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1.
BMC Cardiovasc Disord ; 24(1): 331, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951773

RESUMO

BACKGROUND: Pulmonary embolisms (PEs) exhibit clinical features similar to those of acute coronary syndrome (ACS), including electrocardiographic abnormalities and elevated troponin levels, which frequently lead to misdiagnoses in emergency situations. CASE PRESENTATION: Here, we report a case of PE coinciding with chronic coronary syndrome in which the patient's condition was obscured by symptoms mimicking ACS. A 68-year-old female with syncope presented to the hospital. Upon admission, she was found to have elevated troponin levels and an electrocardiogram showing ST-segment changes across multiple leads, which initially led to a diagnosis of ACS. Emergency coronary arteriography revealed occlusion of the posterior branches of the left ventricle of the right coronary artery, but based on the complexity of the intervention, the occlusion was considered chronic rather than acute. On the 3rd day after admission, the patient experienced recurrent chest tightness and shortness of breath, which was confirmed as acute PE by emergency computed tomography pulmonary angiography. Following standardized anticoagulation treatment, the patient improved and was subsequently discharged. CONCLUSIONS: This case report highlights the importance of recognizing the nonspecific features of PE. Clinicians should be vigilant when identifying other clinical features that are difficult to explain accompanying the expected disease, and it is necessary to carefully identify the causes to prevent missed diagnoses or misdiagnoses.


Assuntos
Síndrome Coronariana Aguda , Anticoagulantes , Angiografia por Tomografia Computadorizada , Eletrocardiografia , Valor Preditivo dos Testes , Embolia Pulmonar , Humanos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/diagnóstico por imagem , Feminino , Idoso , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico por imagem , Diagnóstico Diferencial , Anticoagulantes/uso terapêutico , Angiografia Coronária , Doença Crônica , Resultado do Tratamento , Erros de Diagnóstico , Biomarcadores/sangue
2.
Front Public Health ; 12: 1407496, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957206

RESUMO

The study aimed to understand the main skills of older adult caregivers and find ways to improve these skills. We selected participants using a method called random cluster sampling, where caregivers from 17 different medical and nursing care facilities across seven districts in Hangzhou were chosen. We collected 492 valid questionnaires and conducted interviews with 150 people. To analyze the data, we used T-tests and Analysis of Variance (ANOVA) to identify what factors affect caregivers' skills. We also performed multiple regression analysis to explore these factors in more depth. The analysis showed that age (p = 0.041), annual income (p < 0.001), and having a training certificate (p < 0.001) significantly influence the skills of older adult caregivers. Specifically, caregivers' age and whether they had a training certificate were linked to how competent they were, with income being a very strong factor. The study highlighted a gap between the caregivers' current skills and the skills needed for high-quality care. This gap shows the need for training programs that are specifically tailored to the caregivers' diverse needs and cultural backgrounds. Medical and eldercare facilities should adjust their work and educational programs accordingly. It's also important to look at how caregivers are paid to make sure their salary reflects their skills and the quality of care they provide. Finally, it's crucial to integrate a comprehensive training program that leads to certification within eldercare organizations.


Assuntos
Cuidadores , Humanos , Cuidadores/educação , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , China , Inquéritos e Questionários , Adulto , Idoso de 80 Anos ou mais
3.
Nanoscale ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958068

RESUMO

In recent years, nanoporous materials, mainly represented by metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), have shown unparalleled potential in critical applications such as energy storage, gas separation and catalysis. The integration of MOFs/COFs into battery technology has garnered substantial research attention since it was found that such materials also play important roles in batteries. The highly controllable nanoporous features of MOFs/COFs enable the regulation of the solvation environment of lithium ions, thereby significantly improving the performance of lithium metal batteries. Moreover, the selective adsorption features of MOFs/COFs make them particularly useful for stabilising high nickel cathodes and sulfur cathodes. This review provides an overview of the application of MOFs/COFs in batteries, and explores potential future directions and challenges in this rapidly evolving interdisciplinary field.

4.
Pest Manag Sci ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958097

RESUMO

BACKGROUND: Aphid infestation adversely affects the yield and quality of crops. Rapid reproduction and insecticidal resistance have made controlling aphids in the field challenging. Therefore, the present study investigated the insecticidal property of Penicillium oxalicum (QLhf-1) and its mechanism of action against aphids, Hyalopterus arundimis Fabricius. RESULTS: Bioassay revealed that the control efficacy of the spores against aphids (86.30% and 89.05% on the third day and fifth day after infection, respectively) were higher than other components, such as the mycelium. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that QLhf-1 invaded the aphid cuticle through spores and used the aphid tissues as a nutrient source for growth and reproduction, causing stiffness and atrophy and a final death. Three extracellular enzymes, lipase, protease, and chitinase had a synergistic effect with spores, and they acted together to complete the infection process by degrading the aphid body wall and accelerating the infection process. CONCLUSION: The newly discovered endophytic penicillin strain P. oxalicum 'QLhf-1' can effectively kill aphids. The results provided strong evidence for the biological control of aphids, and lay a foundation for the development and utilization of QLhf-1. © 2024 Society of Chemical Industry.

5.
J Ethnopharmacol ; : 118513, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969151

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: 2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (TSG) is the principal bioactive compound contained in Polygonum multiflorum Thunb. (PMT), which is traditionally recorded to possess tonic and anti-aging efficacy. AIM OF THE STUDY: To identify the TSG-provided promotion on liver regeneration (LR) following partial hepatectomy (PHx) in mice and to explicate its involved mechanism. MATERIALS AND METHODS: The promotion of TSG on LR was evaluated by hematoxylin and eosin (H&E), 5-bromodeoxyuridinc (BrdU) and Ki-67 staining, and measuring the level of proliferating cell nuclear antigen (PCNA) and Cyclin D1 in mice with PHx at different time points. Gene Expression Omnibus (GEO, GSE15239) database and the label-free quantitative proteomics from liver of mice at 24 h after PHx were integrated to identify potential involved critical proteins, which were verified by Western-blot, Real-time polymerase chain reaction (RT-PCR), molecular docking and luciferase activity assay. Primary hepatocytes isolated from mice were used to investigate the TSG-provided promotion on proliferation in vitro. RESULTS: TSG (20 mg/kg) promoted LR in mice after PHx. Results from RNA expression data from clinical samples and proteomic analysis from liver tissues indicated that peroxisome proliferator-activated receptor α (PPARα)-mediated fatty acid metabolism pathway were crucially associated with the TSG-provided promotion on LR. TSG enhanced the nuclear translocation of PPARα and the mRNA expression of a series of PPARα-regulated downstream genes. In addition, TSG lowered hepatic triglyceride (TG) and non-esterified fatty acid (NEFA) amounts and increased hepatic adenosine triphosphate (ATP) level in mice after PHx. TSG up-regulated the transcriptional activity of PPARα in vitro. Next results displayed that TSG promoted cell proliferation as well as ATP level in mice primary hepatocytes, which were abolished when PPARα was suppressed. Meanwhile, the cell viability was also elevated in mice primary hepatocytes treated with ATP. CONCLUSION: Activating PPARα-mediated fatty acid ß-oxidation (FAO) pathway led to the production of ATP, which contributed to the TSG-provided promotion on LR after PHx in mice.

6.
Front Public Health ; 12: 1409214, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962763

RESUMO

Background: To explore the relationship between body mass index (BMI), age, sex, and blood pressure (systolic blood pressure, SBP; diastolic blood pressure, DBP) in children during COVID-19, providing reference for the prevention and screening of hypertension in children. Methods: This study adopted a large-scale cross-sectional design to investigate the association between BMI and blood pressure in 7-17-year-old students in City N, China, during COVID-19. Thirty-six primary and secondary schools in City N were sampled using a stratified cluster sampling method. A total of 11,433 students aged 7-17 years in City N, China, were selected for blood pressure (Diastolic blood pressure, DBP, Systolic blood pressure, SBP), height, and weight, Resting heart rate (RHR), chest circumference, measurements, and the study was written using the STROBE checklist. Data analysis was conducted using SPSS 26.0, calculating the mean and standard deviation of BMI and blood pressure for male and female students in different age groups. Regression analysis was employed to explore the impact of BMI, age, and sex on SBP and DBP, and predictive models were established. The model fit was evaluated using the model R2. Results: The study included 11,287 primary and secondary school students, comprising 5,649 boys and 5,638 girls. It was found that with increasing age, BMI and blood pressure of boys and girls generally increased. There were significant differences in blood pressure levels between boys and girls in different age groups. In regression models, LC, Age, BMI, and chest circumference show significant positive linear relationships with SBP and DBP in adolescents, while RHR exhibits a negative linear relationship with SBP. These factors were individually incorporated into a stratified regression model, significantly enhancing the model's explanatory power. After including factors such as Age, Gender, and BMI, the adjusted R2 value showed a significant improvement, with Age and BMI identified as key predictive factors for SBP and DBP. The robustness and predictive accuracy of the model were further examined through K-fold cross-validation and independent sample validation methods. The validation results indicate that the model has a high accuracy and explanatory power in predicting blood pressure in children of different weight levels, especially among obese children, where the prediction accuracy is highest. Conclusion: During COVID-19, age, sex, and BMI significantly influence blood pressure in children aged 7-17 years, and predictive models for SBP and DBP were established. This model helps predict blood pressure in children and reduce the risk of cardiovascular diseases. Confirmation of factors such as sex, age, and BMI provide a basis for personalized health plans for children, especially during large-scale infectious diseases, providing guidance for addressing health challenges and promoting the health and well-being of children.


Assuntos
Pressão Sanguínea , Índice de Massa Corporal , COVID-19 , Humanos , Adolescente , Criança , Masculino , Feminino , Estudos Transversais , China/epidemiologia , Pressão Sanguínea/fisiologia , Hipertensão , Fatores Sexuais , SARS-CoV-2 , Fatores Etários
7.
Sci Rep ; 14(1): 15205, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956306

RESUMO

Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and prognosis in septic patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. The primary and secondary outcomes were 28-day and 90-day mortality. The association between PIV and outcomes was assessed by Kaplan-Meier curves, Cox regression analysis, restricted cubic spline curves and subgroup analysis. A total of 11,331 septic patients were included. Kaplan-Meier curves showed that septic patients with higher PIV had lower 28-day survival rate. In multivariable Cox regression analysis, log2-PIV was positively associated with the risk of 28-day mortality [HR (95% CI) 1.06 (1.03, 1.09), P < 0.001]. The relationship between log2-PIV and 28-day mortality was non-linear with a predicted inflection point at 8. To the right of the inflection point, high log2-PIV was associated with an increased 28-day mortality risk [HR (95% CI) 1.13 (1.09, 1.18), P < 0.001]. However, to the left of this point, this association was non-significant [HR (95% CI) 1.01 (0.94, 1.08), P = 0.791]. Similar results were found for 90-day mortality. Our study showed a non-linear relationship between PIV and 28-day and 90-day mortality risk in septic patients.


Assuntos
Sepse , Humanos , Sepse/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Prognóstico , Inflamação/mortalidade , Estimativa de Kaplan-Meier , Biomarcadores , Unidades de Terapia Intensiva , Modelos de Riscos Proporcionais
8.
Cell Biosci ; 14(1): 88, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956702

RESUMO

This study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer's Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD single-cell RNA sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4's role in ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic ferroptosis in AD. Silencing NOX4 mitigated ferroptosis, improved cognition, reduced Aß and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic ferroptosis, underscoring its significance in AD progression.

9.
Phytochemistry ; : 114208, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972441

RESUMO

Acanthopanacis cortex (the dried root bark of Acanthopanax gracilistylus W. W. Smith) has been used for the treatment of rheumatic diseases in China for over 2000 years. Four previously undescribed lignans (1-4) and 12 known lignans (5-16) were isolated from Acanthopanacis cortex. In this study, the inhibitory activities of compounds 1-16 against neutrophil elastase (NE), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are reported. The results show that compounds 1-16 exhibit weak inhibitory activities against NE and COX-1. However, compounds 2, 6∼8 and 13∼16 demonstrate better COX-2 inhibitory effects with IC50 values from 0.75 to 8.17 µΜ. These findings provide useful information for the search for natural selective COX-2 inhibitors.

10.
J Gastrointestin Liver Dis ; 33(2): 269-277, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38944855

RESUMO

Colorectal cancer is a prevalent malignancy, with advanced and metastatic forms exhibiting poor treatment outcomes and high relapse rates. To enhance patient outcomes, a comprehensive understanding of the pathophysiological processes and the development of targeted therapies are imperative. The high heterogeneity of colorectal cancer demands precise and personalized treatment strategies. Colorectal cancer organoids, a three-dimensional in vitro model, have emerged as a valuable tool for replicating tumor biology and exhibit promise in scientific research, disease modeling, drug screening, and personalized medicine. In this review, we present an overview of colorectal cancer organoids and explore their applications in research and personalized medicine, while also discussing potential future developments in this field.


Assuntos
Neoplasias Colorretais , Organoides , Medicina de Precisão , Humanos , Organoides/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Animais
11.
Biomedicines ; 12(6)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38927569

RESUMO

Previous studies have suggested an association between Proton Pump Inhibitors (PPIs) and the progression of chronic kidney disease (CKD). This study aims to assess the association between PPI use and CKD progression by analysing estimated glomerular filtration rate (eGFR) trajectories using a process mining approach. We conducted a retrospective cohort study from 1 January 2006 to 31 December 2011, utilising data from the Stockholm Creatinine Measurements (SCREAM). New users of PPIs and H2 blockers (H2Bs) with CKD (eGFR < 60) were identified using a new-user and active-comparator design. Process mining discovery is a technique that discovers patterns and sequences in events over time, making it suitable for studying longitudinal eGFR trajectories. We used this technique to construct eGFR trajectory models for both PPI and H2B users. Our analysis indicated that PPI users exhibited more complex and rapidly declining eGFR trajectories compared to H2B users, with a 75% increased risk (adjusted hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.49 to 2.06) of transitioning from moderate eGFR stage (G3) to more severe stages (G4 or G5). These findings suggest that PPI use is associated with an increased risk of CKD progression, demonstrating the utility of process mining for longitudinal analysis in epidemiology, leading to an improved understanding of disease progression.

12.
Sci Rep ; 14(1): 14482, 2024 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914707

RESUMO

Artificial intelligence (AI) decision support systems in pediatric healthcare have a complex application background. As an AI decision support system (AI-DSS) can be costly, once applied, it is crucial to focus on its performance, interpret its success, and then monitor and update it to ensure ongoing success consistently. Therefore, a set of evaluation indicators was explicitly developed for AI-DSS in pediatric healthcare, enabling continuous and systematic performance monitoring. The study unfolded in two stages. The first stage encompassed establishing the evaluation indicator set through a literature review, a focus group interview, and expert consultation using the Delphi method. In the second stage, weight analysis was conducted. Subjective weights were calculated based on expert opinions through analytic hierarchy process, while objective weights were determined using the entropy weight method. Subsequently, subject and object weights were synthesized to form the combined weight. In the two rounds of expert consultation, the authority coefficients were 0.834 and 0.846, Kendall's coordination coefficient was 0.135 in Round 1 and 0.312 in Round 2. The final evaluation indicator set has three first-class indicators, fifteen second-class indicators, and forty-seven third-class indicators. Indicator I-1(Organizational performance) carries the highest weight, followed by Indicator I-2(Societal performance) and Indicator I-3(User experience performance) in the objective and combined weights. Conversely, 'Societal performance' holds the most weight among the subjective weights, followed by 'Organizational performance' and 'User experience performance'. In this study, a comprehensive and specialized set of evaluation indicators for the AI-DSS in the pediatric outpatient clinic was established, and then implemented. Continuous evaluation still requires long-term data collection to optimize the weight proportions of the established indicators.


Assuntos
Inteligência Artificial , Sistemas de Apoio a Decisões Clínicas , Humanos , Pediatria/métodos , Instituições de Assistência Ambulatorial , Criança
14.
Biochem Soc Trans ; 52(3): 1243-1251, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38884788

RESUMO

Mitochondrial DNA replication is initiated by the transcription of mitochondrial RNA polymerase (mtRNAP), as mitochondria lack a dedicated primase. However, the mechanism determining the switch between continuous transcription and premature termination to generate RNA primers for mitochondrial DNA (mtDNA) replication remains unclear. The pentatricopeptide repeat domain of mtRNAP exhibits exoribonuclease activity, which is required for the initiation of mtDNA replication in Drosophila. In this review, we explain how this exonuclease activity contributes to primer synthesis in strand-coupled mtDNA replication, and discuss how its regulation might co-ordinate mtDNA replication and transcription in both Drosophila and mammals.


Assuntos
Replicação do DNA , DNA Mitocondrial , Mitocôndrias , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Animais , Mitocôndrias/metabolismo , Mitocôndrias/genética , Humanos , RNA Polimerases Dirigidas por DNA/metabolismo , Transcrição Gênica , Drosophila/genética , Drosophila/metabolismo , Exorribonucleases/metabolismo , Exorribonucleases/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo
15.
Lung ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914868

RESUMO

BACKGROUND: Critically ill patients with chronic obstructive pulmonary disease (COPD) face significant mortality after hospital discharge. Delirium is common in patients with COPD, but its impact on long-term mortality in critically ill COPD patients who survive to discharge remains uncertain. METHODS: Critically ill patients with COPD who survived to discharge were selected from the Medical Information Mart for Intensive Care IV database. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. The primary outcome was 365- and 180-day mortality after discharge. The secondary outcomes included 90- and 30-day mortality following discharge, length of intensive care unit (ICU) and hospital stays, and nursing care needs after hospital discharge. RESULTS: Of the 2621 survivors of critically ill COPD patients, 982 had suffered delirium during their ICU stay and 709 died within 365 days after hospital discharge. Delirium was significantly associated with 365-day mortality after hospital discharge (adjusted hazard ratio [HR] 1.22; 95% confidence interval [CI] 1.02-1.47). The results were consistent for 180-, 90-, and 30-day post-discharge mortality (adjusted HR [95% CI]: 1.35 [1.09-1.66], 1.48 [1.16-1.89], and 1.68 [1.21-2.32], respectively). Additionally, patients with delirium had longer ICU and hospital stay (adjusted ß 2.75; 95% CI 2.35-3.16 and 4.25; 95% CI 3.51-4.98, respectively) and increased nursing care needs after hospital discharge (adjusted odds ratio, 1.56; 95% CI 1.13-2.14). CONCLUSION: ICU delirium was an independent risk factor for both long-term and short-term mortality in critically ill patients with COPD who survived to discharge.

16.
mBio ; : e0114424, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916345

RESUMO

The cAMP receptor proteins (CRPs) play a critical role in bacterial environmental adaptation by regulating global gene expression levels via cAMP binding. Here, we report the structure of DdrI, a CRP family protein from Deinococcus radiodurans. Combined with biochemical, kinetic, and molecular dynamics simulations analyses, our results indicate that DdrI adopts a DNA-binding conformation in the absence of cAMP and can form stable complexes with the target DNA sequence of classical CRPs. Further analysis revealed that the high-affinity cAMP binding pocket of DdrI is partially filled with Tyr113-Arg55-Glu65 sidechains, mimicking the anti-cAMP-mediated allosteric transition. Moreover, the second syn-cAMP binding site of DdrI at the protein-DNA interface is more negatively charged compared to that of classical CRPs, and manganese ions can enhance its DNA binding affinity. DdrI can also bind to a target sequence that mimics another transcription factor, DdrO, suggesting potential cross-talk between these two transcription factors. These findings reveal a class of CRPs that are independent of cAMP activation and provide valuable insights into the environmental adaptation mechanisms of D. radiodurans.IMPORTANCEBacteria need to respond to environmental changes at the gene transcriptional level, which is critical for their evolution, virulence, and industrial applications. The cAMP receptor protein (CRP) of Escherichia coli (ecCRP) senses changes in intracellular cAMP levels and is a classic example of allosteric effects in textbooks. However, the structures and biochemical activities of CRPs are not generally conserved and there exist different mechanisms. In this study, we found that the proposed CRP from Deinococcus radiodurans, DdrI, exhibited DNA binding ability independent of cAMP binding and adopted an apo structure resembling the activated CRP. Manganese can enhance the DNA binding of DdrI while allowing some degree of freedom for its target sequence. These results suggest that CRPs can evolve to become a class of cAMP-independent global regulators, enabling bacteria to adapt to different environments according to their characteristics. The first-discovered CRP family member, ecCRP (or CAP) may well not be typical of the family and be very different to the ancestral CRP-family transcription factor.

17.
Am J Physiol Cell Physiol ; 327(1): C168-C183, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38826139

RESUMO

In ovarian cancer (OC), identifying key molecular players in disease escalation and chemoresistance remains critical. Our investigation elucidates the role of the DNA polymerase mu (POLM), especially G312R mutation, in propelling oncogenesis through dual pathways. POLMG312R markedly augments the ribonucleotide insertion capability of POLM, precipitating genomic instability. In addition, our research reveals that POLMG312R perturbs collagen alpha-1 (XI) chain (COL11A1) expression-a gene that plays a key role in oncogenesis-and modulates the NF-κB signaling pathway, alters the secretion of downstream inflammatory cytokines, and promotes tumor-macrophage interactions. We illustrate a bidirectional regulatory interaction between POLM, particularly its G312R variant, and COL11A1. This interaction regulates NF-κB signaling, culminating in heightened malignancy and resistance to chemotherapy in OC cells. These insights position the POLM as a potential molecular target for OC therapy, shedding light on the intricate pathways underpinning POLM variant disease progression.NEW & NOTEWORTHY Our research reveals that POLM plays an important role in ovarian cancer development, especially the mutation G312R. We uncover the POLMG312R mutation as a driver of genomic instability in ovarian cancer via aberrant ribonucleotide incorporation. We reveal that POLMG312R upregulates COL11A1 and activates NF-κB signaling, contributing to tumor progression and chemoresistance. This study identifies the POLM-COL11A1-NF-κB axis as a novel oncogenic pathway.


Assuntos
Colágeno Tipo XI , Instabilidade Genômica , NF-kappa B , Neoplasias Ovarianas , Transdução de Sinais , Feminino , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Instabilidade Genômica/genética , NF-kappa B/metabolismo , NF-kappa B/genética , Colágeno Tipo XI/genética , Colágeno Tipo XI/metabolismo , Linhagem Celular Tumoral , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Mutação , Animais
18.
Int Immunopharmacol ; 137: 112366, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38852526

RESUMO

AIMS: Endometriosis is characterized by an abnormal immune microenvironment. Despite the extensive use of immune therapies, the application of immune checkpoint inhibitors in endometriosis lacks confidence due to the instability of preclinical research data. This study aims to elucidate the regulation of the immune inhibitory checkpoint VISTA and its effects on T cells from the perspective of microbiota and metabolism. MAIN METHODS: We divided endometriosis patients into high and low groups based on the expression levels of VISTA in lesion tissues. We collected peritoneal fluid samples from these two groups and performed 16 s RNA sequencing and metabolomics analysis to investigate microbial diversity and differential metabolites. Through combined analysis, we identified microbial-associated metabolites and validated their correlation with VISTA and CD8 + T cells using ELISA and immunofluorescence. In vitro experiments were conducted to confirm the regulatory relationship among these factors. KEY FINDINGS: Our findings revealed a distinct correlation between VISTA expression and the microbial colony Escherichia.Shigella. Moreover, we identified the metabolites LTD4-d5 and 2-n-Propylthiazolidine-4-carboxylic acid as being associated with both Escherichia.Shigella and VISTA expression. In vitro experiments confirmed the inhibitory effects of these metabolites on VISTA expression, while they demonstrated a positive regulation of CD8 + T cell infiltration into endometriotic lesions. SIGNIFICANCE: This study reveals the connection between microbial diversity, metabolites, and VISTA expression in the immune microenvironment of endometriosis, providing potential targets for therapeutic interventions.

19.
Imeta ; 3(1): e165, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38868519

RESUMO

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.

20.
Medicine (Baltimore) ; 103(23): e38421, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847682

RESUMO

PURPOSE: The goal of this study was to evaluate the dose-response relationship between dexmedetomidine and propofol in sedating patients and to determine the optimal dosage of dexmedetomidine during gastrointestinal endoscopy. METHODS: One hundred fifty patients were divided into 5 groups, each receiving a loading dose of dexmedetomidine (0.4, 0.6, 0.8, 1.0 µg/kg) or saline, with propofol for sedation. The median effective concentration (EC50) of propofol was calculated using the modified Dixon up-and-down approach. Adverse effects, vital signs, procedure, and recovery times were recorded. RESULTS: The EC50 of propofol in groups NS, D0.4, D0.6, D0.8, and D1.0 were 3.02, 2.44, 1.97, 1.85, and 1.83 µg/mL, respectively. Heart rate in the dexmedetomidine groups decreased more than the NS group (P < .001). The mean arterial pressure (MAP) in the NS group experienced a decline compared to groups D0.8 and D1.0 when the plasma concentration and effect-site concentration reached equilibrium. Additionally, the respiratory rate was found to be lower in groups NS, D0.4, D0.6, and D0.8 (P < .05). Recovery time in groups D0.8 and D1.0 was longer than the NS group (P < .05). Bruggemann comfort scales score was higher in group D1.0 (P < .05). No significant difference was found in the incidences of hypotension and bradycardia, and the dose of ephedrine and atropine. Respiratory depression was significantly reduced in groups D0.8 and D1.0 compared to the NS group. CONCLUSION: A single dose of 0.6 to 0.8 µg/kg of dexmedetomidine should be recommended in combination with propofol for gastrointestinal endoscopy. And the EC50 of propofol is 1.97 to 1.85 µg/mL.


Assuntos
Dexmedetomidina , Relação Dose-Resposta a Droga , Endoscopia Gastrointestinal , Hipnóticos e Sedativos , Propofol , Humanos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/efeitos adversos , Propofol/administração & dosagem , Propofol/efeitos adversos , Masculino , Feminino , Método Duplo-Cego , Endoscopia Gastrointestinal/métodos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Adulto , Pessoa de Meia-Idade , Frequência Cardíaca/efeitos dos fármacos
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