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1.
Biomed Chromatogr ; : e5960, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992861

RESUMO

Coptidis Rhizoma (CR) holds significant clinical importance. In this study, we conducted a comparative analysis of CR's dispensing granule decoction (DGD) and traditional decoction (TD) to establish a comprehensive evaluation method for the quality of DGD. We selected nine batches of DGD (three from each of manufacturers A, B and C) and 10 batches of decoction pieces for analysis. We determined the content of representative components using high-performance liquid chromatography and assessed the content of blood components in vivo post-administration using ultra-performance liquid chromatography-mass spectrometry. The antibacterial activity was measured using the drug-sensitive tablet method. To evaluate the overall consistency of DGD and TD, we employed the CRITIC method and Grey relational analysis method. Our CRITIC results indicated no significant difference between the CRITIC scores of DGD-B and TD, with DGD-B exhibiting the highest consistency and overall quality. However, DGD-A and DGD-C showed variations in CRITIC scores compared with TD. After equivalent correction, the quality of DGD-A and DGD-C approached that of TD. Furthermore, our Grey relational analysis results supported the findings of the CRITIC method. This study offers a novel approach to evaluate the consistency between DGD and TD, providing insights into improving the quality of DGD.

2.
Front Endocrinol (Lausanne) ; 15: 1414908, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989000

RESUMO

Background: Lipodystrophy is a rare disease that is poorly diagnosed due to its low prevalence and frequent phenotypic heterogeneity. The main therapeutic measures for patients with clinical lipodystrophy are aimed at improving general metabolic complications such as diabetes mellitus, insulin resistance, and hypertriglyceridemia. Therefore, there is an urgent need to find new biomarkers to aid in the diagnosis and targeted treatment of patients with congenital generalized lipodystrophy (CGL). Methods: Dataset GSE159337 was obtained via the Gene Expression Omnibus database. First, differentially expressed genes (DEGs) between CGL and control samples were yielded via differential expression analysis and were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment to explore the functional pathways. Next, protein-protein interaction analysis and the MCC algorithm were implemented to yield candidate genes, which were then subjected to receiver operating characteristic (ROC) analysis to identify biomarkers with an area under the curve value exceeding 0.8. Moreover, random forest (RF), logistic regression, and support vector machine (SVM) analyses were carried out to assess the diagnostic ability of biomarkers for CGL. Finally, the small-molecule drugs targeting biomarkers were predicted, and ibuprofen was further validated in lipodystrophy mice. Results: A total of 71 DEGs in GSE159337 were sifted out and were involved in immune receptor activity, immune response-regulating signaling pathway, and secretory granule membrane. Moreover, CXCR2, TNFSF10, NLRC4, CCR2, CEACAM3, TLR10, TNFAIP3, and JUN were considered as biomarkers by performing ROC analysis on 10 candidate genes. Meanwhile, RF, logistic regression, and SVM analyses further described that those biomarkers had an excellent diagnosis capability for CGL. Eventually, the drug-gene network included ibuprofen-CXCR1, ibuprofen-CXCR1, cenicriviroc-CCR2, fenofibrate-JUN, and other relationship pairs. Ibuprofen treatment was also validated to downregulate CXCR1 and CXCR2 in peripheral blood mononuclear cells (PBMCs) and improve glucose tolerance, hypertriglyceridemia, hepatic steatosis, and liver inflammation in lipodystrophy mice. Conclusion: Eight biomarkers, namely, CXCR2, TNFSF10, NLRC4, CCR2, CEACAM3, TLR10, TNFAIP3, and JUN, were identified through bioinformatic analyses, and ibuprofen targeting CXCR1 and CXCR2 in PBMCs was shown to improve metabolic disturbance in lipodystrophy, contributing to studies related to the diagnosis and treatment of lipodystrophy.


Assuntos
Biologia Computacional , Animais , Camundongos , Biologia Computacional/métodos , Humanos , Lipodistrofia/genética , Lipodistrofia/tratamento farmacológico , Lipodistrofia/metabolismo , Biomarcadores/metabolismo , Biomarcadores/análise , Masculino , Mapas de Interação de Proteínas , Perfilação da Expressão Gênica , Camundongos Endogâmicos C57BL
3.
Metabolism ; 158: 155959, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942170

RESUMO

OBJECTIVE: The molecular control of feeding after fasting is essential for maintaining energy homeostasis, while overfeeding usually leads to obesity. Identifying non-coding microRNAs (miRNAs) that control food intake could reveal new oligonucleotide-based therapeutic targets for treating obesity and its associated diseases. This study aims to identify a miRNA modulating food intake and its mechanism in neuronal regulation of food intake and energy homeostasis. METHODS: A comprehensive genome-wide miRNA screening in the arcuate nucleus of the hypothalamus (ARC) of fasted mice and ad libitum mice was performed. Through stereotactic virus injections, intracerebroventricular injections, and miRNA sponge technology, miR-7a-5p was inhibited specifically in AgRP neurons and the central nervous system, and metabolic phenotypes were monitored. Quantitative real-time PCR, Western blotting, immunofluorescence, whole-cell patch-clamp recording, and luciferase reporter assay were used to investigate the mechanisms underlying miR-7a-5p's regulation of food intake. RESULTS: We found a significant increase in miR-7a-5p levels after fasting. miR-7a-5p was highly expressed in the ARC, and inhibition of miR-7a-5p specifically in AgRP neurons reduced food intake and body weight gain. miR-7a-5p inhibited S6K1 gene expression by binding to its 3'-UTR. Furthermore, the knockdown of ribosomal S6 kinase 1 (S6K1) in AgRP neurons can partially reverse the effects caused by miR-7a-5p inhibition. Importantly, intracerebroventricular administration of the miR-7a-5p inhibitor could also reduce food intake and body weight gain. CONCLUSION: Our findings suggest that miR-7a-5p responds to energy deficit and regulates food intake by fine-tuning mTOR1/S6K1 signaling in the AgRP neurons, which could be a promising oligonucleotide-based therapeutic target for treating obesity and its associated diseases.

4.
ESC Heart Fail ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690587

RESUMO

AIMS: Previous studies have investigated the relationship between heart failure (HF) and levels of zinc and copper, but conflicting results have been reported. This meta-analysis aims to clarify the role of zinc and copper in HF progression by examining the associations between HF and concentrations of these minerals. METHODS AND RESULTS: We utilized STATA 12.0 software to calculate the standard mean difference (SMD) and 95% confidence interval (CI) for serum zinc and copper levels in patients with HF compared with healthy controls (HCs). The meta-analysis indicated a lower serum zinc level in patients with HF compared with HCs, using a random effects model (SMD = -0.77; 95% CI: -1.01, -0.54; I2 = 61.9%, the P-value for Q test = 0.002). Additionally, the meta-analysis showed an increased serum copper level in patients with HF compared with HCs, using a random effects model (SMD = 0.66; 95% CI: 0.09, 1.23; I2 = 93.8%, the P-value for Q test < 0.001). Meta-regression analysis indicated that publication year, age, and gender were not responsible for heterogeneity across studies. CONCLUSIONS: This meta-analysis demonstrates that patients with HF have lower serum zinc and higher copper concentrations compared with healthy subjects. However, the potential of zinc supplementation as a therapy for HF should be approached with caution. The heterogeneity among the included studies was found to be high. It is recommended that further well-designed large sample studies be conducted to validate these findings.

5.
Food Res Int ; 186: 114305, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729687

RESUMO

Kefir is a traditional dairy beverage, usually made from cow or goat milk fermented with kefir grains, and has many health benefits. To elucidate the fermentation patterns of animal milk kefirs during the fermentation process and find the optimal milk types, cow, camel, goat, and donkey milk were fermented with kefir grains for 0, 1, 3, 5, and 7 days. Volatile and non-volatile metabolites and microbial changes were dynamically monitored. The results showed that volatile flavor substances were massively elevated in four kefirs on days 1-3. Lipids and carbohydrates gradually decreased, while amino acids, small peptides, and tryptophan derivatives accumulated during fermentation in four kefirs. Besides, four kefirs had similar alterations in Lactobacillus and Acetobacter, while some distinctions existed in low-abundance bacteria. Association analysis of microorganisms and volatile and non-volatile metabolites also revealed the underlying fermentation mechanism. This study found that appropriately extending the fermentation time contributed to the accumulation of some functional nutrients. Furthermore, goat and donkey milk could be the better matrices for kefir fermentation.


Assuntos
Equidae , Fermentação , Cabras , Kefir , Leite , Animais , Kefir/microbiologia , Bovinos , Leite/microbiologia , Leite/química , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/metabolismo , Paladar , Camelus , Microbiologia de Alimentos , Lactobacillus/metabolismo , Microbiota , Acetobacter/metabolismo , Aminoácidos/metabolismo , Aminoácidos/análise
6.
Oral Dis ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696357

RESUMO

OBJECTIVE: This study aimed to clarify the relationship between FADD amplification and overexpression and the tumor immune microenvironment. METHODS: Immunohistochemical staining and bioanalysis were used to analyze the association between FADD expression in tumor cells and cells in tumor microenvironment. RNA-seq analysis was used to detect the differences in gene expression upon FADD overexpression. Flow cytometry and multicolor immunofluorescence staining (mIHC) were used to detect the differences in CD8+ T-cell infiltration in FADD-overexpressed cells or tumor tissues. RESULTS: Overexpression of FADD significantly promoted tumor growth. Cells with high FADD expression presented high expression of CD276 and FGFBP1 and low expression of proinflammatory factors (such as IFIT1-3 and CXCL8), which reduced the percentage of CD8+ T cells and created a "cold tumor" immune microenvironment, thus promoting tumor progression. In vivo and in vitro experiment confirmed that tumor tissues with excessive FADD expression exhibited CD8+ T-cell exclusion in the microenvironment. CONCLUSION: Our preliminary investigation has discovered the association between FADD expression and the immunosuppressive microenvironment in HNSCC. Due to the high frequent amplification of the chromosomal region 11q13.3, where FADD is located, targeting FADD holds promise for improving the immune-inactive state of tumors, subsequently inhibiting HNSCC tumor progression.

7.
Anal Chim Acta ; 1309: 342673, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772656

RESUMO

BACKGROUND: Over-consumption of drugs can result in drug-induced liver damage (DILI), which can worsen liver failure. Numerous studies have shown the significant role ferroptosis plays in the pathophysiology of DILI, which is typified by a marked imbalance between the generation and breakdown of lipid reactive oxygen species (ROS). The content of peroxynitrite (ONOO-) rapidly increased during this process and was thought to be a significant marker of early liver injury. Therefore, the construction of fluorescence probe for the detection and imaging of ONOO- holds immense importance in the early diagnosis and treatment of ferroptosis-mediated DILI. RESULTS: We designed a probe DILI-ONOO based on the ICT mechanism for the purpose of measuring and visualizing ONOO- in ferroptosis-mediated DILI processes and associated studies. This probe exhibited significant fluorescence changes with good sensitivity, selectivity, and can image exogenous and endogenous ONOO- in cells with low cytotoxicity. Using this probe, we were able to show changes in ONOO- content in ferroptosis-mediated DILI cells and mice models induced by the intervention of acetaminophen (APAP) and isoniazid (INH). By measuring the concentration of ferroptosis-related indicators in mice liver tissue, we were able to validate the role of ferroptosis in DILI. It is worth mentioning that compared to existing alanine transaminase (ALT) and aspartate aminotransferase (AST) detection methods, this probe can achieve early identification of DILI prior to serious liver injury. SIGNIFICANCE: This work has significant reference value in researching the relationship between ferroptosis and DILI and visualizing research. The results indicate a strong correlation between the progression of DILI and ferroptosis. Additionally, the use of DILI-ONOO shows promise in investigating the DILI process and assessing the effectiveness of medications in treating DILI.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Ferroptose , Corantes Fluorescentes , Ácido Peroxinitroso , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Ferroptose/efeitos dos fármacos , Animais , Ácido Peroxinitroso/metabolismo , Camundongos , Corantes Fluorescentes/química , Humanos , Acetaminofen/toxicidade , Imagem Óptica , Camundongos Endogâmicos C57BL , Masculino , Isoniazida/química , Raios Infravermelhos
8.
Artigo em Inglês | MEDLINE | ID: mdl-38758151

RESUMO

Objective: To develop a classification model for the five flavors of Chinese medicine using advanced multi-source intelligent sensory information fusion technology. The primary aim is to investigate the feasibility of applying this model to classify and identify the flavors of various Chinese medicines effectively. Methods: We selected 122 representative Chinese medicines, each exhibiting a single distinct flavor (sour, pungent, salty, sweet, bitter), along with 14 common foods. Utilizing the nature and flavors of these decoction pieces specified in Chinese Pharmacopeia (ChP)2020 and the inherent attributes of food components, we obtained valuable data from various sensors, including the PEN3 electronic nose, ASTREE electronic tongue, and SA402B electronic tongue. We then collected single-source data matrices from these sample sensors and a multi-source data matrix that combined the data from all sensors. Using discriminant analysis (DA), principal component analysis-discriminant analysis (PCA-DA), and K-nearest neighbor algorithm (KNN) three kinds of chemometric methods were used to establish five flavors and five-category discrimination models. The results were comprehensively evaluated with the highest correct rate of the model of leave-one-out cross-validation as the index. Results: Upon leave-one-out cross-validation, the correct judgment rate of the five flavors, five-category two-source fusion DA discrimination model (83.8%; ASTREE + SA402B) was significantly higher than the correct judgment rate of the single-source optimal DA and KNN model (73.5%; ASTREE). Following full-sample modeling, the correct judgment rate of the five flavors, five-category three-source fusion DA discrimination model (94.9%; PEN3+ASTREE+SA402B) rose substantially. This was higher than the correct judgment rate of the single-source optimal DA model (77.9%; ASTREE) and slightly higher than the two-source optimal correct judgment rate (89.7%; PEN3 + ASTREE). Conclusions: Compared to single-source identification, multi-source intelligent senses information fusion (MISIF) significantly improved accuracy, providing a new outlook for identifying flavor in Chinese medicine.

9.
Am J Clin Nutr ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729573

RESUMO

BACKGROUND: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVES: Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

10.
Anal Chem ; 96(3): 1345-1353, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38190289

RESUMO

Designing a metal-organic framework (MOF)-derived nanozyme with highly dispersed active sites and high catalytic activity as well as robust structure for colorimetric biosensing of diverse biomolecules remains a substantial challenge. Here, an MOF-derived highly dispersed and pure α-cobalt confined in a nitrogen-doped carbon nanofiber (α-Co@NCNF) nanozyme with superior glucose oxidase (GOD)- and peroxidase (POD)-like activities was constructed for colorimetric assay of multiple biomolecules. Specifically, the α-Co@NCNF nanozyme was synthesized, utilizing in situ electrospinning Co-MOFs into polyacrylonitrile nanofiber (PAN) followed by a pyrolysis process. Taking advantage of the in situ electrospinning strategy, the α-Co nanoparticles were confined in continuous porous NCNF to restrict the growth and prevent the aggregation and oxidation during the pyrolysis process. The resulting special structure considerably improved the enzyme-like performance. A series of experiments validate that the enzyme-like activity of the α-Co@NCNF nanozyme was superior to that of Co@CoO@NCNF (derivatives from Co-MOFs grown on the surface of PAN nanofiber) and nature enzymes. Furthermore, α-Co@NCNF nanozyme-based colorimetric biosensing was developed for monitoring glucose, hydrogen peroxide (H2O2), and glutathione (GSH) and the corresponding linear ranges are 0.1-50 and 50-900 µM and 5-55 and 0.1-20 µM accompanied by the corresponding low detection of 0.03, 1.66, and 0.03 µM. The proposed method for the construction of α-Co@NCNF nanozyme with dual enzyme-like properties provides a new insight for designing novel nanozymes and has prospects for application in colorimetric biosensing.


Assuntos
Estruturas Metalorgânicas , Nanofibras , Peróxido de Hidrogênio , Estruturas Metalorgânicas/química , Carbono/química , Nitrogênio/química , Cobalto , Antioxidantes , Colorimetria/métodos
11.
Drug Dev Ind Pharm ; 50(2): 150-162, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38194223

RESUMO

OBJECTIVE: This study aims to investigate the quality consistency between traditional decoction (TD) of Amomum villosum and its dispensing granule decoction (DGD). Fifteen batches of TD and nine batches of dispensing granules (manufactured by A, B, and C) were prepared and evaluated for their consistency. METHODS: Firstly, The chemical similarity of TD and DGD was examined using GC and HPLC, coupled with hierarchical cluster analysis (HCA), criteria importance though intercrieria correlation(CRITIC) weighting method, and principal component analysis (PCA). Secondly, the gastrointestinal motility experiments in mice, along with the CRITIC weighting method, were employed to assess the bioequivalence of TD and DGD of Amomum villosum. Finally, the entropy weight technique-gray relative analysis(GRA) method was used to compare the quality of Amomum villosum decoctions. RESULTS: ①The CRITIC weighting method indicated significantly higher scores for TD than DGD (p < 0.01). HCA and PCA results demonstrated a clear distinction between TD and DGD. ②Gastrointestinal motility test results revealed no significant difference between TD and DGD in other indicators (p > 0.05).③Gray relative analysis results showed that the relative correlation of TD was more significant than that of DGD. CONCLUSION: The chemical composition of DGD and TD differed. The biological activity of DGD-A/B was consistent with that of TD, while the difference between DGD-C and TD was significant. A comprehensive evaluation showed that TD exhibited better quality than DGD. DGD manufacturers should optimize the preparation process to enhance product quality.


Assuntos
Amomum , Medicamentos de Ervas Chinesas , Animais , Camundongos , Medicamentos de Ervas Chinesas/química , Amomum/química , Equivalência Terapêutica , Cromatografia Líquida de Alta Pressão/métodos , Análise de Componente Principal
12.
Foods ; 13(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38254538

RESUMO

Water boiling under atmospheric pressure (CAP) and water boiling under high pressure (CHP) are two popular domestic cooking methods for Chinese porridge making. In this study, we aimed to evaluate the effects of these two methods on the phenolic acid composition, antioxidant activity, and starch digestibility of triticale porridges. The contents of total free and total bound phenolic acids in the CHP sample were 1.3 and 1.6 times higher than those in the CAP counterpart, respectively, although the DPPH and ABTS values of these two samples were comparable. CAP induced more small pieces of starch than CHP, and the gelatinization enthalpy was 19% higher in the CHP sample than that in the CAP. Both cooking methods increased the starch digestibility, while the CHP sample (58.84) showed a lower GI than the CAP (61.52). These results may promote the application of triticale in health-promoting staple foods.

13.
Cell Host Microbe ; 32(1): 63-78.e7, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38056459

RESUMO

Propionate is a short-chain fatty acid that is generated upon microbiome-mediated fiber fermentation in the intestine. By modulating immune and metabolic pathways, propionate exerts many health benefits. Key bacterial species, such as Bacteroides thetaiotaomicron, generate propionate, but the biochemical pathways and specific functions remain undetermined. We identified a gene operon-encoding methylmalonyl-CoA mutase (MCM) that contributes to propionate biosynthesis in B. thetaiotaomicron. Colonization of germ-free mice with wild-type or MCM-deficient strains as well as in vitro examination demonstrated that MCM-mediated propionate production promotes goblet cell differentiation and mucus-related gene expression. Intestinal organoids lacking the propionate receptor, GPR41, showed reduced goblet cell differentiation upon MCM-mediated propionate production. Furthermore, although wild-type B. thetaiotaomicron alleviated DSS-induced intestinal inflammation, this effect was abolished in mice receiving the MCM-deficient strain but restored upon propionate supplementation. These data emphasize the critical role of MCM-mediated propionate biosynthesis in goblet cell differentiation, offering potential pathways to ameliorate colitis.


Assuntos
Metilmalonil-CoA Mutase , Propionatos , Camundongos , Animais , Metilmalonil-CoA Mutase/genética , Metilmalonil-CoA Mutase/metabolismo , Propionatos/farmacologia , Propionatos/metabolismo , Bacteroides/metabolismo , Diferenciação Celular , Homeostase
14.
Diabetes ; 73(2): 225-236, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37976214

RESUMO

Endothelial cells (EC) play essential roles in retinal vascular homeostasis. This study aimed to characterize retinal EC heterogeneity and functional diversity using single-cell RNA sequencing. Systematic analysis of cellular compositions and cell-cell interaction networks identified a unique EC cluster with high inflammatory gene expression in diabetic retina; sphingolipid metabolism is a prominent aspect correlated with changes in retinal function. Among sphingolipid-related genes, alkaline ceramidase 2 (ACER2) showed the most significant increase. Plasma samples of patients with nonproliferative diabetic retinopathy (NPDR) with diabetic macular edema (DME) or without DME (NDME) and active proliferative DR (PDR) were collected for mass spectrometry analysis. Metabolomic profiling revealed that the ceramide levels were significantly elevated in NPDR-NDME/DME and further increased in active PDR compared with control patients. In vitro analyses showed that ACER2 overexpression retarded endothelial barrier breakdown induced by ceramide, while silencing of ACER2 further disrupted the injury. Moreover, intravitreal injection of the recombinant ACER2 adeno-associated virus rescued diabetes-induced vessel leakiness, inflammatory response, and neurovascular disease in diabetic mouse models. Together, this study revealed a new diabetes-specific retinal EC population and a negative feedback regulation pathway that reduces ceramide content and endothelial dysfunction by upregulating ACER2 expression. These findings provide insights into cell-type targeted interventions for diabetic retinopathy.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Animais , Camundongos , Humanos , Retinopatia Diabética/metabolismo , Células Endoteliais/metabolismo , Retina/metabolismo , Ceramidas , Esfingolipídeos
15.
Gut ; 73(2): 268-281, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37734910

RESUMO

BACKGROUND AND AIMS: Deregulation of RNA N6-methyladenosine (m6A) modification in intestinal epithelial cells (IECs) influences intestinal immune cells and leads to intestinal inflammation. We studied the function of fat mass-and obesity-associated protein (FTO), one of the m6A demethylases, in patients with ulcerative colitis (UC). METHODS: We analysed colon tissues of Ftoflox/flox; Villin-cre mice and their Ftoflox/flox littermates with dextran sulfate sodium (DSS) using real-time PCR and 16s rRNA sequencing. RNA and methylated RNA immunoprecipitation sequencing were used to analyse immunocytes and IECs. Macrophages were treated with conditioned medium of FTO-knockdown MODE-K cells or sphingosine-1-phosphate (S1P) and analysed for gene expression. Liquid chromatograph mass spectrometry identified C16-ceramide. RESULTS: FTO downregulation was identified in our in-house cohort and external cohorts of UC patients. Dysbiosis of gut microbiota, increased infiltration of proinflammatory macrophages, and enhanced differentiation of Th17 cells were observed in Ftoflox/flox;Villin-cre mice under DSS treatment. FTO deficiency resulted in an increase in m6A modification and a decrease in mRNA stability of CerS6, the gene encoding ceramide synthetase, leading to the downregulation of CerS6 and the accumulation of S1P in IECs. Subsequentially, the secretion of S1P by IECs triggered proinflammatory macrophages to secrete serum amyloid A protein 1/3, ultimately inducing Th17 cell differentiation. In addition, through bioinformatic analysis and experimental validation, we identified UC patients with lower FTO expression might respond better to vedolizumab treatment. CONCLUSIONS: FTO downregulation promoted UC by decreasing CerS6 expression, leading to increased S1P accumulation in IECs and aggravating colitis via m6A-dependent mechanisms. Lower FTO expression in UC patients may enhance their response to vedolizumab treatment.


Assuntos
Colite Ulcerativa , Colite , Humanos , Animais , Camundongos , Colite Ulcerativa/metabolismo , RNA Ribossômico 16S/metabolismo , Mucosa Intestinal/metabolismo , Colite/induzido quimicamente , Colite/genética , Colo/metabolismo , Esfingolipídeos/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo
16.
Bioresour Technol ; 394: 130273, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38160851

RESUMO

Four kinds of Fe/N co-doped porous hydrochar were prepared by one/two-step N-doping schemes using microwave/traditional pyrolysis methods for removing Cr(VI) from aqueous phase. Heterocyclic-N was introduced through CO(NH2)2-based hydrothermal carbonization process, which could adjust the electronic structure of the hydrochar framework. Furthermore, Fe0 and Fe3O4 were embedded into hydrochar via carbothermal reduction reaction using FeCl3 as the precursor, which improved the reducibility and magnetism of the material. The modified hydrochar exhibited pH-dependency and rapid kinetic equilibrium, and the maximal adsorption amount of magnetic porous hydrochar obtained by microwave-assisted one-step N-doping (MP1HCMW) reached 274.34 mg/g. Meanwhile, the modified hydrochar had a high tolerance to multiple co-existing ions and the removal efficiency maintained above 73.91 % during five regeneration cycles. Additionally, MP1HCMW efficiently removed Cr(VI) via pore filling, electrostatic attraction, ion exchange, reduction, complexation, and precipitation. Summarily, Fe/N co-doped porous hydrochar was a feasible adsorbent with outstanding remediation potential for Cr(VI)-contaminated water.


Assuntos
Poluentes Químicos da Água , Água , Adsorção , Porosidade , Poluentes Químicos da Água/química , Concentração de Íons de Hidrogênio , Cromo/química , Cinética , Fenômenos Magnéticos
17.
J Clin Endocrinol Metab ; 109(6): 1474-1484, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38157274

RESUMO

CONTEXT: Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear. OBJECTIVE: The objective of this work is to examine the alteration of gut microbiota in patients with CS. METHODS: We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS. RESULTS: We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus, that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro. CONCLUSION: This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health.


Assuntos
Síndrome de Cushing , Disbiose , Fezes , Microbioma Gastrointestinal , Hidrocortisona , Humanos , Disbiose/microbiologia , Disbiose/metabolismo , Masculino , Feminino , Microbioma Gastrointestinal/fisiologia , Síndrome de Cushing/microbiologia , Síndrome de Cushing/metabolismo , Hidrocortisona/metabolismo , Pessoa de Meia-Idade , Adulto , Fezes/microbiologia , Estudos de Casos e Controles , Clostridiales/isolamento & purificação , Clostridiales/metabolismo
18.
J Sci Food Agric ; 104(2): 818-828, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37683050

RESUMO

BACKGROUND: Lima bean protein isolate (LPI) is an underutilized plant protein. Similar to other plant proteins, it may display poor emulsification properties. In order to improve its emulsifying properties, one effective approach is using protein and polysaccharide mixtures. This work investigated the structural and emulsifying properties of LPI as well as the development of an LPI/xanthan gum (XG)-stabilized oil-in-water emulsion. RESULTS: The highest protein solubility (84.14%) of LPI was observed and the molecular weights (Mw ) of most LPI subunits were less than 35 kDa. The enhanced emulsifying activity index (15.97 m2 g-1 ) of LPI might be associated with its relatively high protein solubility and more low-Mw subunits (Mw < 35 kDa). The effects of oil volume fraction (ϕ) on droplet size, microstructure, rheological behavior and stability of emulsions were investigated. As ϕ increased from 0.2 to 0.8, the emulsion was arranged from spherical and dispersed oil droplets to polyhedral packing of oil droplets adjacent to each other, while the LPI/XG mixtures changed from particles (in the uncrowded interfacial layer) to lamellae (in the crowded interfacial layer). When ϕ was 0.6, the emulsion was in a transitional state with the coexistence of particles and lamellar structures on the oil droplet surface. The LPI/XG-stabilized emulsions with ϕ values of 0.6-0.8 showed the highest stability during a 14-day storage period. CONCLUSION: This study developed a promising plant-based protein resource, LPI, and demonstrates potential application of LPI/XG as an emulsifying stabilizer in foods. © 2023 Society of Chemical Industry.


Assuntos
Phaseolus , Proteínas de Plantas , Emulsões/química , Proteínas de Plantas/química , Polissacarídeos Bacterianos/química , Água/química
19.
Diabetes Res Clin Pract ; 207: 111058, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38104902

RESUMO

AIMS: Current evidence regarding iron status and mortality risk among patients with diabetes is limited. This study aimed to evaluate association of iron indices with all-cause and cause-specific mortality risk among patients with diabetes. METHODS: The current study included 2080 (with ferritin data), 1974 (with transferrin saturation (Tsat) data), and 1106 (with soluble transferrin receptor (sTfR) data) adults with diabetes from NHANES 1999-2018. Death outcomes were obtained from National Death Index through December 31, 2019. Cox proportional hazards models were employed to calculate hazard ratios and 95% confidence intervals for mortality. RESULTS: Association with all-cause mortality was demonstrated to be J-shaped for serum ferritin (Pnonlinearity < 0.01), U-shaped for Tsat (Pnonlinearity < 0.01) and linear for sTfR (Plinearity < 0.01). Ferritin 300-500 ng/mL possessed lower all-cause mortality risk than ferritin ≤ 100 ng/mL, 100-300 ng/mL, and > 500 ng/mL. Tsat 25-32 % showed a protective effect on all-cause mortality risk compared with Tsat ≤ 20 %, 20-25 %, and > 32 %. Individuals with sTfR < 4 mg/L were associated with a lower risk of all-cause mortality than those with higher sTfR. CONCLUSIONS: Moderate levels of serum ferritin (300-500 ng/mL), Tsat (25 %-32 %) and a lower concentration of sTfR (< 4 mg/L) identified adults with diabetes with lower all-cause mortality risk, adding novel modifiers to diabetes management.


Assuntos
Diabetes Mellitus , Ferro , Adulto , Humanos , Ferro/metabolismo , Causas de Morte , Inquéritos Nutricionais , Ferritinas
20.
Food Chem ; 440: 138210, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38118320

RESUMO

Panax notoginseng powder (PNP) has high medicinal value and is widely used in the medical and health food industries. However, the adulteration of PNP in the market has dramatically reduced its efficacy. Therefore, this study intends to use artificial intelligence sensory (AIS) and multi-source information fusion (MIF) technology to try to establish a quality evaluation system for different grades of PNP and adulterated Panax notoginseng powder (AD-PNP). The highest accuracy rate reached 100% in identifying PNP grade and adulteration. In the prediction of adulteration ratio and total saponin content, the optimal determination coefficients of the test set were 0.9965 and 0.9948, respectively, and the root mean square errors were 0.0109 and 0.0123, respectively. Therefore, the grade identification method of PNP and the evaluation system of AD-PNP based on AIS and MIF technology can rapidly and accurately evaluate the quality of PNP.


Assuntos
Medicamentos de Ervas Chinesas , Panax notoginseng , Panax , Saponinas , Pós , Inteligência Artificial , Controle de Qualidade
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