Activation of M1 muscarinic acetylcholine receptors by proline-rich oligopeptide 7a (

Background: The bioactive peptides derived from snake venoms of the Viperidae family species have been promising as therapeutic candidates for neuroprotection due to their ability to prevent neuronal cell loss, injury, and death. Therefore, this study aimed to evaluate the cytoprotective effects of a synthetic proline-rich oligopeptide 7a (PRO-7a; <EDGPIPP) from Bothrops jararaca snake, on oxidative stress-induced toxicity in neuronal PC12 cells and astrocyte-like C6 cells. Methods: Both cells were pre-treated for four hours with different concentrations of PRO-7a, submitted to H2O2-induced damage for 20 h, and then the oxidative stress markers were analyzed. Also, two independent neuroprotective mechanisms were investigated: a) L-arginine metabolite generation via argininosuccinate synthetase (AsS) activity regulation to produce agmatine or polyamines with neuroprotective properties; b) M1 mAChR receptor subtype activation pathway to reduce oxidative stress and neuron injury. Results: PRO-7a was not cytoprotective in C6 cells, but potentiated the H2O2-induced damage to cell integrity at a concentration lower than 0.38 μM. However, PRO-7a at 1.56 µM, on the other hand, modified H2O2-induced toxicity in PC12 cells by restoring cell integrity, mitochondrial metabolism, ROS generation, and arginase indirect activity. The α-Methyl-DL-aspartic acid (MDLA) and L-NΩ-Nitroarginine methyl ester (L-Name), specific inhibitors of AsS and nitric oxide synthase (NOS), which catalyzes the synthesis of polyamines and NO from L-arginine, did not suppress PRO-7a-mediated cytoprotection against oxidative stress. It suggested that its mechanism is independent of the production of L-arginine metabolites with neuroprotective properties by increased AsS activity. On the other hand, the neuroprotective effect of PRO-7a was blocked in the presence of dicyclomine hydrochloride (DCH), an M1 mAChR antagonist. Conclusions: For the first time, this work provides evidence that PRO-7a-induced neuroprotection seems to be mediated through M1 mAChR activation in PC12 cells, which reduces oxidative stress independently of AsS activity and L-arginine bioavailability.(AU)

Analysis of Association of Brain Natriuretic Peptide Levels and Blood Pressure Variability

Objective: The present study aimed to investigate the relationship between brain natriuretic peptide (BNP) levels and blood pressure variability among hypertensive patients aged over 40 years. Methods: The study recruited 120 patients from a cardiology outpatient clinic who had been diagnosed with hypertension and taking antihypertensive medication for at least 6 months. Demographic and clinical information, blood pressure measurements, and blood samples were collected to measure BNP levels. The standard deviation of the mean arterial pressure over 24 hours was calculated as a measure of blood pressure variability. Linear regression was used to examine the association between BNP levels and blood pressure variability while controlling for age, sex, BMI, and medication history. Results: The study found a significant positive association between BNP levels and blood pressure variability (?=0.31, p=0.002), even after controlling for other variables. The linear regression model explained 20% of the variance in blood pressure variability (R2=0.20, F=9.52, p<0.001). Conclusion: The findings suggest that higher BNP levels are associated with increased blood pressure variability among hypertensive patients. Further studies are needed to explore the underlying mechanisms and the potential implications of this association.

Recomendaciones de expertos acerca del uso de teduglutide en pacientes pediátricos con sindrome de intestino corto / Expert recommendations on the use of teduglutide in pediatric patients with short bowel syndrome

Resumen El síndrome de intestino corto es una entidad de baja incidencia en los pacientes pediátricos, pero se asocia con elevadas tasas de morbimortalidad. El abordaje de estos pacientes por un equipo interdisciplinario de expertos enfocados en la rehabilitación intestinal mejora los resultados a corto y a largo plazo. Entre los recursos disponibles para el tratamiento se incluye el teduglutide, un análogo del péptido similar al glucagón tipo 2 (GLP-2) elaborado mediante técnicas recombinantes. Por medio de la aplicación del método Delphi, a partir de la evidencia disponible y de la experiencia de los autores, se proponen recomendaciones para el uso de teduglutide, dirigidas a los profesionales de la salud que tratan a los pacientes pediátricos con síndrome de intestino corto, así como a las autoridades sanitarias.

Abstract Short bowel syndrome is a low-incidence disorder among pediatric patients, but it is associated with high morbidity and mortality rates. Management of these patients by an interdisciplinary team of experts focused on intestinal rehabilitation improves short- and long-term outcomes. Available resources for treatment include teduglutide, a glucagon-like peptide type 2 (GLP-2) analog made by recombinant techniques. Considering the available evi dence and the authors' experience, Delphi-based recommendations for the use of teduglutide are suggested for healthcare professionals who treat pediatric patients with short bowel syndrome, as well as for health authorities.

Utilidad del NT-proBNP en la evaluación pronóstica de pacientes con estenosis aórtica grave asintomáticos, con fracción de eyección ventricular izquierda preservada / Prognostic Value of NT-proBNP in Asymptomatic Patients with Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction

RESUMEN Introducción : La indicación de reemplazo valvular aórtico (RVA) en pacientes con estenosis aórtica (EA) grave asintomáticos con función conservada es motivo de creciente debate. Objetivos : Evaluar si la elevación de la fracción aminoterminal del pro-péptido natriurético tipo B (NT-proBNP) predice la aparición de síntomas y la indicación de reemplazo valvular en pacientes inicialmente asintomáticos, con EA grave y fracción de eyección ventricular izquierda (FEVI) conservada. Material y métodos : Se incluyeron en forma prospectiva pacientes con EA grave, FEVI conservada (≥55%) que fueron considerados asintomáticos, sin indicación inicial de RVA. A todos se les realizó laboratorio con medición de NT-proBNP en forma basal y ecocardiograma con Doppler tisular consignando la onda S de la pared lateral (S lat) y la relación E/e´. Se consideró como punto final el requerimiento de reemplazo valvular durante el seguimiento. Resultados : Se incluyeron 133 pacientes con una edad de 69 ± 8 años, 49% mujeres. Luego de un seguimiento de 570 (rango intercuartilo 380-680) días, el 23,3% (n = 31) de los pacientes presentaron requerimiento de reemplazo valvular. En el aná lisis multivariado, el NT-proBNP y la relación E/e´ fueron predictores independientes de requerimiento de cirugía (HR 1,02, IC95% 1,001-1,03, p <0,001; y HR 1,42, IC95% 1,21-2,45, p<0,001, respectivamente). El NT-proBNP presentó un Área Bajo la Curva (ABC) mayor que la relación E/e´ (0,88 versus 0,64, p = 0,02). Se estableció como mejor punto de corte de NT-proBNP un valor >350 pg./mL (HR ajustado 1,55, IC95% 1,38-2,01, p <0,001). Conclusiones : El NT-proBNP y la relación E/e´ fueron predictores independientes de requerimiento de cirugía. El NT-proBNP presentó una muy buena capacidad de discriminación, mayor que la relación E/e´.

ABSTRACT Background : The aortic valve replacement (AVR) indication in asymptomatic patients with severe aortic stenosis (AS) and preserved function is being increasingly discussed. Objective : The aim of this study was to evaluate whether the elevation of the N-terminal fraction of the pro-B-type natriuretic peptide (NT-proBNP) predicts the occurrence of symptoms and the AVR indication in patients with severe AS and preserved left ventricular ejection fraction (LVEF), initially asymptomatic. Methods : Asymptomatic patients with severe AS, preserved EF (≥55%) and no initial AVR indication were prospectively included. All patients underwent laboratory tests measuring NT-proBNP at baseline and an echocardiogram with tissue Doppler recording the lateral wall S wave (lat. S) and the E/e´ ratio. The endpoint was the aortic valve replacement indication at follow-up. Results : We included 133 patients aged 69 ± 8 years, 49% of which were women. After a follow-up of 570 (interquartile range 380-680) days, 23.3% (n=31) of them required aortic valve replacement. In the multivariate analysis, NT-proBNP value and the E/e´ ratio were 2 independent predictors of surgery (HR 1.02, 95% CI 1.001-1.03) p<0.001 and HR 1.42, 95% CI 1.21- 2.45, p< 0.001, respectively). NT-proBNP presented an area under the curve (AUC) greater than the E/e' ratio (0.88 versus 0.64, p=0.02). The best NT-proBNP cut-off point was determined >350 pg/mL (adjusted HR 1.55, 95% CI 1.38-2.01, p<0.001) Conclusion : NT-proBNP value and the E/e´ ratio were independent predictors of the AVR requirement. NT-proBNP had a very good discrimination capacity, greater than the E/e´ ratio.

Síndrome inflamatorio multisistémico en pediatría: importancia de la evaluación inicial de los parámetros de laboratorio / Multisystem Inflammatory Syndrome in children: the importance of evaluation of early laboratory parameters

RESUMEN Introducción : El síndrome inflamatorio multisistémico en pediatría (SIM-C) es una infrecuente entidad asociada a COVID-19 con un amplio espectro de presentación: desde un cuadro similar a la enfermedad de Kawasaki a una afectación multisistémica con shock. Se han descripto asociaciones entre valores de laboratorio y mala evolución, pero no existen puntos de corte que predigan la misma. Objetivo : El objetivo de este estudio fue describir y analizar las características de los pacientes con SIM-C y las relaciones de estas con los hallazgos de laboratorio. Material y métodos : Se realizó un estudio analítico y retrospectivo de niños internados con diagnóstico de SIM-C entre mayo 2020 y junio 2021 en el HNRG. Se estudiaron 32 pacientes, 17 femeninas (53,13%) y 15 masculinos (46,87%), edad promedio de 7,67 años (rango 0,5-14,91). Diez de los pacientes (31,25%) presentaron shock. Se obtuvieron datos clínicos, ecocardiográficos y valores de troponina I ultrasensible, NT-proBNP, plaquetas y linfocitos al momento del diagnóstico; y se analizaron comparativamente entre quienes presentaron shock durante la evolución (Grupo 1) y quienes no (Grupo 2). Resultados : La diferencia en un valor inicial de NT-proBNP elevado fue estadísticamente significativa entre ambos grupos (p=0,008), en tanto que la troponina y el recuento de linfocitos y plaquetas, no. De los 13 pacientes que requirieron inotrópicos, el 58% presentó linfopenia inicialmente (p=0,006 vs aquellos que no los necesitaron). Conclusiones : Si bien la mortalidad debido al SIM-C es baja, la afectación cardiovascular y el compromiso hemodinámico en los paci entes que presentaron este síndrome puede ser frecuente. Poder contar con una herramienta de laboratorio ampliamente difundida para la categorización de pacientes podría ayudar a mitigar riesgos y obtener una derivación temprana a centros especializados.

ABSTRACT Background : Multisystem inflammatory syndrome in children (MIS-C) is an uncommon condition associated with COVID-19 with a wide spectrum of presentations, ranging from Kawasaki-like disease to multisystem involvement with shock. The as sociation between the laboratory characteristics and unfavorable outcome has been described, but the cut-off points associated with higher risk have not yet been defined. Objective : The aim of this study was to describe and analyze the characteristics of patients with MIS-C and their associations with the laboratory findings. Methods : We conducted an analytical and retrospective study of pediatric patients hospitalized between May 2020 and June 2021 with diagnosis of MIS-C in Hospital General de Niños Dr. Ricardo Gutiérrez (HNRG). The cohort was made up of 23 patients, 17 female (53.13%) and 15 male (46.87%); mean age was 7.67 years (range 0.5-14.91). Ten patients (31.25%) presented shock. Clinical and echocardiographic data and values of high-sensitive troponin I, N-terminal pro-B-type natriuretic peptide (NT-proBNP), platelets and lymphocytes at the time of diagnosis were obtained and compared between those with shock during evolution (group 1) and those without shock (group 2). Results : There was a significant difference in baseline elevated NT-proBNP values between both groups (p = 0.008), but not in troponin levels and lymphocyte and platelet counts. Of the 13 patients who required inotropic agents, 58% had baseline lymphopenia (p = 0.006 vs those who did not require inotropic drugs). Conclusions : Although mortality due to MIS-C is low, cardiac involvement and hemodynamic impairment may be common. The availability of a commonly used laboratory tool for patient categorization could help to mitigate risks and obtain early referral to specialized centers.

Shared epitope classification methods according to Gregersen and de Vries allow adequate characterization of patients with rheumatoid arthritis in a Colombian population

Introduction: The most important genetic association in rheumatoid arthritis (RA) is presented with some alleles from the HLA-DRB1 gene that encode the shared epitope (SE). Objectives: To apply the SE classification methods of Gregersen, de Vries, Raychaudhuri, Mattey, and Tezenas du Montcel in a group of Colombian patients with RA and determine the most common HLA-DRB1 alleles in the population. Methods: RA diagnosis, genetic study of the HLA-DRB1 region using Luminex technology in 50 RA and 50 healthy subjects. For the classification analysis, Fisher's exact test and chi-squared test were applied. Tables were created to count the RA-related alleles. We used odds ratio to determine the risk between the presence of the shared epitope (SE) and anti-cyclic citrullinated peptides (Anti-CCP). Results: Gregersen and de Vries methods were suitable for the characterization of RA in this population (p = .006). The most prevalent HLA-DRB1 alleles in the RA group were 14:02,04:04, 08:02,04:05, and 10:01. High frequencies of the 07:01, 03:01,13:02,01:02, and 12:01 HLA-DRB1 alleles were found in the healthy population. HLA-DRB1 alleles with similar distribution in both populations were 04:07, 15:01, 11:01, 16:02, and 01:01. A high frequency of SE + was observed in Anti-CCP + individuals (63.15%); however, this was not statistically significant [OR2.4 (.63-9.01); p = .19]. Conclusion: The SE classification methods of Gregersen and de Vries were adequate in characterizing RA in a Colombian population group. An equivalence of 100% was verified between the susceptibility alleles defined by de Vries and the alleles assigned as SE according to Gregersen.

Introducción: La asociación genética más importante en artritis reumatoide (AR) se presenta con algunos alelos del gen HLA DRB1 que codifican el epítope compartido (EC). Objetivos: Aplicar los métodos de clasificación de EC de Gregersen et al., de Vries et al., Raychaudhuri et al., Mattey et al., y Tezenas du Montcel et al., en un grupo de pacientes colombianos con AR, y determinar los alelos HLA DRB1 más frecuentes en esta población. Métodos: Diagnóstico para AR, estudio genético de la región HLA DRB1 por tecnología Luminex® de 50 sujetos AR y 50 sanos. Para análisis comparativos de clasificaciones EC, se aplicaron las pruebas test exacto de Fisher y Chi-cuadrado y se realizaron tablas de conteos para los alelos relacionados con AR. Se estimó la razón de odds para determinar el riesgo entre la presencia de EC y los anticuerpos antipéptidos cíclicos citrulinados (anti-PCC). Resultados: Los métodos de Gregersen et al. y de Vries et al. fueron adecuados para la caracterización de AR en esta población (p = 0,006). Los alelos HLA DRB1 más prevalentes en el grupo AR fueron 14:02, 04:04, 08:02, 04:05 y 10:01. Se encontraron altas frecuencias de los alelos HLA DRB1 07:01, 03:01,13:02, 01:02 y 12:01 en población sana. Alelos HLA DRB1 con distribución similar en ambas poblaciones fueron: 04:07, 15:01, 11:01, 16:02 y 01:01. Se observó alta frecuencia de individuos EC+ en el grupo AR anti-PCC+ (63,15%); no obstante, sin asociación estadística (OR: 2,4 [0,63-9,01]; p = 0,19). Conclusión: Los métodos de clasificación para EC de Gregersen et al. y de Vries et al. fueron adecuados caracterizando AR en un grupo de población colombiana. Se corroboró equivalencia del 100% entre los alelos de susceptibilidad definidos por de Vries y los alelos asignados como EC según Gregersen et al.

N-terminal del péptido natriurético tipo B y la amplitud de distribución eritrocitaria como factor pronóstico de severidad en pacientes con insuficiencia cardiaca aguda descompensada

Introducción: El estudio de predictores de desenlaces negativos en pacientes con insuficiencia cardiaca ha incluido la combinación de péptidos natriuréticos y el ancho de distribución eritrocitaria (RDW). Objetivo: Evaluar el uso combinado de la porción N-terminal del propéptido natriurético tipo B (NT-proBNP) y el RDW como pronóstico de fallecimiento por cualquier causa, hospitalización prolongada y reingreso al año del alta en pacientes con insuficiencia cardiaca aguda (ICA) descompensada. Métodos: Realizamos un estudio observacional retrospectivo. Construimos un índice combinado = NT-proBNP x RDW/100. Elaboramos curvas ROC, se estimó la sensibilidad y especificidad en base a los puntos de corte y se estimó el riesgo relativo para desarrollar los desenlaces. Comparamos las áreas bajo las curvas del índice combinado versus el NT-proBNP y RDW, por separado. Resultados: Analizamos los datos de 471 pacientes. El índice combinado tuvo su mejor corte en 927,79 para pronosticar fallecimiento durante el primer año de ingreso. Aquellos con valores ≥ 927,79 tuvieron un riesgo relativo de 32,7 (IC95%: 4,8 - 222,3). Para hospitalización ≥7 días el punto de corte fue 752,67, aquellos con este valor o superiores tuvieron un riesgo relativo de 22,4 (IC95%: 9,7 - 51,8). Para pronosticar reingreso al año del alta el corte fue 858,47 y el riesgo relativo fue 4,7 (IC95%: 3,3 - 6,8). Conclusiones: El índice combinado generó riesgos relativos que muestran una fuerte fuerza de asociación para fallecimiento por cualquier causa, hospitalización ≥ 7 días y reingresos al año del alta. Sin embargo, la superioridad para discriminar no fue concluyente respecto a los componentes individuales.

Introduction: The study of predictors of negative outcomes in patients with heart failure has included the combination of natriuretic peptides and red cell distribution width (RDW). Objective: To evaluate the combined use of the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and RDW as a prognostic factor for death from any cause, prolonged hospitalization, and readmission one year after discharge in patients with decompensated acute heart failure (AHF). Methods: We conducted a retrospective observational study. We constructed a combined index = NT-ProBNP x RDW/100. ROC curves were constructed, sensitivity and specificity were estimated based on the cut-off points, and the relative risk was estimated to develop the outcomes studied. We compared the area under curve of combined index versus NT-proBNP and RDW, separately. Results: We analyzed data from 471 patients. The combined index had its best cut of 927.79 to predict death during the first year of admission. Those with values ≥ 927,79 had a relative risk of 32.7 (95% CI: 4.8 - 222.3). To predict hospitalization ≥ 7 days, the cut-off point was 752.67; those with this value or higher had a relative risk of 22.4 (95% CI: 9.7 - 51.8). To predict readmission one year after discharge, the cutoff was 858.47 and the relative risk was 4.7 (95% CI: 3.3 - 6.8). Conclusions: The combined index used generate relative risks that show a strong strength of association for death from any cause, hospitalization ≥7 days, and readmissions one year after discharge. However, the superiority to discriminate was inconclusive with respect to the individual components.

La semaglutida en el tratamiento de las personas con diabesidad / Semaglutide in the Treatment of Diabesity Individuals

Introducción: La semaglutida es un fármaco que contribuye a la liberación de insulina por el páncreas y a la supresión del apetito por lo que lo convierte en un importante candidato para ser usado en el tratamiento de la diabesidad. Objetivo: Describir el efecto de la semaglutida en el tratamiento de las personas con diabesidad. Métodos: Se revisó la literatura publicada en el período comprendido de enero-febrero de 2021. Las palabras clave utilizadas fueron obesidad; diabetes mellitus; diabesidad; semaglutida; análogo del péptido similar al glucagón tipo 1. Se utilizaron como motores de búsqueda las bases de datos de Google Académico, PubMed y SciELO. Se evaluaron diferentes trabajos de revisión, investigación y páginas web que tenían menos de 10 años de publicados en idioma español, portugués o inglés, y que por el título trataban el tema de estudio. Fueron excluidos los artículos que no abordaron la relación entre diabetes y obesidad, así como el tratamiento con análogos del péptido similar al glucagón tipo 1. Esto permitió la consulta de 84 artículos, de los cuales 59 fueron referenciados. Conclusiones: El empleo de semaglutida favorece una mejor evolución en paciente con diabesidad, como complemento de una dieta y una actividad física adecuada. Al optimizar el control glucémico, contribuir a la pérdida de peso y a la mejoraría de ciertas comorbilidades, entre ellas la salud cardiovascular(AU)

Introduction: Semaglutide is a drug that contributes to the release of insulin from the pancreas and suppresses appetite, which makes it an important candidate for treating diabesity. Objective: To describe the role of semaglutide in the treatment of diabesity individuals. Methods: The necessary information to write this article was obtained in the 2022 two-month period January-February. The keywords used were obesity; Mellitus diabetes; diabesity; semaglutide; type 1 glucagon-like peptide analogue. The search engines corresponding to the Google Scholar, PubMed and SciElO databases were used. Different review, research and web pages were evaluated, which in general were published no more than 10 years ago, in Spanish, Portuguese or English and which dealt with the subject of study by title. Articles that did not address the relationship between diabetes and obesity, as well as treatment with glucagon-like peptide 1 analogues, were excluded. This allowed the consultation of 84 articles, 59 of them were referenced. Conclusions: The use of semaglutide, as a complement to a diet and physical activity appropriate to the needs of patients with diabesity, brought about several effects that favor better evolution of this health problem, by optimizing glycemic control, contributing to the loss of weight and the improvement of certain comorbidities, including cardiovascular health(AU)

Distribution of calcitonin gene-related peptide and vascular endothelial growth factor in the mouse lung at the embryonic and postnatal stages / Distribución del péptido relacionado con el gen de la calcitonina y el factor de crecimiento endotelial vascular en el pulmón de ratón en las etapas embrionaria y posnatal

SUMMARY: Neuropeptide calcitonin gene-related peptide (CGRP) is a neurotransmitter related to vasculogenesis during organ development. The vascular endothelial growth factor A (VEGF-A) is also required for vascular patterning during lung morphogenesis. CGRP is primarily found in organs and initially appears in pulmonary neuroendocrine cells during the early embryonic stage of lung development. However, the relationship between CGRP and VEGF-A during lung formation remains unclear. This study investigates CGRP and VEGF-A mRNA expressions in the embryonic, pseudoglandular, canalicular, saccular, and alveolar stages of lung development from embryonic day 12.5 (E12.5) to postnatal day 5 (P5) through quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Further, we analyzed the expression of CGRP via immunohistochemistry. The VEGF-A mRNA was mainly scattered across the whole lung body from E12.5. CGRP was found to be expressed in a few epithelial cells of the canalicular and the respiratory bronchiole of the lung from E12.5 to P5. An antisense probe for CGRP mRNA was strongly detected in the lung from E14.5 to E17.5. Endogenous CGRP may regulate the development of the embryonic alveoli from E14.5 to E17.5 in a temporal manner.

El péptido relacionado con el gen de la calcitonina (CGRP) es un neurotransmisor vinculado con la vasculogénesis durante el desarrollo de órganos. El factor de crecimiento endotelial vascular A (VEGF-A) también se requiere para el patrón vascular durante la morfogénesis pulmonar. El CGRP se encuentra principalmente en los órganos y aparece inicialmente en las células neuroendocrinas pulmonares durante la etapa embrionaria temprana del desarrollo pulmonar. Sin embargo, la relación entre CGRP y VEGF-A durante la formación de los pulmones sigue sin estar clara. Este estudio investiga las expresiones de ARNm de CGRP y VEGF-A en las etapas embrionaria, pseudoglandular, canalicular, sacular y alveolar del desarrollo pulmonar desde el día embrionario 12,5 (E12,5) hasta el día postnatal 5 (P5) a través de la reacción en cadena de la polimerasa cuantitativa en tiempo real. (qRT-PCR) e hibridación in situ. Además, analizamos la expresión de CGRP mediante inmunohistoquímica. El ARNm de VEGF-A se dispersó principalmente por todo parénquima pulmonar desde E12,5. Se encontró que CGRP se expresaba en unas pocas células epiteliales de los bronquiolos canaliculares y respiratorios del pulmón desde E12,5 a P5. Se detectó fuertemente una sonda antisentido para ARNm de CGRP en el pulmón de E14,5 a E17,5. El CGRP endógeno puede regular el desarrollo de los alvéolos embrionarios de E14,5 a E17,5 de manera temporal.

Correlación entre la glucosa salival con la glucosa de ayuno, la Hemoglobina glicada y el Péptido-C en personas con diabetes mellitus tipo 2

Objetivo : Determinar la correlación entre la glucosa salival con la glucosa en ayunas, HbA1c y el péptido C en personas con Diabetes Mellitus tipo 2 (DM2). Materiales y métodos : Estudio transversal llevado a cabo en el Centro de Investigación en Diabetes, Obesidad y Nutrición (CIDON) en Lima, Perú durante el año 2021. Se categorizó en buen control metabólico (HbA1c<7 %) y mal control metabólico (HbA1c≥7 %). Se midió la glucosa basal, HbA1c y el péptido C en sangre. La glucosa salival se midió con el método glucosa oxidasa. La correlación de Spearman fue usada para determinar la asociación entre la glucosa salival con la glucosa en ayunas, HbA1c y el péptido- C. Resultados : Participaron un total de 142 personas con DM2. La concentración de glucosa salival fue significativamente más elevada en DM2 con mal control metabólico (p<0.01). Se observó una correlación positiva débil significativa entre la glucosa salival y la glucosa basal (r=0.23, p=0.04) y HbA1c (r=0.26, p=0.02) en DM2 con mal control metabólico y una correlación negativa insignificante (r=-0.08; p=0.47) con el péptido C. Conclusiones : La glucosa salival presenta una asociación significativa y positiva con la glucosa en sangre y la HbA1c, pero no con el péptido C en personas con DM2 con mal control metabólico. Sin embargo, hay muchos factores que deben ser considerados y analizados más a fondo para determinar su posible uso.

Objetivo : To determine the correlation between salivary glucose levels with fasting blood glucose, HbA1c, and C-peptide in patients with type 2 diabetes mellitus (T2DM). Materials and methods : This is a cross-sectional study performed at the Centro de Investigación en Diabetes, Obesidad y Nutrición (CIDON) in Lima, Peru, during 2021. Patients were categorized as those with good metabolic control (HbA1c<7 %), and poor metabolic control (HbA1c≥7 %). Baseline fasting blood glucose, as well as blood HbA1c and C-peptide values were measured. Salivary glucose was measured using the glucose oxidase method. Spearman's correlation was used for determining an association between salivary glucose levels and fasting blood glucose, HbA1c, and C-peptide. Results : One-hundred and forty-two subjects with T2DM participated in the study. Salivary glucose was significantly higher in T2DM subjects with poor metabolic control (p<0.01). A weak positive correlation between salivary glucose and fasting blood glucose (r= 0.23, p= 0.04) and HbA1c (r= 0.26, p= 0.02) was observed in subjects with T2DM and poor metabolic control, and also a non-significant negative correlation (r=-0.08; p= 0.47) with C-peptide. Conclusions : Salivary glucose levels show significant and positive association with fasting blood glucose and HbA1c, but not with C-peptide in persons with T2DM and poor metabolic control. However, there are many factors that should be considered and analyzed in detail aiming to determine its potential use.

Effect of Modified Gegen Qinliantang on TGR5/cAMP/GLP-1 Signaling Pathway in Pancreatic Tissue of Type 2 Diabetes Mellitus db/db Mice / 中国实验方剂学杂志

ObjectiveTo discuss the effect of modified Gegen Qinliantang （MGQT） on blood glucose and lipids and Takeda G protein-coupled receptor 5 （TGR5）-related pathways in pancreatic tissue of obese type 2 diabetes mellitus （T2DM） mice. MethodA total of 10 male specific pathogen free （SPF） m/m mice （7 weeks old） and 50 male SPF （7 weeks old） were adaptively fed for one week in SPF laboratory. The m/m mice were included in the blank group. T2DM was induce d in the 50 db/db mice. The model mice were randomized into the model group， metformin group （0.2 g·kg-1）， high-dose， medium-dose， and low-dose （31.9， 19.1， 6.4 g·kg-1） MGQT groups， with 10 in each group， and the drug dose was10 mL·kg-1. The model group and the blank group received distilled water of the same volume. The administration lasted 12 weeks （once/day）. Fasting blood glucose （FBG） was detected regularly. After 12 weeks of administration， serum levels of glycated serum protein （GSP）， serum glucose （GLU）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected. Pathological changes in the pancreatic tissue were based on hematoxylin-eosin （HE） staining. Western blot was used to determine the protein expression of TGR5， protein kinase A （PKA）， phosphorylated （p）-PKA， cyclic-AMP response element binding protein （CREB）， p-CREB， proprotein convertase 1/3 （PC1/3）， and glucagon-like peptide-1 （GLP-1） in pancreatic tissues. The level of cyclic adenosine monophosphate （cAMP） in pancreatic tissue was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the blank group， the model group had pathological changes in pancreatic tissue， high levels of FBG， GSP， GLU， TC， TG， and LDL-C （P<0.01）， low level of HDL-C （P<0.05）， low protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in pancreatic tissue （P<0.01）， and low content of cAMP in the pancreas （P<0.01）. Pancreatic tissue lesion in the treatment groups were milder than that in the model group. Both the high-dose MGQT and metformin can reduce the levels of FBG， GSP， GLU， TC， TG， and LDL-C in db/db mice （P<0.05， P<0.01） and increase the level of HDL-C （P<0.01）. Except the GLP-1 protein in the medium-dose MGQT group， the protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in the high-dose and medium-dose MGQT groups and the metformin group increased compared with that in the model group （P<0.05， P<0.01）. The content of cAMP in the pancreatic tissue of the high-dose and medium-dose MGQT groups and the metformin group was raised compared with that in model group （P<0.05， P<0.01）. ConclusionMGQT can improve the glucose homeostasis in db/db mice with T2DM by regulating TGR5/cAMP/GLP-1 signaling pathway-related protein expression.

Dock-able linear and homodetic di,tri,tetra and pentapeptide library from canonical amino acids:SARS-CoV-2 Mpro as a case study / 药物分析学报

Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity.Although noncanonical residues can always be used,employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico screening.Towards this goal,the dataset comprising all possible di-,tri-,and tetra-peptide com-binations of the canonical residues has been previously reported.However,with increasing computa-tional power,the comprehensive set of pentapeptides is now also feasible for screening as the comprehensive set of cyclic peptides comprising four or five residues.Here,we provide both the com-plete and prefiltered libraries of all di-,tri-,tetra-,and penta-peptide sequences from 20 canonical amino acids and their homodetic(N-to-C-terminal)cyclic homologues.The FASTA,simplified molecular-input line-entry system(SMILES),and structure-data file(SDF)-three dimension(3D)libraries can be readily used for screening against protein targets.We also provide a simple method and tool for conducting identity-based filtering.Access to this dataset will accelerate small peptide screening workflows and encourage their use in drug discovery campaigns.As a case study,the developed library was screened against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)main protease to identify po-tential small peptide inhibitors.

Evaluation of monitoring on serum silent information regulator-related enzyme 3, glucagon-like peptide-1 and angiopoietin-like protein 4 in patients with acute ischemic stroke / 中国医师进修杂志

Objective:To investigate the value of monitoring on serum silent information regulator-related enzyme 3 (SIRT3), glucagon-like peptide-1 (GLP-1) and angiopoietin-like protein 4 (ANGPTL4) in patients with acute ischemic stroke (AIS).Methods:Eighty patients with AIS who treatment in Qiongzhong Li and Miao Autonomous County People′s Hospital from May 2019 to April 2022 were selected retrospectively as the observation group, and 60 healthy volunteers who underwent physical examination during the same period were selected as the normal control group. The levels of serum SIRT3, GLP-1, and ANGPTL4 between the two groups were compared. The neurological deficit degree of AIS patients was evaluated by National Institutes of Health Stroke Scale(NIHSS) and the correlation of SIRT3, GLP-1 and ANGPTL4 with neurological deficit degree were analyzed. The levels of serum SIRT3, GLP-1 and ANGPTL4 before and after treatment and their difference value were compared between different clinical outcome of AIS patients, the risk factors for poor clinical outcome of AIS patients were analyzed by Logistic regression analysis, the value of prediction was analyzed by receiver operating characteristic (ROC) curve.Results:The level of serum GLP-1 in the observation group was lower than that in the normal control group: (50.37 ± 5.69) nmol/L vs. (34.89 ± 4.26) nmol/L; and the levels of serum SIRT3 and ANGPTL4 in the observation group were higher than those in the normal control group: (50.37 ± 5.69) ng/L vs. (34.89 ± 4.26) ng/L, (15.07 ± 3.12) μg/L vs. (11.15 ± 2.63) μg/L, there were statistical differences ( P<0.05). The results of correlation analysis showed that the levels of serum SIRT3 and ANGPTL4 were positively correlated with the degree of neurological impairment in AIS patients( r = 0.631, 0.776, P<0.05), and the level of serum GLP-1 was negatively correlated with the degree of neurological impairment in AIS patients ( r = - 0.693, P<0.05). After treatment, 66 patients obtained good clinical outcome, the good outcome rate was 82.50%(66/80). The levels of serum SIRT3 and ANGPTL4 in the poor clinical outcome patients were higher than those in the good clinical outcome patients: (41.33 ± 4.74) ng/L vs. (37.82 ± 4.05) ng/L, (12.98 ± 2.17) μg/L vs. (11.69 ± 2.06) μg/L; the level of serum GLP-1 in the poor clinical outcome patients was lower than that in the good clinical outcome patients: (592.33 ± 98.44) nmol/L vs. (709.41 ± 125.31) nmol/L; the difference value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in the poor clinical outcome patients were lower than those in the good clinical outcome patients: (10.22 ± 2.05) ng/L vs. (12.31 ± 2.94) ng/L, (268.21 ± 70.12) nmol/L vs. (379.92 ± 85.33) nmol/L, (2.18 ± 0.65) μg/L vs. (3.36 ± 0.94) μg/L, there were statistical differences ( P<0.05). The results of Logistic regression analysis showed that differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment were all independent influencing factors of poor clinical outcome in patients with AIS ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in predicting poor clinical outcome were 0.701, 0.758 and 0.844, respectively, and had certain predictive value, the AUC of joint evaluation was the largest (0.912). Conclusions:The levels of serum SIRT3 and ANGPTL4 in patients with AIS are increased, and the level of serum GLP-1 is decreased, and they are related to the degree of neurological deficit. Clinical monitoring of their level changes is helpful for clinical evaluation of the clinical outcome of patients with AIS.

Correlation of serum pro-gastrin-releasing peptide, sugar chain antigen 242, procalcitonin levels in patients with chronic atrophic gastritis with intestinal metaplasia and Helicobacter pylori infection and prognosis / 中国医师进修杂志

Objective:To investigate the correlation of serum pro-gastrin-releasing peptide (ProGRP), sugar chain antigen 242(CA242), procalcitonin(PCT) levels in patients with chronic atrophic gastritis (CAG) with intestinal metaplasia and Helicobacter pylori(Hp) infection and prognosis.Methods:One hundred patients with CAG intestinal metaplasia in Emergency General Hospital were selected as the research objects, and they were divided into infection group (75 cases) and non-infected group (25 cases) according to whether they had Hp infection. The clinical data, levels of serum ProGRP, CA242, and PCT were compared between the two groups, and the diagnostic value of the combination of serum indicators in the diagnosis of Hp infection in CAG intestinal metaplasia patients and their correlation with prognosis were analyzed.Results:The degree of atrophy and intestinal metaplasia in the infected group were higher than those in the non-infected group ( P<0.05). The levels of serum ProGRP, CA242 and PCT in the infected group were higher than those in the non-infected group: (159.41 ± 42.38) ng/L vs. (105.84 ± 18.29) ng/L, (7.24 ± 2.28) kU/L vs. (4.12 ± 1.30) kU/L, (3.84 ± 1.12)μg/L vs. (2.57 ± 0.82) μg/L, there were statistical differences ( P<0.05). The results of Spearman analysis showed that the levels of ProGRP, CA242, PCT had positive correlation with atrophy degree ( r = 0.614, 0.629, 0.672, P<0.05), and had positive correlation with intestinal metaplasia degree ( r = 0.574, 0.591, 0.603, P<0.05). The area under the curve (AUC) for the combined diagnosis of Hp infection in patients with CAG intestinal metaplasia by serum ProGRP, CA242, and PCT was 0.874 (95% CI 0.793 - 0.932), the diagnostic sensitivity and specificity were 76.00% and 92.00%, respectively. The incidence of gastric neoplasms in patients with Hp positive combined diagnosis of serum ProGRP, CA242, and PCT within 2 years (11.86%) was higher than that of negative patients (0), but the difference was not statistically significant ( P>0.05). Conclusions:The levels of serum ProGRP, CA242 and PCT in patients with CAG intestinal metaplasia are closely related to Hp infection. The combination of various indicators has high application value in the diagnosis of Hp infection.

Changes and significance of triglyceride-glucose index, C-peptide and lipid metabolism in patients with type 2 diabetes mellitus complicated with hyperuricemia / 中国医师进修杂志

Objective:To explore the changes and significance of triglyceride-glucose (TyG) index, C-peptide and lipid metabolism in patients with type 2 diabetes mellitus (T2DM) complicated with hyperuricemia (HUA).Methods:A prospective research method was adopted. One hundred and three patients with T2DM treated in Tongling Hospital of Traditional Chinese Medicine were selected between March 2019 and November 2021, and they were divided into HUA group (34 cases) and non-hyperuricemia (NUA) group (69 cases) according to whether they were complicated with HUA. The general data, fasting blood glucose (FBG), serum uric acid (SUA), serum C-peptide, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and serum creatinine (SCr) were compared among the patients, and the TyG index was calculated. The relationship between the above different indicators and SUA was analyzed, and the possible risk factors of HUA with T2DM were analyzed.Results:There were no statistical differences in gender, disease course of diabetes and smoking history between HUA group and NUA group ( P>0.05), but the age in HUA group was younger than that in NUA group: (46.71 ± 10.23) years old vs. (58.74 ± 11.22) years old, and the body mass index (BMI) was higher than that in NUA group: (24.48 ± 2.26) kg/m 2 vs. (22.05 ± 2.14) kg/m 2, and the proportion of patients with alcohol drinking history was higher than that in NUA group: 55.88% (18/34) vs. 24.64% (17/69) ( P<0.05). There were no statistically significant differences in the levels of FBG, TC and LDL-C between HUA group and NUA group ( P>0.05), but the TG, TyG index, C-peptide, SUA and SCr were higher in HUA group than those in NUA group: (2.68 ± 0.57) mmol/L vs. (1.57 ± 0.33) mmol/L, 10.58 ± 3.52 vs. 7.03 ± 2.14, (2.59 ± 0.67) μg/L vs. (2.07 ± 0.41) μg/L, (356.74 ± 56.47) μmol/L vs. (319.87 ± 50.92) μmol/L, (72.05 ± 8.31) μmol/L vs. (58.59 ± 8.04) μmol/L, while the HDL-C level was lower than that in NUA group: (1.09 ± 0.33) mmol/L vs. (1.38 ± 0.41) mmol/L ( P<0.05). Pearson correlation results showed that TyG index, C-peptide, TG, LDL-C and SCr were positively correlated with SUA ( r = 0.42, 0.49, 0.41, 0.30 and 0.51; P<0.05), and HDL-C was negatively correlated with SUA ( r = -0.47, P<0.05). Multivariate Logistic regression analysis showed that increased BMI, alcohol drinking, increased TyG index and C-peptide, TG and SCr and reduced HDL-C were risk factors for HUA in patients with T2DM ( P<0.05). Conclusions:The TyG index, serum C-peptide and TG in patients with T2DM complicated with HUA are abnormally increased and are positively correlated with SUA, while HDL-C is decreased and is negatively correlated with SUA. High BMI, alcohol drinking, high TyG index, C-peptide, TG and SCr, and low HDL-C level are risk factors for HUA in patients with T2DM.

Clinical characteristics and genetic analysis of 6 cases of neonatal diabetes mellitus / 中国新生儿科杂志

Objective:To study the clinical features, genetic characteristics and prognosis of neonatal diabetes mellitus (NDM).Methods:From January 2015 to January 2022, neonates with NDM admitted to the Department of Neonatology of our hospital were retrospectively reviewed.Their clinical manifestations, biochemical data, genetic tests, treatments and outcomes were analyzed.Results:A total of 6 cases with NDM were included, with 3 males and 3 females. All 6 cases were full-term infants, 5 were low birth weight infants and 1 had family history of diabetes. High blood glucose were found on 1~11 d (average 4 d) after birth. 3 cases were diagnosed during blood glucose screening for low birth weight and 3 cases were diagnosed due to infection and/or diabetic ketoacidosis. Blood C-peptide levels were below normal range in all 6 cases. Blood insulin levels were decreased in 5 cases and remained at the lower limit of normal range in 1 case. All infants received genetic tests and 4 showed abnormal results, including 2 cases of ABCC8 gene mutation [c.2060C>T (p.T687M), not reported; c.674T>C (p.L225P), reported], 1 case of KCNJ11 gene mutation [c.602G>A (p.Arg201His), not reported] and 1 case of paternal uniparental disomy (UPD)6q24 (reported). All 6 cases were treated with insulin. Glibenclamide was experimented to replace insulin in 3 cases and 1 case was successful. During follow-up (at the age 4 months~5 years old), 4 cases were diagnosed with transient NDM, 1 case with permanent NDM and 1 case died at the age of 4 months without classification. 1 case showed psychomotor and language delay and the others had otherwise normal development.Conclusions:Most NDM infants are low birth weight infants with reduced blood insulin and C-peptide.Transient NDM are common. Proactive genetic testing may help treatment.

The effects of a novel brain-derived peptide HIBDAP regulating the pyroptosis of oxygen-glucose deprived microglia / 中国新生儿科杂志

Objective:To study the role of a novel brain-derived peptide hypoxic-ischemic brain damage associated peptide (HIBDAP) in regulating pyroptosis of oxygen-glucose deprived (OGD) microglia.Methods:The sequence of HIBDAP was coupled with the sequence of cell-penetrating peptide transactivator of transcription (TAT) to form TAT-HIBDAP. Fluorescein isothiocyanate (FITC) labeled TAT-HIBDAP was added to microglia cells and observed under fluorescence microscope. Microglia cells were treated with different concentrations of TAT-HIBDAP (1, 5, 10, 20 μmol/L) and then OGD process. Cell pyroptosis was analyzed using lactate dehydrogenase (LDH) assay. The concentration of TAT-HIBDAP with the most prominent inhibiting effects was determined and selected for subsequent experiments. The pyroptosis morphology of the control group, the OGD group and the HIBDAP group (5 μmol/L TAT-HIBDAP+OGD) was observed using transmission electron microscope. The mRNA and protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes were examined using real-time quantitative PCR and Western Blot analysis.Results:Fluorescence microscope showed FITC-labeled TAT-HIBDAP could successfully enter microglia cells. Compared with the OGD group, low concentrations of TAT-HIBDAP (1, 5, 10 μmol/L) could significantly reduce microglia pyroptosis and the concentration of 5 μmol/L showed the most prominent effects. Compared with the control group, OGD group showed typical pyroptosis morphology and HIBDAP group showed significantly improved morphology. The mRNA and protein expression of NLRP3 inflammasomes in the OGD group were significantly higher than the control group and also the HIBDAP group.Conclusions:The novel brain-derived peptide HIBDAP may reduce the expression of NLRP3 inflammasomes and inhibit the pyroptosis of OGD microglia.

Value of monitoring serum t-PINP/β-CTX ratio and 25 (OH) D levels in the prevention and treatment of osteoporosis after surgery for differentiated thyroid cancer in elderly women / 中华内分泌外科杂志

Objective:To investigate the level change of serum total n-terminal propeptide of type Ⅰ precollagen (t-PINP) /type Ⅰ collagen carboxy-terminal peptide (beta-CTX) ratio, 25-hydroxyvitamin D (25-hydroxyvitamin D, 25 (OH) ) ratio, and 25-hydroxyvitamin D in elderly women with differentiated thyroid cancer (DTC) after surgery and its value in the prevention and treatment of osteoporosis (OP) .Methods:From Jan. 2020 to May. 2021, 112 elderly female postoperative DTC patients treated with thyroid stimulating hormone (TSH) suppression in Department of Endocrinology of Wenzhou Hospital of Integrative Medicine were collected for a prospective study, and the incidence of OP after 1 year of treatment was counted, and according to the incidence of OP, they were divided into incidence group ( n=78) and non-incidence group ( n=34). The general information, thyroid parameters [TSH, free triiodothyronine (FT3), free thyroxine (FT4) ], bone mineral density (BMD), and serum t-titrosine (BMD) were compared between the two groups. SPSS22.0 software was used, and the counting data was described by examples χ2 test. Grade data was expressed in u, Ridit test was used, measurement data was described in mean±standard deviation ( ±s), t test was used, Pearson correlation coefficient model was used to analyze postoperative thyroid index and serum t-PINP/β- Correlation between CTX ratio and 25 (OH) D level, and serum t-PINP after 1 year of treatment was analyzed through interaction/β- The role of CTX ratio and 25 (OH) D level in OP occurrence. Results:The incidence of OP after 1 year of TSH suppression treatment in 112 elderly female post-DTC patients in this study was 69.64% (78/112) ; serum TSH levels (0.63±0.19) mIU/ml after 1 year of treatment in patients who developed OP were lower than those in patients who did not develop OP (0.81±0.22) mIU/ml, and serum FT3 (6.15±1.71) pmol/ml and FT4 levels (24.63±4.28) pmol/ml were higher than those of patients without OP (4.32±1.29) pmol/ml and (20.36±3.70) pmol/ml ( t1=4.391, t2=5.581, t3=5.050,all P<0.05) .Serum t-PINP/β-CTX ratio (130.27±18.09) and 25 (OH) D level (20.18±4.15) ng/ml after 1 year of treatment in patients with OP were lower than those in patients without OP (148.56±20.37) and (23.36±4.36) ng/ml ( t1=4.733, t2=3.672, both P<0.05) ; serum TSH levels were positively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels, and serum FT3 and FT4 levels were negatively correlated with serum t-PINP/β-CTX ratio and 25 (OH) D levels after 1 year of treatment in patients with OP ( P<0.05) ; low serum t-PINP/β-CTX ratio after 1 year of treatment expression, and low 25 (OH) D levels showed a positive interaction in OP occurrence in a superphase multiplicative model ( P<0.05) . Conclusion:Serum t-PINP/β-CTX ratio and 25 (OH) D level are closely associated with the occurrence of OP after DTC in elderly women, and postoperative monitoring can help prevent and treat OP.

Effect of histone methylase EZH2 on proliferation and apoptosis of hypertrophic myocardial cells of AC16 / 国际生物医学工程杂志

Objective:To explore the molecular mechanism of the effect of the histone methylase zeste gene enhancer homolog 2 (EZH2) on the proliferation and apoptosis of human hypertrophic cardiomyocytes AC16.Methods:The AC16 hypertrophic cardiomyocyte model was constructed by adding angiotensin Ⅱ to the AC16 cell culture medium. The cells were divided into four groups, including the blank control group, the angiotensin Ⅱ group, the empty vector + angiotensin Ⅱ group, and the EZH2 overexpression + angiotensin Ⅱ group. The expression levels of EZH2 and brain natriuretic peptide ( BNP) genes were measured using fluorescent quantitative PCR. The EZH2, trimethylation of lysine at position 27 of histone H3 (H3K27me3), and BNP proteins expression were detected by Western Blot. The MTS method was used to detect the proliferation of AC16 cell. The Annexin V-FITC/PI double staining method was used to detect the apoptosis of AC16 cell. Results:Compared with the blank control group, the expression levels of EZH2 and H3K27me3 in the angiotensin Ⅱ group were decreased, the expression level of BNP was increased, cell proliferation was decreased, and apoptosis was increased (all P < 0.001). Compared with the empty vector + angiotensin Ⅱ group, the expression levels of EZH2 and H3K27me3 in the EZH2 overexpression + angiotensin Ⅱ group were increased, the expression level of BNP was decreased, the cell proliferation level was increased, and the apoptosis level was decreased (all P < 0.001). There was no significant difference between the angiotensin Ⅱ group and the empty vector + angiotensin Ⅱ group (all P > 0.05). Conclusions:Histone methylase EZH2 has an effect on the proliferation and apoptosis of AC16 cell, providing a reference for the treatment of myocardial hypertrophy and revealing the exact pathogenesis of myocardial hypertrophy.

Preparation of a polypeptide fluorescent probe based on aggregation induced luminescence and its application in the detection of early dental caries / 国际生物医学工程杂志

Objective:To prepare a peptide fluorescent probe based on aggregation-induced emission and to investigate its application in the detection of early caries.Methods:Eight aspartate-serine-serine (DSS) were combined with aggregation-induced emission material to prepare peptide fluorescent probes, and an artificial demineralization model was established in vitro. The samples were immersed in the peptide fluorescent probe solution for 1 min, and a fluorescence imaging system was applied to examine the tooth samples and collect images and fluorescence data. Scanning electron microscopy was also applied to observe the phenotype of the teeth, and electron microscopy was applied to detect the calcium-phosphorus ratio on the enamel surface of the teeth. Polarized light microscopy was also applied to observe the enamel area of the teeth. Results:The fluorescence intensity of demineralized teeth was clearly observed to be lower than that of normal teeth in the peptide fluorescent probe-treated area, and the difference was statistically significant ( P < 0.05). The results of scanning electron microscopy showed that the enamel surface of the demineralized group had more irregular pores, while the enamel surface of the undemineralized group was flatter with only some irregular accumulation of flakes. The results of polarized light microscopy showed that a clear birefringence could be observed in the enamel region of normal teeth, while a black area or the disappearance of the birefringence effect accompanied by a partial black dark shadow could be observed in the enamel region of demineralized teeth. Conclusions:An aggregation-induced luminescence-based peptide fluorescent probe was successfully prepared, which can precisely localize the enamel and show some application value in early caries detection.