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1.
BMC Cancer ; 24(1): 620, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38773564

RESUMO

BACKGROUND: The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC. METHODS: Information for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected. Patients were divided into adjuvant TACE and observation groups according to whether they received adjuvant TACE or not. The recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after propensity score matching (PSM). RESULTS: Of the 225 patients enrolled, the median time of HCC recurrence was 11 months (IQR, 6-16 months). After repeated surgery or radiofrequency ablation (RFA) for recurrent tumors, 45 patients (20%) received adjuvant TACE while the remaining 180 (80%) didn't. There were no significant differences in RFS (P = 0.325) and OS (P = 0.072) between adjuvant TACE and observation groups before PSM. There were also no significant differences in RFS (P = 0.897) and OS (P = 0.090) between the two groups after PSM. Multivariable analysis suggested that multiple tumors, liver cirrhosis, and RFA were independent risk factors for the re-recurrence of HCC. CONCLUSION: Adjuvant TACE after repeated resection or ablation for early recurrent HCCs was not associated with a long-term survival benefit in this single-center cohort.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Pontuação de Propensão , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Quimioembolização Terapêutica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Hepatectomia/métodos , Idoso , Ablação por Radiofrequência/métodos , Estudos Retrospectivos , Terapia Combinada , Resultado do Tratamento , Quimioterapia Adjuvante/métodos
2.
Int J Med Sci ; 21(6): 1079-1090, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774751

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a rare, chronic and progressively worsening lung disease that poses a significant threat to patient prognosis, with a mortality rate exceeding that of some common malignancies. Effective methods for early diagnosis and treatment remain for this condition are elusive. In our study, we used the GEO database to access second-generation sequencing data and associated clinical information from IPF patients. By utilizing bioinformatics techniques, we identified crucial disease-related genes and their biological functions, and characterized their expression patterns. Furthermore, we mapped out the immune landscape of IPF, which revealed potential roles for novel kinase 1 and CD8+T cells in disease progression and outcome. These findings can aid the development of new strategies for the clinical diagnosis and treatment of IPF.


Assuntos
Linfócitos T CD8-Positivos , Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/tratamento farmacológico , Linfócitos T CD8-Positivos/imunologia , Biologia Computacional , Progressão da Doença , Prognóstico
3.
Sci Rep ; 14(1): 10833, 2024 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-38734835

RESUMO

Our aim was to develop a machine learning-based predictor for early mortality and severe intraventricular hemorrhage (IVH) in very-low birth weight (VLBW) preterm infants in Taiwan. We collected retrospective data from VLBW infants, dividing them into two cohorts: one for model development and internal validation (Cohort 1, 2016-2021), and another for external validation (Cohort 2, 2022). Primary outcomes included early mortality, severe IVH, and early poor outcomes (a combination of both). Data preprocessing involved 23 variables, with the top four predictors identified as gestational age, birth body weight, 5-min Apgar score, and endotracheal tube ventilation. Six machine learning algorithms were employed. Among 7471 infants analyzed, the selected predictors consistently performed well across all outcomes. Logistic regression and neural network models showed the highest predictive performance (AUC 0.81-0.90 in both internal and external validation) and were well-calibrated, confirmed by calibration plots and the lowest two mean Brier scores (0.0685 and 0.0691). We developed a robust machine learning-based outcome predictor using only four accessible variables, offering valuable prognostic information for parents and aiding healthcare providers in decision-making.


Assuntos
Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Aprendizado de Máquina , Humanos , Recém-Nascido , Feminino , Masculino , Estudos Retrospectivos , Taiwan/epidemiologia , Lactente , Prognóstico , Hemorragia Cerebral/mortalidade , Idade Gestacional , Hemorragia Cerebral Intraventricular/mortalidade , Hemorragia Cerebral Intraventricular/epidemiologia , Mortalidade Infantil , Peso ao Nascer , Doenças do Prematuro/mortalidade
4.
Am J Cancer Res ; 14(4): 1609-1621, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726282

RESUMO

Young breast cancer (YBC) patients often face a poor prognosis, hence it's necessary to construct a model that can accurately predict their long-term survival in early stage. To realize this goal, we utilized data from the Surveillance, Epidemiology, and End Results (SEER) databases between January 2010 and December 2020, and meanwhile, enrolled an independent external cohort from Tianjin Medical University Cancer Institute and Hospital. The study aimed to develop and validate a prediction model constructed using the Random Survival Forest (RSF) machine learning algorithm. By applying the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, we pinpointed key prognostic factors for YBC patients, which were used to create a prediction model capable of forecasting the 3-year, 5-year, 7-year, and 10-year survival rates of YBC patients. The RSF model constructed in the study demonstrated exceptional performance, achieving C-index values of 0.920 in the training set, 0.789 in the internal validation set, and 0.701 in the external validation set, outperforming the Cox regression model. The model's calibration was confirmed by Brier scores at various time points, showcasing its excellent accuracy in prediction. Decision curve analysis (DCA) underscored the model's importance in clinical application, and the Shapley Additive Explanations (SHAP) plots highlighted the importance of key variables. The RSF model also proved valuable in risk stratification, which has effectively categorized patients based on their survival risks. In summary, this study has constructed a well-performed prediction model for the evaluation of prognostic factors influencing the long-term survival of early-stage YBC patients, which is significant in risk stratification when physicians handle YBC patients in clinical settings.

5.
Front Surg ; 11: 1366982, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726470

RESUMO

Introduction: Radical nephroureterectomy with concurrent bladder cuff excision (RNUBCE) is the gold standard surgical approach for high-risk primary upper tract urothelial carcinoma (UTUC). Given the notably high incidence of bladder tumor recurrence following this procedure, this study aimed to evaluate the effect and safety of intraoperative mitomycin-C (MMC) instillation vs. deferred instillation on overall oncological outcomes following robot-assisted RNUBCE. Methods: This is a retrospective chart review study. Patients with non-invasive (N0, not T3/T4) UTUC who underwent robotic RNUBCE combined an intraoperative MMC instillation or a deferred MMC instillation after surgery at a medical center in Taiwan between November 2013 and June 2020 were eligible for inclusion. Patients with prior bladder UC, carcinomas of other origins, received neoadjuvant chemotherapy, and had undergone kidney transplantation were excluded. All surgeries were executed by a single surgical team under the guidance of the same surgeon. The primary outcomes was the risk of bladder tumor recurrence between patients received intraoperative (IO) vs. deferred MMC instillation postoperatively (PO) during one-year follow-up. The secondary outcome was postoperative adverse events assessed by the Clavien-Dindo classification. Univariate and multivariable Cox regression analyses were performed to determine the associations between study variables and the outcomes. Results: A total of 54 patients were included in the analysis. 12 (22.2%) patients experienced a bladder tumor recurrence during follow-up (IO: 7.7%, PO: 35.7%, p < 0.021). After adjustment in the multivariable, intraoperative MMC instillation was significantly associated with lower risk of bladder recurrence [adjusted hazard ratio (aHR) = 0.15, 95% CI: 0.03-0.81, p = 0.028]. No MMC-related Clavien-Dindo Grade III-IV adverse events were found in either group. Conclusion: IIntraoperative MMC instillation is safe and associated with a lower bladder tumor recurrence risk in patients undergoing robotic RNUBCE for UTUC than deferred instillation. Future large, prospective studies are still warranted to confirm the findings.

6.
Nutrients ; 16(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38732585

RESUMO

BACKGROUND: This study aimed to examine the prevalence and associated factors of malnutrition in older community-dwellers and explore the interaction between associated factors. METHODS: A total of 474,467 older community-dwellers aged 65 or above were selected in Guangzhou, China. We used a two-step methodology to detect the associated factors of malnutrition and constructed logistic regression models to explore the influencing factors and interactive effects on three patterns of malnutrition. RESULTS: The prevalence of malnutrition was 22.28%. Older adults with both hypertension and diabetes (RERI = 0.13), both meat or fish diet and hypertension (RERI = 0.79), and both meat or fish diet and diabetes (RERI = 0.81) had positive additive interaction effects on the risk of obesity, whereas those on a vegetarian diet with hypertension (RERI = -0.25) or diabetes (RERI = -0.19) had negative additive interaction effects. Moreover, the interactions of physical activity with a meat or fish diet (RERI = -0.84) or dyslipidemia (RERI = -0.09) could lower the risk of obesity. CONCLUSIONS: Malnutrition was influenced by different health factors, and there were interactions between these influencing factors. Pertinent dietary instruction should be given according to different nutritional status indexes and the prevalence of metabolic diseases to avoid the occurrences of malnutrition among older adults.


Assuntos
Mineração de Dados , Hipertensão , Desnutrição , Humanos , Idoso , China/epidemiologia , Masculino , Feminino , Desnutrição/epidemiologia , Prevalência , Hipertensão/epidemiologia , Fatores de Risco , Idoso de 80 Anos ou mais , Vida Independente , Estado Nutricional , Diabetes Mellitus/epidemiologia , Obesidade/epidemiologia , Dieta , Exercício Físico , Modelos Logísticos , Dislipidemias/epidemiologia
7.
Pediatr Pulmonol ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742254

RESUMO

With the progress in neonatal intensive care, there has been an increase in the survival rates of premature infants. However, this has also led to an increased incidence of neonatal hyperoxia lung injury and bronchopulmonary dysplasia (BPD), whose pathogenesis is believed to be influenced by various prenatal and postnatal factors, although the exact mechanisms remain unclear. Recent studies suggest that multiple mechanisms might be involved in neonatal hyperoxic lung injury and BPD, with sex also possibly playing an important role, and numerous drugs have been proposed and shown promise for improving the treatment outcomes of hyperoxic lung injury. Therefore, this paper aims to analyze and summarize sex differences in neonatal hyperoxic lung injury, potential pathogenesis and treatment progress to provide new ideas for basic and clinical research in this field.

8.
BMC Bioinformatics ; 25(1): 177, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704528

RESUMO

BACKGROUND: Hepatitis B virus (HBV) integrates into human chromosomes and can lead to genomic instability and hepatocarcinogenesis. Current tools for HBV integration site detection lack accuracy and stability. RESULTS: This study proposes a deep learning-based method, named ViroISDC, for detecting integration sites. ViroISDC generates corresponding grammar rules and encodes the characteristics of the language data to predict integration sites accurately. Compared with Lumpy, Pindel, Seeksv, and SurVirus, ViroISDC exhibits better overall performance and is less sensitive to sequencing depth and integration sequence length, displaying good reliability, stability, and generality. Further downstream analysis of integrated sites detected by ViroISDC reveals the integration patterns and features of HBV. It is observed that HBV integration exhibits specific chromosomal preferences and tends to integrate into cancerous tissue. Moreover, HBV integration frequency was higher in males than females, and high-frequency integration sites were more likely to be present on hepatocarcinogenesis- and anti-cancer-related genes, validating the reliability of the ViroISDC. CONCLUSIONS: ViroISDC pipeline exhibits superior precision, stability, and reliability across various datasets when compared to similar software. It is invaluable in exploring HBV infection in the human body, holding significant implications for the diagnosis, treatment, and prognosis assessment of HCC.


Assuntos
Vírus da Hepatite B , Integração Viral , Vírus da Hepatite B/genética , Humanos , Integração Viral/genética , Software , Aprendizado Profundo , Masculino , Feminino , Hepatite B/genética , Hepatite B/virologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Biologia Computacional/métodos
9.
Int J Biomed Imaging ; 2024: 6114826, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706878

RESUMO

A challenge in accurately identifying and classifying left ventricular hypertrophy (LVH) is distinguishing it from hypertrophic cardiomyopathy (HCM) and Fabry disease. The reliance on imaging techniques often requires the expertise of multiple specialists, including cardiologists, radiologists, and geneticists. This variability in the interpretation and classification of LVH leads to inconsistent diagnoses. LVH, HCM, and Fabry cardiomyopathy can be differentiated using T1 mapping on cardiac magnetic resonance imaging (MRI). However, differentiation between HCM and Fabry cardiomyopathy using echocardiography or MRI cine images is challenging for cardiologists. Our proposed system named the MRI short-axis view left ventricular hypertrophy classifier (MSLVHC) is a high-accuracy standardized imaging classification model developed using AI and trained on MRI short-axis (SAX) view cine images to distinguish between HCM and Fabry disease. The model achieved impressive performance, with an F1-score of 0.846, an accuracy of 0.909, and an AUC of 0.914 when tested on the Taipei Veterans General Hospital (TVGH) dataset. Additionally, a single-blinding study and external testing using data from the Taichung Veterans General Hospital (TCVGH) demonstrated the reliability and effectiveness of the model, achieving an F1-score of 0.727, an accuracy of 0.806, and an AUC of 0.918, demonstrating the model's reliability and usefulness. This AI model holds promise as a valuable tool for assisting specialists in diagnosing LVH diseases.

10.
Data Brief ; 54: 110438, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38708306

RESUMO

Tennis is a popular sport, and the introduction of technology has allowed players to diversify their training. Tennis ball tracking is currently a focal point, serving not only to assist referees but also to enhance sports analysis. We introduce the Tennis Shot Side-View and Top-View Dataset, which serves as an invaluable resource for analyzing tennis movements and verifying landing positions after flight. This dataset combines side-view and top-view video clips, capturing various shot types and player movements from both outdoor and indoor fields. The dataset includes the actual ball positions of each clip for verification purposes. The Tennis Shot Side-View and Top-View Dataset represents a significant advancement in tennis research. Its multidimensional nature opens doors for in-depth player analysis, performance enhancement, and strategy development. We believe that this dataset will be a valuable asset to the tennis community, fostering innovation and excellence in the sport.

11.
Environ Toxicol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717028

RESUMO

Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1ß levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.

13.
Cell Calcium ; 121: 102875, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38701708

RESUMO

The core functions of the anoctamins are Cl- channel activity and phosphatidylserine (and perhaps other lipids) scrambling. These functions have been extensively studied in various tissues and cells. However, another function of the anoctamins that is less recognized and minimally explored is as tethers at membrane contact sites. This short review aims to examine evidence supporting the localization of the anoctamins at membrane contact sites, their tether properties, and their functions as tethers.

14.
Acupunct Med ; : 9645284241248465, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702866

RESUMO

BACKGROUND: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). METHODS: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). RESULTS: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1ß, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. CONCLUSION: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.

15.
Child Care Health Dev ; 50(3): e13270, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38706405

RESUMO

INTRODUCTION: Chronic physical disease (CPD) makes life filled with many negative events in adolescents, but not all adolescents experiencing negative life events proceed to develop emotional distress, only those with low emotional distress tolerance (EDT). A valid and reliable scale to measure EDT in CPD adolescents is important for caring for their emotional distress. Therefore, the purpose of this study is to translate the 15-item English version Distress Tolerance Scale (DTS) into a Chinese version and then validate the scale for measuring EDT of adolescents with CPD. METHODS: The 15-item English version DTS was translated into a Chinese version using the translation guidelines for cross-cultural research. Two cohorts of adolescents with CPD were recruited from four hospitals in southern Taiwan, with the first cohort including 124 adolescents with CPD employed to conduct exploratory factor analysis, corrected item-total correlation and reliability testing, while the second cohort, consisting of 238 adolescents with CPD, was utilized to examine confirmatory factor analysis and concurrent validity. RESULTS: The two-factor nine-item Chinese version DTS for Adolescents with CPD (C-DTS-A) was developed. Lower scores of the C-DTS-A were significantly associated with higher diabetes distress, poorer self-management, and worse glycaemic control; their correlation coefficients sequentially were -.40, .17 and -.23. Cronbach's α and the test-retest reliability of the two-factor C-DTS-A ranged from .81 to .87 and from .79 to .89, respectively. CONCLUSION: The two-factor nine-item C-DTS-A with good cross-cultural translation quality was a reliable and valid scale to assess EDT for adolescents with CPD.


Assuntos
Comparação Transcultural , Angústia Psicológica , Psicometria , Traduções , Humanos , Adolescente , Feminino , Masculino , Reprodutibilidade dos Testes , Doença Crônica , Taiwan , Inquéritos e Questionários/normas , Estresse Psicológico/diagnóstico , Análise Fatorial , Tradução
16.
J Prosthodont ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38706414

RESUMO

PURPOSE: To evaluate the effects of two base types and three restoration designs on the resin consumption and trueness of the 3D-printed dental casts. Additionally, the study explored the dimensional stability of these 3D-printed dental casts after 1 year of storage. MATERIALS AND METHODS: Various types of reference dental casts were specifically designed to represent three types of dental restoration fabrications, including full-arch (FA), long-span (LS), and single-unit (SU) prostheses. The reference casts were digitized with a dental laboratory scanner and used to create flat and hollow base designs (N = 18) for the 3D-printed study casts. The 3D-printed study casts were digitized and evaluated against their corresponding references immediately after 3D printing and again after 1 year of storage, with the trueness quantified using the root mean square error (RMSE) at both time points. Volumes of resin used were recorded to measure resin consumption, and the weights of the 3D-printed study casts were also measured. The data were analyzed using two-way ANOVA and a Tukey post hoc test, α = 0.05. RESULTS: Volumetric analysis showed the flat-base design had significantly higher resin consumption with weights for the FA group at 42.51 ± 0.16 g, the LS group at 31.64 ± 0.07 g, and the SU group at 27.67 ± 0.31 g, as opposed to 26.22 ± 1.01 g, 22.86 ± 0.93 g, and 20.10 ± 0.19 g for the hollow designs respectively (p < 0.001). Trueness, assessed through two-way ANOVA, revealed that the flat-base design had lower RMSE values indicating better trueness in the LS (54 ± 6 µm) and SU (59 ± 7 µm) groups compared to the hollow-base design (LS: 73 ± 5, SU: 99 ± 11 µm, both p < 0.001), with no significant difference in the FA group (flat-base: 50 ± 3, hollow: 47 ± 5 µm, p = 0.398). After 1 year, the flat-base design demonstrated superior dimensional stability in the LS (flat base: 56 ± 6 µm, hollow base: 149 ±45 µm, p < 0.001) and SU groups (flat base: 95 ± 8 µm, hollow base: 183 ±27 µm, p < 0.001), with the FA group showing no significant difference in the base design (flat base: 47 ± 9, hollow base: 62 ± 12 µm, p = 0.428). CONCLUSIONS: The hollow-base design group showed lower resin consumption than the flat-base design group. However, the flat-base designs exhibited superior trueness and less distortion after 1 year of storage. These findings indicate that despite the higher material usage, flat-base designs provide better initial accuracy and maintain their dimensional stability over time for most groups.

17.
Immunol Lett ; 267: 106862, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38702033

RESUMO

BACKGROUND: Diabetic retinopathy (DR) stands as a prominent complication of diabetes. Berberine (BBR) has reported to be effective to ameliorate the retinal damage of DR. Studying the potential immunological mechanisms of BBR on the streptozotocin (STZ) induced DR mouse model will explain the therapeutic mechanisms of BBR and provide theoretical basis for the clinical application of this drug. METHODS: C57BL/6 J mice were induced into a diabetic state using a 50 mg/(kg·d) dose of STZ over a 5-day period. Subsequently, they were subjected to a high-fat diet (HFD) for one month. Following a 5-week treatment with 100 mg/(kg·d) BBR, the concentrations of inflammatory factors in the mice's peripheral blood were determined using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin staining was employed to scrutinize pathological changes in the mice's retinas, while flow cytometry assessed the proportions of T-lymphocyte subsets and the activation status of dendritic cells (DCs) in the spleen and lymph nodes. CD4+T cells and DC2.4 cell lines were utilized to investigate the direct and indirect effects of BBR on T cells under high glucose conditions in vitro. RESULTS: Following 5 weeks of BBR treatment in the streptozotocin (STZ) mouse model of DR, we observed alleviation of retinal lesions and a down-regulation in the secretion of inflammatory cytokines, namely TNF-α, IL-1ß, and IL-6, in the serum of these mice. And in the spleen and lymph nodes of these mice, BBR inhibited the proportion of Th17 cells and promoted the proportion of Treg cells, thereby down-regulating the Th17/Treg ratio. Additionally, in vitro experiments, BBR directly inhibited the expression of the transcription factor RORγt and promoted the expression of the transcription factor Foxp3 in T cells, resulting in a down-regulation of the Th17/Treg ratio. Furthermore, BBR indirectly modulated the Th17/Treg ratio by suppressing the secretion of TNF-α, IL-1ß, and IL-6 by DCs and enhancing the secretion of indoleamine 2,3-dioxygenase (IDO) and transforming growth factor-beta (TGF-ß) by DCs. This dual action inhibited Th17 cell differentiation while promoting Treg cells. CONCLUSION: Our findings indicate that BBR regulate T cell subpopulation differentiation, reducing the Th17/Treg ratio by directly or indirectly pathway. This represents a potential therapeutic avenue of BBR for improving diabetic retinopathy.

18.
Protein Sci ; 33(6): e5012, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723180

RESUMO

The enormous LysR-type transcriptional regulators (LTTRs), which are diversely distributed amongst prokaryotes, play crucial roles in transcription regulation of genes involved in basic metabolic pathways, virulence and stress resistance. However, the precise transcription activation mechanism of these genes by LTTRs remains to be explored. Here, we determine the cryo-EM structure of a LTTR-dependent transcription activation complex comprising of Escherichia coli RNA polymerase (RNAP), an essential LTTR protein GcvA and its cognate promoter DNA. Structural analysis shows two N-terminal DNA binding domains of GcvA (GcvA_DBD) dimerize and engage the GcvA activation binding sites, presenting the -35 element for specific recognition with the conserved σ70R4. In particular, the versatile C-terminal domain of α subunit of RNAP directly interconnects with GcvA_DBD, σ70R4 and promoter DNA, providing more interfaces for stabilizing the complex. Moreover, molecular docking supports glycine as one potential inducer of GcvA, and single molecule photobleaching experiments kinetically visualize the occurrence of tetrameric GcvA-engaged transcription activation complex as suggested for the other LTTR homologs. Thus, a general model for tetrameric LTTR-dependent transcription activation is proposed. These findings will provide new structural and functional insights into transcription activation of the essential LTTRs.


Assuntos
RNA Polimerases Dirigidas por DNA , Escherichia coli , Ativação Transcricional , Escherichia coli/genética , Escherichia coli/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Regiões Promotoras Genéticas , Microscopia Crioeletrônica , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Modelos Moleculares , Simulação de Acoplamento Molecular , Regulação Bacteriana da Expressão Gênica , Multimerização Proteica , Sítios de Ligação
19.
J Nutr Health Aging ; 28(8): 100260, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38772099

RESUMO

BACKGROUND: Multimorbidity, individuals suffering from two or more chronic diseases, has become a major health challenge worldwide, especially in populous and prosperous cities, where studies of this phenomenon in China are limited. We examined the prevalence, trends, patterns, and associated factors of multimorbidity from 2009 to 2018 among community-dwelling adults in Guangzhou, China. METHODS: We conducted serial cross-sectional surveys for chronic diseases in Guangzhou, China, in 2009, 2013, and 2018. General and stratified prevalence were standardized using demographic data. Multivariable logistic regression and hierarchical cluster analysis were applied to identify associated factors and to assess the correlations and patterns of multimorbidity, respectively. RESULTS: This study included 23,284 adults aged 18 and over in 2009, 18,551 in 2013, and 15,727 in 2018. The standardized prevalence of multimorbidity increased substantially, with 12.69% (95% CI: 10.45-15.33) in 2009, 25.44% (95% CI: 23.47-27.52) in 2013, and 35.13% (95% CI:32.64-37.70) in 2018 (P for trend <0.001). The highest bi- and triple-conditions of multimorbidity were dyslipidemia (DP) and overweight or obesity (OO) (12.54%, 95% CI: 11.68-13.46), and DP, OO, and Hypertension (HT) (3.99%, 95% CI: 3.47-4.58) in 2018. From 2009 to 2018, (1) The majority of multimorbidity patterns showed a high prevalence; (2) The percentage of participants with only one chronic condition was found lower, while the percentage with multiple conditions was higher. CONCLUSIONS: The prevalence of chronic disease multimorbidity in Guangzhou China, has increased substantially among adults. Effective policies targeting multimorbidity are urgently needed, especially for the health management of primary medical institutions.

20.
J Agric Food Chem ; 72(20): 11452-11464, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38736181

RESUMO

In this work, a new rapid and targeted method for screening α-glucosidase inhibitors from Hypericum beanii was developed and verified. Ten new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperlagarol A-J (1-10), and nine known PPAPs (11-19) were obtained from H. beanii. Their structures were identified by using comprehensive analyses involving mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and electron capture dissociation calculations. 1 and 2 are two new rare 2,3-seco-spirocyclic PPAPs, 3 and 4 are two novel 12,13-seco-spirocyclic PPAPs, 5 and 6 are two novel spirocyclic PPAPs, 7 and 8 are two new unusual spirocyclic PPAPs with complex bridged ring systems, and 9 and 10 are two novel nonspirocyclic PPAPs. α-GC inhibitory activities of all isolated compounds were tested. Most of them displayed inhibitory activities against α-glucosidase, with the IC50 values ranging from 6.85 ± 0.65 to 112.5 ± 9.03 µM. Moreover, the inhibitory type and mechanism of the active compounds were further analyzed using kinetic studies and molecular docking.


Assuntos
Inibidores de Glicosídeo Hidrolases , Hypericum , Simulação de Acoplamento Molecular , Extratos Vegetais , alfa-Glucosidases , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo , Hypericum/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Estrutura Molecular , Ligantes , Relação Estrutura-Atividade , Cinética
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