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1.
J Clin Transl Hepatol ; 12(2): 162-171, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38343613

RESUMO

Background and Aims: SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports. However, the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases (AILD) is still unknown. Methods: Eighty-four patients with AILD were prospectively followed up after the second dose (primary) of inactivated SARS-CoV-2 vaccine. Some of them received the third dose (booster) of inactivated vaccine. Adverse events (AEs), autoimmune activation, and liver inflammation exacerbation after primary and booster vaccination were recorded. Meanwhile, dynamics of antireceptor-binding-domain IgG (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD-specific B cells responses were evaluated. Results: The overall AEs in AILD patients after primary and booster vaccination were 26.2% and 13.3%, respectively. The decrease of C3 level and increase of immunoglobulin light chain κ and λ levels were observed in AILD patients after primary vaccination, however, liver inflammation was not exacerbated, even after booster vaccination. Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination. Notably, the antibody titers were significantly elevated after booster vaccination (10-fold in anti-RBD-IgG and 7.4-fold in NAbs, respectively), which was as high as in healthy controls. Unfortunately, the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants. Changes of atypical memory B cells were inversely related to antibody levels, which indicate that the impaired immune memory was partially restored partly by the booster vaccination. Conclusions: The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.

2.
Cancer Cell Int ; 24(1): 64, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336680

RESUMO

BACKGROUND: Esophageal cancer (EC) is a global canker notorious for causing high mortality due to its relentless incidence rate, convoluted with unyielding recurrence and metastasis. However, these intricacies of EC are associated with an immoderate expression of NY-ESO-1 antigen, presenting a lifeline for adoptive T cell therapy. We hypothesized that naturally isolated higher-affinity T cell receptors (TCRs) that bind to NY-ESO-1 would allow T lymphocytes to target EC with a pronounced antitumor response efficacy. Also, targeting TRPV2, which is associated with tumorigenesis in EC, creates an avenue for dual-targeted therapy. We exploited the dual-targeting antitumor efficacy against EC. METHODS: We isolated antigen-specific TCRs (asTCRs) from a naive library constructed with TCRs obtained from enriched cytotoxic T lymphocytes. The robustness of our asTCRs and their TCR-T cell derivatives, Tranilast (TRPV2 inhibitor), and their bivalent treatment were evaluated with prospective cross-reactive human-peptide variants and tumor cells. RESULTS: Our study demonstrated that our naive unenhanced asTCRs and their TCR-Ts perpetuated their cognate HLA-A*02:01/NY-ESO-1(157-165) specificity, killing varying EC cells with higher cytotoxicity compared to the known affinity-enhanced TCR (TCRe) and its wild-type (TCR0) which targets the same NY-ESO-1 antigen. Furthermore, the TCR-Ts and Tranilast bivalent treatment showed superior EC killing compared to any of their monovalent treatments of either TCR-T or Tranilast. CONCLUSION: Our findings suggest that dual-targeted immunotherapy may have a superior antitumor effect. Our study presents a technique to evolve novel, robust, timely therapeutic strategies and interventions for EC and other malignancies.

3.
Diagnostics (Basel) ; 14(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38337824

RESUMO

BACKGROUND: Hematoma expansion (HE) following an intracerebral hemorrhage (ICH) is a modifiable risk factor and a treatment target. We examined the association of HE with neurological deterioration (ND), functional outcome, and mortality based on the time gap from onset to baseline CT. METHODS: We included 567 consecutive patients with supratentorial ICH and baseline head CT within 24 h of onset. ND was defined as a ≥4-point increase on the NIH stroke scale (NIHSS) or a ≥2-point drop on the Glasgow coma scale. Poor outcome was defined as a modified Rankin score of 4 to 6 at 3-month follow-up. RESULTS: The rate of HE was higher among those scanned within 3 h (124/304, 40.8%) versus 3 to 24 h post-ICH onset (53/263, 20.2%) (p < 0.001). However, HE was an independent predictor of ND (p < 0.001), poor outcome (p = 0.010), and mortality (p = 0.003) among those scanned within 3 h, as well as those scanned 3-24 h post-ICH (p = 0.043, p = 0.037, and p = 0.004, respectively). Also, in a subset of 180/567 (31.7%) patients presenting with mild symptoms (NIHSS ≤ 5), hematoma growth was an independent predictor of ND (p = 0.026), poor outcome (p = 0.037), and mortality (p = 0.027). CONCLUSION: Despite decreasing rates over time after ICH onset, HE remains an independent predictor of ND, functional outcome, and mortality among those presenting >3 h after onset or with mild symptoms.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38332514

RESUMO

STUDY DESIGN: Retrospective observational study. OBJECTIVE: To describe the epidemiology of Schmorl's nodes (SN) of primarily developmental cause (SNd) and SN of primarily acquired cause (SNa) separately in the thoracic spine in subjects aged 35-90 years old. SUMMARY OF BACKGROUND DATA: The epidemiology of SN and its relationship with age and gender remain controversial. Based on a pathophysiological hypothesis and the different morphological characteristics, two subtypes of SN may exist and should be considered separately. PATIENTS AND METHODS: Chest CT scans of subjects who came to our institution for health check aged 35-90 years old were retrospectively reviewed. Presence or absence of SN was recorded for each thoracic vertebra. The SNs were further classified into SNd and SNa. The prevalence, location and relationship with age, gender and bone mineral density (BMD) were evaluated separately for the two subtypes. RESULTS: Of the 848 subjects (407 female, mean age, 53±12.2 y) included, 15.7% had SNs. Of the 303 SNs, 49.2% were SNd and 48.5% were SNa. Aging increased the prevalence of SNa while it was not related to the prevalence of SNd. Males had significantly more SNd than females (11.3% vs 4.7%, P<0.001), while the prevalence of SNa was not different between the two genders (10.2% vs 9.1%, P=0.666). A similar distribution of SNd and SNa among thoracic vertebral levels was appreciated, with T9 most frequently involved. Subjects with SNa had lower lumbar BMD than controls (P=0.006), while no significant difference in BMD was found between subjects with SNd and controls (P=0.166). CONCLUSIONS: The clinical characteristics of SN differ based on the developmental and acquired subtype, including the relationship with age, gender and BMD. The subtypes may be considered as distinct clinical entities as a result.

5.
iScience ; 27(2): 108834, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38303703

RESUMO

Current diagnostic methods for diabetic nephropathy (DN) lack precision, especially in early stages and monitoring progression. This study aims to find potential biomarkers for DN progression and evaluate their accuracy. Using serum samples from healthy controls (NC), diabetic patients (DM), early-medium stage DN (DN-EM), and late-stage DN (DN-L), researchers employed quantitative proteomics and Mfuzz clustering analysis revealed 15 proteins showing increased expression during DN progression, hinting at their biomarker potential. Combining Mfuzz clustering with weighted gene co-expression network analysis (WGCNA) highlighted five candidates (HMGB1, CD44, FBLN1, PTPRG, and ADAMTSL4). HMGB1 emerged as a promising biomarker, closely correlated with renal function changes. Experimental validation supported HMGB1's upregulation under high glucose conditions, reinforcing its potential as an early detection biomarker for DN. This research advances DN understanding and identifies five potential biomarkers, notably HMGB1, as a promising early monitoring target. These findings set the stage for future clinical diagnostic applications in DN.

6.
Artigo em Chinês | MEDLINE | ID: mdl-38297848

RESUMO

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome(AS) patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33(25 males, 8 females, aged 3.4-27.8 years) were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease(ESRD), predominantly males (6/7). The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group(P=0.013). There was no correlation between the progression of renal disease and long-term hearing level(P>0.05). kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss(P=0.048), and there was no correlation with the severity of hearing loss(P>0.05). Among 11 cases, theCOL4A5mutationwas most common (8 out of 11), but there was no significant correlation between the mutation type and hearing phenotype(P>0.05). Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.


Assuntos
Surdez , Perda Auditiva , Falência Renal Crônica , Nefrite Hereditária , Masculino , Criança , Feminino , Humanos , Nefrite Hereditária/genética , Nefrite Hereditária/patologia , Estudos Retrospectivos , Rim , Perda Auditiva/genética , Falência Renal Crônica/genética , Falência Renal Crônica/patologia , Mutação
7.
Nat Prod Res ; : 1-7, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38303493

RESUMO

Two new guaiane sesquiterpenoids were isolated from the dried aerial parts of Dracocephalum tanguticum Maxim., named as dracotangusions A (1) and B (2), together with four known sesquiterpenoids, which were identified as Curcumenone (3), (4Z,7Z,9Z)-11-Hydroxy-4,7,9-germacratriene-1,6-dione (4), Kobusone (5), and (1S,10S), (4S, 5S)-(+)-germacrone-1(10)-4-diepoxide (6). The structures of isolates were determined by UV, IR, HR-ESI-MS, and NMR analysis. What is noteworthy is that four known sesquiterpenoids were isolated for the first time from the genus of Dracocephalum L. All compounds inhibited the extremely significant difference (p < 0.01) in anti-inflammatory activity, suggesting that these compounds may be promising candidates as an anti-inflammatory agent.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38315582

RESUMO

AIMS: To investigate the current situation of mental psychology and quality of life (QoL) in patients with inflammatory bowel disease (IBD) in China, and analyze the influencing factors. METHODS: A unified questionnaire was developed to collect clinical data on IBD patients from 42 hospitals in 22 provinces from September 2021 to May 2022. Multivariate Logistic regression analysis was conducted, and independent influencing factors were screened out to construct nomogram. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical utility of the nomogram model. RESULTS: A total of 2478 IBD patients were surveyed, including 1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD). Among them, 25.5%, 29.7%, 60.2%, and 37.7% of IBD patients had anxiety, depression, sleep disturbance and poor QoL, respectively. The proportion of anxiety, depression, and poor QoL in UC patients was significantly higher than that in CD patients (all p < 0.05), but there was no difference in sleep disturbance between them (p = 0.737). Female, higher disease activity and the first visit were independent risk factors for anxiety, depression and sleep disturbance in IBD patients (all p < 0.05). The first visit, higher disease activity, abdominal pain and diarrhea symptoms, anxiety, depression and sleep disturbance were independent risk factors for the poor QoL of patients (all p < 0.05). The AUC value of the nomogram prediction model for predicting poor QoL was 0.773 (95% CI: 0.754-0.792). The calibration diagram of the model showed that the calibration curve fit well with the ideal curve, and DCA showed that the nomogram model could bring clinical benefits. CONCLUSION: IBD patients have higher anxiety, depression, and sleep disturbance, which affect their QoL. The nomogram prediction model we constructed has high accuracy and performance when predicting QoL.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38317440

RESUMO

BACKGROUND AND HYPOTHESIS: To explore the association between the differences between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) with the risk of mortality and cardiovascular (CV) events in individuals with diabetes. METHODS: Three prospective cohorts analyzed data of adults with diabetes from the Incident, Development, and Prognosis of Diabetic Kidney Disease (INDEED) study (2016-2017 to 2020) in China, the National Health, Nutrition Examination Survey (NHANES, 1999-2004 to 2019) in the United States, and UK Biobank (UKB, 2006-2010 to 2022). Baseline eGFRdiff was calculated using both absolute difference between cystatin C- and creatinine-based calculations (eGFRabdiff), and the ratio between them (eGFRrediff). Cox proportional hazards regression models were used to investigate the association between eGFRdiff and outcomes including all-cause mortality and incident CV events. RESULTS: A total of 8,129 individuals from the INDEED (aged 60.7±10.0 years), 1,634 from the NHANES (aged 62.5±14.4 years), and 29,358 from the UKB (aged 59.4±7.3 years;) were included. At baseline, 43.6%, 32.4% and 42.1% of participants in the INDEED, NHANES and UKB had an eGFRabdiff value ≥15 ml/min/1.73 m2. During a median follow-up of 3.8 years for the INDEED, 15.2 years for the NHANES, and 13.5 years for the UKB, a total of 430, 936 and 6143 deaths and a total of 481, 183 and 5583 CV events occurred, respectively. Each 1-standard deviation higher baseline eGFRabdiff was independently associated with a lower risk of all-cause mortality and CV events, with hazard ratios (HRs) of 0.77 and 0.82 in the INDEED, 0.70 and 0.68 in the NHANES, and 0.66 and 0.78 in the UKB. Similar results were observed for eGFRrediff. CONCLUSIONS: eGFRdiff represents a marker of adverse events for diabetes among general population. Monitoring both eGFRcys and eGFRcr yields additional prognostic information and has clinical utility in identifying high-risk individuals for mortality and CV events.

10.
Eur Radiol ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319428

RESUMO

OBJECTIVES: This study aimed to externally validate the Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) recommendations for differentiation/follow-up of central cartilage tumours (CCTs) of the proximal humerus, distal femur, and proximal tibia and to propose BACTIP adaptations if the results provide new insights. METHODS: MRIs of 123 patients (45 ± 11 years, 37 men) with an untreated CCT with MRI follow-up (n = 62) or histopathological confirmation (n = 61) were retrospectively/consecutively included and categorised following the BACTIP (2003-2020 / Ghent University Hospital/Belgium). Tumour length and endosteal scalloping differences between enchondroma, atypical cartilaginous tumour (ACT), and high-grade chondrosarcoma (CS II/III/dedifferentiated) were evaluated. ROC-curve analysis for differentiating benign from malignant CCTs and for evaluating the BACTIP was performed. RESULTS: For lesion length and endosteal scalloping, ROC-AUCs were poor and fair-excellent, respectively, for differentiating different CCT groups (0.59-0.69 versus 0.73-0.91). The diagnostic performance of endosteal scalloping and the BACTIP was higher than that of lesion length. A 1° endosteal scalloping cut-off differentiated enchondroma from ACT + high-grade chondrosarcoma with a sensitivity of 90%, reducing the potential diagnostic delay. However, the specificity was 29%, inducing overmedicalisation (excessive follow-up). ROC-AUC of the BACTIP was poor for differentiating enchondroma from ACT (ROC-AUC = 0.69; 95%CI = 0.51-0.87; p = 0.041) and fair-good for differentiation between other CCT groups (ROC-AUC = 0.72-0.81). BACTIP recommendations were incorrect/unsafe in five ACTs and one CSII, potentially inducing diagnostic delay. Eleven enchondromas received unnecessary referrals/follow-up. CONCLUSION: Although promising as a useful tool for management/follow-up of CCTs of the proximal humerus, distal femur, and proximal tibia, five ACTs and one chondrosarcoma grade II were discharged, potentially inducing diagnostic delay, which could be reduced by adapting BACTIP cut-off values. CLINICAL RELEVANCE STATEMENT: Mostly, Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) assesses central cartilage tumours of the proximal humerus and the knee correctly. Both when using the BACTIP and when adapting cut-offs, caution should be taken for the trade-off between underdiagnosis/potential diagnostic delay in chondrosarcomas and overmedicalisation in enchondromas. KEY POINTS: • This retrospective external validation confirms the Birmingham Atypical Cartilage Tumour Imaging Protocol as a useful tool for initial assessment and follow-up recommendation of central cartilage tumours in the proximal humerus and around the knee in the majority of cases. • Using only the Birmingham Atypical Cartilage Tumour Imaging Protocol, both atypical cartilaginous tumours and high-grade chondrosarcomas (grade II, grade III, and dedifferentiated chondrosarcomas) can be misdiagnosed, excluding them from specialist referral and further follow-up, thus creating a potential risk of delayed diagnosis and worse prognosis. • Adapted cut-offs to maximise detection of atypical cartilaginous tumours and high-grade chondrosarcomas, minimise underdiagnosis and reduce potential diagnostic delay in malignant tumours but increase unnecessary referral and follow-up of benign tumours.

11.
Front Public Health ; 12: 1249880, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38317798

RESUMO

Introduction: Numerous studies suggest that the risk of tuberculosis (TB) is linked to gene polymorphisms of the interleukin-12 receptor b subunit 1 (IL12RB1), but the association between IL12RB1 polymorphisms and TB susceptibility has not been thoroughly investigated. Methods: A meta-analysis was conducted based on eight case-control studies with 10,112 individuals to further explore this topic. A systematic search of PubMed, Web of Science, Excerpt Medica Database, and Google Scholar up until April 6th, 2023 was performed. ORs and 95% CIs were pooled using the random-effect model. The epidemiological credibility of all significant associations was assessed using the Venice criteria and false-positive report probability (FPRP) analyses. Results: The IL12RB1 rs11575934 and rs401502 showed solid evidence of no significant association with TB susceptibility. However, a weak association was observed between the IL12RB1 rs375947 biomarker and pulmonary tuberculosis (PTB) susceptibility (OR = 1.64, 95% CI: 1.22, 2.21). Discussion: These findings should be confirmed through larger, better-designed studies to clarify the relationship between biomarkers in IL12RB1 gene and different types of TB susceptibility.


Assuntos
Predisposição Genética para Doença , Tuberculose , Humanos , Receptores de Interleucina-12/genética , Tuberculose/genética , Polimorfismo Genético , Fatores de Risco
12.
J Nutr Health Aging ; 28(3): 100036, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38320382

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a major public health concern. However, validated and broadly applicable biomarkers for early CKD diagnosis are currently not available. We aimed to identify serum metabolic signatures at an early stage of CKD to provide a reference for future investigations into the early diagnostic biomarkers. METHODS: Serum metabolites were extracted from 65 renal dysfunction (RD) patients and 121 healthy controls (discovery cohort: 12 RD patients and 55 health participants; validation cohort: 53 RD patients and 66 health participants). Metabolite extracts were analyzed by ultraperformance liquid chromatography coupled with quadrupole-electrostatic field orbital trap mass spectrometry (UPLC-QE-Orbitrap MS) for untargeted metabolomics. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was performed to detect different compounds between groups. Receiver operating characteristic (ROC) curve analysis was carried out to determine the diagnostic value of the validated differential metabolites between groups. We referred to the Kyoto Encyclopedia of Gene and Genomes (KEGG) to elucidate the metabolic pathways of the validated differential metabolites. RESULTS: A total of 22 and 23 metabolites had significantly different abundances in the discovery and validation cohort, respectively. Six of them (creatinine, L-proline, citrulline, butyrylcarnitine, 1-methylhistidine, and valerylcarnitine) in the RD group was more abundant than that of the health group in both cohorts. The combination of the six validated differential metabolites were able to accurately detect RD (AUC 0.86). Three of the six metabolites are involved in the metabolism of arginine and proline. CONCLUSIONS: The present study highlights that creatinine, L-proline, citrulline, butyrylcarnitine, 1-methylhistidine, and valerylcarnitine are metabolite indicators with potential predictive value for CKD.

13.
Biomed Environ Sci ; 37(1): 42-53, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38326720

RESUMO

Objective: This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue. Methods: A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis. Results: Six potential active components, namely quercetin, ß-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment. Conclusion: Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.


Assuntos
Medicamentos de Ervas Chinesas , Quercetina , Humanos , Quercetina/farmacologia , Quercetina/uso terapêutico , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Fadiga/tratamento farmacológico
14.
Sci Adv ; 10(8): eadk7140, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394197

RESUMO

Acaryochloris marina is a unique cyanobacterium using chlorophyll d (Chl d) as its major pigment and thus can use far-red light for photosynthesis. Photosystem II (PSII) of A. marina associates with a number of prochlorophyte Chl-binding (Pcb) proteins to act as the light-harvesting system. We report here the cryo-electron microscopic structure of a PSII-Pcb megacomplex from A. marina at a 3.6-angstrom overall resolution and a 3.3-angstrom local resolution. The megacomplex is organized as a tetramer consisting of two PSII core dimers flanked by sixteen symmetrically related Pcb proteins, with a total molecular weight of 1.9 megadaltons. The structure reveals the detailed organization of PSII core consisting of 15 known protein subunits and an unknown subunit, the assembly of 4 Pcb antennas within each PSII monomer, and possible pathways of energy transfer within the megacomplex, providing deep insights into energy transfer and dissipation mechanisms within the PSII-Pcb megacomplex involved in far-red light utilization.

15.
Ecotoxicol Environ Saf ; 273: 116123, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38394754

RESUMO

High levels of copper released in the soil, mainly from anthropogenic activity, can be hazardous to plants, animals, and humans. The present research aimed to estimate the suitability and effectiveness of rapeseed (Brassica napus L.) as a possible soil remediation option and to uncover underlying adaptive mechanisms A pot experiment was conducted to explore the effect of copper stress on agronomic and yield traits for 32 rapeseed genotypes. The copper-tolerant genotype H2009 and copper-sensitive genotype ZYZ16 were selected for further physiological, metabolomic, and transcriptomic analyses. The results exhibited a significant genotypic variation in copper stress tolerance in rapeseed. Specifically, the ratio of seed yield under copper stress to control ranged from 0.29 to 0.74. Furthermore, the proline content and antioxidant enzymatic activities in the roots were greater than those in the shoots. The accumulated copper in the roots accounted for about 50% of the total amount absorbed by plants; thus, the genotypes possessing high root volumes can be used for rhizofiltration to uptake and sequester copper. Additionally, the pectin and hemicellulose contents were significantly increased by 15.6% and 162%, respectively, under copper stress for the copper-tolerant genotype, allowing for greater sequestration of copper ions in the cell wall and lower oxidative stress. Comparative analysis of transcriptomes and metabolomes revealed that excessive copper enhanced the up-regulation of functional genes or metabolites related to cell wall binding, copper transportation, and chelation in the copper-tolerant genotype. Our results suggest that copper-tolerant rapeseed can thrive in heavily copper-polluted soils with a 5.85% remediation efficiency as well as produce seed and vegetable oil without exceeding food quality standards for the industry. This multi-omics comparison study provides insights into breeding copper-tolerant genotypes that can be used for the phytoremediation of heavy metal-polluted soils.

17.
Int J Surg ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38363991

RESUMO

BACKGROUND: Indocyanine green (ICG) clearance test is a classical measurement of hepatic reserve, which involves surgical safety and patient recovery of hepatocellular carcinoma (HCC). We aim to compare effects of hepatic arterial infusion chemotherapy (HAIC) and transcatheter arterial chemoembolization (TACE) on liver function and outcomes of subsequent hepatectomy. MATERIAL AND METHODS: HCC patients receiving HAIC/TACE in SYSUCC with repeated ICG clearance tests were retrospectively enrolled. ICG eliminating rate (ICG-K), ICG retention rate at 15-minutes (ICG-R15) and ordinary laboratory tests were collected. Peri-therapeutic changes of values were compared between the groups. Propensity score matching (PSM) and inverse probability of treatment weighing (IPTW) were employed to validate findings. Post-hepatectomy liver failure (PHLF), overall survival (OS) and recurrence-free survival (RFS) were analyzed in patients with subsequent curative hepatectomy. RESULTS: 204 patients treated with HAIC (n=130) and TACE (n=74) were included. ΔICG-R15 was greater in the HAIC arm before matching (mean, 3.8% vs. 0.7%, P<0.001), after PSM (mean, 4.7% vs. 1.1%, P=0.014) and IPTW (mean, 2.0% vs. -3.6%, P<0.001). No difference was found for ΔALB, ΔALBI, ΔTBIL, ΔALT, ΔAST and ΔPT-INR. Multivariable analyses revealed elder age, cirrhosis, HAIC, greater ΔTBIL and ΔALBI were associated with deteriorating ICG-R15. Among those (105 for HAIC and 48 for TACE) receiving hepatectomy, occurrence of grade B/C PHLF (4.8% vs. 8.3%, P=0.616), OS (median, unreached vs. unreached, P=0.94) and RFS (median, 26.7 vs. 17.1 mo, P=0.096) were comparable between the two arms. In subgroup analyses, preoperative HAIC yield superior RFS (median, 26.7 vs. 16.2 mo, P=0.042) in patients with baseline ICG-R15≤10%. CONCLUSION: Preoperative FOLFOX-HAIC caused apparent impairment of ICG clearance ability than TACE yet comparable impact on liver function and post-hepatectomy outcomes.

18.
Fish Shellfish Immunol ; 147: 109443, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38354964

RESUMO

The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family has been reported to be involved in many immune pathways. In a previous study, we identified 5 TRAF genes, including TRAF2, 3, 4, 6, and 7, in the bay scallop (Argopecten irradians, Air) and the Peruvian scallop (Argopecten purpuratus, Apu). Since TRAF6 is a key molecular link in the TNF superfamily, we conducted a series of studies targeting the TRAF6 gene in the Air and Apu scallops as well as their hybrid progeny, Aip (Air ♀ × Apu ♂) and Api (Apu ♀ × Air ♂). Subcellular localization assay showed that the Air-, Aip-, and Api-TRAF6 were widely distributed in the cytoplasm of the human embryonic kidney cell line (HEK293T). Additionally, dual-luciferase reporter assay revealed that among TRAF3, TRAF4, and TRAF6, only the overexpression of TRAF6 significantly activated NF-κB activity in the HEK293T cells in a dose-dependent manner. These results suggest a crucial role of TRAF6 in the immune response in Argopecten scallops. To investigate the specific immune mechanism of TRAF6 in Argopecten scallops, we conducted TRAF6 knockdown using RNA interference. Transcriptomic analyses of the TRAF6 RNAi and control groups identified 1194, 2403, and 1099 differentially expressed genes (DEGs) in the Air, Aip, and Api scallops, respectively. KEGG enrichment analyses revealed that these DEGs were primarily enriched in transport and catabolism, amino acid metabolism, peroxisome, lysosome, and phagosome pathways. Expression profiles of 28 key DEGs were confirmed by qRT-PCR assays. The results of this study may provide insights into the immune mechanisms of TRAF in Argopecten scallops and ultimately benefit scallop breeding.

19.
Nat Methods ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374262

RESUMO

Studies using antigen-presenting systems at the single-cell and ensemble levels can provide complementary insights into T-cell signaling and activation. Although crucial for advancing basic immunology and immunotherapy, there is a notable absence of synthetic material toolkits that examine T cells at both levels, and especially those capable of single-molecule-level manipulation. Here we devise a biomimetic antigen-presenting system (bAPS) for single-cell stimulation and ensemble modulation of T-cell recognition. Our bAPS uses hexapod heterostructures composed of a submicrometer cubic hematite core (α-Fe2O3) and nanostructured silica branches with diverse surface modifications. At single-molecule resolution, we show T-cell activation by a single agonist peptide-loaded major histocompatibility complex; distinct T-cell receptor (TCR) responses to structurally similar peptides that differ by only one amino acid; and the superior antigen recognition sensitivity of TCRs compared with that of chimeric antigen receptors (CARs). We also demonstrate how the magnetic field-induced rotation of hexapods amplifies the immune responses in suspended T and CAR-T cells. In addition, we establish our bAPS as a precise and scalable method for identifying stimulatory antigen-specific TCRs at the single-cell level. Thus, our multimodal bAPS represents a unique biointerface tool for investigating T-cell recognition, signaling and function.

20.
Circ Res ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38375634

RESUMO

BACKGROUND: Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear. METHODS: High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression of Gsα in atherosclerosis. The differentially expression and activity of Gsα were analyzed by immunofluorescence and cAMP measurements. Macrophage-specific Gsα knockout (Mac-GsαKO) mice were generated to study the effect on atherosclerosis. The role of Gsα was determined by transplanting bone marrow and performing assays for foam cell formation, Dil-ox-LDL (oxidized low-density lipoprotein) uptake, chromatin immunoprecipitation, and luciferase reporter assays. RESULTS: ScRNA-seq showed elevated Gnas in atherosclerotic mouse aorta's cholesterol metabolism macrophage cluster, while bulk sequencing confirmed increased GNAS expression in human plaque macrophage content. A significant upregulation of Gsα and active Gsα occurred in macrophages from human and mouse plaques. Ox-LDL could translocate Gsα from macrophage lipid rafts in short-term and promote Gnas transcription through ERK1/2 activation and C/EBPß phosphorylation via oxidative stress in long-term. Atherosclerotic lesions from Mac-GsαKO mice displayed decreased lipid deposition compared with those from control mice. Additionally, Gsα deficiency alleviated lipid uptake and foam cell formation. Mechanistically, Gsα increased the levels of cAMP and transcriptional activity of the cAMP response element binding protein, which resulted in increased expression of CD36 and SR-A1. In the translational experiments, inhibiting Gsα activation with suramin or cpGN13 reduced lipid uptake, foam cell formation, and the progression of atherosclerotic plaques in mice in vivo. CONCLUSIONS: Gsα activation is enhanced during atherosclerotic progression and increases lipid uptake and foam cell formation. The genetic or chemical inactivation of Gsα inhibit the development of atherosclerosis in mice, suggesting that drugs targeting Gsα may be useful in the treatment of atherosclerosis.

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