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1.
Neural Regen Res ; 20(2): 533-547, 2025 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38819065

RESUMO

JOURNAL/nrgr/04.03/01300535-202502000-00030/figure1/v/2024-05-28T214302Z/r/image-tiff In patients with Alzheimer's disease, gamma-glutamyl transferase 5 (GGT5) expression has been observed to be downregulated in cerebrovascular endothelial cells. However, the functional role of GGT5 in the development of Alzheimer's disease remains unclear. This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer's disease, as well as the underlying mechanism. We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer's disease (Aß1-42-treated hCMEC/D3 and bEnd.3 cells), as well as in the APP/PS1 mouse model. Additionally, injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits. Interestingly, increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-ß in the brains of APP/PS1 mice. This effect may be attributable to inhibition of the expression of ß-site APP cleaving enzyme 1, which is mediated by nuclear factor-kappa B. Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer's disease pathogenesis, and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice. These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer's disease.

2.
Neural Regen Res ; 20(2): 548-556, 2025 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38819066

RESUMO

JOURNAL/nrgr/04.03/01300535-202502000-00031/figure1/v/2024-05-28T214302Z/r/image-tiff Transforming growth factor-beta 1 (TGF-ß1) has been extensively studied for its pleiotropic effects on central nervous system diseases. The neuroprotective or neurotoxic effects of TGF-ß1 in specific brain areas may depend on the pathological process and cell types involved. Voltage-gated sodium channels (VGSCs) are essential ion channels for the generation of action potentials in neurons, and are involved in various neuroexcitation-related diseases. However, the effects of TGF-ß1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear. In this study, we investigated the effects of TGF-ß1 on VGSC function and firing properties in primary cortical neurons from mice. We found that TGF-ß1 increased VGSC current density in a dose- and time-dependent manner, which was attributable to the upregulation of Nav1.3 expression. Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase (PD98059), p38 mitogen-activated protein kinase (SB203580), and Jun NH2-terminal kinase 1/2 inhibitor (SP600125). Interestingly, TGF-ß1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons. These findings suggest that TGF-ß1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway, which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions. Thus, this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(5): 503-507, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38845497

RESUMO

OBJECTIVE: To evaluate the predictive value of a risk prediction model guided by the ratio of respiratory rate to diaphragm thickening fraction (RR/DTF) for noninvasive-invasive mechanical ventilation transition timing in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), through ultrasound evaluation of diaphragm movement indicators. METHODS: Sixty-four patients diagnosed with AECOPD and undergoing non-invasive ventilation (NIV), who were admitted to the department of critical care medicine of the First Affiliated Hospital of Jinzhou Medical University from January 2022 to July 2023 were enrolled. They were divided into NIV successful group and NIV failure group based on the outcome of NIV within 24 hours. Clinical indicators such as RR/DTF, diaphragmatic excursion (DE), tidal volume (VT), respiratory rate (RR), pH value, partial pressure of carbon dioxide (PaCO2), and sputum excretion disorder were compared between the two groups after 2 hours of NIV. The factors influencing NIV failure were included in binary Logistic regression analysis, and an RR/DTF oriented risk prediction model was established. Receiver operator characteristic curve (ROC curve) analysis was used to assess the predictive value of this model for the timing of noninvasive-invasive mechanical ventilation transition in AECOPD patients. RESULTS: Among 64 patients with AECOPD, with 43 in the NIV successful group and 21 in the NIV failure group. There were no statistically significant differences in baseline data such as age, gender, body mass index (BMI), oxygenation index (P/F), smoking history, and acute physiological and chronic health evaluation II (APACHE II) between the two groups of patients, indicating comparability. Compared to the NIV successful group, the NIV failure group showed a significantly increase in RR/DTF, RR, PaCO2, and sputum retention, while VT and DE were significantly decreased [RR/DTF (%): 1.00±0.18 vs. 0.89±0.22, RR (bpm): 21.64±3.13 vs. 19.62±2.98, PaCO2 (mmHg, 1 mmHg ≈ 0.133 kPa): 70.82±8.82 vs. 65.29±9.47, sputum retention: 57.1% vs. 30.2%, VT (mL): 308.09±14.89 vs. 324.48±23.82, DE (mm): 19.91±2.94 vs. 22.05±3.30, all P < 0.05]. Binary Logistic regression analysis showed that RR/DTF [odds ratio (OR) = 147.989, 95% confidence interval (95%CI) was 3.321-595.412, P = 0.010], RR (OR = 1.296, 95%CI was 1.006-1.670, P = 0.045), VT (OR = 0.966, 95%CI was 0.935-0.999, P = 0.044), PaCO2 (OR = 1.086, 95%CI was 1.006~1.173, P = 0.035), and sputum retention (OR = 4.533, 95%CI was 1.025-20.049, P = 0.046) were independent risk factors for predicting NIV failure in AECOPD patients. ROC curve analysis showed that the area under the curve (AUC) of 0.713 with a 95%CI of 0.587-0.839 (P = 0.005). The sensitivity was 72.73%, the specificity was 88.10%, the Youden index was 0.394, and the optimal cut-off value was 0.87. CONCLUSIONS: The RR/DTF risk prediction model has good predictive value for the timing of noninvasive-invasive mechanical ventilation transition in AECOPD patients.


Assuntos
Diafragma , Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica , Taxa Respiratória , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ventilação não Invasiva/métodos , Diafragma/fisiopatologia , Respiração Artificial/métodos , Curva ROC , Modelos Logísticos , Feminino , Masculino , Volume de Ventilação Pulmonar , Valor Preditivo dos Testes , Idoso , Pessoa de Meia-Idade
4.
Mil Med Res ; 11(1): 35, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38835066

RESUMO

Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/diagnóstico , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Intestinais/terapia , Neoplasias Intestinais/epidemiologia , Neoplasias Intestinais/diagnóstico
5.
Neurosurgery ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860769

RESUMO

BACKGROUND AND OBJECTIVES: This study aimed to investigate the clinical, radiological, pathological features, treatment options, and outcomes of isocitrate dehydrogenase (IDH)-mutant brainstem gliomas (BSG-IDHmut). METHODS: A retrospective analysis of 22 patients diagnosed with BSG-IDHmut and treated at our institution from January 2011 to January 2017 was performed. Their clinical, radiological data, and long-term outcomes were collected and analyzed. RESULTS: The median age of patients was 38.5 years, with a male predominance (63.6%). All patients had IDH1 and TP53 mutations, with noncanonical IDH mutations in 59.1% of cases, 06-methylguanine-DNA methyltransferase promoter methylation in 55.6%, and alpha-thalassemia mental retardation X-linked loss in 63.2%, respectively. Tumors were primarily located in the pontine-medullary oblongata (54.5%) and frequently involved the pontine brachium (50%). Most tumors exhibited ill-defined boundaries (68.2%), no T2-FLAIR mismatch (100%), and no contrast enhancement (86.3%). Two radiological growth patterns were also identified: focal and extensively infiltrative, which were associated with the treatment strategy when tumor recurred. Seven patients (31.8%) received surgery only and 15 (68.2%) surgery plus other therapy. The median overall survival was 124.8 months, with 1-year, 2-year, 5-year, and 10-year survival rates of 81.8%, 68.2%, 54.5%, and 13.6%, respectively. Six patients experienced tumor recurrence, and all retained their radiological growth patterns, with 2 transformed into central nervous system World Health Organization grade 4. CONCLUSION: BSG-IDHmut represents a unique subgroup of brainstem gliomas with distinctive features and more favorable prognosis compared with other brainstem gliomas. Further research is required to better understand the molecular mechanisms and optimize treatment strategies for this rare and complex disease.

6.
FASEB J ; 38(12): e23735, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38860936

RESUMO

Identification of potential key targets of melanoma, a fatal skin malignancy, is critical to the development of new cancer therapies. Lysine methyltransferase 2A (KMT2A) promotes melanoma growth by activating the human telomerase reverse transcriptase (hTERT) signaling pathway; however, the exact mechanism remains elusive. This study aimed to reveal new molecular targets that regulate KMT2A expression and melanoma growth. Using biotin-streptavidin-agarose pull-down and proteomics, we identified Damage-specific DNA-binding protein 2 (DDB2) as a KMT2A promoter-binding protein in melanoma cells and validated its role as a regulator of KMT2A/hTERT signaling. DDB2 knockdown inhibited the expression of KMT2A and hTERT and inhibited the growth of melanoma cells in vitro. Conversely, overexpression of DDB2 activated the expression of KMT2A and promoted the growth of melanoma cells. Additionally, we demonstrated that DDB2 expression was higher in tumor tissues of patients with melanoma than in corresponding normal tissues and was positively correlated with KMT2A expression. Kaplan-Meier analysis showed a poor prognosis in patients with high levels of DDB2 and KMT2A. Overall, our data suggest that DDB2 promotes melanoma cell growth through the transcriptional regulation of KMT2A expression and predicts poor prognosis. Therefore, targeting DDB2 may regulate the effects of KMT2A on melanoma growth and progression, providing a new potential therapeutic strategy for melanoma.


Assuntos
Proliferação de Células , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica , Histona-Lisina N-Metiltransferase , Melanoma , Proteína de Leucina Linfoide-Mieloide , Humanos , Melanoma/genética , Melanoma/patologia , Melanoma/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Prognóstico , Linhagem Celular Tumoral , Feminino , Masculino , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo
7.
Phys Med ; 122: 103377, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38838467

RESUMO

PURPOSE: To investigate the clinical impact of plan complexity on the local recurrence-free survival (LRFS) of non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). METHODS: Data from 123 treatment plans for 113 NSCLC patients were analyzed. Plan-averaged beam modulation (PM), plan beam irregularity (PI), monitor unit/Gy (MU/Gy) and spherical disproportion (SD) were calculated. The γ passing rates (GPR) were measured using ArcCHECK 3D phantom with 2 %/2mm criteria. High complexity (HC) and low complexity (LC) groups were statistically stratified based on the aforementioned metrics, using cutoffs determined by their significance in correlation with survival time, as calculated using the R-3.6.1 packages. Kaplan-Meier analysis, Cox regression, and Random Survival Forest (RSF) models were employed for the analysis of local recurrence-free survival (LRFS). Propensity-score-matched pairs were generated to minimize bias in the analysis. RESULTS: The median follow-up time for all patients was 25.5 months (interquartile range 13.4-41.2). The prognostic capacity of PM was suggested using RSF, based on Variable Importance and Minimal Depth methods. The 1-, 2-, and 3-year LRFS rates in the HC group were significantly lower than those in the LC group (p = 0.023), when plan complexity was defined by PM. However, no significant difference was observed between the HC and LC groups when defined by other metrics (p > 0.05). All γ passing rates exceeded 90.5 %. CONCLUSIONS: This study revealed a significant association between higher PM and worse LRFS in NSCLC patients treated with SBRT. This finding offers additional clinical evidence supporting the potential optimization of pre-treatment quality assurance protocols.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Planejamento da Radioterapia Assistida por Computador , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Feminino , Planejamento da Radioterapia Assistida por Computador/métodos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Recidiva Local de Neoplasia , Intervalo Livre de Doença , Estudos Retrospectivos
8.
Biochem Pharmacol ; 226: 116338, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38848780

RESUMO

ITFG2, as an immune-modulatory intracellular protein that modulate the fate of B cells and negatively regulates mTORC1 signaling. ITFG2 is highly expressed in the heart, but its pathophysiological function in heart disease is unclear. In this study, we found that in MI mice, overexpression of ITFG2 via an AAV9 vector significantly reduced the infarct size and ameliorated cardiac function. Knockdown of endogenous ITFG2 by shRNA partially aggravated ischemia-induced cardiac dysfunction. In cardiac-specific ITFG2 transgenic (TG) mice, myocardial infarction size was smaller, eject fraction (EF) and fractional shortening (FS) was higher compared to those in wild-type (WT) mice, suggesting ITFG2 reversed cardiac dysfunction induced by MI. In hypoxic neonatal cardiomyocytes (NMCMs), overexpression of ITFG2 maintained mitochondrial function by increasing intracellular ATP production, reducing ROS levels, and preserving the mitochondrial membrane potential (MMP). Overexpression of ITFG2 reversed the mitochondrial respiratory dysfunction in NMCMs induced by hypoxia. Knockdown of endogenous ITFG2 by siRNA did the opposite. Mechanism, ITFG2 formed a complex with NEDD4-2 and ATP 5b and inhibited the binding of NEDD4-2 with ATP 5b leading to the reduction ubiquitination of ATP 5b. Our findings reveal a previously unknown ability of ITFG2 to protect the heart against ischemic injury by interacting with ATP 5b and thereby regulating mitochondrial function. ITFG2 has promise as a novel strategy for the clinical management of MI.

9.
BMC Psychiatry ; 24(1): 422, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840083

RESUMO

BACKGROUND: Mind wandering is a common phenomenon in daily life. However, the manifestations and cognitive correlates of mind wandering in different subclinical populations remain unclear. In this study, these aspects were examined in individuals with schizotypal traits and individuals with depressive symptoms, i.e., subclinical populations of patients with schizophrenia and depression. METHODS: Forty-two individuals with schizotypal traits, 42 individuals with subclinical depression, and 42 controls were recruited to complete a mind wandering thought sampling task (state level) and a mind wandering questionnaire (trait level). Measures of rumination and cognitive functions (attention, inhibition, and working memory) were also completed by participants. RESULTS: Both subclinical groups exhibited more state and trait mind wandering than did the control group. Furthermore, individuals with schizotypal traits demonstrated more trait mind wandering than individuals with subclinical depression. Rumination, sustained attention, and working memory were associated with mind wandering. In addition, mind wandering in individuals with subclinical depression can be accounted for by rumination or attention, while mind wandering in individuals with high schizotypal traits cannot be accounted for by rumination, attention, or working memory. CONCLUSIONS: The results suggest that individuals with high schizotypal traits and subclinical depression have different patterns of mind wandering and mechanisms. These findings have implications for understanding the unique profile of mind wandering in subclinical individuals.


Assuntos
Atenção , Depressão , Memória de Curto Prazo , Transtorno da Personalidade Esquizotípica , Humanos , Masculino , Feminino , Transtorno da Personalidade Esquizotípica/psicologia , Transtorno da Personalidade Esquizotípica/fisiopatologia , Atenção/fisiologia , Memória de Curto Prazo/fisiologia , Depressão/psicologia , Adulto , Adulto Jovem , Pensamento/fisiologia , Ruminação Cognitiva/fisiologia , Inquéritos e Questionários , Adolescente
10.
Quant Imaging Med Surg ; 14(6): 4098-4109, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38846293

RESUMO

Background: Different image modalities capture different aspects of a patient. It is desirable to produce images that capture all such features in a single image. This research investigates the potential of multi-modal image fusion method to enhance magnetic resonance imaging (MRI) tumor contrast and its consistency across different patients, which can capture both the anatomical structures and tumor contrast clearly in one image, making MRI-based target delineation more accurate and efficient. Methods: T1-weighted (T1-w) and T2-weighted (T2-w) magnetic resonance (MR) images from 80 nasopharyngeal carcinoma (NPC) patients were used. A novel image fusion method, Pixelwise Gradient Model for Image Fusion (PGMIF), which is based on the pixelwise gradient to capture the shape and a generative adversarial network (GAN) term to capture the image contrast, was introduced. PGMIF is compared with several popular fusion methods. The performance of fusion methods was quantified using two metrics: the tumor contrast-to-noise ratio (CNR), which aims to measure the contrast of the edges, and a Generalized Sobel Operator Analysis, which aims to measure the sharpness of edge. Results: The PGMIF method yielded the highest CNR [median (mdn) =1.208, interquartile range (IQR) =1.175-1.381]. It was a statistically significant enhancement compared to both T1-w (mdn =1.044, IQR =0.957-1.042, P<5.60×10-4) and T2-w MR images (mdn =1.111, IQR =1.023-1.182, P<2.40×10-3), and outperformed other fusion models: Gradient Model with Maximum Comparison among Images (GMMCI) (mdn =0.967, IQR =0.795-0.982, P<5.60×10-4), Deep Learning Model with Weighted Loss (DLMWL) (mdn =0.883, IQR =0.832-0.943, P<5.60×10-4), Pixelwise Weighted Average (PWA) (mdn =0.875, IQR =0.806-0.972, P<5.60×10-4) and Maximum of Images (MoI) (mdn =0.863, IQR =0.823-0.991, P<5.60×10-4). In terms of the Generalized Sobel Operator Analysis, a measure based on Sobel operator to measure contrast enhancement, PGMIF again exhibited the highest Generalized Sobel Operator (mdn =0.594, IQR =0.579-0.607; mdn =0.692, IQR =0.651-0.718 for comparison with T1-w and T2-w images), compared to: GMMCI (mdn =0.491, IQR =0.458-0.507, P<5.60×10-4; mdn =0.495, IQR =0.487-0.533, P<5.60×10-4), DLMWL (mdn =0.292, IQR =0.248-0.317, P<5.60×10-4; mdn =0.191, IQR =0.179-0.243, P<5.60×10-4), PWA (mdn =0.423, IQR =0.383-0.455, P<5.60×10-4; mdn =0.448, IQR =0.414-0.463, P<5.60×10-4) and MoI (mdn =0.437, IQR =0.406-0.479, P<5.60×10-4; mdn =0.540, IQR =0.521-0.636, P<5.60×10-4), demonstrating superior contrast enhancement and sharpness compared to other methods. Conclusions: Based on the tumor CNR and Generalized Sobel Operator Analysis, the proposed PGMIF method demonstrated its capability of enhancing MRI tumor contrast while keeping the anatomical structures of the input images. It holds promises for NPC tumor delineation in radiotherapy.

11.
Front Vet Sci ; 11: 1340591, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846786

RESUMO

Objective: Orchitis is a common reproductive disease of male animals, which has serious implications to human and animal reproduction. Additionally, phlorizin (PHN), a common polyphenol in apples and strawberries, has a variety of biological activities, including antioxidant, anti-inflammatory, anti-diabetic, and anti-aging activities. We aimed to determine the protective effects and potential mechanisms of PHN in lipopolysaccharide (LPS)-induced acute orchitis in mice. Method: After 21 days of PHN pretreatment, mice were injected with LPS to induce testicular inflammation, and then the changes of testicular tissue structure, expression of inflammatory factors, testosterone level, expression of testosterone-related genes, adhesion gene and protein expression were detected, and the structural changes in the intestinal flora after PHN treatment were further detected by 16SRNA. Result: Our results demonstrated that PHN treatment reduced LPS-induced testicular injury and body and testicular weight losses. The mRNA expression levels of pro-inflammatory cytokines-related genes and antioxidant enzyme activity were also decreased and elevated, respectively, by PHN administration; however, PHN treatment also reduced the LPS-induced decrease in testosterone levels in the testes. Additionally, further studies found that PHN increased the expression of marker proteins zonula occludens-1 (ZO-1) and occludin associated with the blood testosterone barrier compared with that in LPS treatment groups. To further examine the potential mechanisms of the protective effect of PHN on LPS-induced testicular injury, we compared the differences of gut microbiota compositions between the 100 mg/kg PHN treatment group and the control group using 16SRNA. Metagenomic analyses indicated that the abundances of Bacteroidetes, Muribaculaceae, Lactobacillaceae, uncultured bacterium f Muribaculaceae, and Lactobacillus in the PHN treatment group improved, while potential microbes that can induce intestinal diseases, including Verrucomicrobia, Epsilonbacteraeota, Akkermansiaceae, and Akkermansia decreased in the PHN treatment group. Conclusion: Our results indicate that PHN pretreatment might alleviate orchitis by altering the composition of gut microflora, which may provide a reference for reducing the occurrence of acute orchitis in male animals.

12.
Hepatol Res ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874115

RESUMO

Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti-HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post-transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection.

13.
Water Res ; 260: 121900, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38870862

RESUMO

Membrane science is the key strategy to solve water shortage in the future, and its essence is energy and mass transfer. Due to the complexity and variety of the internal structure of membrane, the energy transfer theory of membrane is still a black box theory. Herein, a new fluid mechanics principle is introduced to establish the energy fluid theory of membrane, which is translated into the energy formula: such as the initial total pressure difference (ΔP), the flow rate of fluid exiting the membrane (v1 and v2), fluid density (ρ), and energy consumption by salt resistance (NSR): { [Formula: see text] +12ρv23}. The theoretical framework is not only helpful for the data analysis of the energy transfer process of membranes, but also helps to allow for more in-depth and specific theoretical research. For instance, the relationship between NSR and the concentration difference (C) of salt can be expressed as NSR = aCb (a-product constant, b-exponential constant, R2>0.99). Hence, the basic theory can not only be widely applied to a variety of membranes with complex internal structure, but also have a profound impact on the application and research of membrane science.

14.
Heliyon ; 10(11): e31789, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38868060

RESUMO

Perforation of the tympanic membrane (TM) is a common condition that often requires a scaffold as a support for surgery. However, because of the external environment of the auditory canal, the scaffold could become bacterially infected and prevent the TM from healing. As a result, the perfect scaffold should have both antibacterial and biomimetic qualities. In this study, the biodegradable biomaterial poly(1,4-butylene carbonate) (PBC) films containing levofloxacin (LEV) was successfully prepared for the first time. The results showed that the hydrophilicity of the LEV/PBC film was improved after the addition of LEV, and the tensile strength was also complied with the requirements of the standard. The created antibacterial film demonstrated excellent antibacterial properties. In vitro hemolysis experiments revealed no risk of hemolysis for the new material, and the cytotoxicity study further confirmed its non-cytotoxic nature. Overall, LEV was a good component of PBC/LEV film, which is expected to be used for TM repair in the future.

15.
Stem Cells Int ; 2024: 2741681, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882598

RESUMO

Background: Joint articular injection of mesenchymal stem cells (MSCs) has emerged as a novel treatment approach for osteoarthritis (OA). However, the effectiveness of MSCs derived from different sources in treating OA patients remains unclear. Therefore, this study aimed to explore the differences between the effectiveness and safety of different sources of MSCs. Materials and Methods: For inclusion consideration, we searched trial registries and published databases, including PubMed, Cochrane Library, Embase, and Web of Science databases. Revman (V5.3), STATA (V16.0), and R (V4.0) were utilized for conducting data analysis, while the Cochrane Risk of Bias Tool was employed for assessing the quality of the studies. We derived outcome measures at 6 and 12 months based on the duration of study follow-up, including visual analog scale (VAS) score, WOMAC score, WOMAC pain, WOMAC Functional Limitation, and WOMAC stiffness. The evaluation time for short-term effectiveness is set at 6 months, while 12 months is utilized as the longest follow-up time for most studies to assess long-term effectiveness. Results: The evaluation of literature quality showed that the included studies had excellent methodological quality. A meta-analysis revealed that different sources of MSCs improved knee function and pain more effectively among patients suffering from knee OA (KOA) than controls. The results of the network meta-analysis showed the following: short-term functional improvement (the indexes were evaluated after 6 months of follow-up) (WOMAC total score: bone marrow-derived MSC (BMMSC) vs. adipose-derived MSC (ADMSC) (mean difference (MD) = -20.12, 95% confidence interval (CI) -125.24 to 42.88), umbilical cord-derived MSC (UCMSC) (MD = -7.81, 95% CI -158.13 to 74.99); WOMAC stiffness: BMMSC vs. ADMSC (MD = -0.51, 95% CI -7.27 to 4.29), UCMSC (MD = -0.75, 95% CI -9.74 to 6.63); WOMAC functional limitation: BMMSC vs. ADMSC (MD = -12.22, 95% CI -35.05 to 18.86), UCMSC (MD = -9.31, 95% CI -44.26 to 35.27)). Long-term functional improvement (the indexes were evaluated after 12 months of follow-up) (WOMAC total: BMMSC vs. ADMSC (MD = -176.77, 95% CI -757.1 to 378.25), UCMSC (MD = -181.55, 95% CI -937.83 to 541.13); WOMAC stiffness: BMMSC vs. ADMSC (MD = -0.5, 95% CI -26.05 to 18.61), UCMSC (MD = -1.03, 95% CI -30.44 to 21.69); WOMAC functional limitation: BMMSC vs. ADMSC (MD = -5.18, 95% CI -316.72 to 177.1), UCMSC (MD = -8.33, 95% CI -358.78 to 218.76)). Short-term pain relief (the indexes were evaluated after 6 months of follow-up) (VAS score: UCMSC vs. BMMSC (MD = -10.92, 95% CI -31.79 to 12.03), ADMSC (MD = -14.02, 95% CI -36.01 to 9.81), PLMSC (MD = -17.09, 95% CI -46.31 to 13.17); WOMAC pain relief: BMMSC vs. ADMSC (MD = -11.42, 95% CI -39.52 to 11.77), UCMSC (MD = -6.73, 95% CI -47.36 to 29.15)). Long-term pain relief (the indexes were evaluated after 12 months of follow-up) (VAS score: BMMSC vs. UCMSC (MD = -4.33, 95% CI -36.81 to 27.08), ADMSC (MD = -11.43, 95% CI -37.5 to 13.42); WOMAC pain relief: UCMSC vs. ADMSC (MD = 0.23, 95% CI -37.87 to 38.11), BMMSC (MD = 5.89, 95% CI -25.39 to 51.41)). According to the GRADE scoring system, WOMAC, VAS, and AE scores were of low quality. Conclusion: Meta-analysis suggests MSCs can effectively treat KOA by improving pain and knee function compared to control groups. In terms of functional improvement in KOA patients, both short-term (6-month follow-up) and long-term (12-month follow-up) results indicated that while the differences between most treatments were not statistically significant, bone marrow-derived MSCs may have some advantages over other sources of MSCs. Additionally, BM-MSCs and UC-MSCs may offer certain benefits over ADMSCs in terms of pain relief for KOA patients, although the variances between most studies were not statistically significant. Therefore, this study suggests that BM-MSCs may present clinical advantages over other sources of MSCs.

16.
Clin Exp Pharmacol Physiol ; 51(7): e13900, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38843865

RESUMO

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.


Assuntos
Proliferação de Células , Medicamentos de Ervas Chinesas , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares , Neoplasias de Mama Triplo Negativas , Animais , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Camundongos , Proliferação de Células/efeitos dos fármacos , Feminino , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia
17.
Phys Chem Chem Phys ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873765

RESUMO

The Brust-Schiffrin two-phase method is a facile way to prepare thiolate-protected metal nanoparticles, but its mechanism remains controversial. In this work, we demonstrate the use of the Brust-Schiffrin method based on coordination compound theory. We confirmed that the formation of stable complexes is the driving force for a series chemical reaction in the organic phase. We found that the stable Cu(I)-thiolate complex decreased the half-cell reduction potential of Cu(I)/Cu(0). Thus, when thiol ligands were in excess, thiolate-protected Cu(I) clusters formed rather than Cu(0)-cored nanoparticles. The thiolate-protected metal-hydride nanoclusters were the intermediate between the metal complexes and nanoparticles. The "metallophilic" interactions of the d10 closed-shell electronic configuration of the metal coordination centers were proposed as the driving force for nanocluster and nanoparticle formation. To confirm this mechanism, we synthesized Au, Ag, and Cu monometallic nanoparticles and bi- and trimetallic nanoparticles. We found that although thiolate-protected Cu(I) nanoclusters are not easily reduced, they can combine with Au and/or Ag nanoclusters to form nanoparticles. The proposed mechanism is expected to provide deeper insight into the Brust-Schiffrin method and further extend its application to metals other than Au, Ag and Cu.

18.
Front Pharmacol ; 15: 1415740, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881878

RESUMO

Dementia is a devastating disorder characterized by progressive and persistent cognitive decline, imposing a heavy public health burden on the individual and society. Despite numerous efforts by researchers in the field of dementia, pharmacological treatments are limited to relieving symptoms and fail to prevent disease progression. Therefore, studies exploring novel therapeutics or repurposing classical drugs indicated for other diseases are urgently needed. Metformin, a first-line antihyperglycemic drug used to treat type 2 diabetes, has been shown to be beneficial in neurodegenerative diseases including dementia. This review discusses and evaluates the neuroprotective role of metformin in dementia, from the perspective of basic and clinical studies. Mechanistically, metformin has been shown to improve insulin resistance, reduce neuronal apoptosis, and decrease oxidative stress and neuroinflammation in the brain. Collectively, the current data presented here support the future potential of metformin as a potential therapeutic strategy for dementia. This study also inspires a new field for future translational studies and clinical research to discover novel therapeutic targets for dementia.

19.
World J Stem Cells ; 16(4): 334-352, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38690516

RESUMO

Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

20.
Eur J Med Res ; 29(1): 283, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735989

RESUMO

BACKGROUND: It remains unclear whether additional fluid supplementation is necessary during the acute resuscitation period for patients with combined inhalational injury (INHI) under the guidance of the Third Military Medical University (TMMU) protocol. METHODS: A 10-year multicenter, retrospective cohort study, involved patients with burns ≥ 50% total burn surface area (TBSA) was conducted. The effect of INHI, INHI severity, and tracheotomy on the fluid management in burn patients was assessed. Cumulative fluid administration, cumulative urine output, and cumulative fluid retention within 72 h were collected and systematically analyzed. RESULTS: A total of 108 patients were included in the analysis, 85 with concomitant INHI and 23 with thermal burn alone. There was no significant difference in total fluid administration during the 72-h post-burn between the INHI and non-INHI groups. Although no difference in the urine output and fluid retention was shown in the first 24 h, the INHI group had a significantly lower cumulative urine output and a higher cumulative fluid retention in the 48-h and 72-h post-burn (all p < 0.05). In addition, patients with severe INHI exhibited a significantly elevated incidence of complications (Pneumonia, 47.0% vs. 11.8%, p = 0.012), (AKI, 23.5% vs. 2.9%, p = 0.037). For patients with combined INHI, neither the severity of INHI nor the presence of a tracheotomy had any significant influence on fluid management during the acute resuscitation period. CONCLUSIONS: Additional fluid administration may be unnecessary in major burn patients with INHI under the guidance of the TMMU protocol.


Assuntos
Queimaduras , Hidratação , Ressuscitação , Humanos , Hidratação/métodos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Adulto , Queimaduras/terapia , Queimaduras/complicações , Ressuscitação/métodos
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