Maternal hypothyroidism during pregnancy alters the function of the retinol-binding protein 4-mediated mitochondrial permeability conversion pore in the kidneys of offspring rats

OBJECTIVES To determine the role of the RBP4/PiC/SIRT3 signaling pathway in the opening of the mitochondria permeability transition pore (mPTP) in offspring rats with hypothyroidism during pregnancy. METHODS Sixty Sprague-Dawley (SD) rats were employed in this study. Pregnancy was deemed successful when a sperm was found in the uterus. After one week of pregnancy, offspring rats were divided into the following groups: overall hypothyroidism group (OH group), subclinical hypothyroidism group (SCH group), and normal control group (CON group). The establishment of the hypothyroidism model was confirmed when the serum thyroid stimulating hormone (TSH) levels were higher than normal value and TT4 level was within the normal range. The renal mitochondria of offspring rats were extracted on the 14th postnatal day (P14) and 35th postnatal day (P35). RESULTS At P14, no significant differences in the degree of mPTP opening and expression of phosphoric acid carrier vector (PiC) were detected between the rats in the OH group and the SCH group. However, the expression level of silent mating-type information regulation 3 homolog (SIRT3) was markedly reduced. Retinol-binding protein 4 (RBP4) expression increased in the rats from the OH group, relative to that in those from the SCH group. At P35, the degree of mPTP opening and the expression levels of PiC and RBP4 in the OH group were higher than those in the SCH group. However, SIRT3 expression in the OH group was lower than that observed in the SCH group. CONCLUSION RBP4 plays an important role in early renal mitochondrial damage and renal impairment in rats suffering from hypothyroidism during pregnancy. The RBP4/PiC/SIRT3 pathway is thus involved in the opening of the renal mPTP in offspring rats with hyperthyroidism.

Cardio vascular response to core stability exercises in healthy individuals

Background: Low back pain is the most common problem which is present among 60 to 80 percent of population in the world at least once in their life time. It is considered as the most influencing aspect of health of an individual as well as their daily living status. Objective: To examine the cardiovascular responses (Heart Rate, Systolic Blood pressure and Rate Pressure Product) in the abdominal techniques that are (bracing and hollowing) used in core stability exercises. Core stability exercises have been used in the management of low back pain. The cardiovascular effects of exercises that involve postural stabilization, arms and exercises in a lying position are well known. Therefore, the purpose of this study was to examine the cardiovascular effects of 6 core stability exercises on cardiac patients which were used commonly for the treatment of low back ache. Materials and methods: This was a descriptive study which was conducted on a single group of 40 healthy males and females volunteers between age group of 18-25 years. With the mean age group of 21.12+1.042. Subjects were undergraduate students of MNR Sanjeevani College of physiotherapy, Sangareddy and were taken on the basis of convenient sampling. Prior to the participation all subjects were explained briefly about the aims and objectives of the study, health benefits of the core stability exercises and about the procedure of measuring Heart rate (HR), Systolic Blood pressure (SBP) and Rate Pressure product (RPP). All subjects were screened and a detail medical history was taken to exclude any serious illness. Health screening tool questionnaire (AACVPR) was used to identify the serious illness in the subject. One day before to the exercise session subjects were taken to the Gayathri Balakavi, Sreenivasu Kotagiri, Anup Kumar Songa, S. Purna Chandra Shekhar. Cardio vascular response to core stability exercises in healthy individuals. IAIM, 2019; 6(10): 35-42. Page 36 experimental room for familiarization of the procedure. The selected core stability exercises were demonstrated and subjects were instructed not to eat an hour before and not to wear tight clothes, Exercise protocol was designed properly and perfectly for the subjects so that they will be able to perform the exercises easily and effectively and the subjects were asked to participate in the exercise sessions after taking all the necessary measures. Pre and post exercise measurements of Systolic Blood pressure (SBP), Heart rate (HR) and Rate pressure product (RPP) values were measured. Before starting the exercise session subjects were made to relax for 15- 20 minutes, then the initial parameters of cardiovascular performance Systolic Blood pressure (SBP) were measured using automatic BP apparatus Omron M 10. BP cuff was tied to the left arm and patient was in high sitting position with arm supported at heart. Heart rate (HR) and Rate pressure product (RPP) were also measured at the same time along with (SBP). Subjects were asked to do 5 repetitions of all the exercises without any rest period. Post exercise Heart rate (HR), Systolic Blood pressure (SBP), and Rate Pressure Product (RPP) were recorded immediately after they finish the exercise. Now they were made to take rest till resting heart rate (RHR) was achieved. So for the given exercise sessions Systolic Blood pressure (SBP), Heart rate (HR) and, Rate Pressure Product (RPP) were measured for pre and post exercises. Results: There was marked increase in the cardiovascular parameters (heart rate, Systolic Blood pressure, and Rate Pressure Product). After exercise was performed, all the exercises were hemodynamically demanding. The study was done on single group of 40 healthy subjects with the mean age of 21.12 ± 1.04 in which 20 were males and 20 were female subjects. The baseline systolic blood pressure was 110.30 ±11.00 and baseline rate pressure product was 8797.15 ± 1419. The study was done with the aim to measure the acute cardiovascular responses to the core stability exercises. Repeated measures of ANOVA were used as the statistical tool. Conclusion: Core stability exercises can have cardiovascular effects in people with no cardiovascular or cardiopulmonary conditions. These cardiovascular effects may be important with respect to cardiac work, in Cardiac patients for whom these exercises are indicated. So, There was a significant increase in the cardiovascular parameters (Heart Rate, Systolic Blood Pressure, Rate Pressure Product) after the entire exercise session was performed by the subjects of the study.

Effects of Corni Fructus on retinol transport in mice with dry eye syndrome induced by benzalkonium chloride / 中草药

objective: To investigate the regulatory effect of Corni Fructus on retinol transport, and to elucidate its molecular mechanism in the treatment of dry eye syndrome and enrich the basis of “acid tonifying liver and improving vision”. Methods: A total of 60 BALB/c mice were randomly divided into six groups with 10 mice in each group, including control group, model group (saline 0.02 mL/g), positive control group (Dendrobium Nocturnal Pills 2.9 g/kg), Corni Fructus low, medium, and high dose group (12, 24, and 48 g/kg). The dry eye model mice were induced by the benzalkonium chloride eye drops. After successful modeling, mice were treated with different doses of Corni Fructus decoction for four consecutive weeks. One hour after the last dose, the intervention of Corni Fructus decoction on dry eye model mice was evaluated by determining the amount of tear secretion and tear film rupture time. The content of serum preprotein (PA), RBP, and retinol in liver was detected by ELISA method. The expression of CRBP and STRA6 in lacrimal gland was detected by IHC and Western blotting. Results: Compared with the control group, the tear secretion and tear film rupture time in the model group were significantly decreased, and the serum PA, RBP, and the content of vitamin A in the liver of the other groups were significantly lower than those of the control group (P < 0.01). Compared with the model group, the levels of serum PA, RBP, and vitamin A in liver were significantly increased in each drug intervention group (P < 0.01). Compared with the control group, the content of CRBP and STRA6 in the lacrimal gland of the model group decreased significantly (P < 0.01). Compared with the model group, the content of CRBP and STRA6 in the lacrimal gland of each drug intervention group was significantly higher than those in the model group (P < 0.05, P < 0.01). Conclusion: During the occurrence of dry eye, there are vitamin A deficiency and retinoic acid abnormal transportion in the body. The acid drug Corni Fructus can improve the status of vitamin A deficiency by increasing the absorption of vitamin A, and then regulate the process of retinol transport. This may be one of the molecular mechanisms of acid entering the liver and improving vision.

Advances in the research of musashi family in tumors / 上海交通大学学报（医学版）

RNA binding proteins (RBPs) play a key role in gene regulation and participate in life activities such as RNA synthesis, alternative splicing, modification, transport and translation. It is necessary to study the interaction between RNA and RBP in order to explore RNA functions. The expression changes of RBPs are related to a variety of diseases. Musashi (MSI) family is a class of evolutionarily conserved RBPs including MSI1 and MSI2, which play an important role in many key processes such as tumorigenesis, progression and drug resistance. They were found to be overexpressed in many tumors and associated with prognosis in the blood system, nervous system, digestive system, respiratory system, etc. MSI binds to mRNA to regulate translation and mRNA stability. MSI maintains the number of cancer stem cells and affects tumor proliferation, invasion, metastasis and drug resistance. The preliminary research of MSI gene as a target to guide tumor therapy has achieved some results. This article describes the physiological functions of MSI family and its roles in tumorigenesis and development, and provides an overview of the latest research progress of MSI family as a diagnostic marker or a therapeutic target.

Characterization of the mRNA untranslated regions [UTR] of the Trypanosoma cruzi LYT1 isoforms derived by alternative trans-splicing / Caracterización de las regiones no traducidas ARN [UTR] de las isoformas de Trypanosoma cruzi LYT1 derivadas de un trans-empalme alternativo / Caracterização das regiões não-traduzidas do RNA [UTR] das isoformas de Trypanosoma cruzi LYT1 derivadas de uma junção trans-alternativa

Abstract In trypanosomatids, gene expression is mainly regulated at posttranscriptional level, through mechanisms based on the interaction between RNA Binding Proteins [RBPs] and motifs present in the untranslated regions [UTRs] of the mRNAs, which altogether form ribonucleoproteic complexes [RNP] that define the fate of the mRNA. The pre-mRNA derived from the LYT1 gene of Trypanosoma cruzi, is processed by alternative trans-splicing, resulting in different mRNAs which code for the isoforms mLYTl and kLYTl, proteins having differential expression, cellular location and function. The aim of this study was to characterize the 5' and 3' UTRs of the LYT1 mRNAs as the initial step towards the objective of identification of the RBPs responsible for their differential expression. The presence of the two types of 5' UTRs were confirmed in two T. cruzi isolates belonging to the DTU I, thus, corroborating the occurrence of alternative trans-splicing also in the LYT1 gene of this T. cruzi DTU. In addition, for the first time, was unscovered the existence of two types of LYT1 mRNAs transcripts, differing in length by 116 nts, that are generated by alternative polyadenylation. Furthermore, an in-silico analysis of the experimentally obtained UTRs, and ten additional LYT1 sequences retrieved from TritrypDB and GenBank databases, together with a thoroughly search of structural motifs, showed a remarkable conservation of relevant structural motifs previously associated with RNA metabolism in the different UTRs; these elements might be involved in the differential stage-specific expression of each LYT1 isoform.

Resumen En los trypanosomátidos, la expresión génica se regula principalmente en el nivel post-transcripcional mediante mecanismos basados en la interacción entre las proteínas de unión del ARN [RBP] y las figuras presentes en las regiones no traducidas [UTR] de las ARN, que en conjunto forman complejos ribonucleoproteicos [RNP] que definen el destino de la ARN. El pre-ARN derivado del gen LYT1 del Trypanosoma cruzi es procesado por trans-empalme alternativo, dando como resultado diferentes ARN que codifican las isoformas mLYTl y kLYTl, proteínas con expresión diferencial, localización celular y función. El objetivo de este estudio fue caracterizar los 5' y 3' UTR de las ARN LYT1 como el paso inicial hacia la identificación de los RPB responsables de la expresión diferencial. Se confirmó la presencia de los dos tipos de 5' UTR en dos aislantes del T. cruzi pertenecientes al DTU I; de esta forma también se comprobó la ocurrencia del trans-empalme alternativo en el gen LYT1 de este T. cruzi DTU. Además, por primera vez, se pudo demostrar la existencia de dos tipos de transcripciones de ARN LYT1, que difieren en longitud por 116 nts, y son generadas por poliadenilación alternativa. Adicionalmente, se realizó un análisis in-silico de la UTR obtenida experimentalmente, y otras diez secuencias LYT1 recuperadas de las bases de datos TritrypDB y GenBank, junto con una búsqueda exhaustiva de figuras estructuradas, mostrando una notable conservación de los figuras estructurales asociadas con el metabolismo del ARN en los diferentes UTR; estos elementos podrían estar implicados en la expresión diferenciada de la etapa específica de cada isoforma LYT1.

Resumo Nos tripanossomatídeos, a expressão génica é regulada principalmente a nível pós-transcricional mediante mecanismos baseados na interação entre as proteínas de união do RNA [RBPs] e as fugiras presentes nas regiões não-traduzidas [UTRs] do RNA. O pré-RNA derivado do gene LYT1 do Trypanosoma cruzí é processado por uma junção trans-alternativa, resultando em diferentes RNA que codificam as isoformas mLYTl e kLYTl, proteínas com expressão, localização celular e função diferenciadas. O objetivo de este estudo foi caracterizar as 5' e 3' UTRs dos RNAs LYT1 como sendo o passo inicial na identificação das RBPs responsáveis pela expressão diferenciada. A presença dos dois tipos de 5' UTRs foi confirmada em dois isolados de T. cruzí pertencentes ao DTU I; corroborando assim com a ocorrência da junção trans-alternativa no gene LYT1 de este T. crují DTU. Adicionalmente, se demonstrou pela primeira vez a existência de dois tipos de transcrições de RNA LYT1, que se diferenciam em comprimento por 116 nts, e são geradas por poliadenização alternativa. Além disso, realizou-se uma análise in-sílico da UTR obtida experimentalmente e outras dez sequencias LYT1 recuperadas das bases de dados TritrypDB e GenBank, junto com uma busca exaustiva de figuras estruturadas, mostrando uma notável conservação das figuras estruturais associadas com o metabolismo do RNA nas diferentes UTRs. Estes elementos poderiam estar envolvidos na expressão estágio-específica diferenciada de cada isoforma LYT1.

Expression and its clinical significance of RBP4 in vitreous in patients with proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the concentration of RBP4 and IL-6 in vitreous of proliferative diabetic retinopathy (PDR). METHODS: A total of 65 patients (66 eyes) were enrolled in Department of Ophthalmology, Renmin Hospital of Wuhan University from February 2017 to July 2017 with the informed consent. The patients were divided into PDR group (23 cases) and NPDR group (16 cases). Twenty- six patients without diabetic mellitus (DM) served as control group. The demography was matched among the groups, but the course of DM, the blood glucose level and the HbA1c level were elevated in the PDR group and the NPDR group (all P<0.05). Vitreous samples were collected during the procedure of vitrectomy. RBP4,IL-6,TNF-α concentrations in vitreous specimens were detected by ELISA. The differences of vitreous RBP4, IL-6 and TNF-α in various groups were statistically analyzed by ANOVA, respectively. The correlations between RBP4 and IL - 6, TNF - α were calculated by Pearson correlation analysis. RESULTS:The concentration of RBP4 in PDR group,the NPDR group and control group were 13.68士2.66, 11 03士1 12,10.45士1.17μ g/Ml, and the concentration of IL-6 were 56.0士10.27, 20.92士5.77, 10.26士1.91pg/Ml. RBP4 and IL- 6 concentrations were elevated in PDR group compared with NPDR group and control group, with significant difference among three groups (F = 12. 135, 161.167; P < 0. 01). IL - 6 concentrations in vitreous increased in the NPDR group in comparison with control group(P<0.05). RBP4 concentrations had no significant difference between the NPDR group and the group(P>0 05). Pearson correlation coefficient was significant positive between RBP4 concentration and IL - 6 concentration(r=0.606,P=0.001). CONCLUSION: RBP4 is probability involved in the inflammation pathogenesis of PDR. These results indicate that RBP4 could be a new target for the diagnosis and treatment of PDR.

Circulating omentin-1 might be associated with metabolic health status in different phenotypes of body size

ABSTRACT Objective Adipokines are mediators of body composition and are involved in obesity complications. This study aimed to assess the association of circulating omentin-1, vaspin, and RBP-4 with body composition indices and metabolic health status (MHS) in different phenotypes of body size. Subjects and methods A total of 350 subjects were included in the current cross-sectional study. Body composition was measured using a body composition analyzer, and serum concentrations of omentin-1, vaspin, and RBP-4 were assessed by ELISA kits. Results Circulating omentin-1 was significantly (OR = 1.81, 95% CI: 1.00-1.91, P = 0.01) and marginally (OR = 1.63, 95%CI: 1.00-1.75, P = 0.06) associated with MHS in the overweight and obese subjects, respectively. But no association was seen between omentin-1 and MHS in normal-weight subjects. Serum levels of vaspin and RBP-4 were not correlated with MHS. Furthermore, a significant positive correlation was observed between circulating omentin-1 and body mass index (BMI) as well as fat percentage (P = 0.02) in the MHS group. Serum vaspin concentrations were not related to body composition components in both groups. In addition, in the MHS group, circulating RBP-4 was positively correlated with fat percentage and fat mass (FM) (p < 0.0001) and was negatively correlated with fat-free mass (FFM) and total body water (TBW) (p < 0.0001). In contrast, in the metabolically unhealthy group, RBP-4 was negatively correlated with fat percentage, FM, and BMI (p < 0.0001) and was positively correlated with FFM and TBW (p < 0.0001). Conclusions This study showed that circulating levels of omentin-1 are useful predictors of metabolic health status in overweight and obese people.

Research of RBP1 like protein--a novel autoantigen in RA / 中国免疫学杂志

Objective:Rheumatoid arthritis(RA) is a systemic autoimmune disease,but its etiology is unclear.Therefore,it is urgent to search antigens which is relate to induce this disease,however,there are few reports about the new self-antigens at home and abroad.In this study,we investigate new autoantigen through cloning.Methods: We used antigens in synovium of patients with rheumatoid arthritis as probe,extracted mRNA from synoviocyte,performed cDNA library immunological screening and sequence,and analyzed the conformation and performed Northern blotting.Results: We found that new autoantigen had 36.5% homology with retinoblastoma binding protein 1(RBP1)and it was found that these special protein structure such as AT-rich interaction domain,chromo domain,A+T-hook and TAF homology domain.Therefore,it will be named RBP1-like Protein(Rbik).Rbik RNA is not only expressed in the synovial membrane,but also in the heart,small intestine,muscle and other organs.Conclusion: We report that the discovery of the new autoantibodies to RBP1-like Protein(Rbik)may provide a new possible index and target in diagnosis and therapy.

Expression of Nesfatin -1,RBP4 in maternal blood and umbilical cord blood of gestational diabetes macrosomia and its clinical significance / 中国基层医药

Objective To study the relationship of Nesfatin -1,RBP4 with gestational diabetes mellitus (GDM)and macrosomia,and its clinical significance.Methods 40 patients with GDM were selected as the study subjects,15 cases of newborn children were huge (huge child group),25 cases of neonatal were normal children (normal weight children group).40 cases of normal glucose metabolism (NGT)patients at the same period were selected as the control group.Nesfatin -1,RBP4 levels in maternal blood and umbilical blood were detected by ELISA.Results In the huge child group,the Nesfatin -1 levels in maternal blood and umbilical cord blood were positively correlated (r =0.389,P =0.042),the RBP4 levels in maternal blood and umbilical cord blood were positively correlated(r =0.402,P =0.037).In the huge child group,the Nesfatin -1 levels in maternal blood and blood glucose levels were negatively correlated (r =-0.416,P =0.012),the RBP4 levels in maternal blood and blood glucose levels were positively correlated(r =-0.391,P =0.022).Conclusion Nesfatin -1,RBP4 in GDM and maternal blood and umbilical cord blood of huge children have abnormal expression,and Nesfatin -1,RBP4 levels are closely related to the incidence of GDMand huge children,and Nesfatin -1,RBP4 are important morbidity factors of GDMand huge children.

Pré-história e história da Revista Brasileira de Psicanálise / Prehistory and history of the Revista Brasileira de Psicanálise / Prehistoria e historia de la Revista Brasileira de Psicanálise

O autor trata dos percalços por que passou a Revista Brasileira de Psicanálise, desde que surgiu a ideia de se ter uma revista até os dias de hoje, em que ela se tornou um órgão oficial da Associação Brasileira de Psicanálise, após cumprir uma trajetória tumultuada, em que não faltaram obstáculos a vencer. Nascida a ideia de uma revista de psicanálise, com a finalidade de estimular a produção de trabalhos psicanalíticos, primeiramente de São Paulo e posteriormente de todas as Sociedades brasileiras, instalou-se um longo processo de amadurecimento do projeto, que permaneceu à espera de condições favoráveis que o fizessem vicejar. O primeiro passo para a concretização da ideia da revista foi dado quando passou a ser publicado o Jornal de Psicanálise. Com o apoio entusiasta de alguns colegas, a revista foi lentamente se tornando uma realidade. Nabantino Ramos, ligado à imprensa e à psicanálise, orientou todo o processo de estruturação da revista, que afinal foi lançada em 1967, por ocasião da I Jornada Brasileira de Psicanálise. O autor, que foi diretor editorial da revista por quatro anos e seu redator-chefe no biênio 1969-1970, relata as dificuldades econômicas que levaram à doação da revista, por parte da Sociedade de São Paulo, à abp. Sendo veículo de expressão de todos os psicanalistas brasileiros, ela vem cumprindo as finalidades que lhe foram atribuídas, até os dias de hoje.

The author writes about mishaps the Revista Brasileira de Psicanálise has gone through since the emerging idea of having a journal. After taking a tumultuous path with several obstacles to overcome, the Revista Brasileira de Psicanálise is today an official organization of the Brazilian Psychoanalytic Association. Once the idea of a psychoanalytic journal was introduced - a journal whose goal was to foment the production of psychoanalytic papers, at first in São Paulo and later in all the Brazilian Societies -, it was time to set up a long process to mature the project, which had to wait for propitious conditions to succeed. The first step to realize the idea of the journal was the publication of the Jornal de Psicanálise. With an enthusiastic support of some colleagues, the journal little by little turned to reality. Nabantino Ramos, who was related to Press and Psychoanalysis, guided the whole process for structuring the journal. The journal was finally launched in 1967, in the First Brazilian Meeting of Psychoanalysis. The author, who was the editorial director of the journal for four years, and its head writer for a two-year period (1969-1970), writes about economic challenges which resulted in the donation of the journal by the Psychoanalytic Society of São Paulo to the Brazilian Psychoanalytic Association. As a mean of expression for all Brazilian psychoanalysts, the Revista Brasileira de Psicanálise has fulfilled all its goals so far.

El autor aborda los percances por los que pasó la Revista Brasileira de Psicanálise, desde que surgió la idea de tener una revista hasta la actualidad, cuando pasó a ser órgano oficial de la Asociación Brasileña de Psicoanálisis, después de una trayectoria difícil en la que no faltaron obstáculos a ser vencidos. Nacida a partir de la idea de una revista de psicoanálisis, con el objetivo de estimular la producción de trabajos psicoanalíticos, inicialmente de São Paulo y posteriormente de todas las Sociedades brasileñas, tuvo lugar un largo proceso de preparación del proyecto, que permaneció en espera de condiciones favorables que lo hicieran prosperar. El primer paso para concretar la idea de la revista fue dado cuando pasó a ser publicado el Jornal de Psicanálise. Con el apoyo entusiasta de algunos colegas, lentamente la revista fue tornándose una realidad. Nabantino Ramos, relacionado con la prensa y el psicoanálisis, guio todo el proceso de estructuración de la revista, que finalmente fue lanzada en 1967, con motivo de la I Jornada Brasileña de Psicoanálisis. El autor, que fue director editorial de la revista durante cuatro años y su redactor jefe en el bienio 1969- 1970, narra las dificultades económicas que llevaron a la donación de la revista, por parte de la Sociedad de São Paulo, a la ABP. Como vehículo de expresión de todos los psicoanalistas brasileños, continúa cumpliendo las finalidades que le fueron atribuidas, hasta el día de hoy.

RBP-J is required for M2 macrophage polarization in response to chitin and mediates expression of a subset of M2 genes

Development of alternatively activated (M2) macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBP-J as an essential regulator of differentiation and function of alternatively activated macrophages.

Role of Notch signaling in regulating innate immunity and inflammation in health and disease

The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. Relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.

Values of multiple biochemical indexes in diagnosis of early diabetic nephropathy / 国际检验医学杂志

Objective To explore the diagnostic values of serum cystatin(CysC),retinol binding protein(RBP),β2 microglobulin (β2-MG),and urine microalbumin(mALB)and transferrin(TRF )in the diagnosis of early diabetic nephropathy(DN).Methods 118 patients with diabetes mellitus(DM)were divided into three groups according to the urinary albumin excretion rate (UAER), simple DM group,early DN group and clinical stage DN group.The immunity turbidimetry method was applied to measure the ser-um CysC,RBP,β2-MG and urine mALB,TRF;the enzymatic method was applied to measure the serum Cr;the rate method was applied to measure the serum Bun.The detection results were analyzed statistically.Results serum CysC,RBP,β2-MG and urine mALB,TRF levels in the early DN group and the clinical stage DN group were significantly higher then those in the simple DM group,the differences had statistical significance(P 0.05 ),serum Cr and Bun levels in the clinical stage DN group were significantly higher than those in the simple DM group with statistical difference(P <0.05).Conclu-sion Serum CysC,RBP,β2-MG and urine mALB,TRF levels in the patients with DN are significantly increased,which has the im-portant clinical value for early diagnosing and monitoring DN.

bFGF involved in the protection effect of radiation-induced apoptosis of neural stem cells by modulate the expression of Notch signal system protein / 中华行为医学与脑科学杂志

Objective To observe the effects of exogenous basic fibroblast growth factor (bFGF) on radiation-induced apoptosis of C17.2 neural stem cells(NSCs) and explore the relationship between bFGF and Hes1,RBP-JK protein.Methods The cell viability was assessed using the MTT assay.After the cells attach to the flasks they were irradiated by the linear accelerator.And 5 min later,different concentrations of bFGF in accordance with the experimental design and cultured cells 48 h.Extracted total protein of each group and Western blot analysis showed the changes of the Hes1,RBP-JK protein.Results Compared with the control group,irradiation group cell growth was inhibited,the OD of 0 ng/ml bFGF group was 0.61±0.81,the OD of 80 ng/ml bFGF group was 1.21±1.01 and the control group was 1.51± 1.13.Compared with the control group,all groups showed statistically significant difference (P＜ 0.05).Western blot analysis showed that with the increasing concentrations of bFGF,RBP-JK expression gradually decreased,but Hes1 expression gradually increased.Conclusion Exogenous basic fibroblast growth factor (bFGF) can inhibit apoptosis of C17.2 NSCs.bFGF can regulate Notch signaling pathway downstream proteins Hes1,RBP-JK expression and inhibit neural stem cell apoptosis which were irradiated.

Histone demethylase retinoblastoma binding protein 2 regulates the expression of -smooth muscle actin and vimentin in cirrhotic livers

Liver cirrhosis is one of the most common diseases of Chinese patients. Herein, we report the high expression of a newly identified histone 3 lysine 4 demethylase, retinoblastoma binding protein 2 (RBP2), and its role in liver cirrhosis in humans. The siRNA knockdown of RBP2 expression in hepatic stellate cells (HSCs) reduced levels of α-smooth muscle actin (α-SMA) and vimentin and decreased the proliferation of HSCs; and overexpression of RBP2 increased α-SMA and vimentin levels. Treatment with transforming growth factor β (TGF-β) upregulated the expression of RBP2, α-SMA, and vimentin, and the siRNA knockdown of RBP2 expression attenuated TGF-β-mediated upregulation of α-SMA and vimentin expression and HSC proliferation. Furthermore, RBP2 was highly expressed in cirrhotic rat livers. Therefore, RBP2 may participate in the pathogenesis of liver cirrhosis by regulating the expression of α-SMA and vimentin. RBP2 may be a useful marker for the diagnosis and treatment of liver cirrhosis.

Retinol binding protein 4 and incident diabetes the Atherosclerosis Risk in Communities Study (ARIC Study) / Proteina carreadora de retinol 4 e diabetes incidente Atherosclerosis Risk in Communities Study (ARIC Study)

Background: Retinol binding protein 4 (RBP4) has been described as a link between impaired glucose uptake in adipocytes and systemic insulin sensitivity. Objective: To determine whether RBP4 fasting levels predict the development of type 2 diabetes. Methods: Using a case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 537 who did not over ~9 years within the population-based Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses permitted statistical inference of the RBP4 – incident diabetes associations to the entire cohort. Results: Women in the highest tertile of RBP4 presented greater risk of developing diabetes (HR = 1.74; 95%CI 1.03 – 2.94) in analyses adjusted for age, ethnicity, study center, parental history of diabetes, hypertension, glomerular filtration rate, body mass index, waist-hip ratio, nonesterified fatty acids, adiponectin, leptin, triglycerides and HDL-C. When additionally adjusted for fasting insulin, this association's significance became borderline (HR = 1.68; 95%CI 1.00 – 2.82). No association between RBP4 levels and incident diabetes was found in men. Conclusion: These findings suggest that RBP4 levels may be directly involved in the pathogenesis of type 2 diabetes in women. .

Introdução: A proteína carreadora de retinol 4 (RBP4) tem sido descrita como elo entre uma menor captura de glicose pelos adipócitos e sensibilidade sistêmica à insulina. Objetivo: Determinar se os níveis de RBP4 em jejum predizem diabetes tipo 2. Método: Em um delineamento de caso-coorte, foram acompanhados 543 indivíduos de meia-idade que desenvolveram diabetes e 537 que não desenvolveram diabetes ao longo de 9 anos no estudo Atherosclerosis Risk in Communities Study (ARIC). Foi realizada análise ponderada de riscos proporcionais de Cox para inferência estatística da associação entre os níveis de RBP4 e diabetes incidente na coorte. Resultados: Mulheres com níveis de RBP4 no terceiro tercil apresentaram maior risco de desenvolver diabetes (HR = 1,74; 95% CI 1,03 – 2,94) em análises ajustadas para idade, etnia, centro, história familiar de diabetes, hipertensão, taxa de filtração glomerular, índice de massa corporal, razão cintura-quadril, níveis de ácidos graxos não esterificados, adiponectina, leptina, triglicerídeos e HDL-C. Quando adicionalmente ajustado para os níveis de insulina de jejum, a significância dessa associação se tornou limítrofe (HR = 1,68; 95% CI 1,00 – 2,82). Nenhuma associação foi observada entre RBP4 e diabetes incidente em homens. Conclusão: Esses achados sugerem que os níveis de RBP4 possam estar diretamente envolvidos na patogênese do diabetes tipo 2 em mulheres. .

High plasma retinol-binding protein 4 levels as risk factor of Type 2 Diabetes Mellitus in abdominal obesity / Journal of the ASEAN Federation of Endocrine Societies

Background@#Abdominal obesity is a risk factor for cardiovascular disease and type 2 diabetes mellitus (T2DM). Plasma retinol-binding protein 4 (RBP4) levels have been reported to increase in the abdominally obese subjects and it has been hypothesized that high plasma protein levels were considered to play an important role in the occurrence of T2DM. @*Objective@#We assessed the value of high plasma RBP4 levels as risk factor of T2DM in abdominally obese subjects. @*Methodology@#A case-control study, nested within a cross-sectional study, on 81 abdominally obese subjects was performed. We studied 33 patients with T2DM, compared with 33 matched controls. The plasma RBP4 levels were measured by ELISA. Insulin resistance (IR) status of the patients were determined using HOMA-IR; β-cell function was determined using HOMA-B. Analysis of variance (ANOVA) was used to test the equality of continuous variables. Forward conditional logistic regression analyses were performed to examine the odds ratios (OR) between high plasma RBP4 levels and consequent T2DM. Path analyses models were performed to assess the influence of risk factors on occurrence of T2DM. @*Result@#Plasma RBP4 levels were significantly increased, while HOMA-B was significantly lower in cases with respect to controls. In analyses adjusted for multiple T2DM risk factors, we observed positive association with high plasma RBP4 levels 9.74 (CI 95%; 2.03 – 46.67) (p = 0.004). It has been proven that high RBP4 level was a dominant risk factor (66.9%, p = < 0.001) influencing incidence of T2DM in the abdominally obese subjects.@*Conclusion@#The present study confirmed that high plasma RBP4 level is associated with increased incident T2DM in the abdominally obese subjects, and suggested that RBP4 has a major effect in the development of T2DM.

Effect of kidney-supplementing and blood-activating method on expression of Malb and RBP in senile patients with isolated systolic hypertension / 国际中医中药杂志

Objective Kidney-supplementing and blood-activating method was adopted in treating senile patients with isolated systolic hypertension to observe its decompression effects and influences on microalbunminuria (Malb),retinol binding protein (RBP) level in 24 hours.Methods 90 patients with simple systolic hypertension were randomly recurited into two groups.52 cases in the treatment group were administered with kidney-supplementing and blood-activating decoction,including 1 case falling off and 51 cases entering statistical analysis; 38 cases in the control group were administered with oral placebo,among them 2 cases were fallen offand 36 cases were entered statistical analysis.Both groups were treated for 8 weeks.Results () Blood pressure:systolic blood pressure at 4 and 8 weeks after the treatment in the treatment group [(144.03±12.33)mmHg (1 mmHg=0.133kPa) and (132.27±13.15)mmHg] wassignificantlyimproved than before the treatment [(156.32±12.05)mm Hg] (P＜0.05),and also significantly better than the control group at 4,8 weeks after the treatment [(151.19± 13.83)mm Hg,(152.74± 12.03)mm Hg] (P＜0.05).②The Malb,RBP level:Malb,RBP level [(40.80±13.51)mg/L,(150.43±23.62)mg/L] after the treatment in the treatment group was reduced than before the treatment [(50.14± 15.61)mg/L,(220.04±30.20) mg/L] (P＜0.05),and was significantly different to the control group after treatment [(52.12±14.69)mg/L,(219.34±34.37)mg/L] (P＜0.05).Conclusion Kidney-supplementing and blood-activating method can improve kidney function,and thus to reduce the effect of systolic blood pressure.

The regulatory epicenter of miRNAs.

miRNAs are small non-coding RNAs with average length of ~21 bp. miRNA formation seems to be dependent upon multiple factors besides Drosha and Dicer, in a tissue/stage-specific manner, with interplay of several specific binding factors. In the present study, we have investigated transcription factor binding sites in and around the genomic sequences of precursor miRNAs and RNA-binding protein (RBP) sites in miRNA precursor sequences, analysed and tested in comprehensive manner. Here, we report that miRNA precursor regions are positionally enriched for binding of transcription factors as well as RBPs around the 3′ end of mature miRNA region in 5′ arm. The pattern and distribution of such regulatory sites appears to be a characteristic of precursor miRNA sequences when compared with non-miRNA sequences as negative dataset and tested statistically.When compared with 1 kb upstreamregions, a sudden sharp peak for binding sites arises in the enriched zone near the mature miRNA region. An expression-data-based correlation analysis was performed between such miRNAs and their corresponding transcription factors and RBPs for this region. Some specific groups of binding factors and associated miRNAs were identified. We also identified some of the overrepresented transcription factors and associated miRNAs with high expression correlation values which could be useful in cancer-related studies. The highly correlated groups were found to host experimentally validated composite regulatory modules, in which Lmo2-GATA1 appeared as the predominant one. For many of RBP–miRNAs associations, coexpression similarity was also evident among the associated miRNA common to given RBPs, supporting the Regulon model, suggesting a common role and common control of these miRNAs by the associated RBPs. Based on our findings, we propose that the observed characteristic distribution of regulatory sites in precursor miRNA sequence regions could be critical inmiRNA transcription, processing, stability and formation and are important for therapeutic studies. Our findings also support the recently proposed theory of self-sufficient mode of transcription by miRNAs, which states that miRNA transcription can be carried out in host-independent mode too.

Association of Serum Retinol Binding Protein 4 with Adiposity and Pubertal Development in Korean Children and Adolescents

Retinol binding protein 4 (RBP4) has been postulated to provide a new link between obesity and insulin resistance. We aimed to assess the relationship between serum RBP4 and insulin resistance by investigating serum RBP4 levels in children and adolescents according to degree of obesity and pubertal stage. A total of 103 (30 lean, 39 overweight, 34 obese) were evaluated for serum RBP4, adiponectin, insulin, glucose and lipid profiles. RBP4 levels of obese and overweight groups were higher than those of lean group. RBP4 level was higher in pubertal group than in prepubertal group. RBP4 was positively correlated with age, height, weight, body mass index (BMI), abdominal circumference, systolic blood pressure, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol and triglyceride, and inversely with adiponectin. In the multiple linear regression analysis, RBP4 was found to be independently associated with pubertal stage, BMI and triglyceride but not with HOMA-IR. In conclusion, serum RBP4 level is related with degree of adiposity and pubertal development. The association of RBP4 with insulin resistance is supposed to be secondary to the relation between RBP4 and adipose tissue in children and adolescents.