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1.
PLoS One ; 19(7): e0297410, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38950015

RESUMEN

BACKGROUND: Epilepsy is a common and serious chronic neurological disorder, and some patients suffer from cognitive dysfunction. We aim to assess the efficacy and safety of acupuncture combined with traditional Chinese herbal for primary epilepsy patients with cognitive impairment. METHODS: To search the randomized control trials (RCTs) published before April 20, 2023 from PubMed, Embase, Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Web of science, and Wanfang Database. The risk of bias within each individual trial was evaluated using the Cochrane Collaboration tool. RevMan5.3 software was used for statistical analysis. The odds ratio (OR) or weighted mean difference (WMD) with a 95% confidence interval (CI) was calculated for each RCT before data pooling. RESULTS: The primary outcomes involve changes in cognitive function and behavioral disturbances. The secondary outcomes focused on quality of life and adverse effects. CONCLUSION: The results of this review are expected to provide new guidelines for the treatment of primary epilepsy patients with cognitive impairment. TRIAL REGISTRATION: This systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (Registration number: CRD42023415355).


Asunto(s)
Terapia por Acupuntura , Disfunción Cognitiva , Medicamentos Herbarios Chinos , Epilepsia , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto , Humanos , Disfunción Cognitiva/terapia , Disfunción Cognitiva/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Epilepsia/terapia , Epilepsia/complicaciones , Terapia por Acupuntura/métodos , Medicamentos Herbarios Chinos/uso terapéutico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Calidad de Vida , Terapia Combinada
2.
Chem Sci ; 15(26): 10073-10083, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38966352

RESUMEN

Cytosine modifications, particularly 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), play crucial roles in numerous biological processes. Current analytical methods are often constrained to the separate detection of either 5mC or 5hmC, or the combination of both modifications. The ability to simultaneously detect C, 5mC, and 5hmC at the same genomic locations with precise stoichiometry is highly desirable. Herein, we introduce a method termed engineered deaminase-assisted sequencing (EDA-seq) for the simultaneous quantification of C, 5mC, and 5hmC at the same genomic sites. EDA-seq utilizes a specially engineered protein, derived from human APOBEC3A (A3A), known as eA3A-M5. eA3A-M5 exhibits distinct deamination capabilities for C, 5mC, and 5hmC. In EDA-seq, C undergoes complete deamination and is sequenced as T. 5mC is partially deaminated resulting in a mixed readout of T and C, and 5hmC remains undeaminated and is read as C. Consequently, the proportion of T readouts (P T) reflects the collective occurrences of C and 5mC, regulated by the deamination rate of 5mC (R 5mC). By determining R 5mC and P T values, we can deduce the precise levels of C, 5mC, and 5hmC at particular genomic locations. We successfully used EDA-seq to simultaneously measure C, 5mC, and 5hmC at specific loci within human lung cancer tissue and their normal counterpart. The results from EDA-seq demonstrated a strong concordance with those obtained from the combined application of BS-seq and ACE-seq methods. EDA-seq eliminates the need for bisulfite treatment, DNA oxidation or glycosylation and uniquely enables simultaneous quantification of C, 5mC and 5hmC at the same genomic locations.

3.
J Colloid Interface Sci ; 675: 293-301, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38970914

RESUMEN

Lignite, as one of the coal materials, has been considered a promising precursor for hard carbon anodes in sodium-ion batteries (SIBs) owing to its low cost and high carbon yield. Nevertheless, hard carbon directly derived from lignite pyrolysis typically exhibits highly ordered microstructure with narrow interlayer spacing and relatively unreactive interfacial properties, owing to the abundance of polycyclic aromatic hydrocarbons and inert aromatic rings within its molecular composition. Herein, an innovative demineralization activating strategy is established to simultaneously modulate the interfacial properties and the microstructure of lignite-derived carbon for the development of high-performance SIBs. Demineralization process not only creates numerous void spaces in the matrix of lignite precursor to assist aromatic hydrocarbon rearrangement, thereby reducing the ordering and expanding interlayer spacing, but also exposes more interfacial oxygen-containing functional groups to effectively increasing the sodium storage active sites. As a result, the optimal demineralized lignite-derived hard carbon (DLHC 1300) delivers a high reversible capacity of 335.6 mAh g-1 at 30 mA g-1, superior rate performance of 246.3 mAh g-1 at 6 A g-1 and nearly 100 % capacity retention after 1100 cycles at 1A g-1. Furthermore, the optimized DLHC 1300 material functions as an outstanding anode in sodium ion full cells. This work significantly advances the development of low-cost, high-performance commercial hard carbon anodes for SIBs.

4.
Food Res Int ; 190: 114627, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38945580

RESUMEN

The effect of varying proportions (w/w) of natural aromatic extract of black tea (NAEBT) with pre-emulsification on the water-holding capacity (WHC) of pork meat batter was investigated. The addition of NAEBT significantly reduced the cooking loss (CL) of pork meat batter from 23.95 % to 18.30 % (P < 0.05). Furthermore, NAEBT with pre-emulsification significantly improved the color stability and increased the springiness (P < 0.05). The results of TBARS and carbonyls indicated that NAEBT with pre-emulsification significantly alleviated oxidative damage to proteins (P < 0.05), resulting in an increased level of ß-sheet (P < 0.05), as confirmed by FT-IR analysis. As a result, the water mobility of pork meat batter was restricted (P < 0.05), resulting in an increase in the energy storage modulus (P < 0.05) and a decrease in the pore size. In summary, the WHC of pork meat batter was improved by the antioxidant effect of the NAEBT.


Asunto(s)
Antioxidantes , Productos de la Carne , Extractos Vegetales , Carne de Cerdo , , Agua , Agua/química , Extractos Vegetales/química , Carne de Cerdo/análisis , Animales , Té/química , Productos de la Carne/análisis , Antioxidantes/análisis , Porcinos , Culinaria , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Espectroscopía Infrarroja por Transformada de Fourier
5.
Sci Rep ; 14(1): 14639, 2024 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918463

RESUMEN

This study aimed to develop a deep learning model to predict the risk stratification of all-cause death for older people with disability, providing guidance for long-term care plans. Based on the government-led long-term care insurance program in a pilot city of China from 2017 and followed up to 2021, the study included 42,353 disabled adults aged over 65, with 25,071 assigned to the training set and 17,282 to the validation set. The administrative data (including baseline characteristics, underlying medical conditions, and all-cause mortality) were collected to develop a deep learning model by least absolute shrinkage and selection operator. After a median follow-up time of 14 months, 17,565 (41.5%) deaths were recorded. Thirty predictors were identified and included in the final models for disability-related deaths. Physical disability (mobility, incontinence, feeding), adverse events (pressure ulcers and falls from bed), and cancer were related to poor prognosis. A total of 10,127, 25,140 and 7086 individuals were classified into low-, medium-, and high-risk groups, with actual risk probabilities of death of 9.5%, 45.8%, and 85.5%, respectively. This deep learning model could facilitate the prevention of risk factors and provide guidance for long-term care model planning based on risk stratification.


Asunto(s)
Aprendizaje Profundo , Cuidados a Largo Plazo , Humanos , Femenino , Masculino , Anciano , China/epidemiología , Estudios Prospectivos , Anciano de 80 o más Años , Causas de Muerte , Personas con Discapacidad/estadística & datos numéricos , Medición de Riesgo , Mortalidad/tendencias , Factores de Riesgo , Pronóstico
6.
J Org Chem ; 89(13): 9543-9550, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38874168

RESUMEN

A visible-light-initiated C-H trifluoromethylation of quinoxalin-2(1H)-ones was established using a Z-scheme V2O5/g-C3N4 heterojunction as a recyclable photocatalyst in an inert atmosphere at room temperature under additive-free and mild conditions. A variety of trifluoromethylated quinoxalin-2-(1H)-one derivatives were heterogeneously generated in moderate to high yields, exhibiting good functional group tolerance. Remarkably, the recyclable V2O5/g-C3N4 catalyst could be reused five times with a slight loss of catalytic activity.

7.
BMC Nurs ; 23(1): 391, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844934

RESUMEN

BACKGROUND: The period of standardized training is a transitional stage when Generation Z newly graduated registered nurses (Gen Z NGRNs) change their role from student to nurse. Affected by the COVID-19, they lack clinical practice and practicum experience in emergency departments in their university studies. At the beginning of career, they are under great pressure. Resilience is one of the factors that reduce their stress level and increases endurance. It is of interest to understand how this representative group of nurses gained and played the experience of resilience early in their careers. OBJECTIVE: To explore Gen Z NGRNs' experience and process of resilience, to provide a new perspective and theoretical basis for psychological rehabilitation or intervention of medical staff who experienced transition shock. METHODS: This study employed a qualitative design based on the phenomenological approach. 18 nurses from a third-level class-A hospital in Shanghai who participated in standardized training in emergency department were enrolled using purposive sampling. Data collection was through in-depth and semi-structured interviews and continued until reaching data saturation. RESULTS: The investigation uncovered three themes and ten subthemes. Pressure and challenge contained high workload and high risk coexist, death's stress response, more emergencies and high professional requirements. Coping and adaptation contained team help, psychological restructuring, peer support, transformational leadership. Reflection and planning contained enhance learning, appreciate life. CONCLUSIONS: Our study described the embodiment and coping experience of the physical and mental stress faced by Gen Z NGRNs during their standardized training in the emergency department. It is emphasized that nurse educators should pay attention to the character and actual needs of Gen Z NGRNs, explore and formulate strategies, so as to guide NGRNs to quickly adapt and grow in the new role. The ultimate goal is to increase nurse retention and improve the quality of nursing.

8.
Front Surg ; 11: 1344269, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38872725

RESUMEN

Objective: To assess the feasibility, safety, and efficiency of simultaneous anterograde video laparoscopic inguinal and pelvic lymphadenectomy for penile cancer. Materials and methods: We reviewed retrospectively the records of 22 patients (44 lateral) who underwent inguinal lymph nodes dissection for penile cancer. The procedure was standardized as two planes, three holes, and six steps. Two Separate-planes: superior plane of eternal oblique aponeurosis/ / fascia lata; inferior plane of superficial camper fascia. Three holes: two artificial lateral boundary holes, the internal and external boundary holes, and the hole of oval fossa. Six steps: separate the first separate-plane; separate the second layer; separate two artificial lateral boundary holes; free great saphenous vein; separate the third hole and clean up the deep inguinal lymph nodes; pelvic lymphadenectomy. Results: A total of 22 cases were included and 9 patients underwent simultaneous pelvic lymphadenectomy. The average operation time on both sides was 7.52 ± 3.29 h, which was 0.5-1 h/side after skilled. The average amount of bleeding was 93.18 ± 50.84 ml. A total of 8 patients had postoperative complications, accounting for 36.36%, and no complications great than Clavien-Dindo class III occurred. Conclusion: This study demonstrated that the video laparoscopic simultaneous anterograde inguinal and pelvic lymphadenectomy is a feasible and safe technique. Indocyanine Green was helpful for lymph node identify.

9.
Int Nurs Rev ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38899768

RESUMEN

AIMS: This study aimed to examine the relationship between emergency capacity, coping styles, and mental workload among nurses. BACKGROUND: Emergency capacity, coping styles, and mental workload are all variables associated with work. Identifying the relationship between these variables can facilitate administrators to implement tailored and effective intervention strategies to improve individual performance, quality of care, and medical safety. METHODS: A quantitative cross-sectional study was carried out to investigate 605 Chinese clinical nurses in seven tertiary hospitals by using personal information form, emergency capacity scale for nurses, simplified coping skill questionnaire, and the NASA-Task Load Index. RESULTS: Emergency capacity and mental workload were found at moderate levels. The multiple linear regression model suggested that spinsterhood, no children, high workload, always anxiety or nervousness, and lower monthly income were the influencing factors of mental workload. Positive coping style was positively correlated with emergency capacity and negatively correlated with mental workload. Negative coping style was negatively related to emergency capacity and positively related to mental workload. Additionally, coping styles played a partial mediating role in the relationship between emergency capacity and mental workload through constructing a structural equation model, but the effects of positive coping style and negative coping style are opposite. CONCLUSION: Our results showed that coping styles played a mediating role in the relationship between emergency capacity and mental workload. Managers can alleviate the mental workload of nurses by cultivating positive coping styles and improving emergency capacity. IMPLICATIONS FOR NURSING AND NURSING POLICY: Mental workload of nurses deserves more attention in medical institutions. The results of our study provide evidence for improving employee health, promoting positive behaviors, and optimizing organizational management. Nursing managers should take feasible measures to fulfill nurses' needs for emergency capacity and coping strategies to alleviate nurses' mental workload, so as to stimulate their intrinsic motivation and positive organizational behavior.

10.
Front Aging Neurosci ; 16: 1404756, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887608

RESUMEN

Purpose: The purpose of the present study was to identify predictors of severe white matter hyperintensity (WMH) with obesity (SWO), and to build a prediction model for screening obese people with severe WMH without Nuclear Magnetic Resonance Imaging (MRI) examination. Patients subjects and methods: From September 2020 to October 2021, 650 patients with WMH were recruited consecutively. The subjects were divided into two groups, SWO group and non-SWO group. Univariate and Logistic regression analysis were was applied to explore the potential predictors of SWO. The Youden index method was adopted to determine the best cut-off value in the establishment of the prediction model of SWO. Each parameter had two options, low and high. The score table of the prediction model and nomogram based on the logistic regression were constructed. Of the 650 subjects, 487 subjects (75%) were randomly assigned to the training group and 163 subjects (25%) to the validation group. By resampling the area under the curve (AUC) of the subject's operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram's clinical usefulness. By resampling the area under the curve (AUC) of the subject's operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram's clinical usefulness. Results: Logistic regression demonstrated that hypertension, uric acid (UA), complement 3 (C3) and Interleukin 8 (IL-8) were independent risk factors for SWO. Hypertension, UA, C3, IL-8, folic acid (FA), fasting C-peptide (FCP) and eosinophil could be used to predict the occurrence of SWO in the prediction models, with a good diagnostic performance, Areas Under Curves (AUC) of Total score was 0.823 (95% CI: 0.760-0.885, p < 0.001), sensitivity of 60.0%, specificity of 91.4%. In the development group, the nomogram's AUC (C statistic) was 0.829 (95% CI: 0.760-0.899), while in the validation group, it was 0.835 (95% CI: 0.696, 0.975). In both the development and validation groups, the calibration curves following 1,000 bootstraps showed a satisfactory fit between the observed and predicted probabilities. DCA showed that the nomogram had great clinical utility. Conclusion: Hypertension, UA, C3, IL-8, FA, FCP and eosinophil models had the potential to predict the incidence of SWO. When the total score of the model exceeded 9 points, the risk of SWO would increase significantly, and the nomogram enabled visualization of the patient's WMH risk. The application prospect of our models mainly lied in the convenient screening of SWO without MRI examination in order to detect SWO and control the WMH hazards early.

11.
CNS Neurosci Ther ; 30(6): e14786, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38828694

RESUMEN

PURPOSE: To investigate dynamic functional connectivity (dFC) within the cerebellar-whole brain network and dynamic topological properties of the cerebellar network in obstructive sleep apnea (OSA) patients. METHODS: Sixty male patients and 60 male healthy controls were included. The sliding window method examined the fluctuations in cerebellum-whole brain dFC and connection strength in OSA. Furthermore, graph theory metrics evaluated the dynamic topological properties of the cerebellar network. Additionally, hidden Markov modeling validated the robustness of the dFC. The correlations between the abovementioned measures and clinical assessments were assessed. RESULTS: Two dynamic network states were characterized. State 2 exhibited a heightened frequency, longer fractional occupancy, and greater mean dwell time in OSA. The cerebellar networks and cerebrocerebellar dFC alterations were mainly located in the default mode network, frontoparietal network, somatomotor network, right cerebellar CrusI/II, and other networks. Global properties indicated aberrant cerebellar topology in OSA. Dynamic properties were correlated with clinical indicators primarily on emotion, cognition, and sleep. CONCLUSION: Abnormal dFC in male OSA may indicate an imbalance between the integration and segregation of brain networks, concurrent with global topological alterations. Abnormal default mode network interactions with high-order and low-level cognitive networks, disrupting their coordination, may impair the regulation of cognitive, emotional, and sleep functions in OSA.


Asunto(s)
Cerebelo , Red Nerviosa , Apnea Obstructiva del Sueño , Humanos , Masculino , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Cerebelo/fisiopatología , Persona de Mediana Edad , Adulto , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Imagen por Resonancia Magnética , Conectoma , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Red en Modo Predeterminado/fisiopatología , Red en Modo Predeterminado/diagnóstico por imagen
12.
Mol Cell Endocrinol ; : 112321, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38936596

RESUMEN

The tricarboxylic acid (TCA) cycle is an essential interface that coordinates cellular metabolism and is as a primary route determining the fate of a variety of fuel sources, including glucose, fatty acid and glutamate. The crosstalk of nutrients replenished TCA cycle regulates breast cancer (BC) progression by changing substrate levels-induced epigenetic alterations, especially the methylation, acetylation, succinylation and lactylation. Long non-coding RNAs (lncRNA) have dual roles in inhibiting or promoting energy reprogramming, and so altering the metabolic flux of fuel sources to the TCA cycle, which may regulate epigenetic modifications at the cellular level of BC. This narrative review discussed the central role of the TCA cycle in interconnecting numerous fuels and the induced epigenetic modifications, and the underlying regulatory mechanisms of lncRNAs in BC.

13.
Ageing Res Rev ; 98: 102339, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38754634

RESUMEN

Alzheimer's disease (AD) is the most common neurodegenerative disorder that affects the cerebral cortex and hippocampus, and is characterised by progressive cognitive decline and memory loss. A recent report of a patient carrying a novel gain-of-function variant of RELN (H3447R, termed RELN-COLBOS) who developed resilience against presenilin-linked autosomal-dominant AD (ADAD) has generated enormous interest. The RELN-COLBOS variant enhances interactions with the apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor (VLDLR), which are associated with delayed AD onset and progression. These findings were validated in a transgenic mouse model. Reelin is involved in neurodevelopment, neurogenesis, and neuronal plasticity. The evidence accumulated thus far has demonstrated that the Reelin pathway links apolipoprotein E4 (ApoE4), amyloid-ß (Aß), and tubulin-associated unit (Tau), which are key proteins that have been implicated in AD pathogenesis. Reelin and key components of the Reelin pathway have been highlighted as potential therapeutic targets and biomarkers for AD.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Apolipoproteína E4 , Moléculas de Adhesión Celular Neuronal , Proteínas de la Matriz Extracelular , Proteínas del Tejido Nervioso , Proteína Reelina , Serina Endopeptidasas , Proteínas tau , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/genética , Proteínas de la Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/genética , Moléculas de Adhesión Celular Neuronal/metabolismo , Moléculas de Adhesión Celular Neuronal/genética , Humanos , Serina Endopeptidasas/metabolismo , Serina Endopeptidasas/genética , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Animales , Péptidos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Proteínas tau/genética , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Ratones
14.
Curr Gene Ther ; 24(4): 331-345, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38783531

RESUMEN

BACKGROUND: Osteoarthritis (OA) is a highly debilitating, degenerative pathology of cartilaginous joints affecting over 500 million people worldwide. The global economic burden of OA is estimated at $260-519 billion and growing, driven by aging global population and increasing rates of obesity. To date, only the multi-injection chondroanabolic treatment regimen of Fibroblast Growth Factor 18 (FGF18) has demonstrated clinically meaningful disease-modifying efficacy in placebo-controlled human trials. Our work focuses on the development of a novel single injection disease-modifying gene therapy, based on FGF18's chondroanabolic activity. METHODS: OA was induced in Sprague-Dawley rats using destabilization of the medial meniscus (DMM) (3 weeks), followed by intra-articular treatment with 3 dose levels of AAV2-FGF18, rh- FGF18 protein, and PBS. Durability, redosability, and biodistribution were measured by quantifying nLuc reporter bioluminescence. Transcriptomic analysis was performed by RNA-seq on cultured human chondrocytes and rat knee joints. Morphological analysis was performed on knee joints stained with Safranin O/Fast Green and anti-PRG antibody. RESULTS: Dose-dependent reductions in cartilage defect size were observed in the AAV2-FGF18- treated joints relative to the vehicle control. Total defect width was reduced by up to 76% and cartilage thickness in the thinnest zone was increased by up to 106%. Morphologically, the vehicle- treated joints exhibited pronounced degeneration, ranging from severe cartilage erosion and bone void formation, to subchondral bone remodeling and near-complete subchondral bone collapse. In contrast, AAV2-FGF18-treated joints appeared more anatomically normal, with only regional glycosaminoglycan loss and marginal cartilage erosion. While effective at reducing cartilage lesions, treatment with rhFGF18 injections resulted in significant joint swelling (19% increase in diameter), as well as a decrease in PRG4 staining uniformity and intensity. In contrast to early-timepoint in vitro RNA-seq analysis, which showed a high degree of concordance between protein- and gene therapy-treated chondrocytes, in vivo transcriptomic analysis, revealed few gene expression changes following protein treatment. On the other hand, the gene therapy treatment exhibited a high degree of durability and localization over the study period, upregulating several chondroanabolic genes while downregulating OA- and fibrocartilage-associated markers. CONCLUSION: FGF18 gene therapy treatment of OA joints can provide benefits to both cartilage and subchondral bone, with a high degree of localization and durability.


Asunto(s)
Cartílago Articular , Dependovirus , Modelos Animales de Enfermedad , Factores de Crecimiento de Fibroblastos , Terapia Genética , Osteoartritis , Ratas Sprague-Dawley , Animales , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/farmacología , Terapia Genética/métodos , Ratas , Humanos , Osteoartritis/terapia , Osteoartritis/genética , Osteoartritis/patología , Cartílago Articular/patología , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Dependovirus/genética , Condrocitos/metabolismo , Vectores Genéticos , Masculino
15.
Biomaterials ; 309: 122617, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38788457

RESUMEN

Effectively addressing retinal issues represents a pivotal aspect of blindness-related diseases. Novel approaches involving reducing inflammation and rebalancing the immune response are paramount in the treatment of these conditions. This study delves into the potential of a nanogel system comprising polyethylenimine-benzene boric acid-hyaluronic acid (PEI-PBA-HA). We have evaluated the collaborative impact of cerium oxide nanozyme and chemokine CX3CL1 protein for targeted immunomodulation and retinal protection in uveitis models. Our nanogel system specifically targets the posterior segment of the eyes. The synergistic effect in this area reduces oxidative stress and hampers the activation of microglia, thereby alleviating the pathological immune microenvironment. This multifaceted drug delivery system disrupts the cycle of oxidative stress, inflammation, and immune response, suppressing initial immune cells and limiting local retinal structural damage induced by excessive immune reactions. Our research sheds light on interactions within retinal target cells, providing a promising avenue for the development of efficient and innovative drug delivery platforms.


Asunto(s)
Cerio , Quimiocina CX3CL1 , Nanogeles , Uveítis , Animales , Cerio/química , Cerio/farmacología , Uveítis/tratamiento farmacológico , Nanogeles/química , Quimiocina CX3CL1/metabolismo , Ratas , Retina/efectos de los fármacos , Retina/metabolismo , Inmunomodulación/efectos de los fármacos , Modelos Animales de Enfermedad , Polietileneimina/química , Estrés Oxidativo/efectos de los fármacos , Ácido Hialurónico/química , Masculino , Polietilenglicoles
16.
Front Immunol ; 15: 1365226, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38812511

RESUMEN

Objective: The aberrant mobilization and activation of various T lymphocyte subpopulations play a pivotal role in the pathogenesis of diabetic kidney disease (DKD), yet the regulatory mechanisms underlying these processes remain poorly understood. Our study is premised on the hypothesis that the dysregulation of immune checkpoint molecules on T lymphocytes disrupts kidney homeostasis, instigates pathological inflammation, and promotes DKD progression. Methods: A total of 360 adult patients with DKD were recruited for this study. The expression of immune checkpoint molecules on T lymphocytes was assessed by flow cytometry for peripheral blood and immunofluorescence staining for kidney tissue. Single-cell sequencing (scRNA-seq) data from the kidneys of DKD mouse model were analyzed. Results: Patients with DKD exhibited a reduction in the proportion of CD3+TIM-3+ T cells in circulation concurrent with the emergence of significant albuminuria and hematuria (p=0.008 and 0.02, respectively). Conversely, the incidence of infection during DKD progression correlated with an elevation of peripheral CD3+TIM-3+ T cells (p=0.01). Both univariate and multivariate logistic regression analysis revealed a significant inverse relationship between the proportion of peripheral CD3+TIM-3+ T cells and severe interstitial mononuclear infiltration (OR: 0.193, 95%CI: 0.040,0.926, p=0.04). Immunofluorescence assays demonstrated an increase of CD3+, TIM-3+ and CD3+TIM-3+ interstitial mononuclear cells in the kidneys of DKD patients as compared to patients diagnosed with minimal change disease (p=0.03, 0.02 and 0.002, respectively). ScRNA-seq analysis revealed decreased gene expression of TIM3 on T lymphocytes in DKD compared to control. And one of TIM-3's main ligands, Galectin-9 on immune cells showed a decreasing trend in gene expression as kidney damage worsened. Conclusion: Our study underscores the potential protective role of TIM-3 on T lymphocytes in attenuating the progression of DKD and suggests that monitoring circulating CD3+TIM3+ T cells may serve as a viable strategy for identifying DKD patients at heightened risk of disease progression.


Asunto(s)
Nefropatías Diabéticas , Receptor 2 Celular del Virus de la Hepatitis A , Linfocitos T , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Humanos , Nefropatías Diabéticas/inmunología , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/patología , Femenino , Persona de Mediana Edad , Masculino , Animales , Ratones , Linfocitos T/inmunología , Linfocitos T/metabolismo , Anciano , Adulto , Inflamación/inmunología , Riñón/patología , Riñón/inmunología , Ratones Endogámicos C57BL , Progresión de la Enfermedad
17.
Sci Total Environ ; 937: 173482, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38795982

RESUMEN

Extensive application of rare earth element oxide nanoparticles (REE NPs) has raised a concern over the possible toxic health effects after human exposure. Once entering the body, REE NPs are primarily processed by phagocytes in particular macrophages and undergo biotic phosphate complexation in lysosomal compartment. Such biotransformation affects the target organs and in vivo fate of REE NPs after escaping the lysosomes. However, the immunomodulatory effects of intraphagolysosomal dissolved REE NPs remains insufficient. Here, europium oxide (Eu2O3) NPs were pre-incubated with phagolysosomal simulant fluid (PSF) to mimic the biotransformation of europium oxide (p-Eu2O3) NPs under acid phagolysosome conditions. We investigated the alteration in immune cell components and the hematopoiesis disturbance on adult mice after intravenous administration of Eu2O3 NPs and p-Eu2O3 NPs. Our results indicated that the liver and spleen were the main target organs for Eu2O3 NPs and p-Eu2O3 NPs. Eu2O3 NPs had a much higher accumulative potential in organs than p-Eu2O3 NPs. Eu2O3 NPs induced more alterations in immune cells in the spleen, while p-Eu2O3 NPs caused stronger response in the liver. Regarding hematopoietic disruption, Eu2O3 NPs reduced platelets (PLTs) in peripheral blood, which might be related to the inhibited erythrocyte differentiation in the spleen. By contrast, p-Eu2O3 NPs did not cause significant disturbance in peripheral PLTs. Our study demonstrated that the preincubation with PSF led to a distinct response in the immune system compared to the pristine REE NPs, suggesting that the potentially toxic effects induced by the release of NPs after phagocytosis should not be neglected, especially when evaluating the safety of NPs application in vivo.


Asunto(s)
Europio , Hematopoyesis , Lisosomas , Nanopartículas del Metal , Óxidos , Animales , Europio/toxicidad , Ratones , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Óxidos/toxicidad , Hematopoyesis/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Bazo/efectos de los fármacos , Nanopartículas/toxicidad
18.
Sci Total Environ ; 937: 173449, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38797425

RESUMEN

Accurate identification and rapid analysis of PM2.5 sources and formation mechanisms are essential to mitigate PM2.5 pollution. However, studies were limited in developing a method to apportion sources to the total PM2.5 mass in real-time. In this study, we developed a real-time source apportionment method based on chemical mass balance (CMB) modeling and a mass-closure PM2.5 composition online monitoring system in Shenzhen, China. Results showed that secondary sulfate, secondary organic aerosol (SOA), vehicle emissions and secondary nitrate were the four major PM2.5 sources during autumn 2019 in Shenzhen, together contributed 76 % of PM2.5 mass. The novel method was verified by comparing with other source apportionment methods, including offline filter analysis, aerosol mass spectrometry, and carbon isotopic analysis. The comparison of these methods showed that the new real-time method obtained results generally consistent with the others, and the differences were interpretable and implicative. SOA and vehicle emissions were the major PM2.5 and OA contributors by all methods. Further investigation on the OA sources indicated that vehicle emissions were not only the main source of primary organic aerosol (POA), but also the main contributor to SOA by rapid aging of the exhaust in the atmosphere. Our results demonstrated the great potential of the new real-time source apportionment method for aerosol pollution control and deep understandings on emission sources.

19.
Cont Lens Anterior Eye ; : 102178, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724427

RESUMEN

OBJECTIVE: This study aimed to compare the changes in corneal morphological characteristics in corneal topography assessments performed after wearing orthokeratology (OK) lenses with different back optic zone diameters (BOZDs). These changes included the change ratios of the apical corneal power (ACP), the maximum relative corneal refractive power (mRCRP), and the treatment zone diameter (TZD). METHODS: Data from 133 children with myopia (average age 9.50 ± 1.23 years) treated at Fudan University Eye and Ear, Nose, and Throat Hospital were retrospectively analyzed. All participants wore the same brand of tangent-design OK lens (corneal refractive therapy, CRT). According to the BOZD, the patients were divided into two groups, of 5.0 and 6.0 mm BOZD, respectively. Corneal topography was analyzed at baseline, as well as 1 day, 1 week, and 1 month after wearing the lenses, and the change ratios of ACP, mRCRP, and TZD were compared between the two groups. RESULTS: The change ratio of the ACP did not differ significantly between the BOZD 5.0 and 6.0 groups after 1 day or 1 week of lens wear (P = 0.170 and P = 0.113, respectively). However, after 1 month of lens wear, the change ratio of the ACP in the BOZD 5.0 group was significantly larger than that in the BOZD 6.0 group (P < 0.001). After 1 month of lens wear, the mRCRP along the horizontal and vertical meridians was higher (P < 0.05) and the TZD was significantly smaller (P < 0.001) in the BOZD 5.0 group than in the BOZD 6.0 group. CONCLUSION: In CRT OK lenses, a small BOZD lens can produce faster corneal shaping, a larger mRCRP, and a smaller TZD, which may have a better effect on slowing ocular axial length elongation. The lens parameters are also a factor affecting the TZD.

20.
J Adv Res ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38704089

RESUMEN

INTRODUCTION: Aging of hematopoietic stem cells (HSCs) has emerged as an important challenge to human health. Recent advances have raised the prospect of rejuvenating aging HSCs via specific medical interventions, including pharmacological treatments. Nonetheless, efforts to develop such drugs are still in infancy until now. OBJECTIVES: We aimed to screen the prospective agents that can rejuvenate aging HSCs and explore the potential mechanisms. METHODS: We screened a set of natural anti-aging compounds through oral administration to sub-lethally irradiated mice, and identified 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) as a potent rejuvenating agent for aging HSCs. Then naturally aged mice were used for the follow-up assessment to determine the HSC rejuvenating potential of TSG. Finally, based on the transcriptome and DNA methylation analysis, we validated the role of the AMP-activated protein kinase (AMPK)-ten-eleven-translocation 2 (Tet2) axis (the AMPK-Tet2 axis) as the underlying mechanisms of TSG for ameliorating HSCs aging. RESULTS: TSG treatment not only significantly increased the absolute number of common lymphoid progenitors (CLPs) along with B lymphocytes, but also boosted the HSCs/CLPs repopulation potential of aging mice. Further elaborated mechanism research demonstrated that TSG supplementation restored the stemness of aging HSCs, as well as promoted an epigenetic reprograming that was associated with an improved regenerative capacity and an increased rate of lymphopoiesis. Such effects were diminished when the mice were co-treated with an AMPK inhibitor, or when it was performed in Tet2 knockout mice as well as senescent cells assay. CONCLUSION: TSG is effective in rejuvenating aging HSCs by modulating the AMPK- Tet2 axis and thus represents a potential candidate for developing effective HSC rejuvenating therapies.

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