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1.
FASEB J ; 38(3): e23459, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38329343

RESUMO

Wound healing is facilitated by neoangiogenesis, a complex process that is essential to tissue repair in response to injury. MicroRNAs are small, noncoding RNAs that can regulate the wound healing process including stimulation of impaired angiogenesis that is associated with type-2 diabetes (T2D). Expression of miR-409-3p was significantly increased in the nonhealing skin wounds of patients with T2D compared to the non-wounded normal skin, and in the skin of a murine model with T2D. In response to high glucose, neutralization of miR-409-3p markedly improved EC growth and migration in human umbilical vein endothelial cells (HUVECs), promoted wound closure and angiogenesis as measured by increased CD31 in human skin organoids, while overexpression attenuated EC angiogenic responses. Bulk mRNA-Seq transcriptomic profiling revealed BTG2 as a target of miR-409-3p, where overexpression of miR-409-3p significantly decreased BTG2 mRNA and protein expression. A 3' untranslated region (3'-UTR) luciferase assay of BTG2 revealed decreased luciferase activity with overexpression of miR-409-3p, while inhibition had opposite effects. Mechanistically, in response to high glucose, miR-409-3p deficiency in ECs resulted in increased mTOR phosphorylation, meanwhile BTG-anti-proliferation factor 2 (BTG2) silencing significantly decreased mTOR phosphorylation. Endothelial-specific and tamoxifen-inducible miR-409-3p knockout mice (MiR-409IndECKO ) with hyperglycemia that underwent dorsal skin wounding showed significant improvement of wound closure, increased blood flow, granulation tissue thickness (GTT), and CD31 that correlated with increased BTG2 expression. Taken together, our results show that miR-409-3p is a critical mediator of impaired angiogenesis in diabetic skin wound healing.


Assuntos
Diabetes Mellitus Tipo 2 , Proteínas Imediatamente Precoces , MicroRNAs , Proteínas Supressoras de Tumor , Animais , Humanos , Camundongos , Proliferação de Células/fisiologia , Diabetes Mellitus Tipo 2/genética , Glucose , Células Endoteliais da Veia Umbilical Humana/metabolismo , Proteínas Imediatamente Precoces/genética , Luciferases , Camundongos Obesos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro , Serina-Treonina Quinases TOR , Proteínas Supressoras de Tumor/genética , Cicatrização/genética
2.
Med Sci Monit ; 30: e944015, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38314443

RESUMO

The authors informed the journal that errors occurred in their manuscript, and were not noticed by the authors during the proofreading. Corrections: 1. Figure 1, top entry: "Predipocytes" should read "Preadipocytes". 2. Figure 3, chart "TIGAR": "-9" value on y axis should read "-8". 3. Figure 4, chart "let-7g-5p": the upper "-4" value on y axis should read "0". 4. Figure 5: the title of the bottom right chart should read "TIGAR". 5. Figure 6, chart "miR-26a-5p": the values on y axis should read from the top: 2, 1, 0, -1, -2. 6. Figure 6, chart "miR-374a-5p": the values on y axis should read from the top: 0, -1, -2, -3, -4. 7. Table 4., in the 6 rows from the bottom: in column "miRNAs", "hsa-miR-21-5" should read "hsa-miR-21-5p". 8. Supplementary Table1, 1st column on the left: "TG-HDL" should read "TG/HDL" Reference: Adam Wróblewski, Justyna Strycharz, Katarzyna Oszajca, Piotr Czarny, Ewa Swiderska, Tomasz Matyjas, Andrzej Zieleniak, Monika Rucinska, Lech Pomorski, Józef Drzewoski, Agnieszka Sliwinska, Janusz Szemraj: Dysregulation of Inflammation, Oxidative Stress, and Glucose Metabolism-Related Genes and miRNAs in Visceral Adipose Tissue of Women with Type 2 Diabetes Mellitus. Med Sci Monit, 2023; 29: e939299. DOI: 10.12659/MSM.939299.


Assuntos
Diabetes Mellitus Tipo 2 , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Diabetes Mellitus Tipo 2/genética , Gordura Intra-Abdominal/metabolismo , Inflamação/genética , Estresse Oxidativo/genética , Glucose
3.
Sci Rep ; 14(1): 2973, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316940

RESUMO

The nuclear factor erythroid 2-related factor 2 (NRF2) is a crucial transcription factor that plays a central role in regulating oxidative stress pathways by binding antioxidant response elements, but its involvement in early embryo development remains largely unexplored. In this study, we demonstrated that NRF2 mRNA is expressed in porcine embryos from day 2 to day 7 of development, showing a decrease in abundance from day 2 to day 3, followed by an increase on day 5 and day 7. Comparable levels of NRF2 mRNA were observed between early-cleaving and more developmental competent embryos and late-cleaving and less developmental competent embryos on day 4 and day 5 of culture. Attenuation of NRF2 mRNA significantly decreased development of parthenote embryos to the blastocyst stage. When NRF2-attenuated embryos were cultured in presence of 3.5 mM or 7 mM glucose, development to the blastocyst stage was dramatically decreased in comparison to the control group (15.9% vs. 27.8% for 3.5 mM glucose, and 5.4% vs. 25.3% for 7 mM glucose). Supplementation of melatonin moderately improved the development of NRF2-attenuated embryos cultured in presence of 0.6 mM glucose. These findings highlight the importance of NRF2 in early embryo development, particularly in embryos cultured under metabolically stressful conditions.


Assuntos
Desenvolvimento Embrionário , Fator 2 Relacionado a NF-E2 , Suínos , Animais , Desenvolvimento Embrionário/genética , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Blastocisto/metabolismo , Glucose/metabolismo , Estresse Fisiológico , RNA Mensageiro/metabolismo , Técnicas de Cultura Embrionária
6.
Transl Psychiatry ; 14(1): 79, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320995

RESUMO

The brain neurotramsmitter dopamine may play an important role in modulating systemic glucose homeostasis. In seven hundred and four drug- naïve patients with first-episode schizophrenia, we provide robust evidence of positive associations between negative symptoms of schizophrenia and high fasting blood glucose. We then show that glucose metabolism and negative symptoms are improved when intermittent theta burst stimulation (iTBS) on prefrontal cortex (PFC) is performed in patients with predominantly negative symptoms of schizophrenia. These findings led us to hypothesize that the prefrontal cortical dopamine deficit, which is known to be associated with negative symptoms, may be responsible for abnormal glucose metabolism in schizophrenia. To explore this, we optogenetically and chemogenetically inhibited the ventral tegmental area (VTA)-medial prefrontal cortex (mPFC) dopamine projection in mice and found both procedures caused glucose intolerance. Moreover, microinjection of dopamine two receptor (D2R) neuron antagonists into mPFC in mice significantly impaired glucose tolerance. Finally, a transgenic mouse model of psychosis named Disc1tr exhibited depressive-like symptoms, impaired glucose homeostasis, and compared to wild type littermates reduced D2R expression in prefrontal cortex.


Assuntos
Dopamina , Esquizofrenia , Camundongos , Humanos , Animais , Dopamina/metabolismo , Esquizofrenia/metabolismo , Área Tegmentar Ventral/metabolismo , Camundongos Transgênicos , Córtex Pré-Frontal/metabolismo , Glucose/metabolismo , Proteínas do Tecido Nervoso/metabolismo
7.
Nat Commun ; 15(1): 1102, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321044

RESUMO

The Entner-Doudoroff (ED) pathway provides an alternative to glycolysis. It converts 6-phosphogluconate (6-PG) to glyceraldehyde-3-phosphate and pyruvate in two steps consisting of a dehydratase (EDD) and an aldolase (EDA). Here, we investigate its distribution and significance in higher plants and determine the ED pathway is restricted to prokaryotes due to the absence of EDD genes in eukaryotes. EDDs share a common origin with dihydroxy-acid dehydratases (DHADs) of the branched chain amino acid pathway (BCAA). Each dehydratase features strict substrate specificity. E. coli EDD dehydrates 6-PG to 2-keto-3-deoxy-6-phosphogluconate, while DHAD only dehydrates substrates from the BCAA pathway. Structural modeling identifies two divergent domains which account for their non-overlapping substrate affinities. Coupled enzyme assays confirm only EDD participates in the ED pathway. Plastid ancestors lacked EDD but transferred metabolically promiscuous EDA, which explains the absence of the ED pathway from the Viridiplantae and sporadic persistence of EDA genes across the plant kingdom.


Assuntos
Escherichia coli , Via de Pentose Fosfato , Escherichia coli/genética , Glicólise , Ácido Pirúvico , Plantas/metabolismo , Hidroliases/metabolismo , Glucose/metabolismo
8.
Int J Med Sci ; 21(3): 583-592, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322591

RESUMO

Sodium-glucose cotransporter 2 (SGLT2) inhibitors revealed the protective function on various systemic diseases. This study aimed to determine whether the usage of SGLT2 inhibitors associates with incidences of superficial keratopathy and infectious keratitis in type 2 diabetes mellitus (T2DM) patients. A retrospective cohort study with the usage of National Health Insurance Research Database of Taiwan was conducted. The T2DM patients were divided into the SGLT2 inhibitors and control groups according to the usage of SGLT2 inhibitors or not. The major outcomes were defined as the occurrence of superficial keratopathy and infectious keratitis. There were 766 and 1037 episodes of superficial keratopathy in the SGLT2 inhibitors and control groups and SGLT2 inhibitors group showed a significantly lower incidence of superficial keratopathy than the control group (aHR: 0.721, 95% CI: 0.656-0.791, P < 0.0001). Also, there were 166 and 251 infectious keratitis events in the SGLT2 inhibitors and control groups and patients in the SGLT2 inhibitors group revealed a significantly lower infectious keratitis incidence than those in the control group (aHR: 0.654, 95% CI: 0.537-0.796, P < 0.0001). In addition, the patients that received SGLT2 inhibitors demonstrated lower cumulative incidences of both superficial keratopathy and infectious keratitis compared to the non-SGLT2 inhibitors users (both P < 0.0001). In conclusion, the usage of SGLT2 inhibitors correlates to lower incidence of superficial keratopathy and infectious keratitis in T2DM individuals, which is more significant in patients with persistent SGLT2 inhibitors application.


Assuntos
Doenças da Córnea , Diabetes Mellitus Tipo 2 , Ceratite , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/complicações , Incidência , Hipoglicemiantes , Estudos Retrospectivos , Doenças da Córnea/complicações , Ceratite/complicações , Glucose , Sódio
9.
Front Endocrinol (Lausanne) ; 15: 1290226, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323107

RESUMO

Background: There were seven novel and easily accessed insulin resistance (IR) surrogates established, including the Chinese visceral adiposity index (CVAI), the visceral adiposity index (VAI), lipid accumulation product (LAP), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR). We aimed to explore the association between the seven IR surrogates and incident coronary heart disease (CHD), and to compare their predictive powers among Chinese population. Methods: This is a 10-year prospective cohort study conducted in China including 6393 participants without cardiovascular disease (CVD) at baseline. We developed Cox regression analyses to examine the association of IR surrogates with CHD (hazard ratio [HR], 95% confidence intervals [CI]). Moreover, the receiver operating characteristic (ROC) curve was performed to compare the predictive values of these indexes for incident CHD by the areas under the ROC curve (AUC). Results: During a median follow-up period of 10.25 years, 246 individuals newly developed CHD. Significant associations of the IR surrogates (excepted for VAI) with incident CHD were found in our study after fully adjustment, and the fifth quintile HRs (95% CIs) for incident CHD were respectively 2.055(1.216-3.473), 1.446(0.948-2.205), 1.753(1.099-2.795), 2.013(1.214-3.339), 3.169(1.926-5.214), 2.275(1.391-3.719) and 2.309(1.419-3.759) for CVAI, VAI, LAP, TyG, TyG-BMI, TyG-WC and TyG-WHtR, compared with quintile 1. Furthermore, CVAI showed maximum predictive capacity for CHD among these seven IR surrogates with the largest AUC: 0.632(0.597,0.667). Conclusion: The seven IR surrogates (excepted for VAI) were independently associated with higher prevalence of CHD, among which CVAI is the most powerful predictor for CHD incidence in Chinese populations.


Assuntos
Resistência à Insulina , Produto da Acumulação Lipídica , Humanos , Estudos Prospectivos , Glucose , Circunferência da Cintura , Triglicerídeos , Obesidade Abdominal/complicações
10.
JAMA Netw Open ; 7(2): e2354595, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38324312

RESUMO

Importance: Pediatric data on inpatient home insulin pumps are absent in the literature. Understanding safety of home insulin pumps, managed by patients or caregivers, during times of illness will help diabetes technology securely move into pediatric hospitals. Objective: To examine whether insulin can be safely and accurately delivered to hospitalized children through home insulin pumps when managed by patients or caregivers. Design, Setting, and Participants: This single-center, retrospective, observational cohort study included children with insulin-dependent diabetes admitted to a tertiary children's hospital from January 1, 2016, to December 31, 2021. In all these patients, diabetes was the primary or secondary diagnosis on admission. Exposure: Insulin delivery via home insulin pump, hospital insulin pump, or subcutaneous injection. Main Outcomes and Measures: Hyperglycemia (glucose, >250 mg/dL) and hypoglycemia (glucose, <45 mg/dL) rates (quantified as the proportion of total insulin-days), glucose variability, and diabetic ketoacidosis (DKA) recurrences were compared for hospital pumps (manual mode), home pumps (manual mode), and subcutaneous injections using bivariate tests. Results: There were 18 096 insulin-days among 2738 patients aged 0.5 to 25 years (median age, 15.8 years [IQR, 12.3-18.3 years]). Overall, 990 (5.5%) of insulin-days involved hospital insulin pumps, and 775 (4.3%) involved home pumps. A total of 155 insulin-days (15.7%) involving hospital pumps were hyperglycemic, compared with 209 (27.0%) involving home pumps and 7374 (45.2%) involving injections (P < .001). Moderate hypoglycemia days comprised 31 insulin-days (3.1%) involving hospital pumps compared with 35 (4.5%) involving home pumps and 830 (5.1%) involving injections (P = .02). Severe hypoglycemia did not differ significantly according to insulin delivery method. Two patients using injections (0.01%) developed DKA; no patients using hospital or home pumps developed DKA. Conclusions and Relevance: In this cohort study, home insulin pump use was found to be safe in a children's hospital regarding hyperglycemia and hypoglycemia. These data support use of home insulin pumps during pediatric admissions in patients who do not require intensive care and without active DKA.


Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Hiperglicemia , Hipoglicemia , Humanos , Criança , Adolescente , Criança Hospitalizada , Estudos de Coortes , Estudos Retrospectivos , Insulina Regular Humana , Insulina , Glucose , Hospitais Pediátricos
11.
Sci Rep ; 14(1): 2886, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38311611

RESUMO

Increasing attention has been given to mango (Mangifera indica) fruits owing to their characteristic taste, and rich nutritional value. Mango kernels are typically discarded as a major waste product in mango industry, though of potential economic value. The present study aims to outline the first comparison of different mango kernel cvs. originated from different localities alongside Egypt, e.g., Sharqia, Suez, Ismailia, and Giza. Gas chromatography-mass spectroscopy (GC-MS) post silylation analysis revealed that sugars were the major class being detected at 3.5-290.9 µg/mg, with some kernels originating from Sharqia province being the richest amongst other cvs. In consistency with sugar results, sugar alcohols predominated in Sharqia cvs. at 1.3-38.1 µg/mg represented by ribitol, iditol, pinitol, and myo-inositol. No major variation was observed in the fatty acids profile either based on cv. type or localities, with butyl caprylate as a major component in most cvs. identified for the first time in mango. Regarding phenolics, Sedeeq cv. represented the highest level at 18.3 µg/mg and showing distinct variation among cvs. posing phenolics as better classification markers than sugars. Multivariate data analyses (MVA) confirmed that the premium cvs "Aweis and Fons" were less enriched in sugars, i.e., fructose, talose, and glucose compared to the other cvs. Moreover, MVA of Zabdeya cv. collected from three localities revealed clear segregation to be chemically distinct. Sharqia originated mango kernels were rich in sugars (e.g., glucose and fructose), whilst sarcosine esters predominated in other origins.


Assuntos
Mangifera , Cromatografia Gasosa-Espectrometria de Massas , Mangifera/química , Egito , Resíduos/análise , Frutas/química , Açúcares/metabolismo , Glucose/metabolismo , Frutose/metabolismo
12.
FASEB J ; 38(3): e23458, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38315453

RESUMO

Diabetic kidney disease (DKD), a major microvascular complication of diabetes, is characterized by its complex pathogenesis, high risk of chronic renal failure, and lack of effective diagnosis and treatment methods. GSK3ß (glycogen synthase kinase 3ß), a highly conserved threonine/serine kinase, was found to activate glycogen synthase. As a key molecule of the glucose metabolism pathway, GSK3ß participates in a variety of cellular activities and plays a pivotal role in multiple diseases. However, these effects are not only mediated by affecting glucose metabolism. This review elaborates on the role of GSK3ß in DKD and its damage mechanism in different intrinsic renal cells. GSK3ß is also a biomarker indicating the progression of DKD. Finally, the protective effects of GSK3ß inhibitors on DKD are also discussed.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta , Proteínas Serina-Treonina Quinases , Rim/metabolismo , Glucose/metabolismo
14.
Transpl Int ; 37: 11900, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38304198

RESUMO

The generation of insulin-producing cells from human-induced pluripotent stem cells holds great potential for diabetes modeling and treatment. However, existing protocols typically involve incubating cells with un-physiologically high concentrations of glucose, which often fail to generate fully functional IPCs. Here, we investigated the influence of high (20 mM) versus low (5.5 mM) glucose concentrations on IPCs differentiation in three hiPSC lines. In two hiPSC lines that were unable to differentiate to IPCs sufficiently, we found that high glucose during differentiation leads to a shortage of NKX6.1+ cells that have co-expression with PDX1 due to insufficient NKX6.1 gene activation, thus further reducing differentiation efficiency. Furthermore, high glucose during differentiation weakened mitochondrial respiration ability. In the third iPSC line, which is IPC differentiation amenable, glucose concentrations did not affect the PDX1/NKX6.1 expression and differentiation efficiency. In addition, glucose-stimulated insulin secretion was only seen in the differentiation under a high glucose condition. These IPCs have higher KATP channel activity and were linked to sufficient ABCC8 gene expression under a high glucose condition. These data suggest high glucose concentration during IPC differentiation is necessary to generate functional IPCs. However, in cell lines that were IPC differentiation unamenable, high glucose could worsen the situation.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células Secretoras de Insulina , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Insulina/metabolismo , Diferenciação Celular , Glucose/farmacologia , Glucose/metabolismo
15.
Nat Commun ; 15(1): 1032, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310110

RESUMO

Glutarate is a key monomer in polyester and polyamide production. The low efficiency of the current biosynthetic pathways hampers its production by microbial cell factories. Herein, through metabolic simulation, a lysine-overproducing E. coli strain Lys5 is engineered, achieving titer, yield, and productivity of 195.9 g/L, 0.67 g/g glucose, and 5.4 g/L·h, respectively. Subsequently, the pathway involving aromatic aldehyde synthase, monoamine oxidase, and aldehyde dehydrogenase (AMA pathway) is introduced into E. coli Lys5 to produce glutarate from glucose. To enhance the pathway's efficiency, rational mutagenesis on the aldehyde dehydrogenase is performed, resulting in the development of variant Mu5 with a 50-fold increase in catalytic efficiency. Finally, a glutarate tolerance gene cbpA is identified and genomically overexpressed to enhance glutarate productivity. With enzyme expression optimization, the glutarate titer, yield, and productivity of E. coli AMA06 reach 88.4 g/L, 0.42 g/g glucose, and 1.8 g/L·h, respectively. These findings hold implications for improving glutarate biosynthesis efficiency in microbial cell factories.


Assuntos
Escherichia coli , Glutaratos , Escherichia coli/genética , Escherichia coli/metabolismo , Glutaratos/metabolismo , Glucose/metabolismo , Engenharia Metabólica/métodos , Aldeído Desidrogenase/metabolismo
16.
PLoS One ; 19(2): e0282773, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38300917

RESUMO

AIMS: To evaluate the association between ideal cardiovascular health metrics (ICVHM) and incident low estimated glomerular filtration rate (eGFR) among the Iranian population. METHODS: The study population included 6927 Iranian adults aged 20-65 years (2942 male) without prevalent low eGFR [i.e., eGFR < 60 ml/min/1.73 m2] and free of cardiovascular disease. The ICVHM was defined according to the 2010 American Heart Association. The multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratios (HRs) of ICVHM both as continuous and categorical variables. RESULTS: Over the median of 12.1 years of follow-up, we found 1259 incident cases of low eGFR among the study population. In this population, ideal and intermediate categories of body mass index (BMI) and blood pressure (BP) and only the ideal category of fasting plasma glucose (FPG) significantly decreased the risk of developing low eGFR; the corresponding HRs and (95% confidence intervals) were (0.87, 0.77-0.99), (0.84, 0.76-0.99), (0.79, 0.68-0.93), (0.70, 0.60-0.83) and (0.76, 0.64-0.91). Also, one additional ICVHM was associated with a reduced risk of low eGFR for the global (0.92, 0.88-0.97) and biological cardiovascular health (0.88, 0.82-0.93) in these participants. A sensitivity analysis using the interval-censoring approach demonstrated that our method is robust, and results remained essentially unchanged. In a subgroup population with dietary data (n = 2285), we did not find the beneficial impact of having intermediate/ideal categories of nutrition status compared to its poor one on incident low eGFR. CONCLUSION: We found a strong inverse association between having higher global ICVHM with incident low eGFR among the non-elderly Iranian population; the issue is mainly attributable to normal BP, BMI, and FPG levels.


Assuntos
Doenças Cardiovasculares , Glucose , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Seguimentos , Indicadores de Qualidade em Assistência à Saúde , Taxa de Filtração Glomerular , Irã (Geográfico)/epidemiologia , Lipídeos , Fatores de Risco , Incidência
17.
Clin Exp Pharmacol Physiol ; 51(3): e13842, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38302074

RESUMO

The effects of SGLT2 inhibitors on hepatic fibrosis in diabetes remain unclear. This study aimed to investigate the effects of empagliflozin on liver fibrosis in high-fat diet/streptozotocin-induced mice and the correlation with gut microbiota. After the application of empagliflozin for 6 weeks, we performed oral glucose tolerance and intraperitoneal insulin tolerance tests to assess glucose tolerance and insulin resistance, and stained liver sections to evaluate histochemical and hepatic pathological markers of liver fibrosis. Moreover, 16S rRNA amplicon sequencing was performed on stool samples to explore changes in the composition of intestinal bacteria. We finally analysed the correlation between gut microbiome and liver fibrosis scores or indicators of glucose metabolism. The results showed that empagliflozin intervention improved glucose metabolism and liver function with reduced liver fibrosis, which might be related to changes in intestinal microbiota. In addition, the abundance of intestinal probiotic Lactobacillus increased, while Ruminococcus and Adlercreutzia decreased after empagliflozin treatment, and correlation analysis showed that the changes in microbiota were positively correlated with liver fibrosis and glucose metabolism. Overall, considering the contribution of the gut microbiota in metabolism, empagliflozin might have improved the beneficial balance of intestinal bacteria composition. The present study provides evidence and indicates the involvement of the gut-liver axis by SGLT2 inhibitors in T2DM with liver fibrosis.


Assuntos
Compostos Benzidrílicos , Microbioma Gastrointestinal , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose , Camundongos , Animais , Estreptozocina/metabolismo , Estreptozocina/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Dieta Hiperlipídica/efeitos adversos , RNA Ribossômico 16S/metabolismo , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Glucose/metabolismo , Camundongos Endogâmicos C57BL
18.
Nutr J ; 23(1): 16, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302919

RESUMO

Labels do not disclose the excess-free-fructose/unpaired-fructose content in foods/beverages. Objective was to estimate excess-free-fructose intake using USDA loss-adjusted-food-availability (LAFA) data (1970-2019) for high fructose corn syrup (HFCS) and apple juice, major sources of excess-free-fructose, for comparison with malabsorption dosages (~ 5 g-children/ ~ 10 g-adults). Unlike sucrose and equimolar fructose/glucose, unpaired-fructose triggers fructose malabsorption and its health consequences. Daily intakes were calculated for HFCS that is generally-recognized-as-safe/ (55% fructose/45% glucose), and variants (65/35, 60/40) with higher fructose-to-glucose ratios (1.9:1, 1.5:1), as measured by independent laboratories. Estimations include consumer-level-loss (CLL) allowances used before (20%), and after, subjective, retroactively-applied increases (34%), as recommended by corn-refiners (~ 2012). No contributions from crystalline-fructose or agave syrup were included due to lack of LAFA data. High-excess-free-fructose-fruits (apples/pears/watermelons/mangoes) were not included. Eaten in moderation they are less likely to trigger malabsorption. Another objective was to identify potential parallel trends between excess-free-fructose intake and the "unexplained" US asthma epidemic. The fructose/gut-dysbiosis/lung axis is well documented, case-study evidence and epidemiological research link HFCS/apple juice intake with asthma, and unlike gut-dysbiosis/gut-fructosylation, childhood asthma prevalence data spans > 40 years. Results Excess-free-fructose daily intake for individuals consuming HFCS with an average 1.5:1 fructose-to-glucose ratio, ranged from 0.10 g/d in 1970, to 11.3 g/d in 1999, to 6.5 g/d in 2019, and for those consuming HFCS with an average 1.9:1 ratio, intakes ranged from 0.13 g/d to 16.9 g/d (1999), to 9.7 g/d in 2019, based upon estimates with a 20% CLL allowance. Intake exceeded dosages that trigger malabsorption (~ 5 g) around ~ 1980. By the early 1980's, tripled apple juice intake had added ~ 0.5 g to average-per-capita excess-free-fructose intake. Contributions were higher (~ 3.8 g /4-oz.) for individuals consuming apple juice consistent with a healthy eating pattern (4-oz. children, 8-oz. adults). The "unexplained" childhood asthma epidemic (1980-present) parallels increasing average-per-capita HFCS/apple juice intake trends and reflects epidemiological research findings. Conclusion Displacement of sucrose with HFCS, its ubiquitous presence in the US food-supply, the industry practice of adding more fructose to HFCS than generally-recognized-as-safe, and increased use of apple juice/crystalline fructose/agave syrup in foods/beverages has contributed to unprecedented excess-free-fructose intake levels, fructose malabsorption, gut-dysbiosis and gut-fructosylation (immunogen burden)-gateways to chronic disease.


Assuntos
Asma , Xarope de Milho Rico em Frutose , Leucemia Linfocítica Crônica de Células B , Malus , Adulto , Humanos , Criança , Xarope de Milho Rico em Frutose/efeitos adversos , Frutose/efeitos adversos , Disbiose , Glucose , Doença Crônica , Asma/epidemiologia , Sacarose
19.
BMC Pediatr ; 24(1): 88, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302960

RESUMO

BACKGROUND AND OBJECTIVE: Evidence-based research has shown that golden hour quality improvement (QI) measures can improve the quality of care and reduce serious complications of premature infants. Herein, we sought to review golden hour QI studies to evaluate the impact on the outcome of preterm infants. METHODS: A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and SinoMed databases from inception to April 03, 2023. Only studies describing QI interventions in the golden hour of preterm infants were included. Outcomes were summarized and qualitative synthesis was performed. RESULTS: Ten studies were eligible for inclusion. All studies were from single centers, of which nine were conducted in the USA and one in Israel. Seven were pre-post comparative studies and three were observational studies. Most included studies were of medium quality (80%). The most common primary outcome was admission temperatures and glucose. Five studies (n = 2308) reported improvements in the admission temperature and three studies (n = 2052) reported improvements in hypoglycemia after QI. Four studies (n = 907) showed that the incidence of bronchopulmonary dysplasia (BPD) was lower in preterm infants after QI: 106/408 (26.0%) vs. 122/424(29.5%) [OR = 0.68, 95% CI 0.48-0.97, p = 0.04]. CONCLUSIONS: Our study showed that the golden hour QI bundle can improve the short-term and long-term outcomes for extremely preterm infants. There was considerable heterogeneity and deficiencies in the included studies, and the variation in impact on outcomes suggests the need to use standardized and validated measures. Future studies are needed to develop locally appropriate, high-quality, and replicable QI projects.


Assuntos
Displasia Broncopulmonar , Hipoglicemia , Lactente , Recém-Nascido , Humanos , Melhoria de Qualidade , Lactente Extremamente Prematuro , Displasia Broncopulmonar/terapia , Glucose
20.
BMC Plant Biol ; 24(1): 85, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308226

RESUMO

BACKGROUND: Onion seeds have limited storage capacity compared to other vegetable seeds. It is crucial to identify the mechanisms that induce tolerance to storage conditions and reduce seed deterioration. To address this goal, an experiment was conducted to evaluate changes in germination, biochemical, physiological, and molecular characteristics of onion seed landraces (Horand, Kazerun landraces and Zargan cultivar) at different aging levels (control, three-days and six-days accelerated aging, and natural aging for one year). RESULTS: The findings suggest that there was an increase in glucose, fructose, total sugar, and electrolyte leakage in the Horand (HOR), Kazerun (KAZ) landraces, and Zarghan (ZAR) cultivar, with Kazerun exhibiting the greatest increase. The percentage and rate of germination of Kazerun decreased by 54% and 33%, respectively, in six-day accelerated aging compared to the control, while it decreased by 12% and 14%, respectively, in Horand. Protein content decreased with increasing levels of aging, with a decrease of 26% in Kazerun landrace at six days of aging, while it was 16% in Horand landrace. The antioxidant activities of catalase, superoxide dismutase, and glutathione peroxidase decreased more intensively in Kazerun. The expression of AMY1, BMY1, CTR1, and NPR1 genes were lower in Kazerun landraces than in Horand and Zargan at different aging levels. CONCLUSIONS: The AMY1, BMY1, CTR1, and NPR1 genes play a pivotal role in onion seed germination, and their downregulation under stressful conditions has been shown to decrease germination rates. In addition, the activity of CAT, SOD, and GPx enzymes decreased by seed aging, and the amount of glucose, fructose, total sugar and electrolyte leakage increased, which ultimately led to seed deterioration. Based on the results of this experiment, it is recommended to conduct further studies into the molecular aspects involved in onion seed deterioration. More research on the genes related to this process is suggested, as well as investigating the impact of different priming treatments on the genes expression involved in the onion seed aging process.


Assuntos
Germinação , Cebolas , Cebolas/genética , Germinação/genética , Sementes/metabolismo , Eletrólitos/análise , Eletrólitos/metabolismo , Frutose/análise , Frutose/metabolismo , Glucose/metabolismo , Açúcares/metabolismo
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