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1.
Nat Commun ; 15(1): 1757, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413612

RESUMO

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.


Assuntos
Candida albicans , Proteínas Fúngicas , Humanos , Camundongos , Animais , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Candida albicans/metabolismo , Peptídeos/metabolismo
2.
Sci Rep ; 14(1): 1686, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38242975

RESUMO

Most proton pump inhibitors (PPIs) inhibit the bioactivation of clopidogrel to its active metabolite. There is controversy concerning whether PPIs alter the effectiveness of clopidogrel in reducing the risk of ischemic stroke (IS). We therefore aimed to examine the risk of IS associated with concomitant use of clopidogrel and omeprazole, a PPI commonly used in clinical settings. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study cohorts comprised 407 patients diagnosed with acute coronary syndrome (ACS) and with concomitant use of clopidogrel and omeprazole (the exposed cohort), 814 ACS patients with single use of clopidogrel (the comparison cohort), and 230 ACS patients with concurrent use of clopidogrel and pantoprazole (the reference cohort). The primary outcome was incident IS. The hazard ratios (HRs) and 95% confidence intervals (CIs) derived from the time-dependent Cox regression model were used to assess the association between concomitant use of clopidogrel and omeprazole and the risk of IS. The incidence rate of IS was significantly higher in the exposed cohort (81.67 per 1000 person-years) than in the comparison cohort (57.45 per 1000 person-years), resulting in an adjusted HR of 1.39 (95% CI 1.03-1.74). By contrast, there was no significant difference in the risk of IS between the exposed and reference cohorts (adjusted HR 1.11; 95% CI 0.81-1.52). The present study revealed that patients taking both clopidogrel and omeprazole was associated with an increased risk of IS.


Assuntos
Síndrome Coronariana Aguda , AVC Isquêmico , Humanos , Clopidogrel/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos , Estudos de Coortes , Omeprazol/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/efeitos adversos , Estudos Retrospectivos , AVC Isquêmico/tratamento farmacológico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/induzido quimicamente , Interações Medicamentosas
3.
Heliyon ; 10(2): e24632, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38293442

RESUMO

Due to the uniqueness and interactivity of its scenario, the cultural and tourism commercial space consistently enriches and enhances the user experience while satisfying users' consumption and shopping. However, there is limited research on the participatory aspect of cultural tourism business spaces from the perspective of users. To this end, the present study investigates the participatory experience of cultural tourism commercial spaces by selecting 305 tourists who visited Huaihai Street in Suzhou for consumption and entertainment and quantifies the relationship between the public's flow experience, aesthetic judgments, and behavioral outcomes using a structural equation modeling approach. The results of the study confirm that aesthetic judgments and flow experiences positively impact behavioral outcomes and that flow experiences also affect aesthetic judgments and behavioral outcomes. These findings contribute to a better understanding of the significance of user participation in cultural tourism business spaces.

4.
Chem Biol Drug Des ; 103(1): e14364, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37806947

RESUMO

With the emergence of the human pathogen Candida auris as a threat to human health, there is a strong demand to identify effective medicines to prevent the harm caused by such drug-tolerant human fungi. Herein, a series of 33 new derivatives of bensulfuron methyl (BSM) were synthesized and characterized by 1 H NMR, 13 C NMR, and HRMS. Among the target compounds, 8a possessed the best Ki value of 1.015 µM against C. auris acetohydroxyacid synthase (CauAHAS) and an MIC value of 6.25 µM against CBS10913, a clinically isolated strain of C. auris. Taken together the structures of BSM and the synthesized compounds, it was found that methoxy groups at both meta-position of pyrimidine ring are likely to provide desirable antifungal activities. Quantum calculations and molecular dockings were performed to understand the structure-activity relationships. The present study has hence provided some interesting clues for the discovery of novel antibiotics with this distinct mode of action.


Assuntos
Candida auris , Candida , Compostos de Sulfonilureia , Humanos , Antifúngicos/farmacologia , Relação Estrutura-Atividade , Testes de Sensibilidade Microbiana
5.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(6): 993-999, 2023 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-38101779

RESUMO

OBJECTIVE: To analyze the clinical features of overweight and obese rheumatoid arthritis (RA)patients, and the relationship between body mass index (BMI) and disease characteristics. METHODS: The demographic data, extra-articular manifestations, comorbidities, and disease activity of RA patients admitted to the Rheumatology and Immunology Department of Peking University Third Hospital from January 2015 to December 2020 were collected, and the above characteristics of overweight and obese RA patients were retrospectively analyzed. According to the WHO, BMI≥30 kg/m2 referred to obese individuals, 25≤BMI < 30 kg/m2 referred to overweight individuals, 18.5≤BMI < 25 kg/m2 referred to normal individuals, BMI < 18.5 kg/m2 referred to reduced body mass individuals. t test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non-normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, Chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. Analyzing whether overweight or obesity was associated with comorbidities using Logistic regression adjusted confounding factors. RESULTS: A total of 481 RA patients were included in this study, with an average BMI value of (23.28±3.75) kg/m2.Of the patients, 31 cases (6.5%) were with BMI < 18.5 kg/m2, 309 cases (64.2%) with 18.5≤ BMI < 25 kg/m2, amounting to 340 cases (70.7%). There were 119 overweight individuals (25≤ BMI < 30 kg/m2, 24.7%) and 22 obese individuals (BMI≥30 kg/m2, 4.6%), totaling 141 (29.3%).The proportion of the overweight and obese RA patients suffering from hypertension (57.4% vs. 39.1%, P < 0.001), diabetes (25.5% vs. 15.0%, P=0.006), hyperlipidemia (22.7% vs. 10.9%, P=0.001), fatty liver (28.4% vs. 7.4%, P < 0.001), osteoarthritis (39.0% vs. 29.4%, P=0.040) was significantly higher, and the proportion of the patients with osteoporosis(59.6% vs. 70.9%, P=0.016) and anemia (36.2% vs. 55.6%, P < 0.001) was significantly lower. However, there was no difference between the two groups in coronary heart disease (5.7% vs. 7.6%, P=0.442), cerebrovascular disease (6.4% vs. 8.8%, P=0.372) and peripheral atherosclerosis (9.2% vs. 7.6%, P=0.565).The median C-reactive protein (CRP, 1.52 mg/dL vs. 2.35 mg/dL, P=0.008), median erythrocyte sedimentation rate (ESR, 34.0 mm/h vs. 50.0 mm/h, P=0.003), pain visual simulation score (VAS) (3.66±3.08 vs. 4.40±2.85, P=0.011), and 28 joint disease activity scores (DAS-28, 5.05±1.60 vs. 5.45±1.52, P=0.010) in the overweight and obese RA group were all lower than those in the normal and reduced weight groups. Multivariate regression analysis showed that overweight and obesity was an independent risk factor for hypertension, diabetes, hyperlipidemia and fatty liver, and had protective effects on osteoporosis and anemia. CONCLUSION: In RA patients, RA disease activity is lower in overweight and obesity patients. Overweight and obesity is associated with hypertension, diabetes and hyperlipidemia, but not with cardiovascular and cerebrovascular diseases.


Assuntos
Anemia , Artrite Reumatoide , Diabetes Mellitus , Fígado Gorduroso , Hiperlipidemias , Hipertensão , Osteoporose , Humanos , Índice de Massa Corporal , Sobrepeso/complicações , Sobrepeso/epidemiologia , Estudos Retrospectivos , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Hipertensão/complicações , Fígado Gorduroso/complicações , Hiperlipidemias/complicações , Osteoporose/complicações
6.
Plant J ; 116(4): 1030-1040, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37856620

RESUMO

Fruit traits are critical determinants of plant fitness, resource diversity, productive and quality. Gene regulatory networks in plants play an essential role in determining fruit traits, such as fruit size, yield, firmness, aroma and other important features. Many research studies have focused on elucidating the associated signaling pathways and gene interaction mechanism to better utilize gene resources for regulating fruit traits. However, the availability of specific database of genes related to fruit traits for use by the plant research community remains limited. To address this limitation, we developed the Gene Improvements for Fruit Trait Database (GIFTdb, http://giftdb.agroda.cn). GIFTdb contains 35 365 genes, including 896 derived from the FR database 1.0, 305 derived from 30 882 articles from 2014 to 2021, 236 derived from the Universal Protein Resource (UniProt) database, and 33 928 identified through homology analysis. The database supports several aided analysis tools, including signal transduction pathways, gene ontology terms, protein-protein interactions, DNAWorks, Basic Local Alignment Search Tool (BLAST), and Protein Subcellular Localization Prediction (WoLF PSORT). To provide information about genes currently unsupported in GIFTdb, potential fruit trait-related genes can be searched based on homology with the supported genes. GIFTdb can provide valuable assistance in determining the function of fruit trait-related genes, such as MYB306-like, by conducting a straightforward search. We believe that GIFTdb will be a valuable resource for researchers working on gene function annotation and molecular breeding to improve fruit traits.


Assuntos
Frutas , Genes de Plantas , Frutas/metabolismo , Fenótipo , Plantas/genética , Anotação de Sequência Molecular
7.
Glob Health Res Policy ; 8(1): 38, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670331

RESUMO

Since the twenty first century, the outbreaks of global infectious diseases have caused several public health emergencies of international concern, imposing an enormous impact on population health, the economy, and social development. The COVID-19 pandemic has once again exposed deficiencies in existing global health systems, emergency management, and disease surveillance, and highlighted the importance of developing effective evaluation tools. This article outlines current challenges emerging from infectious disease control from the perspective of global health, elucidated through influenza, malaria, tuberculosis, and neglected tropical diseases. The discordance among government actors and absent data sharing platforms or tools has led to unfulfilled targets in health system resilience and a capacity gap in infectious disease response. The current situation calls for urgent action to tackle these threats of global infectious diseases with joined forces through more in-depth international cooperation and breaking governance barriers from the purview of global health. Overall, a systematic redesign should be considered to enhance the resilience of health systems, which warrants a great need to sustain capacity-building efforts in emergency preparedness and response and raises an emerging concern of data integration in the concept of One Health that aims to address shared health threats at the human-animal-environment interface.


Assuntos
COVID-19 , Doenças Transmissíveis , Animais , Humanos , Pandemias , Programas Governamentais , Surtos de Doenças , Doenças Negligenciadas
8.
Int J Biol Macromol ; 253(Pt 3): 126830, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37717868

RESUMO

Interfacial solar vapor generation (ISVG) has shown extraordinary promise in achieving high-efficiency water purification. However, the rapid water supply often leads to excessive water in the solar absorber, resulting in undesired heat loss and a decrease in evaporation rate. To tackle this issue, we developed a bio-based solar evaporator comprising cellulose-based water retention resin (CRR) and straw-derived photothermal sponge. CRR serves as an effective water storage platform with a high binding capacity for water molecules, preventing water from entering the absorber and reducing the water evaporation enthalpy. The water management of CRR confines the solar-to-vapor conversion to the interface between CRR and the photothermal sponge, thereby eliminating the adverse effects of excess water. Additionally, the ISVG process operates based on the principle of Distribution-according-to-work, meaning that the quantity of generated vapor depends on the evolution of the sponge structure. Optimal sponge configuration enables evaporation rates of 2.28 and 1.53 kg/m2/h under solar irradiation of 1.0 and 0.5 kW/m2, respectively. Additionally, the obtained evaporator is capable of producing 7.1 kg/m2/day of freshwater in outdoor experiment. This report proposes a novel approach to designing an ISVG device that incorporates effective water management strategy for achieving high-efficiency water purification in real-world scenarios.


Assuntos
Bandagens , Água , Água Doce , Celulose , Gases
9.
Bioact Mater ; 28: 206-226, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37274446

RESUMO

Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts; however, their efficacy needs to be enhanced. Here we tested the hypotheses that the combination of decellularized porcine small intestinal submucosal extracellular matrix (SIS-ECM) with hCVPCs, hCMs, or dual of them (Mix, 1:1) could provide better therapeutic effects than the SIS alone, and dual hCVPCs with hCMs would exert synergic effects in cardiac repair. The data showed that the SIS patch well supported the growth of hCVPCs and hCMs. Epicardially implanted SIS-hCVPC, SIS-hCM, or SIS-Mix patches at 7-day post-myocardial infarction significantly ameliorated functional worsening, ventricular dilation and scar formation at 28- and 90-day post-implantation in C57/B6 mice, whereas the SIS only mildly improved function at 90-day post-implantation. Moreover, the SIS and SIS-cell patches improved vascularization and suppressed MI-induced cardiomyocyte hypertrophy and expression of Col1 and Col3, but only the SIS-hCM and the SIS-Mix patches increased the ratio of collagen III/I fibers in the infarcted hearts. Further, the SIS-cell patches stimulated cardiomyocyte proliferation via paracrine action. Notably, the SIS-Mix had better improvements in cardiac function and structure, engraftments, and cardiomyocyte proliferation. Proteomic analysis showed distinct biological functions of exclusive proteins secreted from hCVPCs and hCMs, and more exclusive proteins secreted from co-cultivated hCVPCs and hCMs than mono-cells involving in various functional processes essential for infarct repair. These findings are the first to demonstrate the efficacy and mechanisms of mono- and dual-hCVPC- and hCM-seeding SIS-ECM for repair of infarcted hearts based on the side-by-side comparison.

10.
Ying Yong Sheng Tai Xue Bao ; 34(4): 1063-1072, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37078326

RESUMO

Construction and optimization of ecological security network is an efficient way to ensure regional ecological security and achieve sustainable development. Based on the morphological spatial pattern analysis method, circuit theory and other methods, we constructed the ecological security network of the Shule River Basin. The PLUS model was used to predict the land use change in 2030, with the aim to explore the current ecological protection direction and propose reasonable optimization strategies. The results showed that there were 20 ecological sources in the Shule River Basin, with a total area of 15774.08 km2, accounting for 12.3% of the total area of study area. The ecological sources were mainly distributed in the south part of the study area. A total of 37 potential ecological corridors were extracted, including 22 important ecological corridors, which showed the overall spatial characteristics of vertical distribution. Meanwhile, 19 ecological pinch points and 17 ecological obstacle points were identified. We predicted that the expansion of construction land would continue to squeeze the ecological space by 2030, and identified 6 warning areas of ecological protection space to effectively avoid conflicts between ecological protection and economic development. After optimization, 14 new ecological sources and 17 stepping stones were added, and the circuitry, ratio of line to node and connectivity index of the ecological security network increased by 18.3%, 15.5%, and 8.2% respectively compared with those before optimization, forming a structurally stable ecological security network. The results could provide scientific basis for ecological security network optimization and ecological restoration.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Rios , China , Desenvolvimento Sustentável , Ecologia
11.
Biomed Chromatogr ; 37(8): e5656, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37060570

RESUMO

Vancomycin (VAN) has a narrow therapeutic window and variable pharmacokinetic properties, which require timely monitoring of plasma concentration to adjust the dosage for better effectiveness. A sensitive and quantitative immunochromatographic method was developed to detect VAN in plasma. The linear response range of the method to detect plasma VAN was 1.25-50 µg/mL. The intra- and inter-assay coefficients were 4.68% and 8.81%, respectively, while the recovery was 89.10%-98.32%. The clinical comparative experiment results demonstrated a good correlation (r > 0.90) between the fluorescent immunochromatographic strip test and the mass spectrum. In this study, a simple, rapid, and high-sensitivity immunochromatographic method was established for detecting VAN, which helped establish the basis for further application of monitoring plasma concentration.


Assuntos
Vancomicina , Cromatografia de Afinidade/métodos
12.
Front Cardiovasc Med ; 10: 1101765, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910524

RESUMO

Introduction: The primary factor for cardiovascular disease and upcoming cardiovascular events is atherosclerosis. Recently, carotid plaque texture, as observed on ultrasonography, is varied and difficult to classify with the human eye due to substantial inter-observer variability. High-resolution magnetic resonance (MR) plaque imaging offers naturally superior soft tissue contrasts to computed tomography (CT) and ultrasonography, and combining different contrast weightings may provide more useful information. Radiation freeness and operator independence are two additional benefits of M RI. However, other than preliminary research on MR texture analysis of basilar artery plaque, there is currently no information addressing MR radiomics on the carotid plaque. Methods: For the automatic segmentation of MRI scans to detect carotid plaque for stroke risk assessment, there is a need for a computer-aided autonomous framework to classify MRI scans automatically. We used to detect carotid plaque from MRI scans for stroke risk assessment pre-trained models, fine-tuned them, and adjusted hyperparameters according to our problem. Results: Our trained YOLO V3 model achieved 94.81% accuracy, RCNN achieved 92.53% accuracy, and MobileNet achieved 90.23% in identifying carotid plaque from MRI scans for stroke risk assessment. Our approach will prevent incorrect diagnoses brought on by poor image quality and personal experience. Conclusion: The evaluations in this work have demonstrated that this methodology produces acceptable results for classifying magnetic resonance imaging (MRI) data.

13.
Front Psychiatry ; 14: 1128971, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816399

RESUMO

Background and Aim: Fear of childbirth (FOC) is one of the most common mental health concerns among expectant fathers, which can cause adverse consequences for themselves and their families. A valid and accurate tool is the key to the identification of FOC. This study aimed to translate and culturally adapt the fathers' fear of childbirth scale (FFCS) into simplified Chinese and test the scale's psychometric properties among expectant fathers in mainland China. Methods: Researchers obtained translation permission and followed the multiphase translation guidelines to develop the Chinese version of the fathers' fear of childbirth scale (C-FFCS). Relevant psychometric properties were selected for the scale's psychometric validation on the basis of the Consensus-based Standards for the Selection of Health Status Measurement Instruments checklist. In this cross-sectional study, two samples of expectant fathers were collected in a university-affiliated hospital in Hangzhou between September and October 2022. Results: A total of 381 expectant fathers completed the C-FFCS, resulting in an effective response rate of 95.6%. The C-FFCS is a 3-factor structure consisting of 16 items, which explained 66.374% of the total variance. The content validity index of items ranged from 0.833 to 1.00, and the scale-level content validity index was 0.931. The confirmatory factor analysis confirmed the scale's 3-factor structure. Evidence of convergent validity (average variance extracted = 0.508-0.780) as well as discriminant validity offered excellent psychometric support. The Cronbach's α coefficient, McDonald's ω coefficient, intraclass correlation coefficient, Spearman-Brown coefficient, and Guttman split-half coefficient are within the satisfactory range (> 0.80). Significant correlations between the scores of the C-FFCS and Childbirth Attitude Questionnaire (r = 0.658, p < 0.01) and Fear of Birth Scale (r = 0.555, p < 0.01) both revealed good concurrent validity. The structure of C-FFCS was invariant across different parity groups, with no floor and ceiling effect. Conclusion: The C-FFCS was demonstrated to be a sound instrument with good reliability and validity for measuring Chinese expectant fathers' FOC levels. However, further studies are advocated to verify the C-FFCS among a larger sample that is more representative of the Chinese expectant father population.

14.
Med Care Res Rev ; 80(2): 205-215, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35815591

RESUMO

Inadequate consideration has been given to patient preferences for patient-centered care (PCC) across countries or cultures in our increasingly global society. We examined what 1,698 participants from the United States, Hong Kong, Philippines, and Australia described as important when making health care decisions. Analysis of frequencies following directed content coding of open-ended questions revealed differences in patients' preferences for doctor behaviors and decision-making considerations across countries. Being well informed by their doctor emerged as most important in decision-making, especially in Hong Kong. Participants in Australia and the United States wanted their doctor to meet their emotional needs. The safety and efficacy of treatments were the most common consideration, especially for Hong Kong. Findings suggest that doctors should focus on information exchange and identifying patient concerns about efficacy, lifestyle impact, cost, and recovery speed. Rather than assuming patients prefer shared decision-making, doctors must assess patient's decision control preferences.


Assuntos
Preferência do Paciente , Médicos , Humanos , Estados Unidos , Preferência do Paciente/psicologia , Tomada de Decisões , Assistência Centrada no Paciente , Participação do Paciente , Relações Médico-Paciente
15.
J Appl Anim Welf Sci ; 26(2): 218-228, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34470518

RESUMO

Enriched environment (EE) is an important animal experimental paradigm to decipher gene-environment interaction. It is thought to be efficient in aiding recovery from certain metabolism disorders or cognitive impairments. Recently, the effects of EE during adolescence in mice gradually draw much attention. We first established an EE model in adolescent mice, dissected lipid metabolism, and further examined baseline level of anxiety and depression by multiple behavioral tests, including open field test (OFT), elevated zero maze (EZM), tail suspension test (TST), and forced swimming test (FST). EE mice exhibited lower weights, lower cholesterol than standard housing (SH) mice. Behaviorally, EE mice traveled more distance and had higher velocity than SH mice in OFT and EZM. Besides, EE mice showed reduced anxiety levels in OFT and EZM. Furthermore, EE mice also had less immobility time than SH mice in TST and FST. Thus, these results suggest that EE during adolescence has metabolic and behavioral benefits in mice.


Assuntos
Ansiedade , Metabolismo dos Lipídeos , Animais , Camundongos , Ansiedade/metabolismo , Ansiedade/psicologia , Natação , Comportamento Animal
17.
Infect Drug Resist ; 15: 7339-7350, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36536860

RESUMO

Aim: To analyze the metabolites of the most common sepsis-related pathogen and their correlation with clinical indicators. Methods: Information of bacterial-infection patients in Huzhou Central hospital was retrospectively investigated and analyzed. The most common pathogen inducing sepsis was selected. Then, the metabolic profiles of pathogens from blood were detected by liquid chromatography/mass spectrometry. Cluster and classification analysis, KEGG pathway enrichment analysis, multidimensional OPLS-DA, Z scores, correlation analysis were used to analyze the metabolites. Results: Escherichia coli (E. coli) was the pathogen that caused the most infection (about 21%) and sepsis. Amino acids, peptides, terpene glycosides, carbohydrates were the main metabolites of E.coli and they were mainly digestive and endocrine-related compounds. Most of them were related to amino acids metabolism, cofactors and vitamins metabolism, biosynthesis of secondary metabolites, et al. Moreover, metabolites were involved in purine metabolism, neuroactive ligand-receptor interaction, ABC transporters, etc. Then, over 70 differential metabolites such as tyramine, tryptophan, 3- hydroxymalondialdehyde were screened in E.coli from nonseptic and septic patients. They were mainly involved in phenylalanine metabolism, tryptophan metabolism, protein digestion and absorption. Distribution of metabolites of E. coli from nonseptic and septic patients was obviously different. What is more, differential metabolites had evidently correlation with SOFA score, APPACHE II score, C-reactive protein, erythrocyte, platelet, aspartate aminotransferase, coagulation function, lactic acid (p < 0.01). Conclusion: The different metabolic profile of E. coli from nonseptic and septic patients indicated that differential metabolites might be associated with sepsis.

19.
Front Psychiatry ; 13: 958688, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072455

RESUMO

Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the Enhancing Neuroimaging Genetics through Meta-Analysis for TS (ENIGMA-TS) working group. The ENIGMA-TS working group is an international collaborative effort bringing together a large network of investigators who aim to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with TS genomic data, as well as equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and the identification of biomarkers that could help inform improved clinical practice.

20.
Urolithiasis ; 50(5): 545-556, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35913552

RESUMO

Calcium oxalate (CaOx) crystals can activate autophagy, causing damage to renal tubular epithelial cells (TECs). Puerarin has been shown to have protective and therapeutic effects against a variety of diseases by inhibiting autophagy activation. However, the protective effect of puerarin against CaOx crystals and the underlying molecular mechanisms are unclear. Cell Counting Kit-8 (CCK-8) assays were used to evaluate the effects of puerarin on cell viability. Intracellular reactive oxygen species (ROS) levels were measured by the cell-permeable fluorogenic probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Immunofluorescence, immunohistochemistry, and western blotting were used to examine the expression of SIRT1, Beclin1, p62, and LC3, and explore the underlying molecular mechanisms in vivo and in vitro. Puerarin treatment significantly attenuated CaOx crystal-induced autophagy of TECs and CaOx cytotoxicity to TECs by altering SIRT1 expression in vitro and in vivo, whereas the SIRT1-specific inhibitor EX527 exerted contrasting effects. In addition, we found that the protective effect of puerarin was related to the SIRT1/AKT/p38 signaling pathway. The findings suggest that puerarin regulates CaOx crystal-induced autophagy by activating the SIRT1-mediated signaling pathway, and they suggest a series of potential therapeutic targets and strategies for treating nephrolithiasis.


Assuntos
Oxalato de Cálcio , Cálculos Renais , Autofagia , Oxalato de Cálcio/metabolismo , Células Epiteliais/metabolismo , Humanos , Isoflavonas , Cálculos Renais/metabolismo , Estresse Oxidativo , Transdução de Sinais , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia
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