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1.
Cell Metab ; 33(10): 1943-1956.e2, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478633

RESUMO

Metabolic dysfunction is becoming a predominant risk for the development of many comorbidities. Ischemic heart disease (IHD) still imposes the highest disease burden among all cardiovascular diseases worldwide. However, the contributions of metabolic risk factors to IHD over time have not been fully characterized. Here, we analyzed the global disease burden of IHD and 15 associated general risk factors from 1990 to 2019 by applying the methodology framework of the Global Burden of Disease Study. We found that the global death cases due to IHD increased steadily during that time frame, while the mortality rate gradually declined. Notably, metabolic risk factors have become the leading driver of IHD, which also largely contributed to the majority of IHD-related deaths shifting from developed countries to developing countries. These findings suggest an urgent need to implement effective measures to control metabolic risk factors to prevent further increases in IHD-related deaths.

2.
Cell Metab ; 33(10): 2059-2075.e10, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34536344

RESUMO

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

3.
Heart Lung ; 50(6): 885-892, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34411870

RESUMO

BACKGROUND: The role of blood high mobility group box-1 (HMGB-1) protein in predicting mortality of sepsis remains controversial. OBJECTIVE: Here we conducted a meta-analysis to seek evidence for the association between blood HMGB-1 concentrations and mortality in patients with sepsis. METHODS: Eligible studies were identified by a comprehensive search of six digital databases, supplemented by a manual search of related references. Standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs) were calculated as effect estimates. RESULTS: A total of eighteen studies, covering 1163 patients with sepsis, were included. Compared with survival groups of sepsis, non-survival groups had significantly higher blood HMGB-1 concentrations at enrollment (SMD: 0.45, 95% CI: 0.21-0.69). Subgroup analyses showed that no significant differences were found between two groups among patients with more severe sepsis (SMD: 0.18, 95% CI: -0.02-0.38). A significant association between initial HMGB-1 levels and ≤30-day mortality remained (SMD: 0.43, 95% CI: 0.09-0.78). Besides, HMGB-1 levels were observed to be more significantly higher in non-survival groups after the third day of admission (SMD: 1.33, 95% CI: 1.05-1.62) but two groups attained comparable HMGB-1 levels on day 7 (SMD: 1.01, 95% CI: -0.31-2.33). CONCLUSIONS: Initial high blood HMGB-1 levels are significantly associated with short-term (≤30 days) mortality of patients with sepsis, and the association may be affected by the severity of sepsis. Subsequent monitoring of HMGB-1 levels, on the third and seventh day after admission, is encouraged for better evaluation of HMGB-1 as a prognostic marker of mortality in sepsis.

4.
BMJ Open ; 11(7): e049114, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315796

RESUMO

OBJECTIVES: To examine primary care physicians' (PCPs) perception of patients' trust and associated factors for enhancing perceived trust in rural China. DESIGN: A cross-sectional questionnaire study. SETTING: All township health centres (primary care facilities in rural areas of China) in both developed and less developed counties of Zhejiang province, China, were chosen as the study sites. PARTICIPANTS: A total of 849 questionnaires were distributed from December 2019 to January 2020, and 673 PCPs working in township health centres completed the questionnaires. The response rate was 79.3%. OUTCOME MEASURES: PCPs' perceived patients' trust in them, PCPs' practices to meet patients' expectations and PCPs' perceived conflicting patient and employer interests were measured by a self-designed and verified questionnaire. Confirmatory factor analysis was applied to verify the measurement model of PCPs' practices. Multivariable logistic regression analyses were performed to explore the association between clinical practice characteristics, discordant patient and employer interests and perceived patient trust after controlling for social-demographic characteristics. RESULTS: Among all participants, 572 (85.0%) PCPs often/always perceived patients' trust in their clinical competence, and over two-thirds of PCPs reported ever perceived patient worries about overprescriptions. After adjustment for social-demographic characteristics, regression model results indicated that, among PCPs' clinical practices characteristics, emotional support (OR=1.23, 95% CI=1.06 to 1.42) and accurate diagnosis and treatment (OR=1.35, 95% CI=1.17 to 1.55) were positively associated with PCPs' perceived patients' trust in their clinical competence. A strong association was found between accurate diagnosis and treatment (OR=1.20, 95% CI=1.08 to 1.34, p<0.001; OR=1.22, 95% CI=1.10 to 1.35, p<0.001), conflicting patient and employer interests (OR=1.35, 95% CI=1.12 to 1.63, p<0.01; OR=1.29, 95% CI=1.07 to 1.54, p<0.01) and PCPs' perceived patient worries about unnecessary medicine or tests, respectively. CONCLUSIONS: PCPs' emotional support to patients as well as their abilities to make accurate diagnosis and provide appropriate treatment is positively associated with PCPs' self-reported patients' trust. It is recommended that reforms to realign patient and employer's interests be investigated.


Assuntos
Médicos de Atenção Primária , Atitude do Pessoal de Saúde , China , Estudos Transversais , Humanos , Inquéritos e Questionários , Confiança
6.
BMJ Open ; 11(6): e044072, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187815

RESUMO

OBJECTIVE: The survival benefit of using mechanical circulatory support (MCS) in patients with acute myocardial infarction (AMI) is still controversial. It is necessary to explore the impact on clinical outcomes of MCS in patients with AMI undergoing stenting. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Cochrane Library, Medline, PubMed, Web of Science, ClinicalTrials.gov and Clinicaltrialsregister.eu databases were searched from database inception to February 2021. ELIGIBILITY CRITERIA: Randomised clinical trials (RCTs) on MCS use in patients with AMI undergoing stent implantation were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted and summarised independently by two reviewers. Risk ratios (RRs) and 95% CIs were calculated for clinical outcomes according to random-effects model. RESULTS: Twelve studies of 1497 patients with AMI were included, nine studies including 1382 patients compared MCS with non-MCS, and three studies including 115 patients compared percutaneous ventricular assist devices (pVADs) versus intra-aortic balloon pump (IABP). Compared with non-MCS, MCS was not associated with short-term (within 30 days) (RR=0.90; 95% CI 0.57 to 1.41; I2=46.8%) and long-term (at least 6 months) (RR=0.82; 95% CI 0.57 to 1.17; I2=37.6%) mortality reductions. In the subset of patients without cardiogenic shock (CS) compared with non-MCS, the patients with IABP treatment significantly had decreased long-term mortality (RR=0.49; 95% CI 0.27 to 0.90; I2=0), but without the short-term mortality reductions (RR=0.51; 95% CI 0.22 to 1.19; I2=17.9%). While in the patients with CS, the patients with MCS did not benefit from the short-term (RR=1.09; 95% CI 0.67 to 1.79; I2=46.6%) or long-term (RR=1.00; 95% CI 0.75 to 1.33; I2=22.1%) survival. Moreover, the application of pVADs increased risk of bleeding (RR=1.86; 95% CI 1.15 to 3.00; I2=15.3%) compared with IABP treatment (RR=1.86; 95% CI 1.15 to 3.00; I2=15.3%). CONCLUSIONS: In all patients with AMI undergoing stent implantation, the MCS use does not reduce all-cause mortality. Patients without CS can benefit from MCS regarding long-term survival, while patients with CS seem not.


Assuntos
Coração Auxiliar , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Balão Intra-Aórtico , Infarto do Miocárdio/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Choque Cardiogênico/terapia , Stents , Resultado do Tratamento
7.
Circ Res ; 128(11): 1747-1765, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34043417

RESUMO

Cardiac arrhythmias and the resulting sudden cardiac death are significant cardiovascular complications that continue to impose a heavy burden on patients and society. An emerging body of evidence indicates that nonalcoholic fatty liver disease (NAFLD) is closely associated with the risk of cardiac arrhythmias, independent of other conventional cardiometabolic comorbidities. Although most studies focus on the relationship between NAFLD and atrial fibrillation, associations with ventricular arrhythmias and cardiac conduction defects have also been reported. Mechanistic investigations suggest that a number of NAFLD-related pathophysiological alterations may potentially elicit structural, electrical, and autonomic remodeling in the heart, contributing to arrhythmogenic substrates in the heart. NAFLD is now the most common liver and metabolic disease in the world. However, the upsurge in the prevalence of NAFLD as an emerging risk factor for cardiac arrhythmias has received little attention. In this review, we summarize the clinical evidence and putative pathophysiological mechanisms for the emerging roles of NAFLD in cardiac arrhythmias, with the purpose of highlighting the notion that NAFLD may serve as an independent risk factor and a potential driving force in the development and progression of cardiac arrhythmias.

8.
Appl Opt ; 60(12): 3482-3486, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33983255

RESUMO

The optical approach to estimate the direction-of-arrival (DOA) estimation of microwave signals has attracted a lot of attention recently. Most of the existing methods are based on a one-sensor array system, which converts the DOA estimation problem into an optical power estimation problem. Their main disadvantage is that additional work is needed to represent the relationship between the phase shifts and the optical powers before estimation. The algorithm proposed in this paper is based on an N-sensor array (N>2), where the optical power vector is obtained first and then a compressive sensing-based approach is applied to directly estimate the phase shift. As demonstrated by simulation results, the proposed algorithm can achieve much better estimation accuracy and robustness than existing optical DOA estimation algorithms considered.

9.
Food Chem ; 358: 129837, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33940299

RESUMO

There is evidence that moderate coffee consumption is beneficial in the prevention of type 2 diabetes, however, the underlying mechanism is not understood. In this study, the effects of an extract of ground coffee on the in vitro enzymatic digestion of starch were investigated. The coffee extract decreased the rate and extent of starch digestion, with kinetic analysis showing that the extract reduced the binding affinity of the enzymes for the substrate and their catalytic turnover. Fluorescence quenching indicated that the coffee extract formed complexes with the digestive enzymes through a static quenching mechanism. Ultraviolet absorption and circular dichroism spectra of the digestive enzymes confirmed that the coffee extract decreased the proportion of ß-sheet structures in the enzymes. Therefore, we conclude that compounds in the soluble coffee extract can interact with porcine pancreatic amylase and amyloglucosidase causing inhibition of the enzymes and decreasing in vitro starch digestion.


Assuntos
Café , Glucana 1,4-alfa-Glucosidase/antagonistas & inibidores , Extratos Vegetais/farmacologia , Amido/metabolismo , alfa-Amilases/antagonistas & inibidores , Animais , Digestão , Glucana 1,4-alfa-Glucosidase/metabolismo , Hidrólise , Cinética , Suínos/metabolismo , alfa-Amilases/metabolismo
10.
J Int Med Res ; 49(4): 300060521995273, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33866841

RESUMO

OBJECTIVE: To examine the clinical effects of revision endoscopic frontal sinus surgery (RESS) through modified agger nasi (MAN)-middle turbinate resection on refractory chronic rhinosinusitis (CRS). METHODS: We reviewed 156 patients who were treated for refractory CRS from February 2012 to August 2014. These patients had been diagnosed with refractory CRS by computed tomography and endoscopy and had received several surgical and medical treatments in the past, but their condition had not been cured. They were divided into the observation group (RESS through MAN-middle turbinate resection, n = 78) and the control group (endoscopic sinus surgery, n = 78). Complete or partial control of the patient's symptoms and signs suggested that the treatment was effective, and no improvement in the symptoms and signs indicated that the treatment was ineffective. RESULTS: The 6-month treatment efficacy rate was significantly higher in the observation group (91.03%) than in the control group (71.79%). The observation group had a significantly lower complication rate (7.69%) and recurrence rate (3.85%) than the control group (17.95% and 12.82%, respectively). CONCLUSION: RESS through MAN-middle turbinate resection together with adequate perioperative preparation has a significant effect on the outcome of refractory CRS and is worthy of clinical promotion.


Assuntos
Endoscopia/métodos , Seio Frontal/cirurgia , Sinusite Frontal/cirurgia , Procedimentos Cirúrgicos Nasais/métodos , Rinite/cirurgia , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Seio Frontal/diagnóstico por imagem , Sinusite Frontal/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Estudos Retrospectivos , Rinite/diagnóstico por imagem , Resultado do Tratamento , Conchas Nasais/diagnóstico por imagem , Conchas Nasais/cirurgia
11.
Microb Drug Resist ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33835874

RESUMO

A clinically isolated pan-resistant Klebsiella pneumoniae strain (ST11), KPN142 was subjected to whole-genome sequencing. Genomic sequence of KPN142 showed that limited antibiotic resistances (ß-lactams [blashv-11], sulfonamides [sul1 and dfrA22], bacitracin [bacA], tetracycline [tet34], aminoglycosides [ksgA, kdpE, aph(3)Ia, aac(3)III, and ant(3)Ia], and chloramphenicol [catA1]) were mediated by enzymes, and efflux pumps contributed most to pan resistance. Five types of multidrug resistance efflux pump families were identified, including the resistance nodulation division superfamily (AcrAB-TolC, AcrD, MdtABC, and KexD), the ATP-binding cascade superfamily (MacAB), the small multidrug resistance family (KpnEF), the multidrug and toxic compound extrusion family (KdeA), and the major facilitator superfamily (EmrAB). There was an AcrAB-TolC efflux pump system, and inhibitory regulatory gene acrR and ramR of system carried deletion mutation, which lead to overexpression of AcrAB-TolC efflux pump, and in turn plays key role in the pan resistance of KPN142. Moreover, we did not find mgrb, a suppressor in the expression of phoPQ, overexpression of which may confer the resistance of KPN142 to colistin B. In addition, K. pneumoniae KPN142 carries IS1, IS3, and IntI1, which means that KPN142 is able to transfer drug-resistance genes. Of note, we detected the overexpression of acrB, ramA, phoP, and phoQ by real-time quantitative reverse transcription-polymerase chain reaction, and carbonyl cyanide chlorophenylhydrazone was able to reverse the resistance patterns of K. pneumoniae KPN142. In conclusion, we consider that the overexpression of AcrAB-TolC efflux pump mediates the resistance to most common clinical antimicrobial agents, and the overexpression of phoPQ mediates the resistance to colistin B in K. pneumoniae KPN142.

12.
J Dairy Sci ; 104(5): 5166-5184, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33714582

RESUMO

In the present study 114 lactic acid bacteria strains, isolated from raw mare milks from pastoral areas for ethnic minorities in northwest China, were screened for probiotic traits, and their characteristics were compared with those of Lactobacillus rhamnosus GG, a commercial strain. Among the 114 strains identified, the most common species was Pediococcus pentosaceus (n = 52), followed by Leuconostoc lactis (n = 35), Lactobacillus helveticus (n = 7), Lactobacillus plantarum (n = 6), Lactobacillus kefiri (n = 5), Lactobacillus curvatus (n = 4), Lactobacillus paracasei (n = 3), and Lactococcus garvieae (n = 3). Based on acid and bile salt tolerance, 15 strains were further selected. All selected strains were subjected to a series of in vitro tests to assess their technological properties, including cell surface hydrophobicity (13.6-56.2%), autoaggregation ability (9.26-38.30%), coaggregation ability, and heat and lysozyme survival rates (84.74-94.01% and 80.52-99.37%, respectively). In vitro antagonism showed that Lb. plantarum (M5-19, M8-60, M8-59) exhibited the most strong inhibitory activity against 7 tested pathogens. Moreover, antibiotic resistance and hemolytic activity were investigated for safety assessment. No strain exhibited hemolytic activity, and most of the strains were sensitive to a series of 14 antibiotics of clinical importance. Ultimately, the principal component analysis of all data obtained above showed that 2 Lb. plantarum strains (M8-59, M8-60) and Lb. paracasei M1-36 exhibited the best potential for their inclusion as adjunct functional cultures in local fermented dairy products.


Assuntos
Produtos Fermentados do Leite , Lactobacillales , Probióticos , Animais , China , Feminino , Fermentação , Cavalos , Lactobacillus , Lactococcus , Leuconostoc , Leite
13.
Med (N Y) ; 2021 Jan 08.
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).

14.
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
15.
Exp Eye Res ; 204: 108446, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33476605

RESUMO

Neovascular age-related macular degeneration (neoAMD) is the leading cause of blindness in AMD and manifests as choroidal neovascularization (CNV). Anti-vascular endothelial growth factor (VEGF) therapies are the mainstay treatments but with limited efficacy and cause detrimental effects on the retina after long-term application. These disadvantages warrant alternative strategy. Herein, we examined the effect on CNV by intravitreal injection of bortezomib, a reversible proteasome inhibitor, and further dissected the mechanism. Krypton red Laser was used to create CNV model in mice. The angiogenesis volume was assessed in choroidal flat-mount with isolectin GS-IB4 labeling and the leakage was examined with fluorescein fundus angiography. Injection of Borsub inhibited angiogenesis in the CNV model which was dose-dependent; the injection significantly inhibited leakage as well. Furthermore, Borsub injection reduced the contents of VEGF-A, macrophage chemotactic factor 1 (MCP-1), and platelet-derived growth factor (PDGF)-D but not PDGF-B, examined by enzyme-linked immunosorbent assay, in choroid/retinal pigment epithelium (RPE) tissue. These injections also reduced phospho-VEGFR-2 and phospho-PDGFRß in choroid/RPE tissue examined by immunoblotting. Moreover, Borsub inhibited the recruitment of mural cells or macrophages to laser-injured spots. Injection of Borsub indicated negative effect on scotopic and photopic responses recorded by electroretinogram. Altogether, intravitreal injection of Borsub significantly reduced CNV by antagonizing VEGF-A/Flk-1 and PDGF-D/PDGFRß pathways without impacting electroretinography parameters. Thus, Borsub may offer an invaluable therapy for the prevention and treatment of neoAMD.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Modelos Animais de Doenças , Linfocinas/antagonistas & inibidores , Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Western Blotting , Quimiocina CCL2/antagonistas & inibidores , Quimiocina CCL2/metabolismo , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/fisiopatologia , Reposicionamento de Medicamentos , Eletrorretinografia/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Angiofluoresceinografia , Marcação In Situ das Extremidades Cortadas , Injeções Intravítreas , Linfocinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
J Agric Food Chem ; 69(32): 9086-9093, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-33449697

RESUMO

In this study, the effects of debranching on the structure and properties of the starch-lauric acid (LA)-ß-lactoglobulin (ßLG) complex were studied. Gel permeation chromatography and high-performance anion-exchange chromatography showed that debranching of amylopectin generated short linear chains, which increased in proportions with debranching time. Analyses from differential scanning calorimetry, laser confocal micro-Raman spectroscopy, and X-ray diffraction showed that debranching promoted the formation of starch-LA and starch-LA-ßLG complexes, as characterized by the increased enthalpy changes and crystallinity and decreased full width at half maximum of the band at 480 cm-1. Debranching treatment for 6 and 18 h promoted complexation between starch and LA, while extensive debranching was unfavorable for the formation of starch-LA complexes. Similar results were also observed for the starch-LA-ßLG complexes. Starch-LA-ßLG complexes had more type II and less type I crystallites than starch-LA complexes. From this study, we conclude that debranching of starch favors the formation of starch-LA and starch-LA-ßLG complexes, with more type II crystallites formed in starch-LA-ßLG complexes.


Assuntos
Lactoglobulinas , Zea mays , Ácidos Láuricos , Amido , Difração de Raios X
17.
Neurol Sci ; 42(3): 857-861, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33420613

RESUMO

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (AE) is a common cause of nonviral infectious encephalitis, which can be triggered by herpes simplex virus infection. Previous studies have shown that approximately 27% of herpes simplex encephalitis (HSE) patients produce anti-NMDAR antibodies within 3 months. Immunotherapy is recommended in this situation, but some symptoms usually remain in the 1-year follow-up. CASE PRESENTATION: A previously healthy 23-year-old Chinese young woman developed epileptic attack followed by psychiatric symptoms of confusion and irritation as well as cognitive deficits. Brain MRI showed hyperintense lesions of the right temporal lobe on DWI and T2 without contrast enhancement effects. Twenty-one days of acyclovir was administered based on the primary diagnosis of HSE. The anti-NMDAR antibody (IgG) was detected positively on day 11 after disease onset. She had improved cognitive function but suffered another grand mal epilepsy after the first course of intravenous immunoglobulin (IVIG) therapy combined with 1000 mg intravenous methylprednisolone. After discussion, another course of IVIG was started for 5 days. Her symptoms were well controlled with only mild cognitive deficits at the 1-year follow-up (mRS = 1). CONCLUSIONS: Our case indicated that anti-NMDAR antibodies could develop earlier after HSE compared with previous data from adults. We suggested detecting AE antibodies simultaneously with each CSF analysis. Meanwhile, the second course of IVIG therapy was reasonable when symptoms were not controlled after the first course of IVIG combined with IV steroid treatment.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Encefalite por Herpes Simples , Aciclovir , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Encefalite por Herpes Simples/complicações , Encefalite por Herpes Simples/diagnóstico por imagem , Encefalite por Herpes Simples/tratamento farmacológico , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos , Receptores de N-Metil-D-Aspartato , Adulto Jovem
18.
Ecotoxicol Environ Saf ; 211: 111881, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33444878

RESUMO

BACKGROUND: Cadmium is the most prevalent form of heavy metal contaminant globally and its exposure rises serious health concern. Chronic exposure to cadmium causes immune disturbances. However, few studies have addressed how it affects circulating immune cells, one of the most essential elements for the host defense system, at both population and molecular level. Therefore, this is the first single-cell transcriptomic analysis of the response of the human circulating immune system to plasma cadmium level. METHODS: We conducted a cross-sectional study in Hunan province, which has the highest level of cadmium land contamination in China. A total of 3283 individuals were eligible for analyzing the association between plasma cadmium levels and the monocyte counts and its subgroups. Another 780 individuals were assigned for validation. Thirty propensity-matched individuals without chronic disease from the lowest- and highest-quartile groups according to serum cadmium levels were selected for single-cell RNA sequencing (scRNA-seq) and flow cytometry analyses. Moreover, the monocyte phenotypic alterations in the heavy metal-exposed population were validated with a cecal ligation and puncture sepsis mouse model. RESULTS: From August 2016 to July 2017, we conducted a cross-sectional study to identify phenotypic alterations in peripheral immune cells in cadmium polluted areas in China. Monocyte percentages were negatively associated with plasma cadmium levels in multivariable linear regression analysis. Peripheral blood mononuclear cell scRNA-seq revealed that the CD14+ monocyte subset was dramatically reduced in the highest-quartile cadmium-exposed group. Moreover, we assessed different hallmarks of immune cell dysfunction-such as host defense capability, apoptotic signaling, cellular diversity and malignant gene expression in monocytes. Importantly, cadmium induced phenotypic alterations in the immune system were validated in the cecal ligation and puncture sepsis mouse model, in which chronic exposure to cadmium not only increased the death rate but also decreased monocyte numbers and the ability to clear bacterial infections. CONCLUSION: This transcriptomic analysis provides molecular information about how the most important hallmarks of immune cell dysfunction are affected by plasma cadmium level. The significant phenotypic alterations in monocytes serving as early indicators of increased susceptibility to infectious and malignant diseases.


Assuntos
Cádmio/toxicidade , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/toxicidade , Monócitos/efeitos dos fármacos , China , Estudos Transversais , Citometria de Fluxo , Humanos , Contagem de Leucócitos , Leucócitos Mononucleares , Masculino , Monócitos/citologia , Transcriptoma
19.
Hepatology ; 73(1): 104-125, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32191345

RESUMO

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, which has no specific pharmacological treatments partially because of the unclear pathophysiological mechanisms. Regulator of G protein signaling (RGSs) proteins are proteins that negatively regulate G protein-coupled receptor (GPCR) signaling. The members of the R4/B subfamily are the smallest RGS proteins in size, and RGS5 belongs to this family, which mediates pluripotent biological functions through canonical G protein-mediated pathways and non-GPCR pathways. This study combined a genetically engineered rodent model and a transcriptomics-sequencing approach to investigate the role and regulatory mechanism of RGS5 in the development of NAFLD. APPROACH AND RESULTS: This study found that RGS5 protects against NAFLD and nonalcoholic steatohepatitis. Using RNA sequencing and an unbiased systematic investigative approach, this study found that the activation of mitogen-activated protein kinase signaling cascades in response to metabolic challenge is negatively associated with hepatic RGS5 expression. Mechanistically, we found that the 64-181 amino-acid-sequence (aa) fragment of RGS5 directly interacts with transforming growth factor beta-activated kinase 1 (TAK1) through the 1-300aa fragment and inhibits TAK1 phosphorylation and the subsequent c-Jun-N-terminal kinase (JNK)/p38 pathway activation. CONCLUSIONS: In hepatocytes, RGS5 is an essential molecule that protects against the progression of NAFLD. RGS5 directly binds to TAK1, preventing its hyperphosphorylation and the activation of the downstream JNK/p38 signaling cascade. RGS5 is a promising target molecule for fine-tuning the activity of TAK1 and for the treatment of NAFLD.


Assuntos
Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/patologia , MAP Quinase Quinase Quinases/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas RGS/metabolismo , Transdução de Sinais , Animais , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Humanos , Resistência à Insulina , Masculino , Camundongos , Camundongos Knockout
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