Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 155
Filtrar
1.
Parasitol Res ; 123(10): 361, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39453579

RESUMEN

Fleas, along with one of their host species, Meriones unguiculatus, possess the capability to act as vectors in the transmission of plague. Parasitism by fleas may markedly influence the physiology and immune system of their hosts. Gut microbiota plays an important role in the growth and development of rodents. However, few studies have explored the impacts of ectoparasitic flea on the gut microbiome of rodents. This study investigated the immunological responses and changes in the gut microbial diversity and composition in both wild and laboratory rodents infested with fleas and laboratory rodents infested with Ctenocephalides felis. We measured immune reactions post-infestation by enzyme-linked immunosorbent assay (ELISA) and explored the effects of ectoparasitic infestation on the diversity and composition of the rodent gut microbiota in microbiome studies by 16S rRNA gene sequencing techniques. After flea infestation, results from 16S rRNA gene sequencing techniques indicated a significant increase in alpha diversity, affecting the composition of the gut microbiota. At the genus level, the abundance of the harmful bacterium Desulfovibrio increased. Beta diversity analyses showed significant differences between the gut microbiota of the experimental and control groups. ELISA results revealed significantly elevated levels of IgG in parasitized mice, while the differences in IgA levels were not significant. Flea infections affect the composition and diversity of the gut microbiota in the M. unguiculatu, and it has been found that the biomarker Desulfovibrio increases following flea infection in these rodents. Our results indicate that the gut microbiota can regulate the stability of the rodent-flea system. These findings may provide a foundation for exploring preventive measures against plague and aid in developing more effective treatments for the infection.


Asunto(s)
Infestaciones por Pulgas , Microbioma Gastrointestinal , Gerbillinae , ARN Ribosómico 16S , Animales , Infestaciones por Pulgas/veterinaria , Infestaciones por Pulgas/parasitología , ARN Ribosómico 16S/genética , Ctenocephalides/microbiología , Siphonaptera/microbiología , Femenino , Enfermedades de los Roedores/parasitología , Enfermedades de los Roedores/microbiología , Masculino , Ensayo de Inmunoadsorción Enzimática , Ratones
2.
Cell Commun Signal ; 22(1): 505, 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39420317

RESUMEN

BACKGROUND: Normal cells express functional tumor suppressor WW domain-containing oxidoreductase (WWOX), designated WWOXf. UV irradiation induces WWOXf cells to undergo bubbling cell death (BCD) - an event due to the accumulation of nuclear nitric oxide (NO) gas that forcefully pushes the nuclear and cell membranes to form one or two bubbles at room temperature (22 °C) and below. In contrast, when WWOX-deficient or -dysfunctional (WWOXd) cells are exposed to UV and/or cold shock, the cells undergo nuclear pop-out explosion death (POD). We aimed to determine the morphological and biochemical changes in WWOXf cells during BCD versus apoptosis. METHODS: WWOXf and WWOXd cells were exposed to UV followed by measuring BCD or POD by time-lapse microscopy and/or time-lapse holographic microscopy at 4, 22, or 37 °C to visualize morphological changes. Live cell stains were used to measure the kinetics of nitric oxide (NO) production and Ca2+ influx. Extent of cell death was measured by uptake of propidium iodide and by internucleosomal DNA fragmentation using agarose gel electrophoresis. RESULTS: WWOXf cells were exposed to UV and then cold shock, or cold shock and then UV, and cultured at 4, 10, and 22 °C, respectively. Initially, UV induced calcium influx and NO production, which led to nuclear bubbling and final death. Cold shock pretreatment completely suppressed UV-mediated bubbling at 37 °C, so the UV/cold shock-treated cells underwent apoptosis. Without cold shock, UV only induced bubbling at all temperatures, whereas the efficiency of bubbling at 37 °C was reduced by greater than 50%. Morphologically, the WWOXf cell height or thickness was significantly increased during cell division or apoptosis, but the event did not occur in BCD. In comparison, when WWOXd cancer cells received UV or UV/cold shock, these cells underwent NO-independent POD. UV/cold shock effectively downregulated the expression of many proteins such as the housekeeping α-tubulin (> 70%) and ß-actin (< 50%), and cortactin (> 70%) in WWOXf COS7 cells. UV/cold shock induced relocation of α-tubulin to the nucleus and nuclear bubbles in damaged cells. UV induced co-translocation of the WWOX/TRAF2 complex to the nuclei, in which the prosurvival TRAF2 blocked the proapoptotic WWOX via its zinc finger domain. Without WWOX, TRAF2 did not relocate to the nuclei. Cold shock caused the dissociation of the WWOX/TRAF2 complex in the nucleus needed for BCD. In contrast, the formation of the WWOX/TRAF2 complex, plus p53, was strengthened at 37 °C required for apoptosis. CONCLUSIONS: The temperature-sensitive nuclear WWOX/TRAF2 complex acts as a molecular switch, whose dissociation favors BCD at low temperatures, and the association supports apoptosis at 37 °C in UV-treated WWOXf cells.


Asunto(s)
Núcleo Celular , Frío , Óxido Nítrico , Rayos Ultravioleta , Oxidorreductasa que Contiene Dominios WW , Oxidorreductasa que Contiene Dominios WW/genética , Oxidorreductasa que Contiene Dominios WW/metabolismo , Humanos , Núcleo Celular/metabolismo , Núcleo Celular/efectos de la radiación , Óxido Nítrico/metabolismo , Muerte Celular/efectos de la radiación , Apoptosis/efectos de la radiación , Calcio/metabolismo , Proteínas Supresoras de Tumor
3.
Sci Total Environ ; 951: 175643, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39173746

RESUMEN

Soil contamination by microplastics (MPs) has emerged as a significant global concern. Although traditionally associated with crop production, contemporary understanding of soil health has expanded to include a broader range of factors, including animal safety, microbial diversity, ecological functions, and human health protection. This paradigm shifts underscores the imperative need for a comprehensive assessment of the effects of MPs on soil health. Through an investigation of various soil health indicators, this review endeavors to fill existing knowledge gaps, drawing insights from recent studies conducted between 2021 and 2024, to elucidate how MPs may disrupt soil ecosystems and compromise their crucial functions. This review provides a thorough analysis of the processes leading to MP contamination in soil environments and highlights film residues as major contributors to agricultural soils. MPs entering the soil detrimentally affect crop productivity by hindering growth and other physiological processes. Moreover, MPs hinder the survival, growth, and reproductive rates of the soil fauna, posing potential health risks. Additionally, a systematic evaluation of the impact of MPs on soil microbes and nutrient cycling highlights the diverse repercussions of MP contamination. Moreover, within soil-plant systems, MPs interact with other pollutants, resulting in combined pollution. For example, MPs contain oxygen-containing functional groups on their surfaces that form high-affinity hydrogen bonds with other pollutants, leading to prolonged persistence in the soil environment thereby increasing the risk to soil health. In conclusion, we succinctly summarize the current research challenges related to the mediating effects of MPs on soil health and suggest promising directions for future studies. Addressing these challenges and adopting interdisciplinary approaches will advance our understanding of the intricate interplay between MPs and soil ecosystems, thereby providing evidence-based strategies for mitigating their adverse effects.


Asunto(s)
Monitoreo del Ambiente , Microplásticos , Contaminantes del Suelo , Suelo , Contaminantes del Suelo/análisis , Microplásticos/análisis , Suelo/química , Microbiología del Suelo , Contaminación Ambiental , Ecosistema
4.
Ecol Evol ; 14(7): e11621, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39026961

RESUMEN

Pulex simulans and Polygenis gwyni are vectors of many flea-borne diseases. They were widely recorded in the United States and Mexico between 1970 and 2000. Maximum entropy models were used to explore the habitats of both fleas under different climate scenarios to provide the scientific basis for the surveillance and control of flea-borne diseases. We screened climate variables by principal component analysis and Pearson's correlation test and evaluated model performance by ROC curve. ArcMap was used to visualize expressions. Under current climatic conditions, the medium and highly suitable areas for P. simulans are estimated to be 9.16 × 106 km2 and 4.97 × 106 km2, respectively. These regions are predominantly located in South America, along the Mediterranean coast of Europe, the southern part of the African continent, the Middle East, North China, and Australia. For P. gwyni, the medium and highly suitable areas under current climatic conditions are approximately 4.01 × 106 and 2.04 × 106 km2, respectively, with the primary distribution in North China extending to the Himalayas, near the Equator in Africa, and in a few areas of Europe. Under future climate scenarios, in the SSP3-7.0 scenario for the years 2081-2100, the area of high suitability for P. simulans is projected to reach its maximum. Similarly, in the SSP2-4.5 scenario for 2061-2080, the area of high suitability for P. gwyni is expected to reach its maximum. Under global climate change, there is a large range in the potential distribution for both fleas, with an overall upward trend in the area of habitat under future climate scenarios. Governments should develop scientific prevention and control measures to prevent the invasive alien species flea.

5.
China CDC Wkly ; 6(23): 547-552, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38933660

RESUMEN

Introduction: Plague is a significant global infectious disease, its spread is linked to host and flea populations. Meteorological conditions can impact flea populations and host densities, hence influencing plague outbreaks. Investigating the connection between meteorological factors, flea populations, and rodent densities in Inner Mongolia's natural plague foci can aid in predicting and managing plague outbreaks. Methods: Monthly data on flea index, rodent density, meteorological factors, and normalized difference vegetation index (NDVI) were collected for the study area. Generalized additive modeling (GAM) was used to analyze the non-linear and lag effects of meteorological factors on flea index and rodent density. Structural equation modeling (SEM) was employed to investigate the relationships among meteorological factors, NDVI, flea index, and rodent density. Results: GAM analysis revealed that temperature, precipitation, relative humidity, and NDVI had significant linear, non-linear, and time-lagged impacts on the density of Mongolian gerbils and the flea index. SEM analysis indicated that meteorological factors could directly influence the density and flea index of Mongolian gerbils, or indirectly impact NDVI, subsequently influencing gerbil density and the flea index. Conclusions: Meteorological factors primarily influence gerbil density and flea index indirectly by affecting NDVI and the relationship between flea index and gerbil density. This study offers additional support for the significance of meteorological factors and NDVI in influencing the vector-rodent system, offering valuable insights for predicting and managing plague outbreaks.

6.
J Hazard Mater ; 476: 135043, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38941835

RESUMEN

Cadmium (Cd) accumulation in rice, a global environmental issue, poses a significant threat to human health due to its widespread presence and potential transfer through the food chain. Selenium (Se), an essential micronutrient for humans and plants, can reduce Cd uptake in rice and alleviate Cd-induced toxicity. However, the effects and mechanisms of Se supplementation on rice performance in Cd-contaminated soil remain largely unknown. Here, a global meta-analysis was conducted to evaluate the existing knowledge on the effects and mechanisms by which Se supplementation impacts rice growth and Cd accumulation. The result showed that Se supplementation has a significant positive impact on rice growth in Cd-contaminated soil. Specifically, Se supplementation decreased Cd accumulation in rice roots by 16.3 % (11.8-20.6 %), shoots by 24.6 % (19.9-29.1 %), and grain by 37.3 % (33.4-40.9 %), respectively. The grain Cd reduction was associated with Se dose and soil Cd contamination level but not Se type or application method. Se influences Cd accumulation in rice by regulating the expression of Cd transporter genes (OSLCT1, OSHMA2, and OSHMA3), enhancing Cd sequestration in the cell walls, and reducing Cd bioavailability in the soil. Importantly, Se treatment promoted Se enrichment in rice and alleviated oxidative damage associated with Cd exposure by stimulating photosynthesis and activating antioxidant enzymes. Overall, Se treatment mitigated the health hazard associated with Cd in rice grains, particularly in lightly contaminated soil. These findings reveal that Se supplementation is a promising strategy for simultaneous Cd reduction and Se enrichment in rice.


Asunto(s)
Cadmio , Oryza , Selenio , Contaminantes del Suelo , Oryza/metabolismo , Oryza/efectos de los fármacos , Cadmio/toxicidad , Cadmio/metabolismo , Selenio/metabolismo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos
7.
Molecules ; 29(9)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38731608

RESUMEN

In this paper, Cu-BTC derived mesoporous CuS nanomaterial (m-CuS) was synthesized via a two-step process involving carbonization and sulfidation of Cu-BTC for colorimetric glutathione detection. The Cu-BTC was constructed by 1,3,5-benzenetri-carboxylic acid (H3BTC) and Cu2+ ions. The obtained m-CuS showed a large specific surface area (55.751 m2/g), pore volume (0.153 cm3/g), and pore diameter (15.380 nm). In addition, the synthesized m-CuS exhibited high peroxidase-like activity and could catalyze oxidation of the colorless substrate 3,3',5,5'-tetramethylbenzidine to a blue product. Peroxidase-like activity mechanism studies using terephthalic acid as a fluorescent probe proved that m-CuS assists H2O2 decomposition to reactive oxygen species, which are responsible for TMB oxidation. However, the catalytic activity of m-CuS for the oxidation of TMB by H2O2 could be potently inhibited in the presence of glutathione. Based on this phenomenon, the colorimetric detection of glutathione was demonstrated with good selectivity and high sensitivity. The linear range was 1-20 µM and 20-300 µM with a detection limit of 0.1 µM. The m-CuS showing good stability and robust peroxidase catalytic activity was applied for the detection of glutathione in human urine samples.


Asunto(s)
Colorimetría , Cobre , Glutatión , Peróxido de Hidrógeno , Nanoestructuras , Glutatión/análisis , Glutatión/química , Colorimetría/métodos , Cobre/química , Nanoestructuras/química , Catálisis , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisis , Porosidad , Oxidación-Reducción , Ácidos Ftálicos/química , Humanos , Bencidinas/química , Límite de Detección
8.
Front Cardiovasc Med ; 11: 1265378, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38685981

RESUMEN

Introduction: Bicuspid aortic valve (BAV) is the most prevalent congenital cardiovascular defect and known to cause thoracic aortic aneurysms (TAAs). To improve our understanding of BAV pathogenesis, we characterized the cellular composition of BAV tissues and identified molecular changes in each cell population. Methods: Tissue samples from two patients with BAV and two heart transplant donors were analyzed using single-cell RNA sequencing, assay for transposase-accessible chromatin using sequencing, and weighted gene coexpression network analysis for differential gene analysis. TAA-related changes were evaluated by comparing the proportion of each cell type and gene expression profiles between TAA and control tissues. Further, by combining our single-cell RNA sequencing data with publicly available data from genome-wide association studies, we determined critical genes for BAV. Results: We found 20 cell subpopulations in TAA tissues, including multiple subtypes of smooth muscle cells, fibroblasts, macrophages, and T lymphocytes. This result suggested that these cells play multiple functional roles in BAV development. Several differentially expressed genes, including CD9, FHL1y, HSP90AA1, GAS6, PALLD, and ACTA2, were identified. Discussion: We believe that this comprehensive assessment of the cellular composition of TAA tissues and the insights into altered gene expression patterns can facilitate identification of novel diagnostic biomarkers and therapeutic targets for BAV-associated TAA.

9.
Int J Mol Sci ; 25(6)2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38542478

RESUMEN

We reported that a 31-amino-acid Zfra protein (zinc finger-like protein that regulates apoptosis) blocks neurodegeneration and cancer growth. Zfra binds WW domain-containing oxidoreductase (WWOX) to both N- and C-termini, which leads to accelerated WWOX degradation. WWOX limits the progression of neurodegeneration such as Alzheimer's disease (AD) by binding tau and tau-hyperphosphorylating enzymes. Similarly, Zfra binds many protein targets and accelerates their degradation independently of ubiquitination. Furthermore, Zfra4-10 peptide strongly prevents the progression of AD-like symptoms in triple-transgenic (3xTg) mice during aging. Zfra4-10 peptide restores memory loss in 9-month-old 3xTg mice by blocking the aggregation of a protein cascade, including TPC6AΔ, TIAF1, and SH3GLB2, by causing aggregation of tau and amyloid ß. Zfra4-10 also suppresses inflammatory NF-κB activation. Zfra-activated Hyal-2+ CD3- CD19- Z cells in the spleen, via Hyal-2/WWOX/Smad4 signaling, are potent in cancer suppression. In this perspective review, we provide mechanistic insights regarding how Zfra overrides WWOX to induce cancer suppression and retard AD progression via Z cells.


Asunto(s)
Péptidos beta-Amiloides , Neoplasias , Ratones , Animales , Oxidorreductasa que Contiene Dominios WW/genética , Oxidorreductasa que Contiene Dominios WW/metabolismo , Apoptosis , Transducción de Señal/fisiología , Neoplasias/metabolismo
10.
Environ Pollut ; 348: 123787, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38548159

RESUMEN

The co-occurrence of microplastics (MPs) and heavy metal(loid)s (HMs) has attracted growing scientific interest because of their wide distribution and environmental toxicity. Nevertheless, the interactions between MPs and HMs in soil-plant systems remain unclear. We conducted a meta-analysis with 3226 observations from 87 independent studies to quantify the impact of MPs addition on the plant biomass and HMS accumulation. Co-occurrence of MPs and HMs (except for As) induced synergistic toxicity to plant growth. MPs promoted their uptake in the shoot by 11.0% for Cd, 30.0% for Pb, and 47.1% for Cu, respectively. In contrast, MPs caused a significant decrease (22.6%, 17.9-26.9%) in the shoot As accumulation. The type and dose of MPs were correlated with the accumulation of HMs. MPs increased available concentrations of Cd, Pb, and Cu, but decreased available As concentration in soils. Meanwhile, MPs addition significantly lowered soil pH. These findings may provide explanations for MPs-mediated effects on influencing the accumulation of HMs in plants. Using a machine learning approach, we revealed that soil pH and total HMs concentration are the major contributors affecting their accumulation in shoot. Overall, our study indicated that MPs may increase the environmental risks of HMs in agroecosystems, especially metal cations.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Cadmio/análisis , Microplásticos , Plásticos , Plomo/análisis , Metales Pesados/análisis , Plantas , Suelo , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis
11.
Sci Total Environ ; 918: 170663, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38311087

RESUMEN

Arsenic (As) and cadmium (Cd) are two toxic metal(loid)s that pose significant risks to food security and human health. Silicon (Si) has attracted substantial attention because of its positive effects on alleviating the toxicity and accumulation of As and Cd in crops. However, our current knowledge of the comprehensive effects and detailed mechanisms of Si amendment is limited. In this study, a global meta-analysis of 248 original articles with over 7000 paired observations was conducted to evaluate Si-mediated effects on growth and As and Cd accumulation in rice (Oryza sativa L.), wheat (Triticum aestivum L.), and maize (Zea mays L.). Si application increases the biomass of these crops under As and/or Cd contamination. Si amendment also decreased shoot As and Cd accumulation by 24.1 % (20.6 to 27.5 %) and 31.9 % (29.0 to 31.9 %), respectively. Furthermore, the Si amendment reduced the human health risks posed by As (2.6 %) and Cd (12.9 %) in crop grains. Si-induced inhibition of Cd accumulation is associated with decreased Cd bioavailability and the downregulation of gene expression. The regulation of gene expression by Si addition was the driving factor limiting shoot As accumulation. Overall, our analysis demonstrated that Si amendment has great potential to reduce the toxicity and accumulation of As and/or Cd in crops, providing a scientific basis for promoting food safety globally.


Asunto(s)
Arsénico , Oryza , Contaminantes del Suelo , Humanos , Grano Comestible/química , Cadmio/análisis , Silicio/farmacología , Arsénico/metabolismo , Contaminantes del Suelo/análisis , Suelo , Oryza/metabolismo , Triticum/metabolismo
12.
Proc Natl Acad Sci U S A ; 121(4): e2312556121, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38227655

RESUMEN

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease caused by the rodent-transmitted orthohantaviruses (HVs), with China possessing the most cases globally. The virus hosts in China are Apodemus agrarius and Rattus norvegicus, and the disease spread is strongly influenced by global climate dynamics. To assess and predict the spatiotemporal trends of HFRS from 2005 to 2098, we collected historical HFRS data in mainland China (2005-2020), historical and projected climate and population data (2005-2098), and spatial variables including biotic, environmental, topographical, and socioeconomic. Spatiotemporal predictions and mapping were conducted under 27 scenarios incorporating multiple integrated representative concentration pathway models and population scenarios. We identify the type of magistral HVs host species as the best spatial division, including four region categories. Seven extreme climate indices associated with temperature and precipitation have been pinpointed as key factors affecting the trends of HFRS. Our predictions indicate that annual HFRS cases will increase significantly in 62 of 356 cities in mainland China. Rattus regions are predicted to be the most active, surpassing Apodemus and Mixed regions. Eighty cities are identified as at severe risk level for HFRS, each with over 50 reported cases annually, including 22 new cities primarily located in East China and Rattus regions after 2020, while 6 others develop new risk. Our results suggest that the risk of HFRS will remain high through the end of this century, with Rattus norvegicus being the most active host, and that extreme climate indices are significant risk factors. Our findings can inform evidence-based policymaking regarding future risk of HFRS.


Asunto(s)
Fiebre Hemorrágica con Síndrome Renal , Ratas , Animales , Fiebre Hemorrágica con Síndrome Renal/epidemiología , Fiebre Hemorrágica con Síndrome Renal/etiología , Clima , Zoonosis , China/epidemiología , Murinae , Incidencia
13.
Biol Trace Elem Res ; 202(10): 4554-4566, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38148432

RESUMEN

This study aimed to examine the immuntoxic effects of arsenic in the nervous system. Our results showed that arsenic increased corticocerebral and hippocampal weights (p < 0.05). Morris water maze tests revealed that arsenic significantly increased the time spent in latency to platform on the fourth day in 50 mg/L arsenic exposure and the fifth day in 25 and 50 mg/L arsenic exposure, as well as reduced the path length in target quadrant, time spent in target quadrant, and crossing times of the platform (p < 0.05). Hematoxylin-eosin staining showed that the vacuolated degeneration and pyknosis was found in the cerebral cortex and hippocampus of arsenic-treated mice. The mRNA levels of corticocerebral and hippocampal brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were decreased in the 50 mg/L arsenic-treated group (p < 0.05). In addition, immunofluorescence staining showed that 25 and 50 mg/L arsenic all increased the expression of CD11b and glial fibrillary acidic protein (GFAP) in the cerebral cortex and hippocampus (p < 0.05). Arsenic markedly raised antigen-presenting molecule MHCII and CD40 mRNA levels in the cerebral cortex and hippocampus and upregulated the cell chemokine receptor 5 (CCR5) and CCR7 mRNA levels in the cerebral cortex at the 50 mg/L arsenic group, and increased the CCR7 mRNA levels in the hippocampus at the 25 and 50 mg/L arsenic groups (p < 0.05). Arsenic activated the nucleotide-binding domain-like receptor protein-3 (NLRP3) inflammasome, and enhanced its upstream promoter NF-κB protein level and downstream regulators IL-18 mRNA levels. Collectively, these results provide new evidences for the neuro-immune toxicity of arsenic.


Asunto(s)
Arsénico , Corteza Cerebral , Hipocampo , Inflamasomas , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Ratones , Arsénico/toxicidad , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Neuroglía/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Femenino
14.
Antioxidants (Basel) ; 12(12)2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-38136144

RESUMEN

Unfolded protein response (UPR) signaling and endoplasmic reticulum (ER) stress have been linked to pulmonary fibrosis. However, the relationship between UPR status and pulmonary function and prognosis in idiopathic pulmonary fibrosis (IPF) patients remains largely unknown. Through a series of bioinformatics analyses, we established a correlation between UPR status and pulmonary function in IPF patients. Furthermore, thrombospondin-1 (TSP-1) was identified as a potential biomarker for prognostic evaluation in IPF patients. By utilizing both bulk RNA profiling and single-cell RNA sequencing data, we demonstrated the upregulation of TSP-1 in lung fibroblasts during pulmonary fibrosis. Gene set enrichment analysis (GSEA) results indicated a positive association between TSP-1 expression and gene sets related to the reactive oxygen species (ROS) pathway in lung fibroblasts. TSP-1 overexpression alone induced mild ER stress and pulmonary fibrosis, and it even exacerbated bleomycin-induced ER stress and pulmonary fibrosis. Mechanistically, TSP-1 promoted ER stress and fibroblast activation through CD47-dependent ROS production. Treatment with either TSP-1 inhibitor or CD47 inhibitor significantly attenuated BLM-induced ER stress and pulmonary fibrosis. Collectively, these findings suggest that the elevation of TSP-1 during pulmonary fibrosis is not merely a biomarker but likely plays a pathogenic role in the fibrotic changes in the lung.

17.
Neural Regen Res ; 18(8): 1734-1742, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36751799

RESUMEN

Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species, which causes abnormal mitochondrial function and secondary reactive oxygen species generation. This creates a vicious cycle leading to reactive oxygen species accumulation, resulting in progression of the pathological process. Therefore, breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage. Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NADPH oxidase 4, NOX4) led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage. The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress, mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage. We found that NOX4 knockdown by adeno-associated virus (AAV-NOX4) in rats enhanced neuronal tolerance to oxidative stress, enabling them to better resist the oxidative stress caused by intracerebral hemorrhage. Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria, relieved mitochondrial damage, prevented secondary reactive oxygen species accumulation, reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats. Finally, we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4. The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis, which is similar to the effect of AAV-NOX4. This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production, and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.

18.
Int J Mol Sci ; 23(23)2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36498839

RESUMEN

When WWOX is downregulated in middle age, aggregation of a protein cascade, including TRAPPC6AΔ (TPC6AΔ), TIAF1, and SH3GLB2, may start to occur, and the event lasts more than 30 years, which results in amyloid precursor protein (APP) degradation, amyloid beta (Aß) generation, and neurodegeneration, as shown in Alzheimer's disease (AD). Here, by treating neuroblastoma SK-N-SH cells with neurotoxin MPP+, upregulation and aggregation of TPC6AΔ, along with aggregation of TIAF1, SH3GLB2, Aß, and tau, occurred. MPP+ is an inducer of Parkinson's disease (PD), suggesting that TPC6AΔ is a common initiator for AD and PD pathogenesis. Zfra, a 31-amino-acid zinc finger-like WWOX-binding protein, is known to restore memory deficits in 9-month-old triple-transgenic (3xTg) mice by blocking the aggregation of TPC6AΔ, SH3GLB2, tau, and amyloid ß, as well as inflammatory NF-κB activation. The Zfra4-10 peptide exerted a strong potency in preventing memory loss during the aging of 3-month-old 3xTg mice up to 9 months, as determined by a novel object recognition task (ORT) and Morris water maize analysis. Compared to age-matched wild type mice, 11-month-old Wwox heterozygous mice exhibited memory loss, and this correlates with pT12-WWOX aggregation in the cortex. Together, aggregation of pT12-WWOX may link to TPC6AΔ aggregation for AD progression, with TPC6AΔ aggregation being a common initiator for AD and PD progression.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Enfermedad de Alzheimer , Péptidos beta-Amiloides , Enfermedad de Parkinson , Animales , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Modelos Animales de Enfermedad , Trastornos de la Memoria , Ratones Transgénicos , Transducción de Señal , Proteínas tau/metabolismo , Enfermedad de Parkinson/metabolismo
20.
Appl Bionics Biomech ; 2022: 1493221, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36016919

RESUMEN

With the high development of sports, football has attracted more and more attention from the public. However, the hot competition has made football players undergo high-intensity training, and the risk of injury caused by training is also increasing. Lateral incision knee ACL injury is one of the most common types of injuries in football players, which has a serious impact on the athlete's physiology and daily training. The comprehensive, multi-level, convenient and fast medical system brought by the medical Internet of Things has become the growing demand of the medical industry. Based on the medical Internet of Things, this paper studies the rehabilitation nursing of football players' ACL injury by lateral cutting and running combined with optical microscope. In this paper, 36 male and female football players were selected for group experiments, and the landing and peak torque indexes of the experimental group and the control group of male and female athletes were analyzed under the observation of an optical microscope. Group (P <0.05), coxa valgus (P <0.01), internal rotation and knee valgus angles were greater than those in the EM group. And the peak hip flexion angle and knee valgus moment in NF group were lower than those in EF group (P <0.05). After 12 weeks of rehabilitation training, there was a significant difference in the Q/H joint contraction index between the REF group and the CON group (P <0.05), and there was no statistical difference in the other groups. After 12 weeks of rehabilitation training, there was a significant difference in the Q/H joint contraction index between the REF group and the CON group (P <0.05), and there was no statistical difference in the other groups. That is to say, after the systematic rehabilitation training proposed in this paper, the joint contraction performance of the hamstrings/quadriceps in the REF group has been significantly improved. This shows that the rehabilitation nursing under the optical microscope based on the medical Internet of Things has a good effect on the rehabilitation of the football player's side-cut running knee joint ACL injury.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...