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ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?
RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?
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Introducción La diabetes mellitus tipo 2 es una enfermedad de alta prevalencia y está asociada a mayor morbimortalidad. Debido al bajo porcentaje de compensación, se han buscado nuevas estrategias de tratamiento farmacológico, como los inhibidores del cotransportador sodio-glucosa tipo 2. Objetivo Describir la evolución de pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor, ubicado en el sector poniente de la Región Metropolitana, Chile. El objetivo primario fue evaluar la eficacia del medicamento respecto a hemoglobina glicosilada A1c. Los objetivos secundarios fueron registrar el logro de hemoglobina glicosilada A1c igual o menor a 7,5% según análisis de supervivencia. Luego, consignar el cambio en la velocidad de filtración glomerular y en la excreción urinaria de albúmina post tratamiento. Métodos Revisión de ficha clínica de todos los pacientes tratados con empagliflozina desde noviembre de 2019 a junio de 2023. Media de seguimiento de 19 (de 16,3 a 40) meses. Para comparación entre valores de hemoglobina glicosilada A1c según rangos de seguimiento, se utilizó prueba T de Student de términos pareados o prueba de Wilcoxon. Resultados Se estudió a 58 pacientes, 15 hombres y 43 mujeres (74,1%). Edad 58,5 ± 9,2 años, rango de 35 a 75 años. Hemoglobina glicosilada A1c basal de 10,3 ± 1,6% y 8,98% ± 2,2 en un rango de seguimiento de 18 a 24 meses post tratamiento, resultando en un descenso de 1,27% (p = 0,002; intervalo de confianza 95%: 0,5 a 2,03). El efecto adverso más frecuente fue infección del tracto urinario. Conclusiones Los pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor lograron un mejor control glicémico con pocos efectos adversos.
Background Type 2 diabetes mellitus is a highly prevalent disease and is associated with increased morbidity and mortality. Due to the low percentage of adequate glycemic control, new strategies for the treatment of type 2 diabetes mellitus have been sought, including sodium-glucose cotransporter type 2 inhibitorss. Objective To describe the evolution of patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital. The primary objective was to evaluate the efficacy of the medication regarding glycosylated hemoglobin A1c (HbA1c). The secondary objectives were: 1) achievement of HbA1c equal to or less than 7.5% according to survival analysis. 2) Change in glomerular filtration rate and urinary albumin excretion post treatment. Methods Review of clinical records of all patients treated with empagliflozin from November 2019 to June 2023. Average follow-up of 19 (16.3 to 40) months. To compare HbA1c values according to follow-up ranges, the paired T test or Wilcoxon test was used. Results We included 58 patients, 15 men and 43 women (74.1%), with an average age of 58.5 ± 9.2 years, ranging from 35 to 75 years. Baseline HbA1c of 10.3 ± 1.6% and 8.98% ± 2.2 in a follow-up of 18 to 24 months post-treatment, resulted in a decrease of 1.27% (p = 0.002; confidence interval 95%: 0.5 to 2.03). The most common adverse effect was urinary tract infection. Conclusions Patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital achieved better glycemic control with few adverse effects.
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ABSTRACT FGF21 is a hormone produced primarily by the liver with several metabolic functions, such as induction of heat production, control of glucose homeostasis, and regulation of blood lipid levels. Due to these actions, several laboratories have developed FGF21 analogs to treat patients with metabolic disorders such as obesity and diabetes. Here, we performed a systematic review and meta-analysis of randomized controlled trials that used FGF21 analogs and analyzed metabolic outcomes. Our search yielded 236 articles, and we included eight randomized clinical trials in the meta-analysis. The use of FGF21 analogs exhibited no effect on fasting blood glucose, glycated hemoglobin, HOMA index, blood free fatty acids or systolic blood pressure. However, the treatment significantly reduced fasting insulinemia, body weight and total cholesterolemia. None of the included studies were at high risk of bias. The quality of the evidence ranged from moderate to very low, especially due to imprecision and indirection issues. These results indicate that FGF21 analogs can potentially treat metabolic syndrome. However, more clinical trials are needed to increase the quality of evidence and confirm the effects seen thus far.
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Introducción: la diabetes mellitus tipo 2 (DM2) se define como un trastorno metabólico caracterizado por niveles de glucosa en sangre crónicamente elevados. La DM2 representa el paradigma de las enfermedades crónicas en las que existe una estrecha asociación entre factores familiares y ambientales. Por este motivo, este estudio tiene como finalidad determinar la asociación del riesgo a desarrollar DM2 y los hábitos tóxicos no ilícitos en pacientes que residen en una comunidad rural de Peravia, República Dominicana. Tales incluyen: alcohol, café y té. Metodología: Estudio observacional, transversal, analítico y prospectivo. Se aplicó cuestionario, recolectaron datos antropométricos y se determinó glucosa capilar a la muestra (n=304). Resultados: la prevalencia a presentar un alto riesgo a desarrollar DM2 en la población es de 35.5%, mientras que la prevalencia a presentar riesgo bajo es de 64.5%. En cuanto a hábitos tóxicos, no existió correlación positiva entre consumo de té y desarrollo de DM2. Sin embargo, sí entre el consumo de café y alcohol. Conclusiones: los habitantes de salinas presentan un bajo riesgo a desarrollar DM2, pero utilizan factores de riesgos modificables que aumentan la prevalencia a DM2.
Introduction: Type 2 diabetes mellitus (DM2) is defined as a metabolic disorder characterized by chronically elevated blood glucose levels. DM2 represents the paradigm of chronic diseases in which there is a close association between family and environmental factors. Therefore, the purpose of this study is to determine the association of the risk of developing DM2 and non-illicit toxic habits in patients residing in a rural community in Peravia, Dominican Republic. Such habits include alcohol, coffee and tea. Methodology: Observational, cross-sectional, analytical and prospective study. A questionnaire was applied, anthropometric data was collected, and capillary glucose was determined in the study sample (n=304). Results: the prevalence of presenting a high risk of developing DM2 in the population is 35.5%, while the prevalence of presenting low risk is 64.5%. Regarding toxic habits, there was no positive correlation between tea consumption and the development of DM2. However, this result differed between consumption of coffee and alcohol. Conclusions: the inhabitants of Salinas have a low risk of developing DM2 but are subject to modifiable risk factors that increase said prevalence.
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Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Diabetes Mellitus, Type 2 , Chronic Disease , Risk Factors , Dominican RepublicABSTRACT
OBJECTIVES@#To explore the relationship of triglyceride-glucose index (TyG), triglyceride-glucose-body mass index (TyG-BMI), and triglyceride-glucose-waist circumference index (TyG-WC) with blood pressure abnormalities in adolescents, providing theoretical basis for the prevention and control of hypertension in adolescents.@*METHODS@#A stratified cluster sampling method was used to select 1 572 adolescents aged 12 to 18 years in Yinchuan City for questionnaire surveys, physical measurements, and laboratory tests. Logistic regression analysis and restricted cubic spline analysis were employed to examine the relationship of TyG, TyG-BMI, and TyG-WC with blood pressure abnormalities in adolescents.@*RESULTS@#Multivariable logistic regression analysis revealed that after adjusting for confounding factors, the groups with the highest quartile of TyG, TyG-BMI, and TyG-WC had 1.48 times (95%CI: 1.07-2.04), 3.71 times (95%CI: 2.67-5.15), and 4.07 times (95%CI: 2.89-5.73) higher risks of blood pressure abnormalities compared to the groups with the lowest quartile, respectively. Moreover, as the levels of TyG, TyG-BMI, and TyG-WC increased, the risk of blood pressure abnormalities gradually increased (P<0.05). A non-linear dose-response relationship was observed between TyG-BMI and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.002). Linear dose-response relationships were found between TyG and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearit =0.232), and between TyG-WC and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.224).@*CONCLUSIONS@#Higher levels of TyG and its derivatives are associated with an increased risk of blood pressure abnormalities in adolescents, with linear or non-linear dose-response relationships.
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Adolescent , Humans , Blood Pressure , Body Mass Index , Hypertension/etiology , Glucose , TriglyceridesABSTRACT
Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.
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ObjectiveTo explore the effect of precocious puberty on glucose metabolism and lipid metabolism in female rats. MethodsSixty two-day-old female rats were randomly divided into 2 groups. When aged 5 days， the precocious puberty group and normal group were given a single subcutaneous injection of danazol and solvent soybean oil respectively. The vaginal opening of rats was monitored from their 21 days of age. After 12 hours of fasting， all successful modeling rats were randomly executed within 3 days after vaginal opening， when aged 7 and 12 weeks. Then we measured the rats’ body weight and length， determined the concentrations of glucose， insulin， blood lipids， estradiol， leptin and adiponectin with enzyme-linked immunosorbent assay and observed the pathological changes of perirenal fat， uterus and ovary. ResultsFor body weight and length， rats in the precocious puberty group were smaller than those in the normal group within 3 days after vaginal opening， but which did not affect their subsequent growth and development， and there was no significant difference between the two groups at 7 and 12 weeks of age. Within 3 days after vaginal opening， insulin levels had significant difference between the two groups （P = 0.001）， the precocious group showed hyperinsulinemia and increased number of perirenal adipocytes. At three execution times， no significant difference was noted in estradiol， leptin and adiponectin levels between the two groups. The same was true in the ratios of ovary or uterus to body weight between the two groups. ConclusionsPrecocious puberty makes earlier onset of pubertal development and allows body maladaptation to the sudden changes of the internal environment. However， the changes due to precocious puberty are temporary and reversible， and they may become normal in adulthood.
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Aim To observe the effects of oral puerarin (Pue) on the maternal gestational diabetes mellitus (GDM) rats and its fetal growth and development, so as to provide references for the application of Pue in the treatment of GDM. Methods The GDM rat model was established by injecting streptozotocin (STZ) into the tail vein of pregnant female rats, and the rats were treated with Pue orally for 12 days; the body weight and abortion of pregnant rats were recorded. The fasting blood glucose of pregnant rats was detected before and at the end of the treatment, and the glucose tolerance was tested on the 5th and 10th days after the administration of the drug. The cesarean sections were carried out on the 20th day of pregnancy. The blood glucose content of the fetal rats was detected, and the state of development was observed. The body weight and length were measured, as well as the placenta and the important organs weight, and the indexes of the organs were calculated. Results Compared with the model group, Pue could significantly reduce the fasting blood glucose of GDM pregnant rats and fetal rats, improve the glucose tolerance of pregnant rats, effectively alleviate the excessive weight gain of pregnant rats and overweight of fetal rats caused by GDM, and reduce the abortion rate; it could also reverse the decrease in the indexes of the organs of brain, heart, and liver, and the increase in the indexes of organs of kidney in fetal rats caused by GDM. Conclusions Pue can relieve the maternal and the fetal hyperglycemia in GDM, reduce the rate of miscarriage, reduce the incidence of macrosomia, and promote the development of vital fetal organs.
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Background Long-term exposure to ambient fine particulate matter (PM2.5) may increase the risk of diabetes, and a healthy diet can effectively control fasting blood glucose levels. However, it is unclear whether dietary factors have a moderating effect on the risk of diabetes associated with atmospheric PM2.5 exposure. Objective To investigate the association between long-term exposure to PM2.5 and diabetes in rural areas of Ningxia, and potential interaction of long-term exposure to atmospheric PM2.5 and diet on diabetes. Methods The study subjects were selected from the baseline survey data of the China Northwest Cohort-Ningxia (CNC-NX) , a natural population cohort. A total of 13917 subjects were included, excluding participants with missing covariate information. We utilized the annual average ambient PM2.5 concentration from 2014 to 2018 as the long-term exposure level. Logistic regression and multiple linear regression were employed to analyze the associations of long-term atmospheric PM2.5 exposure with diabetes and fasting blood glucose levels. Stratification by frequency of vegetable consumption, frequency of fruit consumption, and salty taste was used to examine moderating effects on the diabetes risk associated with atmospheric PM2.5 exposure. Results The mean age of the 13917 subjects was (56.8±10.0) years, and the prevalence of diabetes was 9.8%. Between 2014 and 2018, the average annual concentration of PM2.5 was (38.10±4.67) μg·m−3. The risk (OR) of diabetes was 1.018 (95%CI: 1.005, 1.032) and the fasting blood glucose was increased by 0.011 (95%CI: 0.004, 0.017) mmol·L−1 for each 1 μg·m−3 increase in PM2.5 concentration. Compared to those who consumed vegetables < 1 time per week, individuals who consume vegetables 1-3 times per week and ≥4 times per week had a reduced risk of developing diabetes by 27.1% (OR=0.729, 95%CI: 0.594, 0.893) and 16.8% (OR=0.832, 95%CI: 0.715, 0.971) respectively. Similarly, when compared to those who consumed fruits <1 time per week, individuals who consumed fruits 1-3 times per week and ≥4 times per week exhibited a reduced risk of diabetes by 16.4% (OR=0.836, 95%CI: 0.702, 0.998) and 18.2% (OR=0.818, 95%CI: 0.700, 0.959) respectively. Fasting blood glucose decreased by 0.202 (95%CI: -0.304, -0.101) mmol·L−1 in participants who ate vegetables 1-3 times per week. The effect of salty taste on diabetes and fasting blood glucose was not significant. The results of stratified analysis by dietary factors and PM2.5 concentration showed that the risks of diabetes were increased in the low PM2.5 pollution-low vegetable intake frequency group and the high PM2.5 pollution-low vegetable intake frequency group compared with the low PM2.5 pollution-high vegetable intake frequency group, with OR values of 3.987 (95%CI: 2.943, 5.371) and 1.433 (95%CI: 1.143, 1.796) respectively. The risk of diabetes was 50.1% higher in participants with high PM2.5 pollution and low fruit intake frequency than in participants with low PM2.5 pollution and high fruit intake frequency (OR=1.501, 95%CI: 1.171, 1.926). No interaction was found between salty taste and PM2.5 on diabetes. Conclusion Long-term exposure to ambient PM2.5 is associated with an increased fasting blood glucose and an elevated risk of diabetes in rural Ningxia population. Increasing the frequency of weekly consumption of vegetables or fruits may have a certain protective effect against diabetes occurrence, as well as a moderating effect on diabetes and fasting blood glucose levels associated with long-term exposure to atmospheric PM2.5.
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ObjectiveBased on network pharmacology and transcriptomics， the mechanism of Zishen Qinggan prescription （ZSQGF） in improving glucose and lipid metabolism in type 2 diabetes （T2DM） model rats was explored. MethodBased on network pharmacology analysis of the differential genes between ZSQGF and T2DM， gene ontology（GO）analysis and Kyoto encyclopedia of genes and genomes（KEGG） analysis were conducted， and molecular docking analysis was used to verify the binding between components and targets. A T2DM rat model was established by high-fat feeding and injection of streptozotocin （STZ）. The rats were randomly divided into the control group， model group， metformin （Met， 72 mg·kg-1） group， and ZSQGF high-， medium-， and low-dose groups （ZSQGF-H， ZSQGF-M， and ZSQGF-L， with 4.8， 2.4， and 1.2 g·kg-1 raw drug in the solution）. The living status of rats was monitored and the levels of total cholesterol （TC）， total triglycerides （TG）， high density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in rat serum were detected. The liver tissues were subjected to Hematoxylin eosin（HE） staining and oil red O staining. The differential genes were analyzed through transcriptomics， GO and KEGG analysis， and the protein-protein interaction（PPI） network was obtained to screen key targets. With network pharmacology and transcriptomics analysis results， the protein pathways were identified. The expression levels of nuclear factor-κB （NF-κB）， matrix metalloproteinase（MMP）-1 and MMP-9 proteins in liver tissues were detected by Western blot. The mRNA expression of B-cell lymphoma-2（Bcl-2） modifying factor（BMF）， nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4）， and fatty acid synthase（FASN） was detected by real-time polymerase chain reaction（Real-time PCR）. The expression of MMP-1 and MMP-9 in the liver was detected by immunofluorescence staining. ResultTranscriptomics and network pharmacology analysis suggested that ZSQGF may protect the liver through the glucose and lipid metabolism pathway and the inflammation pathway. Experiments showed that after 8 weeks of administration， the body weight， blood sugar， serum indicators， and pathological staining results of rats were improved. Western blot results indicated a decrease in the relative expression levels of NF-κB， MMP-1 and MMP-9 proteins in the liver. Real-time PCR results showed a decrease in the transcriptional expression of BMF， NOX4， and FASN in the ZSQGF-H group， while immunofluorescence staining results present decreased expression of MMP-1 and MMP-9 in the ZSQGF groups. ConclusionZSQGF can improve the glucose and lipid metabolism by inhibiting the expression of FASN， reducing lipid synthesis， and regulating the NF-κB signaling pathway.
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Solute carriers (SLCs) constitute the largest superfamily of membrane transporter proteins. These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions. They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake (e.g., SLC2A4/GLUT4), glucose reabsorption (e.g., SLC5A2/SGLT2), thermogenesis (e.g., SLC25A7/UCP-1), and ATP production (e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone (SLCO1B1/OATP1B1) and metformin (SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.
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ObjectiveTo investigate the association between estimated glucose disposal rate （eGDR） and the severity of coronary heart disease. MethodsWe conducted a hospital-based cross-sectional study that included 1258 patients （mean age： 62（53-68） years） who underwent coronary angiography for suspected coronary artery disease （53.9% were male）. Insulin resistance level （IR） was calculated according to eGDR formula： eGDR = 21.158 - （0.09 × WC） - （3.407 × hypertension） - （0.551 × HbA1c） ［hypertension （yes = 1 / no = 0）， HbA1c = HbA1c （%）］. Subjects were grouped according to the eGDR quantile. CAD severity was determined by the number of narrowed vessels： no-obstructive CAD group （all coronary stenosis were<50%， n=704）， Single-vessel CAD group （only one involved major coronary artery stenosis≥50%， n=205）， Multi-vessel CAD group （two or more involved major coronary arteries stenosis≥50%， n=349）； Multivariate logistic regression model was used to analyze the association between eGDR and CAD severity. The linear relationship between eGDR and CAD in the whole range of eGDR was analyzed using restricted cubic spline. Subgroup analyses were used to assess the association between eGDR and CAD severity in different diabetic states. Receiver operating characteristic （ROC） curve analysis were used to evaluate the value of eGDR in improving CAD recognition. ResultsA decrease in the eGDR index was significantly associated with an increased risk of CAD severity （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. In multivariate logistic regression models， individuals with the lowest quantile of eGDR （T1） were 2.79 times more likely to develop multi-vessel CAD than those with the highest quantile of eGDR （T3） （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. Multivariate restricted cubic spline analysis showed that eGDR was negatively associated with CAD and multi-vessel CAD （P-nonlinear>0.05）. In non-diabetic patients， compared with the reference group （T3）， the T1 group had a significantly increased risk of CAD （OR： 1.42； 95% CI： 1.00~2.01； P<0.05） and multi-vessel CAD （OR： 1.86； 95%CI： 1.21~2.86； P<0.05）. No statistical association was found between eGDR and CAD in diabetic patients. In ROC curve analysis， when eGDR was added to traditional model for CAD， significant improvements were observed in the model's recognition of CAD and multi-vessel CAD. ConclusionOur study shows eGDR levels are inversely associated with CAD and CAD severity. eGDR， as a non-insulin measure to assess IR， could be a valuable indicator of CAD severity for population.
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Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L−1), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L−1), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg−1). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.
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Objective To study the distribution characteristics of blood uric acid level and blood glucose status and their potential interaction in elderly hypertensive patients. Methods The randomized study enrolled elderly patients with essential hypertension who were treated in our hospital from January 2020 to January 2022 and received antihypertensive therapy. Collected patients’ sociodemographic information, medical history, treatment history, etc., and detected their blood uric acid and blood glucose levels. Analyzed and described the subjects’ basic characteristics and the distribution of blood uric acid and blood glucose, and the potential interaction between them. Results A total of 205 subjects were included in this study, including 108 males and 97 females, with an average age of 70.94 years and an average BMI of 23.19kg/m2. During the study period, the average blood pressure level was controlled at SBP 151.34±10.96mmHg and DBP 96.24±9.87mmHg, and the proportion of excellent blood pressure control reached 89.27%. The blood uric acid level of the subjects was elevated by increasing of subjects' age and BMI (P < 0.05), and blood glucose only elevated by the increasing of BMI (P < 0.001). High BMI, high DBP, family history of hypertension, high blood uric acid level, and current history of diabetes were risk factors for elevated hypertension grade. Conclusions High DBP, high BMI, high blood uric acid level, current history of diabetes and family history of hypertension are risk factors in elderly hypertensive patients, we could make clinical treatment strategies for these patients accordingly.
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Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.
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Hydrogen peroxide (H2O2) and nitric oxide (NO) has a short half-life, low bioavailability, poor tumor targeting and systemic adverse reactions in the physiological environment. In this study, phacoemulsification and nano-precipitation were used to synthesize didecyl dimethyl ammonium bromide (DDAB)/polylactic acid nanoparticles (PLA), then L-arginine (L-Arg) and glucose oxidase (GOx)-loaded nanoparticles (GADP) were prepared, and the in vitro antitumor activity was investigated．The particle size, potential, embedding rate and the ability to produce H2O2/NO of the nanoparticles were investigated. Meanwhile, in vitro cell cytotoxicity against human hepatoma cells (HepG2) was evaluated．The results showed that the prepared L-Arg-DDAB/PLA (ADP) nanoparticles were spherical particles. And the particle size and zeta potential were (225.7 ± 6.33) nm and (+23.5 ± 0.12) mV, respectively. The adsorption rate of GOx was 87.23% ± 0.02%. The drug loading of L-Arg was 15.6% ± 0.22%. The pH value of glucose solution and the amount of H2O2 showed that GADP had good catalytic activity. In vitro cytotoxicity experiments showed that blank nanoparticles were nontoxic, while the drug-loaded nanoparticles presented enhanced antitumor effect on HepG2 cells. And can inhibit tumor cell migration. The low dose nano-scale NO delivery system GADP can effectively inhibit the migration of tumor cells and kill tumor cells, thus producing therapeutic benefits.
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Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (P < 0.01) and GSP (P < 0.01) in the combined group were lower, and the insulin resistance was improved, which was better than that in the berberine group. Combined treatment increased the relative abundance of Bacteroides, Prevotella and Lactobacillus, reversed the decrease in Lactobacillus in the berberine alone induction group, and the combination of the two could promote the expression of TGR5 and GLP-1. In summary, the combined application of cinnamon and berberine can regulate glucose metabolism better than the application of berberine alone. Berberine combined with cinnamon can improve the function of pancreatic islet β cells in diabetes mellitus type 2 rats by changing the intestinal microbiota, increasing the expression of TGR5 and GLP-1 proteins, and thereby better regulating glucose metabolism.
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ObjectiveTo observe and compare the intervention effect of modified Cangfu Daotantang on glucose and lipid metabolism in simple obese children with phlegm dampness and stagnation. MethodA total of 60 children with simple obesity were randomly divided into two groups according to the simple randomization method of the random number table. The odd number was included in the test group， and the even number was included in the basic treatment group， with 30 cases in each group. On the basis of signing the informed consent notice， the treatment group was given modified Cangfu Daotantang combined with basic treatment， while the control group was only given basic treatment. After three months of treatment， the body mass index （BMI）， glucose and lipid metabolism level ［total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， fasting plasma glucose （FPG）， fasting insulin （FINS）， and homeostasis model assessment-insulin resistance （HOMA-IR）］， the change in the total score of traditional Chinese medicine （TCM） syndromes， and the effective rate of treatment were observed and compared. ResultAfter treatment， the BMI of the observation group and the control group decreased significantly （P<0.01）. Compared with the control group， the BMI level in the observation group decreased significantly （P<0.05）. After treatment， the levels of TC， TG， and LDL-C in the observation group and the control group decreased significantly （P<0.01）. Compared with the control group， the levels of TC， TG， and LDL-C in the observation group decreased significantly （P<0.05）. In addition， the level of TC in the observation group improved significantly compared with that in the control group （P<0.01）. The levels of FPG， FINS， and HOMA-IR in the observation group and the control group were significantly lower than those before treatment （P<0.05）. After treatment， compared with the control group， the levels of FPG， FINS， and HOMA-IR in the observation group were significantly reduced （P<0.05）. The level of FPG in the observation group was significantly improved compared with that in the control group （P<0.01）. After treatment， the total score of TCM syndromes in the two groups decreased significantly （P<0.01）. Compared with the control group， the total score of TCM syndromes in the observation group was lower （P<0.01）. After treatment， the total effective rate of treatment was 86.67% （26/30） in the observation group and 73.33% （22/30） in the control group. By rank sum test， the total effective rate of the observation group was better than that of the control group （Z=-2.100， P<0.05）. ConclusionModified Cangfu Daotantang combined with basic treatment can effectively reduce the BMI of obese children and improve their glucose and lipid metabolism. It has good clinical effects and high clinical application value， which is worth further in-depth research and promotion.
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ObjectiveTo investigate the effect and mechanism of salvianolic acid B combined with puerarin in protecting the SH-SY5Y cells from the damage by oxygen-glucose deprivation/reoxygenation （OGD/R） based on pyroptosis. MethodSH-SY5Y cells were used to establish the model of OGD/R， and cells were classified into the control， OGD/R， 10 μmol·L-1 salvianolic acid B， 100 μmol·L-1 puerarin， 10 μmol·L-1 salvianolic acid B + 100 μmol·L-1 puerarin， and 10 μmol·L-1 NOD-like receptor protein 3 （NLRP3） inhibitor MCC950 groups. Except the control group， other groups were rapidly reoxygenated for 12 h after 6 h OGD for modeling. The cell survival rate was determined by the methyl thiazolyl tetrazolium （MTT） assay. An optical microscope was used to observe the cell morphology. A spectrophotometer was used to determine the content of lactic dehydrogenase （LDH） in culture supernatant. Cell damage was measured by Hoechst/PI staining. The mRNA levels of NLRP3， cysteinyl aspartate specific proteinase-1 （Caspase-1）， gasdermin D （GSDMD）， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β） were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein activation of Caspase-1 and NLRP3 was detected by immunofluorescence. Western blot was employed to determine the protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1. ResultCompared with the control group， the OGD/R group showed decreased cell survival rate （P<0.01）， damaged cell morphology， increased leakage rate of LDH （P<0.01）， up-regulated mRNA levels of NLRP3， Caspase-1， GSDMD， ASC， and IL-1β （P<0.01）， and up-regulated protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1 （P<0.01）. Compared with the OGD/R group， salvianolic acid B， puerarin， and salvianolic acid B combined with puerarin improved cell survival rate （P<0.01）， and the combined treatment group outperformed salvianolic acid B and puerarin used alone （P<0.01）. Salvianolic acid B combined with puerarin and MCC950 both improved cell morphology， reduced the leakage of LDH （P<0.01）， alleviated cell damage， and down-regulated the mRNA levels of NLRP3， Caspase-1， GSDMD， ASC， and IL-1β （P<0.05， P<0.01） and also the protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1 （P<0.05， P<0.01）. ConclusionThe results indicated that salvianolic acid B combined with puerarin can alleviate the OGD/R-induced damage of SH-SY5Y cells by inhibiting pyroptosis.
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AIM:To investigate the influencing factors of abnormal telangiectasia secondary to diabetic retinopathy(DR).METHODS: Prospective studies. A total of 153 cases(240 eyes)with DR treated in our hospital from January 2021 to January 2023 were selected to analyze the risk factors of abnormal telangiectasia secondary to DR and its predictive efficacy.RESULTS: The patients were divided into dilated group(77 eyes of 40 cases)and non-dilated group(163 eyes of 113 cases)according to whether they had secondary abnormal telangiectasia. There were significant differences in diabetic macular edema, hard exudates grade and fasting blood glucose level between the two groups(P&#x003C;0.05). Logistic regression analysis showed that diabetic macular edema, high hard exudates grade and high blood glucose level were the risk factors for abnormal telangiectasia secondary to DR(P&#x003C;0.05).CONCLUSION: The occurrence of telangiectasia secondary to DR may be related to diabetic macular edema, grade 3 hard exudates and high blood glucose level.