Inhibition of HSP70 release by geniposide improves angiogenesis in moist heat arthralgia spasm syndrome collagen induced arthritis rats / 中国药理学通报

Aim To investigate the relation between the effect of geniposide (GE) in improving angiogenesis in arthralgia spasm syndrome collagen induced arthritis (CIA) rats and the modulation of heat shock proteins 70 (HSP70) release. Methods A CIA model was constructed by multiple intradermal injections of complete Freund's adjuvant (CFA) and an equal volume mixture of chicken type II collagen (CCII) into the dorsal and caudal root regions of rats, on the basis of which a rheumatic fever stimulus was given to build up a moist heat arthralgia spasm syndrome in CIA rats. After successful modeling, the groups were randomly grouped, and the administered groups were gavaged with GE (60, 120 mg · kg

Preparation of tripterygium glycoside nanoparticles and therapeutic effect on arthritis rats / 中国药理学通报

Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.

Alcohol extract of root and root bark of Toddalia asiatica alleviates CIA in rats through anti-inflammatory and proapoptotic effects / 中国中药杂志

This study aims to investigate the therapeutic effect of alcohol extract of root and root bark of Toddalia asiatica(TAAE) on collagen-induced arthritis(CIA) in rats through phosphatidylinoinosidine-3 kinase/protein kinase B(PI3K/Akt) signaling pathway. To be specific, CIA was induced in rats, and then the rats were treated(oral, daily) with TAAE and Tripterygium Glycoside Tablets(TGT), respectively. The swelling degree of the hind leg joints was scored weekly. After 35 days of administration, the histopathological changes were observed based on hematoxylin and eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the levels of cytokines [tumor necrosis factor-α(TNF-α), interleukin(IL)-6)]. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining was performed to detect the apoptosis of synoviocytes in rats. Western blot was used to detect the expression levels of apoptosis-related proteins B-cell lymphoma 2(Bcl-2)-associated X(Bax), Bcl-2, and caspase-3 and pathway-related proteins phosphoinositide 3-kinase(PI3K), phosphorylated(p)-PI3K, protein kinase B(Akt), and p-Akt. RT-qPCR was conducted to examine the mRNA levels of Bax, Bcl-2, caspase-3, TNF-α, IL-6, and IL-1β and pathway-related proteins PI3K, p-PI3K, Akt, and p-Akt. TAAE can alleviate the joint swelling in CIA rats, reduce serum levels of inflammatory cytokines, improve synovial histopathological changes, promote apoptosis of synoviocytes, and inhibit synovial inflammation. In addition, RT-qPCR and Western blot results showed that TAAE up-regulated the level of Bax, down-regulated the level of Bcl-2, and activated caspase-3 to promote apoptosis in synoviocytes. TAAE effectively down-regulated the protein levels of p-PI3K and p-Akt. In this study, TAAE shows therapeutic effect on CIA in rats and reduces the inflammation. The mechanism is that it suppresses PI3K/Akt signaling pathway and promotes synoviocyte apoptosis. Overall, this study provides a new clue for the research on the anti-inflammatory mechanism of TAAE and lays a theoretical basis for the better clinical application of TAAE in the treatment of inflammatory and autoimmune diseases.

Huanglian Jiedutang Regulates Inflammatory Immunity to Relieve Rheumatoid Arthritis / 中国实验方剂学杂志

ObjectiveTo observe the effects of Huanglian Jiedutang on pathological and immune damage in collagen-induced arthritis （CIA） model mice， and to explore the possible mechanism of Huanglian Jiedutang in relieving rheumatoid arthritis. MethodTwenty-four DBA/1 mice were randomly divided into normal group， model group， methotrexate group and Huanglian Jiedutang group， with six mice in each group. The CIA mice model were established using type Ⅱ collagen induction. The administration groups were respectively treated with Huanglian Jiedutang （5 g·kg-1） and methotrexate （0.5 mg·kg-1）. The joint swelling symptoms of the mice were observed， and the arthritis index was scored every 3 days. Flow cytometry was employed to detect granulocytes， monocytes， and T lymphocytes in peripheral blood. The expression of inflammatory cytokines in joint was determined by real-time polymerase chain reaction （Real-time PCR）. The ankle joint was scanned by micro-computed tomography （Micro-CT）， and the histopathological changes were observed through hematoxylin-eosin （HE） staining. ResultCompared with the normal group， the modeling led to joint swelling， elevated the joint index score （P<0.05）， increased the proportion of granulocytes （P<0.05） and decreased that of monocytes and T lymphocytes （P<0.01） in peripheral blood， and raised the neutrophil-to-lymphocyte ratio （NLR） （P<0.01）. Further， it up-regulated the expression of inflammatory cytokines such as tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 in joint （P<0.01）. Micro-CT showed obvious bone destruction in the ankle joint， and pathological examination revealed the infiltration of a large number of inflammatory cells and the synovial hyperplasia of joint tissue. Compared with the model group， Huanglian Jiedutang alleviated the symptoms of joint swelling， lowered the score of arthritis index （P<0.05）， increased the proportion of T lymphocytes and lowered NLR （P<0.01）. Moreover， it down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in joint （P<0.01） and alleviated the bone destruction and pathological injury of joint tissue. ConclusionType Ⅱ collagen caused systemic and local inflammatory immune damage in CIA mice. Huanglian Jiedutang alleviates such injury， especially for that in local joint， thereby inhibiting joint injury and bone destruction in CIA mice.

Therapeutic Mechanism of Huangqi Guizhi Wuwutang on Rheumatoid Arthritis / 中国实验方剂学杂志

ObjectiveTo reveal the mechanism of action of Huangqi Guizhi Wuwutang in the treatment of rheumatoid arthritis by pharmacological research based on its clinical application. MethodThe collagen-induced arthritis （CIA） rat model was established by injecting bovine type Ⅱ collagen and Freund's adjuvant at the tail， and was treated with different concentrations of Huangqi Guizhi Wuwutang. The rats were randomly divided into blank group， model group， methotrexate （0.9 mg·kg-1） group， and Huangqi Guizhi Wuwutang low- and high-dose （5.13， 20.52 g·kg-1·d-1） groups， with continuous intragastric administration for 4 weeks. The degree of joint swelling， weight， degree of foot swelling and arthritis index score were determined and the pathological changes of ankle joints were detected by hematoxylin and eosin （HE） staining to observe the therapeutic effect of Huangqi Guizhi Wuwutang on rheumatoid arthritis. In addition， enzyme-linked immunosorbent assay （ELISA） and Western blot were used to measure the expression of interleukin 1β （IL-1β）， interleukin 6 （IL-6）， interleukin 10 （IL-10） and tumor necrosis factor-α （TNF-α） in serum and the expression of nuclear factor kappa-B （NF-κB） pathway related proteins in synovial tissue， respectively to clarify the molecular mechanism of Huangqi Guizhi Wuwutang in the treatment of rheumatoid arthritis. ResultCompared with the conditions in blank group， the body weight and IL-10 level were decreased （P<0.01）， and the degree of foot swelling and arthritis index score， the levels of IL-1β， IL-6 and TNF-α， and the expression of NF-κB pathway related proteins were increased （P<0.01，） in the model group， with impaired morphology and function of the ankle joint. Additionally， compared with the model group， Huangqi Guizhi Wuwutang low- and high-dose groups had increased body weight of rats and IL-10 level （P<0.01）， and reduced degree of foot swelling and arthritis index score （P<0.05， P<0.01）， levels of IL-1β， IL-6 and TNF-α （P<0.01） and expression of NF-κB pathway related proteins （P<0.05， P<0.01）， with improved function and morphology of the ankle joint. ConclusionHuangqi Guizhi Wuwutang can significantly alleviate joint inflammatory injury by down-regulating NF-κB pathway and reducing the inflammatory response in CIA rats.

Mechanism of Duanteng Yimu Decoction on Expression of MEKK2 in Rheumatoid Arthritis Synovial Fibroblasts and Arthritis in CIA Mice / 中国实验方剂学杂志

Objective::Duanteng Yimu decoction(DTYMD)is effective in treatment of rheumatoid arthritis (RA) by relieving joint inflammation and down-regulating some inflammatory factors in a short period of time, but the mechanism is still unclear. We aimed to investigate upstream kinase of mitogen activated protein kinases(MAPK) and define the anti-inflammatory mechanism of DTYMD. Method::Fibroblasts-like synovial cells(FLSs) were divided into blank group, model group (IL-1β), high-dose DTYMD group (1 000 mg·L-1), medium-dose DTYMD group (800 mg·L-1), low-dose DTYMD group (600 mg·L-1) and armour ammonia butterfly(MTX) group (20 μmol·L-1). The protein and mRNA expressions of mitogen-activated protein kinase kinase kinase 2 (MEKK2) were analyzed by real-time fluorescence quantitative PCR(Real-time PCR). Totally 42 male DBA/1J mice were randomly divided into 6 groups, with 7 mice in each group, namely normal group, model group and MTX group (2 mg·kg-1), low-dose DTYMD group (6.25 mg·kg-1), medium-dose DTYMD group (12.5 mg·kg-1), and high-dose DTYMD group (25 mg·kg-1). Except for the normal group, the other five groups were included in collagen-induced arthritis(CIA) model by secondary immunoassay. After administration, the posterior limbs and ankle joints were stained with htoxylin-eosin(HE), and the pathological scores of the joints were evaluated. Result::Compared with the model group, DTYMD inhibited the activity of FLSs in a concentration-dependent manner (P<0.01). Compared with the blank control group, the cell proliferation rate of the model group increased (P<0.01). Compared with the model group, high and middle-dose DTYMD groups could inhibit protein and mRNA expressions of MEKK2 (P<0.01), but there was no significant difference in low-dose group. However, the expression of DTYMD protein in high/medium/low-dose groups was significantly higher than that in blank group (P<0.01), but there was no significant difference in MTX group. Compared with the model group, the expressions of matrix metalloprotease-1 (MMP-1), tumor necrosis factor-α(TNF-α) and interleukin(IL)-6 were negatively regulated in different DTYMD groups(P<0.01), and the expressions of MMP-1, IL-6, TNF-α in the model group were significantly higher than those in the blank group (P<0.05, P<0.01). In the animal experiment, compared with the model group, high/middle-dose DTYMD groups could decrease the degree of joint swelling in CIA mice (P<0.01), but there was no significant difference in the low dose group, and the joint swelling in the model group was significantly higher than that in the blank group (P<0.05). In HE staining of ankle joint of CIA mice, the pathological scores of high/small-dose DTYMD groups were significantly lower those of model group (P<0.05, P<0.01), and the pathological score of model group was higher than that of blank group (P<0.01). Conclusion::DTYMD might down-regulate MEKK2 to negatively regulate inflammatory cytokines IL-6, TNF-α and MMP-1, thereby alleviating the inflammatory response in rheumatoid arthritis.

Effect of Sanbi Granules on TLR4/MAPKs/NF-κB Signal Pathway in Type Ⅱ Collagen Induced Arthritis Rats / 中国药学杂志

OBJECTIVE: To discuss the effect of Sanbi granules on type Ⅱ collagen induced arthritis (CIA) rats by regulating the TLR4/MAPKs/NF-κB signal pathway. METHODS: Sixty of Wistar rats were randomly divided into normal control group (CTL group, n=10), model group (n=10), positive control group (n=10) and low dose of Sanbi group (n=10), middle dose of Sanbi group (n=10), high dose of Sanbi group (n=10). The collagen induced arthritis (CIA) model of rats was adopted and treated for 20 days by intragastric administration from 2 weeks after primary immune. After exposure to sanbi for 35 d, the rats status, paw swelling, arthritis index (AI) and pathological change of synovial tissue were observed. The serum IL-1β, IL-6, tumor necrosis factor α (TNF-α) levels were detected by ELISA. And the expressions of Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB) (p65), p-NF-κB (p65), p38, p-p38, extracellular signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2, c-Jun NH2-terminal kinase (JNK), p-JNK mRNA or proteins in synovial tissues were detected by qRT-PCR and Western blot. RESULTS: At the end of experiment, compared with model group, the paw swelling degree and arthritis index (AI) of CIA rats in DXM group and low, middle, high dose of Sanbi groups were lower (P0.05). Besides, compared with CTL group, TLR4, p-NF-κB (p65), p-p38, p-ERK1/2, p-JNK mRNA and proteins in synovial tissues of CIA rats in model group, DXM group and low, middle, high dose of Sanbi groups were higher (P<0.05). And these mRNAs and proteins in DXM group and low, middle, high dose of Sanbi groups were lower than these in model group, particularly in DXM group and high dose of Sanbi group (P<0.05). CONCLUSION: There are significant evidences that Sanbi granules could protect joint synovial tissues injury by down-regulation TLR4/MAPKs/NF-κB signal pathway on CIA rats.

Effect of Tripterygium Glycosides Tablets on reproductive toxicity in male rats with Ⅱ type collagen induced arthritis / 中国中药杂志

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets on the reproductive system of Ⅱ type collagen induced arthritis(CIA) male rats, and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group(Con), model group(CIA), Tripterygium Glycosides Tablets clinical equivalent dose groups of 1, 2, 4 times(9, 18, 36 mg·kg~(-1)), 10 rats in each group, and were given by gavage once a day for 42 days after the first immunization. The organ index of testis and epididymis were calculated on days 21 and 42. Histopathological and morphological changes of testis and epididymis were observed under optical microscope. Sperm count, sperm malformation rate and sperm kinetic parameters in epididymal tissues were observed by computer assisted sperm analysis(CASA). The concentration of testosterone(T), nitric oxide synthase(NOS) and aromatase(CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of testis and epididymis. The results showed that, compared with Con group, CIA group significantly increased the rate of testicular spermatogenic tubule lesion and sperm malformation, decreased the average path speed, and no significant changes were observed in other groups. Tripterygium Glycosides Tablets at 4 times clinical equivalent dose can significantly reduce the testis index(P<0.01), each dose group can reduce the epididymis index(P<0.05). Each dose group of Tripterygium Glycosides Tablets could cause different degrees of damage to the testis and epididymis, the proportion of testicular histopathology lesions increased, the number of spermatogenic cells in the seminiferous tubules decreased, and so on. It could reduce the number of sperm, increase the rate of sperm deformity, make the parameters of sperm dynamics abnormal, and so on. Tripterygium Glycosides Tablets at 4 times dose could significantly reduce the content of serum sex hormone T and key enzyme of androgen synthesis(P<0.05 or P<0.01), but had no effect on CYP19 A1. The expression of Bax and Bcl-2 in testis and epididymis were increased by 2 and 4 times doses of Tripterygium Glycosides Tablets(P<0.05, P<0.01 or P<0.01). The results showed that 21 d administration of Tripterygium Glycosides Tablets at equal or higher doses could induce obvious toxic effect to the reproductive organs of CIA male rats, and lower the level of serum sex hormone T and the key enzyme of androgen synthesis, NOS. The mechanism of abnormal changes of Bax and Bcl-2 in Testis and epididymis is still to be elucidated.

Novel approach for real-time monitoring of carrier-based DPIs delivery process pulmonary route based on modular modified Sympatec HELOS

An explicit illustration of pulmonary delivery processes (PDPs) was a prerequisite for the formulation design and optimization of carrier-based DPIs. However, the current evaluation approaches for DPIs could not provide precise investigation of each PDP separately, or the approaches merely used a simplified and idealized model. In the present study, a novel modular modified Sympatec HELOS (MMSH) was developed to fully investigate the mechanism of each PDP separately in real-time. An inhaler device, artificial throat and pre-separator were separately integrated with a Sympatec HELOS. The dispersion and fluidization, transportation, detachment and deposition processes of pulmonary delivery for model DPIs were explored under different flow rates. Moreover, time-sliced measurements were used to monitor the PDPs in real-time. The Next Generation Impactor (NGI) was applied to determine the aerosolization performance of the model DPIs. The release profiles of the drug particles, drug aggregations and carriers were obtained by MMSH in real-time. Each PDP of the DPIs was analyzed in detail. Moreover, a positive correlation was established between the total release amount of drug particles and the fine particle fraction (FPF) values ( = 0.9898). The innovative MMSH was successfully developed and was capable of illustrating the PDPs and the mechanism of carrier-based DPIs, providing a theoretical basis for the design and optimization of carrier-based DPIs.

Therapeutic effect of ethanol extract of pterocarya hupehensis skan on collagen-induced arthritis rats and its mechanism / 中国药理学通报

Aim To observe the therapeutic effect of Pterocarya hupehensis Skan ethanol extract ( PHSEE ) on CIA model of SL) rats and to explore the mechanism of anti-inflammation and pro-apoptosis. Methods After the CIA model was established, the body weight, paw swelling rate, as well as arthritis index were recorded every 7 days. The rats were continuously fed with PI ISEE or TG for 28 days. The pathological changes of knee joint synovial membrane were observed in each group, while the apoptotic synoviocytes were evaluated by TUNEL assay. The changes of TNF-c∗, IL-lp, ALT, AST, BUN and SCr in the serum were tested by ELISA. And the expressions of NF-kB p65 phosphorylation ( p-p65 ) , cleaved caspase-3, Bcl-2 and Bax in the synovial tissue protein of the knee joint were detected by Western blot. Results Compared with model group, the paw swelling rate and arthritis index decreased in TG and PHSEE-lreated groups with statistical significance ( /' eulic efficacy on CIA rat. The mechanism may be related to down-regulating the expression of inflammatory cytokines and inducing apoptosis of synovial cells. At the same time, the extract can improve impaired liver and kidney function in CIA rats.

Effect of Tripterygium Glycosides Tablets on reproductive toxicity in female rats with Ⅱ type collagen induced arthritis / 中国中药杂志

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets( TG) on the reproductive system of Ⅱ type collagen induced arthritis( CIA) male rats,and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group( Con),model group( CIA),Tripterygium Glycosides Tablets clinical equivalent dose groups of 1,2,4 times( 9,18,36 mg·kg-1),10 rats in each group,and were given by gavage once a day for 42 days after the first immunization.The organ indexes of uterine and ovarian were calculated on days 21 and 42. Histopathological and morphological changes of uterine and ovarian were observed under optical microscope. The concentration of estradiol( E2),follicle-stimulating hormone( FSH),luteinizing hormone( LH),17α-hydroxylase( CYP17 A1) and cytochrome P450 19 A1( CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of uterus and ovary. The results showed that compared with the Con group,CIA group could reduce the number of uterine glands( P<0.05),but no significant changes were observed in other groups. Compared with the CIA group,there were no significant changes in the coefficients of uterus and ovary in the Tripterygium Glycosides Tablets groups. The number of uterine glands,total follicles in the ovary,mature follicles and corpus luteum,the distribution of blood vessels and mitochondria had a certain inhibitory trend,and also slightly increased the number of atresia follicles,but the histopathological quantitative indicators were not statistically different. Except that 2 times clinical dose of Tripterygium Glycosides Tablets could significantly reduce the content of CYP19 A1( P<0. 05) after 42 d administration,there were no significant changes in serum estrogen E2,FSH,LH and estrogen synthesis key enzymes CYP17 A1 in each administration group. Medium and high doses of Tripterygium Glycosides Tablets could increase the expression of apoptotic protein Bax in uterine and ovarian tissues( P<0. 05,P<0. 01),and all the administration groups could inhibit the expression of apoptotic inhibiting protein Bcl-2( P <0. 05,P<0. 01,P<0.001),42 d was more obvious than 21 d. In conclusion,4 times and less than 4 times Tripterygium Glycosides Tablets did not cause obvious toxicity and histopathological changes in the reproductive organs of CIA rats,but it could reduce the level of serum estrogen synthesis key enzyme CYP19 A1 and affect the content of apoptosis-related proteins Bax and Bcl-2 in uterus and ovary tissues. The relevant mechanism needs further study.

Comparative study on dose-toxicity-effect of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets on CIA model rats / 中国中药杂志

The aim of this paper was to compare the properties of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets from dose-effect-toxicity on type Ⅱ collagen-induced arthritis( CIA) in rats. SD rats were randomly divided into eight groups,including normal group,model group,Tripterygium Glycosides Tablets groups( 1 times equivalent dose 0.009 g·kg-1,4 times equivalent dose 0.036 g·kg-1,16 times equivalent dose 0.144 g·kg-1),Tripterygium wilfordii Tablets groups( 1 times equivalent dose 0.007 5 mg·kg-1,4 times equivalent dose 0.030 mg·kg-1,16 times equivalent dose 0.120 mg·kg-1). Beginning on the first immunization,Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets administered intraperitoneally once a day. After the second immunization,the symptoms such as redness and swelling of joints were observed,and the clinical score and incidence of arthritis were evaluated. HE and Masson staining were used to examine the histopathological changes of joints. The expression level of anti-type Ⅱ collagen antibody Ig G in serum was detected by ELISA,routine testing of blood components,the concentration of ALP( alkaline phosphatase),ALT( alanine aminotransferase),AST( aspartate aminotransferase),GGT( gamma-glutamyltransferase),TBi L( total bilirubin),CRE( creatinine) and UREA( urea) in serum were detected by enzymatic assay. The rate of sperm deformity in the epididymis was evaluated under light microscope. The extent of damage to the testis and ovarian tissue was assessed by HE staining. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets attenuated the inflammation,redness,swelling and deformity of joints and reduced the clinical score and incidence of arthritis in CIA rats. Meanwhile,it also exhibited obvious reduction in all pathological features such as joint synovitis,pannus,cartilage erosion and bone destruction. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets reduced Ig G in a dose-dependent manner,and Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets( P<0.05 or P<0.01). The high doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase the organ coefficient of liver and spleen and reduced RBC and HGB in CIA rats( P<0.01),and severity leading to death. Gastric mucosal injury and morphological changes of liver and kidney were not observed in CIA rats of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets treatment group. The 4 and 16 times doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase serum ALT,GGT and decrease CRE( P<0.05 or P<0.01). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could increase the sperm deformity rate and damage the testicular seminiferous tubules of CIA male rats. Severity increased with dose and time increasing. The effect of Tripterygium Glycosides Tablets( 16 times) is more significant than Tripterygium wilfordii Tablets( 16 times). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets significantly delayed onset of arthritis and inhibited the paw edema and arthritic score. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets also caused male reproductive damage,high dose affected hematopoiesis,and maximum dose leading to death. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets all depended on dose-effect-toxicity manner. Anti-arthritis effect of Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets,but the toxicity of Tripterygium Glycosides Tablets maximum dose is more obvious. The relevant conclusions of our study will provide experimental references for clinical rational use of drugs,and further clinical studies are needed to confirm our conclusions.

Evaluación Y Manejo De La Enfermedad Temprana Y Localmente Avanzada: 1er Consenso Nacional Del Cáncer De Mama de la Sociedad Panameña de Oncología (SPO) / Evaluation and Management of Early and Loc ally Adv anced Disease: 1st National Con­ sens us of Breas t Canc er of the Panamanian Soc iety of Oncology (SPO

El manejo de los pacientes con cáncer de mama temprano o localmente avanzado requiere de la evaluación inicial de un grupo de médicos familiarizados con el diagnóstico, estadificación y trata­mientos de estas enfermedades, de tal manera que se pueda optimizar los resultados no solamen­te oncológicos (Curación), sino también cosméticos. La decisión sobre el tratamiento local (cirugía y Radioterapia) y sistémico (Quimioterapia y Hormonoterapia) está basada en las características clí­nicas y moleculares de tumor, así como por las preferencias del paciente

The management of patients with earlyor locally advanced breast cancer requires the initial evalua­tion of a group of physicians familiar with the diagnosis, staging and treatment of these diseases, in order to optimize the results not only oncological (Healing), but also cosmetics. The decision on local treatment (surgery and Radiotherapy) and systemic treatment (Chemotherapy and Hormonot­herapy) is based on the clinical and molecular characteristics of the tumor, aswell as on the pa­tient's preferences

Intervenção educativa e expectativas positivas sobre o uso do álcool entre estudantes / Educational intervention and positive expectancies about the alcohol use among students

Objetivou-se avaliar as expectativas positivas sobre o uso recente de álcool por estudantes de ensino Fundamental e Médio antes e após uma intervenção educativa e verificar diferenças na frequência de uso e nas informações sobre essa substância, segundo o sexo. Estudo quase-experimental, realizado com 231 estudantes. Foram utilizados: Formulário sociodemográfico; Inventário de Triagem do Uso de Drogas; Escala de Expectativas Positivas acerca do Álcool, aplicados antes e após 60 dias da intervenção. Foram realizadas análises estatísticas descritivas e inferenciais. A hipótese do estudo não foi confirmada. Para o grupo geral, não foram observadas mudanças significativas nas expectativas positivas sobre o álcool após a intervenção. A frequência de consumo se manteve elevada após a atividade, com destaque para o sexo feminino. Os resultados demonstraram que a intervenção educativa não foi efetiva para influenciar mudanças do uso do álcool, todavia, foi eficaz para a aquisição de informações sobre a substância

It aimed to evaluate the positive expectancies about the recent alcohol use by elementary and high school students before and after an educational intervention and verify differences in the frequency of use and in the information about this substance, according to sex. A quasi-experimental study, carried out with 231 students. We made use of: Sociodemographic form; Drug Use Screening Inventory; Alcohol Expectancies Scale, applied 60 days before and after the intervention. We used descriptive and inferential statistical analyses. The hypothesis of the study was not confirmed. In general group, no significant changes were seen about the alcohol after the intervention. The consumption frequency remained high after the activity, with emphasis for the female gender. The results have shown that the educational intervention was ineffective to influence changes of the alcohol use, however, it was effective for the acquisition of information about the substance.

Study on inhibitory effects of Triperygium Wilfordii Polyglucoside on Dipeptidyl peptidase I and regulatory mechanism / 中国免疫学杂志

Objective:Dipeptidyl peptidase I(DPPI),a lysosomal cysteine protease for serine proteases activation,highly expressed in granule immune cells.This study used collagen induced arthritis(CIA) rat model to investigate the effects of Triperygium Wilfordii Polyglucoside(TWP) on DPPI activity and the pharmacological mechanism in RA treatment.Methods:Rats were divided into four groups randomly,the blank control group,the CIA model group,the high dose (5.0 mg/100 g body-weight) and low dose(2.5 mg/100 g body-weight)treatment group.Bovine collagen-Ⅱ plus complete Freund′s adjuvant injected twice in rats.Physical assessments were carried out.12 days post-injections,the rats of treatment group were intragastric administered with TWP every day.The rats were killed after two week administrations.Serum and synovial membrane homogenates were collected and DPPI activity was detected by fluorescence substrate.Joint HE staining and cell counting were carried out,Zymography was used to detect the MMP-2/9 activity in synovial fluids.Total protein in synovial membrane homogenates were measured by BCA method.Results:TWP could reduce the number of CIA synovial tissue mast cells,inhibited DPPI activity in the synovial fluids and in serum.The expression levels of MMP-2/9 activity and synovium total protein content were also reduced by TWP.Conclusion:Triperygium Wilfordii Polyglucoside has inhibitory effects on DPPI activity on CIA rats,which might be the one of the pharmacological mechanisms in RA treatment.

Study of Qingluo Tongbi Compound treating rheumatoid arthritis based on miRNA network / 中国免疫学杂志

Objective:To study the mechanism of Qingluo Tongbi Compound (QLT) treating rheumatoid arthritis(RA)by observing miRNA Network of QLT on collagen-induced arthritis ( CIA) mice.Methods:The model of RA was induced by collagenⅡin DBA/1 mice and randomly divided into control group , CIA group, QLT group.Differently expressed miRNAs were detected by miRCURYTM LNA Array.Real-time PCR was applied to verify the reliability of miRNA array.Results:The bioinformatics software and database were applied to predict and analyze target genes.MiRNA array results showed that 221 miRNAs changed in CIA group compared with the control group ,and 169 miRNAs changed in QLT group compared with CIA group.And the results of real-time PCR were consistent with the array.Compared with the control group ,miR-143 was significantly reduced in CIA group ,intervention of QLT obviously upregulated the expression of miR-143.The target genes of miR-143 were significantly stored in VEGF , T cell receptor, MAPK,signaling pathway.Conclusion: Multiple abnormal expression of miRNAs involved in the pathological process of CIA.QLT affected the expression of various miRNAs ,which might be related to immunity ,inflammation,pain pathological process of RA and miR-143 could be a potential target in the treatment.

Expression of bone morphology proteins in mice with collagen-induced arthritis / 重庆医学

Objective To establish collagen‐induced arthritis (CIA) model used of DBA/1J mouse ,a preliminary study of the expression levels of BM Ps in mononuclear cells of peripheral blood and the joints tissue of CIA mice .Methods We induced DBA/1J mice and developed arthritis pathology by using of bovine type Ⅱ ;then ,we detected mRNA and protein expression levels of BMPs by using quantitative PCR and immunohistochemical staining .Results We successfully established CIA mouse model .The expres‐sion of BMP4 and BMP9 mRNA was significantly down‐regulated in peripheral blood mononuclear cells and in the pathogenesis of joint tissues of CIA mice (P<0 .05) .It showed that BMP9 protein significantly decreased in joint tissues of CIA mice by immuno‐fluorescence technique (P=0 .002) .Conclusion At the genetic level ,the expression of BMP4 and BMP9 could be significantly down‐regulated in the CIA mouse .At the protein level ,BMP9 could be significantly down‐regulated in the CIA mouse .

Dendritic Cell-based Immunotherapy for Rheumatoid Arthritis: from Bench to Bedside

Dendritic cells (DCs) are professional antigen presenting cells, and play an important role in the induction of antigen-specific adaptive immunity. However, some DC populations are involved in immune regulation and immune tolerance. These DC populations are believed to take part in the control of immune exaggeration and immune disorder, and maintain immune homeostasis in the body. Tolerogenic DCs (tolDCs) can be generated in vitro by genetic or pharmacological modification or by controlling the maturation stages of cytokine-derived DCs. These tolDCs have been investigated for the treatment of rheumatoid arthritis (RA) in experimental animal models. In the last decade, several in vitro and in vivo approaches have been translated into clinical trials. As of 2015, three tolDC trials for RA are on the list of ClinicalTrial.gov (www.clinicaltrials.gov). Other trials for RA are in progress and will be listed soon. In this review, we discuss the evolution of tolDC-based immunotherapy for RA and its limitations and future prospects.

Relationship of serum neuroglobin and neuron-specific enolase level in preterm infants with brain damage / 国际儿科学杂志

Objective To study the relationships of serum neuroglobin and neuron-specific enolase level with periventricular hemorrhage-intraventricular hemorrhage ( PVH-IVH) and periventricular leucumalacia ( PVL) in preterm infants. Methods There were 241 cases of preterm infants whose gestational age was less than 34 weeks and were admitted in NICU of Guangzhou Women and Children′s Medical Center, Guangzhou Huadu District Matermal and Child Health Hospital and Dongguan Taiping Hospital from Jan. 2010 to May. 2013, enrolled in the study. The serum level of neuroglobin and neuron-specific enolase were detected within 12 hours and on the 3 d, 7 d, 14 d after birth. Cranial ultrasound was preformed 2~3 d, 1week, 2weeks, 3weeks, and 4 weeks after birth. They also received Cranial MRI examination before discharge or when the correct gestational age reached 40 weeks. All 241 cases were divided into 3 groups ( no brain damage group, PVH-IVH group and PVL group) according to the result of cranial US and MRI. The differences of the serum levels of neuroglobin and neuron-specific enolase among each groups were compared. Results The results of cranial ultrasound and /or MRI showed: 162 cases had no brain damage ( in no brain damage group) , 50 cases had PVH-IVH ( in PVH-IVH group) , and 20 cases had PVL, 9 cases had PVL and PVH-IVH ( both in PVL group) . Within 12 h and 3 d after birth, the serum levels of neuroglobin in PVL group and PVH-IVH group was significantly higher than those in no brain damage group (P0. 05 ) , and there were still significantly higher than those in no brain damage group and PVH-IVH group (all P0. 05). On 7 d and 14 d after birth, the serum levels of neuron-specific enolase in PVL group were no significant difference compared with PVH-IVH group and no brain damage group (all P>0. 05). Conclusion The increased serum levels of neuroglobin and neuron-specific enolase in preterm infants within 12 h and 3 d after birth would have certain clinical significance for judging whether early brain damage and PVL would happen.

Avaliação da microdureza Knoop e tração diametral de resinas compostas de uso direto / Evaluating Knoop microhardness and diametral tensile strength of composite resins of direct use

Objetivo: as propriedades mecânicas dos compósitos odontológicos podem fornecer importantes informações sobre o seu provável desempenho clínico. Nessa perspec-tiva, este artigo tem por objetivo avaliar a microdureza e a resistência à tração diametral de resinas compostas de uso direto. Materiais e método: foram avaliadas quatro resinas compostas: Filtek Z-250® (3M ESPE, Sumaré, São Paulo, Brasil), Filtek Z-350 XT® (3M ESPE, Sumaré, São Paulo, Brasil), Filtek P-90® (3M ESPE, Sumaré, São Paulo, Brasil) e Opallis® (FGM, Joinville, Santa Catarina, Brasil). Foram confeccionados 40 espécimes cilíndricos (n=10) de 4 mm de diâmetro por 2 mm de altura. Após a confecção, as amostras foram armazenadas em saliva artificial por 24h e, em seguida, foram polidas e submetidas aos ensaios mecânicos. Para o ensaio de dureza, um endentador Kno-op foi utilizado com carga de 50g por 5s nas superfícies de topo e base. Após a mensuração da dureza, as amostras foram submetidas ao teste de tração diametral. Os dados foram analisados por ANOVA e teste de Tukey (? = 0,05). Resultados: os resultados obtidos foram: Os compósitos Z-250® e Z-350 XT® apresentaram os maiores valores de dureza sem diferença estatística entre eles. Não hou-ve diferença entre P-90® e Opallis®. O ensaio de tração diametral Z-250® registrou maiores valores que P-90® e Opallis®. Conclusão: com base nesses dados, conclui-se que os compósitos Z-250® e Z-350 XT® apresentaram me-lhores propriedades mecânicas do que o P-90® e Opallis®.