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1.
J Affect Disord ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39029686

RESUMEN

BACKGROUND: Depression is a significant public health issue, closely associated with epilepsy and oxidative stress (OS). This study aims to explore the level of OS in patients with epilepsy and its relationship with moderate to severe depression (MSD). METHODS: This cross-sectional study includes 10,819 participants aged 20-80 from the National Health and Nutrition Examination Survey (NHANES) database (2013-2020 pre-pandemic). Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and epilepsy was diagnosed based on antiepileptic drug use in the past 30 days. The oxidative balance score (OBS) was calculated from dietary recall and lifestyle habits over the previous 24 h. RESULTS: Compared to non-epileptic subjects, epileptic patients have a significantly higher prevalence of depression. Epileptic patients exhibit lower OBS and Dietary Oxidative Balance Scores (DOBS), while there is no significant difference in Lifestyle Oxidative Balance Scores (LOBS). Depressed patients show lower OBS, DOBS, and LOBS. The mediation model indicates that DOBS mediates 3.44 % of epilepsy-related MSD. CONCLUSIONS: Epileptic patients exhibit significantly higher levels of OS and consume more pro-oxidant foods compared to the general population. However, their lifestyle habits do not differ significantly from those of the control group. Additionally, epileptic patients are at a higher risk of developing MSD. Although a pro-oxidant diet may be associated with epilepsy-mediated MSD, its mediating effect is relatively weak.

2.
Neural Regen Res ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38993125

RESUMEN

ABSTRACT: The cGAS-STING pathway plays an important role In Ischemla/reperfuslon Injury In the heart, liver, brain, and kidney, but its role and mechanisms in cerebral ischemia/reperfusion injury have not been systematically reviewed. Here, we outline the components of the cGAS-STING pathway and then analyze its role in autophagy, ferroptosis, cellular pyroptosis, disequilibrium of calcium homeostasis, inflammatory responses, disruption of the blood-brain barrier, microglia transformation, and complement system activation following cerebral ischemia/reperfusion injury. We further analyze the value of cGAS- STING pathway inhibitors in the treatment of cerebral ischemia/reperfusion injury and conclude that the pathway can regulate cerebral ischemia/reperfusion injury through multiple mechanisms. Inhibition of the cGAS-STING pathway may be helpful in the treatment of cerebral ischemia/reperfusion injury.

3.
Epilepsy Behav ; 157: 109896, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38905914

RESUMEN

BACKGROUND: Neuroinflammation plays an important pathophysiological role in epilepsy; however, the precise connection between immune cells and epilepsy remains unclear. This study used Mendelian randomization (MR) to analyze the causal relationship between 731 immune cell traits and epilepsy. METHODS: Based on data from a genome-wide association study (GWAS), a bidirectional two-sample MR analysis was conducted to investigate the potential influence of immune cell phenotypes on epilepsy. Five MR methods were used to analyze the results, with the inverse variance weighted (IVW) method as the primary method, and the results were corrected using the false discovery rate (FDR) method. Sensitivity analyses were performed to test for heterogeneity and horizontal pleiotropy. RESULTS: After correction for FDR, four immune traits remained significantly associated with epilepsy risk: CD25 expression on memory (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06,P = 2.55 × 10-4), IgD+CD38dim (OR = 1.05, 95 % CI = 1.02 âˆ¼ 1.08, P = 4.73 × 10-4), CD24+CD27+ (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 4.82 × 10-4), and IgD-CD38dim (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 1.04 × 10-3) B cells. The risk of generalized epilepsy was significantly associated with two immune cell traits, whereas that of focal epilepsy was significantly associated with seven immune cell traits. Furthermore, immune cell phenotypes are not affected by genetically predicted epilepsy. CONCLUSION: This MR study affirms the causal connection between circulating immune cells and epilepsy, offering guidance for further understanding of the immune mechanisms that underlie epilepsy and the discovery of novel targets for therapy.

4.
JPRAS Open ; 41: 25-32, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38868740

RESUMEN

Background: Atrophic scarring is a severe form-disfiguring sequela of acne, which can lead to negative effect on patients' life. Fractional microplasma radiofrequency (RF) has emerged as a promising modality, leveraging dermal fibroblast remodeling to enhance aesthetic results for scars and hyperpigmentation. This study evaluates the efficacy and safety of high-power fractional microplasma RF for atrophic acne scars, considering patient tolerance to procedural discomfort. Methods: In this prospective study, 95 Chinese patients with atrophic facial acne scars underwent three sessions of fractional microplasma RF treatment, with assessments at 1, 3, and 6 months post-treatment. Patients were categorized based on treatment power: Group A (50-70 W) and Group B (70-85 W). Efficacy was determined by three independent dermatologists using digital photographs and Echelle d'Evaluation Clinique des Cicatrices d'Acné (ECCA) scores, and patient-reported outcomes gauged satisfaction levels. Results: Eighty-six patients completed the study. Significant improvements were observed, with a reduction in ECCA scores from 107.21 to 42.27 (P<0.05), demonstrating notable scar amelioration across both groups, albeit with a superior outcome in Group B. All patients experienced transient side effects such as pain, erythema, and edema, deemed tolerable with no long-term adverse effects reported. The treatment was well-received, with high satisfaction rates, underscoring its efficacy and acceptable safety profile. Conclusion: Fractional microplasma RF therapy, particularly at higher power settings, is an effective and safe option for treating atrophic acne scars, offering significant aesthetic improvement with manageable discomfort. This modality presents a valuable addition to acne scar management strategies, especially for patients with darker skin tones seeking minimal downtime and reduced risk of hyperpigmentation.

5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(6): 708-714, 2024 Jun 10.
Artículo en Chino | MEDLINE | ID: mdl-38818555

RESUMEN

OBJECTIVE: To explore the distribution and hematological characteristics of rare thalassemia-associated mutations in Chenzhou region of Hunan Province with an aim to provide a basis for genetic counseling and effective prevention. METHODS: A total of 37 370 individuals enrolled from January 2015 to December 2021 were screened by routine blood test and hemoglobin electrophoresis. The genotypes were determined with high-throughput sequencing. RESULTS: A total of 8 455 thalassemia mutations (including 185 rare ones) were detected, which had involved 27 mutational types. Rare type α-Thalassemia --THAI and CD31 (AGG>AAG) have the typical microcytic hypochromic hematological features, whilst SEA-HPFH, CD14 (CTG>-TG), CD37 (TGG>TAG), -90(C>T), Codon 15 (G>A), IVS-I-128 (T>G), CD86 (GCC>GC-) and Chinese Gγ+(Aγδß)0 had typical microcytic hypochromic and ß-thalassemia-associated hematological features of elevated HbA2 or HbF. In addition, the -50(G>A)heterozygotes of ß-thalassemia had normal or slightly decreased MCV and MCH without an increase in HbA2. CONCLUSION: Various forms of thalassemia-associated mutations have been identified in the Chenzhou region of Hunan Province. Above finding has facilitated development of preventive and control strategies for thalassemia as well as birth health programs.


Asunto(s)
Mutación , Humanos , China , Femenino , Masculino , Adulto , Talasemia/genética , Talasemia/sangre , Talasemia alfa/genética , Adulto Joven , Adolescente , Niño , Genotipo , Talasemia beta/genética , Talasemia beta/sangre , Preescolar , Persona de Mediana Edad
6.
Front Aging Neurosci ; 16: 1394738, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737586

RESUMEN

Background: An increasing body of research has demonstrated a robust correlation between circulating inflammatory proteins and neuromyelitis optica spectrum disorders (NMOSD). However, whether this association is causal or whether immune cells act as mediators currently remains unclear. Methods: We employed bidirectional two-sample Mendelian randomization (TSMR) analysis to examine the potential causal association between circulating inflammatory proteins, immune cells, and NMOSD using data from genome-wide association studies (GWAS). Five different methods for Mendelian randomization analyses were applied, with the inverse variance-weighted (IVW) method being the primary approach. Sensitivity analyses were further performed to assess the presence of horizontal pleiotropy and heterogeneity in the results. Finally, a two-step Mendelian randomization (MR) design was employed to examine the potential mediating effects of immune cells. Results: A notable causal relationship was observed between three circulating inflammatory proteins (CSF-1, IL-24, and TNFRSF9) and genetically predicted NMOSD. Furthermore, two immune cell phenotypes, genetically predicted CD8 on naive CD8+ T cells, and Hematopoietic Stem Cell Absolute Count were negatively and positively associated with genetically predicted NMOSD, respectively, although they did not appear to function as mediators. Conclusion: Circulating inflammatory proteins and immune cells are causally associated with NMOSD. Immune cells do not appear to mediate the pathway linking circulating inflammatory proteins to NMOSD.

7.
J Agric Food Chem ; 72(20): 11308-11320, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38720452

RESUMEN

The dearomatization at the hydrophobic tail of the boscalid was carried out to construct a series of novel pyrazole-4-carboxamide derivatives containing an oxime ether fragment. By using fungicide-likeness analyses and virtual screening, 24 target compounds with theoretical strong inhibitory effects against fungal succinate dehydrogenase (SDH) were designed and synthesized. Antifungal bioassays showed that the target compound E1 could selectively inhibit the in vitro growth of R. solani, with the EC50 value of 1.1 µg/mL that was superior to that of the agricultural fungicide boscalid (2.2 µg/mL). The observations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that E1 could reduce mycelial density and significantly increase the mitochondrial number in mycelia cytoplasm, which was similar to the phenomenon treated with boscalid. Enzyme activity assay showed that the E1 had the significant inhibitory effect against the SDH from R. solani, with the IC50 value of 3.3 µM that was superior to that of boscalid (7.9 µM). The mode of action of the target compound E1 with SDH was further analyzed by molecular docking and molecular dynamics simulation studies. Among them, the number of hydrogen bonds was significantly more in the SDH-E1 complex than that in the SDH-boscalid complex. This research on the dearomatization strategy of the benzene ring for constructing pyrazole-4-carboxamides containing an oxime ether fragment provides a unique thought to design new antifungal drugs targeting SDH.


Asunto(s)
Diseño de Fármacos , Inhibidores Enzimáticos , Fungicidas Industriales , Oximas , Pirazoles , Succinato Deshidrogenasa , Succinato Deshidrogenasa/antagonistas & inhibidores , Succinato Deshidrogenasa/química , Succinato Deshidrogenasa/metabolismo , Pirazoles/química , Pirazoles/farmacología , Pirazoles/síntesis química , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Fungicidas Industriales/síntesis química , Relación Estructura-Actividad , Oximas/química , Oximas/farmacología , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Proteínas Fúngicas/química , Proteínas Fúngicas/antagonistas & inhibidores , Proteínas Fúngicas/metabolismo , Simulación del Acoplamiento Molecular , Rhizoctonia/efectos de los fármacos , Éteres/química , Éteres/farmacología , Estructura Molecular
8.
Mol Divers ; 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38609691

RESUMEN

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.

9.
Materials (Basel) ; 17(3)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38591471

RESUMEN

A new type of poly-diamond plate without a catalyst was produced via the high-pressure high-temperature (HPHT) compression of diamond powders. The densification of diamond powders and sp3 to sp2 carbon on the surface under HPHT compression was investigated through the characterization of the microstructure, Raman spectroscopy analysis and electrical resistance measurement. The densification and sp3-sp2 transformation on the surface are mainly affected by the pressure, temperature and particle size. The quantitative analysis of the diamond sp3 and sp2 carbon amount was performed through the peak fitting of Raman spectra. It was found that finer diamond particles under a higher temperature and a lower pressure tend to produce more sp2 carbon; otherwise, they produce less. In addition, it is interesting to note that the local residual stresses measured using Raman spectra increase with the diamond particle size. The suspected reason is that the increased particle size reduces the number of contact points, resulting in a higher localized pressure at each contact point. The hypothesis was supported by finite element calculation. This study provides detailed and quantitative data about the densification of diamond powders and sp3 to sp2 transformation on the surface under HPHT treatment, which is valuable for the sintering of polycrystalline diamonds (PCDs) and the HPHT treatment of diamonds.

10.
Tob Induc Dis ; 222024.
Artículo en Inglés | MEDLINE | ID: mdl-38550907

RESUMEN

INTRODUCTION: This study analyzes the impact of active smoking and secondhand smoke on the ischemic stroke burden of Pakistan, 1990-2019. METHODS: We used data from the Global Burden of Disease (GBD) database to conduct a comprehensive evaluation of ischemic stroke-related indicators in Pakistan, including the number of deaths, mortality rates, disability-adjusted life years (DALYs), DALY rates, and the estimated annual percentage change (EAPC). Joinpoint analysis was applied to assess sex-specific temporal trends in the burden of active smoking and secondhand smoke in Pakistan and regions of Pakistan. These assessments incorporated the Socio-Demographic Index (SDI) and we have made comparative analyses of epidemiological differences between active smoking and secondhand smoke exposure. RESULTS: The burden of ischemic stroke related to tobacco use is presented in terms of the age-standardized mortality rate (ASMR) and the age-standardized disability-adjusted life year rate (ASDR) per 100000 population. The results (ASMR/ASDR) for Pakistan were 6.04/130.81, in the middle SDI region 7.69/176.54, and low-middle SDI region 5.64/124.22. Pakistan's ASMR is higher than the global average of 5.85, while ASDR is lower than the global average of 140.23. From 1990 to 2019, a downward trend in both ASMR and ASDR was observed, indicating progress in controlling tobacco-related stroke burdens. Individuals aged ≥70 years experienced the highest rates of stroke (ASMR: 66.31; ASDR: 1091.20). Gender disparities were evident: men were more affected by active smoking (ASMR: 3.08; ASDR: 78.47) than women (ASMR: 0.79; ASDR: 20.76), while women faced a higher burden from secondhand smoke (ASMR: 0.66; ASDR: 16.33) compared to men (ASMR: 0.79; ASDR: 9.93). Regional differences within Pakistan show fluctuating death and DALY rates. Notably, an increasing trend in female ASDR due to secondhand smoke in the Khyber Pakhtunkhwa Region (annual percentage change, APC=0.17 from 2010 to 2019) calls for focused health interventions. CONCLUSIONS: The study finds ASMR for tobacco-related ischemic stroke in Pakistan exceeds global averages, with significant gender and age disparities in exposure to smoke, highlighting the need for targeted health interventions.

11.
Int J Mol Med ; 53(3)2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38299236

RESUMEN

Stroke, a debilitating cerebrovascular ailment, poses significant threats to human life and health. The intricate interplay between the gut­brain­microbiota axis (GBMA) and cerebral ischemia­reperfusion has increasingly become a focal point of scientific exploration, emerging as a pivotal research avenue in stroke pathophysiology. In the present review, the authors delved into the nexus between the GBMA and neuroinflammation observed post­stroke. The analysis underscored the pivotal roles of histone deacetylase 3 and neutrophil extracellular traps subsequent to stroke incidents. The influence of gut microbial compositions and their metabolites, notably short­chain fatty acids and trimethylamine N­oxide, on neuroinflammatory processes, was further elucidated. The involvement of immune cells, especially regulatory T­cells, and the intricate signaling cascades including cyclic GMP­AMP synthase/stimulator of interferon genes/Toll­like receptor, further emphasized the complex regulatory mechanisms of GBMA in cerebral ischemia/reperfusion injury (CI/RI). Collectively, the present review offered a comprehensive perspective on the metabolic, immune and inflammatory modulations orchestrated by GBMA, augmenting the understanding of its role in neuroinflammation following CI/RI.


Asunto(s)
Isquemia Encefálica , Daño por Reperfusión , Accidente Cerebrovascular , Humanos , Enfermedades Neuroinflamatorias , Eje Cerebro-Intestino , Isquemia Encefálica/metabolismo , Accidente Cerebrovascular/metabolismo , Daño por Reperfusión/metabolismo
12.
Eur J Neurol ; 31(5): e16226, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38323746

RESUMEN

BACKGROUND AND PURPOSE: Ischemic stroke, a major contributor to global disability and mortality, is underpinned by intricate pathophysiological mechanisms, notably neuroinflammation and immune cell dynamics. Prior research has identified a nuanced and often paradoxical link between immune cell phenotypes and ischemic stroke susceptibility. The aim of this study was to elucidate the potential causal links between the median fluorescence intensity (MFI) and morphological parameters (MP) of 731 immune cell types and ischemic stroke risk. METHODS: By analyzing extensive genetic datasets, we conducted comprehensive Mendelian randomization (MR) analyses to discern the genetic correlations between diverse immune cell attributes (MFI and MP) and ischemic stroke risk. RESULTS: Our study identified key immune cell signatures linked to ischemic stroke risk. Both B cells and T cells, among other immune cell types, have a bidirectional influence on stroke risk. Notably, the regulatory T-cell phenotype demonstrates significant neuroprotective properties, with all odds ratio (OR) values and confidence intervals (CIs) being less than 1. Furthermore, CD39 phenotype immune cells, particularly CD39+ CD8+ T cells (inverse variance weighting [IVW] OR 0.92, 95% CI 0.87-0.97; p = 0.002) and CD39+ activated CD4 regulatory T cells (IVW OR 0.93, 95% CI 0.90-0.97; p < 0.001), show notable neuroprotection against ischemic stroke. CONCLUSION: This investigation provides new genetic insights into the interplay between various immune cells and ischemic stroke, underscoring the complex role of immune processes in stroke pathogenesis. These findings lay a foundation for future research, which may confirm and expand upon these links, potentially leading to innovative immune-targeted therapies for stroke prevention and management.


Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Análisis de la Aleatorización Mendeliana , Accidente Cerebrovascular/genética , Linfocitos B , Neuroprotección , Estudio de Asociación del Genoma Completo
13.
Adv Mater ; 36(9): e2309046, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38011581

RESUMEN

Developing a robust strategy for profiling heterogeneous circular tumor cells specifically, distinguishing the phenotypes of which in blood sample of cancer patient precisely, and releasing them sequentially, is significant for cancer management by liquid biopsy. Herein, a bio-inspired free-standing and flexible film composed of TiO2 nanotube and silk fibroin, fabricated with multiply dynamic bioactive surface (TSF/MDBS) by a simple and eco-friendly way including using polydopamine chemistry and dual dynamic covalent chemistry, is reported. The as-prepared TSF/MDBS binds specific peptides toward cells with epithelial biomarker and human epithelial growth factor receptor 2 (HER2) biomarker, and antifouling agents bovine serum albumin for obviating platelets and proteins adhering of blood, can capture heterogeneous CTCs with enhanced capability due to the cytocompatible soft film and exquisite surface design, and further release the captured cells as program, by specifically breaking down the covalent bonds in sequence via the action of adding biocompatible molecules fructose and glutathione. By applying the TSF/MDBS, it can be tailored into desired pieces for identifying CTCs with different phenotypes (HER2-high and HER2-low) from the unprocessed blood samples of breast cancer patients, and finally profiling these heterogeneous CTCs, to discriminate HER2 positive or negative of breast cancer patients in clinical applications.


Asunto(s)
Neoplasias de la Mama , Fibroínas , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Plaquetas , Tipificación Molecular , Biomarcadores
14.
Seizure ; 114: 44-49, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38039807

RESUMEN

BACKGROUND: Inflammation plays a role in the development and advancement of epilepsy, but the relationship between inflammatory cytokines and epilepsy is still not well understood. Herein, we use two-sample Mendelian randomization (MR) to examine the causal association between systemic inflammatory cytokines and epilepsy. METHODS: We conducted a bidirectional two-sample MR analysis based on genome-wide association study data of 41 serum cytokines from 8293 Finnish individuals with various epilepsy subtypes from the International League against Epilepsy Consortium. RESULTS: Our study showed that three inflammatory cytokines were associated with epilepsy, five were associated with generalized epilepsy, four were associated with focal epilepsy, one was associated with focal epilepsy-documented lesion negative, three were associated with juvenile absence epilepsy, one was associated with childhood absence epilepsy, two were associated with focal epilepsy-documented lesion other than hippocampal sclerosis, and two were associated with juvenile myoclonic epilepsy. Furthermore, the expression of systemic inflammatory cytokines was unaffected by genetically predicted epilepsy. CONCLUSION: This study suggested that several inflammatory cytokines are probably the factors correlated with epilepsy. Additional research is required to ascertain if these biomarkers have therapeutic potential to prevent or manage epilepsy.


Asunto(s)
Epilepsias Parciales , Epilepsia Tipo Ausencia , Humanos , Niño , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Citocinas/genética
15.
Front Mol Neurosci ; 16: 1294450, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38089678

RESUMEN

Introduction: The causal relationship between inflammatory factors and stroke subtypes remains unclear. This study aimed to analyze the causal relationship between 41 inflammatory factors and these two factors using Mendelian randomization (MR). Methods: We performed a two-sample MR analysis to assess the causal effects of 41 inflammatory cytokines on stroke and its subtypes and conducted a genome-wide association study (GWAS) data. The inverse-variance weighted (IVW) method was adopted as the main MR method, and we performed a series of two-sample Mendelian randomizations and related sensitivity analyses. Results: The study indicated some suggestive evidences: using the IVW approach, we found that lower possible levels of IL-4 were positively associated with the occurrence of stroke (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.99, p = 0.014), higher interleukin (IL)-1ß, IL-12p70 levels may be positively correlated with the occurrence of stroke (OR = 1.09, 95% CI: 1.01-1.18, p = 0.027; OR = 1.08, 95% CI: 1.02-1.15, p = 0.015). For IS, results showed that lower levels of IL-4, tumor necrosis factor-related apoptosis-inducing ligand were positively associated with the occurrence of possible ischemic stroke (IS) (OR = 0.92, 95% CI: 0.87-0.98, p = 0.006; OR = 0.95, 95% CI: 0.91-1.00, p = 0.031), higher levels of IL-1ß, IL-12p70 and vascular endothelial growth factor (VEGF) may be positively correlated with the occurrence of IS (OR = 1.09, 95% CI: 1.00-1.19, p = 0.042; OR = 1.07, 95% CI: 1.01-1.15, p = 0.035; OR = 1.06, 95% CI: 1.00-1.12, p = 0.034). Our findings suggest that decreased IL-17 levels could potentially be linked to a higher likelihood of intracerebral hemorrhage (ICH) (OR = 0.51, 95% CI: 0.28-0.93, p = 0.028). For subtypes of stroke, IS and ICH, higher levels of growth regulated oncogene-α, beta nerve growth factor, IL-18, macrophage colony-stimulating factor, and induced protein 10 upregulated the risk factors while lower levels of IL-2ra and IL-17 upregulated the risk factors. Conclusion: In summary, our research validated that inflammatory markers have a pivotal impact on the development of stroke and could potentially offer a fresh approach to treating this condition.

16.
Front Neurol ; 14: 1269237, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37965164

RESUMEN

Background: Leukodystrophies are hereditary white matter diseases characterized by genetic polymorphisms and considerable phenotypic variability. They can be classified into myelin and non-myelin malformations. These diseases are rare, affecting 1 out of 250,000-500,000 individuals and can manifest at any age. A subtype of leukodystrophy, associated with missense mutations in the RNA polymerase subunit III (POLR3A) gene, is inherited in an autosomal recessive manner. Case report: We report and analyse a case of a 34-year-old female who presented with ataxia. Magnetic Resonance Imaging (MRI) of the brain revealed demyelinating lesions in the white matter. Genetic testing identified the c.4044C > G and c.1186-2A > G variants in the POLR3A gene. The patient was diagnosed with hypomyelinating leukodystrophy type 7 and received neurotrophic and symptomatic supportive therapy. However, after 1 month of follow-up, there was no improvement in her symptoms. Conclusion: POLR3A-induced leukodystrophy is relatively rare and not well understood, making it challenging to diagnose and easy to overlook. The prognosis for this disease is generally poor, significantly impacting the quality of life of affected individuals. Currently, no cure is available for this condition, and treatment is limited to managing symptoms. Further research into new treatment methods for POLR3A-induced leukodystrophy is imperative to improve the quality of life and potentially extend the life expectancy of patients.

17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(10): 1197-1203, 2023 Oct 10.
Artículo en Chino | MEDLINE | ID: mdl-37730217

RESUMEN

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses. METHODS: 46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis. RESULTS: Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77). CONCLUSION: NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.


Asunto(s)
Trastornos de los Cromosomas , Variaciones en el Número de Copia de ADN , Embarazo , Femenino , Humanos , Aberraciones Cromosómicas , Trastornos de los Cromosomas/diagnóstico , Trastornos de los Cromosomas/genética , Aneuploidia , Feto
18.
Int J Radiat Biol ; 99(12): 1879-1889, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37523652

RESUMEN

PURPOSE: The application of high-intensity focused ultrasound (HIFU) in hepatocellular carcinoma (HCC) was promising. However, whether the effect of HIFU is comparable with that of transarterial chemoembolization (TACE) has not been determined. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, WanFang Data, CqVip, CNKI, and CBM databases were searched for randomized controlled trials (RCTs), cohort studies, and case-control studies. The methodological quality of each study was evaluated. When there is no statistical heterogeneity, the fixed effect model would be used to merge data. Otherwise, the random effect model would be utilized. Sensitivity analyses were conducted by excluding one study each time. Subgroup analyses were conducted based on age, sex, tumor number, relative number of the patients with Child-Pugh C grade in each group, the percentage of patients with Child-Pugh C grade in the whole study, and tumor load. Publication bias was evaluated by Egger's test and Begg's test. RESULTS: Six cohort studies including 188 patients from HIFU group and 224 patients from TACE group were obtained for further analysis. The meta-analysis suggested HIFU and TACE showed no differences in postoperative 1-year overall survival (OS) rate, tumor response (including complete response, partial response, stable disease, and progressive disease), and postoperative complications. Moreover, compared with TACE, HIFU showed higher postoperative 6-month and 2-year OS rates. Subgroup analyses, meta regression analysis and sensitivity analyses indicated the findings above were reliable. Additionally, no potential publication bias was detected. CONCLUSION: For HCC, when compared with TACE, HIFU might show comparable safety but better effect. Considering the limitations of current studies, more well-designed studies are needed to validate our conclusion.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Resultado del Tratamiento , Quimioembolización Terapéutica/efectos adversos , Estudios de Cohortes
19.
Biomater Sci ; 11(15): 5232-5239, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37338183

RESUMEN

Piezoelectric polymer nanofibers are attracting increasing attention in the stimulation of cell growth and proliferation in tissue engineering and wound healing applications. However, their intrinsic non-biodegradability in vivo hinders widespread applications in the biological fields. Herein, we designed, synthesized and characterized composite materials of silk fibroin (SF)/LiNbO3 (LN) nanoparticles/MWCNTs by electrospinning technology, which displayed good biocompatibility and comparable piezoelectric properties with an output current of up to 15 nA and output voltage of up to 0.6 V under pressure stimulation, remaining stable after 200 cycles of pressure release without significant decay. Meanwhile, the mechanical properties of the LN/CNTs/SF-nanofiber scaffolds (SF-NFSs) are also enhanced, with a tensile strength reaching 12.84 MPa and an elongation at break reaching 80.07%. Importantly, in vitro cell proliferation experiments showed that the LN/CNTs/SF-NFSs promoted cell proliferation at a rate of 43%. Accordingly, the mouse wound healing experiments further indicated that they could accelerate the healing of skin wounds in mice that were continuously moving. Therefore, SF-based piezoelectric nanofibrous scaffolds exhibit potential for use in rapid wound healing and this sheds light on smart treatment for tissue engineering in biomedicine.


Asunto(s)
Fibroínas , Nanofibras , Ratones , Animales , Andamios del Tejido , Cicatrización de Heridas , Ingeniería de Tejidos , Seda
20.
Biomaterials ; 300: 122206, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37348325

RESUMEN

Postoperative recurrence frequently occurs in patients with colorectal cancer (CRC) due to residual microtumors and host cellular immune dysfunction, leading to major setbacks in clinical outcomes and CRC staging. As an increasingly prevalent therapeutic option for CRC patients, neoadjuvant chemoradiotherapy bears unmet challenges of limited tumor targeting and common side effects of gastrointestinal reaction and radiodermatitis. It is highly desirable to develop neoadjuvant treatment paradigms that impart both tumor-targeting accuracy and protection against recurrence of resectable CRC. Here we report a versatile photo-regulated nanoagonist of plasmonic gold blackbody (AuPB) with a polydopamine (PDA) coating carrying manganese ion (Mn2+) payloads (AuPB@PDA/Mn). When armed with second near-infrared (NIR-II) light, AuPB@PDA/Mn with broad-band localized surface plasmon resonance generates local hyperthermia and discharges Mn2+ ions, which evidently amplify the effects of immunogenic cell death in tumor cells and activate the cyclic GMP-AMP synthase/stimulator of interferon genes pathway in dendritic cells (DCs), hence potentiating the maturation of DC and the secretion of type I interferon in a synergistic way. Matured DCs undertake the task of tumor antigen presentation as the crosstalk to adaptive immunity. As such, the administration of AuPB@PDA/Mn coupled with NIR-II laser irradiation has eminently augmented the infiltration of CD8+ T cells as well as the development of memory CD8+ T cells in colorectal tumor models, substantiating enhanced immunomodulatory efficacy against primary and recurrent CRC. Our strategy highlights the potency of an integrated NIR-II photothermal and immunoregulatory modality by photo-activate delivery of Mn2+ ions, as a neoadjuvant paradigm for presurgical tumor debulking and against postoperative tumor recurrence.


Asunto(s)
Neoplasias Colorrectales , Neoplasias , Humanos , Terapia Neoadyuvante , Linfocitos T CD8-positivos , Recurrencia Local de Neoplasia , Fotones , Neoplasias Colorrectales/tratamiento farmacológico , Línea Celular Tumoral
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