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1.
Biomed Pharmacother ; 180: 117483, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39353319

RESUMEN

The progression of high-grade squamous intraepithelial lesion (HSIL) to invasive cervical cancer (ICC) is a complex process involving persistent human papillomavirus (HPV) infection and changes in signal transduction regulation, energy and material metabolism, cell proliferation, autoimmune, and other biological process in vaginal microenvironment and immune microenviroment. Signaling pathways are a series of interacting molecules in cells that regulate various physiological functions of cells, such as growth, differentiation, metabolism, and death. In the progression of HSIL to ICC, abnormal activation or inhibition in signaling pathways plays an essensial role. This review presented some signaling pathways related to the malignant progression of HSIL to ICC, including p53, Rb, PI3K/AKT/mTOR, Wnt/ß-catenin, Notch, NF-κB, MAPK, TGF-ß, JAK-STAT, Hippo, and Hedgehog. The molecular mechanisms involved in the biological process of pathway regulation were also analyzed, in order to illustrate the molecular pathway of HSIL progression to ICC and provide references for the development of more effective prevention and treatment methods.

2.
Clin Otolaryngol ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358666

RESUMEN

OBJECTIVE: To assess the prevalence of depression, anxiety, insomnia and somatic symptom disorder (SSD) in chronic rhinosinusitis (CRS) patients who were waiting for surgery and to predict these psychiatric disorders using the 22-item Sinonasal Outcome Test (SNOT-22). DESIGN: A prospective cross-sectional study. SETTING: The rhinology ward at our institution, a tertiary hospital. PARTICIPANTS: Adult patients (> 18 years) diagnosed with CRS who were admitted to the rhinology ward for endoscopic sinus surgery and were able to understand and complete the study questionnaires. MAIN OUTCOME MEASURES: Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7), Insomnia Severity Index (ISI), Patient Health Questionnaire-15 (PHQ-15) and SNOT-22. RESULTS: Of the 159 participants recruited, 58 were at risk of depression (defined by PHQ-9 > 4, while 25 with PHQ-9 > 9), 49 were at risk of anxiety (defined by GAD-7 > 4, while 25 with GAD-7 > 9), 81 were at risk of insomnia (defined by ISI > 7, while 51 with ISI > 14) and 69 were at risk of SSD (defined by PHQ-15 > 4, while 24 with PHQ-15 > 9). The SNOT-22 score was closely correlated with the scores of psychometric tests and was an independent predictor of these psychiatric disorders. Patients with a high SNOT-22 score (> 30) are likely to be affected by comorbid psychiatric disorders and should be further evaluated by otolaryngologists. CONCLUSION: Depression, anxiety, insomnia and SSD are prevalent in CRS patients. Otolaryngologists should have a low threshold to ask the patient about psychiatric symptoms, especially for patients with an SNOT-22 score > 30.

3.
Alpha Psychiatry ; 25(4): 541-547, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39360302

RESUMEN

Objective: To investigate whether the combination of repetitive transcranial magnetic stimulation (rTMS) and auricular point pressure bean could effectively ameliorate postoperative affective disorder in elderly patients suffering from cerebral hemorrhage. Methods: From June 2020 to September 2023, 116 elderly patients with depression after cerebral hemorrhage, who underwent surgical procedures were divided into the exposure group and the control group. The division was determined based on whether received rTMS and traditional Chinese medicine auricular point pressure bean therapy. Hamilton anxiety scale (HAMA), Hamilton Depression scale (HAMD), National Institutes of Health Stroke scale (NIHSS), Montreal Cognitive Assessment scale (MoCA) and Mini Mental State examination scale (MMSE) were collected and compared between before intervention and after intervention. Results: In accordance with a 1 : 1 matching ratio, the patients in the study were paired using propensity score matching (PSM), with 53 patients in both the exposure group and the control group. There were no notable differences in baseline characteristics between the 2 groups (P > .05). Following the intervention, the HAMA score and the NIHSS score of the exposure group were markedly lower than those of the control group (P < .001). Additionally, theMoCA scores (P = .001) and MMSE scores (P < .001) in the exposure group were significantlyhigher. The difference score have a significant difference in HAMA score (P = .001), NIHSS score (P < .001), MoCA (P < .001) and MMSE scores (P < .001). Conclusion: The combination of rTMS therapy and auricular point pressure bean therapy in traditional Chinese medicine demonstrates can effectively relieve the anxiety level, postoperative emotional and cognitive disorders of elderly patients after intracerebral hemorrhage, and provide certain ideas and support for clinical treatment.

4.
Netw Neurosci ; 8(3): 673-696, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39355432

RESUMEN

Patients presenting with drug-resistant epilepsy are eligible for surgery aiming to remove the regions involved in the production of seizure activities, the so-called epileptogenic zone network (EZN). Thus the accurate estimation of the EZN is crucial. Data-driven, personalized virtual brain models derived from patient-specific anatomical and functional data are used in Virtual Epileptic Patient (VEP) to estimate the EZN via optimization methods from Bayesian inference. The Bayesian inference approach used in previous VEP integrates priors, based on the features of stereotactic-electroencephalography (SEEG) seizures' recordings. Here, we propose new priors, based on quantitative 23Na-MRI. The 23Na-MRI data were acquired at 7T and provided several features characterizing the sodium signal decay. The hypothesis is that the sodium features are biomarkers of neuronal excitability related to the EZN and will add additional information to VEP estimation. In this paper, we first proposed the mapping from 23Na-MRI features to predict the EZN via a machine learning approach. Then, we exploited these predictions as priors in the VEP pipeline. The statistical results demonstrated that compared with the results from current VEP, the result from VEP based on 23Na-MRI prior has better balanced accuracy, and the similar weighted harmonic mean of the precision and recall.


For the first time quantitative 23Na-MRI were used as prior information to improve estimation of epileptogenic network (EZN) using VEP pipeline, a personalized whole-brain network modeling from patient's specific data. The prior information of EZN can be derived from 23Na-MRI features using logistic regression predictions. The 23Na-MRI priors inferred EZNs has a better balanced accuracy than the previously used priors or the no-prior condition.

5.
Front Nutr ; 11: 1464046, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39371943

RESUMEN

Introduction: The relationship between serum uric acid (SUA) and cervical cancer is inconclusive. This study aims to investigate the causal relationship between SUA levels and cervical cancer incidence, and to evaluate the potential role of nutritional interventions in cervical cancer prevention. Methods: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis using genetic instruments from publicly available genome-wide association studies (GWASs) of individuals of predominantly European ancestry. Methods such as inversevariance weighted, weighted-median, weighted model, and MR-Egger were applied. Sensitivity tests, including leave-one-out, MR-PRESSO, and Cochran's Q test, assessed heterogeneity and pleiotropy. Results: Our findings revealed that a high SUA concentration significantly increased the risk of malignant cervical cancer: a 1 mg/mL increase in SUA was associated with a 71% higher risk (OR = 1.71, 95% CI = 1.10-2.67; p = 0.018). Stratification by histological type showed a significant causal effect on cervical adenocarcinoma risk (OR = 2.56, 95% CI = 1.14-5.73; p = 0.023). However, no clear evidence was found for a causal effect of cervical cancer on SUA levels. Conclusion: This study identified a causal relationship between elevated SUA levels and the risk of malignant cervical cancer, particularly cervical adenocarcinoma. These findings provide novel insights into the mechanisms of cervical carcinogenesis and suggest that managing SUA levels could be a potential strategy for cervical cancer prevention through dietary management.

6.
Langmuir ; 2024 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-39370613

RESUMEN

Solar-driven interfacial water evaporation has become one of the most promising approaches to effectively harvesting freshwater, yet the fabrication of high-performance and multifunctional solar interfacial evaporators (SIEs) still remains a huge challenge to date. In this study, a multifunctional MXene and Fe-MOF@cellulose acetate/polyvinylpyrrolidone (MXM@CP) SIE was prepared via a facile "electrospinning and suction filtration deposition" coupling strategy. Thanks to the incorporation of MXene, MXM@CP displayed excellent photothermal conversion performance. Together with the fast water transport channel provided by the porous cellulose acetate electrospinning substrate, a remarkable solar-driven water evaporation property was achieved for MXM@CP, showing a higher water evaporation rate of 1.1 kg m-2 h-1 under one sun irradiation. Moreover, the resultant composite film also exhibited excellent Fenton catalytic activity to effectively degrade volatile organic compounds (VOCs) due to the synergistic effect of the MXene and Fe-based MOF (Fe-MOF). Particularly, a relatively higher degradation rate of 82.8% was acquired for the resulting evaporator toward the benzene contaminant. These results provide new insights into the construction of high-performance and multifunctional SIEs toward clean freshwater collection from the VOC-contaminated water system.

7.
Biomaterials ; 314: 122809, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39303415

RESUMEN

Targeted therapies have revolutionized traditional cancer treatments by precisely targeting tumor cells, enhancing efficacy and safety. Despite this advancement, the proportion of cancer patients eligible for such therapies remains low due to the absence of suitable targets. Here, we investigate whether the translocation of the immunogenic cell death (ICD) marker calreticulin (CALR) from the endoplasmic reticulum (ER) to the cell surface following ICD induction can serve as a target for targeted therapies. To target CALR, a nanobody Nb215 identified from a naïve VHH phage library with high binding affinity to both human and mouse CALR was employed to engineer probiotic EcN 1917. Our results demonstrated that CALR nanobody-modified EcN-215 coupled with the photothermal dye indocyanine green (ICG) was able to exert NIR-II imaging-guide photothermal therapy (PTT). Moreover, PTT with EcN-215/ICG can reshape the tumor microenvironment by enhancing the infiltration of CD45+CD3+ T cells and CD11b+F4/80+ macrophages. Furthermore, the antitumor activity of CALR-targeted EcN-215/ICG is synergistically enhanced by blocking CD47-SIRPα axis. Collectively, our study provides a proof of concept for CALR-targeted therapy. Given that CALR translocation can be induced by various anticancer therapies across numerous tumor cell lines, CALR-targeted therapies hold promise as a novel approach for treating multiple types of cancers.

8.
Artículo en Inglés | MEDLINE | ID: mdl-39288328

RESUMEN

OBJECTIVE: Interstitial fibrosis and tubular atrophy (IFTA) were frequent histologic features of lupus nephritis (LN), and LN patients with IFTA have poor renal outcomes. In this study, we aimed to construct prediction models for the IFTA in LN patients. METHODS: This retrospective study included 303 patients with biopsy proven LN at the Affiliated Hospital of Qingdao University and Union Hospital of Fujian Medical University. The participants were randomly divided into development and validation cohorts. They were further divided into IFTA and non-IFTA groups. The least absolute shrinkage and selection operator (LASSO) regression model with laboratory test results collected at the time of kidney biopsy was used to optimize feature selection for the risk model. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the LASSO regression model. Discrimination, calibration, and clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and ROC curve analysis. Internal validation was assessed using the bootstrapping validation. A nomogram for individual assessment was constructed based on the preferable model. RESULTS: Predictors contained in the prediction nomogram included age, body mass index (BMI), mean arterial pressure (MAP), logANA, C3, eGFR and serum uric acid. The model displayed good discrimination with a C-index of 0.794 (95% CI 0.734-0.854) and good calibration. High C-index value of 0.857 (95% CI 0.776-0.938) could still be reached in the interval validation. A nomogram model based on the LASSO model was created for producing a probability score of IFTA in LN patients. CONCLUSION: With excellent predictive abilities, the nomogram may provide a simple and reliable tool to distinguish LN patients with IFTA and helps physicians make clinical decisions in their comprehensive assessment.

9.
Chem Commun (Camb) ; 60(77): 10692-10695, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39239662

RESUMEN

A mechanism based on multiple hydrogen bonds was proposed to describe the great water stability of some hydrated Cu paddle-wheel-based MOFs, which was demonstrated through density functional theory (DFT) calculations and single-crystal X-ray diffraction (SCXRD) of water-loaded MOFs. This mechanism endowed Cu-TDPAT with exceptional water stability and outstanding atmospheric water harvesting capability.

11.
Sci Rep ; 14(1): 20525, 2024 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227624

RESUMEN

To evaluate the repeatability of a novel automated technique called Smart ERA (Smart Endometrial Receptivity Analysis) for the automated segmentation and volume calculation of the endometrium in patients with normal uteri,, and to compare the agreement of endometrial volume measurements between Smart ERA, the semi-automated Virtual Organ Computer-aided Analysis (VOCAL) technique and manual segmentation. This retrospective study evaluated endometrial volume measurement in infertile patients who underwent frozen-thawed embryo transfer (FET). Transvaginal three-dimensional ultrasound scans were performed using a Resona R9 ultrasound machine. Data was collected from patients between 2021 and 2022. Patients with normal uteri and optimal ultrasound images were included. Endometrial volumes were measured using Smart ERA, VOCAL at 15° rotation, and manual segmentation. Intra-observer repeatability and agreement between techniques were assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. A total of 407 female patients were evaluated (mean age 33.2 ± 4.7 years). The repeatability of Smart ERA showed an ICC of 0.983 (95% CI 0.984-0.991). The agreement between Smart ERA and the manual method, Smart ERA and VOCAL, and VOCAL and the manual method, as assessed by ICC, were 0.986 (95% CI 0.977-0.990), 0.943 (95% CI 0.934-0.963), and 0.951 (95% CI 0.918-0.969), respectively. The Smart ERA technique required approximately 3 s for endometrial volume calculation, while VOCAL took around 5 min and the manual segmentation method took approximately 50 min. The Smart-ERA software, which employs a novel three-dimensional segmentation algorithm, demonstrated excellent intra-observer repeatability and high agreement with both VOCAL and manual segmentation for endometrial volume measurement in women with normal uteri. However, these findings should be interpreted with caution, as the algorithm's performance may not be generalizable to populations with different uterine characteristic. Additionally, Smart ERA required significantly less time compared to VOCAL and manual segmentation.


Asunto(s)
Endometrio , Ultrasonografía , Humanos , Femenino , Endometrio/diagnóstico por imagen , Endometrio/anatomía & histología , Adulto , Estudios Retrospectivos , Ultrasonografía/métodos , Útero/diagnóstico por imagen , Imagenología Tridimensional/métodos , Reproducibilidad de los Resultados , Transferencia de Embrión/métodos , Tamaño de los Órganos , Procesamiento de Imagen Asistido por Computador/métodos , Infertilidad Femenina/diagnóstico por imagen
12.
Eur J Pharmacol ; 983: 176998, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39271038

RESUMEN

BACKGROUND: Bacterial keratitis is a common cause of blindness. Antibiotic treatment leads to the rapid release of lipopolysaccharide (LPS), which can activate corneal fibroblasts and cause persistent and excessive inflammatory responses. The anti-inflammatory drugs currently used to treat keratitis have serious side effects. Therefore, the ability of sodium butyrate (NaB), which can suppress the production of proinflammatory cytokines and promote the production of anti-inflammatory cytokines, to ameliorate keratitis was assessed in the present study. METHODS: The effect of NaB on the viability of primary human corneal fibroblasts was assayed with a CCK-8 kit. Cell migration was assessed by an in vitro scratch assay. Cell phenotypes were assessed by Western blotting and immunofluorescence staining. An antibody array was used to measure the production of proinflammatory cytokines and chemokines. RESULTS: At 0-1 mM, NaB had no significant effect on cell viability, promoted the expression of the keratocyte marker keratocan and inhibited the fibroblast marker vimentin. Inhibition of cell migration was observed in the wound healing assay. By targeting the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway, NaB decreased the levels of inflammation-related cytokines and chemokines whose expression was induced by LPS. CONCLUSIONS: NaB maintained the keratocyte phenotype, inhibited cell migration, and relieved LPS-induced inflammatory responses through the JAK/STAT signalling pathway.


Asunto(s)
Ácido Butírico , Movimiento Celular , Córnea , Fibroblastos , Quinasas Janus , Lipopolisacáridos , Factores de Transcripción STAT , Transducción de Señal , Humanos , Lipopolisacáridos/farmacología , Ácido Butírico/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Transducción de Señal/efectos de los fármacos , Quinasas Janus/metabolismo , Movimiento Celular/efectos de los fármacos , Córnea/efectos de los fármacos , Córnea/patología , Córnea/metabolismo , Factores de Transcripción STAT/metabolismo , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/patología , Inflamación/metabolismo , Células Cultivadas , Supervivencia Celular/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
13.
Sensors (Basel) ; 24(17)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39275365

RESUMEN

This paper presents a robust adaptive beamforming algorithm based on an attention convolutional neural network (ACNN) for coprime sensor arrays, named the CAWE-ACNN algorithm. In the proposed algorithm, via a spatial and channel attention unit, an ACNN model is constructed to enhance the features contributing to beamforming weight vector estimation and to improve the signal-to-interference-plus-noise ratio (SINR) performance, respectively. Then, an interference-plus-noise covariance matrix reconstruction algorithm is used to obtain an appropriate label for the proposed ACNN model. By the calculated label and the sample signals received from the coprime sensor arrays, the ACNN is well-trained and capable of accurately and efficiently outputting the beamforming weight vector. The simulation results verify that the proposed algorithm achieves excellent SINR performance and high computation efficiency.

14.
J Cancer Res Ther ; 20(4): 1214-1223, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39206984

RESUMEN

INTRODUCTION: Accumulating evidence suggests the significant involvement of GADD45G in the development of various cancers. This study investigates GADD45G's involvement and methylation status in endometrial cancer (EC), along with molecular mechanisms and potential therapies. METHODS: The expression of GADD45G in EC tissues and controls was evaluated using RNA-seq, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting (WB). Methylation-specific PCR (MSP) evaluated GADD45G's methylation status. Protein-protein interaction (PPI) prediction identified potential interactors of GADD45G, and co-immunoprecipitation (co-IP) confirmed GADD45G interact with Cyclin-dependent kinase 1 (CDK1) and cyclin B1 (CCNB1). Several cell behavior assays were conducted in both in vitro and in vivo settings to comprehensively understand the impact of GADD45G dysregulation in EC. RESULTS: Our findings revealed a significant decrease in the expression of GADD45G in endometrial cancer tissues and cells, which was attributed to its methylation status. Reduced GADD45G expression correlated with increased invasive behaviors in EC cells. Furthermore, GADD45G negatively regulated CDK1 and CCNB1, promoting invasive behaviors at transcript and protein levels. CONCLUSION: This study demonstrated that the downregulation of GADD45G, mediated by methylation, facilitates the invasive behaviors of EC cells through interaction with the CDK1/CCNB1. These findings enhance understanding of the molecular mechanisms underlying endometrial cancer and suggest potential therapeutic strategies targeting GADD45G for treatment.


Asunto(s)
Proteína Quinasa CDC2 , Ciclina B1 , Metilación de ADN , Neoplasias Endometriales , Proteinas GADD45 , Regulación Neoplásica de la Expresión Génica , Animales , Femenino , Humanos , Ratones , Proteína Quinasa CDC2/metabolismo , Proteína Quinasa CDC2/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Ciclina B1/genética , Ciclina B1/metabolismo , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Neoplasias Endometriales/metabolismo , Proteinas GADD45/genética , Proteinas GADD45/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Theor Appl Genet ; 137(9): 203, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39134836

RESUMEN

The common wheat line 4N0461 showed adult-plant resistance to leaf rust. 4N0461 was crossed with susceptible cultivars Nongda4503 and Shi4185 to map the causal resistance gene(s). Segregation of leaf rust response in F2 populations from both crosses was 9 resistant:7 susceptible, indicative of two complementary dominant resistance genes. The genes were located on chromosome arms 3BS and 4BL and temporarily named LrN3B and LrN4B, respectively. Subpopulations from 4N0461 × Nongda4503 with LrN3B segregating as a single allele were used to fine-map LrN3B locus. LrN3B was delineated in a genetic interval of 0.07 cM, corresponding to 106 kb based on the Chinese Spring reference genome (IWGSC RefSeq v1.1). Four genes were annotated in this region, among which TraesCS3B02G014800 and TraesCS3B02G014900 differed between resistant and susceptible genotypes, and both were required for LrN3B resistance in virus-induced gene silencing experiments. Diagnostic markers developed for checking the polymorphism of each candidate gene, can be used for marker-assisted selection in wheat breeding programs.


Asunto(s)
Basidiomycota , Mapeo Cromosómico , Cromosomas de las Plantas , Resistencia a la Enfermedad , Genes de Plantas , Enfermedades de las Plantas , Triticum , Triticum/genética , Triticum/microbiología , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Basidiomycota/patogenicidad , Basidiomycota/fisiología , Cromosomas de las Plantas/genética , Marcadores Genéticos , Genotipo , Alelos
16.
J Nanobiotechnology ; 22(1): 481, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39135072

RESUMEN

Photothermal therapy (PTT) for cancers guided by optical imaging has recently shown great potential for precise diagnosis and efficient therapy. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescence imaging (FLI) is highly desirable owing to its good spatial and temporal resolution, deep tissue penetration, and negligible tissue toxicity. Organic small molecules are attractive as imaging and treatment agents in biomedical research because of their low toxicity, fast clearance rate, diverse structures, ease of modification, and excellent biocompatibility. Various organic small molecules have been investigated for biomedical applications. However, there are few reports on the use of croconaine dyes (CRs), especially NIR-II emission CRs. To our knowledge, there have been no prior reports of NIR-II emissive small organic photothermal agents (SOPTAs) based on CRs. Herein, we report a croconaine dye (CR-TPE-T)-based nanoparticle (CR NP) with absorption and fluorescence emission in the NIR-I and NIR-II windows, respectively. The CR NPs exhibited intense NIR absorption, outstanding photothermal properties, and good biological compatibility. In vivo studies showed that CR NPs not only achieved real-time, noninvasive NIR-II FLI of tumors, but also induced significant tumor ablation with laser irradiation guided by imaging, without apparent side effects, and promoted the formation of antitumor immune memory in a colorectal cancer model. In addition, the CR NPs displayed efficient inhibition of breast tumor growth, improved longevity of mice and triggered efficient systemic immune responses, which further inhibited tumor metastasis to the lungs. Our study demonstrates the great potential of CRs as therapeutic agents in the NIR-II region for cancer diagnosis.


Asunto(s)
Ratones Endogámicos BALB C , Nanopartículas , Imagen Óptica , Terapia Fototérmica , Animales , Terapia Fototérmica/métodos , Ratones , Femenino , Imagen Óptica/métodos , Línea Celular Tumoral , Nanopartículas/química , Nanopartículas/uso terapéutico , Humanos , Colorantes Fluorescentes/química , Rayos Infrarrojos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/terapia
17.
Mol Immunol ; 173: 40-52, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39053388

RESUMEN

HIV-1 chronically infects host CD4+ T lymphocytes and further affects a variety of immune cells, including CD8+ T cells. In our previous study, by analyzing unbiased high-dimensional single-cell RNA-seq data (scRNA-seq), we found that the frequency of GZMK+CD8+ T cells expressing granzyme K (GZMK) was increased in people living with HIV-1 (PLWHs). However, the phenotypic and functional characteristics of these cells in chronic HIV-1 infection and their correlation with disease are not well understood. In this study, we conducted a comprehensive analysis of scRNA-seq and matched T-cell receptor repertoire (TCR) sequencing data to delve into the characterizations of GZMK+CD8+ T cells, which was further validated by flow cytometry. We observed heterogeneity within the GZMK+CD8+ T cells, which could be further subdivided into a GZMK+GZMB- subset and a GZMK+GZMB+ subset, with the latter being significantly enriched in PLWHs. The GZMK+GZMB+ cells are a unique subset within CD8+ T cells, characterized by high proliferation, activation, inflammatory response, clone transition, etc., and are one of the differentiation endpoints by pseudotemporal analysis of CD8+αß T cells. Despite being predominantly composed of effector memory T cells (Tem), similar to the GZMK+GZMB- subset, the GZMK+GZMB+ subset exhibits differentiation at a later stage than the GZMK+GZMB- subset. We also observed that the frequency/count of GZMK+GZMB+CD8+ T cells was negatively correlated with CD4/CD8 ratio, and positively correlated with HIV DNA, IP-10, and MIG levels in PLWHs. In vitro experiments demonstrate that GZMK can potentiate the stimulatory effects of lipopolysaccharide (LPS) on THP-1 macrophages via the TLR-4 pathway, significantly enhancing the secretion of IP-10, MIG, and MCP-1, as well as increasing the proportion of TNF-α+ cells. In conclusion, in PLWHs, GZMK+GZMB+CD8+ T cells are a highly reactive and inflammatory-inducing subset that may be associated with systemic inflammation.


Asunto(s)
Granzimas , Infecciones por VIH , VIH-1 , Inflamación , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linfocitos T CD8-positivos/inmunología , Granzimas/metabolismo , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Inflamación/inmunología , Subgrupos de Linfocitos T/inmunología
18.
Front Immunol ; 15: 1435838, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011045

RESUMEN

Background: IgA nephropathy (IgAN) is a significant contributor to chronic kidney disease (CKD). Renal arteriolar damage is associated with IgAN prognosis. However, simple tools for predicting arteriolar damage of IgAN remain limited. We aim to develop and validate a nomogram model for predicting renal arteriolar damage in IgAN patients. Methods: We retrospectively analyzed 547 cases of biopsy-proven IgAN patients. Least absolute shrinkage and selection operator (LASSO) regression and logistic regression were applied to screen for factors associated with renal arteriolar damage in patients with IgAN. A nomogram was developed to evaluate the renal arteriolar damage in patients with IgAN. The performance of the proposed nomogram was evaluated based on a calibration plot, ROC curve (AUC) and Harrell's concordance index (C-index). Results: In this study, patients in the arteriolar damage group had higher levels of age, mean arterial pressure (MAP), serum creatinine, serum urea nitrogen, serum uric acid, triglycerides, proteinuria, tubular atrophy/interstitial fibrosis (T1-2) and decreased eGFR than those without arteriolar damage. Predictors contained in the prediction nomogram included age, MAP, eGFR and serum uric acid. Then, a nomogram model for predicting renal arteriolar damage was established combining the above indicators. Our model achieved well-fitted calibration curves and the C-indices of this model were 0.722 (95%CI 0.670-0.774) and 0.784 (95%CI 0.716-0.852) in the development and validation groups, respectively. Conclusion: With excellent predictive abilities, the nomogram may be a simple and reliable tool to predict the risk of renal arteriolar damage in patients with IgAN.


Asunto(s)
Glomerulonefritis por IGA , Nomogramas , Humanos , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/diagnóstico , Masculino , Femenino , Adulto , Arteriolas/patología , Estudios Retrospectivos , Persona de Mediana Edad , Riñón/patología , Pronóstico , Tasa de Filtración Glomerular , Modelos Estadísticos
19.
Mikrochim Acta ; 191(8): 472, 2024 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-39028442

RESUMEN

A Ti3C2TxMXene-based biosensor has been developed and the photocatalytic atom transfer radical polymerization (photo ATRP) amplification strategy applied to detect target miRNA-21 (tRNA). Initially, Ti3C2TxMXene nanosheets were synthesized from the Ti3AlC2 MAX precursor via selective aluminum etching. Then, functionalization of Ti3C2TxMXene nanosheets with 3-aminopropyl triethoxysilane (APTES) via silylation reactions to facilitate covalent bonding with hairpin DNA biomolecules specifically designed for tRNA detection. Upon binding with the tRNA, the hairpin DNA liberated the azide (N3) group, initiating a click reaction to affix to the photo ATRP initiator. Through the ATRP photoreaction, facilitated by an organic photoredox catalyst and light, a significant amount of ferrocenyl methyl methacrylate (FMMA) monomer was immobilized on the electrode. Therefore, the electrochemical signal is amplified. The electrochemical efficacy of the biosensor was assessed using square wave voltammetry (SWV). Under optimized conditions, the biosensor demonstrated remarkable sensitivity in detecting tRNA, with a linear detection range from 0.01 fM to 10 pM and a detection limit of 2.81 aM. The findings elucidate that the developed biosensor, in conjunction with the photo ATRP strategy, offers reproducibility, stability, and increased sensitivity, underscoring its potential applications within the experimental medical sector of the biomolecular industry.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Límite de Detección , MicroARNs , Titanio , Técnicas Biosensibles/métodos , MicroARNs/análisis , Técnicas Electroquímicas/métodos , Titanio/química , Catálisis , Procesos Fotoquímicos , Humanos , Polimerizacion , Silanos/química
20.
J Med Virol ; 96(7): e29772, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38949201

RESUMEN

The distinct composition and immune response characteristics of bats' innate and adaptive immune systems, which enable them to serve as host of numerous serious zoonotic viruses without falling ill, differ substantially from those of other mammals, it have garnered significant attention. In this article, we offer a systematic review of the names, attributes, and functions of innate and adaptive immune cells & molecules across different bat species. This includes descriptions of the differences shown by research between 71 bat species in 10 families, as well as comparisons between bats and other mammals. Studies of the immune cells & molecules of different bat species are necessary to understand the unique antiviral immunity of bats. By providing comprehensive information on these unique immune responses, it is hoped that new insights will be provided for the study of co-evolutionary dynamics between viruses and the bat immune system, as well as human antiviral immunity.


Asunto(s)
Inmunidad Adaptativa , Quirópteros , Inmunidad Innata , Quirópteros/virología , Quirópteros/inmunología , Animales , Humanos , Virus/inmunología , Virus/clasificación , Virosis/inmunología , Virosis/virología
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