The S1P1 regulator IMMH002 and its therapeutic effect and mechanism on autoimmune hepatitis / 药学学报

This study assessed and explored the pharmacological effects and mechanisms of action of IMMH002 {2-amino-2-(2-(4ʹ-(2-ethyloxazol-4-yl)-[1,1ʹ-biphenyl]-4-yl)ethyl)propane-1,3-dio}, a selective sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, in a concanavalin A (ConA)-induced autoimmune hepatitis (AIH) mouse model. The experimental protocol strictly adhered to the guidelines of the Ethics Committee for Animal Research of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00004046). Male ICR mice were pre-treated with the drug for four days, followed by induction of AIH through tail vein injection of ConA protein. Liver function, hepatic tissue pathology, peripheral blood parameters, as well as immunoglobulin G (IgG), inflammatory cytokines, T cell distribution, and inflammatory pathways were evaluated in mice. Results demonstrated that IMMH002 significantly reduced liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated hepatic tissue inflammation and necrotic damage, decreased serum IgG levels, and lowered the expression of inflammatory mediators including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Additionally, it facilitated T lymphocyte homing, downregulated the phosphorylation of nuclear factor kappa-B (NF-κB), IκB kinase β (IKKβ) and nuclear factor inhibitor protein-α (IκBα) proteins in hepatic tissue and cellular inflammation models. Collectively, IMMH002 effectively ameliorated ConA-induced autoimmune hepatitis in mice, exhibiting extensive anti-inflammatory and anti-necrotic effects, thereby laying a theoretical foundation for AIH clinical treatment.

The polymorphic inheritance of DIO2 rs225014 may predict body weight variation after Graves' disease treatment

ABSTRACT Objective: We aimed to investigate the role of DIO2 polymorphisms rs225014 and rs12885300 in Graves' disease patients, mainly for controlling body weight following treatment. Subjects and methods: We genotyped 280 GD patients by the time of diagnosis and 297 healthy control individuals using a TaqMan SNP Genotyping technique. We followed up 141 patients for 18.94 ± 6.59 months after treatment. Results: There was no relationship between the investigated polymorphisms with susceptibility to GD and gain or loss of weight after GD treatment. However, the polymorphic inheritance (CC+CT genotype) of DIO2 rs225014 was associated with a lower body weight variation after GD treatment (4.26 ± 6.25 kg) when compared to wild type TT genotype (6.34 ± 7.26 kg; p = 0.0456 adjusted for the follow-up time). This data was confirmed by a multivariate analysis (p = 0.0138) along with a longer follow-up period (p = 0.0228), older age (p = 0.0306), treatment with radioiodine (p-value = 0.0080) and polymorphic inheritance of DIO2 rs12885300 (p = 0.0306). Conclusion: We suggest that DIO2 rs225014 genotyping may have an auxiliary role in predicting the post-treatment weight behavior of GD patients.

Interleukin-27 decreases ghrelin production through signal transducer and activator of transcription 3-mechanistic target of rapamycin signaling

Interleukin-27 (IL-27), a heterodimeric cytokine, plays a protective role in diabetes. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. The relationship between IL-27 and ghrelin is still unexplored. Here we investigated that signal transducer and activator of transcription 3 (STAT3)-mechanistic target of rapamycin (mTOR) signaling mediates the suppression of ghrelin induced by IL-27. Co-localization of interleukin 27 receptor subunit alpha (WSX-1) and ghrelin was observed in mouse and human gastric mucosa. Intracerebroventricular injection of IL-27 markedly suppressed ghrelin synthesis and secretion while stimulating STAT3-mTOR signaling in both C57BL/6J mice and high-fat diet-induced-obese mice. IL-27 inhibited the production of ghrelin in mHypoE-N42 cells. Inhibition of mTOR activity induced by siRNA or rapamycin blocked the suppression of ghrelin production induced by IL-27 in mHypoE-N42 cells. siRNA also abolished the inhibitory effect of IL-27 on ghrelin. IL-27 increased the interaction between STAT3 and mTOR in mHypoE-N42 cells. In conclusion, IL-27 suppresses ghrelin production through the STAT3-mTOR dependent mechanism.

Quality Evaluation of Curcumae Radix Introduced in Zhongshan by Gray Relational Model / 中国实验方剂学杂志

Objective:To establish the gray relational analysis for quality evaluation of the samples of Curcumae Radix introduced in Zhongshan. Method:With volatile oil and curcumin as Q-markers,and alcohol extract,germacrone,germacr-1(10)-ene-5,8-dione and curcumin as comprehensive evaluation index, the contents of the four main components in 72 samples of Curcumae Radix of 3 different varieties introduced in Zhongshan from 3 different regions were determined. The grey relational method was used to build the gray correlation evaluation model for Curcumae Radix introduced in Zhongshan. Result:The relative correlation degree (γi) of 72 samples was between 0.262 and 0.697,in which γi was above 0.450 for 10 samples,and below 0.300 for 37 samples,indicating great differences in the quality of Curcumae Radix after introduction. The γi was 0.697 and 0.525 respectively for No.MY-W-4 and No.MY-W-1 from Curcumae Radix in Mayu with the best quality. The average values of γi for the samples of 3 different varieties from 3 different regions were between 0.281 and 0.420,and Mayu samples had the maximum average value,indicating that Mayu samples had the highest overall quality of,and could be introduced as excellent resources. Conclusion:The evaluation method combined with GRA method and multi-index quantification was simple,objective and comprehensive, and could be used to evaluate the quality of Curcumae Radix introduced in Zhongshan,so as to provide references for screening high-quality provenance.

Anti-inflammatory effects of Agar free-Gelidium amansii (GA) extracts in high-fat diet-induced obese mice

BACKGROUND/OBJECTIVES: Gelidium amansii (GA) contains plenty of agars and various biological substances, which make them a popular functional food to control body weight in previous studies. Unlike previous studies focused on agar in GA, objectives of this study were to investigate the effects of agar-free GA extract (AfGAE) on preventive and treatment models by using diets-induced obese (DIO) C57BL/6J mice. MATERIALS/METHODS: AfGAE were used to test their effects on the prevention (Exp-1) and treatment (Exp-2) against obesity after pilot study in DIO mice. The weight changes of the body and fat tissues and protein expression related to lipid metabolism and inflammation as well as plasma lipid profile and insulin were detected. RESULTS: Although AfGAE did not prevent long-term DIO, it did increase the levels of anti-inflammatory cytokine production and lipolysis protein. We further evaluated various doses of AfGAE in preventive and treatment models. As a result, our findings suggested that an AfGAE administration as a preventive model might be a better approach to achieve its anti-inflammatory and lipolysis-promoting effects in DIO mice. CONCLUSION: Although future studies to investigate the target materials such as polyphenols in AfGAE are required, the result suggests that GA without agar might be a therapeutic tool to improve health conditions related to inflammation.

Qualidade da dieta e consumo de sódio por pacientes em hemodiálise de uma clínica renal da fronteira oeste do Rio Grande do Sul / Quality of diet and sodium consumption by hemodialysis patients in a renal clinic of the border west of Rio Grande do Sul

Objetivo: Avaliar a qualidade da dieta e estado nutricional de pacientes submetidos à hemo- diálise em Clínica Renal de um município do sul do Brasil. Método: Neste estudo descritivo, observacional foram incluídos 15 pacientes. Dados sociodemográficos, clínicos e laboratoriais foram coletados dos prontuários de cada paciente. Para avaliação dos dados antropométricos, foram aferidas medidas de peso seco, peso pré e pós-diálise, altura e circunferência da cintura. Dados dietéticos foram coletados por meio de um recordatório de 24h e avaliados pelo Índice de Qualidade da Dieta Revisado. O consumo de alimentos ricos em sódio foi avaliado por meio de questionário de frequência específico. Resultados: Na população estudada, a média de idade foi de 57,3 anos, sendo a maioria dos pacientes do sexo masculino (60%). A classificação do índice de massa corporal foi de eutrofia para metade dos pacientes (53,3%). A média da circunferência da cintura foi de 89,67 cm, sendo que 73,3% dos pacientes apresentaram valores adequados. Conforme avaliação dos dados dietéticos, o consumo de sódio diário foi de 3,98 g e a pontuação média do Índice de Qualidade da Dieta foi de 63,33 pontos; 66,7% da população apresentaram necessidade de modificação da dieta. Conclusões: Os pacientes apresentaram hábitos alimentares que necessitam de modificações, principalmente no que diz respeito ao consumo de frutas, verduras e cereais integrais. Também se destaca o elevado consumo de sódio, sendo o sódio adicional o mais prevalente entre o consumo total diário. Desta maneira, tornam-se necessárias estratégias de educação nutricional para uma mudança efetiva dos hábitos alimentares destes pacientes.(AU)

Objective: To evaluate dietary quality and nutritional status of hemodialysis patients in a Renal Clinic of southern Brazil. Methods: Fifteen patients were included in the study. Sociodemo- graphic, clinical and laboratory data were collected from medical records. To evaluate the anthropometric measurements were measured dry weight, weight pre and post-dialysis, height, and waist circumference. Dietary data were collected using 24-hour recalls and evaluated by the Diet Quality Index - Revised. The consumption of foods high in sodium was assessed by a food frequency questionnaire. Results: In this study the mean age was 57.3 years and most patients were male (60%). Body mass index classification was eutrophic to half of patients (53.3%). The average waist circumference was 89.67 cm, and 73.3% of patients had appro- priate values. According to the assessment of dietary data, daily sodium intake was 3.98 g and the mean score of the Diet Quality Index was 63.33 points; 66.7% of the population was classified as "need a diet modification". Conclusions: Patients of the renal clinic need dietary changes, especially regarding to the consumption of fruits, vegetables and whole grains. Also highlights the high sodium intake, being the added sodium the most prevalent among total daily consumption. Therefore, become necessary nutritional education strategies for effective change in eating habits of these patients.(AU)

Suicide risk in cocaine addicts with a current depressive episode: feelings and experiences / Risco de suicídio em dependentes de cocaína com episódio depressivo atual: sentimentos e vivências / Riesgo de suicidio en dependientes de cocaína con episodio depresivo actual: sentimientos y vivencias

Death by suicide is now the third most frequent cause of death in the population 15-44 years old. This self-inflicted death has meaning that requires understanding and attention. The objective of this study was to understand the experiences and feelings of cocaine users within the relationship of addiction and suicide. This is a qualitative study conducted from August 2012 to February 2013. The 18 individuals who met criteria for a depressive episode responded to the semi-structured interview for suicide risk, the Mini International Neuropsychiatric Interview. During the analysis of the narrated content, there were three categories established: previous history, previous suicide attempts, and depression. The results were evaluated seeking to reflect and understand the experiences exposed by users. This study helps to understand the meaning of the experiences and feelings of crack/cocaine users who are at the risk for suicide...

Synergic actions of polyphenols and cyanogens of peanut seed coat (Arachis hypogaea) on cytological, biochemical and functional changes in thyroid.

In animals, long-term feeding with peanut (Arachis hypogaea) seed coats causes hypertrophy and hyperplasia of the thyroid gland. However, to date there have been no detailed studies. Here, we explored the thyroidal effects of dietary peanut seed coats (PSC) in rats. The PSC has high levels of pro-goitrogenic substances including phenolic and other cyanogenic constituents. The PSC was mixed with a standard diet and fed to rats for 30 and 60 days, respectively. Animals fed with the PSC-supplemented diet showed a significant increase in urinary excretion of thiocyanate and iodine, thyroid enlargement, and hypertrophy and/or hyperplasia of thyroid follicles. In addition, there was inhibition of thyroid peroxidase (TPO) activity, 5’-deiodinase-I (DIO1) activity, and (Na+-K+)-ATPase activity in the experimental groups of rats as compared to controls. Furthermore, the PSC fed animals exhibited decreased serum circulating total T4 and T3 levels, severe in the group treated for longer duration. These data indicate that PSC could be a novel disruptor of thyroid function, due to synergistic actions of phenolic as well as cyanogenic constituents.

Computational DIO2 rSNP Analysis, Transcriptional Factor Binding Sites and Disease.

Purpose: The DIO2 gene transcribes the deiodinase type 2 enzyme that changes the thyroid prohormone, thyroxine (T4), to the biologically active triiodothyronine (T3) hormone. T3 plays a vital part in the regulation of energy balance and glucose metabolism. DIO2 single-nucleotide polymorphisms (SNPs) were computationally examined with respect to changes in punitive transcriptional factor binding sites (TFBS) and these changes were discussed in relation to human disease. Methods: The JASPAR CORE and ConSite databases were instrumental in identifying the TFBS. The Vector NTI Advance 11.5 computer program was employed in locating all the TFBS in the DIO2 gene from 2.4 kb upstream of the transcriptional start site to 508 bp past the 3’UTR. The JASPAR CORE database was also involved in computing each nucleotide occurrence (%) within the TFBS. Results: Regulatory SNPs (rSNPs) in the promoter region novel SNP (-2035bp), 5’UTR (rs12885300), intron one (rs225010, 225011 and rs225012), exon two [rs225014 (Thr92Ala)] and 3’ UTR (rs6574549, rs225015 and rs225017) of the DIO2 gene are in linkage disequilibrium. These rSNP alleles were found to alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in TFBS. Conclusion: The alleles of each rSNP were found to generate unique TFBS resulting in potential changes in TF DIO2 regulation. These regulatory changes were discussed with respect to changes in human health resulting in disease or sickness.

Photoperiodic regulation of seasonal reproduction in higher vertebrates.

Long-lived animals such as birds and mammals adapt readily to seasonal changes in their environment. They integrate environmental cues with their internal clocks to prepare and time seasonal physiological changes. This is reflected in several seasonal phenotypes, particularly in those linked with migration, hibernation, pelage growth, reproduction and molt. The two endocrine secretions that play key roles in regulating the seasonal physiology are melatonin and thyroid hormone. Whereas, melatonin is used as an endocrine index of day length (and consequently duration of night), the seasonal up- and down-regulation of thyroid hormone affects the physiology, perhaps by influencing different pathways. Both of these hormones are shown to act via a ‘photoperiodic axis’ constituted by the photoreceptors, hypothalamus and pituitary. Recent studies have revealed that the pars tuberalis that connects hypothalamus and pituitary, locally synthesizes the thyroid stimulating hormone (TSH) in response to light (birds) or melatonin (mammals). The levels of TSH regulate the DIO2 and DIO3 synthesis in the ependymal cells in hypothalamus, and in turn affect the release of gonadotropin releasing hormone. This review mainly focuses on the current understanding of the mechanisms of photoperiodic regulation of seasonal responses in the higher vertebrates.

Temos nosso próprio tempo: grupo de orientação das escolhas profissionais com alunos do ensino médio / We have our own time: group of the professional guidance in the secondary education / Nosostros tenemos nuestro tiempo: grupo de orientación profesional con estudiantes del educación secundaria

Este estudo teve por objetivo analisar uma intervenção em grupo desenvolvida com alunos do terceiro ano do Ensino Médio para refletir sobre o tema da escolha profissional. Participaram 70 jovens de uma escola pública, entre 17 e 19 anos de idade. Os grupos ocorreram na prrópria sala de aula e foram coordenados por estagiários de um curso de licenciatura em Psicologia durante aulas regulares dessa disciplina. A partir da discussão acerca das escolhas profissionais e com auxílio de disparadores, como questionários breves e músicas, os adolescentes refletiram acerca de como a escolha profissional estava sendo pensada na vida de cada um. Os pontos levantados foram: mercado de trabalho, influências da família e do meio social, adolescência e vivência das mudanças nesta fase do desenvolvimento. A disciplina de Psicologia no Ensino Médio mostrou-se um espaço no qual esses conteúdos poderiam ser discutidos e elaborados, tanto por meios didáticos como a partir de recursos como o grupo, que possibilitou a discussão sobre desejos e visões de mundo, levando ao enriquecimento do ambiente escolar, do trabalho interdisciplinar e da formação integral dos adolescentes.

The study aims to analyzing a group intervention with students of the third year of secondary education to reflect upon professional choice. 70 students of a public school aging from 17 and 19 years participated. Groups were conducted at the studentâÇÕs classroom and were coordinated by trainees of a Psychology undergrad course. Based on the concerns with professional choices and aided by of discussion triggers such as brief questionnaires and songs, the students reflected upon the process of professional choice in their lives. Themes discussed were: work market, influences of family and the social environment, adolescence and how they experience the changes in this stage of their development. The intervention was considered a space in which these contents could be discussed and elaborated, both by didactic means and by group discussion. It made possible the discussion about the desires and world views, that ultimately lead to the enrichment of the classroom environment, the interdisciplinary work and the students development.

El objetivo fue analizar una intervención en grupo con estudiantes de la educación secundaria para reflexionar sobre la opción profesional. Participaron 70 jóvenes de una escuela pública, entre 17 y 19 años. Los grupos se desarrollaron en la sala de clases y fueron coordinados por pasantes de un curso de licenciatura en Psicología durante las lecciones regulares de esta disciplina. A partir de la discusión sobre las opciones profesionales y con la ayuda de disparadores como cuestionarios breves y músicas, los adolescentes reflexionaron respecto a como la opción profesional era pensada en la vida de cada uno de ellos. Los temas planteados fueron: el mercado de trabajo, las influencias de la familia y del ambiente social, adolescencia y los cambios en esta fase del desarrollo. La Psicología en educación secundaria se mostró como un espacio en el cual estes contenidos podría ser discutidos y elaborados, tanto para medios didácticos como a través de recursos como grupos, que hicieron posible la comunión de deseos y de visiones del mundo, llevando al enriquecimiento del ambiente escolar, del trabajo interdisciplinar y la formación integral de los adolescentes.

Comparison of Dio-Bacit, Bacitracin-Trimethoprim/ Sulphamethoxazole and Latex Agglutination in the Diagnosis of Group A Beta-Hemolytic Streptococci

Not only is Group A beta-hemolytic Streptococcus (GAS) the most frequent cause of bacterial pharyngitis, it is also the culprit in various skin and systemic infections, acute rheumatic fever, post streptococcal glomerulonephritis, and other disorders and complications. A new, ready-to-use media, Dio-Bacit, in a two section plate containing 5% sheep blood agar on one side and sheep blood agar with bacitracin (2microgram/ml) on the other was compared for its efficiency in identifying GAS with bacitracin and bacitracin + sulphamethaxazole / trimethoprim disk tests applied after isolation of beta-hemolytic colonies. We also used the latex-agglutination test as the gold standard method for differentiating GAS from streptococci belonging to other groups. Compared with the latex-agglutination test, we found the sensitivity and specificity of the Dio-Bacit method to be 92.0% and 96.9%, respectively. Dio-Bacit plates provide an easy and very useful way to identify GAS within one day, saving time, labor, and money for routine diagnostic microbiology laboratories.

One new C_(21) steroid from canes of Marsdenia tenacissima / 中草药

Objective To study chemcial constituents in the canes of Marsdenia tenacissima.Methods Chemical constituents were isolated and purified by silica gel and ODS column chromatography.The structures were identified by means of physico-chemical and spectral data.Results From the 70% ethanol extract of the material,four compounds were isolated.Their structures were identified as 11?,12?-di-O-2-methylbutyryl-tenacigenin B (Ⅰ),11?-O-2-methylbutyryl-12?-O-acetyl-tenacigenin B (Ⅱ),tenacissoside H (Ⅲ),and marsdenoside A (Ⅳ),respectively.Conclusion Compound Ⅰ is a new C21 steroid compound,named tenacissoside O.