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1.
J Nanobiotechnology ; 22(1): 24, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191388

RESUMO

The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs' preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs' biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials.


Assuntos
Antibacterianos , Nanopartículas Magnéticas de Óxido de Ferro , Animais , Humanos
2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(3): 357-365, 2021 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-34238411

RESUMO

Objective To establish a mouse model of exogenous iron overload combined with tuberculosis(TB). Methods C57BL/6N mice were divided into negative control, low-, medium-, and high-dose iron groups and received intraperitoneal injection of iron dextran at 0, 3.75, 7.50, and 15.00 mg/dose(3 times/week for 4 weeks), respectively.After 4 weeks, the organ morphology and body weight of the mice were evaluated.The content of serum iron, ferritin, transferrin, and transferrin receptor was determined by ELISA.Heart, liver, spleen, lung, kidney, and small intestine were analyzed for tissue iron content and iron deposition pathology.Mycobacterium tuberculosis(Mtb)standard strain H37Rv was injected via tail vein to infect the mice receiving moderate-dose iron to establish an iron-overloaded mouse model of active TB.HE staining and Mtb culture were employed to analyze tuberculous lesions and bacterial loads of lung, spleen and liver tissues. Results The weight gain percentages of mice in the negative control, low-, medium-, and high-dose iron groups were 25.47%, 25.22%, 24.74%, and 21.36%, respectively, which was significantly lower in the high-dose group than in the negative control(F=17.235, P=0.027), low-dose(F=15.206, P=0.031), and medium-dose(F=11.061, P=0.036)groups.Liver had the highest iron content, followed by spleen, kidney, and small intestine.The iron content in heart and lung tissues of the low-dose group had no significant difference compared with those of the negative control group(F=19.023, P=0.715;F=23.193, P=0.902).Serum iron and ferritin in the iron-overloaded mice increased in a dose-dependent manner, while transferrin and transferrin receptor had no significant changes.HE and Prussian blue staining showed that the iron-overloaded mice had different degrees of iron deposition in tissues and high-dose iron caused liver and kidney damage.The lung(F=23.227, P=0.017), spleen(F=19.023, P=0.021), and liver(F=17.392, P=0.009)of the iron-overloaded mice with TB had a significantly shorter time of bacterial culture than those of the TB-infected mice without iron overload.The lung(F=21.012, P=0.007), spleen(F=20.173, P=0.002), and liver(F=19.091, P=0.005)of the iron-overloaded mice with TB had significantly higher bacterial loads than those of the TB-infected mice without iron overload. Conclusions The exogenous iron-overloaded mouse model with similar symptoms to patients with clinical iron overload can be established by intraperitoneal injection of medium-dose(7.50 mg/dose, 3 times/week for 4 weeks)iron dextran.Mtb injection through the tail vein can help construct a mouse model of iron overload combined with active TB.


Assuntos
Sobrecarga de Ferro , Tuberculose , Animais , Humanos , Ferro , Complexo Ferro-Dextran , Camundongos , Camundongos Endogâmicos C57BL
3.
Microb Pathog ; 145: 104234, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32353576

RESUMO

GPR183/EBI2 is a key chemotactic receptor for the positioning of B cells in lymphoid organs, and also for the migration of T cells and other immune cells. Here, we demonstrate that the downregulation of GPR183 in macrophage induced during Mtb infection restrains the bacterial early infection and intracellular replication. Overexpression of GPR183 or stimulation with its natural ligand favors Mtb replication in macrophage, while treatment with its antagonist represses both Mtb early infection and intracellular replication. With mutational analysis, we find that substitution of Asp-73, Arg-83, Tyr-112, Tyr-256 abolished the promotive effect of GPR183 on Mtb early infection and replication in macrophage. In conclusion, we demonstrated that beside the known role of chemotaxis receptor, GPR183 also functions directly in the interaction between macrophage and Mtb in a cell-autonomous way.


Assuntos
Mycobacterium tuberculosis , Quimiotaxia , Regulação para Baixo , Macrófagos , Mycobacterium tuberculosis/genética
4.
Curr Probl Cardiol ; 49(2): 102238, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38040212

RESUMO

OBJECTIVE: In this study, we assessed the prognostic significance of the mean velocity of the pulmonary artery (mvPA) using CMR in patients who have heart failure with mildly reduced ejection fraction (HFmrEF) and pulmonary hypertension, both as a combined condition and individually. METHODS: This retrospective study involved 284 consecutive patients diagnosed with HFmrEF who were hospitalized and underwent CMR imaging to assess RV-PA coupling parameters, including mvPA. We collected baseline data clinical profiles, lab test results, and cardiac imaging findings of patients with HFmrEF who had at least two echocardiograms conducted three months apart. The primary endpoint was a composite of all-cause mortality or readmission due to heart failure. RESULTS: A total of 139 patients met the primary endpoint during an average follow-up of 49 months. The most effective threshold value for predicting the primary endpoint, determined by a receiver operating curve analysis, was 9. cm/s for mvPA. According to the Kaplan-Meier survival plots, when mvPA ≤ 9.05 cm/s, there was a significantly higher mortality rate (Log-Rank: 71.93, p < 0.001). It is important to highlight that the predictive value of mvPA remained consistent, irrespective of RV function. mvPA ≤ 9.05 cm/s served as an independent prognostic indicator, alongside ischemic cardiomyopathy and hyponatremia. CONCLUSIONS: mvPA has affirmed its significance as an initial prognostic indicator by identifying a group of high-risk patients who have sustained RV function. While the results of this study displayed potential in stratifying the extended prognosis of patients with HFmrEF, additional research is required.


Assuntos
Insuficiência Cardíaca , Artéria Pulmonar , Humanos , Prognóstico , Volume Sistólico , Artéria Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Função Ventricular Esquerda
5.
Zhongguo Zhong Yao Za Zhi ; 38(5): 698-702, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23724679

RESUMO

OBJECTIVE: To study the chemical constituents from Cibotium batometz. METHOD: Column chromatograph and HPLC were used to isolate and purify the compound, and the structure was elucidated on the basis of MS and NMR spectroscopic methods. RESULT: A new phenolic compound, 4-O-caffeoyl-D-glucopyranose, has been isolated from the rhizome of C. barometz. The structure of the new compound was elucidated on the basis of chemical and spectroscopic methods, including intensive 1D, 2D NMR and ESI-MS data analysis. CONCLUSION: 4-O-caffeoyl-D-glucopyranose was a new phenolic compound.


Assuntos
Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Gleiquênias/química , Taninos/análise , Taninos/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Hidrólise , Osteoporose/tratamento farmacológico , Rizoma/química , Taninos/isolamento & purificação , Taninos/uso terapêutico
6.
Microorganisms ; 11(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36677495

RESUMO

Acetoin is an important four-carbon platform chemical with versatile applications. Optically pure (R)-acetoin is more valuable than the racemate as it can be applied in the asymmetric synthesis of optically active α-hydroxy ketone derivatives, pharmaceuticals, and liquid crystal composites. As a cytotoxic solvent, acetoin at high concentrations severely limits culture performance and impedes the acetoin yield of cell factories. In this study, putative genes that may improve the resistance to acetoin for Escherichia coli were screened. To obtain a high-producing strain, the identified acetoin-resistance gene was overexpressed, and the synthetic pathway of (R)-acetoin was strengthened by optimizing the copy number of the key genes. The engineered E. coli strain GXASR-49RSF produced 81.62 g/L (R)-acetoin with an enantiomeric purity of 96.5% in the fed-batch fermentation using non-food raw materials in a 3-L fermenter. Combining the systematic approach developed in this study with the use of low-cost feedstock showed great potential for (R)-acetoin production via this cost-effective biotechnological process.

7.
Endocrinology ; 164(6)2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-36964915

RESUMO

Fructose intolerance in mammals is caused by defects in fructose absorption and metabolism. Fructose-1,6-bisphosphatase 1 (FBP1) is a key enzyme in gluconeogenesis, and its deficiency results in hypoglycemia as well as intolerance to fructose. However, the mechanism about fructose intolerance caused by FBP1 deficiency has not been fully elucidated. Here, we demonstrate that hepatic but not intestinal FBP1 is required for fructose metabolism and tolerance. We generated inducible knockout mouse models specifically lacking FBP1 in adult intestine or liver. Intestine-specific deletion of Fbp1 in adult mice does not compromise fructose tolerance, as evidenced by no significant body weight loss, food intake reduction, or morphological changes of the small intestine during 4 weeks of exposure to a high-fructose diet. By contrast, liver-specific deletion of Fbp1 in adult mice leads to fructose intolerance, as manifested by substantial weight loss, hepatomegaly, and liver injury after exposure to a high-fructose diet. Notably, the fructose metabolite fructose-1-phosphate is accumulated in FBP1-deficient liver after fructose challenge, which indicates a defect of fructolysis, probably due to competitive inhibition by fructose-1,6-bisphosphate and may account for the fructose intolerance. In conclusion, these data have clarified the essential role of hepatic but not intestinal FBP1 in fructose metabolism and tolerance.


Assuntos
Intolerância à Frutose , Frutose , Animais , Camundongos , Frutose-Bifosfatase/genética , Gluconeogênese/genética , Intestinos , Fígado , Mamíferos
8.
J Agric Food Chem ; 70(51): 16263-16272, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36511719

RESUMO

Bio-based propionate attracts increasing attention owing to its green nature and specific food additive market. To date, the time-consuming and costly fermentation process by strict anaerobes makes propionate production not ideal. In this study, we designed a new route for propionate production, in which 1,2-propanediol was first dehydrated to propionaldehyde and then to propionate by taking advantage of the robust oxidization capacity of the Pseudomonas putida KT2440 strain. The high atom economy (0.97 g/g) in this proposed pathway is more advantageous than the previous l-threonine-derived route (0.62 g/g). The molecular mechanism of the extraordinary oxidation capacity of P. putida KT2440 was first deciphered. The propionate production was realized in P. putida KT2440 by screening suitable glycerol dehydratases and optimizing the expression to eliminate the formation of 1-propanol and the accumulation of the intermediate propionaldehyde. The engineered strain produced propionate with a molar conversion rate of >99% from 1,2-propanediol. A high titer of 46.5 g/L pure propionic acid with a productivity of 1.55 g/L/h and a mass yield of 0.96 g/g was achieved in fed-batch biotransformation. Thus, this study provides another idea for the production of high-purity bio-based propionate from renewable materials with high atom economy.


Assuntos
Pseudomonas putida , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Propilenoglicol/metabolismo , Propionatos/metabolismo , Estresse Oxidativo
9.
J Tradit Complement Med ; 12(5): 518-528, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36081820

RESUMO

Background and aim: Moxibustion is widely used in China and other East Asian countries to manage the symptom of ankylosing spondylitis (AS). This study investigated the effects of moxibustion intervention on protein expression through proteomics analysis in AS mice. Experimental procedure: Proteoglycan-induced spondylitis (PGISp) was established in Balb/c mice. PGISp mice were intervened with daily moxibustion at ST36, BL23, and DU4 for four weeks. Various biochemical (including pro-inflammatory cytokines and bone metabolism indexes) and histopathological parameters were determined. The effects of moxibustion on protein changes in AS mice were analyzed using data-independent acquisition-mass spectrometry (DIA-MS). The target proteins were then confirmed by Western blot analysis. Results: Moxibustion significantly decreased pro-inflammatory cytokine expression including IL-1ß, TNF-α, IL-17, and IL-6, reduced the mRNA expression of RANKL, RANK, ALP, and OCN, and improved the histopathological examination in AS mice. DIA-MS proteomic technique has identified 25 candidate proteins involved in the mechanisms of moxibustion for AS mice, most of which are mainly associated with the regulation of Wnt/ß-catenin. Integrated pathway analysis revealed that glycine, serine and threonine metabolism together with lipid metabolism were the most important canonical pathways involved in the anti-AS effect of moxibustion. In line with the multi-omic data, the levels of BPGM, APOC2, APOE, and GPD1 modified in the AS mice, intervened with moxibustion as confirmed by Western blot. In particular, APOE may play a key role in linking the lipid metabolism and the Wnt/ß-catenin pathway of new bone formation. Conclusion: In conclusion, moxibustion may reduce pro-inflammatory cytokines and improve bone erosion for AS mice. The regulation of APOE by moxibustion may have a potential inhibitory effect on the Wnt/ß-catenin pathway in AS mice. However, due to the lack of silencing or overexpression of key molecules of the signal pathway, whether the beneficial and positive effect of moxibustion involved in the regulation of Wnt/ß-catenin signaling pathway by APOE or other aspects, needed to be explored in further study.

10.
Pharm Dev Technol ; 16(4): 377-84, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20370594

RESUMO

The preparation and investigation of sustained-release risperidone-encapsulated microspheres using erodible poly(D, L-lactide-co-glycolide) (PLGA) of lower molecular weight were performed and compared to that of commercial Risperdal Consta™ for the treatment of schizophrenia. The research included screening and optimizing of suitable commercial polymers of lower molecular weight PLGA50/50 or the blends of these PLGA polymers to prepare microspheres with zero-order release kinetics properties. Solvent evaporation method was applied here while studies of the risperidone loaded microsphere were carried out on its drug encapsulation capacity, morphology, particle size, as well as in vitro release profiles. Results showed that microspheres prepared using 50504A PLGA or blends of 5050-type PLGAs exerted spherical and smooth morphology, with a higher encapsulation efficiency and nearly zero-order release kinetics. These optimized microspheres showed great potential for a better depot preparation than the marketed Risperdal Consta™, which could further improve the patient compliance.


Assuntos
Antipsicóticos/administração & dosagem , Química Farmacêutica/métodos , Preparações de Ação Retardada/química , Ácido Láctico/química , Ácido Poliglicólico/química , Risperidona/administração & dosagem , Antipsicóticos/farmacocinética , Preparações de Ação Retardada/farmacocinética , Microesferas , Peso Molecular , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Risperidona/farmacocinética , Esquizofrenia/tratamento farmacológico , Solubilidade
11.
Chin Med J (Engl) ; 134(11): 1276-1285, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34010200

RESUMO

ABSTRACT: Excessive consumption of fructose, the sweetest of all naturally occurring carbohydrates, has been linked to worldwide epidemics of metabolic diseases in humans, and it is considered an independent risk factor for cardiovascular diseases. We provide an overview about the features of fructose metabolism, as well as potential mechanisms by which excessive fructose intake is associated with the pathogenesis of metabolic diseases both in humans and rodents. To accomplish this aim, we focus on illuminating the cellular and molecular mechanisms of fructose metabolism as well as its signaling effects on metabolic and cardiovascular homeostasis in health and disease, highlighting the role of carbohydrate-responsive element-binding protein in regulating fructose metabolism.


Assuntos
Frutose , Doenças Metabólicas , Frutose/efeitos adversos , Homeostase , Humanos , Doenças Metabólicas/etiologia
12.
Sheng Wu Gong Cheng Xue Bao ; 37(5): 1541-1563, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085442

RESUMO

The regulation of the expression of genes involved in metabolic pathways, termed as metabolic regulation, is vital to construct efficient microbial cell factories. With the continuous breakthroughs in synthetic biology, the mining and artificial design of high-quality regulatory elements have substantially improved our ability to modify and regulate cellular metabolic networks and its activities. The research on metabolic regulation has also evolved from the static regulation of single genes to the intelligent and precise dynamic regulation at the systems level. This review briefly summarizes the advances of metabolic regulation technologies in the past 30 years.


Assuntos
Engenharia Metabólica , Biologia Sintética , Redes e Vias Metabólicas/genética
13.
J Agric Food Chem ; 69(46): 13895-13903, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34757739

RESUMO

Bio-based propionate is widely welcome in the food additive industry. The current anaerobic process by Propionibacteria endures low titers and a long fermentation time. In this study, a new route for propionate production from l-threonine was designed. 2-Ketobutyrate, deaminated from l-threonine, is cleaved into propionaldehyde and CO2 and then be oxidized into propionic acid, which is neutralized by ammonia released from the first deamination step. This CoA-independent pathway with only CO2 as a byproduct boosts propionate production from l-threonine with high productivity and purity. The key enzyme for 2-ketobutyrate decarboxylation was selected, and its expression was optimized. The engineered Pseudomonas putida strain, harboring 2-ketoisovalerate decarboxylase from Lactococcus lactis could produce 580 mM (43 g/L) pure propionic acid from 600 mM l-threonine in 24 h in the batch biotransformation process. Furthermore, a high titer of 62 g/L propionic acid with a productivity of 1.07 g/L/h and a molar yield of >0.98 was achieved in the fed-batch pattern. Finally, an efficient sequential fermentation-biotransformation process was demonstrated to produce propionate directly from the fermentation broth containing l-threonine, which further reduces the costs since no l-threonine purification step is required.


Assuntos
Propionatos , Pseudomonas putida , Biotransformação , Fermentação , Pseudomonas putida/metabolismo , Treonina/metabolismo
14.
Microb Biotechnol ; 14(3): 1237-1242, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33739583

RESUMO

Pseudomonas putida KT2440 is becoming a new robust metabolic chassis for biotechnological applications, due to its metabolic versatility, low nutritional requirements and biosafety status. We have previously engineered P. putida KT2440 to be an efficient propionate producer from L-threonine, although the internal enzymes converting propionyl-CoA to propionate are not clear. In this study, we thoroughly investigated 13 genes annotated as potential thioesterases in the KT2440 mutant. One thioesterase encoded by locus tag PP_4975 was verified to be the major contributor to propionate production in vivo. Deletion of PP_4975 significantly decreased propionate production, whereas the performance was fully restored by gene complement. Compared with thioesterase HiYciA from Haemophilus influenza, thioesterase PP_4975 showed a faster substrate conversion rate in vitro. Thus, this study expands our knowledge on acyl-CoA thioesterases in P. putida KT2440 and may also reveal a new target for further engineering the strain to improve propionate production performance.


Assuntos
Pseudomonas putida , Biotecnologia , Propionatos , Pseudomonas putida/genética
15.
Integr Med Res ; 10(1): 100428, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32953451

RESUMO

BACKGROUND: Moxibustion is widely used in East Asian countries to manage the symptom of rheumatic diseases. The aim of this study was to identify potential metabolic profiles of moxibustion on relieving ankylosing spondylitis (AS) mice through UHPLC-Q-TOF/MS metabolomic study. METHODS: Thirty-two female Balb/c mice were randomized into healthy control (HC), AS model, moxibustion at acupuncture points (MA) in AS model, and moxibustion at non-acupuncture points (MNA) AS model groups. Moxibustion was administered daily at GV4, bilateral BL23 and bilateral ST36 acupuncture points for four weeks in the MA group. The overall health status, the thickness of hind paws and the tissue concentrations of IL-1ß, PGE2, IL-6 and TNF-α were assessed. The UHPLC-Q-TOF/MS was used to explore the perturbations of endogenous metabolites in tissue and urine of AS model mice intervened by moxibustion. RESULTS: Compared with the AS group, the overall health status was significantly improved after 4-week moxibustion intervention (p < 0.05). The results also showed that MA significantly reduced the levels of paw thickness and decreased the levels of four cytokines in the tissue (p < 0.01). Thirty-seven endogenous metabolites identified by the OPLS-DA were considered to be contributing to therapeutic effects of moxibustion. Moreover, metabolic pathway analysis further revealed that the identified metabolites were mainly involved in TCA cycle, Lipid metabolism, Amino Acid metabolism, Intestinal flora metabolism and Purine metabolism. CONCLUSIONS: UHPLC-Q-TOF/MS based metabolomics approach, as a novel and powerful tool, can help us to gain the insights into potential mechanisms of action of moxibustion for AS.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32500039

RESUMO

Mycobacterium tuberculosis clinical strains usually possess traits different from the laboratory strains like H37Rv, especially those clinical drug resistant strains. With whole genome and transcriptome sequencing, we depicted the feature of two multi-drug resistant Mtb strains in resistance and virulence. Compared with H37Rv, the differential expressed genes (DEGs) of the MDR strains showed featured enrichment in arginine biosynthesis, fatty acid biosynthesis, and metabolism pathway. In the subset of virulence genes, the overlapping DEGs of the MDR strains exhibited downregulation of the cluster in type VII secretion system. In the mice experiment, the MDR strains showed attenuated but distinct virulence, both in survival rate and pathology. Taken together, the whole genome and transcriptome analysis could help understand the unique feature of the MDR strains both in resistance and virulence.


Assuntos
Mycobacterium tuberculosis , Preparações Farmacêuticas , Animais , Camundongos , Mycobacterium tuberculosis/genética , Fenótipo , Transcriptoma , Virulência
17.
Integr Med Res ; 9(3): 100479, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32766114

RESUMO

BACKGROUND: The aim of this review was to comprehensively summarize and analyze the current guidelines on home-based traditional Chinese medicine (TCM) nursing interventions for discharged patients with COVID-19. METHODS: Eight data sources were searched until June 28, 2020. The frequency of home-based TCM nursing interventions and the use of specific acupuncture points recommended in Chinese guidelines for discharged COVID-19 patients were computed and analyzed. RESULTS: In total, we identified 5 Chinese guidelines that provide for home-based TCM nursing interventions for discharged patients with COVID-19. Moxibustion and acupressure were singled out as the most frequently used intervention of the 11 home-based TCM nursing interventions recommended by these guidelines. RN12 and ST36 were the 2 most promoted acupuncture points for moxibustion and acupressure interventions for these patients. CONCLUSIONS: The present review showed the important role of home-based TCM nursing interventions for discharged COVID-19 patients. However, direct evidence of their efficacy is still insufficient.

18.
J Int Med Res ; 48(7): 300060520937866, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32691685

RESUMO

AIMS: Previous studies suggest that small intestinal bacterial overgrowth (SIBO) is associated with type 2 diabetes. However, few studies have evaluated the association between SIBO and beta-cell function in type 2 diabetes. The aim of this study was to evaluate whether beta-cell function was associated with SIBO. MATERIALS AND METHODS: One hundred four patients with type 2 diabetes were included in this study. Based on the presence of SIBO, the patients were divided into SIBO-positive and SIBO-negative groups. Oral glucose tolerance tests were performed. Insulin sensitivity was measured using 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and the insulin sensitivity index (ISIM). Insulin release was calculated by HOMA-ß, early-phase insulin secretion index InsAUC30/GluAUC30, and total-phase insulin secretion index InsAUC120/GluAUC120. RESULTS: Compared with the SIBO-negative group, patients in the SIBO-positive group showed a higher glucose level at 120 minutes, HbA1c, 1/HOMA-IR, and ISIM and a lower HOMA-ß level, early-phase InsAUC30/GluAUC30, and total-phase InsAUC120/GluAUC120. Multiple linear regression analysis showed that body mass index, glucose at 0 minutes, and SIBO were independently associated with the early-phase and total-phase insulin secretion. CONCLUSION: SIBO may be involved in lower levels of insulin release and worse glycemic control.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Teste de Tolerância a Glucose , Humanos , Insulina/metabolismo , Secreção de Insulina
19.
Diabetes ; 69(4): 591-602, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31974143

RESUMO

Excessive fructose consumption is closely linked to the pathogenesis of metabolic disease. Carbohydrate response element-binding protein (ChREBP) is a transcription factor essential for fructose tolerance in mice. However, the functional significance of liver ChREBP in fructose metabolism remains unclear. Here, we show that liver ChREBP protects mice against fructose-induced hepatotoxicity by regulating liver glycogen metabolism and ATP homeostasis. Liver-specific ablation of ChREBP did not compromise fructose tolerance, but rather caused severe transaminitis and hepatomegaly with massive glycogen overload in mice fed a high-fructose diet, while no obvious inflammation, cell death, or fibrosis was detected in the liver. In addition, liver ATP contents were significantly decreased by ChREBP deficiency in the fed state, which was rendered more pronounced by fructose feeding. Mechanistically, liver contents of glucose-6-phosphate (G6P), an allosteric activator of glycogen synthase, were markedly increased in the absence of liver ChREBP, while fasting-induced glycogen breakdown was not compromised. Furthermore, hepatic overexpression of LPK, a ChREBP target gene in glycolysis, could effectively rescue glycogen overload and ATP reduction, as well as mitigate fructose-induced hepatotoxicity in ChREBP-deficient mice. Taken together, our findings establish a critical role of liver ChREBP in coping with hepatic fructose stress and protecting from hepatotoxicity by regulating LPK.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Frutose/toxicidade , Glucose/metabolismo , Glicogênio/metabolismo , Fígado/metabolismo , Piruvato Quinase/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Glicólise/fisiologia , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout
20.
Zhonghua Yi Xue Za Zhi ; 89(14): 958-61, 2009 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-19671306

RESUMO

OBJECTIVE: To investigate the effects of Helicobacter pylori (Hp) on blood glucose fluctuation in type 2 diabetic mellitus. METHODS: 130 type 2 diabetic patients were selected, 72 patients with Hp infection and 58 without Hp infection. Relevant clinical data: blood pressure, body mass index, cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, glycosylated hemoglobin, insulin resistance index, liver function, and renal function were collected. The data of blood glucose levels at 7 time points, 6 - 7 am, 9 - 10 am, 11 - 12 am, 14 - 15 pm, 17 - 18 pm, 19 - 20 pm, and 22 - 23 pm in 3 days, totally 21 data, were collected. And input into the OTDMS data analysis software to evaluate the blood glucose fluctuation indexes: standard deviation of mean blood glucose (SDBG), mean amplitude of glycemic excursions (MAGE), large amplitude of glycemic excursions (LAGE). RESULTS: There were no significant differences in age, course of disease, blood pressure, body mass index, cholesterol, triglyceride, low density lipoprotein cholesterol, glycosylated hemoglobin, and insulin resistance index between these 2 groups (all P > 0.05). The levels of MBG, SDBG, MAGE, LAGE, (mmol/L: 9.0 +/- 1.1 vs 7.6 +/- 0.5, 3.3 +/- 1.1 vs 1.7 +/- 0.5, 6.7 +/- 4.5 vs 3.0 +/- 1.1, 8.6 +/- 3.8 vs 4.2 +/- 1.5, all P < 0.05) and incidence of hypoglycemia [16.6% (12/72) vs 5.1% (3/58), P < 0.05] were all higher in the Hp positive group than in the Hp negative group. CONCLUSION: Hp infection has a significant effect on the daily blood glucose level and blood glucose fluctuation in the patients with type 2 diabetes.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/microbiologia , Infecções por Helicobacter/metabolismo , Adulto , Feminino , Helicobacter pylori/fisiologia , Humanos , Estudos Retrospectivos
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