Phospholipase D regulates ferroptosis signal transduction in mouse spleen hypoxia response

High-altitude hypoxia exposure can lead to phospholipase D-mediated lipid metabolism disorder in spleen tissues and induce ferroptosis. Nonetheless, the key genes underlying hypoxia-induced splenic phospholipase D and the ferroptosis pathway remain unclear. This study aimed to establish a hypoxia animal model. Combined transcriptomic and proteomic analyses showed that 95 predicted target genes (proteins) were significantly differentially expressed under hypoxic conditions. Key genes in phospholipase D and ferroptosis pathways under hypoxic exposure were identified by combining Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis techniques. Gene set enrichment analysis (GSEA) showed that the differential gene sets of the phospholipase D and ferroptosis signaling pathways were upregulated in the high-altitude hypoxia group. The genes in the phospholipase D signalling pathway were verified, and the expression levels of KIT and DGKG were upregulated in spleen tissues under hypoxic exposure. Subsequently, the mRNA and protein expression levels of genes from the exogenous pathway such as TFRC, SLC40A1, SLC7A11, TRP53, and FTH1 and those from the endogenous pathway such as GPX4, HMOX1, and ALOX15 differentials in the ferroptosis signalling pathway were verified, and the results indicated significant differential expression. In summary, exposure to high-altitude hypoxia mediated phospholipid metabolism disturbance through the phospholipase D signalling pathway and further induced ferroptosis, leading to splenic injury.

Application of PolyPRep tools on HIV protease polyproteins using molecular docking / Aplicação da ferramenta PolyPRep em poliproteínas de protease de HIV usando docking molecular

Abstract In recent years, the development of high-throughput technologies for obtaining sequence data leveraged the possibility of analysis of protein data in silico. However, when it comes to viral polyprotein interaction studies, there is a gap in the representation of those proteins, given their size and length. The prepare for studies using state-of-the-art techniques such as Machine Learning, a good representation of such proteins is a must. We present an alternative to this problem, implementing a fragmentation and modeling protocol to prepare those polyproteins in the form of peptide fragments. Such procedure is made by several scripts, implemented together on the workflow we call PolyPRep, a tool written in Python script and available in GitHub. This software is freely available only for noncommercial users.

Resumo Nos últimos anos, o desenvolvimento de tecnologias de alto rendimento para obtenção de dados sequenciais potencializou a possibilidade de análise de dados proteicos in silico. No entanto, quando se trata de estudos de interação de poliproteínas virais, existe uma lacuna na representação dessas proteínas, devido ao seu tamanho e comprimento. Para estudos utilizando técnicas de ponta como o Aprendizado de Máquina, uma boa representação dessas proteínas é imprescindível. Apresentamos uma alternativa para este problema, implementando um protocolo de fragmentação e modelagem para preparar essas poliproteínas na forma de fragmentos de peptídeos. Tal procedimento é feito por diversos scripts, implementados em conjunto no workflow que chamamos de PolyPRep, uma ferramenta escrita em script Python e disponível no GitHub. Este software está disponível gratuitamente apenas para usuários não comerciais.

Association of vitamin D receptor gene polymorphisms with type 2 diabetes mellitus in Taif population: a case-control study / Associação de polimorfismos do gene do receptor de vitamina D com diabetes mellitus tipo 2 na população Taif: um estudo de caso-controle

Abstract Several reasons may underlie the dramatic increase in type2 diabetes mellitus. One of these reasons is the genetic basis and variations. Vitamin D receptor polymorphisms are associated with different diseases such as rheumatoid arthritis and diabetes. The aim of this study is to investigate the possible association of two identified mutations ApaI (rs7975232) and TaqI (rs731236). Eighty-nine healthy individuals and Fifty-six Type 2 Diabetic (T2D) patients were investigated using RFLP technique for genotyping and haplotyping as well. The distribution of Apal genotypes was not statistically significant among the control (P=0.65) as well as for diabetic patients (P=0.58). For Taql allele frequencies of T allele was 0.61 where of G allele was 0.39. The frequency distribution of Taql genotypes was not statistically significant among the control (P=0.26) as well as diabetic patients (P=0.17). Relative risk of the allele T of Apa1 gene is 1.28 and the odds ratio of the same allele is 1.53, while both estimates were < 1.0 of the allele G. Similarly, with the Taq1 gene the relative risk and the odds ratio values for the allele T are 1.09 and 1.27 respectively and both estimates of the allele C were 0.86 for the relative risk and 0.79 for the odds ratio. The pairwise linkage disequilibrium between the two SNPs Taq1/apa1 was statistically significant in control group (D = 0.218, D' = 0.925 and P value < 0.001) and similar data in diabetic groups (D = 0.2, D' = 0.875 and P value < 0.001). These data suggest that the T allele of both genes Apa1 and Taq1 is associated with the increased risk of type 2 diabetes. We think that we need a larger number of volunteers to reach a more accurate conclusion.

Resumo Várias razões podem estar subjacentes ao aumento dramático da diabetes mellitus tipo 2. Um desses motivos é a base genética e variações. Os polimorfismos do receptor da vitamina D estão associados a diferentes doenças, como artrite reumatoide e diabetes. O objetivo deste estudo é investigar a possível associação de duas mutações identificadas ApaI (rs7975232) e TaqI (rs731236). Oitenta e nove indivíduos saudáveis ​​e 56 pacientes com diabetes tipo 2 (T2D) foram investigados usando a técnica RFLP para genotipagem e haplotipagem também. A distribuição dos genótipos Apal não foi estatisticamente significativa entre o controle (P = 0,65), bem como para os pacientes diabéticos (P = 0,58). Para as frequências do alelo Taql, o alelo T foi de 0,61, onde o alelo G foi de 0,39. A distribuição de frequência dos genótipos Taql não foi estatisticamente significativa entre o controle (P = 0,26), bem como os pacientes diabéticos (P = 0,17). O risco relativo do alelo T do gene Apa1 é 1,28 e a razão de chances do mesmo alelo é 1,53, enquanto ambas as estimativas foram < 1,0 do alelo G. Da mesma forma, com o gene Taq1, os valores de risco relativo e razão de chances para o alelo T são 1,09 e 1,27, respectivamente, e ambas as estimativas do alelo C foram de 0,86 para o risco relativo e 0,79 para o odds ratio. O desequilíbrio de ligação par a par entre os dois SNPs Taq1 / apa1 foi estatisticamente significativo no grupo de controle (D = 0,218, D' = 0,925 e valor P < 0,001) e dados semelhantes em grupos diabéticos (D = 0,2, D' = 0,875 e valor P < 0,001). Esses dados sugerem que o alelo T de ambos os genes Apa1 e Taq1 está associado ao aumento do risco de diabetes tipo 2. Achamos que precisamos de um número maior de voluntários para chegar a uma conclusão mais precisa.

Mitochondrial DNA diversity and maternal origins of Pakistani donkey / Diversidade de DNA mitocondrial e origens maternas do burro do Paquistão

Domestic donkey plays a key role as a draft animal in rural economy of Pakistan where its population is increasing every year. The complete mtDNA control region of forty randomly sampled donkeys was PCR- amplified and sequenced bi-directionally using specific primers. Distinct mtDNA haplotypes obtained in the current study (KY446001−KY446011) were subjected to haplotype (h) and nucleotide diversity (π) measures using DnaS as well as to phylogenetic, Network, and AMOVA analyses. There were a total 27 polymorphic sites present within 11 unique mtDNA haplotypes from the studied 40 animals from different regions. Neighbor-joining network and median-joining network both illustrated the splitting of all these haplotypes into two well-defined Nubian and Somali lineages, confirming African maternal origin of Pakistani domestic donkey. Diversity parameters h (0.967± 0.037) and π (0.02917± 0.00307) were found to reveal high levels of genetic diversity in Pakistani donkeys. AMOVA demonstrated only 1% of genetic differences between two mtDNA maternal lineages, pointing to lack of population substructure in Pakistani donkeys as is the case with worldwide domestic donkey population. Pakistani donkeys have African maternal origin and high levels of mtDNA diversity. High genetic diversity may be due to non-selective breeding and heteroplasmy. We herein provide the first report on mtDNA diversity of control region in Pakistani domestic donkey.

O burro doméstico possui um papel fundamental como animal de tração na economia rural do Paquistão, onde a população desse animal está aumentando a cada ano. A região de controle de mtDNA completa de 40 burros amostrados aleatoriamente foi ampliada por PCR e sequenciada bidirecionalmente por intermédio de primers específicos. Haplótipos distintos de mtDNA obtidos no estudo atual (KY446001 − KY446011) foram submetidos a medidas de haplótipo (h) e diversidade de nucleotídeos (π) por meio de DnaS, bem como análises filogenéticas, de rede e AMOVA. Havia um total de 27 sítios polimórficos presentes em 11 haplótipos de mtDNA exclusivos dos 40 animais estudados de diferentes regiões. A rede de união de vizinhos e a rede de união mediana ilustram a divisão de todos esses haplótipos em duas linhagens núbias e somalis bem definidas, confirmando a origem materna africana do burro doméstico do Paquistão. Os parâmetros de diversidade h (0,967 ± 0,037) e π (0,02917 ± 0,00307) revelaram altos níveis de diversidade genética em burros paquistaneses. AMOVA demonstrou apenas 1% de diferenças genéticas entre as duas linhagens maternas de mtDNA, apontando a falta de subestrutura populacional em burros paquistaneses, como é o caso da população mundial de burros domésticos. Os burros paquistaneses têm origem materna africana e altos níveis de diversidade de mtDNA. A alta diversidade genética pode ser por causa da reprodução não seletiva e de heteroplasmia. Aqui, fornecemos o primeiro relatório sobre a diversidade do mtDNA da região de controle em burros domésticos do Paquistão

Distribution and diversity of aquatic insects in different water bodies of Qatar / Distribuição e diversidade de insetos aquáticos em diferentes corpos de água do Catar

Aquatic insect fauna remains an important tool for bio indication of environmental disturbance, while maintaining a healthy aquatic system. The purpose of the study was to document and to identify the diversity and distribution patterns of aquatic insect, a highly ignored aspect from the Qatar. Following the standard procedures, the samples were collected from aquatic habitats during the period October 2015 to May 2017 on monthly basis. A total of 11,287 individuals, belonging to 6 orders were captured. Dipterans were the abundant with the percentages of 71.01 (n=8,015), while the lowest percentage was observed for Coleoptera 0.04 (n=05). Twelve insects families were identified, among these five were reported under Diptera, followed by Hemiptera (03), while Coleoptera, Tricoptera, Odonata, and Ephemeroptera were represented by single families. Among the selected localities, Dipterans were collected from 10 stations, followed by Hemiptera (9), Coleoptera (4), Odonota (4), Ephemeroptera (3) and Trichoptera (1) respectively. Among the water bodies samples, streams were the most preferred habitats (n=2,767), while drinking water pools were the least (27). Moreover, the highest Simpson diversity index of 1.48 and lowest of 0.47 was recorded for flooded sewage pool and plastic containers respectively, while the low evenness values were observed for ponds, and less than 1 Margalef's diversity values were seen for all habitats. This study documents the patterns of the diversity and distribution of aquatic insects, and provides a baseline for the future studies from Qatar.

A fauna aquática de insetos continua sendo uma ferramenta importante para a bioindicação de distúrbios ambientais, ao mesmo tempo em que mantém um sistema aquático saudável. O objetivo do estudo foi documentar e identificar a diversidade e os padrões de distribuição dos insetos aquáticos, um aspecto altamente ignorado no Catar. Seguindo os procedimentos padrão, as amostras foram coletadas em hábitats aquáticos durante o período de outubro de 2015 a maio de 2017, mensalmente. Um total de 11.287 indivíduos, pertencentes a seis ordens, foram capturados. Dípteros foram os mais abundantes, com as porcentagens de 71,01 (n = 8.015), enquanto a menor porcentagem foi observada para Coleópteros 0,04 (n = 05). Doze famílias de insetos foram identificadas, destas, cinco foram registradas sob Diptera, seguido por Hemiptera (03), enquanto Coleoptera, Tricoptera, Odonata e Ephemeroptera foram representados por famílias únicas. Dentre as localidades selecionadas, Dipterans foram coletados em 10 estações, seguidos por Hemiptera (9), Coleoptera (4), Odonota (4), Ephemeroptera (3) e Trichoptera (1), respectivamente. Entre as amostras de corpos d'água, os riachos foram os hábitats mais preferidos (n = 2.767), enquanto as piscinas de água potável foram os menos (27). Além disso, o maior índice de diversidade de Simpson de 1,48 e o menor de 0,47 foi registrado para piscina de esgoto inundada e recipientes de plástico, respectivamente, enquanto os valores de baixa uniformidade foram observados para lagoas e menos de 1 valores de diversidade de Margalef foram observados para todos os hábitats. Este estudo documenta os padrões de diversidade e distribuição de insetos aquáticos e fornece uma linha de base para os estudos futuros do Catar.

What is known about the effects of vitamin D in neuropsychiatric lupus?

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect several organs and systems. The central and/or peripheral nervous system can suffer from complications known as neuropsychiatric lupus (NPSLE). Studies have associated the manifestations of SLE or NPSLE with vitamin D deficiency. It has been shown that hypovitaminosis D can lead to cognition deficits and cerebral hypoperfusion in patients with NPSLE. In this review article, we will address the main features related to vitamin D supplementation or serum vitamin D levels with neuropsychiatric manifestations, either in patients or in animal models of NPSLE.

Poly-ε-caprolactone based nanoparticles for delivery of genistein in melanoma treatment

Abstract We developed poly-ε-caprolactone (PCL)-based nanoparticles containing D-α-tocopherol polyethylene glycol-1000 succinate (TPGS) or Poloxamer 407 as stabilizers to efficiently encapsulate genistein (GN). Two formulations, referred to as PNTPGS and PNPol, were prepared using nanoprecipitation. They were characterized by size and PDI distribution, zeta potential, nanoparticle tracking analysis (NTA), GN association (AE%), infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). PNTPGS-GN exhibited a particle size of 141.2 nm, a PDI of 0.189, a zeta potential of -32.9 mV, and an AE% of 77.95%. PNPol-GN had a size of 146.3 nm, a better PDI than PNTPGS-GN (0.150), a less negative zeta potential (-21.0 mV), and an AE% of 68.73%. Thermal and spectrometric analyses indicated that no new compounds were formed, and there was no incompatibility detected in the formulations. Cellular studies revealed that Poloxamer 407 conferred less toxicity to PCL nanoparticles. However, the percentage of uptake decreased compared to the use of TPGS, which exhibited almost 80% cellular uptake. This study contributes to the investigation of stabilizers capable of conferring stability to PCL nanoparticles efficiently encapsulating GN. Thus, the PCL nanoparticle proposed here is an innovative nanomedicine for melanoma therapy and represents a strong candidate for specific pre-clinical and in vivo studies.

Xuebijing improves inflammation and pyroptosis of acute lung injury by up-regulating miR-181d-5p-mediated SPP1 inactivation

Abstract Background Xuebijing (XBJ) is widely applied in the treatment of Acute Lung Injury (ALI). This study focused on the potential mechanism of XBJ in Lipopolysaccharide (LPS)-induced ALI. Methods The rat ALI model was established by injection of LPS (10 mg/kg) and pretreated with XBJ (4 mL/kg) three days before LPS injection. BEAS-2B cell line was stimulated with LPS (1 μg/mL) and ATP (5 mM) to induce pyroptosis, and XBJ (2 g/L) was pretreated 24h before induction. The improvement effects of XBJ on pulmonary edema, morphological changes, and apoptosis in ALI lung tissue were evaluated by lung wet/dry weight ratio, HE-staining, and TUNEL staining. Inflammatory cytokines in lung tissue and cell supernatant were determined by ELISA. pyroptosis was detected by flow cytometry. Meanwhile, the expressions of miR-181d-5p, SPP1, p-p65, NLRP3, ASC, caspase-1, p20, and GSDMD-N in tissues and cells were assessed by RT-qPCR and immunoblotting. The relationship between miR-181d-5p and SPP1 in experimental inflammation was reported by dual luciferase assay. Results XBJ could improve inflammation and pyroptosis of ALI by inhibiting contents of inflammatory cytokines, and levels of inflammation- and pyroptosis-related proteins. Mechanistically, XBJ could up-regulate miR-181d-5p and inhibit SPP1 in ALI. miR-181d-5p can target the regulation of SPP1. Depressing miR-181d-5p compensated for the ameliorative effect of XBJ on ALI, and overexpressing SPP1 suppressed the attenuating effect of XBJ on LPS-induced inflammation and pyroptosis. Conclusion XBJ can regulate the miR-181d-5p/SPP1 axis to improve inflammatory response and pyroptosis in ALI.

Proposta de impressão em 3-D de ossos de pessoas idosas vitimadas de fratura: Considerações preliminares / Proposal for 3-D printing of bones from elderly people suffering from fractures: Preliminary considerations / Propuesta de impresión 3D de huesos de personas mayores con fracturas: Consideraciones preliminares

No ano de 1984, foi criada a primeira impressora do tipo 3-D pelo engenheiro de origem norte-americana, Dr. Charles Hull, sendo que, antes disso, mais especificamente a quatro (04) anos, o japonês Dr. Hideo Kodama, desenvolveu a técnica de estereolitografia, que consistia em uma prototipagem rápida, possuindo enquanto intuito, "criar" objetos usando para este intento, luz ultravioleta (UV), ou ainda, um projetor para endurecer uma resina do tipo líquida em plástico sólido e resistente, ficando posteriormente conhecida como a sigla SLA.1,2 Após dois (02) anos, em 1986, Hull patenteou a SLA e, com isso, ele teve a oportunidade de desenvolver a "3-D Systems Corp", presente até hoje, sendo está uma das maiores empresas do ramo e, desta forma, o primeiro objeto então escolhido pelo Dr. Hull para ser impresso, foi uma lâmpada feita com resina, um plástico sintético.

Assessment of maternal knowledge of solar exposure and vitamin D in the neonatal period / Avaliação do conhecimento materno sobre exposição solar e vitamina D no período neonatal

ABSTRACT Objective: To assess mothers' knowledge on sun exposure related to serum vitamin D levels in the neonatal period. Methods: Observational, analytical and cross-sectional study, carried out from August 2020 to May 2021 through a questionnaire directed to mothers of newborns, in a maternity hospital in Southern Brazil. Results: From 141 interviewees, 132 (93.6%) believe it is important to expose the neonate to sun, 101 (71.6%) think this exposure can increase vitamin D levels, 86 (61%) received such information from a doctor, 108 (76.6%) believe there are no risks of sun exposure, 88 (62.4%) claim it isn´t necessary to use any kind of protection, 96 (68.1%) said that only exposure to the sun was necessary to maintain adequate levels of vitamin D during the neonatal period. Only two mothers (1.4%) claim that you should not exposure the neonate to the sun, and only one (0.7%) stated that sun expose can cause skin problems. Conclusions: Most mothers lack satisfactory knowledge about sun exposure related to serum vitamin D levels in the neonatal period. The need to inform and clarify the population about sun exposure during this period is remarkable, in addition to disseminating the proper way to maintain serum levels of vitamin D.

RESUMO Objetivo: Avaliar o conhecimento das mães acerca da exposição solar relacionada com níveis séricos de vitamina D no período neonatal. Métodos: Estudo observacional, analítico e transversal, realizado de agosto de 2020 a maio de 2021 por meio de questionário dirigido às mães de recém-nascidos, em uma maternidade no sul do Brasil. Resultados: De 141 entrevistadas, 132 (93,6%) acreditam ser importante expor o lactente ao sol no primeiro mês de vida, 101 (71,6%) acham que essa exposição aumenta os níveis de vitamina D, 86 (61,0%) receberam tal informação de um médico, 108 (76,6%) acreditam que expor o neonato ao sol não causa riscos para a saúde, 88 (62,4%) acham que não é necessário usar proteção contra radiação solar ao expor o neonato ao sol, e 96 (68,1%) afirmaram que apenas a exposição ao sol basta para manter os níveis adequados de vitamina D durante o período neonatal. Apenas duas mães (1,4%) afirmaram que não se deve expor o neonato ao sol e uma (0,7%) que a exposição solar pode causar problemas de pele. Conclusões: A maioria das mães não possui conhecimento satisfatório acerca da exposição solar relacionada aos níveis séricos de vitamina D no período neonatal. É notável a necessidade de informar e esclarecer a população sobre a exposição solar nesse período, além de disseminar a maneira adequada de manter os níveis séricos de vitamina D.

Terapia Ocupacional Social e Paulo Freire: Uma Revisão de escopo / Terapia Ocupacional Social y Paulo Freire: una revisión de alcance / Social Occupational Therapy and Paulo Freire: a scoping review

Paulo Freire é um importante autor que sustenta a práxis da Terapia Ocupacional Social. O intuito do presente trabalho é ampliar o escopo e adensar o caráter da presença acadêmica deste autor no campo da Terapia Ocupacional Social, tomando como referência produções científicas brasileiras. Como percurso metodológico, foi realizada uma revisão de escopo, com levantamento de estudos publicados em quatro periódicos brasileiros e bases de dados internacionais. As buscas foram realizadas utilizando a língua portuguesa. A revisão não definiu período inicial e considerou os artigos disponíveis online até fevereiro de 2023. Foram incluídos 18 estudos que possuem as obras de Freire em suas referências. Pedagogia do oprimido e Educação como prática de liberdade são as obras que mais aparecem nos artigos encontrados. Foi rea-lizado o refinamento das categorias freireanas, e constatou-se a presença de 42 delas, com destaque para conscientização, com onze ocorrências, transformação/ação transformadora e práxis/ação-reflexão, ambas com dez. Com os dados obtidos pelo estudo foi possível constatar o aumento do número de publicações na área da Terapia Ocupacional Social que utilizam o referencial teórico de Freire. A obra do autor tem colaborado de forma significativa na construção de uma Terapia Ocupacional Social problematizadora e emancipatória

Paulo Freire es un autor importante para apoyar la praxis de la Terapia Ocupacional Social. El propósito de este estudio es ampliar el alcance y profundizar en el carácter de la presencia académica de este autor en el campo de la Terapia Ocupacional Social. Como abordaje metodológico, se realizó una revisión de alcance con relevamiento de estudios publicados en cuatro revistas brasileñas y en bases de datos internacionales. Las búsquedas se realizaron solamente en portugués. No se estableció una fecha de inicio y se consideraron artículos disponibles en línea y publicados hasta febrero de 2023. El corpus estuvo constituido por 18 artículos que incluyen obras de Paulo Freire en sus referencias. Pedagogía del oprimido y Educación como práctica de libertadson las obras que más se referencian. Se depuraron las categorías freireanas y se constató la presencia de 42 de ellas, especialmente: concientización, once veces; transformación / acción transformadora y praxis / acción-reflexión, ambas, diez veces. Los resultados permiten constatar el aumento del número de publicaciones en el área de Terapia Ocupacional Social que utilizan el marco teórico de Freire. La obra del autor ha aportado significativamente a la construcción de una Terapia Ocupacional Social problematizadora y emancipadora.

Paulo Freire's work is important to support the praxis of Social Occupational Therapy. The purpose of this study is to expand the scope and deepen the character of the academic presence of Paulo Freire in Social Occupational Therapy. A scoping review was carried out as a methodological approach, including studies in four Brazilian journals and three international databases. The searches were conducted only in Portuguese; no year parameters were stipulated. The review considered articles published at any time up to February 2023. A total of 18 studies with Freire's works in their references were included; "Pedagogy of the Oppressed" and "Education, the Practice of Freedom" are the works that mostly appeared in the articles included. The refinement of the Freirean categories was carried out, and 42 categories were verified: conscientization, eleven times, transformation/transformative action, and praxis/action-reflection, both ten times. With the data obtained in the study, it was possible to verify the increase in the number of publications in Social Occupational Therapy that use Freire's theoretical framework. The author's work has contributed significantly to the construction of a problematizing and emancipating Social Occupational Therapy.

Estrogen deficiency influences SEC23A gene expression in the odontogenic region of incisors ­ a murine model study / A deficiência de estrógeno influencia a expressão gênica de SEC23A na região odontogênica de incisivos ­ um estudo em modelo murino

Recent scientific evidence suggests a close relationship between estrogen deficiency and vitamin D- related genes. Estrogen and vitamin D were involved with alterations in odontogenesis and tooth eruption process. Objective: The aim of the present study was to evaluate the influence of estrogen deficiency on the expression of genes related to the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model. Material and Methods: This is an experimental clinical study that used female Wistar Hannover rats. The animals were randomly divided into two groups according to the intervention received: Hypoestrogenism Group ­ animals submitted to estrogen deficiency by ovariectomy surgery and Control Group ­ animals submitted to sham surgery. Surgical intervention was performed in the prepubertal period; the animals were followed throughout the pubertal period. After euthanasia, the hemimandibles were removed to evaluate the mRNA expression of the vitamin D-related genes AMDHD1, CYP24A1, NADSYN1 and SEC23A in the odontogenic region of incisors through real time PCR. Student's t test was used to compare means. Kruskal-Wallis test and Dunn's posttest were also used. The level of significance was 5%. Results: SEC23A was overexpressed in the estrogen deficiency condition in the odontogenic region (p=0.021). Conclusion: Estrogen deficiency may influence the expression of the SEC23A gene involved in the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model(AU)

Evidências científicas recentes sugerem uma estreita relação entre a deficiência de estrógeno e os genes relacionados à vitamina D. O estrógeno e a vitamina D estão envolvidos com alterações na odontogênese e no processo de erupção dentária. Objetivo: O objetivo do presente estudo foi avaliar a influência da deficiência de estrógeno na expressão de genes relacionados à ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino. Material e Métodos: Trata-se de um estudo clínico experimental que utilizou ratas Wistar Hannover fêmeas. Os animais foram divididos aleatoriamente em dois grupos de acordo com a intervenção recebida: Grupo Hipoestrogenismo ­ animais submetidos à deficiência de estrógeno pela cirurgia de ovariectomia e Grupo Controle ­ animais submetidos à cirurgia simulada. A intervenção cirúrgica foi realizada no período pré-púbere; os animais foram acompanhados durante todo o período puberal. Após a eutanásia, as hemimandíbulas foram removidas para avaliar a expressão de mRNA dos genes AMDHD1, CYP24A1, NADSYN1 e SEC23A, relacionados à vitamina D, na região odontogênica de incisivos por meio de PCR em tempo real. O teste t de Student foi utilizado para comparar as médias. Também foram utilizados o teste de Kruskal-Wallis e o pós-teste de Dunn. O nível de significância foi de 5%. Resultados: SEC23A foi superexpresso na condição de deficiência de estrógeno na região odontogênica (p=0,021). Conclusão: A deficiência de estrógeno pode influenciar a expressão do gene SEC23A envolvido na ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino (AU)

Prévalence et facteurs associés des déficits neurocognitifs chez les patients diabétiques admis au centre neuro-psychopathologique de Kinshasa / NA

Objectif de l'étude.Préciser, chez les diabétiques, la fréquence et les facteurs associés des troubles neurocognitifs. Patients et Méthode. Une étude cas-témoin menée de janvier à décembre 2020 au Centre Neuro-Psychopathologique de l'Université de Kinshasa. Le diabète sucré (DS) a été diagnostiqué selon les critères biologiques de l'OMS et les fonctions neurocognitives évaluées à l'aide du test de Grober et Buschke après un dépistage avec le community screening interview for dementia (CSI-D). Résultats. Cinquante cas et 50 témoins ont été inclus. La fréquence globale des troubles neurocognitifs était de 58%. L'âge moyen des patients diabétiques atteints de troubles neurocognitifs était de 60,48 ± 6,90 ans avec un sex ratio (H/F) de 0,81. Les troubles neurocognitifs étaient en proportion élevés chez les diabétiques qui avaient un DS évoluant entre 6 et 10 ans. Les troubles mnésiques étaient associées au DS ; OR: 3,58, IC 95% [1,29-5,87], p = 0,003 ; avec prédominance d'amnésie d'évocation (65%). Les troubles neurocognitifs chez les diabétiques étaient influencés par l'âge ≥ 60 ans, l'HTA, le manque de ressource sure de revenue financière, les AVC et la durée du diabète supérieure à 5 ans. Le DS demeurait, après ajustement sur différents facteurs, un facteur de risque des troubles neurocognitifs avec un OR ajusté = 3,63, IC 95% [1,86-6,70] et un p = 0, 0001.Conclusion. Les diabétiques sont plus enclins aux troubles neurocognitifs que les non diabétiques. Des facteurs de risque pouvant influencer la survenue de ces troubles ont été identifiés.

Objective. To specify, in diabetics, the frequency and associated factors of neurocognitive disorders.Patients and Method. A case-control study conducted from January to December 2020 at the Neuro-Psychopathological Center of the University of Kinshasa. Diabetes mellitus (DM) was diagnosed according to WHO biological criteria and neurocognitive functions assessed using the Grober and Buschke test after screening by the community screening interview for dementia (CSI-D).Results. Fifty cases and 50 controls were included. The overall frequency of neurocognitive disorders was 58%. The mean age of diabetic patients with neurocognitive disorders was 60.48 ± 6.90 years with a sex ratio (M/F) of 0.81. Neurocognitive disorders were in high proportion in diabetics who had DM evolving between 6 and 10 years. Memory disorders were associated with DM; OR: 3.58, 95% CI [1.29-5.87], p = 0.003; with predominance of evocation amnesia (65%). Neurocognitive disorders in diabetics were influenced by age ≥ 60 years, hypertension, lack of secure financial income, stroke and duration of diabetes more than 5 years. DM remained, after adjustment for various factors, a risk factor for neurocognitive disorders with an adjusted OR = 3.63, 95% CI [1.86-6.70] and a p = 0.0001.Conclusion. Diabetics are more prone to neurocognitive disorders than non-diabetics. Risk factors that may influence the occurrenceof these disorders have been identified

Facteurs associés à la survenue du diabète chez les patients admis dans les services d' accueil des urgences de deux hôpitaux de Dakar en 2018 (Sénégal): Étude transversale / NA

Introduction :Au Sénégal, le profil épidémiologique en termes de diabète n'est pas clairement établi chez les patients reçus dans les services d'accueil des urgences (SAUs). L'objectif était de déterminer les facteurs associés à la survenue du diabète chez les patients admis dans les SAUs de deux hôpitaux de Dakar.Méthodes : L'étude était transversale et analytique. La collecte des données a eu lieu du 25 janvier au 05 mars 2018. La taille de l'échantillon était de 615 patients. L'entretien en face en face était réalisé. Les facteurs de risque étaient identifiés à l'aide d'une régression logistique. Les résultats étaient exprimés à l' aide de l'odds ratio ajusté (ORa) et entouré de son intervalle de confiance à 95% (IC95%) Résultats : Les patients étaient des hommes, âgés de moins de 40 ans, mariés et sans emploi dans respectivement 52,4%, 44,5%, 64,5% et 53,3% des cas. En outre, la consommation des fruits et légumes et la pratique du sport étaient insuffisantes chez respectivement 96,4% et 72% des patients. Par ailleurs, 16,9% des sujets interrogés étaient diabétiques. Les facteurs de risque de la survenue de la maladie étaient l'âge avancé, le statut sans emploi et l'obésité: patients âgés entre 40 et 69 ans (ORa=21,184; IC95%=[6,11-73,41]), patients âgés d'au moins 70 ans (ORa=12,62; IC95%=[3,29-48,28]), patients sans travail (ORa=3,47; IC95%=[1,69-7,10]) et patients obèses (ORa=3,17; IC95%=[1,35-7,45]).Conclusion : La fréquence du diabète est élevée chez les patients admis en consultation dans les SAUs des hôpitaux de Dakar. Cette étude montre que recherche du diabète chez cette catégorie de patients devrait être une pratique courante et qu'il urge de mettre en place des actions de promotion de la santé.

Association of vitamin D receptor gene polymorphisms with type 2 diabetes mellitus in Taif population: a case-control study

Abstract Several reasons may underlie the dramatic increase in type2 diabetes mellitus. One of these reasons is the genetic basis and variations. Vitamin D receptor polymorphisms are associated with different diseases such as rheumatoid arthritis and diabetes. The aim of this study is to investigate the possible association of two identified mutations ApaI (rs7975232) and TaqI (rs731236). Eighty-nine healthy individuals and Fifty-six Type 2 Diabetic (T2D) patients were investigated using RFLP technique for genotyping and haplotyping as well. The distribution of Apal genotypes was not statistically significant among the control (P=0.65) as well as for diabetic patients (P=0.58). For Taql allele frequencies of T allele was 0.61 where of G allele was 0.39. The frequency distribution of Taql genotypes was not statistically significant among the control (P=0.26) as well as diabetic patients (P=0.17). Relative risk of the allele T of Apa1 gene is 1.28 and the odds ratio of the same allele is 1.53, while both estimates were 1.0 of the allele G. Similarly, with the Taq1 gene the relative risk and the odds ratio values for the allele T are 1.09 and 1.27 respectively and both estimates of the allele C were 0.86 for the relative risk and 0.79 for the odds ratio. The pairwise linkage disequilibrium between the two SNPs Taq1/apa1 was statistically significant in control group (D = 0.218, D' = 0.925 and P value 0.001) and similar data in diabetic groups (D = 0.2, D' = 0.875 and P value 0.001). These data suggest that the T allele of both genes Apa1 and Taq1 is associated with the increased risk of type 2 diabetes. We think that we need a larger number of volunteers to reach a more accurate conclusion.

Resumo Várias razões podem estar subjacentes ao aumento dramático da diabetes mellitus tipo 2. Um desses motivos é a base genética e variações. Os polimorfismos do receptor da vitamina D estão associados a diferentes doenças, como artrite reumatoide e diabetes. O objetivo deste estudo é investigar a possível associação de duas mutações identificadas ApaI (rs7975232) e TaqI (rs731236). Oitenta e nove indivíduos saudáveis e 56 pacientes com diabetes tipo 2 (T2D) foram investigados usando a técnica RFLP para genotipagem e haplotipagem também. A distribuição dos genótipos Apal não foi estatisticamente significativa entre o controle (P = 0,65), bem como para os pacientes diabéticos (P = 0,58). Para as frequências do alelo Taql, o alelo T foi de 0,61, onde o alelo G foi de 0,39. A distribuição de frequência dos genótipos Taql não foi estatisticamente significativa entre o controle (P = 0,26), bem como os pacientes diabéticos (P = 0,17). O risco relativo do alelo T do gene Apa1 é 1,28 e a razão de chances do mesmo alelo é 1,53, enquanto ambas as estimativas foram 1,0 do alelo G. Da mesma forma, com o gene Taq1, os valores de risco relativo e razão de chances para o alelo T são 1,09 e 1,27, respectivamente, e ambas as estimativas do alelo C foram de 0,86 para o risco relativo e 0,79 para o odds ratio. O desequilíbrio de ligação par a par entre os dois SNPs Taq1 / apa1 foi estatisticamente significativo no grupo de controle (D = 0,218, D' = 0,925 e valor P 0,001) e dados semelhantes em grupos diabéticos (D = 0,2, D' = 0,875 e valor P 0,001). Esses dados sugerem que o alelo T de ambos os genes Apa1 e Taq1 está associado ao aumento do risco de diabetes tipo 2. Achamos que precisamos de um número maior de voluntários para chegar a uma conclusão mais precisa.

Application of PolyPRep tools on HIV protease polyproteins using molecular docking

Abstract In recent years, the development of high-throughput technologies for obtaining sequence data leveraged the possibility of analysis of protein data in silico. However, when it comes to viral polyprotein interaction studies, there is a gap in the representation of those proteins, given their size and length. The prepare for studies using state-of-the-art techniques such as Machine Learning, a good representation of such proteins is a must. We present an alternative to this problem, implementing a fragmentation and modeling protocol to prepare those polyproteins in the form of peptide fragments. Such procedure is made by several scripts, implemented together on the workflow we call PolyPRep, a tool written in Python script and available in GitHub. This software is freely available only for noncommercial users.

Resumo Nos últimos anos, o desenvolvimento de tecnologias de alto rendimento para obtenção de dados sequenciais potencializou a possibilidade de análise de dados proteicos in silico. No entanto, quando se trata de estudos de interação de poliproteínas virais, existe uma lacuna na representação dessas proteínas, devido ao seu tamanho e comprimento. Para estudos utilizando técnicas de ponta como o Aprendizado de Máquina, uma boa representação dessas proteínas é imprescindível. Apresentamos uma alternativa para este problema, implementando um protocolo de fragmentação e modelagem para preparar essas poliproteínas na forma de fragmentos de peptídeos. Tal procedimento é feito por diversos scripts, implementados em conjunto no workflow que chamamos de PolyPRep, uma ferramenta escrita em script Python e disponível no GitHub. Este software está disponível gratuitamente apenas para usuários não comerciais.

Mitochondrial DNA diversity and maternal origins of Pakistani donkey

Abstract Domestic donkey plays a key role as a draft animal in rural economy of Pakistan where its population is increasing every year. The complete mtDNA control region of forty randomly sampled donkeys was PCR- amplified and sequenced bi-directionally using specific primers. Distinct mtDNA haplotypes obtained in the current study (KY446001KY446011) were subjected to haplotype (h) and nucleotide diversity () measures using DnaS as well as to phylogenetic, Network, and AMOVA analyses. There were a total 27 polymorphic sites present within 11 unique mtDNA haplotypes from the studied 40 animals from different regions. Neighbor-joining network and median-joining network both illustrated the splitting of all these haplotypes into two well-defined Nubian and Somali lineages, confirming African maternal origin of Pakistani domestic donkey. Diversity parameters h (0.967± 0.037) and (0.02917± 0.00307) were found to reveal high levels of genetic diversity in Pakistani donkeys. AMOVA demonstrated only 1% of genetic differences between two mtDNA maternal lineages, pointing to lack of population substructure in Pakistani donkeys as is the case with worldwide domestic donkey population. Pakistani donkeys have African maternal origin and high levels of mtDNA diversity. High genetic diversity may be due to non-selective breeding and heteroplasmy. We herein provide the first report on mtDNA diversity of control region in Pakistani domestic donkey.

Resumo O burro doméstico possui um papel fundamental como animal de tração na economia rural do Paquistão, onde a população desse animal está aumentando a cada ano. A região de controle de mtDNA completa de 40 burros amostrados aleatoriamente foi ampliada por PCR e sequenciada bidirecionalmente por intermédio de primers específicos. Haplótipos distintos de mtDNA obtidos no estudo atual (KY446001 KY446011) foram submetidos a medidas de haplótipo (h) e diversidade de nucleotídeos () por meio de DnaS, bem como análises filogenéticas, de rede e AMOVA. Havia um total de 27 sítios polimórficos presentes em 11 haplótipos de mtDNA exclusivos dos 40 animais estudados de diferentes regiões. A rede de união de vizinhos e a rede de união mediana ilustram a divisão de todos esses haplótipos em duas linhagens núbias e somalis bem definidas, confirmando a origem materna africana do burro doméstico do Paquistão. Os parâmetros de diversidade h (0,967 ± 0,037) e (0,02917 ± 0,00307) revelaram altos níveis de diversidade genética em burros paquistaneses. AMOVA demonstrou apenas 1% de diferenças genéticas entre as duas linhagens maternas de mtDNA, apontando a falta de subestrutura populacional em burros paquistaneses, como é o caso da população mundial de burros domésticos. Os burros paquistaneses têm origem materna africana e altos níveis de diversidade de mtDNA. A alta diversidade genética pode ser por causa da reprodução não seletiva e de heteroplasmia. Aqui, fornecemos o primeiro relatório sobre a diversidade do mtDNA da região de controle em burros domésticos do Paquistão.

Distribution and diversity of aquatic insects in different water bodies of Qatar

Abstract Aquatic insect fauna remains an important tool for bio indication of environmental disturbance, while maintaining a healthy aquatic system. The purpose of the study was to document and to identify the diversity and distribution patterns of aquatic insect, a highly ignored aspect from the Qatar. Following the standard procedures, the samples were collected from aquatic habitats during the period October 2015 to May 2017 on monthly basis. A total of 11,287 individuals, belonging to 6 orders were captured. Dipterans were the abundant with the percentages of 71.01 (n=8,015), while the lowest percentage was observed for Coleoptera 0.04 (n=05). Twelve insects families were identified, among these five were reported under Diptera, followed by Hemiptera (03), while Coleoptera, Tricoptera, Odonata, and Ephemeroptera were represented by single families. Among the selected localities, Dipterans were collected from 10 stations, followed by Hemiptera (9), Coleoptera (4), Odonota (4), Ephemeroptera (3) and Trichoptera (1) respectively. Among the water bodies samples, streams were the most preferred habitats (n=2,767), while drinking water pools were the least (27). Moreover, the highest Simpson diversity index of 1.48 and lowest of 0.47 was recorded for flooded sewage pool and plastic containers respectively, while the low evenness values were observed for ponds, and less than 1 Margalefs diversity values were seen for all habitats. This study documents the patterns of the diversity and distribution of aquatic insects, and provides a baseline for the future studies from Qatar.

Resumo A fauna aquática de insetos continua sendo uma ferramenta importante para a bioindicação de distúrbios ambientais, ao mesmo tempo em que mantém um sistema aquático saudável. O objetivo do estudo foi documentar e identificar a diversidade e os padrões de distribuição dos insetos aquáticos, um aspecto altamente ignorado no Catar. Seguindo os procedimentos padrão, as amostras foram coletadas em hábitats aquáticos durante o período de outubro de 2015 a maio de 2017, mensalmente. Um total de 11.287 indivíduos, pertencentes a seis ordens, foram capturados. Dípteros foram os mais abundantes, com as porcentagens de 71,01 (n = 8.015), enquanto a menor porcentagem foi observada para Coleópteros 0,04 (n = 05). Doze famílias de insetos foram identificadas, destas, cinco foram registradas sob Diptera, seguido por Hemiptera (03), enquanto Coleoptera, Tricoptera, Odonata e Ephemeroptera foram representados por famílias únicas. Dentre as localidades selecionadas, Dipterans foram coletados em 10 estações, seguidos por Hemiptera (9), Coleoptera (4), Odonota (4), Ephemeroptera (3) e Trichoptera (1), respectivamente. Entre as amostras de corpos d'água, os riachos foram os hábitats mais preferidos (n = 2.767), enquanto as piscinas de água potável foram os menos (27). Além disso, o maior índice de diversidade de Simpson de 1,48 e o menor de 0,47 foi registrado para piscina de esgoto inundada e recipientes de plástico, respectivamente, enquanto os valores de baixa uniformidade foram observados para lagoas e menos de 1 valores de diversidade de Margalef foram observados para todos os hábitats. Este estudo documenta os padrões de diversidade e distribuição de insetos aquáticos e fornece uma linha de base para os estudos futuros do Catar.

Progress of chronic obstructive pulmonary disease patients with different muscle mass levels / 公共卫生与预防医学

Objective To investigate the difference of the disease progression in patients with chronic obstructive pulmonary disease (COPD) with different muscle mass levels and the influence of related factors on the disease progression. Methods A total of 308 newly diagnosed patients with COPD from February 2021 to February 2022 were selected for this study. All patients were below moderate COPD. The patients were divided into two groups according to their muscle mass levels: sarcopenia group (98 cases) and control group (210 cases). The diagnostic criteria for sarcopenia were based on sarcopenia diagnostic thresholds: RSMI 2 in men and 2 for women. All subjects were followed up for 4 months to observe the progress of the patient's condition. The correlation between the muscle mass level and pulmonary function level, as well as the results of 6-minute walking test and CAT score was evaluated, and the influence of muscle mass level on the patient's disease progress was analyzed. At the same time, the potential influence of related factors (body fat rate, vitamin D level, etc.) on the condition of patients with different muscle mass levels was discussed. SPSS 19.0 software was used to perform statistical analysis. Results Under the same treatment intervention, the baseline and follow-up lung function improvement levels of patients in the sarcopenia group were lower than those in the control group, and the difference was statistically significant (P<0.05). At the same time, the baseline and follow-up 6-minute walk test results of the patients in the sarcopenia group were also worse than those of the control group, and the difference was statistically significant (P<0.05). Further correlation analysis was carried out between the patient's muscle mass level and the post-treatment pulmonary function indicators and 6MWD test level. The results showed that the muscle mass level was positively correlated with several pulmonary function indicators (FEV1, FEV1% predict) and 6MWD (both P<0.05). Considering the possible influence of other factors on the control and progress of the patient's condition, the present study used follow-up CAT score results to distinguish the prognosis of the patient's condition improvement, and used improvement and non-improvement as dependent variables to analyze the influence of various potential influencing factors. The results of regression model analysis showed that lower baseline muscle mass, women, lower body fat percentage, and lower vitamin D level were the main risk factors. Conclusion Under the same treatment condition, COPD patients with different muscle mass levels improve more slowly when complicated with sarcopenia and have poor prognosis. Women, lower body fat percentage and lower vitamin D level are potential risk factors for poor prognosis.

Structural identification of the related substances in phloroglucinol injection by two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry / 药学学报

This study aimed to identify the related substances of phloroglucinol injection by two-dimensional liquid chromatography quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF/MS). The first-dimensional separation was carried out on an HSS T3 (250 mm × 4.6 mm, 5 μm) column by gradient elution using 1.36 g·L-1 potassium dihydrogen phosphate buffer solution (pH adjusted to 3.0 with diluted phosphoric acid) and acetonitrile as the mobile phases. The separated components were then trapped in switch valve tube lines respectively and delivered to the second-dimensional desalting gradient elution which was performed with a BDS C18 (100 mm × 4.6 mm, 2.4 μm) column using 0.1% formic acid and methanol as the mobile phases. After rapid desalting, electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry was used for determining the accurate masses and elemental compositions of the parents and their product ions for both phloroglucinol and its related substance. Structures of the related substances were then figured out by mass spectrometry elucidation, organic reaction mechanism analysis, and/or comparison with reference substances. Under the established analytical conditions, phloroglucinol and its related substances were adequately separated, 17 main related substances were detected and identified in the injection and its stressed samples for the first time. The identification results can provide reference for the quality control of phloroglucinol injection.