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BACKGROUND: Sporadic Creutzfeldt-Jakob Disease (SCJD) is a severe neurodegenerative disorder characterized by rapid progression and extensive neuronal loss. Disulfidptosis is an innovative type of programmed cell demise characterized by an accumulation of disulfide bonds within the cellular cytoplasm, subsequently triggering functional disruption and cell demise. METHODS: Through literature review and analysis, we identified 18 candidate disulfidptosis-related genes (DRGs) involved in cellular processes. The dataset used for analysis, GSE124571, was obtained from the GEO database. Gene-gene and protein-protein interactions were analyzed using the GeneMANIA and STRING databases, respectively. We also performed enrichment analysis, DEGs analysis, WGCNA analysis, immune infiltration, consensus clustering and matrix correlation. RESULTS: The analysis showed that 12 out of 18 DRGs were significantly changed between SCJD and control groups. The DRGs had strong interactions such as physical interactions, co-expression and genetic interactions and were enriched in biological processes and pathways related to actin cytoskeletal regulation. The study most notably identified three hub genes (WASF2, TLN1 and G6PD) important for SCJD and emphasized the functional significance of the identified hub genes. The role of the immune system in the pathogenesis of SCJD The study found that the composition of immune cells in SCJD brain tissue is altered. Consensus clustering provided insights into immune infiltration and hub gene expression in SCJD subgroup. CONCLUSION: Our study reveals the possible involvement of disulfidptosis in SCJD and highlights the significance of identified hub genes as potential biomarkers and therapeutic targets for SCJD.
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Exposure to particulate matter 2.5 (PM2.5) is detrimental to multiple organ systems. Given the factor that aging also alters the cellularity and response of immune system and dysfunction of hypothalamic-pituitary-adrenal, -gonad and -thyroid axes, it is imperative to investigate whether chronic exposure to PM2.5 interacts with aging in these aspects. In this study, two-months-old Sprague-Dawley rats were exposed to real world PM2.5 for 16 months. PM2.5 exposure diminished the relative numbers of CD4+ T cells and CD8+ T cells and increased the relative number of B cells in the peripheral blood of male rats. Conversely, only reduced relative number of CD4+ T cells was seen in the blood of female rats. These shifts resulted in elevated levels of proinflammatory factors interleukin-6 and tumor necrosis factor-α in the circulatory systems of both sex, with females also evidencing a rise in interleukin-1ß levels. Moreover, heightened interleukin-6 was solely discernible in the hippocampus of female subjects, while increased tumor necrosis factor-α concentrations were widespread in female brain regions but confined to the male hypothalamus. Notable hormonal decreases were observed following PM2.5 exposure in both sex. These comprised declines in biomolecules such as corticotrophin-releasing hormone and cortisol, generated by the hypothalamic-pituitary-adrenal axis, and thyroid-releasing hormone and triiodothyronine, produced by the hypothalamic-pituitary-thyroid axis. Hormonal elements such as gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone, derived from the hypothalamic-pituitary-gonad axis, were also diminished. Exclusive to male rats was a reduction in adrenocorticotropic hormone levels, whereas a fall in thyroid-stimulating hormone was unique to female rats. Decreases in sex-specific hormones, including testosterone, estradiol, and progesterone, were also noted. These findings significantly enrich our comprehension of the potential long-term health repercussions associated with PM2.5 interaction particularly among the aging populace.
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This review article discusses the potential of nanomaterials in targeted therapy and immunomodulation for stroke-induced immunosuppression. Although nanomaterials have been extensively studied in various biomedical applications, their specific use in studying and addressing immunosuppression after stroke remains limited. Stroke-induced neuroinflammation is characterized by T-cell-mediated immunodepression, which leads to increased morbidity and mortality. Key observations related to immunodepression after stroke, including lymphopenia, T-cell dysfunction, regulatory T-cell imbalance, and cytokine dysregulation, are discussed. Nanomaterials, such as liposomes, micelles, polymeric nanoparticles, and dendrimers, offer advantages in the precise delivery of drugs to T cells, enabling enhanced targeting and controlled release of immunomodulatory agents. These nanomaterials have the potential to modulate T-cell function, promote neuroregeneration, and restore immune responses, providing new avenues for stroke treatment. However, challenges related to biocompatibility, stability, scalability, and clinical translation need to be addressed. Future research efforts should focus on comprehensive studies to validate the efficacy and safety of nanomaterial-based interventions targeting T cells in stroke-induced immunosuppression. Collaborative interdisciplinary approaches are necessary to advance the field and translate these innovative strategies into clinical practice, ultimately improving stroke outcomes and patient care.
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Nanoestruturas , Acidente Vascular Cerebral , Linfócitos T , Animais , Humanos , Citocinas/metabolismo , Citocinas/imunologia , Nanomedicina , Nanopartículas/química , Nanoestruturas/química , Acidente Vascular Cerebral/imunologia , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacosRESUMO
Retinal ischemia-reperfusion injury (RIRI) is a complex condition characterized by immune cell-mediated inflammation and consequent neuronal damage. This review delves into the immune response mechanisms in RIRI, particularly emphasizing the roles played by resident and peripheral immune cells. It highlights the pivotal role of microglia, the primary resident immune cells, in exacerbating neuroinflammation and neuronal damage through their activation and subsequent release of pro-inflammatory mediators. Additionally, the review explores the contributions of other glial cell types, such as astrocytes and Müller cells, in modulating the immune response within the retinal environment. The dual role of the complement system in RIRI is also examined, revealing its complex functions in both safeguarding and impairing retinal health. Inflammasomes, triggered by various danger signals, are discussed as crucial contributors to the inflammatory pathways in RIRI, with an emphasis on the involvement of different NOD-like receptor family proteins. The review further analyzes the infiltration and impact of peripheral immune cells like neutrophils, macrophages, and T cells, which migrate to the retina following ischemic injury. Critical to this discussion is the interplay between resident and peripheral immune cells and its implications for RIRI pathophysiology. Finally, the review outlines future research directions, focusing on basic research and the potential for clinical translation to enhance understanding and treatment of RIRI.
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BACKGROUND: Stroke-Induced Immunodepression (SIID) is characterized by apoptosis in blood immune populations, such as T cells, B cells, NK cells, and monocytes, leading to the clinical presentation of lymphopenia. Disulfidptosis is a novel form of programmed cell death characterized by accumulating disulfide bonds in the cytoplasm, resulting in cellular dysfunction and eventual cell death. OBJECTIVE: In this study, we investigated the association between disulfidptosis and stroke by analyzing gene sequencing data from peripheral blood samples of stroke patients. METHODS: Differential gene expression analysis identified a set of disulfidptosis-related genes (DRGs) significantly associated with stroke. Initial exploration identified 32 DRGs and their interactions. Our study encompassed several analyses to understand the molecular mechanisms of DRGs in stroke. Weighted Gene Co-Expression Network Analysis (WGCNA) uncovered modules of co-expressed genes in stroke samples, and differentially expressed gene (DEG) analysis highlighted 1643 key genes. RESULTS: These analyses converged on four hub genes of DRGs (SLC2A3, SLC2A14, SLC7A11, NCKAP1) associated with stroke. Immune cell composition analysis indicated positive correlations between hub genes and macrophages M1, M2, and neutrophils and negative associations with CD4+ and CD8+ T cells, B cells, and NK cells. Sub-cluster analysis revealed two distinct clusters with different immune cell expression profiles. Gene Set Enrichment Analysis (GSEA) demonstrated enrichment of apoptosis-related pathways, neurotrophin signaling, and actin cytoskeleton regulation. Associations between hub genes and apoptosis, necroptosis, ferroptosis, and cuproptosis, were also identified. CONCLUSION: These results suggest that the DRG hub genes are interconnected with various cell death pathways and immune processes, potentially contributing to stroke pathological development.
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Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/sangue , Apoptose/fisiologiaRESUMO
Rationale: Ischemic stroke poses a significant health burden with limited treatment options. Lymphocyte Cytosolic Protein 1 (LCP1) facilitates cell migration and immune responses by aiding in actin polymerization, cytoskeletal rearrangements, and phagocytosis. We have demonstrated that the long non-coding RNA (lncRNA) Maclpil silencing in monocyte-derived macrophages (MoDMs) led to LCP1 inhibition, reducing ischemic brain damage. However, the role of LCP1 of MoDMs in ischemic stroke remains unknown. Methods and Results: We investigated the impact of LCP1 on ischemic brain injury and immune cell signaling and metabolism. We found that knockdown of LCP1 in MoDMs demonstrated robust protection against ischemic infarction and improved neurological behaviors in mice. Utilizing the high-dimensional CyTOF technique, we demonstrated that knocking down LCP1 in MoDMs led to a reduction in neuroinflammation and attenuation of lymphopenia, which is linked to immunodepression. It also showed altered immune cell signaling by modulating the phosphorylation levels of key kinases and transcription factors, including p-PLCg2, p-ERK1/2, p-EGFR, p-AKT, and p4E-BP1 as well as transcription factors like p-STAT1, p-STAT3, and p-STAT4. Further bioinformatic analysis indicated that Akt and EGFR are particularly involved in fatty acid metabolism and glycolysis. Indeed, single-cell sequencing analysis confirmed that enrichment of fatty acid and glycolysis metabolism in Lcp1high monocytes/macrophages. Furthermore, Lcp1high cells exhibited enhanced oxidative phosphorylation, chemotaxis, migration, and ATP biosynthesis pathways. In vitro experiments confirmed the role of LCP1 in regulating mitochondrial function and fatty acid uptake. Conclusions: These findings contribute to a deeper understanding of LCP1 in the context of ischemic stroke and provide valuable insights into potential therapeutic strategies targeting LCP1 and metabolic pathways, aiming to attenuating neuroinflammation and lymphopenia.
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Lesões Encefálicas , AVC Isquêmico , Linfopenia , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt , Doenças Neuroinflamatórias , Macrófagos , Transdução de Sinais , Receptores ErbB , Ácidos Graxos , Fatores de TranscriçãoRESUMO
Postoperative cognitive dysfunction (POCD) is a cluster of cognitive problems that may arise after surgery. POCD symptoms include memory loss, focus inattention, and communication difficulties. Inflammasomes, intracellular multiprotein complexes that control inflammation, may have a significant role in the development of POCD. It has been postulated that the NLRP3 inflammasome promotes cognitive impairment by triggering the inflammatory response in the brain. Nevertheless, there are many gaps in the current literature to understand the underlying pathophysiological mechanisms and develop future therapy. This review article underlines the limits of our current knowledge about the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome and POCD. We first discuss inflammasomes and their types, structures, and functions, then summarize recent evidence of the NLRP3 inflammasome's involvement in POCD. Next, we propose a hypothesis that suggests the involvement of inflammasomes in multiple organs, including local surgical sites, blood circulation, and other peripheral organs, leading to systemic inflammation and subsequent neuronal dysfunction in the brain, resulting in POCD. Research directions are then discussed, including analyses of inflammasomes in more clinical POCD animal models and clinical trials, studies of inflammasome types that are involved in POCD, and investigations into whether inflammasomes occur at the surgical site, in circulating blood, and in peripheral organs. Finally, we discuss the potential benefits of using new technologies and approaches to study inflammasomes in POCD. A thorough investigation of inflammasomes in POCD might substantially affect clinical practice.
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It is of great scientific and practical importance to explore the mechanisms of accelerated degradation of Hexachlorobenzene (HCB) in soil. Both iron oxide and dithionite may promote the reductive dechlorination of HCB, but their effects on the microbial community and the biotic and abiotic mechanisms behind it remain unclear. This study investigated the effects of goethite, dithionite, and their interaction on microbial community composition and structure, and their potential contribution to HCB dechlorination in a paddy soil to reveal the underlying mechanism. The results showed that goethite addition alone did not significantly affect HCB dechlorination because the studied soil lacked iron-reducing bacteria. In contrast, dithionite addition significantly decreased the HCB contents by 44.0-54.9%, while the coexistence of dithionite and goethite further decreased the HCB content by 57.9-69.3%. Random Forest analysis suggested that indicator taxa (Paenibacillus, Acidothermus, Haliagium, G12-WMSP1, and Frankia), Pseudomonas, richness and Shannon's index of microbial community, and immobilized Fe content were dominant driving factors for HCB dechlorination. The dithionite addition, either with or without goethite, accelerated HCB anaerobic dechlorination by increasing microbial diversity and richness as well as the relative abundance of the above specific bacterial genera. When goethite and dithionite coexist, sulfidation of goethite with dithionite could remarkably increase FeS formation and then further promote HCB dechlorination rates. Overall, our results suggested that the combined application of goethite and dithionite could be a practicable strategy for the remediation of HCB contaminated soil.
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Poluentes do Solo , Solo , Solo/química , Hexaclorobenzeno , Ditionita/metabolismo , Poluentes do Solo/análise , Bactérias/metabolismoRESUMO
ABSTRACT: Aortic valve calcification commonly occurs in patients with chronic kidney disease (CKD). However, the regulatory functions of microRNAs (miRNAs/miRs) in the osteogenic differentiation of human aortic valvular interstitial cells (hAVICs) in patients with CKD remain largely unknown. This study aimed to explore the functional role and underlying mechanisms of miR-93-5p and miR-374a-5p in the osteogenic differentiation of hAVICs. For this purpose, hAVICs calcification was induced with high-calcium/high-phosphate medium and the expression levels of miR-93-5p and miR-374a-5p were determined using bioinformatics assay. Alizarin red staining, intracellular calcium content, and alkaline phosphatase activity were used to evaluate calcification. The expression levels of bone morphogenetic protein-2 (BMP2), runt-related transcription factor 2 (Runx2), and phosphorylated (p)-Smad1/5 were detected by luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. The results revealed that the expression levels of miR-93-5p and miR-374a-5p were significantly decreased in hAVICs in response to high-calcium/high-phosphate medium. The overexpression of miR-93-5p and miR-374a-5p effectively suppressed the high-calcium/high-phosphate-induced calcification and osteogenic differentiation makers. Mechanistically, the overexpression of miR-93-5p and miR-374a-5p inhibits osteogenic differentiation by regulating the BMP2/Smad1/5/Runx2 signaling pathway. Taken together, this study indicates that miR-93-5p and miR-374a-5p suppress the osteogenic differentiation of hAVICs associated with calcium-phosphate metabolic dyshomeostasis through the inhibition of the BMP2/Smad1/5/Runx2 signaling pathway.
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Estenose da Valva Aórtica , Calcinose , MicroRNAs , Humanos , Valva Aórtica/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Estenose da Valva Aórtica/genética , Osteogênese , Cálcio , Células Cultivadas , Calcinose/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais/fisiologia , Diferenciação Celular , FosfatosRESUMO
The dry deposition of heavy metals in atmospheric particulates is one of the important sources of heavy metals in agricultural areas, but there are few observational studies on the atmospheric deposition of heavy metals in agricultural areas. In this study, the concentrations of atmospheric particulates with different particle sizes and ten kinds of metal elements in them were analyzed by sampling a typical rice-wheat rotation area in the suburb of Nanjing for one year, and the dry deposition fluxes were estimated using the big leaf model, so as to understand the input characteristics of particulates and heavy metals. The results showed that the particulate concentrations and dry deposition fluxes were high in winter and spring but low in summer and autumn. In winter and spring, coarse particulates (2.1-9.0 µm) and fine particulates (<2.1 µm) had dual effects on particulate pollution, whereas in summer and autumn, particulate pollution was mainly attributed to the fine particulates. The concentrations of metal elements were the lowest in giant particulates (>9.0 µm) and were similar in coarse particulates and fine particulates, whereas Pb, Mn, As, and Cd elements were relatively high in fine particulates. The average annual dry deposition fluxes[g·(m2·a)-1] of particulates was giant particulates (8.31)>coarse particulates (5.99)>fine particulates (0.629). The order of average annual dry deposition fluxes[mg·(m2·a)-1] of the 10 metals was Ca(2096.4)>Al(1710.4)>Zn(855.0)>Fe(256.1)>Pb(40.35)>Cu(31.93)>V(26.21)>Mn(9.10)>As(2.48)>Cd(0.28). The average annual dry deposition fluxes of the 10 metal elements in fine particulates, coarse particulates, and giant particulates were 179.03, 2124.97, and 2724.18 mg·(m2·a)-1, respectively. These results will provide a reference for a more comprehensive understanding of the impact of human activities on the quality and safety of agricultural products and soil ecological environment.
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As a major agricultural country, the comprehensive accounting of the dynamics and composition of the carbon footprint of major crops in China will provide a decision-making basis for environmental management and agricultural green development in the whole process of the major crop production system in China. To investigate the spatiotemporal dynamics of the carbon footprint for major crops in China, a life cycle-based carbon footprint approach was used to evaluate the carbon footprint per unit area (CFA) and per unit yield (CFY) of eight crops for the period of 1990 to 2019. Our results showed that the CFA for all major crops showed an increasing trend with time before 2016 but slowly decreased afterward, while the CFY decreased by 16-43% over the past 30 years due to the increase in crop yield. The three main grain crops, rice (4871 ± 418 kg CO2-eq · ha-1), wheat (2766 ± 552 kg CO2-eq · ha-1), and maize (2439 ± 530 kg CO2-eq · ha-1), showed the highest carbon footprint and contribution to the total greenhouse gas (GHG) emissions, mainly due to their larger cultivated areas and higher fertilizer application rates. CH4 emission was the major component of the carbon footprint for rice production, accounting for 66% and 48% of the CFA and CFY, respectively, while fertilizer production and usage were the largest components of carbon footprint for dryland crops, making up to 26-49% of the CFA and 26-50% of the CFY for different crops. The present study also highlighted the spatial and temporal patterns of the carbon footprint for major crops in China, which could serve as references for the development of best management practices for different crop production in China, to mitigate agricultural GHG emission and to pursue low-carbon agriculture.
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Gases de Efeito Estufa , Oryza , Pegada de Carbono , Fertilizantes , Dióxido de Carbono , Produção Agrícola , Agricultura/métodos , Produtos Agrícolas , Carbono , ChinaRESUMO
Agricultural Life Cycle Assessment (LCA) is an effective tool for the quantitative evaluation and analysis of agricultural materials production and operation activities in various stages of the agricultural system. Based on the concept of life cycle, it comprehensively summarizes the impact of agriculture on the environment, which is an effective tool to promote the sustainability and green development of agriculture. In recent years, agricultural LCA has been widely used in the agroecosystem for resource and environmental impacts analysis. However, some challenges still exist in agricultural LCA, i.e., the environmental impact assessment index system needs to be improved; its application in different production mode is limited; and combination research with other models needs more attention. This paper discusses the above-mentioned challenges and recommends research priorities for both scientific development and improvements in practical implementation. In summary, further research is needed to construct a regional heterogeneity database and develop innovated methodologies to develop more meaningful functional units for agricultural products to complement LCA by other models. These efforts will make agricultural LCA more robust and effective in environmental impacts assessment to support decision making from individual farm to regional or (inter)national for the sustainable future of agriculture.
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Agricultura , Meio Ambiente , Agricultura/métodos , Animais , Fazendas , Estágios do Ciclo de VidaRESUMO
Background: Maclpil is a proinflammatory long non-coding RNA highly expressed on monocyte-derived macrophages in the ischemic brain. This study investigated the impact and the mechanisms of systemically delivering nanoparticle Maclpil short interfering RNA (siRNA) on experimental ischemic stroke in a mouse model. Methods: Ischemic stroke (focal cerebral ischemia) was induced in male C57BL/6 mice through the middle cerebral artery occlusion. Three hours thereafter, mice were intravenously injected with Maclpil siRNA or scramble siRNA nanoparticles. Bone marrow cell-derived macrophages were transfected with Maclpil or scramble siRNA and subjected to oxygen glucose deprivation culture. The influence of silencing Maclpil on stroke outcomes, neuroinflammation, and macrophage fates was assessed via histology, flow cytometry, Western blotting, and quantitative PCR analysis. Results: Three days following stroke induction, siRNA silencing Maclpil substantially reduced ischemic infarction size and improved neurological behaviors. Silencing Maclpil also markedly attenuated the accumulation of monocyte-derived macrophages, CD4+ T cells, and CD8+ T cells in the ischemic hemisphere without affecting microglia cellularity. Reciprocally, myeloid cells and both subsets of T cells were elevated in mouse peripheral blood following Maclpil siRNA treatment. Under oxygen glucose deprivation conditions that mimicked hypoxia and hypoglycemia in vitro, Maclpil siRNA silencing augmented macrophage apoptosis in conjunction with upregulation of proapoptotic Bax and caspase 3 expressions. siRNA knocking down Maclpil skewed macrophages from proinflammatory classical toward anti-inflammatory alternative activation as evidenced by increased arginase 1, Ym1, and Fizz1 and reduced inducible nitric oxide synthase, IL-1ß, and TNF-α mRNA levels. Consistent with macrophage phenotype switching, silencing Maclpil by siRNA enhanced fatty acid oxidation as indicated by increased mRNA levels of 3 key metabolic enzymes (ACADM, ACADVL, and HADHA). Conclusion: Systemically silencing Maclpil by siRNA nanoparticles attenuated experimental ischemic stroke by promoting macrophage apoptosis and anti-inflammatory alternative activation. Identifying and targeting Maclpil human homolog(s) may help develop a novel therapy for stroke clinical management.
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Background: Visceral fat has been considered an important risk factor of elevated serum uric acid (SUA). Perirenal fat is a unique visceral fat around the kidneys that has special morphological and physiological features while its relationship with SUA remains incompletely elucidated. This study aimed to assess the association between perirenal fat volume (PrFV) and SUA. Methods: A cross-sectional study was conducted in 102 subjects aged ≥ 18 years old recruited from Nanjing,China. The clinical characteristics including age, sex, drinking behavior, history of hypertension, body mass index, waist circumference, total cholesterol, fast plasma glucose, urea, serum creatinine, C-reactive protein, and SUA were recorded. PrFV was measured by ultrasonography. Multivariate linear models and the restricted cubic spline were used to investigate the association between PrFV and SUA. Results: The median age of this study population was 52.5 (42.0-60.0) years and 56.9% were female. The median value of SUA was 5.73 mg/dL (4.58-6.80 mg/dL). The subjects were divided by PrFV tertiles and we found that the subjects in the highest PrFV tertile had a higher level of SUA compared to those in the lowest tertile (ß=1.86, 95%CI 1.23-2.48, P for trend <0.001).The positive association also remained after adjustment for potential covariates (tertile3 versus tertile1: ß=0.99, 95%CI 0.35-1.63, P for trend =0.005). There was an increase of approximately 0.53 mg/dL in SUA per 1-fold increase in PrFV (ß=0.53, 95%CI 0.02-1.04, P for nonlinearity = 0.637). Conclusion: Our results confirmed a positive independent relationship between PrFV and SUA in Chinese adults. This study suggested that perirenal fat might constitute a potential risk factor for elevated serum uric acid levels.
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Gordura Intra-Abdominal , Ácido Úrico , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Rim , Masculino , Pessoa de Meia-IdadeRESUMO
We have previously reported that filtered air (FA) intervention reduces inflammation and hypothalamus-pituitary-adrenal axis activation after fine particulate matter (PM2.5 exposure). Whether FA also modulates the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-gonadal (HPG) axes in rats after PM2.5 exposure is still unknown. Adult Sprague-Dawley rats were exposed to PM2.5 by using a "real-world" PM2.5 exposure system, and the FA intervention was conducted by renewing for 15 days. PM2.5 inhalation decreased thyrotropin-releasing hormone (TRH) and thyroxine (T4) levels in both male and female rats, and thyroid-stimulating hormone (TSH) level in male rats. FA intervention attenuated the reduction in TRH and TSH levels in male rats and reduction in T4 level in female rats. PM2.5 inhalation also reduced testosterone (T) level in male rats, and estradiol (E2) and progesterone (PROG) levels in female rats, and these changes were attenuated after FA intervention. The FA intervention attenuated the decreases in CD8 T cells and T cells induced by PM2.5 inhalation in female rats only by flow cytometry analysis. In blood, FA interventions ameliorated IL-6 and IL-1ß mRNA levels in both male and female rats after PM2.5 exposure. FA intervention restored the IL-4 and IL-10 levels in female rats after PM2.5 exposure. Moreover, FA intervention ameliorated the inflammatory responses induced by PM2.5 inhalation in the thyroid and gonads in both male and female rats. These data indicate that FA intervention exerted an effect on modulating the hormonal balance of the HPT and HPG axes, and this may be related to a reduction in the inflammatory responses in the thyroid and gonads of PM2.5-treated rats, respectively.
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Glândula Tireoide , Hormônio Liberador de Tireotropina , Animais , Estradiol/farmacologia , Feminino , Gônadas/química , Interleucina-10 , Interleucina-4/farmacologia , Interleucina-6 , Masculino , Material Particulado/farmacologia , Progesterona , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Testosterona , Tireotropina , Hormônio Liberador de Tireotropina/análise , Hormônio Liberador de Tireotropina/genética , Hormônio Liberador de Tireotropina/farmacologia , TiroxinaRESUMO
An electrochemical biosensor for determination of DNA is developed based on T7 exonuclease-assisted regulatory strand displacement dual recycling signal amplification strategy. First, the hairpin probe recognized and bound the target DNA to form a double strand nucleotide structure, and then the T7 exonuclease was introduced. After be digested by T7 exonuclease, the target DNA was released and entered the next cycle of T7 exonuclease-assisted recycle amplification, while accompanied by a large number of mimic targets (output DNAs) into another cycle. Second, the mimic target reacted with double-chain substrated DNA (CP) by a regulated toehold exchange mechanism, yielding the product complex of detection probes with the help of assisted DNA (S). Finally, after many cycles, a large number of detection probes were produced for binding numerous streptavidin-alkaline phosphatases. The electrochemical biosensor showed very high sensitivity and selectivity with a dynamic response ranged from 0.1 fM to 10 pM with a detection limit of 31.6 aM. Furthermore, this proposed biosensor was successfully applied to the detection of target DNA in 20% diluted serum. The developed strategy has been demonstrated to have the potential for application in molecular diagnostics.
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Técnicas Biossensoriais , Técnicas Eletroquímicas , DNA/genética , ExodesoxirribonucleasesRESUMO
Objective To explore the performance of mobile health platform for standardized management of pregnant women with gestational diabetes mellitus(GDM). Methods A randomized controlled trial was conducted,in which 295 women with GDM were randomized into two groups(traditional management group and mobile health management group)by a computer-generated sequence.The traditional management group accepted standardized GDM management,and the mobile health management group was supplemented by mobile health management based on the standardized management.The glycemic control rate and the incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit were compared between the two groups. Results The glycemic control rate in mobile health management group was significantly higher than that in the traditional management group [(67.22±22.76)% vs.(60.69±21.28)%,P=0.004].The incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit demonstrated no significant differences between groups(all P > 0.05). Conclusions Mobile health applied in standardized management is conducive to the glycemic control of GDM women,whereas it does not significantly improve the pregnancy outcomes.Due to the short time of intervention,the effects of mobile health on pregnancy outcomes need further study.
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Diabetes Gestacional , Nascimento Prematuro , Telemedicina , Cesárea , Diabetes Gestacional/terapia , Feminino , Macrossomia Fetal , Humanos , Recém-Nascido , Gravidez , Resultado da GravidezRESUMO
ABSTRACT: Calcific aortic valve disease is a common heart disease that contributes to increased cardiovascular morbidity and mortality. There is a lack of effective pharmaceutical therapy because its mechanisms are not yet fully known. Ginkgo biloba extract (EGB761) is reported to alleviate vascular calcification. However, whether EGB761 protects against aortic valve calcification, a disease whose pathogenesis shares many similarities with vascular calcification, and potential molecular mechanisms remain unknown. In this study, porcine aortic valve interstitial cell (pAVIC) calcification was induced by warfarin with or without the presence of EGB761. Immunostaining was performed to establish and characterize the pAVIC phenotype. Calcium deposition and calcium content were examined by Alizarin Red S staining and an intracellular calcium content assay. Alkaline phosphatase activity was detected by the p-nitrophenyl phosphate method. The expression levels of bone morphogenetic protein-2 (BMP2), Runt-related transcription factor 2 (Runx2), homeobox protein MSX-2, and phosphorylated (p)-Smad1/5 were detected by reverse transcription-quantitative polymerase chain reaction (PCR) and Western blot analysis. Consistent with these in vitro data, we also confirmed the suppression of in vivo calcification by EGB761 in the warfarin-induced C57/Bl6 mice. The results indicated that both pAVICs and aortic valves tissue of mice stimulated with warfarin showed increased calcium deposition and expression of osteogenic markers (alkaline phosphatase, BMP2, homeobox protein MSX-2, and Runx2) and promoted p-Smad1/5 translocation from the cytoplasm to the nucleus. The addition of EGB761 significantly inhibited p-Smad1/5 translocation from the cytoplasm to the nucleus, thus suppressing calcification. In conclusion, EGB761 could ameliorate warfarin-induced aortic valve calcification through the inhibition of the BMP2-medicated Smad1/5/Runx2 signaling pathway.
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Valva Aórtica/efeitos dos fármacos , Proteína Morfogenética Óssea 2/metabolismo , Calcinose/prevenção & controle , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Doenças das Valvas Cardíacas/prevenção & controle , Extratos Vegetais/farmacologia , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Calcinose/induzido quimicamente , Calcinose/metabolismo , Calcinose/patologia , Cálcio/metabolismo , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Modelos Animais de Doenças , Ginkgo biloba , Doenças das Valvas Cardíacas/induzido quimicamente , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/patologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Osteogênese/efeitos dos fármacos , Fosforilação , Transdução de Sinais , Sus scrofa , VarfarinaRESUMO
OBJECTIVE: To investigate the effect of health education via clinical nursing pathway (CNP) on self-care agency, quality of life, negative emotions and nursing satisfaction among patients with ovarian carcinoma. METHODS: The clinical data of 61 patients with ovarian carcinoma admitted to the Oncology Department of our hospital from January 2019 to January 2020 were analyzed retrospectively. According to the different nursing methods, the patients were divided into a control group (n=31) and an observation group (n=30). The postoperative complications, the scores of self-care agency and quality of life before and after intervention, sleep quality and negative emotions were compared and analyzed between the two groups. RESULTS: Patients in the observation group had higher mastery of health knowledge and lower incidence of postoperative complications than those in the control group. The scores of SDS, SAS and PSQI were significantly decreased in both groups after intervention compared with those before intervention (P<0.05), and the scores in the observation group were significantly lower than those in the control group (P<0.05). After intervention, both groups showed higher scores of self-care agency and quality of life than before intervention (P<0.05), and patients in the observation group showed higher scores than those in the control group (P<0.05). The overall nursing satisfaction of patient was relatively high. CONCLUSION: Health education via CNP can help patients better understand the diseases, reduce their psychological burden and improve sleep quality. Informing patients of the methods of postoperative restorative exercise through health education is able to reduce complications incidence and improve self-care agency and quality of life of patients.
RESUMO
AIMS: To investigate the effects of mobile health based peripartum management of gestational diabetes mellitus (GDM) on postpartum diabetes and factors associated with postpartum diabetes. METHODS: Women with GDM (n = 309) were randomly assigned to receive standard management (SM) or mobile management (MM). 75-g OGTT was performed at 6 weeks postpartum. RESULTS: The incidence of postpartum T2DM in the MM group was much higher than that in SM group (12.36% vs. 3.88%, P = 0.0291). The fasting, 1-h and 2 h OGTT at 24-28 weeks of gestation of T2DM women were higher than those women without T2DM (fasting, 6.08 vs. 4.90, P = 0.0052; 1-h, 13.20 vs. 10.00, P < 0.0001; 11.96 vs. 8.83, P = 0.0026) in MM group. The 1-h and 2 h OGTT at 24-28 weeks of gestation of T2DM women were higher than those women without T2DM (11.54 vs. 9.78, P = 0.0484; 10.68 vs. 8.68, P = 0.0108) in SM group. Higher OGTT values at 24-28 weeks of gestation were risk factors of postpartum T2DM. CONCLUSIONS: Higher OGTT values at 24-28 weeks of gestation were risk factors to develop postpartum T2DM. Mobile health based peripartum management of GDM increased the risk of postpartum diabetes among women with GDM for lacking of postpartum management. Further studies of mobile health based postpartum management of GDM are needed. ClinicalTrials.gov registration number NCT03748576.