which removed different transmembrane region were designed based on Ustilago maydis cyp51 gene structure analysis. The full cyp51 DNA fragment as well as mutant cyp51 genes were amplified and cloned by using the total DNA from Ustilago maydis as template, then subcloned into different expression vectors. The recombinant expression plasmids were transformed into Escherichia coli BL21 (DE3), BL21 (DE3) pLysS and Rosetta (DE3) respectively. A series of experiments leads to the finding that only pET32-YH-35 could be highly expressed at the optimal condition of 30 degrees C induced with 0.5 mmol/L IPTG The expressed protein (CYP51) showed biological activity by spectra analysis of the protein binding to 4 standard fungicides and to 14 XF-synthetic fungicide compounds, and only one XF-synthetic fungicide compound (XF-113) was similar to standard fungicides in binding constant. This compound is promising to be a new effective antifungal drug. These results will facilitate the further study on the mechanism of pathogenic fungi CYP51 and pesticide molecules, and will provide a new idea for efficient design and development of new anti-fungal drugs.
Antifungal Agents ; isolation & purification ; Cloning, Molecular ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Escherichia coli ; genetics ; metabolism ; Fungal Proteins ; genetics ; metabolism ; Plasmids ; genetics ; Recombinant Proteins ; genetics ; metabolism ; Sterol 14-Demethylase ; Ustilago ; enzymology ; genetics

OBJECTIVE: To investigate the effectiveness and safety of laparoscopic CY Liu non-mesh pelvic floor repair surgery in treatment of pelvic organ prolapse(POP).METHODS: From February 2016 to September 2017,a total of 83 patients with POP were treated in Zhejiang Province People's Hospital,and they were included in this retrospective study.The clinical data were retrospectively analyzed;the POP-Q scores were used as the objective evaluation indicators for POP.Analyze the changes of POP-Q indicator points after surgery,and observe surgery related data and complications.Evaluate the postoperative symptom improvement and subjective satisfaction rate of the patients using pelvic floor impact questionnaire short form(PFIQ-7).RESULTS: All surgeries of the included 83 patients were successfully finished laparoscopically.The average follow-up time was(18.88±3.82)months,but there were 8 cases of loss of follow-up.During the follow-up,the total anatomical success rate of laparoscopic CY Liu non-mesh pelvic floor repair surgery was 97.33%(73/75).The differences in POP-Q scores and PFIQ-7 scores were statistically significant before and after the surgery(P<0.05).Subjective satisfaction rate was 96.00%(72/75)after surgery.CONCLUSION: Laparoscopic CY Liu non-mesh pelvic floor repair surgery is effective in the management of Ⅱ-Ⅳ pelvic organ prolapse.There's no need for mesh,and the recurrence rate is low in short-term follow-up,which is worth paying attention to.

AIMTo investigate the effect of ligustrazine (LGT) on expression of Fas/FasL mRNA during pulmonary ischemia/reperfusion injury (PI/RI) in the rabbits.

METHODSSingle lung ischemia/reperfusion animal model was used in this study. The rabbits were randomly divided into three groups (n = 30, in each): sham operated group (Sham), I/R group (I/R) and I/R + LGT group (I/R + LGT). Changes of several parameters which included apoptotic index (AI), wet to dry ratio of lung tissue weight (W/D) and index of quantitative assessment of histologic lung injury (IQA) were measured at 1h, 3h, 5h after reperfusion in lung tissue. Meanwhile the location and expression of Fas/FasL mRNA were observed. Lung tissue was prepared for light microscopic and electron microscopic ob servation at 1 h, 3 h, 5 h after reperfusion.

RESULTSAs compared with group I/R, Fas/FasL mRNA slightly expressed in intima and extima of small pulmonary artery, alveoli, and bronchiole epithelia in group LGT. The values of AI, W/D and IQA showed significantly lower in group I/R + LGT than that in group I/R at 1 h, 3 h, 5 h after reperfusion in lung tissue (P < 0.01 and P < 0.05). Meanwhile, abnormal changes of the lung tissue in morphologically were lessen markedly in group I/R + LGT.

CONCLUSIONLigustrazine has notable protective effects on PI/RI in rabbits by inhibiting Fas/FasL mRNA express in lung tissue and decreasing apoptosis.

Animals ; Apoptosis ; Fas Ligand Protein ; metabolism ; Lung ; blood supply ; Lung Injury ; metabolism ; pathology ; Pyrazines ; pharmacology ; RNA, Messenger ; genetics ; Rabbits ; Reperfusion Injury ; metabolism ; pathology ; fas Receptor ; metabolism

OBJECTIVEInflammation serves as the initial pathologic step of cardiovascular diseases including atherosclerosis. Resveratrol possesses many pharmacological properties including antioxidant, cardioprotective and anti-cancer effects. In this study, we investigate the anti-inflammatory effect and mechanisms of resveratrol in an atherosclerotic rabbit model.

METHODSRabbit were assigned to six groups (n = 10 each): control, high fat diet group, resveratrol low, medium and high dose groups, resveratrol pretreatment group. The serum tumor necrosis factor-α (TNF- α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were analyzed by Enzyme-linked immuno sorbent assay(ELISA). Phosphorylation levels of mitogen-activated protein kinases (MAPKs) cascades and NF-κB were determined by Western blot.

RESULTSCompared with the control group, the expression of serum inflammatory factors IL-1β, IL-6, TNF-α were increased in high-fat group (all P < 0.05). Compared with high-fat group, the expressions of IL-6, IL-1β, TNF-α were significantly reduced in resveratrol low, medium, high dose groups and resveratrol pretreatment group (all P < 0.01), and this effect is dose-dependent. In addition, the NF-κB, p38MAPK, JNK, ERK1/2 protein phosphorylation in high-fat group were significantly upregulated compared with control group (P < 0.05), which (except ERK1/2 phosphorylation level) were significantly downregulated in resveratrol treatment group and resveratrol pretreatment group.

CONCLUSIONThis study indicates that resveratrol reduces serum inflammatory cytokines in this atherosclerotic rabbit model via down-regulation phosphorylation of NF-κB, and MAPKs signaling, which might serve as the anti-inflammatory molecular basis of resveratrol.

Animals ; Atherosclerosis ; drug therapy ; metabolism ; Disease Models, Animal ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Male ; Mitogen-Activated Protein Kinases ; metabolism ; NF-kappa B ; metabolism ; Phosphorylation ; Rabbits ; Signal Transduction ; drug effects ; Stilbenes ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo explore the effect of electroacupuncture (EA) on the pathomorphology of the sciatic nerve and the role of P2X3 receptors in EA analgesia.

METHODSThe chronic constriction injury (CCI) model was adopted in this study. A total of 32 rats were randomly divided into four groups: sham CCI, CCI, CCI plus contralateral EA (CCI + conEA) and CCI plus ipsilateral EA (CCI + ipsEA). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured. EA began at day 7 after the CCI operation and was applied to the Zusanli (ST 36) and Yanglingquan acupoints (GB 34). At day 14, the pathomorphologic changes of the operated sciatic nerve were demonstrated by hematoxylin and eosin staining. In addition, dorsal root ganglion (DRG) neurons isolated from rats were examined by electrophysiological recording to determine if the P2X3 receptor agonists, adenosine 5'-triphosphate disodium (ATP) and α,β-methylen-ATP (α,β-meATP) evoked inward currents.

RESULTSPain thresholds in the CCI group were obviously decreased post CCI surgery (P<0.01). In the EA groups, thermal and mechanical threshold values were increased after the last EA treatment (P<0.05, P<0.01). There was no significant difference in light microscopic examination among the four groups (P>0.05). Current amplitude after application of ATP and α,β-meATP in DRG neurons were much larger in the CCI group compared to those obtained in sham CCI (P<0.05). ATP and α, β-meATP invoked amplitudes in the CCI + EA groups were reduced. There was no signififi cant difference between the CCI + conEA group and the CCI + ipsEA group (P>0.05).

CONCLUSIONEA analgesia may be mediated by decreasing the response of P2X3 receptors to the agonists ATP and α,β-meATP in the DRG of rats with CCI. No pathological changes of the sciatic nerve of rats were observed after EA treatment.

Adenosine Triphosphate ; analogs & derivatives ; pharmacology ; Animals ; Constriction, Pathologic ; Electroacupuncture ; Ganglia, Spinal ; drug effects ; metabolism ; pathology ; Hyperalgesia ; pathology ; Ion Channel Gating ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Reaction Time ; drug effects ; Receptors, Purinergic P2X3 ; metabolism ; Sciatic Nerve ; injuries ; metabolism ; pathology ; Staining and Labeling

OBJECTIVETo understand the molecular basis for a potential reaction mechanism and develop novel antibiotics with homology modeling for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase (HMGS).

METHODSThe genetic engineering technology and the composer module of SYBYL7.0 program were used, while the HMGS three-dimensional structure was analyzed by homology modeling.

RESULTSThe mvaS gene was cloned from Streptococcus pneumoniae and overexpressed in Escherichia coli from a pET28 vector. The expressed enzyme (about 46 kDa) was purified by affinity chromatography with a specific activity of 3.24 micromol/min/mg. Optimal conditions were pH 9.75 and 10 mmol/L MgCl2 at 37 degrees C. The V(max) and K(m) were 4.69 micromol/min/mg and 213 micromol/L respectively. The 3D model of S. pneumoniae HMGS was established based on structure template of HMGS of Enterococcus faecalis.

CONCLUSIONThe structure of HMGS will facilitate the structure-based design of alternative drugs to cholesterol-lowering therapies or to novel antibiotics to the Gram-positive cocci, whereas the recombinant HMGS will prove useful for drug development against a different enzyme in the mevalonate pathway.

Amino Acid Sequence ; Base Sequence ; Cloning, Molecular ; Gene Expression Regulation, Bacterial ; physiology ; Hydroxymethylglutaryl-CoA Synthase ; chemistry ; genetics ; metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Streptococcus pneumoniae ; enzymology ; genetics

Adult ; Fatty Liver ; diagnosis ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; Waist-Hip Ratio