Involvement of histone modifications in process of uterine injury alleviated by TSA in female mice induced by cigarette smoke exposure / 中国药理学通报

Aim To explore whether histone modifications are involved in the process of uterine injury alleviated by TSA in female mice induced by cigarette smoke (CS) exposure. Methods Female mice were exposed to CS twice daily for 30 days and TSA was injected intraperitoneally into CS-exposed mice on alternate days in the TSA-treated group. HE staining was used to observe the morphological changes of mice uterus after CS exposure; Western blot was used to assess the global modification levels of H3K4mel, H3K4me2, H3K4me3, H3K9mel, H3K9me2, H3K9me3 and H3K27me3 in uteri. GLP (H3K9 his-tone methyltransferase) , G9a (H3K9 histone methyl- transferase) , EZH2 (H3K27me3 histone methyltrans ferase ). Results TSA effectively restored the number of glandular and interstitial cells reduced by CS exposure. Western blot results showed that TSA significantly inhibited global H3K9mel modification and further aggravated H3K27me3 change induced by CS exposure. Furthermore TSA suppressed GLP and G9n expression in mouse uterine tissue induced by CS exposure, but further activated EZH2 increase. Conclusions Histone modifications are involved in the process of uterine injury alleviated by TSA in female mice induced by cigarette smoke exposure.

Consideraciones sobre algunas consecuencias del diagnóstico de trastorno del espectro autista: el desplazamiento de las categorías diagnósticas del DSM-IV al DSM-V / Considérations sur certaines conséquences du diagnostic du trouble du spectre autistique: le déplacement des catégories diagnostiques du DSM-IV au DSM-V / Considerations on certain consequences of autistic spectrum disorder: the shifting of diagnosis categories from DSM-IV to DSM-V / Considerações sobre algumas consequências do diagnóstico do transtorno do espectro autista: o deslocamento das categorias de diagnóstico DSM-IV para DSM-V

El artículo se propone analizar las consecuencias que el diagnóstico de Trastorno del espectro autista (TEA), acarrea sobre los niños y sus familias y los desplazamientos de categorías y criterios diagnósticos del DSM-4 al DSM-5, poniendo en evidencia el cambio de paradigma teórico e ideológico subyacente entre ambos. Rastrea históricamente los fundamentos de los DSM, para distinguir luego en tres niveles (el teórico, clínico y técnico), algunas consecuencias del diagnóstico de TEA(AU)

The article intends to analyze the consequences that the diagnosis of Autistic Spectrum Disorder (ASD) brings upon children and their families, as well as the shifting of diagnosis categories and criteria from DSM-4 to DSM-5, highlighting the underlying theoretical and ideological change of paradigm between the two. We track the historical foundations of the DSM, in order to identify in 3 levels (theoretical, clinical, and technical) various consequences of ASD diagnosis(AU)

L'article propose d'analyser les conséquences que le diagnostic du Trouble du spectre autistique (TSA) produit sur les enfants et leur famille, ainsi que les évolutions dans les catégories et les critères diagnostiques du DSM-4 et DSM-5, mettant en évidence le changement sous-jacent du paradigme théorique et idéologique entre ces derniers. On retrace historiquement les fondements du DSM, pour ensuite identifier certaines conséquences du diagnostic du TSA sur trois niveaux (théorique, clinique, et technique)(AU)

O artigo tem como objetivo analisar as consequências do diagnóstico do Transtorno do Espectro Autista (TEA), sobre as crianças e seus familiares e os deslocamentos de categorias e critérios diagnósticos do DSM-4 para o DSM-5, destacando a mudança no paradigma teórico e ideológico subjacente entre os dois. Ele historicamente traça os fundamentos dos DSMs, e depois distingue em três níveis (teórico, clínico e técnico), algumas consequências do diagnóstico de TEA(AU)

Algunas puntualizaciones sobre el diagnóstico de autismo y el trastorno de espectro autista / Quelques points sur le diagnostic de l'autisme et le trouble du spectre de l'autism / Some clarifications on the autism diagnosis and the autism spectrum disorder / Alguns pontos no diagnóstico do autismo e no transtorno do espectro do autismo

Se presenta un breve recorrido histórico sobre las diversas conceptualizaciones que se realizaron sobre el diagnóstico de autismo, tomando las originarias descripciones desde la perspectiva psiquiátrica para luego describir los postulados teóricos que fueron desarrollados por diferentes autores dentro del psicoanálisis. Se examina la modalidad diagnóstica propia de la psiquiatría a través del uso de manuales (DSM) y se concluye con una reflexión acerca de la incidencia de éste fenómeno actual y la escuela(AU)

Un bref aperçu historique des diverses conceptualisations qui ont été faites sur le diagnostic de l'autisme est présenté, en prenant les descriptions originales faites par la perspective psychiatrique, puis en décrivant les postulats théoriques qui ont été développés par différents auteurs au sein de la psychanalyse. La modalité diagnostique de la psychiatrie est examinée à l'aide de manuels (DSM) et se termine par une réflexion sur l'incidence de ce phénomène actuel et sur l'école(AU)

This study presents a brief historical overview of the various conceptualizations that were made on the diagnosis of autism. For that purpose, it takes the original descriptions made by the psychiatric perspective and then describes the theoretical postulates that were developed by different authors within psychoanalysis. The diagnostic modality of psychiatry is examined using manuals (DSM). The study concludes with a reflection on the incidence of this current autism phenomenon and the school(AU)

Segue uma breve visão histórica das várias conceituações que foram feitas no diagnóstico do autismo, tomando as descrições originais feitas pela perspectiva psiquiátrica e, em seguida, descrevendo os postulados teóricos que foram desenvolvidos por diferentes autores na psicanálise. A modalidade diagnóstica da psiquiatria é examinada segundo o uso de manuais (DSM) e termina com uma reflexão sobre a incidência desse fenômeno atual e da escola(AU)

Meta-analysis and trial sequential analysis of Qingjin Huatan Decoction for treating community-acquired pneumonia in elderly / 中国中药杂志

To systematically evaluate the clinical efficacy and safety of modified Qingjin Huatan Decoction in the treatment of community-acquired pneumonia in the elderly, and provide evidence-based reference for the clinical application of this prescription. Randomized controlled trials of Qingjin Huatan Decoction in the treatment of community-acquired pneumonia in the elderly were collected by searching PubMed, EMbase, Cochrane Library, CNKI, China Biomedical Literature database, VIP database and WanFang database. Outcome indicators included clinical effective rate, inflammation index, symptom improvement time, chest radiograph improvement time, hospitalization time and adverse reactions. RevMan 5.3 and Stata/IC 15.1 software were used for Meta-analysis; TSA 0.9.5.10 Beta software was used for trial sequential analysis, and GRADE profiler 3.6 was used for grade evidence quality evaluation. Thirteen studies were included finally, including 1 058 patients, 536 patients in the experimental group and 522 patients in the control group.Meta-analysis showed that, the clinical effective rate of the experimental group was significantly higher than that of the control group(RR=1.16, 95%CI[1.10, 1.21], P<0.000 01); fever time(MD=-1.32, 95%CI[-1.93,-0.71], P<0.000 1), cough time(MD=-1.95, 95%CI[-2.69,-1.21), P<0.000 01), time to rale disappearance(MD=-1.55, 95%CI[-2.37,-0.73], P=0.000 2), time to chest radiograph improvement(MD=-1.72, 95%CI[-2.98,-0.46], P=0.007), and hospitalization time(MD=-3.16, 95%CI[-4.58,-1.74], P<0.000 01) in the experimental group were significantly shorter than those in the control group. The improvement in CRP(WMD=-3.44,95%CI[-4.50,-2.38],P<0.001), WBC(WMD=-2.04,95%CI[-3.31,-0.78],P<0.01), IL-6(WMD=-4.27,95%CI[-4.62,-3.92],P<0.001), and TNF-α(WMD=-0.47,95%CI[-0.55,-0.39], P<0.001) of the experimental group was significantly better than that of the control group. There was no significant difference in PCT improvement between the two groups(WMD=-0.63, 95%CI[-1.65, 0.40], P=0.23). No serious adverse reactions occurred in both groups. Sequential analysis of the trial showed that in the studies with cumulative inclusion of clinical effective rate, the data passed the traditional threshold and TSA threshold, further confirming its clinical efficacy. GRADE evaluation showed that the evidence level was low to extremely low. Western medicine treatment combined with Qingjin Huatan Decoction may improve clinical efficiency in the treatment of community-acquired pneumonia in the elderly, improve clinical symptoms faster, reduce CRP, WBC and other inflammatory indicators, and shorten hospital stay. The level of evidence obtained in this study is low, which needs to be further verified by high-quality multi-center, randomized controlled trials.

LncRNA Neat1 is upregulated in P19 cell line processed with all-trans-retinoic acid / 基础医学与临床

Objective To investigate the expression of Neat1 in the differentiation of P19 cells induced by all-trans-retinoic acid(atRA) and to explore the effect of histone modification on its expression. Methods The differentiation of P19 cells was induced with the α-MEM culture media containing 0.5 μmol/L all-trans-retinoic( atRA) acid and the expression Mash1 which is the neural differentiation maker gene was measured. The expression of Neat1 was measured with RT-qPCR. The cells were treated with TSA, NAM or AdOx respectively to investigate the effect of the histone modifier inhibitor on the expression of Neat1. Results The model of differentiation of P19 cells induced by atRA was successfully constructed. Mash1 was significantly upregulated in the process of P19 cells differentiation.Neat1 was significantly upregulated with the induction of P19 cells treated with atRA(P＜0.01). The TSA but not the NAM or AdOx could induce the expression of the Neat1.Conclusions The expression of Neat1 is significantly upregulated in the process of P19 differentiation induced by atRA and the the high level of histone acetylation maintained by TSA potentially induce the expression of Neat1.

DNA vaccination with a plasmid encoding LACK-TSA fusion against Leishmania major infection in BALB/c mice

Vaccination would be the most important strategy for the prevention and elimination of leishmaniasis.The aim of the present study was to compare the immune responses induced following DNA vaccinationwith LACK (Leishmania analogue of the receptor kinase C), TSA (Thiol-specific-antioxidant) genesalone or LACK-TSA fusion against cutaneous leishmaniasis (CL). Cellular and humoral immuneresponses were evaluated before and after challenge with Leishmania major (L. major). In addition,the mean lesion size was also measured from 3th week post-infection. All immunized mice showed apartial immunity characterized by higher interferon (IFN)-γ and Immunoglobulin G (IgG2a) levelscompared to control groups (p<0.05). IFN-γ/ Interleukin (IL)-4 and IgG2a/IgG1 ratios demonstratedthe highest IFN-γ and IgG2a levels in the group receiving LACK–TSA fusion. Mean lesion sizesreduced significantly in all immunized mice compared with control groups at 7th week post-infection(p<0.05). In addition, there was a significant reduction in mean lesion size of LACK-TSA andTSA groups than LACK group after challenge (p<0.05). In the present study, DNA immunizationpromoted Th1 immune response and confirmed the previous observations on immunogenicity ofLACK and TSA antigens against CL. Furthermore, this study demonstrated that a bivalent vaccinecan induce stronger immune responses and protection against infectious challenge with L. major.

Effects of Trichostatin A on the Chondrogenesis from Human Mesenchymal Stem Cells

Histone deacetylase inhibitors (HDACi) are a class of compounds that suppress the function of histone deacetylases (HDACs). This study was performed to examine the effects of Trichostatin A (TSA), a typical HDACi, on chondrogenesis of human bone marrow mesenchymal stem cells (hBMMSCs) and related molecular pathways. After evaluating the concentration for cytotoxicity and HDAC activity, hBMMSCs underwent chondrogenic differentiation in pellet culture with or without TSA for 21 days. The weight of TSA-treated pellets was 25% lower than that of untreated pellets. DNA level was not significantly different, but glycosaminoglycan content per DNA level was lower in TSA-treated pellets than that of untreated pellets. Gene expression of the chondrogenic markers (SOX9, Aggrecan, and Col2A1) decreased by by 12.9-fold, 8.9-fold, and 7.6-fold respectively in TSA-treated pellets compared with that in TSA-untreated pellets. TSA-treated pellets had lower cell density and lower proteoglycan staining content compared with those of TSA-untreated pellets. A microarray analysis from TSA-treated pellets showed that 1,467 chondrogenic-related genes were downregulated and 1,524 were upregulated by more than 2-fold compared with TSA-untreated pellets. Col10A1, TGF-β3, and SOX9 decreased significantly by 10-fold, 2.1-fold, and 3.2-fold respectively in TSA-treated pellets compared with those in untreated pellets, whereas expression of BMP4 and FGFR3 increased significantly by 2.1-fold and 5.4-fold respectively. It is concluded that TSAinhibits chondrogenesis and does not seem to be useful for cartilage tissue engineering of hBMMSCs.

Effects of 5-aza-2' -deoxycytidine combined with trichostatin A on cell proliferation and PDX-1 methylation on high glucose-induced toxicity in pancreatic β cells / 实用医学杂志

Objective To investigate the effects of 5-aza-2'-deoxycytidine (5-Aza-dC) alone or combined with trichostatin A(TSA) on cell proliferation, promoter methylation and mRNA expression level of PDX-1 gene in pancreatic β cells induced by high glucose toxicity. Method NIT-1 cells were treated in vitro by high glucose (33.3 mmol/L), then divided into five groups, control group, HG grpup, 5-Aza-dC treatment group, TSA interfere group and 5-Aza-dC + TSA group. Proliferation of NIT-1 cells, insulin secretion, promoter methylation and mRNA expression of PDX-1 gene were detected respectively. Results 5-Aza-dC and TSA alone or in combination could promote cell proliferation and recover insulin secretion in NIT-1 cells , could also reduce PDX-1 gene methylation and enhance expression of PDX-1 mRNA. Compared with single-treatment group , combined group was significantly different (all P < 0.05). Conclusion 5-Aza-dC and TSA could activate the expression of PDX-1 and, then recover insulin secretion in NIT-1 cells induced by high glucose. Combination of them had synergistic effect.

Isolation and Genetic Characterization of Orientia tsutsugamushi from Scrub Typhus Patients in Gyeongsangnam-do, Korea

Orientia tsutsugamushi (O. tsutsugamushi), which is endemic to an Asia-Pacific region, has increased its incidence and caused annually around 10 thousand patients infected with scrub typhus in Korea in the past several years. In the present study, we isolated 44 O. tsutsugamushi from the patients with febrile illness accompanied with or without an eschar in Gyeongsangnam-do, Korea. These isolates were characterized by genetic analysis of the major outer membrane protein, the 56-kDa type-specific antigen (tsa56), which is unique to O. tsutsugamushi. Two types of sequences of tsa56, designated by JJ1 and JJ2, were determined from 37 and 7 isolates of the 44 isolates, respectively. JJ1 and JJ2 showed 74.7~90.8% identity in nucleotide sequence and 66.1~90.5% identity in amino acid sequence with 33 reference strains except for Boryong and Kuroki. JJ1 and JJ2 had 100 and 99.9% nucleotide identity to Boryong strain, and 99.9 and 99.8% to Kuroki, which has been known to be similar to Boryong, respectively. In addition, they showed 77.9~ 81.4% nucleotide identity with the cluster of Gilliam-related genotypes, whereas they showed higher nucleotide identity (89.6~90.8%) with the cluster of Karp-related genotypes. To our knowledge, this is the first report to isolate O. tsutsugamushi and characterize their genotype as the Boryong in Jinju and West Gyeongsangnam-do, Korea, even though it has been reported that the Boryong was the predominant genotype in isolates from chiggers, domestic rodents, and patients in the southern part of Korea. Furthermore, our isolates could be useful source to study on the pathophysiology and epidemiology of scrub typhus in Korea.

The protective effects of histone deacetylases inhibitor TSA on the mice model of rheumatoid arthritis / 中华微生物学和免疫学杂志

Objective To investigate the effects of trichostatin A(TSA)on the mice model of collagen induced arthritis(CIA).Methods Mice model of rheumatoid arthritis(RA)was induced in DBA/1 mice with type Ⅱ collagen.Paws were scored for histological severity of arthritis.The severity of inflammation of mouse joint was evaluated by histological examination.Real-time PGR was used to determine the cytokine mRNA expression.Cytokine production was measured by ELISA from serum,spleen cell culture or dendritic cell and T cell co-culture supematant.T cell proliferation was examined by MTT method.Results TSA can significantly suppress the severity of the arthritis in CIA.IFN-γ was elevated in CIA mice,but was inhibited significantly by TSA introduced either at the same time with immunization or at the onset of manifestation of arthritis.Collagen specific T cell proliferation was significantly suppressed by introduction of TSA.Increased level of IL-4 by T cells was observed in TSA treated group compared to that of control group.Conclusion IL-4 level was increased and played a critical role in the protective effects of TSA in CIA.TSA suppresses the progress of CIA by regulates the balance of Th1/Th2 differentiation.

Pituitary Apoplexy: Surgical Experience with 16 Patients

OBJECTIVE: Pituitary apoplexy, resulting from an acute infarction or hemorrhage mainly in pituitary adenomas, is a rare yet major clinical event with neurological, ophthalmological and hormonal emergent consequences. The authors review our surgical experience with a series of 16 cases of pituitary apoplexy. METHODS: The cases of pituitary apoplexy, operated via trans-sphenoidal approach in our hospital between 1998-2005, were retrospectively analyzed in terms of their clinicoradiological features, pathological findings and surgical outcomes. RESULTS: The mean age of patients (9 male and 7 female) was 47.1 years. The average time of presentation after onset of symptom was 8.9 days. Pituitary apoplexy occurred as an initial manifestation of pituitary adenoma in all patients. Headache was the most common presenting symptom (94%). Visual disturbance was found in 56% of patients. Thirty-one percent of the patients had hypopituitarism. On magnetic resonance imaging, this entire catastrophic event accompanied with macroadenoma in a mean size of 22.5 mm. Only four patients needed postoperative hormone replacement therapy. Three of them showed preoperative hypopituitary function, and one patient in normal pituitary function. There was no specific complication in any of these patients. CONCLUSION: Early trans-sphenoidal decompression with high-dose corticosteroid replacement showed good outcomes of pituitary apoplexy.

Application of Tyramide Signal Amplification (TSA) Both to Biochip Platform and to the Immunoelectron Microscopy to Label Proteins within the Organelle / 대한해부학회지

The tyramide signal amplification (TSA) technique, based on the ability of HRP to catalyze the deposition of tyramide onto the surrounding proteins, has been proved to detect scarce tissue antigens. In this study we applied this technique to a biochip platform and an immunocytochemistry at the electron microscopic level. First, in the optical fluorescence sensing, the signal was amplified by Dako Envision(TM) (goat anti-mouse immunoglobulins IgG conjugated to peroxidase labelled-dextran polymer) and tyramide-Cy3, which was then compared to the non-amplified control using goat antimouse IgG-Cy3 conjugate instead. The result showed that the tyramide method produced a more sensitive signal than the control method. Secondly, in the pre-embedding immunocytochemistry, we investigated to see whether it is possible to label proteins within a organelle in the cell using the TSA method. The signal was amplified by a primary antibody, a biotinylated secondary antibody, streptavidin-HRP, biotinyl-tyramide, and streptavidinnanogold followed by silver enhancement and gold toning. Then, this protocol was compared to the non-amplified or simple protocol that does not include the steps of streptavidin-HRP and biotinyl-tyramide. With the TSA protocol, the labeling for a membrane bound antigen (gp100) that is known to be exclusively localized to melanosomes in melanocyte, was tested in a melanoma cell line (G361) and found to be highly sensitive and more enhanced than with the simple protocol. Moreover, the gold particles were well localized to the subcellular structures or melanosomes both in the TSA and simple protocols, which indicates that resolution of the signals remains high. Control experiment with omission of the primary antibody demonstrated that background levels or nonspecific bindings are negligible. This result showed that the TSA method can be successfully applied to label the intra-organelle protein that is known to be labeled only in the specific fixation condition with the optimal permeability.

Effect of Curcumin and TSA on Human Gastric Cancer Cell Line c-myc Expression / 医学研究杂志

Objective To understand the effect of curcumin and TSA on c-myc gene expression in human gastric cancer and to explore the dynamic balance of the histone acetylation / deacetylation in gene expression in gastric cancer and the significance of the regulation. Methods Gastric cancer cell line SGC-7901 and MGC803 were cultured,and then different concentrations of histone acetylase inhibitors curcumin and histone deacetylase inhibitor TSA were added,respectively.mRNA of c-myc expression wasdetected by RT-PCR. Results With increasing of the concentration of curcumin and redcuing of the TSA concentrations c-myc expression was inhibited (P

Studies on the rationality of TSD combined with TSA on reducing serum uric acid and anti-inflammatory in mice / 中国药理学通报

Aim To investigate the rationality and the dose of TSD combined with TSA on reducing serum uric acid and anti-inflammatory.Methods Mice hyperuricemic models were made by uric acid intraperitoneal injection or yeast extract paste intragastric administration.Mice ear swelling model was induced by locally painting dimethylbenzene.Optimized combination dosage of TSD and TSA was obtained using the Codrug software.Results In the mice hyperuricemic models,the serum uric acid in TSD group,TSD plus TSA group and positive control groups was significantly reduced compared with the model group(P

Transseptal-Transsphenoidal Approach: Objective Assessment of Postoperative Nasal Functions

THE AIM OF STUDY: The transseptal-transsphenoidal approach (TSA) for pituitary tumors may alter nasal functions, including nasal respiration and olfaction. The aim of this study was to investigate the efficacy of TSA in terms of nasal functions. MATERIALS AND METHODS: Twenty two cases of pituitary tumors, managed at Seoul National University Hospital from May 1997 through March 1998, were included in this prospective study. Nasal functions were evaluated preoperatively and 2 months after the operation through symptom questionnaires, rhinomanometry, acoustic rhinometry and the butanol thres-hold test. RESULTS: The subjective nasal symptoms, including nasal obstruction and olfaction, were not changed following the operation in 72% and 86% of the cases, respectively. In the objective findings, total nasal resistance was not grossly changed after the operation, however, cross-sectional areas at C-notch and 3.3 cm from the anterior nasal spine increased significantly after the operation. Mucosal response to a topical vasoconstrictor after the operation was less effective than before the preoperation. CONCLUSION: TSA for pituitary tumors may be a safe and effective technique in preserving nasal functions subjectively and objectively.

Clinical Analysis of Sellar Tumors Treated via Transsphenoidal Route

Between January 1990 and August 1992 sixteen patients with sellar tumors underwent 16 transsphenoidal approaches at Kang-Nam Sacred Heart Hospital. Pathological diagnosis include 14 pituitary adenomas, of which six belonged to microadenomas and the remaining eight cases were classified as macroadenomas. Other pathologies were one craniopharyngioma and one sphenoid mucocele. Thirteen patients underwent TSA as the primary procedures and the remaining three patients were subjected to TSA as the secondary procedures to the primary treanscranial approaches. Of the 13 primary TSAs excellent or good results were achieved in 11 patients and the remaining two patients were subjected to the secondary transcranial approaches to achieve good results. Six patients with microadenomas achieved gross total or subtotal removal of their tumors in all cases(100%) however, satisfactory removal was achieved only in six macroadenoma cases(75%). There was neither surgical mortality nor major morbidity. Transient diabetes insipidus complicated in 6 patients(37.5%) and CSF rhinorrhea complicated in three cases*18.8%), which needed spinal drainage for three to ten days. Meningitis was complicated in one patient with CSF rhinorrhea(6.2%). This preliminary study agrees with that TSA is a safe and effective procedure even in macroadenoma cases.

Diagnostic value of TSGF and combined tumor marker determination in patients with malignant tumors / 重庆医科大学学报

Objective:To explore the value of tumor specific growth factor (TSGF) and combined tumor markers (AFP,CEA,Ft,TSA) in the diagnosis of malignant tumor.Methods:TSGF was measured by chemical method and combined tumor markers by chemical method and ELISA method.The results in 170 cases with malignant tumors and 60 cases with non-tumor patients were analyzed.Results:In cases of single TSGF measurement,the positive rate was 82% in liver carcinoma,87% in lung cancer,and 86% in carcinoma of stomach,colon,or rectum.The positivity rate of TSGF plus combined tumor marker determination was 97.5%,97.7%,and 97.5% respectively.Conclusion:TSGF plus combined tumor marker determination improve the positivity rate for tumor diagnosis,provide evidence for localization,and promote early diagnosis.