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1.
Biosci Rep ; 41(2)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33506866

RESUMO

Background Oxidative stress is considered to be involved in the pathogenesis of coronary heart disease (CHD). Glutathione-S-transferase (GST) enzymes play important roles in antioxidant defenses and may influence CHD risk. The present meta-analysis was performed to investigate the link between glutathione S-transferase M1 (GSTM1) null genotype and CHD and to get a precise evaluation of interaction between GSTM1 null genotype and smoking by the case-only design. Methods PubMed and EMBASE databases were searched through 15 December 2020 to retrieve articles. Odds ratios (ORs) were pooled using either fixed-effects or random-effects models. Results Thirty-seven studies showed that GSTM1 null genotype was associated with risk of CHD in total population, Caucasians and Asians (for total population, OR = 1.38, 95% confidence interval (CI): 1.15, 1.65; for Caucasians, OR = 1.34, 95% CI: 1.04, 1.72; for Asians, OR = 1.40, 95% CI: 1.11, 1.77). After adjustment for heterogeneity, these relationships were still significant. After adjustment for heterogeneity, case-only analysis of 11 studies showed a positive multiplicative interaction between GSTM1 null genotype and smoking (ever smoking vs. never smoking) (OR = 1.27, 95% CI: 1.08, 1.50; I2 = 0%, P=0.553). Conclusions The overall results indicated that GSTM1 null genotype was associated with a higher risk of CHD, and the association may be affected by smoking status. This is the first meta-analysis to prove a positive effect of the interaction between GSTM1 null genotype and smoking status on the risk of CHD. Well-designed studies are needed to investigate the possible gene-gene or gene-environment interactions.

2.
J Hazard Mater ; 409: 124905, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33412473

RESUMO

Persistent organic pollutants (POPs) remain a major point of concern worldwide, and surveillance monitoring of these contaminants presents a significant challenge. Here, we conducted an assessment of combined exposure to multiple POPs components [10 perfluoroalkyl acids (PFAAs), seven polybrominated diphenyl ethers (PBDEs), six polychlorinated biphenyls (PCBs) and 29 dioxin-like compounds (DLCs)] in relation to gestational diabetes mellitus (GDM) risk, and determined the identification and prioritization of potent components in these POPs mixtures. The results indicated a significant mixture effect and the combined exposure index estimated from multiple POPs components was associated with GDM and glucose homeostasis (P < 0.001). Based on the mixture effects on GDM, the procedure of prioritization identified DLCs as the components of the greatest concern, although at the lowest body burden in the population compared with PBDEs, PFAAs, and PCBs. For glucose homeostasis, BDE-153 was the chemical of top-ranked priority of concern. The final effect-based prioritized list of POPs was DLCs > PBDEs >PFAAs > PCBs. This prioritization is important for developing a more cost-effective regulation framework focusing on the POPs components of the greatest concern to human health.

3.
Diabetes Care ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479161

RESUMO

OBJECTIVE: To investigate the association of in-hospital early-phase glycemic control with adverse outcomes among inpatients with coronavirus disease 2019 (COVID-19) in Wuhan, China. RESEARCH DESIGN AND METHODS: The study is a large case series, and data were obtained regarding consecutive patients hospitalized with COVID-19 in the Central Hospital of Wuhan between 2 January and 15 February 2020. All patients with definite outcomes (death or discharge) were included. Demographic, clinical, treatment, and laboratory information were extracted from electronic medical records. We collected daily fasting glucose data from standard morning fasting blood biochemistry to determine glycemic status and fluctuation (calculated as the square root of the variance of daily fasting glucose levels) during the 1st week of hospitalization. RESULTS: A total of 548 patients were included in the study (median age 57 years; 298 [54%] were women, and n = 99 had diabetes [18%]), 215 suffered acute respiratory distress syndrome (ARDS), 489 survived, and 59 died. Patients who had higher mean levels of glucose during their 1st week of hospitalization were older and more likely to have a comorbidity and abnormal laboratory markers, prolonged hospital stays, increased expenses, and greater risks of severe pneumonia, ARDS, and death. Compared with patients with the lowest quartile of glycemic fluctuation, those who had the highest quartile of fluctuation magnitude had an increased risk of ARDS (risk ratio 1.97 [95% CI 1.01, 4.04]) and mortality (hazard ratio 2.73 [95% CI 1.06, 7.73]). CONCLUSIONS: These results may have implications for optimizing glycemic control strategies in COVID-19 patients during the early phase of hospitalization.

4.
Ann Palliat Med ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33302641

RESUMO

BACKGROUND: Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) is widely practiced to palliate cancer pain in patients with inoperable abdominal malignancy. During CPN, the dehydrated alcohol is injected to ablate neural tissue and local anesthetics is to minimize the discomfort from alcohol injection. This study aims to compare the efficacy and safety of bupivacaine and ropivacaine in EUS-CPN. METHODS: We retrospectively pooled and analyzed two large EUS centers' 150 consecutive patients underwent EUS-CPN from January 2012 to March 2019. Patients were divided into 3 groups based on the selection of anesthetics: 0.5% ropivacaine (ROPI, n=23), 0.375% bupivacaine (0.375% BUPI, n=21), 0.75% bupivacaine (0.75% BUPI, n=106). Visual analogue scale (VAS) was used to measure pre/post-operative pain at 11 observation points. Additional data were collected from medical records. RESULTS: The incidence of procedure-related pain within 12 hours after CPN was significantly different among the three groups, 10.38% in 0.75% BUPI [OR =0.26 (95% CI: 0.07-0.94); P=0.04], 26.09% in ROPI and 23.81% in 0.375% BUPI group, respectively. The risk of post-procedural arrhythmia was similar between the 0.375% and 0.75% BUPI groups (19.05% versus 18.87%), while relatively lower in ROPI group (13.04%). No patients in any group developed symptoms of CNS toxicity related to anesthetics. CONCLUSIONS: Compared with 0.375% bupivacaine and 0.5% ropivacaine, 0.75% bupivacaine in CPN can reduce post-procedural pain. Ropivacaine shows a tendency of less arrhythmogenic effect in CPN.

5.
Clin Nutr ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33380357

RESUMO

BACKGROUND & AIMS: Iron is an essential trace element to almost all organism, and the delicate balance between host defend system and viral proliferation plays an important role in infective conditions. While the association of the iron metabolism with the prognosis of COVID-19 remains poorly understood. We aimed to estimate the associations of systemic iron metabolism parameters with the severity and risks of adverse outcomes in COVID-19. METHODS: In this retrospective cohort study, we included 158 confirmed COVID-19 patients in Tongji Hospital, Wuhan, China (27 January to 5 April, 2020). Demographic data, comorbidities, laboratory examinations, treatments, and clinical outcomes were all collected. Multivariable Poisson regression was used to estimate the association of iron parameter levels with the severity and risks of adverse outcomes in COVID-19 patients. RESULTS: We identified 60 (38%) severe cases in 158 COVID-19 patients. The median age was 63 years (interquartile range [IQR]: 54-73) and the median length of hospital stay was 28 days (IQR: 17-40). After adjusting for age, sex, IL-6, and pre-existing comorbidities, all iron parameters were associated with the severity of COVID-19 with adjusted risk ratio of 0.42 [95% CI: 0.22-0.83], 4.38 [95% CI: 1.86-10.33], 0.19 [95% CI: 0.08-0.48], and 0.25 [95% CI: 0.10-0.58] for serum iron, ferritin, transferrin, and total iron-binding capacity, respectively. These iron indices were also related to the risk of ARDS, coagulopathy, acute cardiac injury, acute liver injury, and acute kidney injury in COVID-19 patients and high cytokine concentrations. CONCLUSIONS: Patients with low serum iron status likely suffered from severe condition and multiple-organ injury in COVID-19. The iron metabolism parameters might be risk factors and clinical biomarkers for COVID-19 prognosis.

6.
Diabetes Res Clin Pract ; : 108542, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33227361

RESUMO

OBJECTIVE: Circulating uric acid levels were associated with insulin resistance, but the causality is unclear. We aimed to investigate the association between plasma uric acid and insulin resistance in newly diagnosed type 2 diabetes (T2D). METHODS: We enrolled 1,938 patients who underwent a 75-g oral glucose tolerance test. Insulin resistance was estimated based on the homeostatic model assessment index (HOMA2-IR) and the Matsuda index. Uric acid was measured in fasting plasma by uricase-peroxidase method. We genotyped single nucleotide polymorphisms (SNPs) that were recently identified as top hits in genome-wide association studies of uric acid levels. A weighted genetic risk score (wGRS) was calculated based on the associations between selected SNPs and uric acid levels. RESULTS: The adjusted ß coefficients for Ln-transformed Matsuda index and HOMA2-IR per 1mg/dL uric acid increment were -0.070 (95%CI: -0.089, -0.052) and 0.057 (95%CI: 0.039, 0.075). These associations were more pronounced among women than men. In Mendelian randomization analysis, the wGRS raised uric acid by 0.225 mg/dL (95%CI: 0.138, 0.312) per SD increase of the score. However, no association was observed between the wGRS and insulin resistance indices whether in men or women. CONCLUSIONS: Elevated plasma uric acid was associated with higher risk of insulin resistance, along with observation of gender difference in such association. However, our study does not support a causal role of plasma uric acid on insulin resistance among newly diagnosed T2D patients.

7.
Mol Nutr Food Res ; : e2000660, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141510

RESUMO

SCOPE: Alzheimer's disease (AD) is characterized by amyloid-ß (Aß) related imbalance, tau-hyperphosphorylation, and neuroinflammation, in which Aß and neuroinflammation could induce brain insulin resistance (IR). Gut microbiome disorder is correlated with inflammation in AD. As of yet, there are no effective treatments clinically. Thus, we focus on the potential benefit of quercetin-3-O-glucuronide (Q3G), a pharmacologically active flavonol glucuronide, on AD treatment by regulating brain IR and the gut microbiome. METHODS AND RESULTS: AD mice model built through intracerebroventricular injection of Aß1-42 and AD cell model developed through the SH-SY5Y cell line and Aß1-42 were used to explore the protective effects of Q3G on AD. Neurobehavioral test, brain insulin signaling pathway, and high-throughput pyrosequencing of 16S rRNA were assessed. Data showed that Q3G attenuated neuroinflammation and brain IR in Aß1-42 -injected mice and relieved apoptosis in Aß1-42 -treated SH-SY5Y cells by interrupting the downstream insulin signaling. Q3G ameliorated Aß accumulation and Tau phosphorylation, restored CREB and BDNF levels in the hippocampus, and reversed Aß1-42 -induced cognitive impairment. Besides, Q3G restored Aß1-42 -induced reduction of short-chain fatty acids and gut microbiota dysbiosis. CONCLUSION: Q3G could alleviate brain IR through directly acting on the brain or modulating the gut-brain axis, ultimately to relieve Aß1-42 -induced cognitive dysfunction. This article is protected by copyright. All rights reserved.

8.
Ann Med ; : 1-24, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33183091

RESUMO

OBJECTIVE: To illustrate the effect of corticosteroids and heparin, respectively, on Coronavirus Disease 2019 (COVID-19) patients' CD8+ T cells and D-Dimer. METHODS: In this retrospective cohort study involving 866 participants diagnosed with COVID-19, patients were grouped by severity. Generalized additive models were established to explore the time-course association of representative parameters of coagulation, inflammation and immunity. Segmented regression was performed to examine the influence of corticosteroids and heparin upon CD8+ T cell and D-Dimer, respectively. RESULTS: There were 541 moderate, 169 severe and 156 critically ill patients involved in the study. Synchronous changes of levels of NLR, D-Dimer and CD8+ T cell in critically ill patients were observed. Administration of methylprednisolone before 14 DFS compared with those after 14 DFS (ß = 0.154%, 95% CI=(0, 0.302), p = 0.048) or a dose lower than 40 mg per day compared with those equals to 40 mg per day (ß = 0.163%, 95% CI=(0.027, 0.295), p = 0.020) significantly increased the rising rate of CD8+ T cell in 14 to 56 DFS. CONCLUSION: The parameters of coagulation, inflammation and immunity were longitudinally correlated, and an early low-dose corticosteroid treatment accelerated the regaining of CD8+ T cell to help battle against SARS-Cov-2 in critical cases of COVID-19.

9.
Sci Rep ; 10(1): 17365, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060676

RESUMO

To analyze the clinical characteristics of re-positive discharged COVID-19 patients and find distinguishing markers. The demographic features, clinical symptoms, laboratory results, comorbidities, co-infections, treatments, illness severities and chest CT scan results of 267 patients were collected from 1st January to 15th February 2020. COVID-19 was diagnosed by RT-PCR. Clinical symptoms and nucleic acid test results were collected during the 14 days post-hospitalization quarantine. 30 out of 267 COVID-19 patients were detected re-positive during the post-hospitalization quarantine. Re-positive patients could not be distinguished by demographic features, clinical symptoms, laboratory results, comorbidities, co-infections, treatments, chest CT scan results or subsequent clinical symptoms. However, re-positive rate was found to be correlated to illness severity, according the Acute Physiology and Chronic Health Evaluation II (APACHE II) severity-of-disease classification system, and the confusion, urea, respiratory rate and blood pressure (CURB-65) score. Common clinical characteristics were not able to distinguish re-positive patients. However, severe and critical cases classified high according APACHE II and CURB-65 scores, were more likely to become re-positive after discharge.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Adulto , Idoso , Betacoronavirus/isolamento & purificação , China , Comorbidade , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Alta do Paciente , Pneumonia Viral/virologia , Quarentena , RNA Viral/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X
10.
Mediators Inflamm ; 2020: 3764515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061826

RESUMO

This study aimed at determining the relationship between baseline cystatin C levels and coronavirus disease 2019 (COVID-19) and investigating the potential prognostic value of serum cystatin C in adult patients with COVID-19. 481 patients with COVID-19 were consecutively included in this study from January 2, 2020, and followed up to April 15, 2020. All clinical and laboratory data of COVID-19 patients with definite outcomes were reviewed. For every measure, COVID-19 patients were grouped into quartiles according to the baseline levels of serum cystatin C. The highest cystatin C level was significantly related to more severe inflammatory conditions, worse organ dysfunction, and worse outcomes among patients with COVID-19 (P values < 0.05). In the adjusted logistic regression analyses, the highest cystatin C level and ln-transformed cystatin C levels were independently associated with the risks of developing critically ill COVID-19 and all-cause death either in overall patients or in patients without chronic kidney disease (P values < 0.05). As a potential inflammatory marker, increasing baseline levels of serum cystatin C might independently predict adverse outcomes for COVID-19 patients. Serum cystatin C could be routinely monitored during hospitalization, which showed clinical importance in prognosticating for adult patients with COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Cistatina C/sangue , Pandemias , Pneumonia Viral/sangue , Adulto , Idoso , Biomarcadores/sangue , China/epidemiologia , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Estado Terminal , Feminino , Humanos , Mediadores da Inflamação/sangue , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Dinâmica não Linear , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
11.
J Trauma Acute Care Surg ; 89(6): 1092-1098, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32925581

RESUMO

BACKGROUND: Invasive mechanical ventilation (IMV) is a lifesaving strategy for critically ill patients with coronavirus disease 2019 (COVID-19). We aim to report the case series of critical patients receiving IMV in Wuhan and to discuss the timing of IMV in these patients. METHODS: Data of 657 patients admitted to emergency intensive care unit of Zhongnan Hospital and isolated isolation wards of Wuhan Union Hospital from January 1 to March 10, 2020, were retrospectively reviewed. All medical records of 40 COVID-19 patients who required IMV were collected at different time points, including baseline (at admission), before receiving IMV, and before death or hospital discharge. RESULTS: Among 40 COVID-19 patients with IMV, 31 died, and 9 survived and was discharged. The median age was 70 years (interquartile range [IQR], 62-76 years), and nonsurvivors were older than survivors. The median period from the noninvasive mechanic ventilation (NIV) or high-flow nasal cannula oxygen therapy (HFNC) to intubation was 7 hours (IQR, 2-42 hours) in IMV survivors and 54 hours (IQR, 28-143 hours) in IMV nonsurvivors. We observed that, when the time interval from NIV/HFNC to intubation was less than 50 hours (about 2 calendar days), together with Acute Physiology and Chronic Health Evaluation II (APACHE II) score of less than 10 or pneumonia severity index (PSI) score of less than 100, mortality can be reduced to 60% or less. Prolonged interval from NIV/HFNC to intubation and high levels of APACHE II and PSI before intubation were associated with higher mortality in critically ill patients. Multiple organ damage was common among these nonsurvivors in the course of treatment. CONCLUSION: Early initial intubation after NIV/HFNC might have a beneficial effect in reducing mortality for critically ill patients meeting IMV indication. Considering APACHE II and PSI scores might help physicians in decision making about timing of intubation for curbing subsequent mortality. LEVEL OF EVIDENCE: Therapeutic, level V.


Assuntos
Infecções por Coronavirus/terapia , Estado Terminal/terapia , Mortalidade Hospitalar , Ventilação não Invasiva/métodos , Oxigênio/administração & dosagem , Pneumonia Viral/terapia , APACHE , Idoso , Betacoronavirus , China , Infecções por Coronavirus/mortalidade , Estado Terminal/mortalidade , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Oxigenoterapia/métodos , Pandemias , Pneumonia Viral/mortalidade , Estudos Retrospectivos , Fatores de Tempo
12.
Stroke ; 51(9): 2674-2682, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32755348

RESUMO

BACKGROUND AND PURPOSE: No studies have reported the effect of the coronavirus disease 2019 (COVID-19) epidemic on patients with preexisting stroke. We aim to study the clinical course of COVID-19 patients with preexisting stroke and to investigate death-related risk factors. METHODS: We consecutively included 651 adult inpatients with COVID-19 from the Central Hospital of Wuhan between January 2 and February 15, 2020. Data on the demography, comorbidities, clinical manifestations, laboratory findings, treatments, complications, and outcomes (ie, discharged or death) of the participants were extracted from electronic medical records and compared between patients with and without preexisting stroke. The association between risk factors and mortality was estimated using a Cox proportional hazards regression model for stroke patients infected with severe acute respiratory syndrome coronavirus 2. RESULTS: Of the 651 patients with COVID-19, 49 with preexisting stroke tended to be elderly, male, had more underlying comorbidities and greater severity of illness, prolonged length of hospital stay, and greater hospitalization expenses than those without preexisting stroke. Cox regression analysis indicated that the patients with stroke had a higher risk of developing critical pneumonia (adjusted hazard ratio, 2.01 [95% CI, 1.27-3.16]) and subsequent mortality (adjusted hazard ratio, 1.73 [95% CI, 1.00-2.98]) than the patients without stroke. Among the 49 stroke patients, older age and higher score of Glasgow Coma Scale or Sequential Organ Failure Assessment were independent risk factors associated with in-hospital mortality. CONCLUSIONS: Preexisting stroke patients infected with severe acute respiratory syndrome coronavirus 2 were readily predisposed to death, providing an important message to individuals and health care workers that preventive measures must be implemented to protect and reduce transmission in stroke patients in this COVID-19 crisis.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Comorbidade , Infecções por Coronavirus/terapia , Progressão da Doença , Registros Eletrônicos de Saúde , Feminino , Escala de Coma de Glasgow , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/etiologia , Pandemias , Pneumonia/etiologia , Pneumonia Viral/terapia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
13.
J Atheroscler Thromb ; 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32641646

RESUMO

AIM: We aimed to investigate the relationship of trimethylamine N-oxide (TMAO) concentrations with ischemic stroke in a large-scale case-control study conducted among the hospital-based general population. METHODS: We recruited 953 case-control sex- and age-matched pairs, and cases were confined to first acute ischemic stroke in this study. Fasting plasma TMAO was measured using high-performance liquid chromatography-tandem mass spectroscopy. Conditional logistic regression analysis was conducted to calculate odds ratios (OR) for the association of plasma TMAO with ischemic stroke. RESULTS: We found that plasma TMAO concentrations in patients with ischemic stroke were significantly higher than that in the control group (median: 2.85 µmol/L vs. 2.33 µmol/L, P<0.001). In multivariable conditional logistic regression models, higher plasma TMAO concentrations were associated with increased odds of ischemic stroke [fully adjusted OR for highest vs. lowest TMAO quartile: 1.81; 95% confidence interval (CI): 1.27, 2.59; P for trend <0.001]. The multivariable-adjusted OR for ischemic stroke per 1 µmol/L increment of plasma TMAO was 1.05 (95% CI: 1.02, 1.08). Additionally, the positive association also persisted in subgroups stratified by age, sex, body mass index, smoking status, alcohol habits, history of diabetes, and history of hypertension. CONCLUSIONS: This study suggested a positive association between plasma TMAO and ischemic stroke. Further studies are required to explore the role of plasma TMAO concentrations in predicting stroke risk.

14.
Int J Biol Macromol ; 161: 258-270, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32522544

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease that remarkably imposes a huge global public health burden. Yeast ß-glucans have been incorporated in functional foods and used in prophylactic applications owing to their biological effects. However, few studies had investigated the effects of yeast ß-glucans on neurodegenerative diseases. Here, gut microbiota and metabolites SCFAs were analyzed through high-throughput 16S rRNA gene sequencing and GC-MS, respectively. Results indicated that yeast ß-glucans could prominently shape the intestinal flora and produce SCFAs. Aß1-42-induced AD mice treated with small-molecular yeast ß-glucan (S-ß-Glu) or macro-molecular yeast ß-glucan (M-ß-Glu) exhibited evident alterations of the composition of the gut microbiota, especially in some beneficial bacteria and inflammatory-related bacteria such as Lactobacillus, Bifidobacterium, Desulfovibrio, Oscillibacter, Mucispirillum, Alistipes, Anaerotruncus, and Rikenella. M-ß-Glu regulated gut microbiota act as prebiotics better than S-ß-Glu. Correlation analysis demonstrated the key microbiota closely associated with AD-related pathologies and cognition. Moreover, M-ß-Glu and S-ß-Glu ameliorated neuroinflammation and brain insulin resistance (IR), which played a central role in the process of AD pathology. This study broadened the underlying applications of yeast ß-glucans as a novel dietary supplementation to prevent early-stage pathologies associated with AD by regulating gut microbiota and the potential mechanism might be ameliorating brain IR.

15.
Oncologist ; 25(4): e659-e667, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32297441

RESUMO

BACKGROUND: The objective of this study was to develop and validate a nomogram to predict 1-year overall survival (OS) and 2-year OS in patients with high-grade digestive neuroendocrine neoplasms (NENs) as well as to guide selection of subgroups that could benefit from systemic chemotherapy. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective analysis of 223 patients with NENs of the gut and hepato-biliary-pancreatic system from four centers included in the development cohort. The nomogram was externally validated in a cohort of 90 patients from another one. RESULTS: The final model included lactate dehydrogenase, performance status, stage, Ki67, and site of primary tumor, all of which had a significant effect on OS. The uncorrected C-index was 0.761 for OS, and the bias-corrected C-index was 0.744. Predictions correlated well with observed 1-year and 2-year outcomes (judged by eye). The area under the time-dependent receiver operating characteristic curve at 12 months and 24 months was 0.876 and 0.838, respectively. The nomogram performed well in terms of both discrimination and calibration when applied to the validation cohort, and OS was significantly different between the two groups classified by nomogram score (log-rank p < .001). CONCLUSION: The validated nomogram provided useful prediction of OS, which can be offered for clinicians to improve their abilities to assess patient prognosis, to create clinical risk groups for informing treatment or for patient stratification by disease severity in clinical trials. IMPLICATIONS FOR PRACTICE: The high-grade neuroendocrine neoplasms of the digestive system are rare malignancies with great heterogeneity. An overall survival nomogram was developed and externally validated in this study. Two subgroups were classified by the nomogram score, and platinum-based chemotherapy may not bring clinical benefit for the low-risk patients.

16.
Platelets ; 31(4): 490-496, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32297540

RESUMO

BACKGROUND: Thrombocytopenia has been implicated in patients infected with severe acute respiratory syndrome coronavirus 2, while the association of platelet count and changes with subsequent mortality remains unclear. METHODS: The clinical and laboratory data of 383 patients with the definite outcome by March 1, 2020 in the Central Hospital of Wuhan were reviewed. The association between platelet parameters and mortality risk was estimated by utilizing Cox proportional hazard regression models. RESULTS: Among the 383 patients, 334 (87.2%) were discharged and survived, and 49 (12.8%) died. Thrombocytopenia at admission was associated with mortality of almost three times as high as that for those without thrombocytopenia (P < 0.05). Cox regression analyses revealed that platelet count was an independent risk factor associated with in-hospital mortality in a dose-dependent manner. An increment of per 50 × 109/L in platelets was associated with a 40% decrease in mortality (hazard ratio: 0.60, 95%CI: 0.43, 0.84). Dynamic changes of platelets were also closely related to death during hospitalization. CONCLUSIONS: Baseline platelet levels and changes were associated with subsequent mortality. Monitoring platelets during hospitalization may be important in the prognosis of patients with coronavirus disease in 2019.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Trombocitopenia , Adulto , Idoso , Estudos de Coortes , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Trombocitopenia/etiologia , Trombocitopenia/mortalidade
17.
Clin Nutr ; 39(7): 2151-2157, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31540775

RESUMO

BACKGROUND & AIMS: Drinking water and food are the major sources of strontium in human. Strontium is essential for bone metabolism, while its role in glucose and lipid metabolism is largely unknown. We aimed to investigate the association of strontium, a bone-seeking element, with type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) and to further explore the potential mechanisms. METHODS: The case-control study included 1448 newly diagnosed T2DM patients, 782 IGR patients, and 2230 matched controls with normal glucose tolerance. Plasma strontium and other plasma minerals were quantified via inductively coupled plasma mass spectrometry. Multivariable logistic regression analysis was used to evaluate the independent associations between plasma strontium and T2DM and IGR. RESULTS: Plasma strontium was inversely associated with T2DM and IGR. After adjustment for sociodemographic, lifestyle factors, and multiple plasma metals, the odds ratios (95% confidence intervals) of T2DM and IGR were 0.45 (0.35-0.57) and 0.55 (0.43-0.71), respectively, comparing the highest to the lowest quartile of plasma strontium levels. In spline analysis, the odds of T2DM and IGR decreased remarkably with increasing strontium concentration and followed by a plateau. Additionally, plasma strontium was negatively associated with total cholesterol, low density lipoprotein cholesterol, and lipid peroxidation (plasma malondialdehyde level). CONCLUSIONS: The current study indicated that higher plasma strontium concentration was associated with lower odds of T2DM and IGR. Further studies are warranted to confirm these findings and to clarify the underlying mechanisms.

18.
Arch Toxicol ; 94(2): 573-588, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31848666

RESUMO

Deoxynivalenol (DON) cannot be totally removed due to its stable chemical characteristics and chronic exposure to low doses of DON causes significant toxic effects in humans and animals. However, the potential hazard of such low-dose exposure in target organs still remains not completely understood, especially in liver, which is mainly responsible for detoxification of DON. In the present study, we demonstrated for the first time that estimated human daily DON exposure (25 µg/kg bw) for 30 and 90 days caused low-grade inflammatory infiltration around hepatic centrilobular veins, elevated systemic IL-1ß, IL-6 and TNF-α and impaired liver function evidenced by increased serum ALT activity. At the molecular level, expressions of autophagy-related proteins as well as Cleaved Caspase-3 and Cleaved Caspase-7 were upregulated during DON exposure, which indicated the activation of autophagy and apoptosis. Importantly, AAV-mediated liver-specific overexpression of HO-1 reversed DON-induced liver damages, upregulated autophagy and attenuated apoptosis in liver, while AAV-mediated HO-1 silence aggravated DON-induced liver damages, inhibited autophagy and increased apoptosis. Furthermore, in vitro experiments demonstrated that lentivirus-mediated HO-1 overexpression in Hepa 1-6 cells prolonged the duration of autophagy and delayed the onset of apoptosis. HO-1 silence in Hepa 1-6 cells inhibited activation of autophagy and accelerated occurrence of apoptosis, and these could be recovered by CO pre-treatment. Therefore, we suppose that HO-1 might be a potential research target to protect human and animal from liver injuries induced by low dose of DON exposure.

19.
Mutat Res ; 782: 108285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31843139

RESUMO

Mycotoxins, produced by fungi, are secondary metabolites causing adverse, toxic and pathological effects on human and animals. Studies about the association between mycotoxins and microRNAs (miRNAs) were developed since miRNAs have been demonstrated to play a critical role in many developmental processes for regulating messenger RNA (mRNA). As published studies showed, dozens of miRNAs were influenced by mycotoxins, indicating that miRNAs can play important roles in the occurrence and development of mycotoxicosis. Besides, a hypothesis called competing endogenous RNA (ceRNA) was reported to indirectly modulate the expression of mRNA via miRNA response elements (MREs) to consequently regulate cell functions. As a result, four common miRNAs were focused to predict the corresponding ceRNAs based on their own characteristics and the effects of mycotoxins on them, in hope of providing potential ways or directions of miRNAs regulation for mycotoxicosis, and expanding the research field about mycotoxicosis from ceRNA.


Assuntos
MicroRNAs/genética , Micotoxicose/genética , RNA Mensageiro/genética , Animais , Redes Reguladoras de Genes/genética , Humanos
20.
Wei Sheng Yan Jiu ; 48(1): 94-98, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31032775

RESUMO

OBJECTIVE: To explore the effects of deoxynivalenol-induced mRNA expressions of inflammation and apoptosis in BeWo cells. METHODS: After been cultured and transferred, BeWo cells were seeded for the CCK-8 assay. Then incubated with DON in the appropriate doses and time according to the CCK-8 result. ELISA kit was used to measure the ß-HCG levels in BeWo cells. qPCR was used to measure mRNA expressions of inflammation(IL-6, IL-8, TNF-α and Cox-2) and apoptosis(Caspase-3 and Bcl-xl) in BeWo cells. RESULTS: Compared with the control group, IL-6, TNF-α and Cox-2 significantly increased in BeWo cells which were exposed in 50 nmol/L DON in 3, 12 and 24 h(P<0. 01), while IL-8 only significantly increased in 24 h(P<0. 01). Caspase-3 significantly decreased in 3, 12 and 24 h(P<0. 01), and Bcl-xl significantly increased in 24 h(P<0. 01). CONCLUSION: The change in the level of inflammation and apoptosis may be one of the critical molecular mechanisms for DON-induced embryotoxicity.


Assuntos
Apoptose , Citocinas , RNA Mensageiro , Tricotecenos , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Inflamação , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Tricotecenos/farmacologia
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