OBJECTIVE: This study aims to use Arginine-gingipain A gene vaccine (pVAX1-rgpA) to immunize adult Beagle dogs and to evaluate its effect during peri-implantitis progression and development. METHODS: Plasmid pVAX1-rgpA was constructed. The second and third bilateral mandible premolars of 15 adult Beagle dogs were extracted, and the implants were placed immediately. After 3 months, the animals were randomly divided into groups A, B, and C. Afterward, the animals were immunized thrice with plasmid pVAX1-rgpA, with heat-killed Porphyromonas gingivalis, or pVAX1, respectively. IgG in the serum and secretory IgA (sIgA) in saliva were quantitatively analyzed by enzyme-linked immunosorbent assay before and after 2 weeks of immunization. Peri-implantitis was induced with cotton ligatures fixed around the neck of implants. Probing depth (PD) and bleeding on probing were recorded. All animals were sacrificed after ligaturation for 6 weeks. Decalcified sections with thickness of 50 μm were prepared and dyed with methylene blue to observe the bone phenotype around implants. RESULTS: Levels of serum IgG and sIgA in saliva were higher in groups A and B after immunization than before the process (P<0.05) and higher than those in group C (P<0.05). However, no difference was observed between groups A and B (P>0.05). At 4 and 6 weeks after ligaturation, PD of the ligatured side in group C was higher than that in groups A and B (P<0.05). On the other hand, no difference was identified between groups A and B (P>0.05). Bone loss in group A was significantly lower than that of the other groups (P<0.05). Abundant inflammatory cells and bacteria were present in the bone loss area around the implants in the three groups, as identified through hard tissue section observation. However, group C presented the most number of inflammatory cells and bacteria in the bone loss area around the implants. CONCLUSIONS IgG and sIgA can be generated by immunity with rgpA DNA vaccine, which can significantly slow down bone loss during experimental peri-implantitis in dogs.
Adhesins, Bacterial ; therapeutic use ; Alveolar Bone Loss ; Animals ; Arginine ; Cysteine Endopeptidases ; therapeutic use ; Dental Implants ; Dogs ; Peri-Implantitis ; prevention & control ; Porphyromonas gingivalis ; chemistry ; Vaccines ; therapeutic use

We describe a patient with rheumatoid arthritis(RA) who developed bronchiolitis obliterans organizing pneumonia(BOOP) during the treatment of bucillamine. A 51 year-old man was admitted to the hospital for an abnormal shadow on his chest radiogragh. He had been diagnosed as having RA 3 years previously and had been receiving 200 mg of bucillamine for 21 months. Two months prior to admission, he presented with a cough and his chest X-ray showed opacities in both lower lungs. He was treated with antibiotics for 2 months after the development of cough and lesions on the chest X-ray, but the symptoms and lung lesions became more aggravated. On admission, an HRCT revealed airspace consolidations in the subpleural space of both basal lungs and a CT-guided fine needle aspiration biopsy showed Masson's body filling air space, interstitial infiltration of acute and chronic inflammatory cells and type II cell hyperplasia, consistent with BOOP. Bucillamine was stopped and 50 mg of prednisolone was administered. His symptoms and infiltrations on the chest X-ray resolved. We suggest that bucillamine should be considered as a drug possibly associated with BOOP.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects* ; Arthritis, Rheumatoid/drug therapy* ; Biopsy, Needle ; Bronchiolitis Obliterans Organizing Pneumonia/diagnosis* ; Bronchiolitis Obliterans Organizing Pneumonia/chemically induced* ; Case Report ; Cysteine/therapeutic use ; Cysteine/analogs & derivatives ; Cysteine/adverse effects* ; Follow-Up Studies ; Human ; Male ; Middle Age ; Radiography, Thoracic ; Risk Assessment ; Tomography, X-Ray Computed

OBJECTIVETo compare the efficacy and safety of Stronger Neo-Minophagen C (SNMC) in the treatment of chronic hepatitis B.

METHODSWe searched MEDLINE, EMBASE, CBM, and CNKI up to December, 2012 to identify randomized controlled trials (RCTs) comparing Stronger Neo-Minophagen C plus other therapy versus others therapy for chronic hepatitis B. Two reviewers independently assessed the risk of bias and extracted data from the included RCTs according to the Cochrane Reviewers Handbook 5.1.0. Meta-analyses were performed using RevMan 5.1 software.

RESULTSThirty-one trials involving 2753 patients were included in the analysis. The results of meta-analyses showed that SNMC improved hepatic functions of the patients by reducing ALT (MD=-31.63, 95% CI: -51.57, -11.70), AST (MD=-18.70, 95% CI:-25.10, -12.30), TBIL (MD=-12.17, 95% CI: -17.63,-6.71), HA (MD=-94.89, 95% CI: -125.19, -64.60), LN (MD=-40.08, 95% CI: -52.38,-27.78), IV-C (MD=-50.61, 95% CI:-63.40, -37.81), PC-III (MD=-49.71, 95% CI: -71.72, -27.69) as compared with the control group. The seroconversion rate of HBeAg (OR=2.23, 95% CI: 1.70, 2.94), HBV-DNA (OR=2.20, 95% CI: 1.70, 2.84), HBsAg (OR=2.25, 95% CI: 1.24 , 4.07), total response rate (OR=4.37, 95% CI: 2.62, 7.28), and ALT normalization rate (OR=3.77, 95% CI: 2.46, 5.79) were all significantly higher in the combined therapy group than in the control group.

CONCLUSIONSNMC plus other therapy is more effective than other therapy alone in improving the hepatic function and hepatic fibrosis and increasing hepatic seroconversion rate in patients with chronic hepatitis B without causing serious adverse events. But considering the low quality of the included studies, the results should be interpreted with caution and awaits further confirmation by high-quality, large-scale RCTs.

Cysteine ; therapeutic use ; Drug Combinations ; Glycine ; therapeutic use ; Glycyrrhetinic Acid ; analogs & derivatives ; therapeutic use ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Liver Cirrhosis ; drug therapy ; Randomized Controlled Trials as Topic

While most types of malignancies remain recalcitrant to treatment, application of natural products or their analogs in daily life has offered some hopes as an effective prophylaxis against cancer onset and progression in the past decades. Emerging evidence supports a link between garlic consumption and decreased cancer incidence. Notably, aged garlic extract (AGE) exhibits stronger anti-cancer activities than that of fresh garlic, by virtue of enrichment of several AGE-specific organosulfur compounds, including S-allylmercaptocysteine (SAMC). In this review, we summarize the up-to-date mechanistic pathways associated with the anti-proliferative, anti-metastatic and pro-apoptotic effects of SAMC in various cancer models. Based upon the proven safety and improved understanding on its anti-neoplastic properties, SAMC has gained recognition as a promising daily food supplement for cancer prevention or management.
Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Cysteine ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Disease Models, Animal ; Garlic ; chemistry ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; metabolism ; Signal Transduction ; drug effects

OBJECTIVE: Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis. METHODS: The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses. RESULTS: Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1. CONCLUSION The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.
Animals ; China ; Cysteine-Rich Protein 61/metabolism* ; Disease Models, Animal ; Drugs, Chinese Herbal/therapeutic use* ; Imiquimod/adverse effects* ; Inflammation/drug therapy* ; Intercellular Adhesion Molecule-1/genetics* ; Interferon-gamma ; Mice ; Mice, Inbred BALB C ; Psoriasis/pathology* ; RNA, Messenger/therapeutic use*

OBJECTIVETo evaluate the effect of decoction of turtle shell for anti-fibrosis combined with stronger neo-minophagen C on the indices of hepatic fibrosis in chronic hepatitis B.

METHODThe 94 cases of chronic viral hepatitis B patients were randomly divided into two groups. The treatment group was treated with stronger neo-minophagen C 100 mL dissolved in 10% dextrose 250 ml once a day intravenously, combined with decoction of turtle shell for anti-fibrosis one powder daily. And the control group was treated with stronger neo-minophagen C alone, 3 months as a course. Liver fibrosis indexes and liver function index were tested for two groups of patients before and after the treatment.

RESULTBoth the difference of liver fibrosis indexes between the treatment group and the control group and before and after the treatment in the treatment group had statistical significance (P < 0.01). Both the difference of liver function index between the treatment group and the control group and before and after the treatment in the treatment group had statistical significance (P < 0.01). The basic cure rate and total effective rate were 40% and 84.0% in the treatment group and 27.27% and 86.18% in the control group respectively with significant difference. The treatment group was superior to control group in the mean size of diameter of portal vein and the thickness of spleen (P < 0.01).

CONCLUSIONDecoction of turtle shell for anti-fibrosis combined with stronger neo-minophagen C could significantly improve the clinical efficacy and the liver fibrosis indexes and liver function index in chronic hepatitis B.

Adult ; Aged ; Alanine Transaminase ; blood ; Animal Shells ; chemistry ; Animals ; Aspartate Aminotransferases ; blood ; Cysteine ; administration & dosage ; therapeutic use ; Drug Combinations ; Drug Therapy, Combination ; Female ; Glycine ; administration & dosage ; therapeutic use ; Glycyrrhetinic Acid ; administration & dosage ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; blood ; drug therapy ; etiology ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Tissue Extracts ; therapeutic use ; Treatment Outcome ; Turtles ; gamma-Glutamyltransferase ; blood

Acetates ; administration & dosage ; therapeutic use ; Asthma ; drug therapy ; etiology ; metabolism ; Bronchiolitis, Viral ; drug therapy ; Cysteine ; metabolism ; Humans ; Infant ; Infant, Newborn ; Leukotriene Antagonists ; administration & dosage ; therapeutic use ; Leukotrienes ; biosynthesis ; Nasopharynx ; secretion ; Quinolines ; administration & dosage ; therapeutic use ; Respiratory Syncytial Virus Infections ; drug therapy ; metabolism ; virology ; Risk Factors

The inhibition of protein degradation through the ubiquitin-proteasome pathway is a recently developed approach to cancer treatment which extends the range of cellular target for chemotherapy. This therapeutic strategy is very interesting since the proteasomes carry out the regulated degradation of unnecessary or damaged cellular proteins, a process that is dysregulated in many cancer cells. Based on this hypothesis, the proteasome complex inhibitor Bortezomib was approved for use in multiple myeloma patients by FDA in 2003. Drug discovery programs in academy and the pharmaceutical industry have developed a range of synthetic and natural inhibitors of the 20S proteasome core particle that have entered human clinical trials as significant anti-cancer leads. The main results from the use of proteasome inhibition in cancer chemotherapy, the structure of several proteasome inhibitors and their synthesis is going to be reviewed in this paper.
Acetylcysteine ; analogs & derivatives ; chemical synthesis ; chemistry ; Antineoplastic Agents ; chemical synthesis ; classification ; therapeutic use ; Boronic Acids ; chemical synthesis ; chemistry ; therapeutic use ; Bortezomib ; Cysteine Proteinase Inhibitors ; chemical synthesis ; classification ; Dipeptides ; chemical synthesis ; chemistry ; Humans ; Multiple Myeloma ; drug therapy ; enzymology ; Peptides, Cyclic ; chemical synthesis ; chemistry ; Proteasome Endopeptidase Complex ; metabolism ; Proteasome Inhibitors ; Pyrazines ; chemical synthesis ; chemistry ; therapeutic use ; Ubiquitin ; antagonists & inhibitors ; metabolism

OBJECTIVETo explore the mechanism of traditional Chinese medicine (TCM) treatment according to syndrome differentiation in treating chronic obstructive pulmonary disease (COPD) by observing the changes of nuclear factor-kappaB (NF-kappaB) and gamma-glutamylcysteine synthetase (gamma-GCS) expression levels in rats.

METHODSCOPD model was established by modified method of combining fumigation and lipopolysaccharide (LPS) intra-tracheal dripping. Model rats were treated respectively for succesive 14 days according to their syndrome, that is, Xiaoqinglong Decoction to the rats of cold-phlegm accumulation in Fei, Maxing Shigan Decoction to those of heat-phlegm accumulation in Fei, Yupingfeng Decoction to those of Fei-qi deficiency, Liujunzi Decoction to those of Pi-qi deficiency, Renshen Gejie Decoction to those of Shen qi-deficiency. Besides, model rats in the model control group received 2mL normal saline daily, and no intervention was applied in the normal control group. The expression of gamma-GCS and NF-kappaB was detected by immunochemistry before and after treatment.

RESULTSCompared with that in the normal rats, the expressions of gamma-GCS and NF-kappaB in bronchial and alveolar epithelium of COPD rats before treatment were significantly higher, but the positive expression rates were lowered after treatment significantly (P<0.05).

CONCLUSIONTCM treatment according to syndrome differentiation could rectify imbalance of oxidation/anti-oxidation and alleviate inflammatory reaction in COPD rats, thus to treat COPD effectively.

Animals ; Diagnosis, Differential ; Drugs, Chinese Herbal ; therapeutic use ; Glutamate-Cysteine Ligase ; biosynthesis ; Immunohistochemistry ; Male ; Medicine, Chinese Traditional ; NF-kappa B ; biosynthesis ; Phytotherapy ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; drug therapy ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Syndrome

BACKGROUNDNon-small cell lung cancer (NSCLC) is one of the most common malignant tumors. Despite the advances in therapy over the years, its mortality remains high. The aim of this study was to evaluate the expression of small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) in NSCLC tissues and its role in the regulation of vascular endothelial growth factor (VEGF) expression. We also investigated the association between the expression level of SENP1 and the clinicopathological features and survival of the patients.

METHODSA SENP1 small interfering RNA (siRNA) was constructed and transfected into the NSCLC cells. VEGF gene expression was analyzed by real-time polymerase chain reaction (RT-PCR). Immunohistochemistry staining was used to assess the expression of SENP1 in 100 NSCLC patients and its association with the clinicopathological features and survival was analyzed.

RESULTSVEGF expression was significantly higher in NSCLC tissues than in normal lung tissues. Inhibition of SENP1 by siRNA was associated with decreased VEGF expression. SENP1 was over-expressed in 55 of the 100 NSCLC samples (55%) and was associated with a moderate and low histological tumor grade (3.6%, 38.2%, and 58.2% in high, moderate and low differentiated tumors, respectively, P = 0.046), higher T stage (10.9% in T1, and 89.1% in T2 and T3 tumor samples, P < 0.001) and TNM stage (10.9% in stage I, and 89.1% in stages II and III tumor samples, P < 0.001). The rate of lymph node metastasis was significantly higher in the SENP1 over-expression group (76.4%) than that in the SENP1 low expression group (33.3%, P < 0.001). Sixty three patients received postoperative chemotherapy, including 34 with SENP1 over-expression and 29 with SENP1 low expression. Among the 34 patients with SENP1 over-expression, 22 (64.7%) patients developed recurrence or metastasis, significantly higher than those in the low expression group 27.6% (8/29) (P = 0.005). Multivariate Cox regression analysis showed that lymph node metastasis (P = 0.015), TNM stage (P = 0.001), and SENP1 expression level (P = 0.002) were independent prognostic factors for the survival of NSCLC patients.

CONCLUSIONSSENP1 may be a promising predictor of survival, a predictive factor of chemo-sensitivity for NSCLC patients, and potentially a desirable drug target for lung carcinoma target therapy.

Antineoplastic Agents ; therapeutic use ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; metabolism ; Cell Line, Tumor ; Cysteine Endopeptidases ; Endopeptidases ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; Male ; Reverse Transcriptase Polymerase Chain Reaction