Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 723.348
Filtrar
1.
Braz. j. biol ; 83: e242818, 2023. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1285628

RESUMO

Abstract The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P<0.05) increase in weight and blood glucose concentration as well as elevated level of inflammatory cytokines (TNF-α, IL-6, and MCP-1) compared to mice receiving CD only. The 16S rRNA gene sequencing of 11 fecal bacteria obtained from three randomly selected animals from each group revealed gut dysbiosis in animals receiving GM. Bacterial strains including Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) and Lactobacillus gasseri (MT152635) were isolated from mice treated with GM+modified diet (HFD/CD) compared to strains Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629) which were isolated from mice receiving CD/HFD. In conclusion, these findings suggest that constitution of GM and diet plays significant role in inflammation leading to onset or/and possibly progression of T2D. .


Resumo O estudo teve como objetivo avaliar o impacto da dieta rica em gordura (HFD) e da microbiota intestinal humana sintética (GM) combinada com HFD e dieta alimentar (CD) na indução de diabetes tipo 2 (T2D) usando modelo de camundongos. Para nosso conhecimento, este é o primeiro estudo usando transplante de GM humano selecionado através do método baseado em cultura acoplada à modulação dietética em camundongos para o estabelecimento in vivo de inflamação que leva a T2D e disbiose intestinal. Vinte bactérias (T2D1-T2D20) de amostras de fezes de indivíduos T2D confirmados verificaram ser morfologicamente diferentes e foram submetidas à purificação em meios diferentes aerobicamente e anaerobicamente, o que revelou sete bactérias mais comuns entre 20 isolados com base na caracterização bioquímica. Com base no sequenciamento do gene 16S rRNA, esses sete isolados foram identificados como Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenides (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). Esses sete isolados foram, posteriormente, usados ​​como microbioma intestinal sintético (GM) por seu papel na indução de T2D em camundongos. Linhagens consanguíneas de camundongos albinos foram divididas em quatro grupos e foram alimentadas com CD, HFD, GM + HFD e GM + CD. Camundongos que receberam a dieta modificada com HFD e GM + (CD / HFD) mostraram um aumento altamente significativo (P < 0,05) no peso e na concentração de glicose no sangue, bem como um nível elevado de citocinas inflamatórias (TNF-α, IL-6 e MCP-1) em comparação com os ratos que receberam apenas CD. O sequenciamento do gene 16S rRNA de 11 bactérias fecais obtidas de três animais selecionados aleatoriamente de cada grupo revelou disbiose intestinal em animais que receberam GM. Cepas bacterianas, incluindo Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) e Lactobacillus Gasseri (MT152635D), foram tratadas com dieta modificada / CD) em comparação com as linhagens Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629), que foram isoladas de camundongos recebendo CD / HFD. Em conclusão, esses resultados sugerem que a constituição de GM e dieta desempenham papel significativo na inflamação levando ao início ou/e possivelmente à progressão de T2D.

2.
Braz. j. biol ; 83: e250179, 2023. graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1339372

RESUMO

Abstract Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer's disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.


Resumo O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis ​​pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

3.
Pergunta e resposta em Português | SOF - Segunda opinião formativa | ID: sof-44592

RESUMO

No exame quantitativo de urina coletada ao acaso, o valor de referência da glicose é menor que 30mg/dl(2). Habitualmente é indetectável(1). A glicosúria só ocorre quando os níveis de glicemia atingem 180 a 200mg/dl. Geralmente, decorre do diabetes mellitus, mas pode ocorrer em outras situações, como dietas ricas em glicose antes da coleta, uso parenteral de glicose, glicosúria renal, diabetes insipidus nefrogênico, feocromocitoma, pancreatite aguda, hipertireoidismo, acromegalia e síndrome de Cushing(2).

A correlação entre a intensidade da glicosúria e os valores estimados da glicose depende do teste utilizado, por isso, os valores de referência que acompanham o exame, devem ser sempre verificados. Abaixo seguem os valores estimados de glicose conforme a pontuação em “+ “ de um teste semiquantitativo de glicosúria(3):

Traços: < 100 mg/dl

+: < 250 mg/dl

++: < 500 mg/dl

+++: < 1000 mg/dl

++++: >2000mg/dl


Assuntos
Glicosúria , Coleta de Urina , Valores de Referência , Transtornos do Metabolismo de Glucose
4.
Sci Rep ; 12(1): 188, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996987

RESUMO

Patients with diabetes are more likely to be infected with Coronavirus disease 2019 (COVID-19), and the risk of death is significantly higher than ordinary patients. Dipeptidyl peptidase-4 (DPP4) is one of the functional receptor of human coronavirus. Exploring the relationship between diabetes mellitus targets and DPP4 is particularly important for the management of patients with diabetes and COVID-19. We intend to study the protein interaction through the protein interaction network in order to find a new clue for the management of patients with diabetes with COVID-19. Diabetes mellitus targets were obtained from GeneCards database. Targets with a relevance score exceeding 20 were included, and DPP4 protein was added manually. The initial protein interaction network was obtained through String. The targets directly related to DPP4 were selected as the final analysis targets. Importing them into String again to obtain the protein interaction network. Module identification, gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were carried out respectively. The impact of DPP4 on the whole network was analyzed by scoring the module where it located. 43 DPP4-related proteins were finally selected from the diabetes mellitus targets and three functional modules were found by the cluster analysis. Module 1 was involved in insulin secretion and glucagon signaling pathway, module 2 and module 3 were involved in signaling receptor binding. The scoring results showed that LEP and apoB in module 1 were the highest, and the scores of INS, IL6 and ALB of cross module associated proteins of module 1 were the highest. DPP4 is widely associated with key proteins in diabetes mellitus. COVID-19 may affect DPP4 in patients with diabetes mellitus, leading to high mortality of diabetes mellitus combined with COVID-19. DPP4 inhibitors and IL-6 antagonists can be considered to reduce the effect of COVID-19 infection on patients with diabetes.

5.
Sci Rep ; 12(1): 264, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34997031

RESUMO

Diabetes can cause microvessel impairment. However, these conjunctival pathological changes are not easily recognized, limiting their potential as independent diagnostic indicators. Therefore, we designed a deep learning model to explore the relationship between conjunctival features and diabetes, and to advance automated identification of diabetes through conjunctival images. Images were collected from patients with type 2 diabetes and healthy volunteers. A hierarchical multi-tasking network model (HMT-Net) was developed using conjunctival images, and the model was systematically evaluated and compared with other algorithms. The sensitivity, specificity, and accuracy of the HMT-Net model to identify diabetes were 78.70%, 69.08%, and 75.15%, respectively. The performance of the HMT-Net model was significantly better than that of ophthalmologists. The model allowed sensitive and rapid discrimination by assessment of conjunctival images and can be potentially useful for identifying diabetes.

6.
Sci Rep ; 12(1): 214, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34997053

RESUMO

We developed a three-step matching algorithm to enhance the between-group comparability for comparative drug effect studies involving prevalent new-users of the newer study drug versus older comparator drug(s). The three-step matching scheme is to match on: (1) index date of initiating the newer study drug to align the cohort entry time between study groups, (2) medication possession ratio measures that consider prior exposure to all older comparator drugs, and (3) propensity scores estimated from potential confounders. Our approach is illustrated with a comparative cardiovascular safety study of glucagon-like peptide-1 receptor agonist (GLP-1ra) versus sulfonylurea (SU) in type 2 diabetes patients using Taiwan's National Health Insurance Research Database 2003-2015. 66% of 3195 GLP-1ra users had previously exposed to SU. The between-group comparability was well-achieved after implementing the matching algorithm (i.e., standardized mean difference < 0.2 for all baseline patient characteristics). Compared to SU, the use of GLP-1ra yielded a significantly reduced risk of the primary composite cardiovascular events (hazard ratio [95% confidence interval]: 0.71 [0.54-0.95], p = 0.022). Our matching scheme can enhance the between-group comparability in prevalent new-user cohort designs to minimize time-related bias, improve confounder adjustment, and ensure the reliability and validity of study findings.

7.
Sci Rep ; 12(1): 154, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34997102

RESUMO

Real-world data comparing the effectiveness of various glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in type 2 diabetes mellitus (T2DM) are limited. We investigated the clinical effectiveness of liraglutide and dulaglutide in Japanese T2DM in a real-world setting. This retrospective study included 179 patients with T2DM who were treated with GLP-1 RA for at least 12 months (liraglutide, n = 97; dulaglutide, n = 82). We used stabilized propensity score-based inverse probability of treatment weighting (IPTW) to reduce selection bias and confounding by observed covariates. Changes in glycated hemoglobin (HbA1c) at the end of the 12-month treatment were evaluated. After adjustment by stabilized propensity score-based IPTW, no significant differences were observed in patient characteristics between the liraglutide and dulaglutide groups. HbA1c was significantly lower at 12 months in both groups (liraglutide, 8.9 to 7.4%; dulaglutide, 8.7 to 7.5%). Multivariate linear regression analysis showed no differences in the extent of changes in HbA1c at 12 months between the two agents. High baseline HbA1c, the addition of GLP-1 RA treatment modality, and in-hospital initiation of GLP-1 RA treatment were identified as significant contributing factors to HbA1c reduction. The effects of liraglutide and dulaglutide on lowering HbA1c levels at 12 months were comparable in a real-world setting.

8.
Sci Rep ; 12(1): 291, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34997128

RESUMO

Elucidating the risk factors for chronic kidney disease is important for preventing end-stage renal disease and reducing mortality. However, little is known about the roles of psychosocial stress and stress coping behaviors in deterioration of the renal function, as measured by the estimated glomerular filtration rate (eGFR). This cross-sectional study of middle-aged and older Japanese men (n = 31,703) and women (n = 38,939) investigated whether perceived stress and coping strategies (emotional expression, emotional support seeking, positive reappraisal, problem solving, and disengagement) were related to the eGFR, with mutual interactions. In multiple linear regression analyses adjusted for age, area, lifestyle factors, and psychosocial variables, we found a significant inverse association between perceived stress and the eGFR in men (Ptrend = 0.02), but not women. This male-specific inverse association was slightly attenuated after adjustment for the history of hypertension and diabetes and was more evident in lower levels of emotional expression (Pinteraction = 0.003). Unexpectedly, problem solving in men (Ptrend < 0.001) and positive reappraisal in women (Ptrend = 0.002) also showed an inverse association with the eGFR. Perceived stress may affect the eGFR, partly through the development of hypertension and diabetes. The unexpected findings regarding coping strategies require the clarification of the underlying mechanisms, including the hormonal and immunological aspects.

9.
Int J Pharm ; 614: 121445, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34998921

RESUMO

Dry powder inhalers (DPI) are well established products for the delivery of actives via the pulmonary route. Various DPI products are marketed or developed for the treatment of local lung diseases such as chronic obstructive pulmonary disease (COPD), asthma or cystic fibrosis as well as systemic diseases targeted through inhaled delivery (i.e. Diabetes Mellitus). One of the key prerequisites of DPI formulations is that the aerodynamic size of the drug particles needs to be below 5 µm to enter deeply into the respiratory tract. These inherently cohesive inhalable size particles are either formulated as adhesive mixture with coarse carrier particles like lactose called carrier-based DPI or are formulated as free-flowing carrier-free particles (e.g. soft agglomerates, large hollow particles). In either case, it is common practice that drug and/or excipient particles of DPI formulations are obtained by processing API and API/excipients. The DPI manufacturing process heavily involves several particle and powder technologies such as micronization of the API, dry blending, powder filling and other particle engineering processes such as spray drying, crystallization etc. In this context, it is essential to thoroughly understand the impact of powder/particle properties and processing on the quality and performance of the DPI formulations. This will enable prediction of the processability of the DPI formulations and controlling the manufacturing process so that meticulously designed formulations are able to be finally developed as the finished DPI dosage form. This article is intended to provide a concise account of various aspects of DPI powder processing, including the process understanding and material properties that are important to achieve the desired DPI product quality. Various endeavors of model informed formulation/process design and development for DPI powder and PAT enabled process monitoring and control are also discussed.

10.
Exp Eye Res ; 215: 108921, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34999080

RESUMO

Low-density lipoprotein receptor-related protein-1 (LRP-1) is a large transmembrane receptor. LRP-1 plays a role in diverse cellular processes, including lipid metabolism, cell growth, migration, and regeneration. Soluble form of LRP-1 (sLRP-1) can be detected in serum. sLRP-1 can serve as a biomarker of atherosclerosis and cardiometabolic diseases. This study investigated the concentrations of the circulating serum sLRP-1 in patients with retinopathy and type 2 diabetes mellitus. Fifty-two patients with diabetic retinopathy and 71 controls were enrolled based on well-defined eligibility criteria. Venous blood samples were collected after 12 h of fasting. sLRP-1 concentrations were measured using the commercially available ELISA in an accredited laboratory. The mean age of patients and control groups were 63.6 and 48.5 years, respectively. The median disease duration was 8.1 years. The median serum sLRP-1 levels were lower in patients with diabetic retinopathy compared to the controls (2.11 µg/mL versus 2.44 µg/mL, p = 0.034). No significant correlation was observed between the sLRP-1 and serum lipid levels. The sLRP-1 levels are low in patients with diabetic retinopathy compared to healthy controls, and future studies are needed to assess sLRP-1 as a potential biomarker in diabetic retinopathy.

11.
Life Sci ; 291: 120299, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34999113

RESUMO

Alzheimer's disease (AD), a type of dementia, is characterized by progressive memory decline and cognition impairment. Despite the considerable body of evidence regarding AD pathophysiology, current therapies merely slow down the disease progression, and a comprehensive therapeutic approach is unavailable. Accordingly, finding an efficient multifunctional remedy is necessary to blunt the increasing rate of AD incidence in the upcoming years. AD shares pathophysiological similarities (e.g., impairment of cognitive functions, insulin sensitivity, and brain glucose metabolism) with noninsulin-dependent diabetes mellitus (NIDDM), which offers the utilization of metformin, a biguanide hypoglycemic agent, as an alternative therapeutic approach in AD therapy. Emerging evidence has revealed the impact of metformin in patients suffering from AD. It has been described that metformin employs multiple mechanisms to improve cognition and memory impairment in pre-clinical AD models, including reduction of hippocampal amyloid-beta (Aß) plaque and neurofibrillary tangles (NFTs) load, suppression of inflammation, amelioration of mitochondrial dysfunction and oxidative stress, restriction of apoptotic neuronal death, and induction of neurogenesis. This review discusses the pre-clinical evidence, which may shed light on the role of metformin in AD and provide a more comprehensive mechanistic insight for future studies in this area of research.

12.
J Affect Disord ; 301: 1-7, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34999125

RESUMO

BACKGROUND: Cardiometabolic diseases (CMDs) are associated with depression. However, it is unclear whether coexisting CMDs may increase the risk of depression. We examined associations between cardiometabolic multimorbidity and depressive symptoms among middle-aged and older Chinese. METHODS: Participants aged ≥45 years were enrolled from the China Health and Retirement Longitudinal Study 2011-2018 (N = 18,002). Cardiometabolic multimorbidity was defined as the coexistence of ≥2 CMDs, including stroke, heart disease, diabetes, hypertension, and dyslipidemia. Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale. We used generalized estimating equation models to examine associations between cardiometabolic multimorbidity and depressive symptoms, including the dose effect of disease count and prevalent disease combinations, as well as individual and additive effects of specific CMDs. RESULTS: The prevalence of cardiometabolic multimorbidity was 24.5%. A higher number of CMDs had an additive dose effect on depressive symptoms that persisted consistently in specific CMDs. Stroke only, heart disease only, and diabetes only were each associated with a higher risk of depressive symptoms compared with no CMDs. CMD combinations involving stroke, heart disease, or diabetes were each associated with an increased risk of depressive symptoms compared with the absence of stroke, heart disease, or diabetes. LIMITATION: Self-reported chronic conditions. CONCLUSION: Stroke, heart disease, and diabetes showed individual and additive effects on CMD combinations, whereas hypertension and dyslipidemia only showed associations with depressive symptoms in combinations with other CMDs. These results suggest person-centered healthcare of mental health prevention and treatment for middle-aged and older adults with individual or multiple CMDs.

13.
Food Chem Toxicol ; 160: 112813, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34999176

RESUMO

Diabetic skin ulcer is one of the most common complications in patients suffering diabetes mellitus. Xanthohumol (XN), a hop-derived prenylated dietary flavonoid, has multiple health beneficial bioactivities. In the present study, we reported XN alleviates oxidative damage and accelerates diabetic wound healing via Nrf2 activation. In vitro, XN attenuated hydrogen peroxide (H2O2)-induced cytotoxicity, ROS production, cell apoptosis, as well as high glucose-induced cell damage. Mechanistic studies further demonstrated that XN could stabilize nuclear factor erythroid 2-related factor 2 (Nrf2) and promote its nuclear translocation, which was associated with AMPKα activation and covalent modification of Keap1 by XN. In vivo, XN increased Nrf2 expression and accelerated diabetic wound healing. Our study revealed a novel function of XN in diabetic wound healing as well as the underlying molecular mechanisms, suggesting XN is a promising lead compound and a potential food and/or drug candidate for the treatment of diabetic skin ulcers.

14.
Pediatr Diabetes ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35001490

RESUMO

OBJECTIVE: The rate of diabetic ketoacidosis (DKA), a preventable, life-threatening complication of diabetes, at the time of diagnosis in children remains unacceptably high worldwide. We describe our initial approach to selecting a national DKA prevention strategy, to be implemented by the Canadian Pediatric Endocrine Group DKA Prevention Working Group, informed by a framework for behavior change interventions. METHODS: Existing interventions were identified from a systematic review and our own gray literature search. We then characterized interventions using the Behavior Change Wheel, a framework to inform and drive behavior change, and matched interventions to behavioral targets, audiences, and identified barriers and facilitators. Feedback from the CPEG DKA prevention working group was incorporated into the intervention plan. RESULTS: We identified 27 interventions. Our proposed target behaviors are: (1) prompt recognition of symptoms of diabetes in children; (2) urgent attendance to medical care with a request for an office-based test for diabetes; and (3) rapid confirmation of diagnosis and urgent consultation with pediatric diabetes experts. We initially identified four possible intervention functions including education, training, environment restructuring, and enablement. Feedback from the working group favored education intervention functions including symptom recognition messages targeting parents, caregivers, teachers, and providers and messages about how to make a rapid diagnosis and need for urgent referral targeting providers. CONCLUSIONS: The Behavior Change Wheel has been used successfully in selecting interventions in other clinical areas. We describe how we used this framework to provide a foundation for developing an intervention to prevent DKA at diabetes diagnosis in children.

15.
Int J Biol Sci ; 18(2): 809-825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35002527

RESUMO

Diabetic keratopathy (DK) is an important diabetic complication at the ocular surface. Chronic low-grade inflammation mediated by the NLRP3 inflammasome promotes pathogenesis of diabetes and its complications. However, the effect of the NLRP3 inflammasome on DK pathogenesis remains elusive. Wild-type (WT) and Nlrp3 knockout (KO) C57 mice were used to establish a type I diabetes model by intraperitoneal injection of streptozotocin. The effect of the NLRP3 inflammasome on diabetic corneal wound healing and never regeneration was examined by a corneal epithelial abrasion model. Western blot, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA) and pharmacological treatment were performed to investigate the regulatory mechanism of advanced glycation end products (AGEs) on NLRP3 inflammasome activation and corneal wound healing in vivo. The cultured mouse corneal epithelial cells (TKE2) were used to evaluate the effect and mechanism of AGEs on NLRP3 inflammasome activation in vitro. We revealed that NLRP3 inflammasome-mediated inflammation and pyroptosis contributed to DK pathogenesis. Under physiological conditions, the NLRP3 inflammasome was required for corneal wound healing and nerve regeneration. However, under a diabetic scenario, sustained activation of the NLRP3 inflammasome resulted in postponed corneal wound healing and impaired nerve regeneration. Mechanistically, the accumulated AGEs promoted hyperactivation of the NLRP3 inflammasome through ROS production. Moreover, genetically and pharmacologically blocking the AGEs/ROS/NLRP3 inflammasome axis significantly expedited diabetic corneal epithelial wound closure and nerve regeneration. Our results revealed that AGEs-induced hyperactivation of the NLRP3 inflammasome resulted in delayed diabetic corneal wound healing and impaired nerve regeneration, which further highlighted the NLRP3 inflammasome as a promising target for DK treatment.

16.
Int J Biol Sci ; 18(2): 826-840, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35002528

RESUMO

Diabetic cardiomyopathy (DCM) is associated with oxidative stress and augmented inflammation in the heart. Neuraminidases (NEU) 1 has initially been described as a lysosomal protein which plays a role in the catabolism of glycosylated proteins. We investigated the role of NEU1 in the myocardium in diabetic heart. Streptozotocin (STZ) was injected intraperitoneally to induce diabetes in mice. Neonatal rat ventricular myocytes (NRVMs) were used to verify the effect of shNEU1 in vitro. NEU1 is up-regulated in cardiomyocytes under diabetic conditions. NEU1 inhibition alleviated oxidative stress, inflammation and apoptosis, and improved cardiac function in STZ-induced diabetic mice. Furthermore, NEU1 inhibition also attenuated the high glucose-induced increased reactive oxygen species generation, inflammation and, cell death in vitro. ShNEU1 activated Sirtuin 3 (SIRT3) signaling pathway, and SIRT3 deficiency blocked shNEU1-mediated cardioprotective effects in vitro. More importantly, we found AMPKα was responsible for the elevation of SIRT3 expression via AMPKα-deficiency studies in vitro and in vivo. Knockdown of LKB1 reversed the effect elicited by shNEU1 in vitro. In conclusion, NEU1 inhibition activates AMPKα via LKB1, and subsequently activates sirt3, thereby regulating fibrosis, inflammation, apoptosis and oxidative stress in diabetic myocardial tissue.

17.
J Diabetes Res ; 2022: 7424748, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35005030

RESUMO

Background: The coronavirus disease 2019 (COVID-19) is a serious global health threat and has spread dramatically worldwide. Prolonged viral shedding is associated with a more severe disease course and inflammatory reaction. Blood glucose levels were significantly associated with an increased hazard ratio (HR) for poor outcomes in COVID-19 patients. Objective: Previous studies focused primarily on the relationship between blood glucose and mortality or severe outcomes, but there were few research studies on the relationship between fasting plasma glucose (FPG) and duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA positive status. To explore the relationship between FPG levels and prolonged duration of SARS-CoV-2 viral positivity, the clinical data of COVID-19 patients were analyzed. Method: In this retrospective study, 99 cases of COVID-19 patients in Beijing Ditan Hospital were recruited, and their clinical and laboratory findings at admission were collected and analyzed. Furthermore, the risk factors for prolonged duration of SARS-CoV-2 RNA shedding were identified, and the relationship between FPG levels and the prolonged presence of SARS-CoV-2 RNA was evaluated. Result: We found that elevated FPG levels were correlated with longer duration of SARS-CoV-2 RNA positivity, classification of COVID-19, imaging changes of chest CT, inflammation-related biomarkers, and CD8+ T cell number in COVID-19 patients. In a logistic regression model, after adjusting for gender and age, COVID-19 patients with elevated FPG were more likely to had longer duration of SARS-CoV-2 RNA positivity than those with normal FPG levels (OR 3.053 [95% CI 1.343, 6.936]). Conclusion: Higher FPG levels (≥6.1 mmol/l) at admission was an independent predictor for prolonged SARS-CoV-2 shedding, regardless of a known history of diabetes. It suggests that intensive monitoring and control of blood glucose are important for all COVID-19 patients.

18.
Environ Int ; 160: 107078, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007898

RESUMO

CONTEXT: Phthalates may disrupt maternal-fetal-placental endocrine pathways, affecting pregnancy outcomes and child development. Placental corticotropin releasing hormone (pCRH) is critical for healthy pregnancy and child development, but understudied as a target of endocrine disruption. OBJECTIVE: To examine phthalate metabolite concentrations (as mixtures and individually) in relation to pCRH. DESIGN: Secondary data analysis from a prospective cohort study. SETTING: Prenatal clinics in Tennessee, USA. PATIENTS: 1018 pregnant women (61.4% non-Hispanic Black, 32% non-Hispanic White, 6.6% other) participated in the CANDLE study and provided data. Inclusion criteria included: low-medical-risk singleton pregnancy, age 16-40, and gestational weeks 16-29. INTERVENTION: None. MAIN OUTCOME MEASURES: Plasma pCRH at two visits (mean gestational ages 23.0 and 31.8 weeks) and change in pCRH between visits (ΔpCRH). RESULTS: In weighted quantile sums (WQS) regression models, phthalate mixtures were associated with higher pCRH at Visit 1 (ß = 0.07, 95 %CI: 0.02, 0.11) but lower pCRH at Visit 2 (ß = -0.08, 95 %CI: -0.14, -0.02). In stratified analyses, among women with gestational diabetes (n = 59), phthalate mixtures were associated with lower pCRH at Visit 1 (ß = -0.17, 95 %CI: -0.35, 0.0006) and Visit 2 (ß = -0.35, 95 %CI: -0.50, -0.19), as well as greater ΔpCRH (ß = 0.16, 95 %CI: 0.07, 0.25). Among women with gestational hypertension (n = 102), phthalate mixtures were associated with higher pCRH at Visit 1 (ß = 0.20, 95 %CI: 0.03, 0.36) and Visit 2 (ß = 0.42; 95 %CI: 0.19, 0.64) and lower ΔpCRH (ß = -0.17, 95 %CI: -0.29, -0.06). Significant interactions between individual phthalate metabolites and pregnancy complications were observed. CONCLUSIONS: Phthalates may impact placental CRH secretion, with differing effects across pregnancy. Differences in results between women with and without gestational diabetes and gestational hypertension suggest a need for further research examining whether women with pregnancy complications may be more vulnerable to endocrine-disrupting effects of phthalates.

19.
Ther Adv Respir Dis ; 16: 17534666211070143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35012387

RESUMO

OBJECTIVES: [1] To investigate the cardiorespiratory fitness (CRF) levels in children and adolescents with cystic fibrosis (CF) with no ventilatory limitation (ventilatory reserve ⩾ 15%) during exercise, and [2] to assess which physiological factors are related to CRF. METHODS: A cross-sectional study design was used in 8- to 18-year-old children and adolescents with CF. Cardiopulmonary exercise testing was used to determine peak oxygen uptake normalized to body weight as a measure of CRF. Patients were defined as having 'low CRF' when CRF was less than 82%predicted. Physiological predictors used in this study were body mass index z-score, P. Aeruginosa lung infection, impaired glucose tolerance (IGT) including CF-related diabetes, CF-related liver disease, sweat chloride concentration, and self-reported physical activity. Backward likelihood ratio (LR) logistic regression analysis was used. RESULTS: Sixty children and adolescents (51.7% boys) with a median age of 15.3 years (25th-75th percentile: 12.9-17.0 years) and a mean percentage predicted forced expiratory volume in 1 second of 88.5% (±16.9) participated. Mean percentage predicted CRF (ppVO2peak/kg) was 81.4% (±12.4, range: 51%-105%). Thirty-three patients (55.0%) were classified as having 'low CRF'. The final model that best predicted low CRF included IGT (p = 0.085; Exp(B) = 6.770) and P. Aeruginosa lung infection (p = 0.095; Exp(B) = 3.945). This model was able to explain between 26.7% and 35.6% of variance. CONCLUSIONS: CRF is reduced in over half of children and adolescents with CF with normal ventilatory reserve. Glucose intolerance and P. Aeruginosa lung infection seem to be associated to low CRF in children and adolescents with CF.

20.
BMC Endocr Disord ; 22(1): 19, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35012530

RESUMO

BACKGROUND: Participants' study satisfaction is important for both compliance with study protocols and retention, but research on parent study satisfaction is rare. This study sought to identify factors associated with parent study satisfaction in The Environmental Determinants of Diabetes in the Young (TEDDY) study, a longitudinal, multinational (US, Finland, Germany, Sweden) study of children at risk for type 1 diabetes. The role of staff consistency to parent study satisfaction was a particular focus. METHODS: Parent study satisfaction was measured by questionnaire at child-age 15 months (5579 mothers, 4942 fathers) and child-age four years (4010 mothers, 3411 fathers). Multiple linear regression analyses were used to identify sociodemographic factors, parental characteristics, and study variables associated with parent study satisfaction at both time points. RESULTS: Parent study satisfaction was highest in Sweden and the US, compared to Finland. Parents who had an accurate perception of their child's type 1 diabetes risk and those who believed they can do something to prevent type 1 diabetes were more satisfied. More educated parents and those with higher depression scores had lower study satisfaction scores. After adjusting for these factors, greater study staff change frequency was associated with lower study satisfaction in European parents (mothers at child-age 15 months: - 0.30,95% Cl - 0.36, - 0.24, p < 0.001; mothers at child-age four years: -0.41, 95% Cl - 0.53, - 0.29, p < 0.001; fathers at child-age 15 months: -0.28, 95% Cl - 0.34, - 0.21, p < 0.001; fathers at child-age four years: -0.35, 95% Cl - 0.48, - 0.21, p < 0.001). Staff consistency was not associated with parent study satisfaction in the US. However, the number of staff changes was markedly higher in the US compared to Europe. CONCLUSIONS: Sociodemographic factors, parental characteristics, and study-related variables were all related to parent study satisfaction. Those that are potentially modifiable are of particular interest as possible targets of future efforts to improve parent study satisfaction. Three such factors were identified: parent accuracy about the child's type 1 diabetes risk, parent beliefs that something can be done to reduce the child's risk, and study staff consistency. However, staff consistency was important only for European parents. TRIAL REGISTRATION: NCT00279318 .

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...