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1.
Exp Ther Med ; 22(5): 1269, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34594406

RESUMO

Selenium (Se) is considered to have antioxidant properties, which are beneficial for heart condition. Hyperhomocysteinemia (HHCY) has been suggested to potentially lead to heart failure and is characterized by cardiac fibrosis; however, investigation on the role of Se and HHCY in cardiac fibrosis is rare. Since previous studies demonstrated the important role of the long non-coding RNA maternally expressed 3 (MEG3) in some heart diseases, the present study aimed to determine how Se and MEG3 might exert regulatory effects on HCY-induced fibrosis in cardiac fibroblasts (CFs). Mouse CFs were isolated and treated with HCY and Se. The expression of α-smooth muscle actin (α-SMA), collagen I and III was detected by western blotting to reflect CF fibrosis. Reverse transcription-quantitative PCR was performed to determine the expression levels of MEG3. Inflammation and oxidative stress responses were analyzed by measuring TNF-α, IL-1ß (ELISA) and reactive oxygen species levels (using a commercial kit), respectively. Cell Counting Kit-8 was used to evaluate CF proliferation. Total and phosphorylated (p) expression of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was evaluated by western blotting. CFs were transfected with adenovirus expressing MEG3 short-hairpin RNA to knock down MEG3 expression. Se treatment downregulated the expression level of MEG3 in HCY-stimulated CFs, whilst inhibiting the inflammatory and oxidative stress response. Furthermore, Se inhibited the increased proliferation of CFs following HCY treatment. In addition, MEG3-knockdown in CFs could improve fibrosis caused by HCY. Furthermore, the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 were decreased following treatment with Se or MEG3 silencing. Taken together, the findings from the present study suggested that Se may alleviate cardiac fibrosis by downregulating the expression of MEG3 and reducing the inflammatory and oxidative stress response in CFs. This suggests that Se may be a potential therapeutic option for treating cardiac fibrosis in the future.

3.
Food Funct ; 12(21): 10950-10966, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34647944

RESUMO

Vascular intimal hyperplasia is a hallmark event in vascular restenosis. The excessive proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMCs) play important roles in the pathological mechanism of vascular intimal hyperplasia. Physalin B is an alcoholate isolated from Physalis (Solanaceae) that has a wide range of biological activities. However, the effect of physalin B on VSMCs is currently unclear. In this study, we demonstrated that physalin B significantly inhibited the proliferation, migration and phenotypic transformation of VSMCs induced by PDGF-BB. Physalin B also reduced inflammation and oxidative stress in VSMCs induced by PDGF-BB. Mechanistic studies showed that physalin B plays a role mainly by activating Nrf2. After Nrf2 activation, physalin B mitigates oxidative stress by enhancing the expression of the antioxidant gene HO-1; on the other hand, physalin B inhibits the NF-κB pathway to alleviate the inflammatory response. These two effects ultimately reduce the proliferation, migration and phenotypic transformation of VSMCs induced by PDGF-BB. In addition, in the mouse carotid artery ligation model, physalin B prevented intimal hyperplasia and inhibited the proliferation, migration and phenotypic transformation of cells in the hyperplastic intima. In conclusion, we provided significant evidence that physalin B abrogates PDGF-BB-induced VSMC proliferation, migration, phenotypic transformation and intimal hyperplasia by activating Nrf2-mediated signal transduction. Therefore, physalin B may be a potential therapeutic agent for preventing or treating restenosis.

4.
Elife ; 102021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34318750

RESUMO

Sensorimotor transformation, a process that converts sensory stimuli into motor actions, is critical for the brain to initiate behaviors. Although the circuitry involved in sensorimotor transformation has been well delineated, the molecular logic behind this process remains poorly understood. Here, we performed high-throughput and circuit-specific single-cell transcriptomic analyses of neurons in the superior colliculus (SC), a midbrain structure implicated in early sensorimotor transformation. We found that SC neurons in distinct laminae expressed discrete marker genes. Of particular interest, Cbln2 and Pitx2 were key markers that define glutamatergic projection neurons in the optic nerve (Op) and intermediate gray (InG) layers, respectively. The Cbln2+ neurons responded to visual stimuli mimicking cruising predators, while the Pitx2+ neurons encoded prey-derived vibrissal tactile cues. By forming distinct input and output connections with other brain areas, these neuronal subtypes independently mediated behaviors of predator avoidance and prey capture. Our results reveal that, in the midbrain, sensorimotor transformation for different behaviors may be performed by separate circuit modules that are molecularly defined by distinct transcriptomic codes.


Assuntos
Perfilação da Expressão Gênica , Mesencéfalo/metabolismo , Córtex Sensório-Motor/fisiologia , Transcriptoma , Animais , Masculino , Mesencéfalo/citologia , Camundongos , Neurônios/fisiologia , Análise de Célula Única , Colículos Superiores
5.
Cell Discov ; 7(1): 12, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33649311

RESUMO

In mammals, many organs lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small molecule-induced cell reprogramming offers a temporally flexible and non-integrative strategy for altering cell fate, which is, in principle, favorable for in vivo reprogramming in organs with notoriously poor regenerative abilities, such as the brain. Here, we demonstrate that in the adult mouse brain, small molecules can reprogram astrocytes into neurons. The in situ chemically induced neurons resemble endogenous neurons in terms of neuron-specific marker expression, electrophysiological properties, and synaptic connectivity. Our study demonstrates the feasibility of in vivo chemical reprogramming in the adult mouse brain and provides a potential approach for developing neuronal replacement therapies.

6.
Med (N Y) ; 2(4): 435-447.e4, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33521746

RESUMO

Background: To develop a sensitive risk score predicting the risk of mortality in patients with coronavirus disease 2019 (COVID-19) using complete blood count (CBC). Methods: We performed a retrospective cohort study from a total of 13,138 inpatients with COVID-19 in Hubei, China, and Milan, Italy. Among them, 9,810 patients with ≥2 CBC records from Hubei were assigned to the training cohort. CBC parameters were analyzed as potential predictors for all-cause mortality and were selected by the generalized linear mixed model (GLMM). Findings: Five risk factors were derived to construct a composite score (PAWNN score) using the Cox regression model, including platelet counts, age, white blood cell counts, neutrophil counts, and neutrophil:lymphocyte ratio. The PAWNN score showed good accuracy for predicting mortality in 10-fold cross-validation (AUROCs 0.92-0.93) and subsets with different quartile intervals of follow-up and preexisting diseases. The performance of the score was further validated in 2,949 patients with only 1 CBC record from the Hubei cohort (AUROC 0.97) and 227 patients from the Italian cohort (AUROC 0.80). The latent Markov model (LMM) demonstrated that the PAWNN score has good prediction power for transition probabilities between different latent conditions. Conclusions: The PAWNN score is a simple and accurate risk assessment tool that can predict the mortality for COVID-19 patients during their entire hospitalization. This tool can assist clinicians in prioritizing medical treatment of COVID-19 patients. Funding: This work was supported by National Key R&D Program of China (2016YFF0101504, 2016YFF0101505, 2020YFC2004702, 2020YFC0845500), the Key R&D Program of Guangdong Province (2020B1111330003), and the medical flight plan of Wuhan University (TFJH2018006).

7.
Cell Metab ; 33(2): 258-269.e3, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33421384

RESUMO

Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.


Assuntos
Corticosteroides/uso terapêutico , COVID-19/tratamento farmacológico , Linfócitos/citologia , Neutrófilos/citologia , Corticosteroides/efeitos adversos , Área Sob a Curva , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Humanos , Hiperglicemia/complicações , Hiperglicemia/patologia , Tempo de Internação , Modelos de Riscos Proporcionais , Curva ROC , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
8.
Sci China Life Sci ; 64(3): 419-433, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32803714

RESUMO

Cenpj is a centrosomal protein located at the centrosomes and the base of cilia, it plays essential roles in regulating neurogenesis and cerebral cortex development. Although centrosomal and cilium dysfunction are one of the causes of obesity, insulin resistance, and type 2 diabetes, the role that Cenpj plays in the regulation of body weight remains unclear. Here, we deleted Cenpj by crossing Cenpjflox/flox mice with Nkx2.1-Cre mice. Loss of the centrosomal protein Cenpj in Nkx2.1-expressing cells causes morbid obesity in mice at approximately 4 months of age with expended brain ventricles but no change of brain size. We found that hypothalamic cells exhibited reduced proliferation and increased apoptosis upon Cenpj depletion at the embryonic stages, resulting in a dramatic decrease in the number of Proopiomelanocortin (POMC) neurons and electrophysiological dysfunction of NPY neurons in the arcuate nucleus (ARC) in adults. Furthermore, depletion of Cenpj also reduced the neuronal projection from the ARC to the paraventricular nucleus (PVN), with decreased melanocortin-4 receptors (MC4R) expression in PVN neurons. The study defines the roles that Cenpj plays in regulating hypothalamus development and body weight, providing a foundation for further understanding of the pathological mechanisms of related diseases.

9.
Microvasc Res ; 134: 104105, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33189731

RESUMO

Vascular calcification, a common pathological basis of vascular disease, is caused by various diseases and is an independent risk factor for cardiovascular events. Therefore, elucidating the pathogenesis of vascular calcification has significant clinical benefits. It is generally believed that vascular calcification is similar to the processes of bone development and cartilage formation. The transformation of vascular smooth muscle cells into osteoblast- and chondrocyte-like cells is a key event. However, recent studies have found that under certain conditions, endothelial cells participate in vascular calcification via endothelial-mesenchymal transition, cytokine secretion, extracellular vesicle synthesis, angiogenesis regulation and hemodynamics. This review aims to explore the relationship between endothelial cells and vascular calcification and to provide a theoretical basis and new ideas for the active prevention and treatment of vascular calcification in the clinic.


Assuntos
Células Endoteliais/patologia , Endotélio Vascular/patologia , Calcificação Vascular/patologia , Animais , Comunicação Autócrina , Microambiente Celular , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Transição Epitelial-Mesenquimal , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Hemodinâmica , Humanos , Mecanotransdução Celular , Neovascularização Patológica , Comunicação Parácrina , Calcificação Vascular/metabolismo , Calcificação Vascular/fisiopatologia
10.
Materials (Basel) ; 13(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339346

RESUMO

To further improve the mechanical properties of the as-cast 7.5 vol.% TiBw/Ti-6Al-2.5Sn-4Zr-0.7Mo-0.3Si composite, multi-directional forging (MDF) and subsequent heat treatments were carried out to adjust TiB whiskers (TiBw) and matrix characteristics. The effect of various microstructures on the tensile properties and fracture toughness of the composites was analyzed in this paper. After MDF, the TiBw are broken into short rods with a low aspect ratio and display a random distribution. Moreover, distinct microstructures were obtained after thermomechanical processing and different heat treatments. Both room-temperature and high-temperature tensile strength and ductility are improved after thermomechanical processing. By increasing the solution-treatment temperature, the microstructures transform from equiaxed to fully lamellar. A simultaneous improvement of the room-temperature and high-temperature properties is associated with the microstructural changes. In addition, the fracture toughness exhibits an increasing trend as the volume fraction of equiaxial α phases decreases. The lamellar microstructure demonstrates excellent fracture toughness due to deflection of the crack propagation path.

11.
Oxid Med Cell Longev ; 2020: 1809408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149805

RESUMO

Notch receptors are transmembrane proteins that are members of the epidermal growth factor-like family. These receptors are widely expressed on the cell surface and are highly conserved. Binding to ligands on adjacent cells results in cleavage of these receptors, and their intracellular domains translocate into the nucleus, where target gene transcription is initiated. In the mammalian kidney, Notch receptors are activated during nephrogenesis and become silenced in the normal kidney after birth. Reactivation of Notch signaling in the adult kidney could be due to the genetic activation of Notch signaling or kidney injury. Notch3 is a mammalian heterodimeric transmembrane receptor in the Notch gene family. Notch3 activation is significantly increased in various glomerular diseases, renal tubulointerstitial diseases, glomerular sclerosis, and renal fibrosis and mediates disease occurrence and development. Here, we discuss numerous recently published papers describing the role of Notch3 signaling in kidney disease.


Assuntos
Nefropatias/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Humanos , Rim/metabolismo , Rim/patologia , Ligantes , Modelos Biológicos , Receptores Notch/química
12.
Cardiovasc Diagn Ther ; 10(4): 778-785, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32968633

RESUMO

Background: Previous study revealed that high glucose (HG) induced endothelial cell (EC) damage via endothelial-to-mesenchymal transition (EndMT). Recent studies suggested the role of Ephrin B2 in mediate ECs damage. However, the underlying mechanism remains unclear. The aim of the present study was to investigate whether Ephrin B2 mediates HG-induced EndMT in human aortic ECs (HAECs) and to determine the possible downstream signaling effector. Methods: Primary HAECs were exposed to normal glucose (NG, 5.5 mM), HG (30 mM) and HG+Ephrin B2 small interfering RNA (siRNA), respectively. The pathological changes were investigated by light microscope and confocal microscopy. To study the effects of focal adhesion kinase (FAK) activation on Ephrin B2 in HAECs, cells were incubated with FAK siRNA in HG group. The expression of EndMT-related markers (CD31 and FSP1), Ephrin B2 and FAK were detected by qRT-PCR and western blot. Results: The results showed that HG significantly inhibited the expression of CD31 and increased FSP1 compared with NG group. Moreover, Ephrin B2 was increased after HG incubation. Ephrin B2 siRNA attenuated HG-induced expression of EndMT-related markers. Furthermore, HG increased the expression of FAK and phosphorylated FAK (pho-FAK) in HAECs. In contrast, blocking Ephrin B2 could partially attenuate HG-induced FAK activation. And FAK siRNA further inhibited the EndMT-related markers in HAECs treated with HG. Conclusions: HG-induced EndMT in HAECs might be partially mediated by Ephrin B2 and the downstream FAK pathway.

13.
Onco Targets Ther ; 13: 6975-6986, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764988

RESUMO

Objective: Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer in adults. The 5-year survival rate of patients with advanced ccRCC is less than 30%. Lack of potential biomarkers for treatment and prognosis is a limitation for early diagnosis and treatment of ccRCC. Methods: We collected microarray profiles of 39 ccRCC and matched normal samples to identify differential expression genes (DEGs). Then, a weighted gene co-expression network analysis (WGCNA) was constructed to identify gene modules associated with the metastasis in ccRCC. The Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (HPA, https://www.proteinatlas.org/) database were used for verification set. Finally, we used biological experiments to preliminary investigate the impact of LTF on the tumor biological behavior of ccRCC, including proliferation, migration, invasion, and apoptosis. Results: A total of 15 genetic modules were identified, and the light-green module is considered the most relevant to tumor metastasis. (P = 0.02, R2 = -0.4). Protein-protein interaction (PPI) network was performed to identify the hub nodes in the light-green module. Finally, combining the results of PPI, WGCNA and DEGs, lactotransferrin (LTF) gene was regarded as "real" hub genes for cancer metastasis risk. LTF was subsequently validated using the TCGA database. Immunohistochemistry confirmed that the expression of LTF in ccRCC tumor tissue was significantly lower than that in normal tissue based on the HPA database. Intriguingly, patients with low expression of LTF had lower survival rates (HR = 0.66, 95% CI: 0.49-0.89, P = 0.0067), the expression level of the sample was negatively correlated with tumor stage (P = 0.0385), and patients with low expression of LTF gene were more likely to have distant metastasis (P = 0.038). Overexpression of LTF inhibited the proliferation, migration, invasion and promoted apoptosis of human ccRCC cells in vitro. Conclusion: LTF might be a novel prognostic biomarker for ccRCC.

14.
Hypertension ; 76(3): 827-838, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32683902

RESUMO

NOX5 (NADPH oxidase 5) is a homolog of the gp91phox subunit of the phagocyte NOX, which generates reactive oxygen species. NOX5 is involved in sperm motility and vascular contraction and has been implicated in diabetic nephropathy, atherosclerosis, and stroke. The function of NOX5 in the cardiac hypertrophy is unknown. Because NOX5 is a Ca2+-sensitive, procontractile NOX isoform, we questioned whether it plays a role in cardiac hypertrophy. Studies were performed in (1) cardiac tissue from patients undergoing heart transplant for cardiomyopathy and heart failure, (2) NOX5-expressing rat cardiomyocytes, and (3) mice expressing human NOX5 in a cardiomyocyte-specific manner. Cardiac hypertrophy was induced in mice by transverse aorta coarctation and Ang II (angiotensin II) infusion. NOX5 expression was increased in human failing hearts. Rat cardiomyocytes infected with adenoviral vector encoding human NOX5 cDNA exhibited elevated reactive oxygen species levels with significant enlargement and associated increased expression of ANP (atrial natriuretic peptides) and ß-MHC (ß-myosin heavy chain) and prohypertrophic genes (Nppa, Nppb, and Myh7) under Ang II stimulation. These effects were reduced by N-acetylcysteine and diltiazem. Pressure overload and Ang II infusion induced left ventricular hypertrophy, interstitial fibrosis, and contractile dysfunction, responses that were exaggerated in cardiac-specific NOX5 trangenic mice. These phenomena were associated with increased reactive oxygen species levels and activation of redox-sensitive MAPK (mitogen-activated protein kinase). N-acetylcysteine treatment reduced cardiac oxidative stress and attenuated cardiac hypertrophy in NOX5 trangenic. Our study defines Ca2+-regulated NOX5 as an important NOX isoform involved in oxidative stress- and MAPK-mediated cardiac hypertrophy and contractile dysfunction.


Assuntos
Acetilcisteína/farmacologia , Cardiomegalia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , NADPH Oxidase 5/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Angiotensina II/farmacologia , Animais , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Sequestradores de Radicais Livres/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Isoenzimas/metabolismo , Camundongos , Camundongos Transgênicos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fagócitos/enzimologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Vasoconstritores/farmacologia , Miosinas Ventriculares/metabolismo
15.
Cardiovasc Toxicol ; 20(6): 618-626, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32632848

RESUMO

Endoplasmic reticulum stress (ERS) is involved in a variety of diseases. Recently, it was found that ERS induces not only apoptosis but also autophagy. Previous studies showed that inhibition of autophagy alleviates cell injury. The purpose of our study was to investigate the involvement of the R-like ER kinase (PERK) in ERS-induced autophagy in H9c2 cardiomyoblasts. To address this aim, therefore, H9c2 cells were treated with PERK agonist and inhibitor after establishment of rapamycin-induced ERS models in H9c2 cardiomyoblasts. Transmission electron microscopy and immunofluorescence staining were used to detect degrees of ERS-induced autophagy, apoptosis and myocardial fibrosis. Western blotting was employed to detect the levels of total and phosphorylated PERK, light chain 3 (LC3), P62, Caspase3, Bcl2 and Bax. Immunofluorescence staining was used to assess α-SMA density. TGF-ß induced H9c2 cardiomyoblasts time-dependently upregulated col I, col III, FN, and LC3 expressions, PERK phosphorylation and α-SMA density, and downregulated P62 level compared with control cells. Treatment with PERK agonist and inhibitor respectively increased and decreased LC3 expression, conversely in P62 level, which is consistent with effect of ERS agonists and inhibitors. And a PERK inhibitor upregulated the expressions of Caspase3 and Bax, and downregulated Bcl2 level, which developed H9c2 cardiomyoblasts. Moreover, siRNA-mediated knockdown of PERK reduced ERS mediated autophagy activity and increased cells apoptosis. On the other hand, elevated autophagy activity could downregulated PERK level. Our finding showed that PERK activity mediates upregulation of ERS-induced autophagy and regulation of cardiomyocyte apoptosis in H9c2 cardiomyoblasts.

16.
Cell Biochem Biophys ; 78(3): 255-265, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32623640

RESUMO

Patients with myocardial ischemic diseases or who are undergoing one of various heart treatments, such as open heart surgery, coronary artery bypass grafting, percutaneous coronary artery intervention or drug thrombolysis, face myocardial ischemia-reperfusion injury (MIRI). However, no effective treatment is currently available for MIRI. To improve the prognosis of people with cardiovascular disease, it is important to research the mechanism of MIRI. Arachidonic acid (AA) is one of the focuses of current research. The various metabolic pathways of AA are closely related to the development of cardiovascular disease, and the roles of various metabolites in ischemia-reperfusion injury have gradually been confirmed. AA is mainly metabolized in the cyclooxygenase (COX) pathway, lipoxygenase (LOX) pathway, and cytochrome P450 monooxygenase (CYP) pathway. This paper summarizes the progress of research on these three major AA metabolic pathways with respect to MIRI.


Assuntos
Ácido Araquidônico/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão/patologia , Animais , Apoptose , Autofagia , Cálcio/metabolismo , Citocromo P-450 CYP4A , Humanos , Sistema Imunitário , Inflamação , Camundongos , Estresse Oxidativo , Prognóstico
17.
Aging (Albany NY) ; 12(12): 11238-11244, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561692

RESUMO

Our study aimed to investigate the factors affecting the prognosis of patients with mental disorders with COVID-19. All patients with mental disorders who were diagnosed with COVID-19 at the intensive care unit of Wuhan Mental Health Center during the period January 3 to March 1, 2020 were selected. The influence of the baseline characteristics, clinical symptoms, laboratory parameters and the types of mental disorders on prognosis were analyzed. According to their final prognosis, the patients were divided into the deceased group (5 patients) and the cured group (25 patients). The mortality rate of patients with dementia was significantly higher than that of patients with other mental disorders (P = 0.001). The levels of certain laboratory parameters in the serum of dementia patients were significantly increased compared with levels in nondementia patients (WBC count: 10.100±6.147 vs. 5.694±3.383, p = 0.029; neutrophil count: 8.504± 5.993 vs. 3.764 ± 2.733, P = 0.008; BUN: 8.300± 4.072 vs. 4.364 ± 1.196, P = 0.001). Our research indicated that the mortality rate of dementia patients with COVID-19 was higher than that of patients with other mental disorders. A focus on the inflammatory response of dementia patients may provide novel ideas for reducing mortality.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Demência/complicações , Transtornos Mentais/complicações , Pneumonia Viral/complicações , Idoso , COVID-19 , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
18.
Cardiovasc Diabetol ; 19(1): 98, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590982

RESUMO

Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are a new type of glucose-lowering drug that can reduce blood glucose by inhibiting its reabsorption in proximal tubules and by promoting urinary glucose excretion. SGLT2i are widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). In recent studies, SGLT2i were found to not only reduce blood glucose but also protect the heart and kidney, which can significantly reduce cardiovascular events, delay the progression of renal failure, greatly improve the quality of life of patients, and reduce medical expenses for families and society. As adverse cardiac and renal events are the most common and serious complications of T2DM, it is very important to understand the cardio- and renoprotective mechanisms of SGLT2i. This article reviews the historical development, pharmacological mechanism, heart and kidney protection and safety of SGLT2i. The information presented provides a theoretical basis for the clinical prevention and treatment of diabetes and its complications and for the development of new glucose-lowering drugs.


Assuntos
Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Rim/efeitos dos fármacos , Insuficiência Renal/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/fisiopatologia , Regulação para Baixo , Humanos , Rim/fisiopatologia , Insuficiência Renal/diagnóstico , Insuficiência Renal/epidemiologia , Insuficiência Renal/fisiopatologia , Medição de Risco , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Resultado do Tratamento
19.
Cell Metab ; 32(2): 176-187.e4, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32592657

RESUMO

Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/efeitos dos fármacos , COVID-19 , Comorbidade , Infecções por Coronavirus/mortalidade , Síndrome da Liberação de Citocina/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A/efeitos dos fármacos , Pneumonia Viral/mortalidade , Estudos Retrospectivos , SARS-CoV-2
20.
Cell Metab ; 31(6): 1068-1077.e3, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32369736

RESUMO

Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.


Assuntos
Glicemia/análise , Infecções por Coronavirus/mortalidade , Diabetes Mellitus Tipo 2/sangue , Índice Glicêmico/fisiologia , Hiperglicemia/sangue , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Diabetes Mellitus Tipo 2/complicações , Suscetibilidade a Doenças/patologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/complicações , Hipoglicemiantes/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/complicações , Insuficiência de Múltiplos Órgãos/mortalidade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2
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