Osteoarthritis （OA） is characterized by articular cartilage degeneration， synovial hyperplasia， hyperosteogeny， and narrowing of joint space， which can be caused by trauma， inflammation， and other factors. With the increasing global population aging， the incidence of OA is rising year by year， making it a major public health problem that urgently needs to be addressed. Exploring effective treatment schemes is particularly important. The pathogenesis of OA is complex， including oxidative stress， autophagy， and apoptosis. Recent studies have found that ferroptosis， a new type of cell death， is also an important pathogenic factor in OA， characterized by a series of complex changes such as iron ion accumulation， glutathione （GSH） depletion， and mitochondrial dysfunction. Research shows that inhibiting ferroptosis in chondrocytes can promote chondrocyte proliferation， delay extracellular matrix （ECM） degradation， and reduce synovial hyperplasia and inflammation. Targeting ferroptosis is a new direction in the treatment of OA. OA treatment includes intra-articular injections of steroids or hyaluronic acid and artificial joint replacement， but there are limitations. Traditional Chinese medicine （TCM） has been widely used in the treatment of various diseases because of its low cost， low drug resistance， and few side effects. Cell and animal experiments have further confirmed that TCM can intervene in the treatment of OA with ferroptosis from multiple targets， multiple levels， and aspects， but the mechanism of its treatment of OA based on ferroptosis has not been clarified. This paper discussed iron metabolism， lipid peroxidation， cysteine/glutamate transporter system Xc^- （system Xc^-）/GSH/glutathione peroxidase 4 （GPX4） pathway， nicotinamide adenine dinucleotide phosphate（NADPH）/ferroptosis suppressor protein 1 （FSP1）/coenzyme Q₁₀ （CoQ₁₀） pathway， tumor protein p53 in OA， and related molecular targets of Chinese medicine monomers and compounds on ferroptosis inhibition. Their potential therapeutic mechanisms were further analyzed to provide theoretical guidance for the treatment of OA by TCM and useful reference for the research and development of related drugs.

Objective To investigate the association between blood glucose level and cardiovascular disease ( CVD) risk in elderly people aged 40 and older in Guiyang City. Methods Population-based cross-sectional studies on diabetes were performed in 10140 adults, aged 40-78 years, living in the Yunyan Community in Guiyang City, during May, 2011 to August, 2011. The fasting venous blood samples were drawn for the measurements of serum creatinine(Cr), fasting plasma glucose(FPG), OGTT 2hPG, fasting triglyceride(TG), total cholesterol(TC), high-density lipoprotein-cholesterol ( HDL-C ) , low-density lipoprotein-cholesterol ( LDL-C ) , and fasting plasma insulin. The diabetes status and the classification system for diabetes in our study were categorized according to the Diabetes Diagnostic Standard which was issued by WHO in 1999. An estimated 10-year Framingham risk for coronary heart disease was calculated. Results Compared with those in normal glucose regulation( NGR) group, the subjects in abnormal glucose metabolism were associated with higher prevalence of various cardiovascular risk factors, including age, body mass index, blood pressure, HbA1C , HOMA-IR, total cholesterol, triglycerides, waist circumference, waist-hip ratio, and creatinine, as well as 10-year Framingham risks for coronary heart disease. The difference was statistically significant ( all P<0. 05 ) . Men were more likely to have cardiovascular risk than women. Women developing the disease only begins to increase after the age of 59. The difference was statistically significant(P<0.05). Compared with the subjects in NGR group, the 10-year Framingham risk for coronary heart disease in impaired fasting glucose ( IFG ) , impaired glucose tolerance ( IGT ) , and diabetes mellitus ( DM ) groups shown 10％of increase were 1.13( OR=1.13, 95％CI 0.81-1.58, P>0.05) , 1.18( OR=1.18, 95％CI 0.95-1.45, P>0.05), and 1.44(OR=1.44, 95％CI 1.10-1.88, P<0.05), respectively, after adjusting for various influencing factors. Conclusion Diabetic patients and pre-diabetic individuals were independently associated with the increased 10-year risks for CVD.

Aim To observe the influence of CCK-8 on expression of MMPs/TIMP-1 in TNF-α-induced rat fibroblast-like synovial cell line RSC-364.Methods The secretion levels of MMP-1, MMP-3, MMP-9 and TIMP-1 were determined using ELISA;MMP-3 and MMP-9 mRNA expressions were detected by RT-PCR.Results MMP-3 and MMP-9 could not be examined in RSC-364 incubated with CCK-8 and unstimulated RSC-364, which was able to product a little MMP-1, TIMP-1 and express even less MMP-3,-9 mRNA.CCK-8 inhibited the increase in MMP-1, MMP-3, MMP-9 secretion and MMP-3,-9 mRNA expression in TNF-α-induced RSC-364.TIMP-1 production was also increased in TNF-α-induced RSC-364.CCK-8 had no effect on TIMP-1 production in TNF-α-induced RSC-364, but was able to reduce the ratios of MMP-1, MMP-3, MMP-9 to TIMP-1.Conclusion The inhibitory effect of CCK-8 on MMPs activity may be related to the decrease of MMPs mRNA expression, MMPs secretion and the ratios of MMPs to TIMP-1 in TNF-α-induced RSC-364, which indicates that CCK-8 might be a possible regulator in the pathogenesis of rheumatoid arthritis.

Objective To investigate the effect of low 1evel laser treatment (LLLT) on periodontal clinical index,high-sensitivity C-reactive protein (hs-CRP) and metabolic control in patients of type 2 diabetes mellitus combined chronic peridontitis.Methods Nighty patients with type 2 diabetes combined chronic peridontitis were divided into three groups:initial periodontal therapy (group A),initial therapy combined with LLLT (group B) and control group (group C).The periodontal clinical parameters including periodontal probing depth (PD),clinical attachment loss (CAL),sulcus bleeding index (SBI),hs-CRP,HbA1c and fasting blood glucose (FBG) were tested before and at three months after therapy.Results The periodontal clinical parameters (PD,CAL,SBI) and hsCRP in group A and B improved significantly compared with that of group C after therapy (P＜0.05),with group B had more significant difference (P＜0.01).For the levels of HbA1c and FPG,group A and B showed downtrend,and more obvious outcome was detected in group B (P＜0.05).Conclusions LLLT can effectively improve periodontal status,hs-CRP levels and metabolic control of patients with type 2 diabetes combined with chronic peridontitis,and thus to prevent the occurrence of diabetes complications.

AscreeningmethodforcriticalaminoacidsinEpitopesusinganti-Epitopeantibodywasdeveloped. The amino acids' frequency of occurrence in Epitopes of shrimp antigen Pen a1 was calculated using MEGA5 software and their conservative property of tropomyosin in SDAP database bank was analyzed using DNAMAN software. Potential critical amino acids based on these two methods were identified, namely Epitope 1 ( K, E, N) , Epitope 2 ( K, L, E) , Epitope 3 ( E, R, D, L, Q) , Epitope 5 ( K, L, Q) . The mutated polypeptides corresponding to these Epitopes in which these critical amino acids were substituted with alanine were synthesized. The IgG binding ability of these mutants was analyzed by competitive immunodot-blot method and indirect ELISA using Epitope antibody to screen the critical amino acids. Experimental results showed that the critical amino acids of the four Epitopes were as follows: Epitope 1 ( Gln ) , Epitope 2 ( Leu and Glu ) , Epitope 3 ( Leu and Asp) , Epitope 5 ( Leu) . The feasibility of this screening method was proved and it also offered a theoretical foundation for research on sensitization mechanism of Pen a1 and desensitization using gene modification.

Objective To screen and clone the genes related to stilbene glucosides biosynthesis in Polygonum multiflorum Thunb. Methods The differentially expressed genes in the root, stem and leaf of Polygonum multiflorum which have different contents of stilbene glucosides were screened by differential display reverse transcription polymerase chain reaction (DDRT-PCR). After pMD19-T carrier was inserted into the obtained differential genes for sequencing and comparison, the gene function was analyzed. Results Fifty-one differentially expressed cDNA fragments were found. Of them, 9 were used for the identification by semi-quantitative PCR. The identification results presented 3 positive fragments, one fragment was specifically expressed in the stem and leaf of Polygon-um multiflorum Thunb., sharing high homology with glycine dehydrogenase, and 2 were specifically expressed in the root of Polygonum multiflorum Thunb., having high homology with enoyl-CoA hydratase and aminopeptidase N, respectively. Conclusion Three homologous gene sequences obtained through DDRT-PCR provide a basis for the further study of biosynthetic pathway of stilbene glucoside from Polygonum multiflorum Thunb..

Objective To study the relationship between the OATP1B1 521T ＞ C genetic polymorphism and essential hypertension.Methods 164 essential hypertension subjects and 159 normotensive subjects were detected by the TaqMan-MGB probe real-time fluorescence quantitative PCR,and the results were compared with those of DNA sequencing.Results The frequencies of T/C genotype and C allele of OATP1B1 521T ＞ C gene of the essential hypertension subjects were obviously lower than those of the normotensive subjects(T/C genotype:0.16 vs 0.25,P ＜0.05 ;C allele:0.10 vs 0.17,P ＜0.05),The difference was significant.Binary logistic stepwise regression analysis was used for evaluatine the risk factors of essential hypertension,there was significant relationship between OATP1 B1 52IT ＞ C gene polymorphism and essential hypertension.Conclusion The SLCO1 B1 521T ＞ C variant was common in Chinese essential hypertension population,but the difference of frequency of SLCO1B1 52IT ＞ Cmuton between the essential hypertension patients and the normotensive controls was of obviously statistical significance,which indicates that the SLCO1B1521T ＞ C variant maybe associate with essential hypertension.

OBJECTIVETo investigate the influence of najanalgesin on glutamate-glial transporter 1(GLT-1) in spinal cord of rats after L5 spinal nerve ligation and transection (SNL), and explore the spinal analgesic mechanism of najanalgesin.

METHODOne hundred male SD rats were randomly divided into 6 groups: sham(A), SNL(B), SNL + najanalgesin(C), SNL + saline (D), SNL + najanalgesin + liposome (E), SNL + najanalgesin + liposome + GLT-1 As-ODNs(F) and treated with intrathecal injections of 10 p.L saline (A and D), 40 ng X kg(-1) najanalgesin (C, E and F), qd, respectively. Besides intrathecal administration of najanalgesin the rats were intrathecally injected with 10 microL of GLT-1 antisense oligodeoxynucleotides (As-ODNs) (F) and 10 micdroL of liposome(E) once daily on day 3. The L4-L6 segments of the spinal cord were isolated in 1, 4 and 7 d(A,B,C and D), 7 d(E and F) after surgery. The mRNA and protein of GLT-1 were determined.

RESULTThe SNL model has successfully been set up. Compared to sham group, the expression of GLT-1 mRNA and protein level in group B and D both increased firstly and decreased later, the expression of GLT-1 in group C was significantly increased and kept stable, which were also higher when compared to group D in day 7th. Compared to SNL + najanalgesin group, after intrathecal injection of GLT-1 As-ODNs the GLT-1, expression of GLT-1 in F group significantly decreased. While intrathecal administration of liposome had no significant effect on the spinal GLT-1 expression.

CONCLUSIONNajanalgesin could increase the mRNA and protein expression of GLT-1 in spinal cord, which may be one of its spinal mechanisms of analgesia.

Animals ; Elapid Venoms ; pharmacology ; Elapidae ; Excitatory Amino Acid Transporter 2 ; genetics ; metabolism ; Gene Expression Regulation ; drug effects ; Male ; Neuralgia ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; drug effects ; metabolism

Type III polyketide synthases (PKSs) from plants produce a variety of plant secondary metabolites with notable structural diversity and biological activity. These metabolites not only afford plants the ability to defend against pathogen attack and other external stresses, but also exhibit a wide range of biological effects on human health. Several plant PKSs have been identified and studied in recent years. This paper summarized what was known about plant PKSs and some of their aspects such as molecular structure, reaction mechanisms, gene expression and regulation, and transgenic engineering. The review provides information for manipulating polyketide formation and further increasing the scope of polyketide biosynthetic diversity, as well as new avenues for developing transgenic engineering of type III PKSs.
Catalysis ; Plants ; enzymology ; Polyketide Synthases ; chemistry ; classification ; metabolism ; Protein Engineering

HIV-1 gp41 has been successfully anchored on the cell surface of yeast Saccharomyces cerevisiae by yeast cell-surface display systems using His-tag for the detection of protein expression. Gp41 activity has been detected by gp41 monoclonal antibody. The vector for gp41 yeast display has been constructed as follows: the gene-encoding gp41 was amplified by PCR using pMD18T-gp41 as a template, and then inserted into shuttle vector pICAS-His by restriction enzyme digestion. Next, the vectors were introduced into Saccharomyces cerevisiae MT8-1. After cultivation, recombinant cells were immunofluorescence labelled. The bright green cells were observed by the microscopy indicating the proteins have been displayed on the cell surface successfully, flow cytometry convinced that gp41 has been folded correctly on the cell surface. Then different concentrations of initial glucose were used to enhance the expression of protein. gp41 has been expressed by 82.46% yeast cells as the concentration of glucose was 1%. Protein expression was depressed when the concentration was increased.
Genetic Engineering ; methods ; Genetic Vectors ; genetics ; metabolism ; HIV Envelope Protein gp41 ; biosynthesis ; genetics ; Humans ; Protein Folding ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Saccharomyces cerevisiae ; cytology ; genetics ; metabolism ; Saccharomyces cerevisiae Proteins ; genetics ; metabolism ; Surface Properties