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1.
J Clin Densitom ; 27(2): 101469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38479134

RESUMO

OBJECTIVE: This study was aimed to create and validate a risk prediction model for the incidence of osteopenia in individuals with abdominal obesity. METHODS: Survey data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2013-2014 and 2017-2018 was selected and included those with waist circumferences ≥102 m in men and ≥88 cm in women, which were defined as abdominal obesity. A multifactor logistic regression model was constructed using LASSO regression analysis to identify the best predictor variables, followed by the creation of a nomogram model. The model was then verified and evaluated using the consistency index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis (DCA). Results Screening based on LASSO regression analysis revealed that sex, age, race, body mass index (BMI), alkaline phosphatase (ALP) and Triglycerides (TG) were significant predictors of osteopenia development in individuals with abdominal obesity (P < 0.05). These six variables were included in the nomogram. In the training and validation sets, the C indices were 0.714 (95 % CI: 0.689-0.738) and 0.701 (95 % CI: 0.662-0.739), respectively, with corresponding AUCs of 0.714 and 0.701. The nomogram model exhibited good consistency with actual observations, as demonstrated by the calibration curve. The DCA nomogram showed that early intervention for at-risk populations has a net positive impact. CONCLUSION: Sex, age, race, BMI, ALP and TG are predictive factors for osteopenia in individuals with abdominal obesity. The constructed nomogram model can be utilized to predict the clinical risk of osteopenia in the population with abdominal obesity.


Assuntos
Índice de Massa Corporal , Doenças Ósseas Metabólicas , Nomogramas , Inquéritos Nutricionais , Obesidade Abdominal , Circunferência da Cintura , Humanos , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Ósseas Metabólicas/epidemiologia , Adulto , Medição de Risco/métodos , Triglicerídeos/sangue , Curva ROC , Fosfatase Alcalina/sangue , Idoso , Fatores Etários , Fatores de Risco , Fatores Sexuais , Modelos Logísticos , Incidência , Área Sob a Curva
2.
BMC Med Imaging ; 24(1): 215, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143526

RESUMO

BACKGROUND: Due to the increasing incidence of ischaemic cerebrovascular diseases, the accurate assessment of internal carotid artery (ICA) stenosis is crucial for the development of treatment plans. This systematic review and meta-analysis aimed to evaluate the diagnostic value of computed tomography angiography (CTA) for severe ICAstenosis, thereby providing support for clinical decision-making and promoting diagnostic updates. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals (VIP), and Chinese Biomedical Literature (CBM) electronic databases were searched from inception to March 21, 2024, to identify publicly available research literature on the use of CTA to diagnose severe ICA stenosis. Literature screening, data extraction, and quality assessment were conducted based on the inclusion and exclusion criteria as well as the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) standards. Data analysis was performed using Stata 17.0 and Meta-Disc 1.4 software. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of the included studies were calculated using Stata 17.0 software, and forest plots and summary receiver operating characteristic (SROC) curves were generated. The area under the curve (AUC) was calculated, and funnel plots were constructed to assess publication bias. RESULTS: A total of 16 studies with 2368 vascular segments were included. The meta-analysis revealed that the combined sensitivity and specificity of CTA for severe ICA stenosis were 0.93 (95% CI: 0.88 ~ 0.96) and 0.99 (95% CI: 0.96 ~ 1.00), respectively. The combined positive likelihood ratio and negative likelihood ratio were 92.0 (95% CI: 24.2 ~ 349.6) and 0.07 (95% CI: 0.04 ~ 0.13), respectively. The diagnostic odds ratio was 1302 (95% CI: 257 ~ 6606), and the AUC of the SROC curve was 0.98. The Deeks funnel plot suggested no publication bias among the included studies. CONCLUSION: CTA demonstrated high sensitivity and specificity for diagnosing severe ICA stenosis. Therefore, this study provided important evidence for the accurate diagnosis and treatment of severe ICA stenosis. However, there was considerable heterogeneity among the included studies, thus indicating the need for additional high-quality prospective studies to confirm the clinical applicability of CTA.


Assuntos
Artéria Carótida Interna , Estenose das Carótidas , Angiografia por Tomografia Computadorizada , Sensibilidade e Especificidade , Humanos , Estenose das Carótidas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Artéria Carótida Interna/diagnóstico por imagem , Curva ROC , Índice de Gravidade de Doença
3.
N Engl J Med ; 382(18): 1708-1720, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32109013

RESUMO

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).


Assuntos
Betacoronavirus , Infecções por Coronavirus , Surtos de Doenças , Pandemias , Pneumonia Viral , Adolescente , Adulto , Idoso , COVID-19 , Criança , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Febre/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , SARS-CoV-2 , Adulto Jovem
4.
Bioorg Chem ; 132: 106381, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36706532

RESUMO

Two enantiomeric pairs of macrocyclic acylphloroglucinols (1a/1b and 2a/2b) with an unprecedented carbon skeleton featuring a bicyclo[12.3.1]octadecane core, together with an undescribed biogenetically related long-chain acylphloroglucinol (3), were isolated from Syzygium szemaoense. Their structures were fully established by spectroscopic method, X-ray crystallographic analysis, and ECD calculation. Compounds 1b and 2a/2b exhibited inhibition against death-associated protein kinase-related apoptosis inducing protein kinase 2 (DRAK2) and ATP citrate lyase (ACLY), respectively.


Assuntos
Syzygium , Estrutura Molecular , Cristalografia por Raios X , Análise Espectral
5.
Semin Dial ; 35(1): 71-80, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34137080

RESUMO

INTRODUCTION: Maintenance hemodialysis (MHD) patients are highly threatened in the novel coronavirus disease 2019 (COVID-19) pandemic, but evidence of risk factors for mortality in this population is still lacking. METHODS: We followed outcomes of the overall MHD population of Wuhan, including 7154 MHD patients from 65 hemodialysis centers, from January 1 to May 4, 2020. Among them, 130 were diagnosed with COVID-19. The demographic and clinical data of them were collected and compared between survivors and nonsurvivors. RESULTS: Compared to the corresponding period of last year, the all-cause mortality rate of the Wuhan MHD population significantly rose in February, and dropped down in March 2020. Of the 130 COVID-19 cases, 51 (39.2%) were deceased. Advanced age, decreased oxygen saturation, low diastolic blood pressure (DBP) on admission, and complications including acute cardiac injury (HR 5.03 [95% CI 2.21-11.14], p < 0.001), cerebrovascular event (HR 2.80 [95% CI 1.14-6.86], p = 0.025) and acute respiratory distress syndrome (HR 3.50 [95% CI 1.63-7.51], p = 0.001) were identified as independent risk factors for the death of COVID-19. The median virus shedding period of survivors was 25 days, longer than the general population. CONCLUSIONS: Maintenance hemodialysis patients are a highly vulnerable population at increased risk of mortality and prolonged virus shedding period in the ongoing COVID-19 pandemic. Advanced age, decreased oxygen saturation, low DBP on admission, and complications like acute cardiac injury are parameters independently associated with poor prognosis.


Assuntos
COVID-19 , Humanos , Saturação de Oxigênio , Pandemias , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
6.
J Nat Prod ; 85(4): 943-950, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35325544

RESUMO

Genome mining and biocatalytic modification of chemical structures are critical methods to develop new antibiotics. In this study, eight new fasamycins (3, 4, 6, and 8-12) along with five known analogues (1, 2, 5, 7, and 13) were obtained by the overexpression of two phosphopantetheinyl transferases (PPtases) in Streptomyces kanamyceticus and biocatalytic transformation with two halogenases. These new compounds displayed significant activity against Staphylococcus aureus and Bacillus subtilis, in particular, C-29-methyl and C-2/C-22-halogen derivatives. This study increases the chemical diversity of bioactive fasamycin derivatives and provides useful halogenation tools for engineering their scaffolds.


Assuntos
Bacillus subtilis , Halogenação , Antibacterianos/química , Antibacterianos/farmacologia , Biocatálise , Staphylococcus aureus
7.
Bioorg Chem ; 124: 105821, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35487074

RESUMO

Three novel dimeric sesquiterpenoids named sarglanoids A-C (1-3), two undescribed monomeric sesquiterpenoids named sarglanoids D (4) and E (5), and seven known compounds (6-12), were isolated and characterized from Sarcandra glabra. Compound 1 represents the first heterodimeric sesquiterpenoid composed of a eudesmane and an eremophilane moiety. Compound 2 possesses two eremophilane monomers featuring an undescribed dimerization pattern. Compound 3 is a symmetric eudesmane dimer with a rare 1,4-epoxy bridge. The structures of 1-5 were fully identified by spectroscopic methods and single-crystal X-ray diffraction experiments. Compounds 3 and 6 suppressed the LPS-triggered inflammatory responses in RAW 264.7 cells.


Assuntos
Sesquiterpenos de Eudesmano , Sesquiterpenos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Camundongos , Estrutura Molecular , Sesquiterpenos Policíclicos , Células RAW 264.7 , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Eudesmano/farmacologia
8.
Planta Med ; 88(8): 678-684, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34715693

RESUMO

Two new maytansinoids, N-methyltreflorine (1: ) and methyltrewiasine (2: ), were isolated from the dried fruits of Trewia nudiflora, together with three known congeners (3:  - 5: ). Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1: and 2: was determined by X-ray crystallographic analysis. Compounds 1:  - 5: exhibited strong cytotoxicity against human tumor cell lines, including HeLa, MV-4 - 11, and MCF-7, with IC50 values ranging from 0.12 to 11 nM. Compounds 1: and 4: also showed inhibitory activity against the MCF-7/ADR cell line with IC50 values of 13 and 28 nM, respectively. Compounds 1: and 2: significantly inhibited tubulin polymerization in vitro with IC50 values of 3.6 and 3.2 µM, respectively.


Assuntos
Antineoplásicos , Tubulina (Proteína) , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Células HeLa , Humanos , Células MCF-7 , Estrutura Molecular , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo
9.
FASEB J ; 34(1): 1620-1636, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914692

RESUMO

Acute kidney injury (AKI) is the leading cause of renal failure, and quite a few patients will advance to chronic kidney disease (CKD) in the long term. Here, we explore the roles and mechanisms of tubular epithelial cells (TECs) during repeated cisplatin (CP) induced AKI to CKD transition (AKI-CKD). Previously, we reported that murine double minute 2 (MDM2), an E3-ubiquitin ligase, is involved in tubulointerstitial fibrosis. However, whether tubular MDM2 is implicated in AKI-CKD is undefined. Currently, we confirmed that during AKI-CKD, MDM2 shifts from nucleus to cell membrane in TECs both in vivo and in vitro. Whereas regulating MDM2 distribution chemically or genetically has a prominent impact on tubular disorders. And then we investigated the mechanisms of the above findings. First, in the nucleus, repeated CP administration leads to MDM2 reduction with escalated p53 and cell cycle G2/M arrest. On the other hand, multiple CP treatment increases the level of membranous MDM2 with ensuing integrin ß8 degradation and TGF-ß1 activation. More interestingly, anchoring MDM2 on cell membranes can mimic the reduction of integrin ß8 arousing by repeated CP exposure. Collectively, our findings provided the evidence that tubular MDM2 subcellular shuttling is involved in AKI-CKD through p53-G2/M arrest and integrin ß8 mediated TGF-ß1 activation.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Cisplatino/farmacologia , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Injúria Renal Aguda/patologia , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/patologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Células Cultivadas , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Cadeias beta de Integrinas/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Insuficiência Renal Crônica/patologia , Fator de Crescimento Transformador beta1/metabolismo , Proteína Supressora de Tumor p53/metabolismo
10.
FASEB J ; 34(9): 11983-11996, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32686857

RESUMO

Previously, selenoprotein T (SelT) expression was shown to be induced in nervous, endocrine, and metabolic tissues during ontogenetic and regenerative processes. However, whether SelT plays a critical role in renal diseases remains unclear. Here, we explored the role of SelT in cisplatin-induced acute kidney injury (AKI). Results revealed that SelT was highly expressed in renal tubules, but its expression was significantly reduced in cisplatin-induced AKI. Importantly, knocking down of SelT expression in kidney cells in vitro resulted in cisplatin-induced cell apoptosis, as indicated by the elevation of cleaved-PARP and Bax expression, Caspase-3 activity, and number of TUNEL-positive cells. Moreover, SelT silencing-induced reactive oxygen species (ROS) production, accompanied by a decrease in intracellular superoxide dismutase (SOD) and catalase (CAT) activity and increase in malondialdehyde (MDA) content. Notably, the protein and mRNA levels of Nox4 were increased in response to SelT downregulation. Furthermore, suppression of Nox4 expression by GKT137831 partially alleviated SelT knockdown-induced ROS generation and cell apoptosis in cisplatin-treated kidney cells. Taken together, our findings provide the first evidence that SelT protects against cisplatin-induced AKI by suppression of oxidative stress and apoptosis.


Assuntos
Injúria Renal Aguda , Apoptose/efeitos dos fármacos , Cisplatino/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Selenoproteínas/biossíntese , Tiorredoxina Dissulfeto Redutase/biossíntese , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/prevenção & controle , Animais , Cisplatino/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Camundongos , Ratos , Ratos Endogâmicos WKY , Ratos Sprague-Dawley
11.
Bioorg Chem ; 112: 104916, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33957537

RESUMO

Three unprecedented dimeric clerodane diterpenoids, dodovisdimers A-C (1-3), along with six known clerodane monomers (4-9), were isolated from Dodonaea viscosa. Compounds 1-3 may be biosynthetically formed via an intermolecular Diels-Alder [4+2] cycloaddition between the coexisting monomers 4-7. The structures of these clerodanes were characterized by spectroscopic techniques, X-ray crystallographic study, and ECD calculations. Some isolates exerted antiviral effects on human influenza A virus (H3N2) in vitro.


Assuntos
Antivirais/farmacologia , Diterpenos Clerodânicos/farmacologia , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Sapindaceae/química , Antivirais/química , Antivirais/isolamento & purificação , Cristalografia por Raios X , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/isolamento & purificação , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
12.
J Am Soc Nephrol ; 31(7): 1387-1397, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32385130

RESUMO

BACKGROUND: Reports indicate that those most vulnerable to developing severe coronavirus disease 2019 (COVID-19) are older adults and those with underlying illnesses, such as diabetes mellitus, hypertension, or cardiovascular disease, which are common comorbidities among patients undergoing maintenance hemodialysis. However, there is limited information about the clinical characteristics of hemodialysis patients with COVID-19 or about interventions to control COVID-19 in hemodialysis centers. METHODS: We collected data retrospectively through an online registration system that includes all patients receiving maintenance hemodialysis at 65 centers in Wuhan, China. We reviewed epidemiologic and clinical data of patients with laboratory-confirmed COVID-19 between January 1, 2020 and March 10, 2020. RESULTS: Of 7154 patients undergoing hemodialysis, 154 had laboratory-confirmed COVID-19. The mean age of the 131 patients in our analysis was 63.2 years; 57.3% were men. Many had underlying comorbidities, with cardiovascular disease (including hypertension) being the most common (68.7%). Only 51.9% of patients manifested fever; 21.4% of infected patients were asymptomatic. The most common finding on chest computed tomography (CT) was ground-grass or patchy opacity (82.1%). After initiating comprehensive interventions-including entrance screening of body temperature and symptoms, universal chest CT and blood tests, and other measures-new patients presenting with COVID-19 peaked at 10 per day on January 30, decreasing to 4 per day on February 11. No new cases occurred between February 26 and March 10, 2020. CONCLUSIONS: We found that patients receiving maintenance hemodialysis were susceptible to COVID-19 and that hemodialysis centers were high-risk settings during the epidemic. Increasing prevention efforts, instituting universal screening, and isolating patients with COVID-19 and directing them to designated hemodialysis centers were effective in preventing the spread of COVID-19 in hemodialysis centers.


Assuntos
Infecções por Coronavirus/epidemiologia , Suscetibilidade a Doenças/epidemiologia , Falência Renal Crônica/epidemiologia , Pneumonia Viral/epidemiologia , Sistema de Registros , Diálise Renal/métodos , Fatores Etários , Idoso , COVID-19 , Distribuição de Qui-Quadrado , China/epidemiologia , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Prevalência , Radiografia Torácica/métodos , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Estatísticas não Paramétricas , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos
13.
Chem Biodivers ; 18(11): e2100672, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34519420

RESUMO

Two new oleanane-triterpenoid saponins, clinograsaponins A (1) and B (2), together with twelve known ones (3-14), were isolated from the whole herb of Clinopodium gracile (Bentham) Matsumura. Their structures were determined by spectroscopic analysis and chemical method. All the isolated compounds were evaluated for their activities against ATP-citrate lyase (ACLY) and nuclear factor kappa B (NF-κB).


Assuntos
ATP Citrato (pro-S)-Liase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Lamiaceae/química , NF-kappa B/antagonistas & inibidores , Extratos Vegetais/farmacologia , ATP Citrato (pro-S)-Liase/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Conformação Molecular , NF-kappa B/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Estereoisomerismo
14.
Am J Physiol Renal Physiol ; 319(4): F636-F646, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32830536

RESUMO

Mitotic spindle assembly checkpoint protein 2 (MAD2B), a well-known anaphase-promoting complex/cyclosome (APC/C) inhibitor and a small subunit of DNA polymerase-ζ, is critical for mitotic control and DNA repair. Previously, we detected a strong increase of MAD2B in the glomeruli from patients with crescentic glomerulonephritis and anti-glomerular basement membrane (anti-GBM) rats, which predominantly originated from activated parietal epithelial cells (PECs). Consistently, in vitro MAD2B was increased in TNF-α-treated PECs, along with cell activation and proliferation, as well as extracellular matrix accumulation, which could be reversed by MAD2B genetic depletion. Furthermore, we found that expression of S phase kinase-associated protein 2 (Skp2), an APC/CCDH1 substrate, was increased in the glomeruli of anti-GBM rats, and TNF-α-stimulated PECs and could be suppressed by MAD2B depletion. Additionally, genetic deletion of Skp2 inhibited TNF-α-induced PEC activation and dysfunction. Finally, TNF-α blockade or glucocorticoid therapy administered to anti-GBM rats could ameliorate MAD2B and Skp2 accumulation as well as weaken PEC activation. Collectively, our data suggest that MAD2B has a pivotal role in the pathogenesis of glomerular PEC activation and crescent formation through induction of Skp2 expression.


Assuntos
Proliferação de Células , Células Epiteliais/metabolismo , Glomerulonefrite/enzimologia , Glomérulos Renais/metabolismo , Proteínas Mad2/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Etanercepte/farmacologia , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Regulação da Expressão Gênica , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/genética , Glomerulonefrite/patologia , Glucocorticoides/farmacologia , Humanos , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Proteínas Mad2/genética , Masculino , Camundongos , Prednisolona/análogos & derivados , Prednisolona/farmacologia , Células RAW 264.7 , Ratos Endogâmicos WKY , Proteínas Quinases Associadas a Fase S/genética , Transdução de Sinais
15.
Eur Respir J ; 55(5)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32217650

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. METHODS: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , COVID-19 , China/epidemiologia , Comorbidade , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Prognóstico , Fatores de Risco , SARS-CoV-2
16.
Eur Respir J ; 55(6)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32269086

RESUMO

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.


Assuntos
Infecções por Coronavirus/mortalidade , Hospitalização , Pneumonia Viral/mortalidade , Adulto , Idoso , Betacoronavirus , COVID-19 , Doenças Cardiovasculares/epidemiologia , China , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Tosse/etiologia , Diabetes Mellitus/epidemiologia , Surtos de Doenças , Dispneia/etiologia , Fadiga/etiologia , Feminino , Febre/etiologia , Geografia , Humanos , Hipertensão/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Faringite/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Prognóstico , Modelos de Riscos Proporcionais , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Tomografia Computadorizada por Raios X
17.
Am J Kidney Dis ; 76(4): 490-499.e1, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32628990

RESUMO

RATIONALE & OBJECTIVE: Patients receiving maintenance hemodialysis (MHD) are highly vulnerable to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current study was designed to evaluate the prevalence of SARS-CoV-2 infection based on both nucleic acid testing (NAT) and antibody testing in Chinese patients receiving MHD. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: From December 1, 2019, to March 31, 2020, a total of 1,027 MHD patients in 5 large hemodialysis centers in Wuhan, China, were enrolled. Patients were screened for SARS-CoV-2 infection by symptoms and initial computed tomography (CT) of the chest. If patients developed symptoms after the initial screening was negative, repeat CT was performed. Patients suspected of being infected with SARS-CoV-2 were tested with 2 consecutive throat swabs for viral RNA. In mid-March 2020, antibody testing for SARS-CoV-2 was obtained for all MHD patients. EXPOSURE: NAT and antibody testing results for SARS-CoV-2. OUTCOMES: Morbidity, clinical features, and laboratory and radiologic findings. ANALYTICAL APPROACH: Differences between groups were examined using t test or Mann-Whitney U test, comparing those not infected with those infected and comparing those with infection detected using NAT with those with infection detected by positive serology test results. RESULTS: Among 1,027 patients receiving MHD, 99 were identified as having SARS-CoV-2 infection, for a prevalence of 9.6%. Among the 99 cases, 52 (53%) were initially diagnosed with SARS-CoV-2 infection by positive NAT; 47 (47%) were identified later by positive immunoglobulin G (IgG) or IgM antibodies against SARS-CoV-2. There was a spectrum of antibody profiles in these 47 patients: IgM antibodies in 5 (11%), IgG antibodies in 35 (74%), and both IgM and IgG antibodies in 7 (15%). Of the 99 cases, 51% were asymptomatic during the epidemic; 61% had ground-glass or patchy opacities on CT of the chest compared with 11.6% among uninfected patients (P<0.001). Patients with hypertensive kidney disease were more often found to have SARS-CoV-2 infection and were more likely to be symptomatic than patients with another primary cause of kidney failure. LIMITATIONS: Possible false-positive and false-negative results for both NAT and antibody testing; possible lack of generalizability to other dialysis populations. CONCLUSIONS: Half the SARS-CoV-2 infections in patients receiving MHD were subclinical and were not identified by universal CT of the chest and selective NAT. Serologic testing may help evaluate the overall prevalence and understand the diversity of clinical courses among patients receiving MHD who are infected with SARS-CoV-2.


Assuntos
Anticorpos Antivirais/análise , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Falência Renal Crônica/terapia , Pneumonia Viral/diagnóstico , Diálise Renal , COVID-19 , China/epidemiologia , Comorbidade , Infecções por Coronavirus/epidemiologia , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Prevalência , Estudos Retrospectivos , SARS-CoV-2 , Testes Sorológicos/métodos , Tomografia Computadorizada por Raios X
18.
Cell Mol Biol (Noisy-le-grand) ; 66(6): 71-75, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33040788

RESUMO

In this study, we investigated the effect of latanoprost on the expression of TGF- ß1 and Wnt / ß - Catenin signal pathway in the choroid of form-deprivation myopia model rats. Forty rats were randomly divided into two groups: the control group and the FDM model group. Each group had 20 rats. The FDM model group was established by feeding latanoprost daily for 28 days. 15 rats in each group were used to measure the length of the ocular axis and the level of TGF-ß1 in choroidal tissue; the remaining 5 rats in each group were used for choroidal fibroblast culture. After modeling, the rats were killed, the length of the ocular axis was measured with a vernier caliper, and the level of TGF - ß1 protein and mRNA in the choroidal tissue of each group were measured with RT-PCR method. Results showed that compared with the control group, there was a significant difference in the axial length of the FDM model group (P< 0.05). There was a significant difference in the expression of TGF- ß1 protein and mRNA between the two groups (P<0.05). The cultured cells were identified as choroidal fibroblasts by immunocytochemistry. There was no significant difference (P>0.05) in the comparison of GSK3 ß protein in choroidal fibroblasts of rats in each group. TGF-ß 1 and APC protein in FDM group were significantly lower than those in the control group (P<0.05), while dcl3, p21-gsk3 ß and ß - Catenin proteins were significantly higher (P<0.05), and there was no significant difference (P>0.05) in the ratio of various indexes protein in FDM + ddk1 group and the comparison of TGF - ß1 and APC protein in FDM + ddk1 group and FDM group The expression of dcl3, p21-gsk3 ß and ß - Catenin decreased significantly (P<0.05). There was no significant difference in the expression of GSK3 ß mRNA in the choroidal fibroblasts of each group (P>0.05). The expression of TGF - ß 1 and APC mRNA in FDM group was significantly lower than that in the control group (P<0.05), while the expression of dcl3, p21-gsk3 ß and ß-catenin mRNA in FDM + ddk1 group was significantly higher than that in the control group (P<0.05) >In FDM + ddk1 group, TGF-ß 1 and APC mRNA were significantly lower than those in FDM group (P<0.05), while dcl3, p21-gsk3 ß and ß-Catenin mRNA were significantly higher (P<0.05).


Assuntos
Corioide/efeitos dos fármacos , Latanoprosta/farmacologia , Miopia/tratamento farmacológico , Fator de Crescimento Transformador beta1/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Células Cultivadas , Corioide/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Masculino , Miopia/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
19.
Zhongguo Zhong Yao Za Zhi ; 44(3): 495-499, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30989914

RESUMO

Twelve alkaloids were isolated from the bulbs of Fritillaria yuminensis by column chromatography over silica gel, ODS, and Sephadex LH-20, as well as RP-HPLC. Their structures were identified mainly by NMR and MS analyses as yubeinine(1), imperialine(2), delavinone(3), tortifoline(4), hupehenizioiside(5), imperialine-ß-D-glucoside(6), kuroyurinidine(7), pengbeisine A(8), walujewine A(9), peimisine-3-O-ß-D-glucopyranoside(10), solanidine-3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranoside(11), and solanidine-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)]-ß-D-glucopyranoside(12). Compounds 4-12 were obtained from F. yuminensis for the first time.


Assuntos
Alcaloides/análise , Fritillaria/química , Raízes de Plantas/química , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos Fitoquímicos/análise
20.
Zhongguo Zhong Yao Za Zhi ; 44(1): 88-94, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30868817

RESUMO

Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) µmol·L-1.


Assuntos
Broussonetia/química , Flavonoides/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Cromatografia Líquida de Alta Pressão , Flavonoides/isolamento & purificação , Espectroscopia de Ressonância Magnética , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
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