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1.
Neural Regen Res ; 20(4): 917-935, 2025 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38989927

RESUMEN

Epilepsy is a severe, relapsing, and multifactorial neurological disorder. Studies regarding the accurate diagnosis, prognosis, and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy. The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression, protein expression, ion channel activity, energy metabolites, and gut microbiota composition. Satisfactory results are lacking for conventional treatments for epilepsy. Surgical resection of lesions, drug therapy, and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy. Non-pharmacological treatments, such as a ketogenic diet, gene therapy for nerve regeneration, and neural regulation, are currently areas of research focus. This review provides a comprehensive overview of the pathogenesis, diagnostic methods, and treatments of epilepsy. It also elaborates on the theoretical basis, treatment modes, and effects of invasive nerve stimulation in neurotherapy, including percutaneous vagus nerve stimulation, deep brain electrical stimulation, repetitive nerve electrical stimulation, in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation. Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures. Additionally, many new technologies for the diagnosis and treatment of epilepsy are being explored. However, current research is mainly focused on analyzing patients' clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level, which has led to a lack of consensus regarding the mechanisms related to the disease.

2.
Sci Rep ; 14(1): 21448, 2024 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271729

RESUMEN

Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) have the potential application in evaluating pathological structural change of the optic nerve. We aimed to evaluate the value of the OCT and OCTA parameters of the optic disk and macular in differentiating early chronic primary angle-closure glaucoma (CPACG) and early pituitary adenoma (PA) in case of mild visual field defects (the mean defect (MD) > 6 dB). The results showed that regarding OCTA parameters, CPACG patients had lower retinal blood flow density of most layers of the optic disk and macular than PA patients. Regarding OCT parameters, CPACG patients had thinner circumpapillary retinal nerve fiber layer (CP-RNFL) in all quadrants and average CP-RNFL, ganglion cell layer (GCL) and macular ganglion cell complex (GCC) in each quadrant of macular inner and outer rings, and inner plexus layer (IPL) of macular inner ring, superior-outer ring and temporal-outer ring than PA patients. The Z test indicated that OCTA parameters and OCT parameters had similar value in the diagnosis of disease. In conclusion, in the case of similar visual field damage, early CPACG patients have smaller blood flow density and thinner optic disk and macular than early PA. OCTA has similar performance to OCT in diagnosing CPACG and PA.


Asunto(s)
Adenoma , Glaucoma de Ángulo Cerrado , Disco Óptico , Neoplasias Hipofisarias , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Glaucoma de Ángulo Cerrado/fisiopatología , Glaucoma de Ángulo Cerrado/diagnóstico , Glaucoma de Ángulo Cerrado/patología , Glaucoma de Ángulo Cerrado/diagnóstico por imagen , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/patología , Masculino , Femenino , Persona de Mediana Edad , Adenoma/patología , Adenoma/diagnóstico por imagen , Disco Óptico/patología , Disco Óptico/diagnóstico por imagen , Adulto , Enfermedad Crónica , Células Ganglionares de la Retina/patología , Campos Visuales/fisiología , Anciano
3.
Int J Biochem Cell Biol ; : 106662, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293559

RESUMEN

Dysregulated protein homeostasis, characterized by abnormal protein accumulation and aggregation, is a key contributor to the progression of neurodegenerative disorders such as Huntington's disease and spinocerebellar ataxia type 3 (SCA3). Previous studies have identified PIAS1 gene variants in patients with late-onset SCA3 and Huntington's disease. This study aims to elucidate the role of PIAS1 and its S510G variant in modulating the pathogenic mechanisms of SCA3. Through in vitro biochemical analyses and in vivo assays, we demonstrate that PIAS1 stabilizes both wild-type and mutant ataxin-3 (ATXN3). The PIAS1 S510G variant, however, selectively reduces the stability and SUMOylation of mutant ATXN3, thereby decreasing its aggregation and toxicity while maintaining the stability of wild-type ATXN3. This effect is mediated by a weakened interaction with the SUMO-conjugating enzyme UBC9 in the presence of mutant ATXN3. In Drosophila models, downregulation of dPIAS1 resulted in reduced levels of mutant ATXN3 and alleviated associated phenotypes, including retinal degeneration and motor dysfunction. Our findings suggest that the PIAS1 S510G variant acts as a genetic modifier of SCA3, highlighting the potential of targeting SUMOylation as a therapeutic strategy for this disease.

4.
Clin Lab ; 70(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39257125

RESUMEN

BACKGROUND: The high sensitivity of HBsAg quantitative tests has led to some challenges in the qualitative interpretation of weakly positive specimens. This study aimed to explore the clinical utility of neutralization confirma-tory testing for specimens with low positive hepatitis B surface antigen (HBsAg). METHODS: A retrospective analysis was conducted on outpatient and inpatient cases, from January 2021 to January 2022, at the Zhongshan City People's Hospital, Zhongshan. Confirmatory testing as well as enzyme-linked immunosorbent assay (ELISA) was applied to reanalyze 382 samples with low positive HBsAg detected by chemilumi-nescence microparticle immunoassay (CMIA). A retrospective analysis of hepatitis B serum markers, including e-antigen, e-antibody, and core antibody patterns, was also performed. RESULTS: When the HBsAg value ranged from 0.05 - 0.09 IU/mL, the positivity rate of the confirmatory testing was 34.5%. The HBsAg true positivity levels were all between 0.07 and 0.09. In the range of 0.10 - 0.49, the positivity rate of confirmatory testing was 96.1%. The three methods exhibited a high consistency, when testing samples with relatively high HBsAg values. A receiver operating characteristic (ROC) analysis showed that the optimal sensitivity and specificity were achieved at 0.14 IU/mL. For the HBV e-antigen-positive and negative groups, the positivity rate of confirmatory testing was 100% and 93.8%, with no statistical difference between them. CONCLUSIONS: For specimens with weakly positive, low-value HBsAg, particularly when the hepatitis B surface an-tigen level is less than 0.14 IU/mL, neutralization confirmatory testing can serve as a means for further confirmation.


Asunto(s)
Antígenos de Superficie de la Hepatitis B , Hepatitis B , Sensibilidad y Especificidad , Humanos , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Estudios Retrospectivos , Hepatitis B/diagnóstico , Hepatitis B/sangre , Hepatitis B/inmunología , Femenino , Masculino , Persona de Mediana Edad , Ensayo de Inmunoadsorción Enzimática/métodos , Adulto , Pruebas de Neutralización/métodos , Curva ROC , Virus de la Hepatitis B/inmunología , Adulto Joven
5.
Nutr Hosp ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39235086

RESUMEN

BACKGROUND: myopia is associated with sight-threatening potential complications, and it becoming increasingly common globally. However, the association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and myopia remains unclear and the evidence is controversial. Thus, this study aimed to investigate the association between serum 25(OH)D concentrations and myopia in the U.S. SUBJECT AND METHODS: this study used the National Health and Nutrition Examination Survey (NHANES) 2001-2008 data. The logistic regression was applied to explore the association between serum 25(OH)D concentrations and myopia. RESULTS: among the 14,051 participants, the prevalence of myopia was 33.2 % (4,668/14,051). In the multivariate regression models, serum 25(OH)D concentrations as continuous variable were non-significantly associated with the prevalence of myopia (adjusted OR, 0.98 [95 % CI, 0.97-1.00]) after adjusting all covariates. As a categorical variable, serum 25(OH)D compared with the lowest tertile, the adjusted ORs with increasing tertiles were 0.96 (95 % CI: 0.89,1.05) and 0.95 (95 % CI: 0.86, 1.06). In myopia participants, serum 25(OH)D concentrations were also non-significantly associated with the progress of myopia. In stratified analyses, the results remain stable with different ages, sex, and education parameters. CONCLUSIONS: serum 25(OH)D concentrations were non-significantly associated with myopia in the U.S. POPULATION: We need more prospective studies to provide evidence.

6.
Medicine (Baltimore) ; 103(31): e39110, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39093742

RESUMEN

The relationship between clinical outcomes and various factors influencing pregnancy was analyzed to provide reference data for patients and clinicians when selecting embryo transfer protocols. This was a retrospective study of 1309 transfer cycles between June 1, 2018, and May 1, 2023, in the Reproductive Medicine Center. Univariate analysis was performed on various factors that may have affected pregnancy outcomes, and further regression analysis was performed on those factors found by univariate analysis to correlate positively with clinical pregnancy outcomes. Finally, the embryo transfer schemes were compared based on the analysis results. The results showed that the stage of embryonic development significantly affected pregnancy outcomes after transplantation (P < .01, 95% confidence interval: 2.554 [1.958-3.332]). There was no significant difference in the pregnancy rate between 1 high-quality blastocyst transfer and 2 cleavage-stage embryos or blastocyst transfer (64.22% vs 70.11%, P = .439); however, the rate of multiple pregnancies after 1 high-quality blastocyst transfer was close to the rate of natural conception. These data show that the transfer of single high-quality blastocysts can significantly reduce the multiple pregnancy rate while ensuring an ideal pregnancy rate, which can be used as a reference for planning the first transplantation in patients with good prognoses.


Asunto(s)
Transferencia de Embrión , Fertilización In Vitro , Resultado del Embarazo , Índice de Embarazo , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Transferencia de Embrión/métodos , Transferencia de Embrión/estadística & datos numéricos , Adulto , Fertilización In Vitro/métodos , Criopreservación/métodos , Embarazo Múltiple/estadística & datos numéricos
7.
Sci Rep ; 14(1): 19274, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164291

RESUMEN

Structure, stability, electronic structure, spectroscopy and chemical bonding properties of a fluorine atom doped gas-phase small to medium-sized magnesium clusters, FMgn (n = 2-20), systematically investigated by CALYPSO software together with density functional theory (DFT). Structural calculations showed that FMgn has a structural diversity which is rarely reported in other magnesium-based clusters before. F atoms were always located in the outer layer of the Mgn host clusters and only two or three Mg atoms surround it. FMg18 was revealed to be supposed to have robust relative stability. Charge transfer and density of states were calculated for analyzing the electronic structure characteristics. Theoretical calculations of IR, Raman and UV-Vis spectra were computed to provide data guidelines for future experimental observations. Finally, the F-Mg and Mg-Mg chemical bonds of the FMgn clusters were analyzed, including the critical bonding points (BCPs) of Laplacian of electron density (Δρ), electron localization function (ELF) and interaction region indicator (IRI). The kind and strength of chemical bonds reveal the mechanism by which the F atom was rapidly stabilized by Mgn (n = 2-20) host clusters.

8.
Sci Transl Med ; 16(760): eadi6626, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141700

RESUMEN

Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions in patients with nvAMD and in mouse models. Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex-mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD.


Asunto(s)
Trampas Extracelulares , Células Asesinas Naturales , Degeneración Macular , Animales , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Degeneración Macular/patología , Humanos , Trampas Extracelulares/metabolismo , Neovascularización Coroidal/patología , Neovascularización Coroidal/metabolismo , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Neutrófilos/metabolismo , Neutrófilos/inmunología , Masculino , Anciano , Femenino
9.
Plant J ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39139125

RESUMEN

Soil salinity significantly limits rice productivity, but it is poorly understood how excess sodium (Na+) is delivered to the grains at the reproductive stage. Here, we functionally characterized OsHAK4, a member of the clade IV HAK/KUP/KT transporter subfamily in rice. OsHAK4 was localized to the plasma membrane and exhibited influx transport activity for Na+, but not for K+. Analysis of organ- and growth stage-dependent expression patterns showed that very low expression levels of OsHAK4 were detected at the vegetative growth stage, but its high expression in uppermost node I, peduncle, and rachis was found at the reproductive stage. Immunostaining indicated OsHAK4 localization in the phloem region of node I, peduncle, and rachis. Knockout of OsHAK4 did not affect the growth and Na+ accumulation at the vegetative stage. However, at the reproductive stage, the hak4 mutants accumulated higher Na+ in the peduncle, rachis, husk, and brown rice compared to the wild-type rice. Element imaging revealed higher Na+ accumulation at the phloem region of the peduncle in the mutants. These results indicate that OsHAK4 plays a crucial role in retrieving Na+ from the phloem in the upper nodes, peduncle, and rachis, thereby preventing Na+ distribution to the grains at the reproductive stage of rice.

10.
Int J Ophthalmol ; 17(8): 1510-1518, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39156768

RESUMEN

Cataract is the main cause of visual impairment and blindness worldwide while the only effective cure for cataract is still surgery. Consecutive phacoemulsification under topical anesthesia has been the routine procedure for cataract surgery. However, patients often grumbled that they felt more painful during the second-eye surgery compared to the first-eye surgery. The intraoperative pain experience has negative influence on satisfaction and willingness for second-eye cataract surgery of patients with bilateral cataracts. Intraoperative ocular pain is a complicated process induced by the nociceptors activation in the peripheral nervous system. Immunological, neuropsychological, and pharmacological factors work together in the enhancement of intraoperative pain. Accumulating published literatures have focused on the pain enhancement during the second-eye phacoemulsification surgeries. In this review, we searched PubMed database for articles associated with pain perception differences between consecutive cataract surgeries published up to Feb. 1, 2024. We summarized the recent research progress in mechanisms and interventions for pain perception enhancement in consecutive second-eye phacoemulsification cataract surgeries. This review aimed to provide novel insights into strategies for improving patients' intraoperative experience in second-eye cataract surgeries.

11.
J Cosmet Dermatol ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177015

RESUMEN

BACKGROUND: Keratosis pilaris (KP) is a prevalent benign dermatological condition characterized by small bumps at the hair follicles alongside surrounding redness, significantly impacting both aesthetics and mental well-being. OBJECTIVE: This study investigated the potential benefits of a non-cross-linked hyaluronic acid (HA) compound for treating KP. METHODS: A split-body, investigator-blinded, randomized, intraindividual comparative clinical trial was conducted. The non-cross-linked HA compound was injected into KP-affected regions on both upper arms. The treatment was delivered across four sessions scheduled at 4-week intervals. Blinded physicians and patients assessed differences in erythema, skin roughness, and overall scores between treated and control areas at the final follow-up visit. At the 12th and 24th weeks post-treatment, a four-point scale was utilized to assess subjects' perceived treatment efficacy. Additionally, dermoscopic images, histological alterations, and adverse events were monitored. RESULTS: Physician assessments revealed a significant reduction in roughness and overall scores for treated areas compared to controls. Patient self-assessments also reflected improvements in roughness, redness, and overall scores for treated sides at the final visit, with 35.71% of patients demonstrating sustained improvement in redness and 71.43% reporting persistent improvements in roughness at 24th weeks post-treatment. The dermatoscopic examinations revealed a notable enhancement in both the quantity of follicular plugs and the extent of erythema among the subjects in the treatment group. Histopathological outcomes also demonstrated improvement. CONCLUSION: This study suggests that the non-cross-linked HA compound effectively improves skin roughness and promotes hair shaft growth in KP treatment, demonstrating a favorable safety profile. These findings position it as a potentially viable alternative therapy in clinical practice.

12.
Front Pediatr ; 12: 1361850, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39149537

RESUMEN

Objective: To preliminarily explore the risk factors for post-infectious bronchiolitis obliterans (PIBO) complicating adenovirus pneumonia (ADVP) in children through a meta-analysis. Methods: A systematic search was conducted on three English-language databases (PubMed, Web of Science and The National Library of Medicine) and two Chinese-language databases (China National Knowledge Infrastructure and the Wanfang Database) between database inception and 1 January 2023. Data analysis was conducted using Stata 15.1 software. Results: A total of 10 articles, reporting 14 risk factors, were included in the analysis, with 8 risk factors taken into consideration. Through the meta-analysis, 5 risk factors were identified for PIBO complicating ADVP in paediatric patients: hypoxaemia [odds ratio (OR) = 9.37, 95% CI: 4.22, 20.77, p < 0.001], persistent wheezing (OR = 4.65, 95% CI: 2.20, 9.82, p < 0.001), mechanical ventilation (OR = 3.87, 95% CI: 2.37, 6.33, p < 0.001), length of hospital stay (LoHS) (OR = 1.25, 95% CI: 1.09, 1.43, p < 0.001) and fever duration (OR = 1.08, 95% CI: 1.02, 1.14, p = 0.009). Conclusion: Existing evidence suggests that hypoxaemia, persistent wheezing, mechanical ventilation, LoHS and fever duration are risk factors for PIBO complicating ADVP in children. These findings underscore the need for enhanced assessment and management in clinical practice. This study may provide such a clinical prediction model from the identified 5 risk factors for PIBO and offer valuable insights for preventing bronchiolitis obliterans in children with ADVP.

13.
Lipids Health Dis ; 23(1): 271, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198852

RESUMEN

BACKGROUND: Adverse atherogenic lipid profile is associated with an increased risk of major adverse cardiac events in patients after acute coronary syndrome (ACS). Knowledge regarding the impact of statins on lipid profile remains limited. METHODS: We retrospectively analysed multicenter, real-world data from the Chinese Cardiovascular Association Database-iHeart Project. Patients with a primary diagnosis of ACS from 2014 to 2021 during index hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed target achievement of atherogenic lipid profile, including apolipoprotein B (< 80 mg/dL), low-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L), lipoprotein(a) [Lp(a)] (< 30 mg/dL), triglycerides (< 1.7 mmol/L), remnant cholesterol (RC) (< 0.78 mmol/L), non-high-density lipoprotein cholesterol (< 2.6 mmol/L) at baseline and follow-up. Multivariate Cox regression models were employed to investigate the association between patient characteristics and target achievement. RESULTS: Among 4861 patients, the mean age was 64.9 years. Only 7.8% of patients had all atherogenic lipids within the target range at follow-up. The proportion of target achievement was for LDL-C 42.7%, Lp(a) 73.3%, and RC 78.5%. Patients with female sex, younger age, myocardial infarction, hypertension, and hypercholesteremia were less likely to control LDL-C, Lp(a), and RC. An increase in the burden of comorbidities was negatively associated with LDL-C and Lp(a) achievements but not with RC. CONCLUSIONS: A substantial gap exists between lipid control and the targets recommended by contemporary guidelines. Novel therapeutics targeting the whole atherogenic lipid profile will be warranted to improve cardiovascular outcomes.


Asunto(s)
Síndrome Coronario Agudo , LDL-Colesterol , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/sangre , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Anciano , LDL-Colesterol/sangre , Estudios Retrospectivos , Triglicéridos/sangre , Aterosclerosis/sangre , Aterosclerosis/tratamiento farmacológico , Bases de Datos Factuales , Lípidos/sangre , Lipoproteína(a)/sangre , China/epidemiología , Factores de Riesgo , Pueblos del Este de Asia
14.
Jpn J Clin Oncol ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39180717

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) reactivation is a recognized complication of cytotoxic chemotherapy in patients with chronic hepatitis B. However, the risk of HBV reactivation with immune checkpoint inhibitors (ICIs) remains uncertain due to their exclusion from clinical trials. This study aimed to assess the incidence of HBV reactivation in patients with cancer undergoing ICI therapy, exploring associated risk factors. METHODS: This retrospective study included patients with cancer who tested positive for hepatitis B surface antigen (HBsAg). The primary endpoint was incidence of HBV reactivation, whereas the secondary endpoint was occurrence of hepatic adverse events during ICI therapy. RESULTS: Among the 162 eligible patients (median age 59 years; 85.8% men), HBV reactivation occurred in 4.3% at a median of 13 weeks post-treatment initiation. At baseline, HBV DNA was undetectable in 78 patients; 88 received antiviral prophylaxis, while 74 patients did not. Reactivation rates were 3.5% in HBsAg-positive and 10% in hepatitis B core antibody (HBcAb)-positive individuals, with an overall rate of 4.3%. These rates were 1.1% with prophylaxis and 8.1% without. Twenty-two patients had grade 3-4 hepatitis, and 25 tested HBsAg-negative but HBcAb-positive. No HBV-related fatalities occurred. The absence of antiviral treatment was a significant risk factor for HBV reactivation. CONCLUSIONS: Our study underscores the risk of HBV reactivation in patients with cancer undergoing ICI therapy, especially among those lacking antiviral prophylaxis. Regular HBV DNA testing and antiviral prophylaxis are crucial preventive measures for HBV reactivation. These findings emphasize the importance of monitoring HBV status in patients receiving ICIs.

15.
Front Cell Infect Microbiol ; 14: 1407807, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39206044

RESUMEN

Background: Cryptococcosis is an invasive infection that commonly affects immunosuppressed individuals, especially patients with HIV infection. Cryptococcal infection in HIV-infected patients should be considered a major health concern because it is associated with high morbidity and mortality rates. In this study, we aimed to evaluate the clinical characteristics and prognostic factors of cryptococcal infections in human immunodeficiency virus (HIV)-infected patients to facilitate effective clinical management and improve patient outcomes. Methods: We reviewed and analyzed the clinical data and relevant laboratory test results of HIV-infected patients with positive cryptococcal cultures and reserved strains between 2013 and 2023 from Beijing Youan Hospital affiliated to Capital Medical University. The clinical characteristics and laboratory test results of the patients were compared, and the correlation between parameters and the prognoses of the patients at different observation timepoints (3, 6, 9, and 12 months) was analyzed. Results: A total of 76 patients (70 males and six females; median age, 37 years) were included in this study. The results indicated that the later the initiation of antiretroviral therapy (ART) after the diagnosis of HIV infection (> 6 months), the higher the probability of death. Analysis of the correlation between the time of ART initiation and the timing of treatment for cryptococcal infections showed that the time of ART initiation was strongly related to survival at different timepoints. Initiation of ART time within 0-4 weeks, 4-6 weeks and more than 6weeks of starting treatment for Cryptococcus infection was associated with a lower mortality rate at 12-month, the 3-month, 6- and 9-month follow-up timepoint separately. Conclusions: Although cryptococcal infection in HIV-infected patients continues to be a challenging and intricate issue, ART is a key factor that affects its prognosis. The later ART is started, the worse the prognosis of the infection. The time of ART initiation and the timing of treatment for cryptococcal infections should be further refined and balanced based on different clinical courses. Thus, clinicians should pay closer attention to cryptococcal infections in patients with HIV infection and initiate ART based on the patient's clinical condition.


Asunto(s)
Criptococosis , Infecciones por VIH , Humanos , Femenino , Masculino , Adulto , Infecciones por VIH/complicaciones , Pronóstico , Criptococosis/mortalidad , Criptococosis/tratamiento farmacológico , Criptococosis/complicaciones , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Infecciones Oportunistas Relacionadas con el SIDA/mortalidad , Antifúngicos/uso terapéutico , Cryptococcus/aislamiento & purificación , Hospitales , China/epidemiología
17.
Nat Commun ; 15(1): 7324, 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-39183203

RESUMEN

During the progression of proliferative vitreoretinopathy (PVR) following ocular trauma, previously quiescent retinal pigment epithelial (RPE) cells transition into a state of rapid proliferation, migration, and secretion. The elusive molecular mechanisms behind these changes have hindered the development of effective pharmacological treatments, presenting a pressing clinical challenge. In this study, by monitoring the dynamic changes in chromatin accessibility and various histone modifications, we chart the comprehensive epigenetic landscape of RPE cells in male mice subjected to traumatic PVR. Coupled with transcriptomic analysis, we reveal a robust correlation between enhancer activation and the upregulation of the PVR-associated gene programs. Furthermore, by constructing transcription factor regulatory networks, we identify the aberrant activation of enhancer-driven RANK-NFATc1 pathway as PVR advanced. Importantly, we demonstrate that intraocular interventions, including nanomedicines inhibiting enhancer activity, gene therapies targeting NFATc1 and antibody therapeutics against RANK pathway, effectively mitigate PVR progression. Together, our findings elucidate the epigenetic basis underlying the activation of PVR-associated genes during RPE cell fate transitions and offer promising therapeutic avenues targeting epigenetic modulation and the RANK-NFATc1 axis for PVR management.


Asunto(s)
Factores de Transcripción NFATC , Epitelio Pigmentado de la Retina , Transducción de Señal , Vitreorretinopatía Proliferativa , Animales , Vitreorretinopatía Proliferativa/metabolismo , Vitreorretinopatía Proliferativa/genética , Vitreorretinopatía Proliferativa/patología , Epitelio Pigmentado de la Retina/metabolismo , Factores de Transcripción NFATC/metabolismo , Factores de Transcripción NFATC/genética , Ratones , Masculino , Ratones Endogámicos C57BL , Humanos , Elementos de Facilitación Genéticos/genética , Epigénesis Genética , Modelos Animales de Enfermedad , Lesiones Oculares/metabolismo , Lesiones Oculares/genética , Lesiones Oculares/patología , Perfilación de la Expresión Génica , Multiómica
18.
Environ Res ; 261: 119707, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39084507

RESUMEN

Soil salinization poses a significant global challenge, exerting adverse effects on both agriculture and ecosystems. Planting halophytes has the potential ability to improve saline-alkali land and enhance ecosystem multifunctionality (EMF). However, it remains unclear which halophytes are effective in improving saline-alkali land and what impact they have on the rhizosphere microbial communities and EMF. In this study, we evaluated the Na+ absorption capability of five halophytes (Grubovia dasyphylla, Halogeton glomeratus, Suaeda salsa, Bassia scoparia, and Reaumuria songarica) and assessed their rhizosphere microbial communities and EMF. The results showed that S. salsa possessed the highest shoot (3.13 mmol g-1) and root (0.92 mmol g-1) Na+ content, and its soil Na+ absorption, along with B. scoparia, was significantly higher than that of other plants. The soil pH, salinity, and Na+ content of the halophyte rhizospheres decreased by 6.21%, 23.49%, and 64.29%, respectively, when compared to the bulk soil. Extracellular enzymes in the halophyte rhizosphere soil, including α-glucosidase, ß-glucosidase, ß-1,4-N-acetyl-glucosaminidase, neutral phosphatase, and alkaline phosphatase, increased by 70.1%, 78.4%, 38.5%, 79.1%, and 64.9%, respectively. Furthermore, the halophyte rhizosphere exhibited higher network complexity of bacteria and fungi and EMF than bulk soil. The relative abundance of the dominant phyla Proteobacteria, Firmicutes, and Ascomycota in the halophyte rhizosphere soil increased by 9.4%, 8.3%, and 22.25%, respectively, and showed higher microbial network complexity compared to the bulk soil. Additionally, keystone taxa, including Muricauda, Nocardioides, and Pontibacter, were identified with notable effects on EMF. This study confirmed that euhalophytes are the best choice for saline-alkali land restoration. These findings provided a theoretical basis for the sustainable use of saline-alkali cultivated land.


Asunto(s)
Rizosfera , Salinidad , Plantas Tolerantes a la Sal , Microbiología del Suelo , Suelo , Plantas Tolerantes a la Sal/crecimiento & desarrollo , Plantas Tolerantes a la Sal/microbiología , Suelo/química , Ecosistema , Microbiota
19.
Int J Biol Macromol ; 276(Pt 1): 133792, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38992539

RESUMEN

Doxorubicin (Dox), a chemotherapeutic agent frequently used to treat cancer, elicits cardiotoxicity, a condition referred to as Dox-induced cardiotoxicity (DIC), and ferroptosis plays a contributory role in its pathophysiology. Fucoidan, a polysaccharide with various biological activities and safety profile, has potential therapeutic and pharmaceutical applications. This study aimed to investigate the protective effects and underlying mechanisms of fucoidan in DIC. Echocardiography, biomarkers of cardiomyocyte injury, serum creatine kinase, creatine kinase isoenzyme and lactate dehydrogenase, as well as histological staining results, revealed that fucoidan significantly reduced myocardial damage and improved cardiac function in DIC mice. Transmission electron microscopy; levels of lipid reactive oxygen species, glutathione, and malondialdehyde; ferroptosis-related markers; and regulatory factors such as glutathione peroxidase 4 (GPX4), transferrin receptor protein-1, ferritin heavy chain-1, heme oxygenase-1 in the heart tissue were measured to explore the effect of fucoidan on Dox-induced ferroptosis. These results suggested that fucoidan could inhibit cardiomyocyte ferroptosis caused by Dox. In vitro experiments revealed that silencing nuclear factor-erythroid 2-related factor 2 (Nrf2) in cardiomyocytes reduced the inhibitory effect of fucoidan on ferroptosis. Hence, fucoidan has the potential to ameliorate DIC by inhibiting ferroptosis via the Nrf2/GPX4 pathway.


Asunto(s)
Cardiotoxicidad , Doxorrubicina , Ferroptosis , Miocitos Cardíacos , Factor 2 Relacionado con NF-E2 , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Polisacáridos , Transducción de Señal , Animales , Polisacáridos/farmacología , Polisacáridos/química , Ferroptosis/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Doxorrubicina/efectos adversos , Doxorrubicina/toxicidad , Ratones , Cardiotoxicidad/tratamiento farmacológico , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Transducción de Señal/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Masculino
20.
J Asian Nat Prod Res ; : 1-13, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958642

RESUMEN

Fuzheng Huayu recipe (FZHYR) is a Chinese patent medicine for the treatment of fibrosis. The effects of FZHYR on pulmonary fibrosis and macrophage polarization were investigated in vitro. FZHYR inhibited pulmonary inflammation and fibrosis and M2 polarization of macrophages in bleomycin-induced pulmonary fibrosis (BPF) of rat model. Differentially expressed genes were screened by high-throughput mRNA sequencing and GSEA showed that oxidative phosphorylation (OXPHOS) was correlated with BPF. FZHYR inhibited expressions of Ndufa2 and Ndufa6 in lung tissues of BPF rats. These findings suggest that OXPHOS pathway serves as a possible target for pulmonary fibrosis therapy by FZHYR.

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