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ABSTRACT Purpose: This study aimed to characterize retinitis pigmentosa associated with the eyes shut homolog gene, which causes hereditary retinal degeneration. Methods: The anatomical and functional findings of retinitis pigmentosa in patients with variants of the eyes shut homolog gene were characterized and compared using multimodal imaging and genetic analysis of the variants. Clinical data such as visual acuity, lens status, and refraction were obtained from medical records. Patients underwent an ophthalmic examination, including static visual field, microperimetry, optical coherence tomography, fundus autofluorescence, and fundus photography. Results: Twenty-two patients were included in the study. Several anatomical and functional characteristics of retinitis pigmentosa-eyes shut homolog were identified, including the presence of cataracts, cystoid macular edema, epiretinal membrane, and a tubular visual field. Genetic results revealed 26 distinct variants in the cohort, with 7 novel variants not previously documented or reported in the scientific literature or databases. Conclusion: The findings demonstrate that eyes shut homolog-retinitis pigmentosa manifests in specific patterns, starting in adolescence with mild progression and advancing with age. The integration of multimodal imaging and genetic analysis has provided a detailed understanding of the anatomical and functional features of retinitis pigmentosa-eyes shut homolog. Seven novel variants of the eyes shut homolog gene have been identified. These findings enhance the understanding of eyes shut homolog-related retinitis pigmentosa characteristics of by detailing the spectrum of mutations in this gene within the Brazilian population.

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Enzymes are very important in the food industry because they naturally speed up and improve various processes. They are used in many areas, including baking, dairy, brewing, and the processing of fruits and vegetables. Enzymes help make food products better in quality, longer-lasting, more stable, and tastier. In baking, enzymes like amylases, proteases, and lipases are essential. Amylases turn starches into sugars, which feed the yeast and help the dough rise more effectively. Proteases change gluten, making the dough easier to work with. Lipases improve the texture and softness of the bread, helping it stay fresh for a longer time. In dairy processing, enzymes such as rennet and lactase are crucial. Rennet is a mix of enzymes used in cheese-making to coagulate milk, which leads to the creation of curds and whey. Lactase breaks down lactose into glucose and galactose, making dairy products suitable for people who are lactose intolerant. These enzymatic actions not only improve the nutritional value of dairy products but also enhance their digestibility and flavouring, in the brewing industry, enzymes like amylases, proteases, and glucanases are used to convert starches into fermented sugars, break down proteins for better clarity, and lower viscosity. These enzymes help with efficient fermentation, resulting in higher alcohol yields and better beer quality. Additionally, ?-glucanase helps break down ?-glucans, which can cause problems during filtration, thus improving the overall brewing process. When it comes to processing fruits and vegetables, enzymes such as pectinases, cellulases, and hemicelluloses play important roles. Pectinases break down pectin, a key component of plant cell walls, leading to clearer juices and more efficient juice extraction. Cellulases and hemicelluloses further assist by breaking down cell walls, which helps release valuable nutrients and improves the texture of the processed products. Enzymes are essential in the food processing industry, providing numerous benefits such as better product quality, longer shelf life, increased nutritional value, and greater efficiency in production. Their ability to work under mild conditions, along with their specificity and biodegradability, makes them ideal for sustainable food production. Continuous research and the development of new enzymes and their applications will keep transforming the industry, leading to healthier, safer, and more sustainable food products.

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Silkworms are susceptible to various pathogens, including bacteria, fungi, viruses, and protozoa. The present study focused on the viral disease known as nucleopolyhedrosis virus, which causes severe infections in silkworms. Silkworms possess several antiviral proteins that play a crucial role in preventing the spread of infection. One protein, which is found in the digestive juice produced in the silkworm's midgut, was focused, and it is lipase. This protein is responsible for controlling the virus infection. To investigate the role of lipase expression in silkworm for virus control, its concentration after post-infection was measured. This was quantified and analysed using SDS-PAGE. The band of interest, with a molecular weight of 29 kDa, was further analysed through MALDI-TOF/MS, and it showed 70% homology to the lipase enzyme.

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During infection, the hepatitis C virus (HCV) can evade immune response and cause chronic disease. Formation of effective T-cell response is important for the control of HCV infection. Dendritic cells derived from peripheral blood monocytes activated by immunodominant epitopes of the pathogen can effectively stimulate T-lymphocytes. Previously, we obtained recombinant proteins containing cytotoxic T-lymphocyte epitopes of NS3 and NS4ab proteins of HCV, the T-helper epitope PADRE, and self-assembling peptides that cause the formation of nanoparticles. Here, we studied the activation of human dendritic cells isolated from peripheral blood monocytes and from monocytes derived from induced pluripotent stem cells. Both types of dendritic cells effectively respond to activation by recombinant HCV proteins and stimulated lymphocytes along the Th1 pathway. Recombinant nanoparticles induced more efficient responses. These results open prospects for immunotherapy of patients with chronic hepatitis C using activated dendritic cells derived from their induced pluripotent stem cells.

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Introducción. Los pacientes con patología abdominal quirúrgica que requieren manejo con abdomen abierto son susceptibles a la pérdida de proteínas desde la cavidad expuesta. El objetivo de este estudio fue caracterizar la pérdida proteica a través de dos tipos de cierre temporal abdominal. Métodos. Se realizó un estudio decohorte prospectivo, con pacientes críticos manejados durante el año 2021 con abdomen abierto mediante dos tipos de cierre temporal: bolsa de Bogotá y ABThera™. Se recolectaron muestras intraoperatorias seriadas de líquido peritoneal (días 1, 3 y 5). Se calcularon frecuencias y promedios, y se compararon con las pruebas de Chi cuadrado y t de Student. Resultados. Se incluyeron 25 pacientes. El promedio de pérdida de proteínas en líquido peritoneal fue mayor con el sistema ABThera™ (44,38 g/L) comparado con la bolsa de Bogotá (25,18 g/L; p=0,0185). Durante el seguimiento se observó la tendencia a la disminución del promedio de proteínas perdidas por ambos sistemas, pero con ABThera™ se perdieron en promedio 15,47 gr/L más de proteínas, independientemente del estado nutricional y del aporte proteico recibido (p=0,042). No hubo diferencias según la etiología que llevó al manejo con abdomen abierto, los procedimientos quirúrgicos realizados o el estado de infección por COVID-19. Conclusiones. El abdomen abierto representa una fuente importante de pérdida de proteínas, que es diferente según el tipo de cierre temporal usado. Estas pérdidas deberían considerarse en los cálculos de soporte nutricional en la unidad de cuidado intensivo.

Introduction. Patients with surgical abdominal pathology requiring management with an open abdomen are susceptible to protein loss from the exposed cavity. The objective of this study was to characterize protein loss through two types of temporary abdominal closure. Methods. A prospective cohort study was carried out with critically ill patients managed during 2021 with an open abdomen using two types of temporary closure: Bogota bag and ABThera™. Serial intraoperative peritoneal fluid samples were collected (days 1, 3, and 5). Frequencies and averages were calculated and compared with the Chi square and Student's t tests. Results. Twenty-five patients were included. The average protein loss in peritoneal fluid was higher with the ABThera™ system (44.38 g/L) compared to the Bogota bag (25.18 g/L; p-value=0.0185). During follow-up, a tendency to decrease the average protein lost by both systems was observed, but with ABThera™ an average of 15.47 gr/L more protein was lost, regardless of the nutritional status and protein intake received (p=0.042). There were no differences based on etiology leading to open abdomen management, surgical procedures performed, or Covid-19 infection status. Conclusions. The open abdomen represents an important source of protein loss, which is different depending on the type of temporary closure used. These losses should be considered in calculations of nutritional support in the intensive care unit.

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O carcinoma papilífero de tireoide (CPT) é a neoplasia maligna mais comum na glândula tireoide. Embora essas lesões geralmente tenham um excelente prognóstico, há casos que apresentam características clínico-patológicas agressivas, com alto índice de metástase linfonodal e recorrência. Diante disso, novos biomarcadores moleculares têm sido pesquisados com a finalidade de esclarecer melhor os processos biológicos e moleculares envolvidos no desenvolvimento e progressão desta neoplasia. Dentre eles destaca-se as proteínas YAP, LATS2 e TEAD, constituintes da Via Hippo (VH), a qual é essencial em diversos processos biológicos, além de participar no processo da carcinogênese quando a via está desregulada. Dessa forma, esta pesquisa teve como objetivo avaliar as proteínas relacionadas YAP, LATS2 e TEAD, nos CPTs, com o intuito de verificar se estas moléculas podem influenciar o comportamento biológico destas lesões. A amostra foi composta por 31 casos de CPTs e 5 de adenomas foliculares (grupo controle). As informações clínico-patológicas foram coletadas e correlacionadas à imunoexpressão das proteínas YAP1, LATS-2 e TEAD nestas lesões. A avaliação da marcação foi realizada no núcleo e citoplasma, onde foram considerados como positivos os casos com mais de 20% dos núcleos marcados para cada um das moléculas. Quanto ao citoplasma, foi avaliado a intensidade para YAP1 e LATS2. Nesse compartimento os casos foram classificados em negativo (sem coloração), fraco (coloração marrom claro) e forte (cor marrom escuro). Os dados foram submetidos à análise estatística por meio dos testes Qui-quadrado de Pearson e Exato de Fisher, com o nível de significância estabelecido em 5% (p < 0,05). Na análise da imunoexpressão, observou-se que, para YAP, todos os casos (n=31;100%) de CPTs apresentaram positividade nuclear. Houve também, uma associação significativa da forte expressão da YAP no citoplasma com casos de CPTs, quando comparado ao grupo controle (p=0,001). Para a LATS2 houve uma baixa expressão citoplasmática na maioria dos casos dos CPTs (58,1%). Já para o TEAD, houve uma maior positividade nuclear para TEAD (p=0,029) nos CPTs. Em relação às associações com os dados clínico-patológicos não houve dados estatisticamente significativos relevantes. A menor expressão citoplasmática de LATS2 nos CPTs sugere que essa proteína pode não estar regulando a YAP, o que resulta em sua translocação para o núcleo. Já a elevada expressão nuclear de YAP e TEAD sugere que essas moléculas podem estar interagindo no núcleo. Com base nisso, propõe-se que a subregulação citoplasmática da LATS 2 e a interação nuclear YAPTEAD podem influenciar o processo de tumorigênese dos CPTs (AU).

Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid gland. Although these lesions generally have an excellent prognosis, there are cases that present aggressive clinicopathological characteristics, with a high rate of lymph node metastasis and recurrence. Given this, new molecular biomarkers have been researched with the aim of better clarifying the biological and molecular processes involved in the development and progression of this neoplasm. Among them, the YAP, LATS2, and TEAD proteins, components of the Hippo Pathway (HP), stand out, which is essential in various biological processes and also participates in the carcinogenesis process when the pathway is deregulated. Therefore, this research aimed to evaluate the related proteins YAP, LATS2, and TEAD in PTCs, to verify whether these molecules can influence the biological behavior of these lesions. The sample consisted of 31 cases of PTCs and 5 follicular adenomas (control group). Clinicopathological information was collected and correlated with the immunoexpression of the YAP, LATS2, and TEAD proteins in these lesions. The evaluation of the staining was performed in the nucleus and cytoplasm, where cases with more than 20% of the nuclei stained for each of the molecules were considered positive. Regarding the cytoplasm, the intensity for YAP1 and LATS2 was evaluated. In this compartment, cases were classified as negative (no staining), weak (light brown staining), and strong (dark brown staining). Data were subjected to statistical analysis using Pearson's Chi-square and Fisher's Exact tests, with a significance level set at 5% (p < 0.05). The immunoexpression analysis showed that all PTC cases (100%) exhibited nuclear positivity for YAP. A significant association was also found between strong cytoplasmic YAP expression and PTC cases compared to the control group (p = 0.001). For LATS2, low cytoplasmic expression was observed in most PTC cases (58.1%). TEAD showed higher nuclear positivity (p = 0.029) in PTC cases. No statistically significant associations with clinicopathological data were found. The lower cytoplasmic expression of LATS2 in PTCs suggests that this protein may not regulate YAP, leading to its nuclear translocation. The elevated nuclear expression of YAP and TEAD indicates possible nuclear interaction. Therefore, the cytoplasmic subregulation of LATS2 and the nuclear YAP-TEAD interaction may influence PTC tumorigenesis (AU).

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RESUMEN Objetivo: Describir el comportamiento de la proteína BCL2 en modelos celulares de cáncer de pulmón de células no pequeñas frente a tratamientos con inhibidores de la tirosina proteína quinasa (crizotinib y alectinib) de ALK (quinasa de linfoma anaplásico) y su potencial inhibición dual BCL2-ALK. Materiales y métodos: Se utilizaron tres modelos celulares de cáncer de pulmón de células no pequeñas: Ba/f3 EML4-ALKWT, Ba/f3 EML4-ALKL1196M y Ba/f3 EML4-ALKG1202R, generados por mutagénesis dirigida. Estos fueron tratados a dosis-respuesta con crizotinib y alectinib, asimismo, se realizó un ensayo de apoptosis para corroborar la susceptibilidad farmacológica. Seguidamente, se procedió a medir la expresión de la proteína BCL2 en tres condiciones de tratamiento (sin tratamiento, 100 nM crizotinib y 50 nM alectinib). Finalmente, se realizó una búsqueda de los ligandos de BCL2 y ALK para la simulación del acoplamiento molecular y cálculo de energía de interacción medido en kcal/mol en el programa YASARA™. Resultados: Se evidenció que el modelo WT mostró sensibilidad a crizotinib y alectinib, con porcentajes de apoptosis de 23 % y 74 %, respectivamente; G1202R, resistencia a ambos fármacos (apoptosis: 5 %); y L1196M, resistencia al crizotinib (apoptosis: 12 %) y sensibilidad al alectinib (apoptosis: 25 %). La expresión de BCL2 reveló sobreexpresión en los modelos WT y G1202R, mientras L1196M evidenció una expresión cercana a la basal. Los hallazgos bioinformáticos apuntaron a ABT-199 (perteneciente a la biblioteca de moléculas pequeñas) como el mejor candidato para inhibir BCL2, mientras que su interacción con ALKL1196M reveló energías de interacción superiores a las obtenidas con el crizotinib y el alectinib. Conclusiones: Los modelos celulares mostraron la susceptibilidad farmacológica descrita según la literatura. La expresión de BCL2 durante los tratamientos mantuvo sobreexpresados a WT y G1202R, mientras L1196M no mostró variación. Finalmente, los hallazgos bioinformáticos sugieren a ABT-199 como potencial acción dual de inhibición por exhibir una mayor energía de interacción con ALK.

ABSTRACT Objective: To describe the behavior of the BCL-2 protein in non-small-cell lung cancer cell models in response to treatment with ALK (anaplastic lymphoma kinase) protein tyrosine kinase inhibitors (crizotinib and alectinib) and their potential dual BCL-2-ALK inhibition. Materials and methods: Three non-small-cell-lung cancer cell models were used: Ba/f3 EML4-ALKWT, Ba/f3 EML4-ALKL1196M and Ba/f3 EML4-ALKG1202R, generated by site-directed mutagenesis. These were treated with crizotinib and alectinib in a dose-responsive manner, and an apoptosis assay was also conducted to confirm pharmacological susceptibility. Subsequently, BCL-2 protein expression was measured under three treatment conditions (no treatment, 100 nM crizotinib and 50 nM alectinib). Finally, a search for BCL-2 and ALK ligands was performed for molecular docking simulation and interaction energy calculation, measured in kcal/mol in the YASARA™ program. Results: The WT model evidenced sensitivity to crizotinib and alectinib, with apoptosis percentages of 23 % and 74 %, respectively; G1202R showed resistance to both drugs (apoptosis: 5 %), and L1196M resistance to crizotinib (apoptosis: 12 %) and sensitivity to alectinib (apoptosis: 25 %). BCL-2 expression revealed overexpression in the WT and G1202R models, while L1196M showed expression close to baseline. Finally, bioinformatics findings identified ABT-199 (which is part of small molecule libraries) as the best candidate to inhibit BCL-2, while its interaction with ALKL1196M revealed interaction energies higher than those obtained in the interaction with crizotinib and alectinib. Conclusions: The cell models exhibited the pharmacological susceptibility described in the literature, BCL-2 expression during treatments remained overexpressed in WT and G1202R, while L1196M showed no variation. Finally, bioinformatics findings suggest ABT-199 as a potential dual action inhibitor due to its higher interaction energy with ALK.

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Differential Scanning Calorimetry (DSC) is an efficient and versatile analytical technique widely used to study the thermal properties and stability of proteins. This review article provides a comprehensive overview of the principles and applications of DSC in protein research. DSC measures the heat flow associated with temperature-induced conformational changes in proteins, allowing for the direct determination of key thermodynamic parameters such as melting temperature (Tm), enthalpy change (?H), and heat capacity change (?Cp). These parameters provide valuable insights into protein and peptide stability, folding mechanisms, and interactions with ligands. The review discusses the methodological aspects of DSC, including sample preparation, experimental setup, and data analysis techniques. It also highlights the application of DSC in various aspects, such as drug discovery, biopharmaceutical development, and the study of protein-ligand interactions. By elucidating the thermal behavior of proteins, DSC contributes significantly to our understanding of protein and peptide structure, function, and stability, making it an indispensable tool in biochemical and biophysical research.

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With the rising prevalence of overweight and obesity, helping people control/ manage their energy intake is important. Foods/ recipes that can confer satiety would help in this regard. Each of the macronutrients has different effects on satiety, with protein conferring greater satiety. In the present study, nine common Indian equicaloric recipes that varied in their macronutrient composition were tested for their satiety. Standard recipes for these were prepared providing approximately 15% energy from protein, 20% from fat and about 40% from carbohydrates. In the test recipes, either energy contribution from protein was raised to 30%, or fat contributed about 40% with carbohydrates, giving about 48% energy. In the high carbohydrate versions, carbohydrate recipes provided about 80% energy while fat provided only 6% energy. Satiety was assessed with 35-47 participants and satiety scores were calculated by area under the curve. Satiety scores were positively correlated with protein and ?bre content but were negatively correlated with fat. There was no correlation between carbohydrate content and satiety scores. High protein variations had higher cooked weights, tended to have lower energy density and delayed hunger for a longer period. The mixture of dairy and plant protein sources gave greater satiety than did plant sources and dairy sources alone gave the lowest satiety. Also, sweet recipes were rated lower than savoury ones. It would be worthwhile to examine the effect of different sources of plant proteins with and without dairy proteins as the latter appeared to be less satiating than plant proteins.

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A high level of disorder in many viral proteins is a direct consequence of their small genomes, which makes interaction with multiple binding partners a necessity for infection and pathogenicity. A segment of the flaviviral capsid protein (C), also known as the molecular recognition feature (MoRF), undergoes a disorder-to-order transition upon binding to several protein partners. To understand their role in pathogenesis, MoRFs were identified and their occurrence across different flaviviral capsids were studied. Despite lack of sequence similarities, docking studies of Cs with the host proteins indicate conserved interactions involving MoRFs across members of phylogenetic subclades. Additionally, it was observed from the protein–protein networks that some MoRFs preferentially bind proteins that are involved in specialized functions such as ribosome biogenesis. The findings point to the importance of MoRFs in the flaviviral life cycle, with important consequences for disease progression and suppression of the host immune system. Potentially, they might have impacted the way flaviviruses evolved to infect varied hosts using multiple vectors.

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Essential oils so far have been investigated for their use in wound healing, treating respiratory disorders, antimicrobial and antioxidant properties. They are now looked upon as novel therapeutic agents to treat bacterial bio?lms. Interactions of four key components of essential oils of Hedychium coronarium J. Koenig, an endangered, medicinal and aromatic plant with matrix proteins viz., Self-associating proteins of Escherichia coli, with Lec B protein of Pseudomonas aeruginosa and Sortase protein of Staphylococcus aureus were studied through molecular docking and molecular dynamics. The key components of the essential oils selected were ?-carotene, caryophyllene oxide, eucalyptol and sitosterol..All the four components showed good, stable interactions with Self-Associating Protein of Escherichia coli. ?-carotene, eucalyptol and sitosterol interactions with Lec B protein of Pseudomonas aeruginosa were also stable with the exception of caryophyllene. In case of Staphylococcus aureus, with the exception of eucalyptol, promising results were seen with ?-carotene, caryophyllene and sitosterol. The selected essential oil components showed good stable interactions with matrix proteins through in silico results thereby validating that natural remedies may be considered for treating fatal illnesses as well.

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Background & objectives: Peptides isolated from different sources of plants have the advantages of specificity, lower toxicity, and increased therapeutic effects; hence, it is necessary to search for newer antivirals from plant sources for the treatment of dengue viral infections. Methods: In silico screening of selected plant peptides against the non-structural protein 1, NS3 protease domain (NS2B-NS3Pro) with the cofactor and ATPase/helicase domain (NS3 helicase domain/NS3hel) of dengue virus was performed. The physicochemical characteristics of the peptides were calculated using Protparam tools, and the allergenicity and toxicity profiles were assessed using allergenFP and ToxinPred, respectively. Results: Among the tested compounds, Ginkbilobin demonstrated higher binding energy against three tested non- structural protein targets. Kalata B8 demonstrated maximum binding energy against NSP-1 and NSP-2, whereas Circulin A acted against the NSP3 protein of dengue virus. Interpretation & conclusion: The three compounds identified by in silico screening can be tested in vitro, which could act as potential leads as they are involved in hampering the replication of the dengue virus by interacting with the three prime non-structural proteins.

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Resumen La interferencia por paraproteínas en los análisis clínicos ha sido extensamente informada a nivel mundial. Si bien se han propuesto estrategias metodológicas para evitar el informe de datos erróneos asociados a interferencias (p. ej. confirmación manual, sistema de alerta), en pocos casos se ha propuesto su detección como herramienta diagnóstica de patologías no sospechadas desde la clínica. A partir del trabajo conjunto de dos hospitales de la provincia de Buenos Aires se describió: i) la presencia de interferencia positiva de paraproteínas en la determinación de bilirrubina total con reactivos y autoanalizadores Wiener, y ii) su contribución, en un período inferior a los seis meses, a la detección de cuatro gammapatías no sospechadas (tres monoclonales). Se recomienda dar difusión de esta inferencia a nivel nacional y se propone un esquema de trabajo en laboratorio para identificar la interferencia así como un perfil mínimo de determinaciones para evaluar la existencia de gammapatías desconocidas.

Abstract Paraprotein interference in clinical biochemistry has been widely reported around the world. Methodological strategies have been proposed to avoid reporting erroneous data due to interferences (i.e. manual check, alert system); however, few cases have suggested its use as a diagnostic tool for unsuspected pathologies. Based on the joint work of two hospitals from Buenos Aires Province, the following has been described: i) the presence of positive interference of paraproteins in the assessment of total bilirubin with Wiener chemistry and autoanalizers, and ii) its contribution, in less than six months, to the diagnosis of four gammophaties previously unsuspected (three monoclonal ones). Sharing the occurrence of this interference in our country is recommended. An interference identification workflow is also propose, as well as a set of biochemical assays to evaluate the occurrence of unsuspected gammophaties.

Resumo A interferência da paraproteína na bioquímica clínica tem sido amplamente relatada em todo o mundo. Embora estratégias metodológicas para evitar a comunicação de dados errôneos associados a interferências tenham sido propostas (p. ex., verificação manual, sistema de alerta), em poucos casos sugerem seu uso como ferramenta diagnóstica para patologias não suspeitas a partir da clínica. Com base no trabalho conjunto de dois hospitais da Província de Buenos Aires, foi descrita: i) a presença de interferência positiva de paraproteínas na determinação da bilirrubina total com reagentes e autoanalisadores Wiener e ii) sua contribuição, em um período inferior aos seis meses, para o diagnóstico de quatro gamopatias não suspeitas (três monoclonais). Recomenda-se difundir essa interferência em nível nacional e se propõe um esquema de trabalho em laboratório para identificar a interferência bem como um perfil mínimo de determinações para avaliar a ocorrência de gamopatias desconhecidas.

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The most predominant form of dementia is Alzheimer’s disease (AD), which most often manifests as loss of cognitive ability and episodic memory. Repressor element-1 silencing transcription factor (REST), generally referred to as neuron-restrictive silencer factor, is a transcriptional repressor that is typically expressed throughout embryogenesis and is essential for regulating the genes that are unique to neurons. The genes modulating neurotransmitter synthetases, synaptic vesicle proteins, transporters, receptors, and various ion channels in the central nervous system are regulated by REST. In neurons from the hippocampus and prefrontal cortical regions, there was a discernible decline in the nuclear REST level in AD patients. Despite the importance of REST, very little is known regarding the regulatory mechanism of REST. In this study, we have computationally explored the role of REST in differential expression of genes in AD by the construction of gene/protein interaction networks. In addition, we have also investigated the interaction between REST and other transcription factors (TFs) in the regulation of genes. When the gene expression data of AD samples were compared with the control samples, 97,457 genes from the 850,125 total examined genes displayed differential expression. 33 genes among the DEGs regulated REST, while 364 genes were controlled by REST. Twenty important TFs were discovered to be directly involved in the REST regulation among the DEGs. In addition, among the DEGs, 17 TFs were found to share common targets with REST that are involved in AD. Gene annotation analysis has shown that REST along with other TFs regulated genes that are involved in processes such as synaptic signaling, neuronal death, metabolic processes etc. The results demonstrated the critical regulatory role of REST in AD pathogenesis.

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Diet therapy in conservative treatment of chronic kidney disease involves protein restriction, but there is not enough evidence to recommend a particular type of protein, whether animal or plant based. However, studies suggest that plant-based diets help reduce the consumption of total and animal protein, reduce the need for nephroprotective drugs, improve complications and bring advantages in terms of disease progression and patient survival. The article considers up-to-date data on the effects of this diet and observed that when low in protein, primarily vegetable and in some cases supplemented with ketoanalogues, it can result in positive clinical outcomes, such as: delay in the decrease in the glomerular filtration rate, lower concentrations of urea, reduction of serum creatinine and phosphorus concentrations, lower metabolic acidosis, higher insulin sensitivity and lower systemic inflammation. As a whole, this dietary pattern may be able to postpone the start of dialysis with less progression of renal insufficiency. Additional research is needed to better characterize this dietary pattern.

La dietoterapia en el tratamiento conservador de la enfermedad renal crónica implica la restricción de proteínas, pero aún no hay pruebas suficientes para recomendar un tipo concreto de proteínas, ya sean animales o vegetales. Sin embargo, los estudios sugieren que las dietas basadas en plantas ayudan a reducir la ingesta de proteínas totales y animales, disminuyen la necesidad de fármacos nefroprotectores, mejoran las complicaciones y presentan ventajas con respecto a la progresión de la enfermedad y la supervivencia de los pacientes. En este artículo se consideran datos actualizados sobre los efectos de esta dieta y se observa que, cuando es hipoproteica, principalmente vegetal y en algunos casos se complementa con cetoanálogos, puede dar lugar a resultados clínicos positivos, como una disminución retardada de la tasa de filtración glomerular, concentraciones más bajas de urea, concentraciones reducidas de creatinina y fósforo séricos, menor acidosis metabólica, mayor sensibilidad a la insulina y menor inflamación sistémica. En conjunto, este patrón dietético tiene el potencial de retrasar el inicio de la diálisis con una menor progresión de la insuficiencia renal. Es necesario seguir investigando para caracterizar mejor este patrón dietético.

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Introduction: The new coronavirus SARS-CoV-2, identified in December 2019 as the cause of COVID-19, has triggered an outbreak of potentially fatal atypical pneumonia. The constant search for new molecules or strategies to combat this disease continues. Thus, the objective of this work was to evaluate, using in silico methods, the compounds present in Dipteryx odorata as inhibitors of crucial targets of SARS-COV-2. Methodology: The methodology included the selection of plant compounds from the Pubchem database and obtaining the structures of SARS-COV-2 proteins (6vxx, 6lu7, 1R42) from the Protein Data Bank (PDB). The molecular docking analysis was performed using the Autodock Tools 1.5.6 and Autodock Vina programs, LigPlus to obtain amino acids, and Chimera v.13.1 to generate 3D images. The absorption, distribution, metabolism, excretion and toxicity (ADME-TOX) properties of the most promising compounds were evaluated with the pkCSM tool. Results: In total, 672 molecular dockings were carried out, tested with 168 ligands, resulting in 17 compounds with binding energies lower than -7.9 kcal.mol-¹. A highlight was the exceptional interaction of the vouacapenic acid compound with the Spike protein, recording an energy of -9.9 kcal.mol-¹. The study revealed that compounds such as vouacapenic acid, taraxasterol and luteolin showed notable interactions with the Spike protein, in addition to positive results in the ADMET-TOX profile. Conclusion: These findings indicate the potential of these compounds and point to the need for in vivo and in vitro studies to validate their antiviral efficacy as therapeutic agents against SARS-COV-2.

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Objective:To study and screen the differential expression of inflammatory proteins in diabetes skin ulcers and common skin ulcers, so as to provide experimental basis for further research on anti-inflammatory and healing drug targets of diabetes skin ulcers.Methods:The tissues of 11 patients with diabetes skin ulcer, 12 patients with common skin ulcer and 11 patients with normal skin were collected from the First Hospital of Hunan University of Chinese Medicine. The levels of inflammatory protein Toll like receptor 4 (TLR4), nuclear factor κB (NF-κB), pro-inflammatory factor interferon -γ (IFN -γ), tumor necrosis factor - α (TNF -α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), macrophage chemotactic protein-1 (MCP-1), anti-inflammatory factors epidermal growth factor (EGF), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detected in three groups of tissues using enzyme-linked immunosorbent assay (ELISA).Results:Compared with normal tissues, the concentrations of TLR4, NF-κB, IFN -γ, TNF -α, IL-1β, IL-6, IL-8, MCP-1 and EGF in common ulcer skin tissues and diabetes ulcer tissues were higher, and the concentrations of IL-10 were lower, with statistically significant differences (all P<0.05); Compared with the normal tissue, the concentration of IL-4 in diabetes ulcer tissue was lower, the difference was statistically significant ( P<0.05); Compared with ordinary ulcer skin tissue, the concentrations of TLR4, NF-κB and MCP-1 in diabetes ulcer tissue were higher, and the concentrations of IL-4 were lower, with statistically significant differences (all P<0.05). Conclusions:The skin ulcer in diabetes patients will have inflammatory reaction, and high glucose promotes the inflammatory reaction of skin ulcer, which may be related to the abnormal expression of TLR4, NF-κB, MCP-1 and IL-4. TLR4/NF-κB signal pathway and inflammatory factors MCP-1 and IL-4 may be the target of the inflammation regulation of diabetes skin ulcer.

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The TMEM family is widely distributed in the plasma membrane and organelle membrane, and has multiple biological functions. The TMEM family has different functions and mechanisms of action in different diseases. Recent research shows that TMEM family members play an important role in the pathogenesis of non tumor diseases, especially in cardiovascular, respiratory and nervous system diseases, such as atherosclerosis, Parkinson′s disease, depression, etc. This article reviews the mechanism of action of the TMEM family in non tumor diseases, which is of great significance for further revealing the disease mechanism and elucidating the biological functions of TMEM family members, and provides a new perspective for disease treatment strategies.

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Prefoldin (PFDN), a hexameric chaperone complex, is crucial for the correct folding of nascent proteins. PFDN5, a subunit of PFDN, also known as MM-1, plays an essential role in regulating cell migration and senescence. Emerging evidences suggest that PFDN-5 deletion or mutation significantly contributes to the initiation and progression of multiple cancers and the prognosis of patients. In this paper, recent researches on the biological underpinnings of PFDN-5 and its anti-cancer prospect are reviewed, aiming to provide a novel potential therapeutic target for the treatment of malignancies.

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Objective To investigate the causal association between 91 kinds of circulating inflammatory proteins and different subtypes of breast cancer (estrogen receptor-positive and -negative breast cancer) using a two-sample Mendelian randomization (MR) method. Methods Corresponding exposure and outcome data were extracted from the genome-wide association study database. The data were analyzed by two-sample MR with inverse-variance weighting (IVW) as the primary study method, and MR-Egger, weighted median, simple mode, and weighted mode were used to complement the results. The results were complemented by sensitivity analysis to verify the reliability of the data. Results The IVW results showed that SULT1A1 (P=0.0007) was associated with an increased risk of total BC, whereas IL-5 (P=0.0011) was associated with a decreased risk of total BC. SULT1A1 (P=0.0011) and CX3CL1 (P=0.0005) were associated with an increased risk of ER+BC, whereas beta-NGF (P=0.0001) was associated with an increased risk of ER−BC. Supplementary analysis methods validated that the findings were consistent in direction and magnitude. The results of the sensitivity analysis showed that the data were reliable and unbiased. Conclusion Using the MR method, this study confirms that SULT1A1 is a risk factor for overall breast cancer, whereas IL-5 is a protective factor for overall breast cancer. SULT1A1 and CX3CL1 are risk factors for estrogen receptor-positive breast cancer, and beta-NGF is a risk factor for estrogen receptor-negative breast cancer.