Association of the protein tyrosine phosphatase non-receptor 22 polymorphism (PTPN22) with endometriosis: a meta-analysis / Associação do polimorfismo da proteína tirosina fosfatase não receptora 22 (PTPN22) com endometriose: uma metanálise

ABSTRACT Objective To evaluate PTPN22 C1858T polymorphism and the risk of endometriosis. Methods A meta-analysis of 10 published case-control studies (from four articles), with a total sample of 971 cases and 1,181 controls, was performed. We estimated risk (odds ratio and 95% confidence intervals) of endometriosis associations with the C1858T polymorphism. Results A significant increased risk in all genetic models of the variant T allele with endometriosis (odds ratio: 3.14-5.55; p<0.00001-0.002) was found. The analysis without the study whose controls deviated from the Hardy-Weinberg equilibrium exacerbated these effects in the homozygous and recessive models (odds ratio: 7.19-9.45; p<0.00001-0.0002). In the Italian subgroup, a significant risk association was found in the homozygous and recessive models (odds ratio: 8.72-11.12; p=0.002). Conclusion The associations observed between PTPN22 (C1858T) and the risk of endometriosis suggest this polymorphism might be a useful susceptibility marker for this disease.

RESUMO Objetivo Avaliar o polimorfismo PTPN22 C1858T e o risco de endometriose. Métodos Foi realizada uma metanálise de 10 estudos caso-controle publicados (a partir de quatro artigos), com uma amostra total de 971 casos e 1.181 controles. O risco da associação da endometriose com o polimorfismo C1858T foi estimado em razão de chance e intervalo de confiança de 95%. Resultados Observou-se um aumento de risco significativo em todos os modelos genéticos com o alelo variante T e a endometriose (razão de chance: 3,14-5,55; p<0,00001-0,002). A análise sem incluir o estudo, em que os controles não estavam em equilíbrio de Hardy-Weinberg, mostrou aumento significativo nos modelos homozigotos e recessivos (razão de chance: 7,19-9,45; p<0,00001-0,0002). No subgrupo italiano, uma associação significativa foi encontrada considerando os modelos homozigoto e recessivo (razão de chance: 8,72-11,12; p=0,002). Conclusão As associações observadas entre PTPN22 (C1858T) e o risco de endometriose sugerem que este polimorfismo pode ser um marcador de suscetibilidade para a endometriose.

The effect of estradiol on renal tubular exression of ATP-binding cassette superfamily member 2 via PI3K/Akt pathway / 中华风湿病学杂志

Objective To compare the serum estradiol level of gouty patients with healthy controls and to investigate whether estradiol upregulatesthe expression of the uric acid transporter ATP-binding cassette superfamily member 2 (ABCG2) of human renal tubular epithelial cells (HK-2)..Methods Serum of 16 male gout patients and 16 male healthy controls and their estradiol level were assessed with ELISA.The HK-2 cells wer cultured with different concentrations of estradiol for 24 hours or 48 hours.mRNA expression of ABCG2 was assessed by quantitative polymerase chain reaction (qPCR).HK-2 cells were cultured with estradiol or estradiol and inhibitor of PI3K/Akt pathway LY294002.mRNA expression of ABCG2 was assessed by qPCR,while the Akt,p-Ser473-Akt,p-Thr308-Akt and ABCG2 expression were investigated by Western blot.Data was analyzed using either the one-way analysis of variance or the t test.Results The level of serum uric acid in gout patients was [(547±18) μmol/L],which was significantly higher than that of healthy controls [(344±12) μmol/L),t=-5.395,P＜0.01].The level of estradiol in gout patients was (45±6) μmol/L,which was significantly lower than that of healthy controls [(100±8) μmol/L,t=9.375,P＜0.01].The mRNA expression of ABCG2 of 10-4 mol/L estradiol group was elevated after 24 hours or 48 hours (t=3.168,t=3.990;P＜0.01).In the group of co-stimulation withestradiol and LY294002,the ABCG2,p-Ser473-Akt and p-Thr308-Akt expression were down regulated compared to the estradiol group.Conclusion There is a significant correlation between serum estradiol and uric acid.Estradiol inducesthe expression of ABCG2 of HK-2 cells by activating PI3K/Akt pathway.

Expression of PTPN13 in human gastric cancer and gastric cancer SGC-7901 cell line and its effect on cell proliferation and invasion / 基础医学与临床

Objective To investigate the expression of PTPN13 in human gastric cancer and gastric cancer SGC-7901celllineanditsassociationwithproliferationandinvasion.Methods 106casesgastriccancertissuesamples and matched normal peritumorial tissues were collected .SGC-7901 cells were cultured and divided into two groups including pcDNA3.1-PTPN13 transfection group and without transfection group .Immunohistochemical technique was used to detecte protein expression of PTPN 13.The association of PTPN13 expression with tumor location , tumor size , depth of invasion and tumor metastasis were analyzed .The survival rate of patients with different PT-PN13 expression was calculated by Kaplan-Meier curves.CCK-8 assay was used to estimate the proliferation chan-ges.Using Trans-well assay analyzed the invasion of SGC-7901 cells.Moreover, Western blot was performed to de-tect the markers of EMT including E-cadherin, Snail and MMP9.Results Immunohistochemistry showed the expression rate of PTPN13 in gastric cancer tissues was lower than normal tissue (31 %vs 83%, P<0.05).The expression of PTPN13 in patients was related to with different tumor size , depth of invasion and tumor metastasis (P<0.05).The 2-year survival rate of patients with negative PTPN13 expression were lower.Overexpression reduced both proliferation and invasion in SGC-7901 cells.Up-regulated PTPN13 may increase E-cadherin level but decreases the level of Snail and MMP9 .Conclusions PTPN13 plays a role in gastric cancer tissue and cells as a tumor suppressor.Lower PTPN13 may predict a poor prognosis.PTPN13 may be used as therapy target in gastric cancer.

Análise imunocitoquímica e de expressão gênica de efeitos do bevacizumabe em explantes de retina de ratos lister e em linhagem celular de glia de Müller humana

INTRODUÇÃO: As doenças retinianas associadas à neovascularização, tais como a degeneração macular relacionada à idade e as retinopatias diabética e da prematuridade são as principais e mais importantes causas da cegueira em todo o mundo. Nos últimos anos, injeções intravítreas de fármacos com ação antiangiogênica, como o bevacizumabe (BVZ), têm sido de grande valia tanto em pacientes na fase adulta quanto nos recém-natos. Todavia, estudos experimentais in vitro e in vivo sugerem que essas drogas promovam efeitos adversos sobre alguns processos celulares, interferindo diretamente em mecanismos fisiológicos que mantém a homeostase do tecido retiniano, incluindo os mecanismos de proliferação, diferenciação e morte celular. OBJETIVO: investigar o efeito do BVZ nos processos de transcrição e tradução de marcadores da gliose: GFAP e vimentina, de morte celular, caspase-3 e beclina-1, e dos proteoglicanos relacionados à manutenção e desenvolvimento de tecido retiniano: neurocam, fosfacam e sindecam-3. MÉTODOS: Dois modelos experimentais foram usados nesse estudo: 1) linhagem celular de Müller de Glia humana adulta (MIO-M1), cultivada em meio de cultura D-MEM na presença e ausência de BVZ por 12 e 24 horas nas concentrações de 0,25 mg/mL e 0,50 mg/mL e 2) explantes de retinas de ratos 2 dias pós-nascidos submetidos à 0,50 mg/mL da droga por 48 horas. Durante este período foram mantidos a 5% de dióxido de carbono à temperatura de 37°C. A análise de proteínas foi realizada por imunocitohistoquímica e Western Blotting e a expressão de RNAm, pela reação em cadeia da polimerase em tempo real (PCR Real Time). Foi utilizado o Teste de ANOVA - fator único para a comparação entre os grupos controle e tratados com BVZ de um mesmo período (12h ou 24h) e o teste t de Student para a comparação entre as mesmas concentrações de 12h e 24h, e para a comparação entre os grupos controle e tratado com BVZ dos explantes (p < 0,05). RESULTADOS...

Backgraound: Vasoproliferative retinal disorders such as age-related macular, degeneration, diabetic retinopathy and retinopathy of prematurity are major causes of blindness in the world. In recent years, intravitreal injections of drugs with antiangiogenic action, as bevacizumab, have been very useful for both patients in adulthood and in newborns. However, experimental studies, in vivo and in vitro, suggest that antiangiogenic drugs may promote side effects in cellular proceedings, interfering directly in physiological mechanisms of cellular proliferation, differentiation and death. POURPOSE: Investigate the bevacizumab effects in transcription and translation processes of gliosis, GFAP and vimentin, cellular death markers, caspase-3 and beclin-1, and proteoglycans involved in retinal tissue maintenance and development, neurocan, phosphacan and syndecan-3. METHODS: Two experimental models were used on this research: cellular lineage of adult and human Müller glial cell(MIO-M1) were cultivated on D-MEM medium with 0,25 and 0,50 mg/mL bevacizumab for 12 and 24 hours, and two days old rat retinal explants submitted to 0,50 mg/mL for 48 hours. During this period were stored in laboratory ovens at 5% carbon dioxide pressure and 37 °C average temperature. Molecular techniques were used to evaluate gene expression and protein content. Protein assessments were performed by immunocytochemistry and western blotting analysis, while Real Time PCR was used to measure mRNA content. ANOVA tests one factor were applied to compare the control and BVZ groups of the same period (12h or 24h) and t test from Student to compare the same conditions of 12h and 24h, and to compare the control and BVZ retinal explants groups (p<0.05). RESULTS...

Advance research on protein tyrosine phosphatase SHP-2 and the regulating role of it in osteoclastogenesis / 医学研究生学报

SHP-2 is one of the protein tyrosine phosphatases which plays a role in the progress of dephosphorylation in organ -isms, participating in many kinds of signal transduction pathways .The mutation of SHP-2 is associated with many kinds of malignant diseases .In recent years , scholars have found that SHP-2 is the key factor in osteoclastogenesis , playing a positive role in the progress of reversible phosphorylation of osteoclasts .The objective of this article is to review the molecular biological characteristics of SHP-2, th diseases associated with the mutation of SHP-2 and the effects of SHP-2 in regulation of osteoclastogenesis .

Expression of protein tyrosine phosphatase receptor T in brains of patients with intractable epilepsy and rats after pilocarpine induced seizures / 中华神经科杂志

Objective To investigate the expression changes of the protein tyrosine phosphatase receptor T (PTPRT) in temporal lobe epileptic foci in the experimental animals and epileptic patients and the relationship between PTPRT and epileptogenesis.Methods After getting the epilepsy lobe tissue from the experimental and control groups,immunohistochemistry,immunofluorescence and Western blot analysis were used to assess the expression of PTPRT and its changes.Results In the temporal lobe tissue of intractable patients and control group,PTPRT was mainly expressed in the neurons.PTPRT was significantly increased in patients with intractable epilepsy (0.277 ± 0.048) than that in the control group(0.171 ±0.025 ; t =9.586,P ＜ 0.05).PTPRT was mainly expressed in the neurons in the temporal lobe brain tissue of the rats in the control group and experimental group.Compared with control group,the expression of PTPRT in the temporal lobe tissue was increased within 24 h post-seizure,and decreased 1 and 2 weeks post-seizure,then it was increased 1 and 2 months post-seizure (A ratio:control 0.443 ± 0.039,6 h 0.840±0.032,24 h 1.113 ±0.064,7 d 0.564 ±0.039,14 d 0.570 ±0.029,30 d 0.899 ±0.034,60 d 1.011 ± 0.074,F =256.427,P ＜ 0.05).Conclusions Through researches into the expression and function of PTPRT in the temporal lobe brain tissue of patients with intractable epilepsy and animal models,we presume that the PTPRT plays a role in the synapses reorganization and mossy fiber sprouting,and participates in the reconstruction of the neural network which leads to the intractable epilepsy.

Roles of the liver regeneration phosphatase-3 and its inhibitors in tumor / 国际肿瘤学杂志

Phosphatase of regenerating liver-3 (PRL-3) is a novel small molecule protein-tyrosine-phosphatase,which plays an important role in the oncogenesis and deveopment of tumors.Studies show that PRL-3 regulates neoplasm progress through participating in multiple signal pathways.Its high expression can significantly promote neoplasm metastasis in cancer tissue.However,there is no expression of PRL-3 in most normal tissue.PRL-3 is expected to be a potential tumor maker of diagnosis and a new target for the therapy of cancer.

The Role of Oxidative Stress in the Pathogenesis of Asthma

Oxidative stress plays a critical role in the pathogenesis of asthma. To effectively control oxidative stress in asthmatics, it is important to investigate the precise intracellular mechanism by which the development of immunity, rather than immune tolerance and progression of airway inflammation, is induced. In this article, we suggest that protein tyrosine phosphatases, as intracellular negative regulators, and intracellular antioxidant enzymes such as peroxiredoxins can be regulated by oxidative stress during intracellular signaling.

Integrative Physiology: Defined Novel Metabolic Roles of Osteocalcin

The prevailing model of osteology is that bones constantly undergo a remodeling process, and that the differentiation and functions of osteoblasts are partially regulated by leptin through different central hypothalamic pathways. The finding that bone remodeling is regulated by leptin suggested possible endocrinal effects of bones on energy metabolism. Recently, a reciprocal relationship between bones and energy metabolism was determined whereby leptin influences osteoblast functions and, in turn, the osteoblast-derived protein osteocalcin influences energy metabolism. The metabolic effects of bones are caused by the release of osteocalcin into the circulation in an uncarboxylated form due to incomplete gamma-carboxylation. In this regard, the Esp gene encoding osteotesticular protein tyrosine phosphatase is particularly interesting because it may regulate gamma-carboxylation of osteocalcin. Novel metabolic roles of osteocalcin have been identified, including increased insulin secretion and sensitivity, increased energy expenditure, fat mass reduction, and mitochondrial proliferation and functional enhancement. To date, only a positive correlation between osteocalcin and energy metabolism in humans has been detected, leaving causal effects unresolved. Further research topics include: identification of the osteocalcin receptor; the nature of osteocalcin regulation in other pathways regulating metabolism; crosstalk between nutrition, osteocalcin, and energy metabolism; and potential applications in the treatment of metabolic diseases.

Tyrosine phosphatase and cytochrome P450 activity are critical in regulating store-operated calcium channels in human fibroblasts

Diverse signaling pathways have been proposed to regulate store-operated calcium entry (SOCE) in a wide variety of cell types. However, it still needs to be determined if all of these known pathways operate in a single cell type. In this study, we examined involvement of various signaling molecules in SOCE using human fibroblast cells (HSWP). Bradykinin (BK)-stimulated Ca2+ entry, previously shown to be via SOCE, is enhanced by the addition of vanadate, an inhibitor of tyrosine phosphatases. Furthermore, SOCE is regulated by cytochrome P-450, as demonstrated by the fact that the products of cytochrome P-450 activity (14,15 EET) stimulated SOCE while econazole, an inhibitor of cytochrome P450, suppressed BK-stimulated Ca2+ entry. In contrast, Ca2+ entry was unaffected by the guanylate cyclase inhibitor LY83583, or the membrane permeant cyclic GMP analog 8-bromo-cyclic GMP (8-Br-cGMP). Neither nitric oxide donors nor phorbol esters affected BK-stimulated Ca2+ entry. SOCE in HSWP cells is primarily regulated by tyrosine phosphorylation and the cytochrome P-450 pathway, but not by cyclic GMP, nitric oxide, or protein kinase C. Thus, multiple pathways do operate in a single cell type leading to the activation of Ca2+ entry and some of these signaling pathways are more prominently involved in regulating calcium entry in different cell types.