Analysis of Germin-like protein genes family in Vitis vinifera (VvGLPs) using various in silico approaches / Análise da família de genes de proteínas semelhantes a germin em Vitis vinifera (VvGLPs) usando várias abordagens in silico

Germin-like proteins (GLPs) play an important role against various stresses. Vitis vinifera L. genome contains 7 GLPs; many of them are functionally unexplored. However, the computational analysis may provide important new insight into their function. Currently, physicochemical properties, subcellular localization, domain architectures, 3D structures, N-glycosylation & phosphorylation sites, and phylogeney of the VvGLPs were investigated using the latest computational tools. Their functions were predicted using the Search tool for the retrieval of interacting genes/proteins (STRING) and Blast2Go servers. Most of the VvGLPs were extracellular (43%) in nature but also showed periplasmic (29%), plasma membrane (14%), and mitochondrial- or chloroplast-specific (14%) expression. The functional analysis predicted unique enzymatic activities for these proteins including terpene synthase, isoprenoid synthase, lipoxygenase, phosphate permease, receptor kinase, and hydrolases generally mediated by Mn+ cation. VvGLPs showed similarity in the overall structure, shape, and position of the cupin domain. Functionally, VvGLPs control and regulate the production of secondary metabolites to cope with various stresses. Phylogenetically VvGLP1, -3, -4, -5, and VvGLP7 showed greater similarity due to duplication while VvGLP2 and VvGLP6 revealed a distant relationship. Promoter analysis revealed the presence of diverse cis-regulatory elements among which CAAT box, MYB, MYC, unnamed-4 were common to all of them. The analysis will help to utilize VvGLPs and their promoters in future food programs by developing resistant cultivars against various biotic (Erysiphe necator and in Powdery Mildew etc.) and abiotic (Salt, drought, heat, dehydration, etc.) stresses.

As proteínas do tipo germin (GLPs) desempenham um papel importante contra vários estresses. O genoma de Vitis vinifera L. contém 7 GLPs; muitos deles são funcionalmente inexplorados. No entanto, a análise computacional pode fornecer informações importantes sobre sua função. Atualmente, as propriedades físico-químicas, localização subcelular, arquitetura de domínio, estruturas 3D, sítios de N-glicosilação e fosforilação e estudos filogenéticos dos VvGLPs foram conduzidos usando as ferramentas computacionais mais recentes. Suas funções foram previstas usando a ferramenta Search para recuperação de genes/proteínas em interação (STRING) e servidores Blast2Go. A maioria dos VvGLPs são extracelulares (43%) na natureza, mas também mostraram expressão periplasmática (29%), na membrana plasmática (14%) e específica para mitocôndrias ou cloroplastos (14%). A análise funcional previu atividades enzimáticas únicas para essas proteínas, incluindo terpeno sintase, isoprenoide sintase, lipoxigenase, fosfato permease, receptor quinase e hidrolases geralmente mediadas por cátion Mn +. VvGLPs mostraram similaridade na estrutura geral, forma e posição do domínio cupin. Funcionalmente, os VvGLPs controlam e regulam a produção de metabólitos secundários para lidar com vários estresses. Filogeneticamente, VvGLP1, -3, -4, -5 e VvGLP7 mostraram maior similaridade devido à duplicação, enquanto VvGLP2 e VvGLP6 revelaram uma relação distante. A análise do promotor revelou a presença de diversos elementos cis-reguladores, entre os quais CAAT box, MYB, MYC, sem nome-4, sendo comum a todos eles. A análise ajudará a utilizar VvGLPs e seus promotores em programas alimentares futuros, desenvolvendo cultivares resistentes contra vários estresses bióticos (Erysiphe necator e no oídio, etc.) e abióticos (sal, seca, calor, estresse hídrico, etc.).

Análises bromatológicas de missô artesanal / Bromatological analysis of handmade misso

Objetivo ­ Realizar análises bromatológicas de umidade, proteínas, pH e cinzas em missôs artesanais. A fermentação é um processo biotecnológico que tem sido utilizado para modificar e produzir alimentos desde a antiguidade. Nas últimas duas décadas, o interesse nos efeitos benéficos dos fermentados na saúde humana aumentou e tornou essa categoria de alimentos cada vez mais popular principalmente no Oriente. No mercado há uma ampla variedade de pastas à base de soja fermentada por microorganismos sendo conhecido popularmente como missô. Métodos ­ As análises realizadas foram secagem direta em estufa a 105°C graus para determinação da umidade (%) e calcinação em mufla para cinzas (%), determinação de pH por meio do peagâmetro e análise de proteínas através do teste de Biureto. Resultados ­ No presente estudo as amostras obtiveram um teor de umidade entre 52,71% a 60,48%, teor de cinzas variando de 1,12% a 22,7%, pH entre 5,35 e 8,68, e um teor de proteínas variando de 11,1% a 13,2%. Discussão ­ Foi interpretado e comparado os resultados obtidos com as análises de outros estudos, além disso, apontado algumas questões do campo bromatológico das pesquisas dos estudos comparados e as limitações do presente trabalho. Conclusão ­ O processo fermentativo de alimentos com microorganismos resulta em um produto diferenciado que pode ser benéfico a saúde com diferentes características organolépticas. Nossos resultados foram parcialmente semelhantes com outras pesquisas sendo que

Hypophysitis an uncommon manifestation of IgG4-related disease: Case report

IgG4-related disease is a recently described disease that can involve various organs and systems. Single organ involvement is the exception to the rule, it is generally a multi-system entity. We present a 36-year-old woman, with no previous pathological history or autoimmune disease, with headache caused by cystic macroadenoma. A transsphenoidal resection was performed and pathology documented areas of fibrosis with a predominantly plasmolymphocytic infíltrate and positive IgG4 staining in more than 20 cells per high-power field, meeting diagnostic criteria for IgG4-related sclerosing disease. Involvement of other organs was ruled out, and the patient improved clinically after management.

La enfermedad relacionada con IgG4 es una entidad recientemente descrita, capaz de involucrar diversos órganos y sistemas. El compromiso de órganos aislados es la excepción a la regla, dado que generalmente se trata de una entidad multisistémica. Se presenta el caso de una mujer de 36 años, sin antecedentes patológicos previos, en quien como causa de cefalea se documenta un macroadenoma quístico llevado a resección transesfenoidal, cuyo resultado de patología documenta zonas de fibrosis con infiltrado de predominio plasmo-linfocitario y la tinción para IgG4 positiva en más de 20 células por campo de alto poder, lo que configura criterios diagnósticos para enfermedad esclerosante relacionada con IgG4; se descartó compromiso de otros órganos y hubo mejoría clínica posterior al manejo.

Schõnlein-Henoch purpura in adults: Report of four cases

Schoenlein-Henoch purpura is a systemic small vessel vasculitis mediated by IgA-1 deposition in organs such as the skin, kidney, and gastrointestinal tract; it has been mainly described in children where it has a favourable prognosis. Although much rarer in adulthood it is associated with an increased risk of severe kidney involvement, gastrointestinal com-plications, and prolonged hospital stay. The therapeutic options are wide and vary according to the degree of involvement of the patient and the organ mainly affected.

La púrpura de Schönlein-Henoch es una vasculitis sistêmica de pequeno vaso mediada por depósito de IgA en órganos como la piel, el riñón y el tracto gastrointestinal. Se ha descrito principalmente en niños, grupo de población en el que tiene un pronóstico favorable. Si bien en la edad adulta es mucho menos frecuente, se asocia con un mayor riesgo de compromiso renal severo, complicaciones gastrointestinales y estancia hospitalaria prolongada. Las opciones terapêuticas son amplias y varían según el grado de compromiso del paciente y el órgano más afectado.

Propiedades nutritivas y tecno funcionales de barras de pseudocereales adicionadas con soya, mango y granada / Nutritional and techno functional properties of pseudocereal bars added with soy, mango and pomegranate

Las barras de cereal (BC), se comercializan como un snack saludable, no obstante, su calidad nutricional es baja. Una alternativa para mejorar esto, es la incorporación de ingredientes como pseudocereales, germinados y subproductos de fruta. Objetivo. Evaluar el contenido nutricional y propiedades tecnofuncionales de una barra de cereal formulada a partir de pseudocereales, germinados de soya y subproductos del procesamiento de frutas. Materiales y Métodos. Se desarrollaron 6 formulaciones (F0-F5). Se determinó el contenido de proteína y fibra cruda, se seleccionó la formulación que presentó el mayor contenido de estos componentes. A la BC seleccionada se le determinó la digestibilidad in-vitro de la proteína, las propiedades tecnofuncionales potencial prebiótico y actividad inhibitoria de ECA-I. Resultados. La formulación seleccionada fue F1 (13,6 g/100 g p.s. proteína y 13,1 g/100 g p.s. fibra cruda). La digestibilidad de la proteína fue del 69 %, el cual es cercano a valores reportados para algunos componentes de la BC. La capacidad de hinchamiento y retención de agua fue 2,55 ml/g; 12,74 %, respectivamente. El crecimiento de L. brevis en medio MRS modificado con BC no presentó diferencias estadísticas con el medio control, indicando el potencial prebiótico presente en la BC. La barra de cereal tuvo un 39% de actividad inhibitoria de ECA-I, demostrando la acción de los compuestos bioactivos posiblemente liberados durante la digestión de la BC. Conclusión. La formulación desarrollada presenta propiedades funcionales importantes y podría generar beneficios para la salud(AU)

Introduction. Cereal bars (CB) are marketed as a healthy snack; however, their nutritional quality is low. An alternative to improve this is the incorporation of ingredients such as soybean sprouts, which have a higher protein content than some seeds; as well as fruit by-products that contain important bioactive compounds. Objective. To evaluate the nutritional content and techno-functional properties of a cereal bar formulated from pseudocereals, soybean sprouts, and fruit processing by-products. Materials and Methods. 6 formulations (F0-F5) were developed. The content of protein and crude fiber was determined, the formulation that presented the highest content of these components was selected. The in-vitro digestibility of the protein, the technofunctional properties, potential prebiotic and inhibitory activity of ACE-I were determined for the selected BC. Results. The selected formulation was F1 (13.6g/100g p.s. protein and 13.1g/100 g p.s. crude fiber). Protein digestibility was 69%, which is close to reported values for some CB components. The swelling and water retention capacity was 2.55 ml/g; 12.74%, respectively. The growth of L. brevis in modified MRS medium with CB did not present statistical differences with the control medium, indicating the prebiotic potential present in CB. The cereal bar had 39% ACE-I inhibitory activity, demonstrating the action of bioactive compounds possibly released during CB digestion. Conclusion. The developed formulation has important functional properties and could generate health benefits(AU)

Proteínas oxidadas de origen animal y su impacto sobre la salud intestinal / Oxidized proteins of animal origin and their impact on intestinal health / Proteínas oxidadas de origem animal e seu impacto na saúde intestinal

Los alimentos de origen animal como la carne de pollo, res, pescado y cerdo poseen una amplia demanda en todo el mundo debido, entre otros aspectos, a su valor nutricional, asociado al alto contenido proteico. No obstante, este tipo de proteínas son susceptibles de sufrir reacciones de oxidación, las cuales pueden mediar procesos de fragmentación, agregación, pérdida de solubilidad, funcionalidad y digestibilidad proteica; eventos implicados en la pérdida de su valor nutricional. En este sentido, las proteínas agrega­das tienden a no ser digeridas en el tracto gastrointestinal y acumularse en el intestino (colon), donde la microbiota colónica las degrada a productos mutagénicos como fenol y p-cresol, lo que incrementa el riesgo de cáncer colorrectal. Por otra parte, los ami­noácidos o péptidos oxidados liberados en la digestión podrían incorporarse en las vías de señalización celular intestinal y favorecer o exacerbar procesos intestinales crónicos como colon irritable o enfermedad de Crohn. Debido al gran interés de esta temática en los últimos años, el objetivo de esta revisión es realizar una descripción general del impacto de proteínas oxidadas de origen animal sobre la salud intestinal.

Animal foods such as chicken, beef, fish and pork are in wide demand throughout the world due, among other things, to their nutritional value, associated with their high protein content. However, this type of protein is susceptible to oxidation reactions, which can mediate processes of fragmentation, aggregation, loss of solubility, functionality, and protein digestibility, which are events involved in the loss of their nutritional value. In this sense, aggregated proteins tend not to be digested in the gastrointestinal tract and accumulate in the intestine (colon), where the colonic microbiota degrades them into mutagenic products such as phenol and p-cresol, which increases the risk of colorectal cancer. On the other hand, the oxidized amino acids or peptides released in digestion could be incorporated into intestinal cell signaling pathways and favor or exacerbate chronic intestinal processes such as irritable bowel syndrome or Crohn's disease. Due to the great interest in this topic in recent years, the objective of this review is to provide a general overview of the impact of oxidized proteins of animal origin on intestinal health.

Alimentos de origem animal como frango, carne bovina, peixe e carne suína são muito procurados em todo o mundo devido, entre outros fatores, ao seu valor nutricional, associado ao seu alto teor de proteínas. No entanto, esse tipo de proteína é suscetível a reações de oxidação, que podem mediar processos de fragmentação, agregação, perda de solubilidade, funcionalidade e digestibilidade da proteína; eventos envolvidos na perda de seu valor nutritivo. Nesse sentido, as proteínas agregadas tendem a não ser digeridas no trato gastrointestinal e se acumulam no intestino (cólon), onde a microbiota colônica as degrada em produtos mutagênicos como fenol e p - cresol, aumentando o risco de câncer colorretal. Por outro lado, os aminoácidos ou peptídeos oxidados liberados na digestão poderiam ser incorporados às vias de sinalização das células intestinais e favorecer ou exacerbar processos intestinais crônicos, como a síndrome do intestino irritável ou a doença de Crohn. Devido ao grande interesse neste tema nos últimos anos, o objetivo desta revisão é fornecer uma descrição geral do impacto das proteínas oxidadas de origem animal na saúde intestinal.

Protein interactions with osseointegrable titanium implants

This review aims to present the mechanisms of protein interactions with titanium dental implant surfaces. Methods: the analyses were based on searches of scientific articles available in English and Portuguese in PubMed (MEDLINE), Bireme (LILACS), Scielo, Web of Science and Google Scholar. Results: titanium dental implant treatments success rates (95-98%) are mainly due to the biocompatibility of titanium oxide on the implant surface, surgical techniques adopted, good implants manufacturing processes and biomechanical knowledge of the systems. Studies in past decades has empirically developed implant surfaces with significant changes in morphologies, roughness, wettability, surface energy, chemical composition, and chemical groups density or deposited molecules. These changes promoted better protein adsorption, osteoblast adhesion, and changes in the mechanisms involved in osseointegration. Thus, the time to put the implant in function has been reduced and the success rates have increased. In the osseointegration process, at the nanoscale, there is no contact between the bone and the implant surface, but there is the formation of a protein anchorage between the periosteum and the implant with an interface formed by proteins. In all the reactions between the body and the implant surface, the activities of fibronectin and integrin are essential, since they are responsible for transmitting information to the cell for its differentiation, adhesion and mobility. Conclusion: thus, the analyses of protein-implant interactions are indispensable for a better understanding of the performance of osseointegrated dental implants

Fisiología respiratoria: fisiología del surfactante pulmonar / Physiology of pulmonary surfactant

El proceso de respiración y el intercambio gaseoso requiere la interacción de variadas fuerzas en los distintos tejidos y órganos involucrados. La tensión superficial a nivel alveolar provocaría colapso de dichas estructuras de no ser por las características del surfactante que lo recubre. Revisaremos en este articulo la fisiología involucrada en su estructura física, producción y efectos pulmonares.

The process of breathing and gas exchange requires the interaction of various forces in the different tissues and organs involved. The surface tension at the alveolus would cause collapse of these structures without of the surfactant that covers it. We will review in this article the physiology involved in its physical structure, production, and pulmonary effects.

The peri-implant ligament: a scoping review

The peri-implant ligament is formed from the interface of bone tissue, through the anchoring of proteins and the surface of the dental implant. In this sense, it is relevant to understand the extent to which this ligament is structured and biomimics the periodontal ligament functions. Aim: The goal of this scoping review is to present and analyze the peri-implant ligament composition and compare the extent to which this ligament is structured and biomimics the periodontal ligament functions. Methods: This scoping review was performed according to the Joanna Briggs Institute methodology for scoping reviews and following the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review. Two independent researchers searched Pubmed, Cochrane, Embase, Virtual Health Library, Scielo, Scopus, Web of Science, Brazilian Bibliography of Dentistry, Latin American and Caribbean Literature in Health Sciences, Digital Library of Theses and Dissertations from the University of São Paulo and Portal Capes. Studies published in English, Portuguese and Spanish, over the last 21 years (2000-2021). Results: A total of 330 titles were identified and after applying inclusion and exclusion factors, 27 studies were included in this review. All proteins were identified regarding their tissue function and classified into 6 major protein groups. After that this new protein ligament was compared with the periodontal ligament regarding its function and composition. The main proteins associated with osseointegration, and thus, with the peri-implant ligament are recognized as belonging to the periodontal ligament. Conclusion: This scoping review results suggest evidence of the composition and function of the periimplant ligament. However, variations may still exist due to the existence of several modulants of the osseointegration process

Advances in machine learning for predicting protein functions / 生物工程学报

Proteins play a variety of functional roles in cellular activities and are indispensable for life. Understanding the functions of proteins is crucial in many fields such as medicine and drug development. In addition, the application of enzymes in green synthesis has been of great interest, but the high cost of obtaining specific functional enzymes as well as the variety of enzyme types and functions hamper their application. At present, the specific functions of proteins are mainly determined through tedious and time-consuming experimental characterization. With the rapid development of bioinformatics and sequencing technologies, the number of protein sequences that have been sequenced is much larger than those can be annotated, thus developing efficient methods for predicting protein functions becomes crucial. With the rapid development of computer technology, data-driven machine learning methods have become a promising solution to these challenges. This review provides an overview of protein function and its annotation methods as well as the development history and operation process of machine learning. In combination with the application of machine learning in the field of enzyme function prediction, we present an outlook on the future direction of efficient artificial intelligence-assisted protein function research.

Cloning, identification and functional analysis of the goat transcription factor c-fos / 生物工程学报

C-fos is a transcription factor that plays an important role in cell proliferation, differentiation and tumor formation. The aim of this study was to clone the goat c-fos gene, clarify its biological characteristics, and further reveal its regulatory role in the differentiation of goat subcutaneous adipocytes. We cloned the c-fos gene from subcutaneous adipose tissue of Jianzhou big-eared goats by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed its biological characteristics. Using real-time quantitative PCR (qPCR), we detected the expression of c-fos gene in the heart, liver, spleen, lung, kidney, subcutaneous fat, longissimus dorsi and subcutaneous adipocytes of goat upon induced differentiation for 0 h to 120 h. The goat overexpression vector pEGFP-c-fos was constructed and transfected into the subcutaneous preadipocytes for induced differentiation. The morphological changes of lipid droplet accumulation were observed by oil red O staining and bodipy staining. Furthermore, qPCR was used to test the relative mRNA level of the c-fos overexpression on adipogenic differentiation marker genes. The results showed that the cloned goat c-fos gene was 1 477 bp in length, in which the coding sequence was 1 143 bp, encoding a protein of 380 amino acids. Protein structure analysis showed that goat FOS protein has a basic leucine zipper structure, and subcellular localization prediction suggested that it was mainly distributed in the nucleus. The relative expression level of c-fos was higher in the subcutaneous adipose tissue of goats (P < 0.05), and the expression level of c-fos was significantly increased upon induced differentiation of subcutaneous preadipocyte for 48 h (P < 0.01). Overexpression of c-fos significantly inhibited the lipid droplets formation in goat subcutaneous adipocytes, significantly decreased the relative expression levels of the AP2 and C/EBPβ lipogenic marker genes (P < 0.01). Moreover, AP2 and C/EBPβ promoter are predicted to have multiple binding sites. In conclusion, the results indicated that c-fos gene was a negative regulatory factor of subcutaneous adipocyte differentiation in goats, and it might regulate the expression of AP2 and C/EBPβ gene expression.

Bavachin induces apoptosis in colorectal cancer cells through Gadd45a via the MAPK signaling pathway / 中国天然药物

Bavachin is a dihydroflavonoid compound isolated from Psoralea corylifolia, and exhibits anti-bacterial, anti-inflammatory, anti-tumor and lipid-lowering activities. Recent attention has gradually drawn on bavachin-induced apoptosis in many human cancer cell lines. However, the anti-cancer effects and related mechanisms in colorectal cancer remain unknown. Here, we investigated the effects of bavachin on colorectal cancer in vivo and in vitro. The results showed that bavachin inhibited the proliferation of human colorectal cancer cells and induce apoptosis. These changes were mediated by activating the MAPK signaling pathway, which significantly up-regulated the expression of Gadd45a. Furthermore, Gadd45a silencing obviously attenuated bavachin-mediated cell apoptosis. Inhibition of the MAPK signaling pathway by JNK/ERK/p38 inhibitors also weakened the up-regulation of Gadd45a by bavachin. The anticancer effect of bavachin was also validated using a mouse xenograft model of human colorectal cancer. In conclusion, these findings suggest that bavachin induces the apoptosis of colorectal cancer cells through activating the MAPK signaling pathway.

Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing / 亚洲男科学杂志(英文版)

Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.

Clinical and genetic analysis of a child with Schaaf-Yang syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a child with Schaaf-Yang syndrome (SYS).@*METHODS@#Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Sanger sequencing was used for family constellation verification, and bioinformatic analysis was performed for the candidate variant.@*RESULTS@#The child, a 1-year-and-9-month-old boy, had clinical manifestations of retarded growth, small penis, and unusual facies. Genetic testing revealed that the child has harbored a novel heterozygous variant of c.3078dupG (p.Leu1027Valfs*28) of the MAGEL2 gene. Sanger sequencing showed that neither parent of the child carried the same variant. The c.3078dupG(p.Leu1027Valfs*28) variant of the MAGEL2 gene has not been included in the databases of ESP, 1000 Genomes and ExAC. According to the Standards and Guidelines for the Interpretation of Sequence Variants of the American College of Medical Genetics and Genomics (ACMG), the variant was judged to be pathogenic.@*CONCLUSION@#The c.3078dupG (p.Leu1027Valfs*28) variant of the MAGEL2 gene probably underlay the SYS in this child, which has further expanded the spectrum of the MAGEL2 gene variants.

Identification and 3D architecture analysis of the LIPC gene mutation in a pedigree with familial hypercholesterolemia-like phenotype / 中华心血管病杂志

Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.

Identification of a novel splice site mutation in the DNAAF4 gene of a Chinese patient with primary ciliary dyskinesia / 亚洲男科学杂志(英文版)

Primary ciliary dyskinesia (PCD) is a rare hereditary orphan condition that results in variable phenotypes, including infertility. About 50 gene variants are reported in the scientific literature to cause PCD, and among them, dynein axonemal assembly factor 4 ( DNAAF4 ) has been recently reported. DNAAF4 has been implicated in the preassembly of a multiunit dynein protein essential for the normal function of locomotory cilia as well as flagella. In the current study, a single patient belonging to a Chinese family was recruited, having been diagnosed with PCD and asthenoteratozoospermia. The affected individual was a 32-year-old male from a nonconsanguineous family. He also had abnormal spine structure and spinal cord bends at angles diagnosed with scoliosis. Medical reports, laboratory results, and imaging data were investigated. Whole-exome sequencing, Sanger sequencing, immunofluorescence analysis, hematoxylin-eosin staining, and in silico functional analysis, including protein modeling and docking studies, were used. The results identified DNAAF4 disease-related variants and confirmed their pathogenicity. Genetic analysis through whole-exome sequencing identified two pathogenic biallelic variants in the affected individual. The identified variants were a hemizygous splice site c.784-1G>A and heterozygous 20.1 Kb deletion at the DNAAF4 locus, resulting in a truncated and functionless DNAAF4 protein. Immunofluorescence analysis indicated that the inner dynein arm was not present in the sperm flagellum, and sperm morphological analysis revealed small sperm with twisted and curved flagella or lacking flagella. The current study found novel biallelic variants causing PCD and asthenoteratozoospermia, extending the range of DNAAF4 pathogenic variants in PCD and associated with the etiology of asthenoteratozoospermia. These findings will improve our understanding of the etiology of PCD.

Clinical characteristics and genetic analysis of a case of infantile Schaaf-Yang syndrome due to a heterozygous variant of MAGEL2 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the diagnosis, treatment and genetic analysis of an infant with Schaaf-Yang syndrome (SYS).@*METHODS@#An infant suspected for SYS at the Hunan Provincial Children's Hospital on June 10, 2022 was subjected to trio-whole exome sequencing, and Sanger sequencing was used to verify the candidate variant. Structure of the wild-type and mutant proteins was constructed to analyze the potential hazard.@*RESULTS@#The infant was found to harbor a heterozygous frameshifting variant of c.1908delG (p.R637Gfs*65) of the MAGEL2 gene, which was found in neither of his parents. The variant has not been recorded by the public databases, and no relevant literature was retrieved. As the result of the variant, the MAGEL2 protein only retained part of its proline domain, which may lead to destruction and/or down-regulation of its function.@*CONCLUSION@#The c.1908delG (p.R637Gfs*65) variant of the MAGEL2 gene probably underlay the pathogenesis in this child. Combined with his clinical characteristics, the child was diagnosed with SYS. Above finding has also enriched the mutational spectrum of the MAGEL2 gene.

Research progress on plant-derived exosome-like nanoparticles and their applications / 中国中药杂志

Plant-derived exosome-like nanoparticles(PELNs) are a class of membranous vesicles with diameters approximately ranging from 30 to 300 nm, isolated from plant tissues. They contain components such as proteins, lipids, and nucleic acids. PELNs play an important role in the metabolism of plant substances and immune defense, and can also cross-regulate the physiological activities of fungi and animal cells, showing significant potential applications. In recent years, research on PELNs has significantly increased, highlighting three main issues:(1) the mixed sources of plant materials for PELNs;(2) the lack of a unified system for isolating and characterizing PELNs;(3) the urgent need to elucidate the molecular mechanisms underlying the cross-regulation of biological functions by PELNs. This article focused on these concerns. It began by summarizing the biological origin and composition of PELNs, discussing the techniques for isolating and characterizing PELNs, and analyzing their biomedical applications and potential future research directions., aiming to promote the establishment of standardized research protocols for PELNs and provide theoretical references for in-depth exploration of the mechanisms underlying PELNs' cross-regulatory effects.

Regulatory effect of eight Chinese herbal medicines on glucose and lipid metabolism and their potential active components based on HCBP6 target / 中国中药杂志

With the improvement of living standards and changes in working style, the prevalence of abnormal glucose and lipid metabolism in humans is increasing in modern society. Clinically, the related indicators are often improved by changing the lifestyle and/or taking hypoglycemic and lipid-lowering drugs, but there are no therapeutic drugs for disorders of glucose and lipid metabolism at present. Hepatitis C virus core protein binding protein 6(HCBP6) is a newly discovered target that can regulate triglyceride and cholesterol content according to level oscillations in the body, thereby regulating abnormal glucose and lipid metabolism. Relevant studies have shown that ginsenoside Rh_2 can significantly up-regulate the expression of HCBP6, but there are few studies on the effect of Chinese herbal medicines on HCBP6. Moreover, the three-dimensional structural information of HCBP6 has not been determined and the discovery of potential active components acting on HCBP6 is not rapidly advanced. Therefore, the total saponins of eight Chinese herbal medicines commonly used to regulate abnormal glucose and lipid metabolism were selected as the research objects to observe their effect on the expression of HCBP6. Then, the three-dimensional structure of HCBP6 was predicted, followed by molecular docking with saponins in eight Chinese herbal medicines to quickly find potential active components. The results showed that all total saponins tended to up-regulate HCBP6 mRNA and protein expression, where gypenosides showed the optimum effect on up-regulating HCBP6 mRNA and ginsenosides showed the optimum effect on up-regulating HCBP6 protein expression. Reliable protein structures were obtained after the prediction of protein structures using the Robetta website and the evaluation of the predicted structures by SAVES. The saponins from the website and literature were also collected and docked with the predicted protein, and the saponin components were found to have good binding activity to the HCBP6 protein. The results of the study are expected to provide ideas and methods for the discovery of new drugs from Chinese herbal medicines to regulate glucose and lipid metabolism.

Three ways for protein aggregation and the control strategies / 生物工程学报

Protein aggregation is a critical issue in the production of biopharmaceuticals. During protein production, transport and storage, various factors can lead to protein aggregation. With the in-depth study, different ways of protein aggregation and various influencing factors were identified. This includes physical and chemical factors, translation modifications and protein structure. Since protein aggregation exerts major impact on the activity and homogeneity of proteins, it is of great importance to study the ways of protein aggregation and how to control it to obtain high-quality proteins. The review focuses on three ways of protein aggregation, namely 3D domain swapping, salt bridge formation, and oxidative stress, as well as methods to control protein aggregation during protein production, transport and storage. This may facilitate reducing the loss caused by the formation of protein aggregation and improving the purity and homogeneity of protein in research and commercial production.