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1.
J Med Virol ; 94(1): 99-109, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34570905

RESUMO

A severe pandemic of Coronavirus Disease (COVID-19) has been sweeping the globe since 2019, and this time, it did not stop, with frequent mutations transforming into virulent strains, for instance, B.1.1.7, B.1.351, and B.1.427. In recent months, a fungal infection, mucormycosis has emerged with more fatal responses and significantly increased mortality rate. To measure the severity and potential alternative approaches against black fungus coinfection in COVID-19 patients, PubMed, Google Scholar, World Health Organization (WHO) newsletters, and other online resources, based on the cases reported and retrospective observational analysis were searched from the years 2015-2021. The studies reporting mucormycosis with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coinfection and/or demonstrating potential risk factors, such as a history of diabetes mellitus or suppressed immune system were included, and reports published in non-English language were excluded. More than 20 case reports and observational studies on black fungus coinfection in COVID-19 patients were eligible for inclusion. The results indicated that diabetes mellitus, hyperglycemic, and immunocompromised COVID-19 patients with mucormycosis were at a higher risk. We found that it was prudent to assess the potential risk factors and severity of invasive mycosis via standardized diagnostic and clinical settings. Large-scale studies need to be conducted to identify early biomarkers and optimization of diagnostic methods has to be established per population and geographical variation. This will not only help clinicians around the world to detect the coinfection in time but also will prepare them for future outbreaks of other potential pandemics.


Assuntos
COVID-19/epidemiologia , Coinfecção/epidemiologia , Mucormicose/epidemiologia , Mucormicose/mortalidade , SARS-CoV-2/isolamento & purificação , Diabetes Mellitus/patologia , Humanos , Hiperglicemia/patologia , Hospedeiro Imunocomprometido/fisiologia , Mucorales/crescimento & desenvolvimento , Mucorales/isolamento & purificação , Mucormicose/patologia , Estudos Retrospectivos , Fatores de Risco
2.
PLoS One ; 16(10): e0258494, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648578

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is an emerging public health issue globally. The prevalence estimates on CKD in South Asia are however limited. This study aimed to examine the prevalence of CKD among the general and high-risk population in South Asia. METHODS: We conducted a systematic review and meta-analysis of population-level prevalence studies in South Asia (Afghanistan, Bangladesh, Bhutan, Maldives, Nepal, India, Pakistan, and Sri Lanka). Three databases namely PubMed, Scopus and Web of Science were systematically searched for published reports of kidney disease in South Asia up to 28 October 2020. A random-effect model for computing the pooled prevalence was used. RESULTS: Of the 8749 identified studies, a total of 24 studies were included in the review. The pooled prevalence of CKD among the general population was 14% (95% CI 11-18%), and 15% (95% CI 11-20%) among adult males and 13% (95% CI 10-17%) in adult females. The prevalence of CKD was 27% (95% CI 20-35%) in adults with hypertension, 31% (95% CI 22-41%) in adults with diabetes and 14% (95% CI 10-19%) in adults who were overweight/obese. We found substantial heterogeneity across the included studies in the pooled estimates for CKD prevalence in both general and high-risk populations. The prevalence of CKD of unknown origin in the endemic population was 8% (95% CI 3-16%). CONCLUSION: Our study reaffirms the previous reports that CKD represents a serious public health challenge in South Asia, with the disease prevalent among 1 in 7 adults in South Asian countries.


Assuntos
Insuficiência Renal Crônica/epidemiologia , Ásia Sudeste/epidemiologia , Ásia Ocidental/epidemiologia , Complicações do Diabetes , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/patologia , Prevalência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Fatores de Risco
3.
PLoS One ; 16(10): e0257940, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618834

RESUMO

The objective of this study was to examine the link between systemic and general psychosocial stress and cardiovascular disease (CVD) risk in a group of U.S. Latinos as a function of acculturation and education within the blended guiding conceptual framework of the biopsychosocial model of the stress process plus the reserve capacity model. We analyzed data from self-identifying Mexican-origin adults (n = 396, 56.9% female, Mage = 58.2 years, 55.5% < 12 years of education, 79% U.S.-born) from the Texas City Stress and Health Study. We used established measures of perceived stress (general stress), neighborhood stress and discrimination (systemic stress) to capture psychosocial stress, our primary predictor. We used the atherosclerotic CVD calculator to assess 10-year CVD risk, our primary outcome. This calculator uses demographics, cholesterol, blood pressure, and history of hypertension, smoking, and diabetes to compute CVD risk in the next 10 years. We also created an acculturation index using English-language use, childhood interaction, and preservation of cultural values. Participants reported years of education. Contrary to expectations, findings showed that higher levels of all three forms of psychosocial stress, perceived stress, neighborhood stress, and perceived discrimination, predicted lower 10-year CVD risk. Acculturation and education did not moderate the effects of psychosocial stress on 10-year CVD risk. Contextualized within the biopsychosocial and reserve capacity framework, we interpret our findings such that participants who accurately reported their stressors may have turned to their social networks to handle the stress, thereby reducing their risk for CVD. We highlight the importance of examining strengths within the sociocultural environment when considering cardiovascular inequities among Latinos.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Fatores de Risco de Doenças Cardíacas , Hipertensão/epidemiologia , Aculturação , Adulto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/psicologia , Criança , Colesterol/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Diabetes Mellitus/psicologia , Feminino , Hispano-Americanos/psicologia , Humanos , Hipertensão/sangue , Hipertensão/patologia , Hipertensão/psicologia , Masculino , Americanos Mexicanos/psicologia , Características de Residência , Fumar , Estresse Psicológico/fisiopatologia
4.
Sci Rep ; 11(1): 17414, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465815

RESUMO

We aimed to analyze the relationship of the distribution of body fat mass (FM) and fat-free mass (FFM) in the limbs and trunk with the prevalence of cardiovascular disease risk factors (CVD-RF). In total, 13,032 adults were selected from the KNHANES (2008-2011). The prevalence of hypertension, diabetes mellitus (DM), dyslipidemia, and metabolic syndrome (MetS) according to the arm-to-leg ratio and limbs-to-trunk ratio for FM and FFM was compared, respectively. The higher the arm-to-leg FM ratio, the higher the prevalence of CVD-RF (DM-male-OR 7.04, 95% CI 4.22-11.74; DM-female-OR 10.57, 95% CI 5.80-19.26; MetS-male-OR 4.47, 95% CI 3.41- 5.86; MetS-female-OR 8.73, 95% CI 6.38-11.95). The higher the limbs-to-trunk FM ratio (DM-male-OR 0.12, 95% CI 0.07-0.21; DM-female-OR 0.12, 95% CI 0.06-0.23; MetS-male-OR 0.06, 95% CI 0.04-0.08; MetS-female-OR 0.02, 95% CI 0.01-0.04), the higher the limbs-to-trunk FFM ratio (DM-male-OR 0.19, 95% CI 0.11-0.31; DM-female-OR 0.46, 95% CI 0.30-0.70; MetS-male-OR 0.39, 95% CI 0.31-0.50; MetS-female-OR 0.62, 95% CI 0.50-0.78), and the higher the arm-to-leg FFM ratio (MetS-male-OR 0.75, 95% CI 0.59-0.94; MetS-female-OR 0.73, 95% CI 0.58-0.92), the lower the prevalence of CVD-RF. The higher the FM of the legs compared to the arms, FFM of the arms compared to the legs, and FM or FFM of the limbs compared to the trunk, the lower the prevalence of CVD-RF.


Assuntos
Braço/fisiopatologia , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Extremidades/fisiopatologia , Perna (Membro)/fisiopatologia , Síndrome Metabólica/epidemiologia , Tronco/fisiopatologia , Adulto , Doenças Cardiovasculares/patologia , Diabetes Mellitus/patologia , Impedância Elétrica , Feminino , Humanos , Masculino , Síndrome Metabólica/patologia , Prevalência , República da Coreia/epidemiologia , Fatores de Risco
5.
Sci Rep ; 11(1): 17796, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493754

RESUMO

Pancreatic islet cells have plasticity, such as the abilities to dedifferentiate and transdifferentiate. Islet cell conversion to other characteristic cell is largely determined by transcription factors, but significance of expression patterns of these transcription factors in human islet cells remained unclear. Here, we present the NKX6.1-positive ratio of glucagon-positive cells (NKX6.1+/GCG+ ratio) and the ARX-negative ratio of glucagon-positive cells (ARX-/GCG+ ratio) in 34 patients who were not administered antidiabetic agents. Both of NKX6.1+/GCG+ ratio and ARX-/GCG+ ratio negatively associated with relative beta cell area. And these ratios did not have significant correlation with other parameters including age, body mass index, hemoglobin A1c, fasting plasma glucose level or relative alpha-cell area. Our data demonstrate that these expression ratios of transcription factors in glucagon-positive cells closely correlate with the reduction of beta-cell volume in human pancreas.


Assuntos
Transdiferenciação Celular , Regulação da Expressão Gênica , Células Secretoras de Glucagon/metabolismo , Proteínas de Homeodomínio/biossíntese , Células Secretoras de Insulina/metabolismo , Fatores de Transcrição/biossíntese , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Glicemia/análise , Peptídeo C/sangue , Tamanho Celular , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Feminino , Células Secretoras de Glucagon/ultraestrutura , Intolerância à Glucose/genética , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Hemoglobina A Glicada/análise , Proteínas de Homeodomínio/genética , Humanos , Células Secretoras de Insulina/ultraestrutura , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Pancreatectomia , Cisto Pancreático/genética , Cisto Pancreático/metabolismo , Cisto Pancreático/patologia , Cisto Pancreático/cirurgia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Pancreaticoduodenectomia , Fatores de Transcrição/genética
6.
Infect Genet Evol ; 95: 105092, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34571275

RESUMO

OBJECTIVES: To compare the demographics, clinical characteristics and severity of patients infected with nine different SARS-CoV-2 variants, during three phases of the COVID-19 epidemic in Marseille. METHODS: A single centre retrospective cohort study was conducted in 1760 patients infected with SARS-CoV-2 of Nextstrain clades 20A, 20B, and 20C (first phase, February-May 2020), Pangolin lineages B.1.177 (we named Marseille-2) and B.1.160 (Marseille-4) variants (second phase, June-December 2020), and B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and A.27 (Marseille-501) variants (third phase, January 2021-today). Outcomes were the occurrence of clinical failures, including hospitalisation, transfer to the intensive-care unit, and death. RESULTS: During each phase, no major differences were observed with regards to age and gender distribution, the prevalence of chronic diseases, and clinical symptoms between variants circulating in a given phase. The B.1.177 and B.1.160 variants were associated with more severe outcomes. Infections occurring during the second phase were associated with a higher rate of death as compared to infections during the first and third phases. Patients in the second phase were more likely to be hospitalised than those in the third phase. Patients infected during the third phase were more frequently obese than others. CONCLUSION: A large cohort study is recommended to evaluate the transmissibility and to better characterise the clinical severity of emerging variants.


Assuntos
COVID-19/patologia , Diabetes Mellitus/patologia , Genoma Viral , Hipertensão/patologia , Obesidade/patologia , SARS-CoV-2/patogenicidade , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/virologia , Comorbidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Feminino , França/epidemiologia , Genótipo , Cardiopatias/epidemiologia , Cardiopatias/mortalidade , Cardiopatias/patologia , Cardiopatias/virologia , Hospitalização/estatística & dados numéricos , Hospitais , Humanos , Hipertensão/epidemiologia , Hipertensão/mortalidade , Hipertensão/virologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/mortalidade , Neoplasias/patologia , Neoplasias/virologia , Obesidade/epidemiologia , Obesidade/mortalidade , Obesidade/virologia , Filogenia , Estudos Retrospectivos , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Análise de Sequência de RNA , Índice de Gravidade de Doença , Análise de Sobrevida
7.
Signal Transduct Target Ther ; 6(1): 300, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381015

RESUMO

Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. In this study, we investigate whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes. First, we identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups. We further demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. Serum exosomes from young people can inhibit SARS-CoV-2 replication and S protein expression, while the inhibitory effect is markedly decreased in the elderly and diabetic patients. Moreover, three out of the four circulating miRNAs are significantly increased in the serum of healthy volunteers after 8-weeks' continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication. Our study demonstrates for the first time that circulating exosomal miRNAs can directly inhibit SARS-CoV-2 replication and may provide a possible explanation for the difference in response to COVID-19 between young people and the elderly or people with comorbidities.


Assuntos
COVID-19/genética , Diabetes Mellitus/genética , MicroRNAs/genética , Glicoproteína da Espícula de Coronavírus/genética , Adulto , Fatores Etários , Idoso , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , China , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Estudos de Coortes , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Diabetes Mellitus/virologia , Exercício Físico , Exossomos/genética , Exossomos/metabolismo , Exossomos/virologia , Feminino , Regulação da Expressão Gênica , Células HEK293 , Interações Hospedeiro-Patógeno/genética , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/sangue , Replicação Viral
8.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360534

RESUMO

Inorganic phosphate (Pi) is an essential nutrient for living organisms and is maintained in equilibrium in the range of 0.8-1.4 mM Pi. Pi is a source of organic constituents for DNA, RNA, and phospholipids and is essential for ATP formation mainly through energy metabolism or cellular signalling modulators. In mitochondria isolated from the brain, liver, and heart, Pi has been shown to induce mitochondrial reactive oxygen species (ROS) release. Therefore, the purpose of this review article was to gather relevant experimental records of the production of Pi-induced reactive species, mainly ROS, to examine their essential roles in physiological processes, such as the development of bone and cartilage and the development of diseases, such as cardiovascular disease, diabetes, muscle atrophy, and male reproductive system impairment. Interestingly, in the presence of different antioxidants or inhibitors of cytoplasmic and mitochondrial Pi transporters, Pi-induced ROS production can be reversed and may be a possible pharmacological target.


Assuntos
Doenças Cardiovasculares/patologia , Diabetes Mellitus/patologia , Mitocôndrias/patologia , Atrofia Muscular/patologia , Fosfatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Metabolismo Energético , Humanos , Mitocôndrias/efeitos dos fármacos , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo
9.
PLoS One ; 16(8): e0255144, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34343179

RESUMO

AIMS: The objective of this study is to analyze how the impact of Diabetes Mellitus [DM] in patients with COVID-19 varies according to altitudinal gradient. METHODS: We obtained 1,280,806 records from adult patients with COVID-19 and DM to analyze the probability of COVID-19, development of COVID-19 pneumonia, hospitalization, intubation, admission to the Intensive Care Unit [ICU] and case-fatality rates [CFR]. Variables were controlled by age, sex and altitude of residence to calculate adjusted prevalence and prevalence ratios. RESULTS: Patients with DM had a 21.8% higher prevalence of COVID-19 and an additional 120.2% higher prevalence of COVID-19 pneumonia. The adjusted prevalence was also higher for these outcomes as well as for hospitalization, intubation and ICU admission. COVID-19 and pneumonia patients with DM had a 97.0% and 19.4% higher CFR, respectively. With increasing altitudes, the probability of being a confirmed COVID-19 case and the development of pneumonia decreased along CFR for patients with and without DM. However, COVID-19 patients with DM were more likely to require intubation when residing at high altitude. CONCLUSIONS: The study suggests that patients with DM have a higher probability of being a confirmed COVID-19 case and developing pneumonia. Higher altitude had a protective relationship against SARS-CoV-2 infection; however, it may be associated with more severe cases in patients with and without DM. High altitude decreases CFR for all COVID-19 patients. Our work also shows that women are less affected than men regardless of altitude.


Assuntos
Altitude , COVID-19/patologia , Diabetes Mellitus/patologia , Adulto , Idoso , COVID-19/mortalidade , COVID-19/virologia , Complicações do Diabetes , Diabetes Mellitus/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Taxa de Sobrevida
10.
Molecules ; 26(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34443506

RESUMO

Macrophages play a prominent role in wound healing. In the early stages, they promote inflammation and remove pathogens, wound debris, and cells that have apoptosed. Later in the repair process, they dampen inflammation and secrete factors that regulate the proliferation, differentiation, and migration of keratinocytes, fibroblasts, and endothelial cells, leading to neovascularisation and wound closure. The macrophages that coordinate this repair process are complex: they originate from different sources and have distinct phenotypes with diverse functions that act at various times in the repair process. Macrophages in individuals with diabetes are altered, displaying hyperresponsiveness to inflammatory stimulants and increased secretion of pro-inflammatory cytokines. They also have a reduced ability to phagocytose pathogens and efferocytose cells that have undergone apoptosis. This leads to a reduced capacity to remove pathogens and, as efferocytosis is a trigger for their phenotypic switch, it reduces the number of M2 reparative macrophages in the wound. This can lead to diabetic foot ulcers (DFUs) forming and contributes to their increased risk of not healing and becoming infected, and potentially, amputation. Understanding macrophage dysregulation in DFUs and how these cells might be altered, along with the associated inflammation, will ultimately allow for better therapies that might complement current treatment and increase DFU's healing rates.


Assuntos
Diabetes Mellitus/patologia , Macrófagos/patologia , Pele/patologia , Cicatrização , Animais , Humanos , Inflamação/patologia , Modelos Biológicos
11.
Int J Mol Sci ; 22(16)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34445256

RESUMO

Recent data demonstrate the anabolic effect of oxytocin on bone. Bone cells express oxytocin receptors. Oxytocin promotes osteoblasts differentiation and function, leading to an increased bone formation with no effect on bone resorption and an improvement of bone microarchitecture. Oxytocin is synthetized by osteoblasts, and this synthesis is stimulated by estrogen. Animal studies demonstrate a direct action of oxytocin on bone, as the systemic administration of oxytocin prevents and reverses the bone loss induced by estrogen deficiency. Although oxytocin is involved in bone formation in both sexes during development, oxytocin treatment has no effect on male osteoporosis, underlining the importance of estrogen that amplifies its local autocrine and paracrine secretion. There are few human data showing a decrease in the oxytocin serum level in anorexia nervosa independently of estrogen and in amenorrheic women associated with impaired bone microarchitecture; in post-menopausal women a higher oxytocin serum level is associated with higher bone density, but not in osteoporotic men. Oxytocin displays many effects that may be beneficial in the management of osteoporosis, cardiovascular diseases, cognitive disorders, breast cancer, diabetes and body fat gain, all age-related diseases affecting elderly women, opening exciting therapeutic perspectives, although the issue is to find a single route, dosage and schedule able to reach all these targets.


Assuntos
Comunicação Autócrina , Densidade Óssea , Osso e Ossos/metabolismo , Ocitocina/metabolismo , Comunicação Parácrina , Caracteres Sexuais , Amenorreia/metabolismo , Animais , Anorexia Nervosa/metabolismo , Osso e Ossos/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Estrogênios/deficiência , Estrogênios/metabolismo , Feminino , Humanos , Masculino , Osteoporose Pós-Menopausa/metabolismo
12.
Nat Commun ; 12(1): 4928, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389720

RESUMO

Diabetes results from a decline in functional pancreatic ß-cells, but the molecular mechanisms underlying the pathological ß-cell failure are poorly understood. Here we report that large-tumor suppressor 2 (LATS2), a core component of the Hippo signaling pathway, is activated under diabetic conditions and induces ß-cell apoptosis and impaired function. LATS2 deficiency in ß-cells and primary isolated human islets as well as ß-cell specific LATS2 ablation in mice improves ß-cell viability, insulin secretion and ß-cell mass and ameliorates diabetes development. LATS2 activates mechanistic target of rapamycin complex 1 (mTORC1), a physiological suppressor of autophagy, in ß-cells and genetic and pharmacological inhibition of mTORC1 counteracts the pro-apoptotic action of activated LATS2. We further show a direct interplay between Hippo and autophagy, in which LATS2 is an autophagy substrate. On the other hand, LATS2 regulates ß-cell apoptosis triggered by impaired autophagy suggesting an existence of a stress-sensitive multicomponent cellular loop coordinating ß-cell compensation and survival. Our data reveal an important role for LATS2 in pancreatic ß-cell turnover and suggest LATS2 as a potential therapeutic target to improve pancreatic ß-cell survival and function in diabetes.


Assuntos
Autofagia , Diabetes Mellitus/metabolismo , Células Secretoras de Insulina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Células Cultivadas , Diabetes Mellitus/genética , Diabetes Mellitus/patologia , Humanos , Células Secretoras de Insulina/citologia , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Serina-Treonina Quinases/genética , Interferência de RNA , Ratos , Transdução de Sinais/genética , Proteínas Supressoras de Tumor/genética
13.
Cells ; 10(7)2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34359881

RESUMO

Proper functioning of the body depends on hormonal homeostasis. White adipose tissue is now known as an endocrine organ due to the secretion of multiple molecules called adipokines. These proteins exert direct effects on whole body functions, including lipid metabolism, angiogenesis, inflammation, and reproduction, whereas changes in their level are linked with pathological events, such as infertility, diabetes, and increased food intake. Vaspin-visceral adipose tissue-derived serine protease inhibitor, or SERPINA12 according to serpin nomenclature, is an adipokine discovered in 2005 that is connected to the development of insulin resistance, obesity, and inflammation. A significantly higher amount of vaspin was observed in obese patients. The objective of this review was to summarize the latest findings about vaspin expression and action in endocrine tissues, such as the hypothalamus, pituitary gland, adipose tissue, thyroid, ovary, placenta, and testis, as well as discuss the link between vaspin and pathologies connected with hormonal imbalance.


Assuntos
Diabetes Mellitus/genética , Células Endócrinas/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Infertilidade/genética , Obesidade/genética , Serpinas/genética , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Células Endócrinas/citologia , Feminino , Regulação da Expressão Gênica , Gônadas/citologia , Gônadas/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/citologia , Infertilidade/metabolismo , Infertilidade/patologia , Resistência à Insulina , Metabolismo dos Lipídeos/genética , Masculino , Neovascularização Fisiológica/genética , Obesidade/metabolismo , Obesidade/patologia , Reprodução/genética , Serpinas/metabolismo , Glândula Tireoide/citologia , Glândula Tireoide/metabolismo
14.
Cells ; 10(7)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34360006

RESUMO

The cluster of differentiation 36 (CD36) is a scavenger receptor present on various types of cells and has multiple biological functions that may be important in inflammation and in the pathogenesis of metabolic diseases, including diabetes. Here, we consider recent insights into how the CD36 response becomes deregulated under metabolic conditions, as well as the therapeutic benefits of CD36 inhibition, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with metabolic diseases. To facilitate this process further, it is important to pinpoint regulatory mechanisms that are relevant under physiological and pathological conditions. In particular, understanding the mechanisms involved in dictating specific CD36 downstream cellular outcomes will aid in the discovery of potent compounds that target specific CD36 downstream signaling cascades.


Assuntos
Antígenos CD36/metabolismo , Diabetes Mellitus/metabolismo , Hiperglicemia/metabolismo , Células Secretoras de Insulina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética , Amiloide/metabolismo , Anti-Inflamatórios/uso terapêutico , Antígenos CD36/antagonistas & inibidores , Antígenos CD36/genética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Diabetes Mellitus/patologia , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/genética , Hiperglicemia/patologia , Inflamação , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/patologia , Lipoproteínas LDL/metabolismo , Terapia de Alvo Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores
15.
PLoS One ; 16(8): e0255786, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34415953

RESUMO

OBJECTIVES: N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) is a diagnostic marker for heart failure and a prognostic factor for cardiovascular disease (CVD). The aim of this study was to examine the association of socioeconomic position (SEP) with NT-proBNP while assessing sex-differences and the impact of CVD risk factors and prevalent CVD on the association. METHODS: Baseline data of 4598 participants aged 45-75 years of the Heinz Nixdorf Recall Study were used. Income and education were used as SEP indicators. Age- and sex-adjusted linear regression models were fitted to calculate effect size estimates and 95% confidence intervals (95%-CIs) for the total effect of SEP indicators on NT-proBNP, while potential mediation was assessed by additionally accounting for traditional CVD risk factors (i.e., systolic blood pressure, HDL cholesterol, LDL cholesterol, diabetes, anti-hypertensive medication, lipid-lowering medication, BMI, current smoking). Education and income were included separately in the models. RESULTS: With an age- and sex-adjusted average change in NT-proBNP of -6.47% (95%-CI: -9.91; -2.91) per 1000€, the association between income and NT-proBNP was more pronounced compared to using education as a SEP indicator (-0.80% [95%-CI: -1.92; 0.32] per year of education). Sex-stratified results indicated stronger associations in men (-8.43% [95%-CI: -13.21; -3.38] per 1000€; -1.63% [95%-CI: -3.23; -0.001] per year of education) compared to women (-5.10% [95%-CI: -9.82; -0.01] per 1000€; -1.04% [95%-CI: -2.59; 0.50] per year of education). After adjusting for CVD risk factors some of the observed effect size estimates were attenuated, while the overall association between SEP indicators and NT-proBNP was still indicated. The exclusion of participants with prevalent coronary heart disease or stroke did not lead to a substantial change in the observed associations. CONCLUSIONS: In the present study associations of education and income with NT-proBNP were observed in a population-based study sample. Only parts of the association were explained by traditional CVD risk factors, while there were substantial sex-differences in the strength of the observed association. Overt coronary heart disease or stroke did not seem to trigger the associations.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Classe Social , Idoso , Anti-Hipertensivos/uso terapêutico , Índice de Massa Corporal , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/patologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fumar/efeitos adversos
16.
Diabetes ; 70(9): 2120-2130, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34417262

RESUMO

Diabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19), the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. We aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of patients with and without diabetes hospitalized for COVID-19. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of the SARS-CoV-2 main receptor system (ACE2/TMPRSS2), and for the main molecule of the leukotriene B4 (LTB4) pathway (ALOX5). We found that diabetes activates the LTB4 pathway and that during COVID-19 it increases ACE2/TMPRSS2 as well as ALOX5 expression. Diabetes was also associated with COVID-19-related disorders, such as reduced oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen (FiO2) and arterial partial pressure of oxygen/FiO2 levels, and increased disease duration. In addition, the expressions of ACE2 and ALOX5 are positively correlated, with increased expression in patients with diabetes and COVID-19 requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB4 is significantly increased in individuals with diabetes. In addition, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB4 and IL-6 systemic levels, as well as ACE2/ALOX5 blood expression, could be early markers of severe COVID-19 in individuals with diabetes.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Araquidonato 5-Lipoxigenase/metabolismo , COVID-19/patologia , Diabetes Mellitus/patologia , Leucotrieno B4/metabolismo , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/genética , Araquidonato 5-Lipoxigenase/genética , COVID-19/metabolismo , Regulação da Expressão Gênica , Humanos , Inflamação/metabolismo , Leucotrieno B4/genética , Fatores de Risco , Transdução de Sinais
17.
Cells ; 10(8)2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34440773

RESUMO

The pancreatic islets of Langerhans secrete several hormones critical for glucose homeostasis. The ß-cells, the major cellular component of the pancreatic islets, secrete insulin, the only hormone capable of lowering the plasma glucose concentration. The counter-regulatory hormone glucagon is secreted by the α-cells while δ-cells secrete somatostatin that via paracrine mechanisms regulates the α- and ß-cell activity. These three peptide hormones are packed into secretory granules that are released through exocytosis following a local increase in intracellular Ca2+ concentration. The high voltage-gated Ca2+ channels (HVCCs) occupy a central role in pancreatic hormone release both as a source of Ca2+ required for excitation-secretion coupling as well as a scaffold for the release machinery. HVCCs are multi-protein complexes composed of the main pore-forming transmembrane α1 and the auxiliary intracellular ß, extracellular α2δ, and transmembrane γ subunits. Here, we review the current understanding regarding the role of all HVCC subunits expressed in pancreatic ß-cell on electrical activity, excitation-secretion coupling, and ß-cell mass. The evidence we review was obtained from many seminal studies employing pharmacological approaches as well as genetically modified mouse models. The significance for diabetes in humans is discussed in the context of genetic variations in the genes encoding for the HVCC subunits.


Assuntos
Glicemia/metabolismo , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Diabetes Mellitus/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Ativação do Canal Iônico , Animais , Canais de Cálcio/genética , Diabetes Mellitus/sangue , Diabetes Mellitus/genética , Diabetes Mellitus/patologia , Exocitose , Humanos , Células Secretoras de Insulina/patologia , Potenciais da Membrana , Via Secretória
18.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34281192

RESUMO

Diabetic retinopathy is one of the leading causes of blindness in the world with the incidence of disease ever-increasing worldwide. The vitreous humor represents an extensive and complex interactive arena for cytokines in the diabetic eye. In recent decades, there has been significant progress in understanding this environment and its implications in disease pathophysiology. In this review, we investigate the vitreous ecosystem in diabetic retinopathy at the molecular level. Areas of concentration include: the current level of knowledge of growth factors, cytokine and chemokine mediators, and lipid-derived metabolites in the vitreous. We discuss the molecular patho-mechanisms of diabetic retinopathy based upon current vitreous research.


Assuntos
Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Corpo Vítreo/metabolismo , Corpo Vítreo/patologia , Humor Aquoso/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interleucinas/metabolismo
19.
Eur J Med Genet ; 64(9): 104285, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34229114

RESUMO

Recently, an autosomal recessive disorder including the triad of microcephaly, infantile epileptic encephalopathy, and permanent neonatal diabetes syndrome (MEDS, OMIM#614231) has emerged as a new distinguishing syndrome. Eight cases of whom seven from Arab countries, have been reported in association with biallelic variants in the IER3IP1 gene (Immediate early response-3 interacting protein-1). Here, we describe a Tunisian boy who presented with permanent neonatal diabetes, microcephaly, generalized seizures and hypovirilized external genitalia consisting of a small genitalia and unilateral cryptorchidism. Chromosomal analysis indicated a 46, XY karyotype in all metaphases. Exome sequencing identified a homozygous missense variant (c.62 T > G; p. Val21Gly) in the IER3IP1 gene, that is predicted to alter the protein structure within the hydrophobic/transmembrane. This variant was previously reported in two cases associated with MEDS. This is the first reported case of MEDS in Tunisia. Our report focuses on the IER3IP1 related phenotypic spectrum and assumes abnormal genitalia as part of the syndrome. Consequently, we recommend to perform hormonal testing on this topic to understand the effect of the IER3IP1 variant on the male genital pathway.


Assuntos
Proteínas de Transporte/genética , Criptorquidismo/patologia , Diabetes Mellitus/patologia , Epilepsia/patologia , Doenças do Recém-Nascido/patologia , Proteínas de Membrana/genética , Transtornos Psicomotores/patologia , Proteínas de Transporte/química , Criptorquidismo/genética , Diabetes Mellitus/genética , Epilepsia/genética , Humanos , Recém-Nascido , Doenças do Recém-Nascido/genética , Cariótipo , Masculino , Proteínas de Membrana/química , Mutação de Sentido Incorreto , Domínios Proteicos , Transtornos Psicomotores/genética , Síndrome
20.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203572

RESUMO

Type 2 diabetes mellitus (T2D) is one of the prominent risk factors for the development and progression of calcific aortic valve disease. Nevertheless, little is known about molecular mechanisms of how T2D affects aortic valve (AV) remodeling. In this study, the influence of hyperinsulinemia and hyperglycemia on degenerative processes in valvular tissue is analyzed in intact AV exposed to an either static or dynamic 3D environment, respectively. The complex native dynamic environment of AV is simulated using a software-governed bioreactor system with controlled pulsatile flow. Dynamic cultivation resulted in significantly stronger fibrosis in AV tissue compared to static cultivation, while hyperinsulinemia and hyperglycemia had no impact on fibrosis. The expression of key differentiation markers and proteoglycans were altered by diabetic conditions in an environment-dependent manner. Furthermore, hyperinsulinemia and hyperglycemia affect insulin-signaling pathways. Western blot analysis showed increased phosphorylation level of protein kinase B (AKT) after acute insulin stimulation, which was lost in AV under hyperinsulinemia, indicating acquired insulin resistance of the AV tissue in response to elevated insulin levels. These data underline a complex interplay of diabetic conditions on one hand and biomechanical 3D environment on the other hand that possesses an impact on AV tissue remodeling.


Assuntos
Valvopatia Aórtica/metabolismo , Estenose da Valva Aórtica/metabolismo , Diabetes Mellitus/patologia , Hiperglicemia/patologia , Hiperinsulinismo/patologia , Insulina/metabolismo , Animais , Valvopatia Aórtica/genética , Estenose da Valva Aórtica/genética , Diabetes Mellitus/metabolismo , Humanos , Hiperglicemia/metabolismo , Hiperinsulinismo/metabolismo
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