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BACKGROUND: Shenqi Compound (SQC) has been used in clinic for several decades in the prevention and treatment of diabetes and its complications. But this is merely a heritage of experience. The primary aim of this study is to scientifically validate the therapeutic effects of SQC on diabetic vascular calcification (DVC) in an animal model and, simultaneously, uncover its potential underlying mechanisms. METHOD: Spontaneous diabetic rat- Goto Kakizaki (GK) rats were selected for rat modeling. We meticulously designed three distinct groups: a control group, a model group, and an SQC treatment group to rigorously evaluate the influence of SQC. Utilizing a comprehensive approach that encompassed methods such as pathological staining, western blot analysis, qRT-PCR, and RNA sequencing, we thoroughly investigated the therapeutic advantages and the underlying mechanistic pathways associated with SQC in the treatment of DVC. RESULT: The findings from this investigation have unveiled the extraordinary efficacy of SQC treatment in significantly mitigating DVC. The underlying mechanisms driving this effect encompass multifaceted facets, including the restoration of aberrant glucose and lipid metabolism, the prevention of phenotypic transformation of vascular smooth muscle cells (VSMCs) into osteogenic-like states, the subsequent inhibition of cell apoptosis, the modulation of inflammation responses, the remodeling of the extracellular matrix (ECM), and the activation of the Hippo-YAP signaling pathway. Collectively, these mechanisms lead to the dissolution of deposited calcium salts, ultimately achieving the desired inhibition of DVC. CONCLUSION: Our study has provided compelling and robust evidence of the remarkable efficacy of SQC treatment in significantly reducing DVC. This reduction is attributed to a multifaceted interplay of mechanisms, each playing a crucial role in the observed therapeutic effects. Notably, our findings illuminate prospective directions for further research and potential clinical applications in the field of cardiovascular health.
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Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Calcificação Vascular , Ratos , Animais , Estudos Prospectivos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/complicações , Calcificação Vascular/metabolismo , Miócitos de Músculo Liso/metabolismoRESUMO
ABSTRACT: Vascular endothelial cells, which make up the inner wall of blood arteries, are susceptible to damage from oxidative stress and apoptosis caused by hyperglycemia. According to certain reports, noncoding RNAs are involved in controlling oxidative stress and apoptosis. ShenQi Compound (SQC), a traditional herbal remedy, has been successfully treating diabetic vascular disease in China for more than 20 years. Although it is well established that SQC protects the vascular endothelium, the molecular mechanism remains unknown. Goto-Kakizaki rats, spontaneous type II diabetes rats, that consistently consume a high-fat diet were chosen as model animals. Six groups (control group, model group, metformin group, and 7.2 g/kg/d SQC group, 14.4 g/kg/d SQC group, and 28.8 g/kg/d SQC group) were included in this work, 15 rats each group. The approach of administration was gavage, and the same volume (5.0 mL/kg/d) was given in each group, once a day, 12 weeks. The thoracic aortas were removed after the rats were sacrificed. Oxidative reduction profile in thoracic aorta, histopathological observation of thoracic aorta, endothelial cell apoptosis in thoracic aorta, whole transcriptome sequencing, bioinformatic analyses, and qRT-PCR were conducted. As a result, SQC prevented the oxidative stress and apoptosis induced by a high glucose concentration. Under hyperglycemia condition, noncoding RNAs, including 1 downregulated novel circRNA (circRNA.3121), 3 downregulated lncRNAs (Skil.cSep08, Shawso.aSep08-unspliced, and MSTRG.164.2), and 1 upregulated mRNA (Pcdh17), were clearly reverse regulated by SQC. SQC plays a role in protecting vascular endothelial cells from high glucose mainly by mediating ncRNA to inhibit cell apoptosis and oxidative stress.
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Diabetes Mellitus Tipo 2 , Hiperglicemia , RNA Longo não Codificante , Ratos , Animais , RNA Longo não Codificante/genética , RNA Circular , RNA Mensageiro/genética , Células Endoteliais , Sequenciamento do Exoma , GlucoseRESUMO
O-linked b-N-acetyl-glucosaminylation (O-GlcNAcylation) is one of the most common post-translational modifications of proteins, and is established by modifying the serine or threonine residues of nuclear, cytoplasmic, and mitochondrial proteins. O-GlcNAc signaling is considered a critical nutrient sensor, and affects numerous proteins involved in cellular metabolic processes. O-GlcNAcylation modulates protein functions in different patterns, including protein stabilization, enzymatic activity, transcriptional activity, and protein interactions. Disrupted O-GlcNAcylation is associated with an abnormal metabolic state, and may result in metabolic disorders. As the liver is the center of nutrient metabolism, this review provides a brief description of the features of the O-GlcNAc signaling pathway, and summarizes the regulatory functions and underlying molecular mechanisms of O-GlcNAcylation in liver metabolism. Finally, this review highlights the role of O-GlcNAcylation in liver-associated diseases, such as diabetes and nonalcoholic fatty liver disease (NAFLD). We hope this review not only benefits the understanding of O-GlcNAc biology, but also provides new insights for treatments against liver-associated metabolic disorders.
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Diabetes Mellitus , Hepatopatia Gordurosa não Alcoólica , Humanos , Acetilglucosamina/metabolismo , Diabetes Mellitus/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Processamento de Proteína Pós-Traducional , Transdução de Sinais , Acilação/fisiologiaRESUMO
Glucokinase-maturity onset diabetes of the young (GCK-MODY) is a kind of rare diabetes with low incidence of vascular complications caused by GCK gene inactivation. This study aimed to investigate the effects of GCK inactivation on hepatic lipid metabolism and inflammation, providing evidence for the cardioprotective mechanism in GCK-MODY. We enrolled GCK-MODY, type 1 and 2 diabetes patients to analyze their lipid profiles, and found that GCK-MODY individuals exhibited cardioprotective lipid profile with lower triacylglycerol and elevated HDL-c. To further explore the effects of GCK inactivation on hepatic lipid metabolism, GCK knockdown HepG2 and AML-12 cell models were established, and in vitro studies showed that GCK knockdown alleviated lipid accumulation and decreased the expression of inflammation-related genes under fatty acid treatment. Lipidomic analysis indicated that the partial inhibition of GCK altered the levels of several lipid species with decreased saturated fatty acids and glycerolipids including triacylglycerol and diacylglycerol, and increased phosphatidylcholine in HepG2 cells. The hepatic lipid metabolism altered by GCK inactivation was regulated by the enzymes involved in de novo lipogenesis, lipolysis, fatty acid ß-oxidation and the Kennedy pathway. Finally, we concluded that partial inactivation of GCK exhibited beneficial effects in hepatic lipid metabolism and inflammation, which potentially underlies the protective lipid profile and low cardiovascular risks in GCK-MODY patients.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/genética , Ácidos Graxos , Glucoquinase/metabolismo , Hepatócitos/metabolismo , Inflamação/complicações , Metabolismo dos Lipídeos , Mutação , TriglicerídeosRESUMO
ATP-binding cassette transporter G1 (ABCG1) is a cellular transmembrane protein that transports oxysterol efflux from cells to high-density lipoprotein (HDL) particles in the plasma. Previous studies have demonstrated that an ABCG1 deficiency exerts an antiatherosclerotic function through the effects of oxysterol accumulation in cells to enhance apoptosis and regulate inflammatory processes. However, whether the deficiency of ABCG1 and the corresponding changes in the efflux of oxysterols could take a series of impacts on the proteomic composition of HDL remains unclear. Here, plasma HDL of ABCG1(-/-) mice and their wild-type controls on a normal chow diet (NCD) or a high-fat diet (HFD) were isolated by ultracentrifugation. The proportion of 7-ketocholesterol and the proteomic composition of samples were comparatively analyzed by LC-MS/MS. In NCD-fed mice, lipid metabolism-related protein (arachidonate 12-lipoxygenase) and antioxidative protein (pantetheinase) exhibited increased accumulation, and inflammatory response protein (alpha-1-antitrypsin) was decreased in accumulation in ABCG1(-/-) mice HDL. In HFD-fed mice, fewer proteins were detected than that of NCD-fed mice. The ABCG1(-/-) mice HDL exhibited increased accumulation of lipid metabolism-related proteins (e.g., carboxylesterase 1C, apolipoprotein (apo)C-4) and decreased accumulation of alpha-1-antitrypsin, as well as significantly reduced proportion of 7-ketocholesterol. Additionally, positive correlations were found between 7-ketocholesterol and some essential proteins on HDL, such as alpha-1-antitrypsin, apoA-4, apoB-100, and serum amyloid A (SAA). These results suggest a detrimental impact of oxysterols on HDL composition, which might affect the antiatherosclerotic properties of HDL.
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Dieta Hiperlipídica , Doenças não Transmissíveis , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Cromatografia Líquida , Dieta Hiperlipídica/efeitos adversos , Lipoproteínas/metabolismo , Camundongos , Camundongos Knockout , Proteômica , Espectrometria de Massas em TandemRESUMO
BACKGROUND: The morning blood pressure surge (MBPS) is related to an exaggerated risk of cardiovascular diseases and mortality. With increasing attention on circadian change in blood pressure and extensive use of ambulatory blood pressure monitoring (ABPM), chronotherapy that administration of medication according to biological rhythm, is reported to improve cardiovascular outcomes. The aim of this study is to evaluate the influence of chronotherapy of antihypertensive drugs upon MBPS in hypertensive patients. METHODS: A search strategy was applied in Ovid MEDLINE, EMBASE, Cochrane (Wiley) CENTRAL Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the Chinese Biomedical literature database. No language and date restrictions. Randomized controlled trials (RCT) assessing the efficacy of evening and morning administration of the same medications in adult patients with primary hypertension were included. RESULTS: A total of ten trials, comprising 1724 participants with a mean age of 61 and 51% female, were included in this study. Combined analysis observed significant reduction of MBPS (- 5.30 mmHg, 95% CI - 8.80 to - 1.80), night-time SBP (- 2.29 mmHg, 95% CI - 4.43 to - 0.15), night-time DBP (- 1.63 mmHg, 95 %CI - 3.23 to - 0.04) and increase in night blood pressure dipping (3.23%, 95% CI 5.37 to 1.10) in evening dosage compared with traditional morning dosage of blood pressure-lowering drugs. No significant difference was found in the incidence of overall adverse effects (RR 0.65, 95% CI 0.30 to 1.41) and withdrawal due to adverse effects (RR 0.95, 95% CI 0.53 to 1.71). CONCLUSIONS: Our study suggested that evening administration of antihypertensive medications exerted better blood pressure-lowering effect on MBPS compared with conventional morning dosage. Safety assessment also indicated that the evening regimen did not increase the risk of adverse events. However, endpoint studies need to be carried out to confirm the significance and feasibility of this treatment regimen in clinical practice.
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Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Ritmo Circadiano , Cronofarmacoterapia , Hipertensão/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/efeitos adversos , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: Glucokinase (GCK) acts as the glucose sensor in maintaining glucose homeostasis. The inactivating mutation of the GCK gene leads to glucokinase-maturity onset diabetes of the young (GCK-MODY). This study aims to gain further insights into the molecular alterations triggered by GCK partial inactivation in hepatocytes, potentially underlying the favorable prognosis of GCK-MODY. MAIN METHODS: A GCK knockdown HepG2 cell model was established, and the integration of proteomics and metabolomics was used to gain a comprehensive understanding of the molecular pathway changes caused by GCK inactivation in the liver. KEY FINDINGS: Proteomic analysis identified 257 differential proteins. KEGG pathway enrichment analysis showed that protein expression changes in the GCK knockdown group were significantly enriched in central carbon metabolism, the TCA cycle, amino acid metabolism and the oxidative phosphorylation pathway. Among them, enzymes in the TCA cycle (PC, IDH2, SDH) were significantly downregulated in GCK-knockdown group. Targeted metabolomics revealed that in the GCK knockdown hepatocytes, TCA cycle intermediates were significantly decreased, including pyruvate, oxaloacetate, citrate and succinic acid, and three metabolites increased including glycine, betaine and homocysteine. These metabolic alterations in turn reduced the accumulation of reactive oxygen species in GCK knockdown hepatocytes. Correlation analysis indicated that TCA cycle metabolites were positively correlated with proteins involved in the TCA cycle, carbon metabolism, glycolysis, Ras signaling, fibrosis and inflammation. SIGNIFICANCE: In conclusion, GCK knockdown reduced TCA cycle flux and oxidative stress in hepatocytes by influencing the levels of key transcription factors and enzymes, providing a comprehensive understanding of the effects of GCK partial inactivation on liver metabolism and molecular mechanisms.
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Diabetes Mellitus Tipo 2 , Glucoquinase , Humanos , Glucoquinase/genética , Glucoquinase/metabolismo , Proteômica , Hepatócitos/metabolismo , Fígado/metabolismo , Glucose , MutaçãoRESUMO
Maternal obesity has long-term effects on offspring metabolic health. Among the potential mechanisms, prior research has indicated potential disruptions in circadian rhythms and gut microbiota in the offspring. To challenge this hypothesis, we implemented a maternal high fat diet regimen before and during pregnancy, followed by a standard diet after birth. Our findings confirm that maternal obesity impacts offspring birth weight and glucose and lipid metabolisms. However, we found minimal impact on circadian rhythms and microbiota that are predominantly driven by the feeding/fasting cycle. Notably, maternal obesity altered rhythmic liver gene expression, affecting mitochondrial function and inflammatory response without disrupting the hepatic circadian clock. These changes could be explained by a masculinization of liver gene expression similar to the changes observed in polycystic ovarian syndrome. Intriguingly, such alterations seem to provide the first-generation offspring with a degree of protection against obesity when exposed to a high fat diet.
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Numerous disinfection by-products (DBPs) are formed from reactions between disinfectants and organic/inorganic matter during water disinfection. More than seven hundred DBPs that have been identified in disinfected water, only a fraction of which are regulated by drinking water guidelines, including trihalomethanes, haloacetic acids, bromate, and chlorite. Toxicity assessments have demonstrated that the identified DBPs cannot fully explain the overall toxicity of disinfected water; therefore, the identification of unknown DBPs is an important prerequisite to obtain insights for understanding the adverse effects of drinking water disinfection. Herein, we review the progress in identification of unknown DBPs in the recent five years with classifications of halogenated or nonhalogenated, aliphatic or aromatic, followed by specific halogen groups. The concentration and toxicity data of newly identified DBPs are also included. According to the current advances and existing shortcomings, we envisioned future perspectives in this field.
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Desinfetantes , Água Potável , Poluentes Químicos da Água , Purificação da Água , Desinfecção , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Desinfetantes/toxicidade , Desinfetantes/análise , Trialometanos/toxicidade , Trialometanos/análise , HalogenaçãoRESUMO
PURPOSE: There have been limited studies examining the prospective association between the Systemic Immune-Inflammation Index (SII), a novel inflammatory marker, and mortality among individuals with diabetes in the United States. METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES), a representative sample of US adults, linked with information from the National Death Index. RESULTS: Our study included 8697 individuals from NHANES spanning the years 1999 to 2018. SII was calculated by dividing the platelet count by the neutrophil count and then dividing that result by the lymphocyte count. We employed multivariable Cox proportional hazards regression analysis to investigate the associations between SII levels and all-cause as well as cause-specific mortality, while adjusting for potential confounding factors. SII levels were categorized into quartiles based on the study population distribution. Over a median follow-up period of 94.8 months (with a maximum of 249 months), we observed a total of 2465 all-cause deaths, 853 deaths from cardiovascular causes, 424 deaths from cancer, and 88 deaths related to chronic kidney disease. After adjusting for multiple variables, higher SII levels were significantly and non-linearly associated with an increased risk of all-cause mortality in Quartile 4 (HR 1.74, 95% CI 1.15-2.63, P for trend = 0.043) when Quartile 1 was used as the reference group. Additionally, we identified a linear association between SII and cardiovascular mortality, with a 70% higher risk of cardiovascular mortality in Quartile 4 (HR 1.70, 95% CI 1.18-3.30, P for trend = 0.041) compared to Quartile 1. CONCLUSION: Our findings indicate that SII is significantly associated with an elevated risk of all-cause and cardiovascular mortality in US adults with diabetes.
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Type 2 diabetes (T2D) is a prevalent metabolic disorder characterized by impaired insulin secretion and insulin resistance, resulting in elevated blood glucose levels. The dysfunction and loss of pancreatic ß-cells, responsible for producing insulin, contribute to the development of T2D. Traditional Chinese medicine (TCM) has emerged as a potential source of innovative therapeutic interventions. However, limited research exists on Chinese herbal formulations specifically targeting the protection of pancreatic ß-cell function and mass. One such formulation is the Shenqi compound (SQC), widely used in China and consisting of Panax Ginseng, Astragali Radix, Rhizoma Dioscoreae, Corni Fructus, Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma, Radix Trichosanthis, and Rhei Radix et Rhizoma. Understanding the mechanisms underlying the therapeutic effects of SQC is crucial for developing novel treatment strategies for T2D. This study aims to comprehensively investigate the scientific evidence supporting the role of SQC in alleviating T2D by targeting the protection of pancreatic ß-cell function and mass. Spontaneously diabetic GK rats were used as the animal model, receiving SQC (14.4 g/kg/d) for 8 weeks. The results demonstrate multiple beneficial effects of SQC, including significant control of blood glucose levels (P < 0.05), inhibition of insulin resistance (measured by Western Blot), reduction of hyperinsulinemia (P < 0.05), attenuation of oxidative stress (P < 0.05), suppression of inflammation (P < 0.05), protection against islet hypertrophy and beta cell proliferation (evaluated through pathological staining), and inhibition of ß-cell apoptosis and senescence (also assessed through pathological staining). These findings indicate the promotion of ß-cell survival and function. In vitro experiments using isolated islets further support these results, revealing improvements in insulin secretion (P < 0.05) and ß-cell function following SQC therapy (P < 0.05). This represents a significant breakthrough in addressing ß-cell dysfunction and preserving mass within the context of TCM. Overall, SQC shows promise as a natural therapeutic approach for T2D, with potential benefits in preserving pancreatic ß-cell function and mass. This enhances the practical applicability and significance of the research by bridging the gap between experimental findings and clinical practice, thereby providing important clinical value in TCM treatment of T2D. Further research is necessary to elucidate its precise mechanisms of action and optimize its clinical application.
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Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Resistência à Insulina , Ratos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glicemia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
Pseudomonas aeruginosa is a conditional Gram-negative pathogen that produces extracellular virulence factors that can lead to bloodstream invasion, severely harm tissues, and disseminate bacteria, ultimately leading to various diseases. In this study, lactic acid bacteria (LAB) with strong antagonistic ability against P. aeruginosa were screened, and the regulatory mechanism of LAB against P. aeruginosa was evaluated. The results showed that the three selected LAB strains had strong inhibition ability on the growth, biofilm formation, and pyocyanin expression of P. aeruginosa and a promoting effect on the expression of autoinducer-2. Among them, Lactipantibacillus plantarum (Lp. plantarum) LPyang is capable of affecting the metabolic processes of P. aeruginosa by influencing metabolic substances, such as LysoPC, oxidized glutathione, betaine, etc. These results indicate that LPyang reduces the infectivity of P. aeruginosa through inhibition of its growth, biofilm formation, pyocyanin expression, and regulation of its metabolome. This study provides new insights into the antagonistic activity of Lp. plantarum LPyang against P. aeruginosa.
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BACKGROUND: Maturity-onset diabetes of the young (MODY) patients have unique clinical manifestations and need individualized treatments. We identified novel serum metabolic biomarkers to distinguish MODY and explore the possible mechanism of the clinical manifestation and complications of MODY. METHODS: Fasting serum samples were collected from MODY3 (n = 17), MODY2 (n = 33), type 1 diabetes (T1DM) (n = 34) and healthy individuals (n = 30), and were analyzed using the ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) metabolomic platform. RESULTS: 4 metabolites were found significantly fluctuated between groups, including glycerophosphocholine, LysoPC(18:2(9Z,12Z)), sphinganine and l-Phenylalanine. Glycerophosphocholine was selected as a diagnostic biomarker. The the area under the ROC curve (AUC) for distinguishing MODYs from healthy controls and differentiating MODY3 from T1DM reached 1.0. The combination of metabolites also gained good diagnostic value. The AUC of the combination of LysoPC(18:2(9Z,12Z)), sphinganine and l-Phenylalanine for discriminating MODY3 from T1DM was 0.983. Besides, the combination of clinical indices and metabolites helped to better differentiate the 2 MODY subtypes. CONCLUSIONS: We identified the metabolic profiles of MODY2 and MODY3 and found promising biomarkers for distinguishing MODY from T1DM, which provides evidence for the pathogenesis and characteristic clinical manifestations of patients with MODY2 and MODY3.
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Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/diagnóstico , Cromatografia Líquida , População do Leste Asiático , Fator 1-alfa Nuclear de Hepatócito , Espectrometria de Massas em Tandem , Biomarcadores , Metabolômica , FenilalaninaRESUMO
Type 2 diabetes (T2D) has emerged as a global epidemic, and conventional treatment approaches often face limitations in achieving long-term glycemic control and preventing complications. Traditional Chinese Medicine (TCM) offers a valuable alternative for managing T2D, with a long history of effectively using herbal formulations in clinical practice. However, the modular characteristics of these herbs and their specific mechanisms of action remain poorly understood. To comprehensively investigate the modular characteristics and mechanisms of Chinese herbs in treating T2D, as well as explore the synergistic interactions among different herbs and their modular components, we employed data mining, systematic pharmacology, and molecular docking. Our aim was to gain a comprehensive understanding of the potential therapeutic targets and pathways involved in herbal T2D treatment. In this study, a total of 1114 studies investigating the effects of TCM interventions in the treatment of T2D in adults were included. The analysis revealed 170 distinct types of Chinese herbs, 118 active components, and 238 common targets shared between the medicine and T2D. Additionally, this study identified six hub proteins (TNF, MMP2, PTGS, CASP3, CASP8, and CASP9) and two key chemicals (Diosgenin and Formononetin) found in TCM-mediated T2D suppression. It was observed that these proteins could bind with the ingredients. The MMP2-Diosgenin interaction exhibited the lowest binding free energy (-13.05 kJ/mol) and was primarily driven by hydrogen bonds with ALA-165. TNF-Diosgenin (-10.5 kcal/mol) showed three hydrogen bonds with LEU-37, ARG-82, and ASN-30. PTGS2 and Diosgenin (-8.71 kJ/mol) demonstrated a hydrogen bond with HIS-214. Furthermore, CASP9-Formononetin (-6.53 kcal/mol) exhibited the lowest binding free energy and hydrogen bonds with GLU-261 and SER-339 as the primary forces involved. CASP3-Formononetin (-6.07 kcal/mol) displayed three hydrogen bonds with ASN-342, TRP-348, and GLU-379. Lastly, CASP8 and Formononetin (-6.06 kJ/mol) formed a hydrogen bond with THR-390, TYR-392, and TYR-334. Moreover, critical therapeutic pathways, such as the immune inflammatory response, AGE-RAGE, and IL-17 signaling pathway, were found to be associated with T2D Chinese herb therapy. In conclusion, this study sheded light on the modular characteristics and mechanism of action of herbs used in Chinese Medicine for the treatment of T2D, which provided valuable insights for both researchers and practitioners in the field of Chinese Medicine, offering potential avenues for improved treatment strategies and personalized approaches to address the complex nature of T2D.
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Is Cannabis a boon or bane? Cannabis sativa has long been a versatile crop for fiber extraction (industrial hemp), traditional Chinese medicine (hemp seeds), and recreational drugs (marijuana). Cannabis faced global prohibition in the twentieth century because of the psychoactive properties of ∆9-tetrahydrocannabinol; however, recently, the perspective has changed with the recognition of additional therapeutic values, particularly the pharmacological potential of cannabidiol. A comprehensive understanding of the underlying mechanism of cannabinoid biosynthesis is necessary to cultivate and promote globally the medicinal application of Cannabis resources. Here, we comprehensively review the historical usage of Cannabis, biosynthesis of trichome-specific cannabinoids, regulatory network of trichome development, and synthetic biology of cannabinoids. This review provides valuable insights into the efficient biosynthesis and green production of cannabinoids, and the development and utilization of novel Cannabis varieties.
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BACKGROUND: Despite the increasing prevalence rate of nonalcoholic fatty liver disease (NAFLD) worldwide, efficient pharmacotherapeutic regimens against NAFLD still need to be explored. Previous studies found that pioglitazone and metformin therapy could partly ameliorate NAFLD, but their combination therapy effects have not been researched. In the present study, we assessed the protective effects of metformin and pioglitazone combination therapy on liver lipid metabolism in high-fat diet (HFD)-fed mice and investigated the molecular mechanism. METHODS: Male C57BL/6 mice were divided into five groups: normal control; HFD control; metformin monotherapy; pioglitazone monotherapy and combined therapy. After 8 weeks of pharmacological intervention, glucose and lipid metabolism characteristics, hepatic histology, lipidomics profiling and RNA-seq analysis were performed. RESULTS: The combination of pioglitazone and metformin significantly ameliorated HFD-induced metabolic disturbance and the hepatic oil red O area. A lipidomics analysis showed that combined therapy could significantly reduce the high levels of free fatty acids (FFA), diacylglycerol and triglycerides, while a set of glycerophospholipids and sphingolipids were increased in the combined therapy group. Consistently, an RNA-seq analysis also showed a remarkable reduction in genes associated with FFA uptake and de novo lipogenesis, including Cd36, Fads1, Fads2, Fasn, Scd1, Elovl5 and Pklr in the combined therapy group. CONCLUSIONS: Pioglitazone and metformin might have a synergistic protective effect on NAFLD by improving hepatic lipid profiles in HFD-induced mice. Further studies are needed to verify the clinical effects.
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Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Pioglitazona/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológicoRESUMO
BACKGROUND: Maturity-onset diabetes of the young type 2 (MODY2) is a rare genetic disorder characterized as mild fasting hyperglycemia with low risk of vascular complications caused by glucokinase gene mutation. This study aims to investigate metabolites alteration associated with MODY2, exploring possible mechanism underlying characteristic clinical manifestations and low cardiovascular risks of MODY2 and providing serum metabolite biomarkers to facilitating MODY2 diagnosis. METHODS: Fasting serum samples from MODY2, type 1 diabetes (T1DM) and healthy individuals were collected. By using targeted metabolomics via liquid chromatography-tandem mass spectrometry platform, we quantified the metabolites involved in tricarboxylic acid (TCA) cycle and one-carbon metabolism. RESULTS: Metabolomic profiling revealed significant difference of intermediates from central metabolism cycle, methionine cycle and several amino acids between MODY2 and T1DM groups. Among these, serum citrate, α-ketoglutaric acid, serine, glycine, glutamine and homocysteine were significantly elevated in MODY2 patients compared with T1DM patients; and compared with healthy subjects, malate and methionine levels were significantly increased in the two groups of diabetic patients. The correlation analysis with clinical indexes showed that α- ketoglutarate, serine, glycine, and glutamine were negatively correlated with blood glucose indicators including fasting blood glucose, HbA1c, and GA, while citrate was positively correlated with C-peptide. And homocysteine displayed positive correlation with HDL and negative with C-reactive protein, which shed light on the mechanism of mild symptoms and low risk of cardiovascular complications in MODY2 patients. A panel of 4 metabolites differentiated MODY2 from T1DM with AUC of 0.924, and a combination of clinical indices and metabolite also gained good diagnostic value with AUC 0.948. CONCLUSION: In this research, we characterized the metabolite profiles of TCA cycle and one-carbon metabolism in MODY2 and T1DM and identified promising diagnostic biomarkers for MODY2. This study may provide novel insights into the pathogenesis and clinical manifestations of MODY2.
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Horse chestnut (Aesculus chinensis) is an important medicinal tree that contains various bioactive compounds, such as aescin, barrigenol-type triterpenoid saponins (BAT), and aesculin, a glycosylated coumarin. Herein, we report a 470.02 Mb genome assembly and characterize an Aesculus-specific whole-genome duplication event, which leads to the formation and duplication of two triterpenoid biosynthesis-related gene clusters (BGCs). We also show that AcOCS6, AcCYP716A278, AcCYP716A275, and AcCSL1 genes within these two BGCs along with a seed-specific expressed AcBAHD6 are responsible for the formation of aescin. Furthermore, we identify seven Aesculus-originated coumarin glycoside biosynthetic genes and achieve the de novo synthesis of aesculin in E. coli. Collinearity analysis shows that the collinear BGC segments can be traced back to early-diverging angiosperms, and the essential gene-encoding enzymes necessary for BAT biosynthesis are recruited before the splitting of Aesculus, Acer, and Xanthoceras. These findings provide insight on the evolution of gene clusters associated with medicinal tree metabolites.
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Aesculus , Escina , Aesculus/genética , Esculina , Escherichia coliRESUMO
The global burden due to microvascular complications in patients with diabetes mellitus persists and even increases alarmingly, the intervention and management are now encountering many difficulties and challenges. This paper reviews the recent advancement and progress in novel biomarkers, artificial intelligence technology, therapeutic agents and approaches of diabetic retinopathy and nephropathy, providing more insights into the management of microvascular complications.
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Diabetes Mellitus , Nefropatias Diabéticas , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/terapia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/terapia , Inteligência ArtificialRESUMO
In the context of sustainable ecological environment, strengthening the scientific management of cultural industry can promote the rapid development of China's cultural industry and further promote the construction of spiritual civilization in China. Starting from culture and art management, this study expounds its position in the development of cultural economy industry and its impact on the development of cultural economy. Through two different methods of culture and art management and conventional management, this paper discusses the social and economic market benefit value, the demand for the healthy development of industry, and the impact of innovative cultural industry resources on the development of cultural industry. It can be concluded that culture and art management plays a certain role in promoting the healthy development of cultural economy industry; we should constantly sum up experience in the actual process of cultural industry management, find and solve problems in time, and gradually form a set of scientific and complete cultural and art management mode, which can realize the transformation of cultural and art industry faster and better promote the sustainable development of cultural economy and industry.