Research advances in primary biliary cholangitis with dyslipidemia / 临床肝胆病杂志

Primary biliary cholangitis （PBC） is an autoimmune liver disease characterized by progressive and non-purulent inflammation of small- and medium-sized bile ducts in the liver. Recent studies have shown that abnormal lipid metabolism is relatively common in patients with PBC， and 76% of PBC patients have dyslipidemia. The effects and harms of dyslipidemia have attracted much attention. Lipid metabolism disorders play an important role in the progression of PBC. This article mainly reviews the research advances in the manifestation， role， diagnosis， and treatment of lipid metabolism disorders in PBC， so as to provide new ideas for the treatment of PBC.

Regulación del calcio por SERC-A antes de la enfermedad de Alzheimer y durante la misma / Calcium regulation by SERC-A before and during Alzheimer disease

Hay muchos factores implicados en la incidencia de la enfermedad de Alzheimer que, en combinación, terminan por impedir o dificultar las funciones neuronales normales. Actualmente, poco se conoce sobre la regulación del calcio, antes de la enfermedad y durante la misma. La inestabilidad interna de los niveles de calcio se asocia a un mayor riesgo vascular, condición prevalente en un gran número de individuos ya comprometidos por la enfermedad de Alzheimer. Esta revisión proporciona una reevaluación de los mecanismos moleculares de la ATPasa dependiente de Ca2+ del retículo sarcoendoplásmico (SERC-A) en la enfermedad y analiza los aspectos más destacados de la función de los canales de calcio dependientes de voltaje; de esta manera, se podrán abrir nuevas alternativas de tratamiento. Estos mecanismos de regulación son clínicamente relevantes, ya que se ha implicado la función irregular de SERC-A en diversas alteraciones de la función cerebral.

There are many factors involved in the incidence of Alzheimer's disease that, in combination, impede or hinder normal neuronal functions. Little is currently known about calcium regulation before and during the disease. Internal instability of calcium levels is associated with increased vascular risk, a prevalent condition in a high number of individuals already compromised by Alzheimer's disease. This review provides a reevaluation of the molecular mechanism of the sarcoendoplasmic reticulum calcium ATPase (SERC-A) in the disease and discusses salient aspects of voltage-gated calcium channel function; in these way new alternatives could be open for its treatment. These regulation mechanisms are clinically relevant since the irregular functions of SERC+A has been implicated in pathologies of brain function.

El ayuno intermitente y sus efectos en la salud metabólica en humanos / Intermittent fasting and human metabolic health

Intermittent fasting (IF) has gained increasing scientific and general attention. Most studied forms of IF include alternate-day fasting, modified alternate-day fasting, and time-restricted eating (TRE). Several cardiometabolic effects of IF have been described in animal models and, to a lesser extent, in humans. This review analyzes the impact of IF on weight loss, glucose metabolism, blood pressure, and lipid profile in humans. A literature search was conducted in the Pubmed/Medline, Scopus, and Google Scholar databases. Controlled observational or interventional studies in humans, published between January 2000 and June 2021, were included. Studies comparing IF versus religious fasting were not included. Most studies indicate that the different types of IF have significant benefits on body composition, inducing weight loss and reducing fat mass. Changes in cardiometabolic parameters show more divergent results. In general, a decrease in fasting glucose and insulin levels is observed, together with an improved lipid profile associated with cardiovascular risk. High heterogeneity in study designs was observed, particularly in studies with TRE, small sample sizes, and short-term interventions. Current evidence shows that IF confers a range of cardiometabolic benefits in humans. Weight loss, improvement of glucose homeostasis and lipid profile, are observed in the three types of IF protocols evaluated.

Research advances in ferroptosis in the pathogenesis and treatment of nonalcoholic fatty liver disease / 临床肝胆病杂志

Ferroptosis is a pattern of non-apoptotic cell death characterized by iron dependence and lipid peroxidation. Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease with fat infiltration as its main pathological feature, and it is closely associated with insulin resistance and genetic susceptibility. The mechanism of transition from hepatic steatosis alone to steatohepatitis remains unclear, and studies have shown that ferroptosis in hepatocytes may be the trigger for the inflammatory initiation of steatohepatitis. This article reviews the role of abnormal iron metabolism and lipid peroxidation in promoting the development and progression of NAFLD and summarizes the application prospect of ferroptosis-related inhibitors in the treatment of NAFLD.

Prevalence of dyslipidemia, atherogenic and cardiovascular risk in overweight and obese adolescents / Prevalência de dislipidemia, risco aterogênico e cardiovascular em adolescentes com sobrepeso e obesidade

Abstract Objective: To analyze the lipid profile and cardiovascular risk of overweight and obese adolescents and correlate the findings with anthropometric measurements. Methods: This is a cross-sectional study on overweight and obese adolescents of both sexes (aged 14 to 18 years old). The collected variables were sex, weight, height, age, total cholesterol, triglycerides, High-density lipoprotein (HDL) and low-density lipoprotein (LDL). The Atherogenic Index of Plasma and Castelli Risk Indices I and II were calculated. These indices were classified into cutoff points to stratify cardiovascular risk. The anthropometric profile was evaluated by Z score according to Body Mass Index for age. Significance level was considered as p≤0.05. Results: A total of 146 adolescents participated in the study; the mean age was 16.4±1.1 years and most of them were girls (74.7%) and obese (52.7%). The prevalent dyslipidemias were high triglycerides (47.9%), LDL (26.7%), total cholesterol (37.7%), and low HDL (46.6%). Most adolescents presented increased atherogenic risk according to the Atherogenic Index of Plasma (55.5%); 15.1% presented high cardiovascular risk according to Castelli Risk Index I; and 13.7%, according to Castelli Risk Index II. Boys presented higher values of anthropometric measurements and Castelli Risk Indices I and II in relation to girls — who, conversely, presented higher values of HDL. There was a positive correlation of the Z score with Atherogenic Index of Plasma and a negative correlation with HDL. Conclusions: The adolescents of the study presented high prevalence of cardiovascular and atherogenic risk according to the evaluated indices. In addition, the increased cardiovascular risk was correlated with higher Body Mass Index.

RESUMO Objetivo: Analisar o perfil lipídico e os índices de risco cardiovascular de adolescentes com sobrepeso e obesidade e correlacionar os achados com medidas antropométricas. Métodos: Estudo transversal com adolescentes com sobrepeso ou obesidade de ambos os sexos (14 a 18 anos). Foram coletadas as variáveis: sexo, peso, altura, idade, colesterol total, triglicerídeos, lipoproteína de alta densidade (HDL-c) e lipoproteína de baixa densidade (LDL-c). Calcularam-se o índice aterogênico plasmático e os índices de Castelli I e II. Eles foram classificados em pontos de corte para estratificar o risco cardiovascular. O perfil antropométrico foi avaliado por meio do escore Z com base no índice de massa corporal para a idade. Considerou-se o nível de significância p≤0,05. Resultados: Foram incluídos 146 adolescentes, com média de idade de 16,4±1,1 anos, a maioria do sexo feminino (74,7%) e obesa (52,7%). As dislipidemias prevalentes foram: triglicerídeos (47,9%), LDL-c (26,7%), colesterol total (37,7%) elevado e HDL-c baixo (46,6%). A maioria apresentou risco aterogênico aumentado pelo índice aterôgenico plasmático (55,5%); 15,1% apresentaram alto risco cardiovascular segundo o índice de Castelli I e 13,7%, segundo o índice de Castelli II. Os meninos apresentaram valores superiores de medidas antropométricas e índices de Castelli I e II em relação às meninas, que, por outro lado, apresentaram valores superiores de HDL-c. Houve correlação positiva do escore Z com o índice aterôgenico plasmático e negativa com HDL-c. Conclusões: Os adolescentes do estudo apresentaram alta prevalência de risco cardiovascular e aterogênico conforme os índices avaliados. Além disso, o risco cardiovascular aumentado foi correlacionado com maior índice de massa corporal.

Alteraciones de la fracción lipídica en los pacientes quemados

Introducción: Las alteraciones lipídicas constituyen un marcador de mal pronóstico y en los últimos tiempos se ha postulado como marcador biológico en la evolución de los pacientes grandes quemados. Objetivo: Determinar las alteraciones de la fracción lipídica en los pacientes quemados. Métodos: Se realizó un estudio analítico, prospectivo y de corte longitudinal con el objetivo de determinar las alteraciones de la fracción lipídica en los pacientes quemados ingresado en el Hospital Universitario Manuel Ascunce Domenech de la ciudad Camagüey, en el período comprendido desde enero de 2019 hasta el mes de febrero de 2022. Se estudiaron 30 pacientes en quienes se tuvieron en cuenta las variables: índice de gravedad, las cifras del colesterol sérico y de los triglicéridos, el por ciento de superficie corporal quemada, los patrones lipídicos, la sepsis y el estado al egreso. Resultados: Las cifras medias más bajas de colesterol sérico y las cifras medias más altas de triglicéridos ocurrieron en aquellos pacientes con más de un 30 por ciento de superficie corporal quemada. En los pacientes con índice de gravedad de muy grave, crítico y crítico extremo fue donde se registraron las cifras más bajas de colesterol. En los períodos evolutivos de siete a 14 días los estados de triglicéridos altos se encontraron en grupos de pacientes muy graves y crítico extremos con cinco pacientes en cada grupo, lo que representa el 16,67 % y cuatro pacientes críticos para el 13,33 %. Del total de los pacientes estudiados, en 13 de ellos se presentó un patrón lipídico formado por colesterol bajo con triglicéridos altos, y el 40 % de este grupo presentaron sepsis. Conclusiones: Los grandes quemados presentan alteraciones importantes en el metabolismo de los lípidos con consecuencias desfavorables en su evolución.

Introduction: The lipid alterations constitute a marker of bad forecast and in recent times it has run for candidate like biological marker in the evolution of the big burnt patients. Objective: To determine the alterations of the lipid fraction in the burned patients. Methods: An analytic, prospective and of longitudinal study was carried out for the sake of determining the alterations of the lipid fraction in the burned patient entered in the Hospital Universitario Manuel Ascunce Domenech of the city Camagüey, in the period understood since January of the 2019 to the month of February of 2022. They studied 30 patients in those who had into account variables: Severity rate, the figures of the serum cholesterol and of the triglycerides, the percent of corporal burned-out surface, the lipid patterns, the sepsis and the state to the medical release. Results: The half a lower amounts of serum cholesterol and the figures the more tall stockings of triglycerides happened in those patients with over 30 percent of corporal burned-out surface. In the patients with severity rate of very severe, critic and the extreme critic was where lower the figures of cholesterol got registered. In the evolutionary periods of seven to 14 days the states of tall triglycerides met fundamentally very seriously ill patients' groups, and critic extreme with five patients in each group, what represents the 16.67 % and four critical patients for the 13.33 %. Of the total of the patients studied, in 13 of them a lipid pattern educated by cholesterol bass with tall triglycerides showed up, and 40 % of this group presented sepsis. Conclusions: The great burned-out patients present important alterations in the metabolism of the lipids with unfavorable consequences in their evolution.

Study of auditory pathways in type 1 diabetes mellitus through brainstem auditory evoked potentials and contralateral acoustic reflex / Estudo das vias auditivas em diabetes mellitus tipo 1 através dos potenciais auditivos evocados de tronco encefálico e reflexo acústico contralateral

ABSTRACT Purpose To investigate the functionalities of the neural pathways through the auditory evoked potentials of the brainstem and the contralateral stapedial acoustic reflexes in normal-hearing individuals with type 1 diabetes mellitus, in order to detect possible alterations in the central auditory pathways. Methods This is a cross-sectional study with a comparison group and a convenience sample, consisting of 32 individuals with type 1 diabetes mellitus and 20 controls without the disease. All subjects had hearing thresholds within normal limits and type A tympanometric curves. The acoustic reflex arc and brainstem auditory potentials were investigated. Statistical analyses were performed using the SPSS 17.0. The Chi-square test, Student´s t-test, and Multiple linear regression were used. Results The auditory thresholds of the acoustic reflex were statistically lower in the group with the disease at frequencies of 0.5 kHz and 1.0 kHz in the left ear (p=0.01 and p=0.01, respectively). The absolute latencies III and V of the auditory potentials of the brainstem in the right ear and V in the left ear were increased in subjects with type 1 diabetes mellitus (p=0.03, p=0.02 and p=0.03, respectively). Conclusion The findings suggest that subjects with type 1 diabetes mellitus are more likely to present alterations in the central auditory pathways, even with auditory thresholds within normal limits.

RESUMO Objetivo Investigar a funcionalidade das vias neurais por meio dos potenciais evocados auditivos de tronco encefálico e os reflexos acústicos estapedianos contralaterais em sujeitos com diabetes mellitus tipo 1 normo-ouvintes, a fim de detectar possíveis alterações nas vias auditivas centrais. Método Trata-se de um estudo transversal com grupo de comparação, e amostra de conveniência, composta por 32 sujeitos com diabetes mellitus tipo 1 e 20 controles sem a doença. Todos os sujeitos apresentavam limiares auditivos dentro dos padrões de normalidade e curva timpanométrica tipo A. Foram investigados o arco-reflexo acústico e os potenciais auditivos de tronco encefálico. As análises dos resultados foram realizadas no SPSS 17.0. Utilizou-se o Teste Qui Quadrado, Teste T de Studant e Regressão linear múltipla. Resultados Os limiares auditivos do reflexo acústico foram estatisticamente menores no grupo com a doença nas frequências de 0,5 kHz e 1,0 kHz na orelha esquerda (p=0,01 e p=0,01, respectivamente). As latências absolutas III e V dos potenciais auditivos de tronco encefálico da orelha direita e V da orelha esquerda estavam aumentadas em sujeitos com diabetes mellitus tipo 1 (p=0,03, p=0.02 e p=0,03, respectivamente). Conclusão Os achados sugerem que sujeitos com diabetes mellitus tipo 1 estão mais propensos a apresentar alterações nas vias auditivas centrais, mesmo com limiares auditivos dentro dos padrões de normalidade.

Complicaciones endocrinológicas del síndrome de down en pediatría: revisión de la literatura

El síndrome de Down constituye la cromosopatía más frecuente a nivel mundial y afecta 6,03 a 7,86 de cada 10.000 nacidos vivos en Colombia. Los pacientes pediátricos de este grupo poblacional presentan una mayor incidencia de complicaciones endocrinológicas comparados con la población general. El objetivo de este artículo es revisar las complicaciones endocrinológicas prevalentes en el paciente pediátrico con síndrome de Down, relacionadas con el hipocrecimiento, desarrollo puberal, patología tiroidea, diabetes mellitus, dislipidemias y obesidad; así como describir su seguimiento y tratamiento. Se realizó una búsqueda en la literatura desde agosto de 2020 hasta diciembre de 2021, en las bases de datos PubMed y Google Scholar; incluyendo un total de 44 publicaciones para la presente revisión. Se concluye que el paciente pediátrico con síndrome de Down evidencia un patrón de hipocrecimiento junto a un mayor riesgo de obesidad y sobrepeso. Adicionalmente, presenta con mayor frecuencia patología tiroidea y diabetes mellitus.

Down syndrome is the most common chromosomal disorder worldwide, affecting 6,03 to 7,86 per 10.000 live births in Colombia. Pediatric patients with Down syndrome have a higher incidence of endocrine disorders compared to the general population. The aim of this paper was to review the endocrinological manifestations prevalent in pediatric patients with Down syndrome related to small stature, pubertal development, thyroid dysfunction, diabetes mellitus, dyslipidemia, and obesity. Additionally, their follow-up and adequate treatment are described. A literature search was carried out from August 2020 to December 2021 in the PubMed and Google Scholar databases. A total of 44 publications were included for this review. It is concluded that pediatric patients with Down syndrome are more likely to have short stature and have a higher risk of obesity and overweight. In addition, thyroid dysfunction and diabetes mellitus are frequent complications.

Diabetes mellitus y ataxia de Friedreich en un niño: una difícil coexistencia / Diabetes mellitus and Friedreich´s ataxia in a child: a complicated coexistence

La ataxia de Friedreich, de herencia autosómica recesiva causada por una expansión repetida de trinucleótidos se asocia, entre otras complicaciones sistémicas, con diabetes mellitus. La aparición de torpeza motriz, con dificultad en la carrera y el salto en un varón de 6 años motivaron el estudio genético para ataxia de Friedrich y permitieron confirmar el diagnóstico. Tres años más tarde, se diagnosticó diabetes mellitus y se inició el tratamiento con insulina. Durante el seguimiento, presentó un importante deterioro neurológico, con necesidad de usar silla de ruedas, lo que dificultó un adecuado control metabólico. Se presenta el manejo y la evolución de un paciente con ataxia de Friedreich y diabetes mellitus

Friedreich's ataxia is an autosomal recessive disease caused by trinucleotide repeat expansion, presenting among other systemic complications, diabetes mellitus. The appearance of motor clumsiness, with running and jumping difficulties in a 6-year-old boy prompted the genetic study of Friedreich's ataxia, confirming his diagnosis. After diagnosis,it was evaluated by Pediatric Cardiology, detecting the presence of non-obstructive hypertrophic cardiomyopathy, and by Pediatric Endocrinology, due to overweight. At 9 years of age, he was diagnosed with diabetes mellitus, a regimen of insulin treatment was initiated. During follow-up, he presented significant neurological deterioration, reaching the use of a wheelchair,which hinders adequate metabolic control. This is a report of a pediatric patient with Friedrich ataxia and diabetes mellitus.

A study on the relationship between serum transferrin and prognosis of elderly patients with sepsis / 中华老年医学杂志

Objective:To investigate the relationship between serum transferrin(TRF)and the characteristics and prognosis of elderly patients with sepsis.Methods:A retrospective analysis was conducted on 49 elderly patients with sepsis treated at the Department of Critical Medicine and the Department of Respiratory and Critical Medicine of the First Affiliated Hospital of Suzhou University between October 2020 and March 2022 who had met the inclusion criteria.These patients were divided into a shock group(n=18)and a non-shock group(n=31); Based on outcomes, they were also divided into a death group(n=16)and a survival group(n=33).Through the random number table method, 30 healthy elderly people from the physical examination center of our hospital were selected as the control group.TRF and ferritin(SF)were measured on the 1st, 3rd and 7th day after admission, and the correlation between TRF and the sequential organ failure assessment score(SOFA)was analyzed.The predictive value of TRF on prognosis was evaluated via the receiver operating characteristic curve.Finally, the influence of multiple factors on prognosis was analyzed using the binary logistic regression model.Results:Compared with the control group at admission, SF levels of elderly patients with sepsis increased[709.20(402.40, 2000.00)μg/L vs.102.05(79.55, 199.75)μg/L, Z=-5.482, P<0.01], but TRF levels decreased[1.43(1.12, 1.72)g/L vs.2.23(1.80, 3.12)g/L, Z=5.395, all P<0.01], with statistical significance.On the 3rd and 7th day, TRF levels in the shock group were lower than in the non-shock group[(1.25±0.35)g/L vs.(1.55 ±0.51)g/L, 1.15(9.68, 1.34)g/L vs.1.56(1.19, 2.03)g/L]( t=-2.186, Z=3.258, P<0.05).There was a linear correlation between TRF and SOFA score on the 1st, 3rd and 7th day( R2=0.177, 0.176, 0.275, all P<0.01).TRF levels in the death group were lower than in the survival group on the 3rd and 7th day( Z=2.208, 3.423, P<0.05 for both).TRF levels on the 3rd and 7th day in elderly patients with sepsis had predictive value in evaluating the prognosis[area under receiver operating characteristic curve( AUC)values=0.696, 0.804, P<0.05, P<0.01].The survival curves based upon the best cutoff values(TRF=1.085 g/L on the 3rd day, TRF=1.330 g/L on the 7th day)between the two groups were statistically significantly( χ2=10.903, 13.318, P<0.01 for both).With TRF<1.085 g/L on the 3rd day, the risk of death in elderly patients with sepsis on the 28th day was 9.388 times the usual risk( OR=9.388, P<0.01), and with TRF<1.330 g/L on the 7th day, the risk of death was 14.625 times the usual risk on the 28th day( OR=14.625, P<0.01). Conclusions:Increased SF in elderly patients with sepsis is not related to disease severity, but the level of TRF is related to disease severity, and the level of TRF on the 3rd and 7th day is related to the prognosis and is an independent risk factor for all-cause death on the 28th day.

Effects of early-life exposure to angiotensinⅡ type 1 receptor autoantibody on lipid metabolism in offspring rats / 中华围产医学杂志

Objective:To investigate the effects of early-life (intrauterine and breastfeeding period) exposure to angiotensin Ⅱ type 1 receptor autoantibody (AT 1-AA) on lipid metabolism in offspring rats. Methods:Thirty-two AT 1-AA negative healthy nonpregnant specific pathogen free female Sprague Dawley rats weighing 150-170 g were randomly divided into two groups. Those in the immune group ( n=16) were subcutaneously injected with the mixture of an equal volume of Freund's adjuvant and the second extracellular loop of human-derived angiotensin Ⅱ receptor type 1 (AT1R-ECⅡ) repeatedly to establish the AT 1-AA-positive rat model by active immunization and those in the control group ( n=16) with normal saline solution. Before each immunization, blood samples were collected from the tail of rats to detect serum AT 1-AA levels of those rats in both groups, and the AT 1-AA-positive rat model was successfully established when the serum AT 1-AA was positive and its level reached a plateau. After eight weeks of immunization, the female rats in the two groups were mated with healthy AT 1-AA-negative male rats to conceive. Serum samples were collected from the maternal and offspring rats at the gestation of 18 days (G18), postnatal 21 days (P21), and from the normally fed offspring rats from the time of weaning to 12 weeks old (W12). Active immunization was not performed on the offspring throughout the experiment. The serum AT 1-AA levels of maternal and offspring rats were determined by enzyme-linked immunosorbent assay, and serum AT1-AA was positive when the ratio of AT1-AA level of the immune group over the control group ≥2.1. The blood lipid levels of maternal and offspring rats were measured by an automatic biochemical analyzer. Serum AT 1-AA levels, total cholesterol (TC), high-density lipoprotein-cholesterol [instead of high-density lipoprotein (HDL)], low-density lipoprotein-cholesterol, and free fatty acid levels of the offspring and maternal rats were determined for correlation analysis. Two independent sample t-test, linear regression analysis, and analysis of variance were adopted for statistical analysis. Results:(1) The serum levels of AT 1-AA in maternal rats at G18 and P21 in the immune group were significantly higher than those in the control group (G18: 1.170±0.190 vs 0.114±0.016, t=14.64; P21: 0.988±0.283 vs 0.084±0.006, t=9.57; both P<0.001). (2) The serum levels of AT 1-AA in the offspring at G18 and P21 in the immune group were significantly higher than those in the control group (offspring at G18: 0.948±0.220 vs 0.105±0.010, t=10.10; male offspring at P21: 0.758±0.273 vs 0.080±0.002, t=7.46; female offspring at P21: 0.774±0.274 vs 0.084±0.005, t=7.55; all P<0.001), which showed a positive correlation with those in maternal rats at the same period (offspring at G18: R=0.78; male offspring at P21: R=0.82; female offspring at P21: R=0.82; all P<0.05). However, there was no significant difference in the serum AT 1-AA level in offspring at W12 between the immune and control group ( P>0.05). (3) The serum levels of TC at G18 and P21, and HDL at P21 in maternal rats in the immune group were all higher than those in the control group [TC at G18: (2.36±0.32) vs (1.95±0.24) mmol/L, t=2.70; P21: (2.82±0.50) vs (2.18±0.26) mmol/L, t=3.41; HDL at P21: (1.94±0.33) vs (1.57±0.23) mmol/L, t=2.80; all P<0.05]. (4) Compared with the offspring in the control group, there was no significant change in lipid metabolism at G18 and W12 in the offspring in the immune group (both P>0.05). The serum levels of TC and HDL in male and female offspring at P21 in the immune group were higher than their counterparts in the control[TC in male offspring: (2.38±0.52) vs (1.83±0.30) mmol/L, t=2.73; HDL in male offspring: (1.44±0.32) vs (1.07±0.18) mmol/L, t=2.98; TC in female offspring: (2.50±0.72) vs (1.70±0.26) mmol/L, t=3.16; HDL in female offspring: (1.41±0.33) vs (1.00±0.14) mmol/L, t=3.41; all P<0.05]. (5) The serum levels of TC and HDL in male and female offspring at P21 in the immune group showed no correlation with those in maternal rats at P21 (all R<0.5, all P>0.05). The serum levels of HDL in male and female offspring at P21 in the immune group had a positive correlation with their own serum TC levels (male offspring: R=0.98; female offspring: R=0.97; both P<0.001) and also with their own serum AT 1-AA levels (male offspring: R=0.74, P=0.023; female offspring: R=0.91, P=0.001). The serum levels of TC in male and female offspring at P21 in the immune group had a positive correlation with their serum AT 1-AA levels (male offspring: R=0.72, P=0.030; female offspring: R=0.90, P=0.001). Conclusion:The early-life exposure to AT 1-AA may cause abnormal expression of TC and HDL in offspring rats.

Effects of iron metabolism and oxidative stress level on blood glucose control during pregnancy in patients with gestational diabetes mellitus / 中国基层医药

Objective:To investigate the effects of iron metabolism and oxidative stress level on blood glucose control during pregnancy in patients with gestational diabetes mellitus (GDM).Methods:A total of 139 pregnant women who received prenatal examination between January 2020 and June 2021 in Wenzhou Central Hospital were included in this study. They were divided into GDM group ( n = 68) and control group ( n = 71) according to oral glucose tolerance test results at 24-48 weeks of gestation. Clinical data were collected. Iron metabolism, oxidative stress and blood glucose levels were measured. The relationships between iron metabolism and oxidative stress levels and blood glucose control in GDM were analyzed. Results:There was no significant difference in age between the GDM and control groups ( P > 0.05). Body mass index, fasting blood glucose, fasting insulin, glycosylated hemoglobin, nuclear factor-κB (NF-κB), malondialdehyde (MDA), ferritin (SF), serum iron, transferrin (TRF) and insulin resistance index (IRI) in the GDM group were (24.11 ± 3.05) kg/m 2, (4.92 ± 0.67) mmol/L, (10.56 ± 2.21) pmol/mL, (6.15 ± 0.62)%, (20.50 ± 1.72) μg/L, (20.34 ± 2.92) μmol/L, (70.77 ± 7.01) μg/L, (30.18 ± 4.25) μmol/L, (3.93 ± 0.69) g/L and (2.50 ± 1.03), respectively, which were significantly higher than those in the control group [(21.41 ± 2.86) kg/m 2, (4.69 ± 0.62) mmol/L, (5.76 ± 2.09) pmol/mL, (5.37 ± 0.58)%, (15.43 ± 1.55) μg/L, (12.93 ± 2.17) μmol/L, (42.53 ± 8.86) μg/L, (18.81 ± 3.85) μmol/L, (2.89 ± 0.53) g/L and (1.74 ± 0.89)] ( t = 5.39, 2.10, 13.16, 7.66, 18.27, 17.03, 20.78, 16.54, 9.99, 4.66, all P < 0.05). Superoxide dismutase (SOD), total antioxidant capacity (TAOC) and insulin sensitivity index in the GDM group were (21.49 ± 3.52) U/L, (10.87 ± 1.34) kU/L and (3.28 ± 0.46), respectively, which were significantly lower than those in the control group [(26.28 ± 3.95) U/L, (13.28 ± 1.52) kU/L, (3.86 ± 0.53), t = 7.54, 9.90, 6.88, all P < 0.05]. Multivariate logistic regression analysis revealed that SOD, TAOC, NF-κB, MDA, SF and TRF were independent influential factors of GDM occurrence [ OR (95% CI) = 1.57 (1.09-2.26), 3.15 (1.71-5.80), 2.18 (1.32-3.61), 3.27 (1.58-6.76), 2.12 (1.29-3.50), 1.23 (0.99-1.53), 3.65 (1.89-7.04), all P < 0.05]. SOD and TAOC levels were negatively correlated with IRI ( r = -0.75, -0.84, both P < 0.05), while NF-κB, MDA, SF, serum iron and TRF were positively correlated with IRI ( r = 0.93, 0.96, 0.98, 0.07, 0.92, all P < 0.05). Conclusion:Increased levels of iron metabolism and oxidative stress are risk factors for the occurrence of GDM, and they are closely related to the degree of insulin resistance. GDM screening should be carried out in advance in pregnant women with increased levels of iron metabolism and oxidative stress indicators, which plays a positive role in clinical diagnosis and treatment of GDM.

Mori Folium Improves Glucose and Lipid Metabolism Disorders in Rats with Type 2 Diabetes Mellitus by Regulating PI3K/Akt/PPARα/CPT-1 Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Mori Folium extract on the glucose and lipid metabolism disorders in the liver of rats with type 2 diabetes mellitus （T2DM） through the phosphatidylinositol 3-kinase/protein kinase B/peroxisome proliferation-activated receptor α/carnitine palmitoyl transferase-1 （PI3K/Akt/PPARα/CPT-1） signaling pathway. MethodThe T2DM model was induced by the high-fat diet combined with the intraperitoneal injection of streptozotocin （STZ）. The model rats were randomly divided into a model group， a metformin （0.2 g·kg-1） group， and a Mori Folium water extract （4.0 g·kg-1） group according to blood glucose and body weight. In the 8-week administration， fasting blood glucose was measured at the same time every week. The histomorphological and fat changes in the rat liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum were measured by biochemical methods. Western blot （WB） was used to quantitatively detect the protein expression of p-PI3K，PI3K，p-Akt，Akt，PPARα，and CPT-1 in the rat liver. ResultAfter 8-week administration， the blood glucose of rats was higher in the model group than that in the control group （P<0.01）， and lower in the Mori Folium water extract group than that in the model group （P<0.01）. The results of HE staining showed that the liver tissue structure of the control group was complete， and the hepatocytes were arranged radially around the central vein， while the hepatocyte injury in the model group was obvious. Compared with the model group， the Mori Folium water extract group showed improved vacuolar degeneration and no lesions such as small bile duct hyperplasia. Oil red O staining showed that there was no obvious steatosis and necrosis in the hepatocytes of rats in the control group， and no lipid droplets in the hepatocytes were observed， while the model group showed increased lipid droplets. Mori Folium significantly reduced the lipid droplets in the liver. Biochemical analysis showed that the levels of TC， TG， LDL-C， AST， and ALT in the model group were significantly higher than those in control group （P<0.01）. The levels of TC， TG， LDL-C， AST， and ALT in the Mori Folium water extract group were significantly lower than those in the model group （P<0.05，P<0.01）. WB showed that the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 in the model group were lower than those in the control group （P<0.01）. Mori Folium water extract could increase the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 （P<0.05 or P<0.01）. ConclusionThe hypoglycemic mechanism of Mori Folium water extract may be related to the regulation of the PI3K/Akt/PPARα/CPT-1 signaling pathway.

Xiaoyao San, a Chinese herbal formula, ameliorates depression-like behavior in mice through the AdipoR1/AMPK/ACC pathway in hypothalamus / 中西医结合学报

OBJECTIVE@#Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.@*METHODS@#An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.@*RESULTS@#XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.@*CONCLUSION@#Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

The strategy change of targeting iron homeostasis for leukemia therapy: from iron chelation to iron overload as a therapeutic strategy to induce ferroptosis / 白血病·淋巴瘤

Iron, an indispensable element for life, is involved in all kinds of vital physiological activities. Due to its potential toxicity, the body has a strict regulation mechanism of iron metabolism to maintain the "iron homeostasis". Dysregulation of iron metabolism and subsequent accumulation of excess iron are closely associated with the development and progression of leukemia. Specifically, due to the pro-oxidative nature of iron and its damaging effects on DNA, excess iron promotes the progression of leukemia; on the other hand, leukemia cells need to obtain more iron than normal cells to maintain rapid growth and proliferation, which is known as "iron addiction". Iron chelators can remove iron in leukemia cells and induce differentiation and apoptosis of leukemia cells. However, "iron addiction" makes leukemia cells more susceptible to iron overload, and is more sensitive to a new form of iron-catalyzed cell death which was named ferroptosis. According to the different needs of leukemia cells and normal cells for iron, the method of selectively killing leukemia cells through iron overload may become a new strategy for leukemia treatment. This paper reviews the strategy of targeting iron homeostasis for leukemia therapy.

Research progress in influence of intrauterine hyper androgen on offspring health and mechanisms / 中华围产医学杂志

Maternal adverse endocrine environment severely affects the growth and development of offspring. This article reviews relevant cohort studies and animal experiments on the influence of intrauterine hyper androgen on offspring health and the mechanisms, aiming to provide a new perspective for further research, mechanism exploration, and early interventions in this field.

Exposure to glyphosate-based herbicide during early stages of development increases insulin sensitivity and causes liver inflammation in adult mice offspring

ABSTRACT Objective: To investigate the effect of pre and postnatal exposure to a glyphosate-based herbicide on glucose metabolism and liver histology in adult F1 mice offspring. Methods: Female mice (C57Bl/6) received 0.5% of glyphosate (Roundup Original DI®) in drinking water or purified water (Glyphosate Group and Control Group respectively) during pregnancy and lactation. Offspring (F1) were submitted to glucose and insulin tolerance tests and euthanized on postnatal day 150. Body and plasma parameters, and liver histology were analyzed. Results: Exposure to glyphosate reduced maternal body weight gain during pregnancy and lactation, with no impacts on litter size. Pre and postnatal exposure to glyphosate did not affect body parameters but increased glucose tolerance on postnatal day 60. In spite of glucose tolerance normalization by postnatal day 143, this effect was associated with higher insulin sensitivity relative to mice in the Control-F1 Group. Mice in the Glyphosate-F1 Group had mild and moderate lobular inflammation in the liver. Conclusion: Maternal exposure to glyphosate affected insulin sensitivity and caused hepatic inflammation in adult F1 mice offspring.

Brazilian family with hyperferritinemia-cataract syndrome: case report

ABSTRACT Hereditary hyperferritinemia-cataract syndrome is a rare autosomal dominant disease caused by a genetic mutation in the iron responsive element in the 5' untranslated region of the ferritin light chain gene. Hereditary hyperferritinemia-cataract syndrome is characterized by elevated serum ferritin levels and bilateral cataract development early in life and may be misdiagnosed as hemochromatosis. This case report describes a Brazilian family with a clinical diagnosis of hereditary hyperferritinemia-cataract syndrome, which was submitted to ferritin light chain gene sequencing. The genetic mutation c.-164C>G was identified in the 5' untranslated region. In conclusion, genetic testing can be used for accurate diagnosis of hereditary hyperferritinemia-cataract syndrome to avoid misdiagnosis of hemochromatosis, other diseases associated with iron overload or ophthalmic diseases.

Agrupamentos de fatores de risco cardiometabólicos e sua associação com aterosclerose e inflamação crônica em adultos e idosos em florianópolis, Sul do Brasil / Clusters of cardiometabolic risk factors and their association with atherosclerosis and chronic inflammation among adults and elderly in florianópolis, Southern Brazil

Resumo Fundamento O aumento significativo de doenças cardiovasculares em países em desenvolvimento alerta sobre seu impacto em populações carentes. Objetivo Identificar a relação de agrupamentos de componentes da síndrome metabólica (SM) com aterosclerose e inflamação crônica em adultos e idosos. Métodos Análise transversal usando dados de dois estudos populacionais de tipo coorte realizados em Florianópolis, sul do Brasil (EpiFloripa Adult Cohort Study, n = 862, 39,9±11,5 anos; EpiFloripa Aging Cohort Study, n = 1197, 69,7±7,1 anos). Pressão arterial (PA), circunferência da cintura (CC), e níveis plasmáticos de lipídio e glicose foram analisados como fatores individuais ou como agrupamentos de componentes da SM (como número de componentes presentes em um indivíduo ou como combinações). Os desfechos incluíram espessura intima-media carotídea (EIMC), placas ateroscleróticas, e níveis de proteína C reativa (CRP). Regressão linear múltipla e regressão logística, ajustadas quanto aos fatores de confusão, foram usadas para análise. O nível de significância adotado foi de 5%. Resultados Indivíduos com PA e CC elevadas, dislipidemia e hiperglicemia (61,5%) apresentaram maiores valores de EIMC e PCR que aqueles que não apresentaram componentes de SM. CC elevada foi um determinante comum de inflamação sistêmica, ao passo que a coexistência de PA elevada e CC elevada (agrupamentos de dois ou três fatores) associou-se com maior EIMC (β entre +3,2 e +6,1 x 10-2 mm; p < 0,05) e PCR (EXPβ entre 2,18 e 2,77; p < 0,05). Conclusão A coexistência de PA e CC elevadas associou-se com maiores valores de EIMC e níveis de PCR. A obesidade central, isolada ou em combinação com outros fatores de risco, teve efeito sobre a inflamação sistêmica.

Abstract Background The significant increase in cardiovascular diseases in developing countries alerts about their impact on underprivileged populations. Objective To identify the relationship of clusters of metabolic syndrome (MS) components with atherosclerosis and chronic inflammation among adults and elderly. Methods Cross-sectional analysis using data from two population-based cohort studies in Florianópolis, Southern Brazil (EpiFloripa Adult Cohort Study, n = 862, 39.9±11.5 years; EpiFloripa Aging Cohort Study, n = 1197, 69.7±7.1 years). Blood pressure (BP), waist circumference (WC), and lipid and glucose levels were analyzed as individual factors or as clusters (either as the number of components present in an individual or as combinations of components). Outcomes included carotid intima-media thickness (IMT), atherosclerotic plaques, and C-reactive protein (CRP) levels. Multiple linear and logistic regression analyses adjusted for confounding factors were used. The statistical significance adopted was 5%. Results Individuals with high BP, elevated WC, dyslipidemia and hyperglycemia (6.1% of the sample) showed higher IMT and CRP than those negatives for all MetS components. Elevated WC was a common determinant of systemic inflammation, while the coexistence of high BP and elevated WC (clusters of two or three factors) was associated with higher IMT (β between +3.2 and +6.1 x 10-2 mm; p value < 0.05) and CRP (EXPβ between 2.18 and 2.77; p value < 0.05). Conclusion The coexistence of high BP and elevated WC was associated with increased IMT and CRP levels, but central obesity affected systemic inflammation either alone or in combination with other risk factors.