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The Bacillus velezensis strain NT35, which has strong biocontrol ability, was isolated from the rhizosphere soil of Panax ginseng. The antifungal effects of the NT35 strain against the mycelium and spore growth of Ilyonectria robusta, which causes ginseng rusty root rot, were determined. The inhibitory rate of I. robusta mycelial growth was 94.12% when the concentration of the NT35 strain was 107 CFU·mL-1, and the inhibitory rates of I. robusta sporulation and spore germination reached 100 and 90.31%, respectively, when the concentration of the NT35 strain was 104 and 108 CFU·mL-1, respectively. Strain NT35 had good prevention effects against ginseng rust rot indoors and in the field with the control effect 51.99%, which was similar to that of commercial chemical and biocontrol agents. The labeled strain NT35-Rif160-Stre400 was obtained and colonized ginseng roots, leaves, stems and rhizosphere soil after 90 days. Bacillus velezensis NT35 can induce a significant increase in the expression of five defensive enzyme-encoding genes and ginsenoside biosynthesis-related genes in ginseng. In the rhizosphere soil, the four soil enzymes and the microbial community improved during different periods of ginseng growth in response to the biocontrol strain NT35. The NT35 strain can recruit several beneficial bacteria, such as Luteimonas, Nocardioides, Sphingomonas, and Gemmatimonas, from the rhizosphere soil and reduce the relative abundance of Ilyonectria, Fusarium, Neonectria and Dactylonectria, which cause root rot and rusty root rot in ginseng plants. The disease indices were significantly negatively correlated with the abundances of Sphingomonas and Trichoderma. Additionally, Sphingomonadales, Sphingomonadaceae and actinomycetes were significantly enriched under the NT35 treatment according to LEfSe analysis. These results lay the foundation for the development of a biological agent based on strain NT35.
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BACKGROUND: Thyroid nodules have attracted much attention due to their high incidence and potential for malignant transformation. Compared with the clinical assessment and diagnosis of thyroid nodules, there are relatively few studies on the epidemiological risk factors for thyroid nodules. The aim of this study was to investigate the prevalence of thyroid nodule among adults in Zhejiang province and to explore their relationship with physiological and psychosocial factors. METHODS: The data used in this study were obtained from the baseline survey of the Zhejiang Provincial Cohort Study on Environment and Health. From June 2022 to December 2023, a total of 21,712 participants from five representative cities in Zhejiang were recruited for the baseline survey. Based on the inclusion and exclusion criteria, 15,595 adults were included in the analysis. The data were collected via self-report questionnaires and physical examinations. Multivariate logistic regression analysis was subsequently performed. RESULTS: The detection rate of thyroid nodules was 50.98% among adults in Zhejiang province. Age, gender, education level, BMI, tea and alcohol consumption all had a statistically significant association with thyroid nodules (p < 0.05). After adjusting for sociodemographic factors, results of logistic regression analysis showed that good life satisfaction (OR = 0.854, 95% CI: 0.780-0.934) had a lower risk of thyroid nodules, however, poor life satisfaction (OR = 1.406, 95% CI: 1.014-1.951), social isolation (OR = 1.294, 95% CI: 1.089-1.538) and a family history of thyroid nodules (OR = 1.334, 95% CI: 1.064-1.672) had a greater risk of thyroid nodules. CONCLUSION: The detection rate of thyroid nodules in adults of Zhejiang province was an increasing trend compared with that in previous years. In addition to the sensitive thyroid nodule screening technology, influencing factors mentioned in this study might also represent credible candidates for this increase. As variable influence factors, weight management, good interpersonal relationships and life satisfaction should be the focus of health interventions.
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Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/psicologia , China/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Prevalência , Adulto , Fatores de Risco , Estudos de Coortes , Idoso , Inquéritos e Questionários , Adulto JovemRESUMO
Hsp40-Hsp70 typically function in concert as molecular chaperones, and their roles in post-infection immune responses are increasingly recognized. However, in the economically important fish species Scophthalmus maximus (turbot), there is still a lack in the systematic identification, interaction models, and binding site analysis of these proteins. Herein, 62 Hsp40 genes and 16 Hsp70 genes were identified in the turbot at a genome-wide level and were unevenly distributed on 22 chromosomes through chromosomal distribution analysis. Phylogenetic and syntenic analysis provided strong evidence in supporting the orthologies and paralogies of these HSPs. Protein-protein interaction and expression analysis was conducted to predict the expression profile after challenging with Aeromonas salmonicida. dnajb1b and hspa1a were found to have a co-expression trend under infection stresses. Molecular docking was performed using Auto-Dock Tool and PyMOL for this pair of chaperone proteins. It was discovered that in addition to the interaction sites in the J domain, the carboxyl-terminal domain of Hsp40 also plays a crucial role in its interaction with Hsp70. This is important for the mechanistic understanding of the Hsp40-Hsp70 chaperone system, providing a theoretical basis for turbot disease resistance breeding, and effective value for the prevention of certain diseases in turbot.
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Doenças dos Peixes , Linguados , Proteínas de Choque Térmico HSP40 , Proteínas de Choque Térmico HSP70 , Filogenia , Animais , Linguados/imunologia , Linguados/genética , Linguados/microbiologia , Linguados/metabolismo , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Doenças dos Peixes/genética , Doenças dos Peixes/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Proteínas de Peixes/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/genética , Simulação de Acoplamento Molecular , Aeromonas salmonicida/imunologia , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genéticaRESUMO
RNAs transcribing more than 200 nucleotides without encoding proteins are termed long non-coding RNAs (LncRNAs). LncRNAs can be used as decoy molecules, signal molecules, scaffolds, and guide molecules. Long non-coding RNAs can interact with DNA, chromatin-modifying complexes, and transcriptional regulatory proteins, regulating gene expression in the cell nucleus. It is distributed in cytoplasm; they also participate in mRNA degradation and translational regulation via miRNAs, other transcription products, and proteins. They play a significant role in the development of various diseases, including tumors. Cancer seriously threatens human life and health. Regretfully, a great deal of newly diagnosed cancer patients found to have metastasized. RNF144A-AS1, also referred to as GRASLND, was initially recognized for its regulation of chondrogenic differentiation in MSCs. Focusing on RNF144A-AS1, this review summarizes and discusses the latest progress of RNF144A-AS1 in bladder cancer, glioblastoma, papillary renal cell carcinoma, gastric cancer, osteosarcoma, head and neck squamous cell carcinoma, and ovarian cancer. RNF144A-AS1 has good potential in tumor treatment and diagnosis.
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The prevalence of autoimmune diseases ranks as the third most common disease category globally, following cancer and heart disease. Numerous studies indicate that long non-coding RNA (lncRNA) plays a pivotal role in regulating human growth, development, and the pathogenesis of various diseases. It is more than 200 nucleotides in length and is mostly involve in the regulation of gene expression. Furthermore, lncRNAs are crucial in the development and activation of immune cells, with an expanding body of research exploring their association with autoimmune disorders in humans. LncRNA Ifng antisense RNA 1 (IFNG-AS1), a key regulatory factor in the immune system, also named NeST or TMEVPG1, is proximally located to IFNG and participates in the regulation of it. The dysregulation of IFNG-AS1 is implicated in the pathogenesis of several autoimmune diseases. This study examines the role and mechanism of IFNG-AS1 in various autoimmune diseases and considers its potential as a therapeutic target.
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Doenças Autoimunes , Interferon gama , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Doenças Autoimunes/genética , Interferon gama/genética , Regulação da Expressão Gênica/genética , Expressão Gênica/genética , Terapia de Alvo MolecularRESUMO
OBJECTIVE: This study aimed to use Mendelian randomization (MR) to investigate the potential causal association between inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). METHODS: Two-sample MR was performed to estimate the causal effect of IBD on AIH. The primary analysis employed the inverse variance weighted (IVW) method in univariable MR analysis, supplemented by additional methods including MR-Egger, weighted median, simple mode, and weighted mode. The p values were adjusted by FDR p-value adjustment. In the replication analysis, the primary IVW analysis was repeated and then pooled by meta-analysis. Sensitivity analyses were performed using Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out, and funnel plot analysis to evaluate the robustness of the MR findings. Additionally, multivariable MR (MVMR) was employed to estimate the direct causal effect of IBD on the risk of AIH. RESULTS: In univariable MR analysis, a significant positive causal association was observed between IBD (both Crohn's disease (CD) or ulcerative colitis (UC)) and the risk of AIH (for CD and AIH, the IVW odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.00-1.16, P = 0.045, FDR P = 0.045; for UC and AIH, the IVW OR = 1.07, 95% CI = 1.00-1.13, P = 0.038, FDR P = 0.076). Furthermore, no significant positive correlation between IBD and the risk of AIH (OR = 1.13, 95% CI = 0.94-1.35, P = 0.194). Sensitivity analysis revealed no pleiotropic bias. MVMR analysis further confirmed the direct causal effect of CD or UC on the risk of AIH after adjusting for the common risk factors (cigarettes per day and osteoporosis). In the replication analysis, the positive causal association between UC and the risk of AIH remain significant (the IVW odds ratio (OR) = 1.32, 95% CI = 1.18-1.48, P = 2.90E-06). While no significant positive association was observed between CD or IBD and the risk of AIH in the replication analysis, a suggestive positive association between the identified risk factors (UC, CD, and IBD) and the risk of AIH was detected in the meta-analysis (OR = 1.09, 95% CI = 1.05-1.13, P<0.0001). CONCLUSION: This MR study revealed a positive impact of the identified risk factors (CD, UC and IBD) on the risk of AIH within the European population.
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Hepatite Autoimune , Doenças Inflamatórias Intestinais , Análise da Randomização Mendeliana , Humanos , Hepatite Autoimune/genética , Hepatite Autoimune/epidemiologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/epidemiologia , Fatores de Risco , Doença de Crohn/genética , Doença de Crohn/epidemiologia , Colite Ulcerativa/genética , Colite Ulcerativa/epidemiologia , Predisposição Genética para Doença , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Psoriasis is a chronic inflammatory disease characterized by increased keratinocyte proliferation and local inflammation. Long noncoding RNAs (lncRNAs) play important regulatory roles in many immune-mediated diseases, including psoriasis. In this study, we aimed to investigate the role and mechanism of lnc-SPRR2G-2 (SPRR2G) in M5-treated psoriatic keratinocytes. Fluorescence in situ hybridization and quantitative real-time polymerase chain reaction (qRT-PCR) showed that lnc-SPRR2G-2 was significantly upregulated in psoriasis tissues and psoriatic keratinocytes. In psoriatic keratinocytes, functional and molecular experiment analyses demonstrated that SPRR2G regulated proliferation, cell cycle and apoptosis, and induced the expression of S100 calcium binding protein A7 (S100A7), interleukin (IL)-1ß, IL-8 and C-X-C motif chemokine ligand 10 (CXCL10). The function of SPRR2G in psoriasis is related to the STAT3 signaling pathway and can be inhibited by a STAT3 inhibitor. Moreover, KH-type splicing regulatory protein (KHSRP) was proved to be regulated by lnc-SPRR2G-2 and to control the mRNA decay of psoriasis-related cytokines (p < 0.05). In summary, we reported the functions of lnc-SPRR2G-2 and KHSRP in psoriasis. Our findings provide new insights for the further exploration of the pathogenesis and treatment of psoriasis.
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Proliferação de Células , Inflamação , Queratinócitos , Psoríase , RNA Longo não Codificante , Fator de Transcrição STAT3 , Transdução de Sinais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Psoríase/genética , Psoríase/patologia , Psoríase/metabolismo , Queratinócitos/metabolismo , Queratinócitos/patologia , Proliferação de Células/genética , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Regulação para Baixo/genética , Proteína A7 Ligante de Cálcio S100/genética , Proteína A7 Ligante de Cálcio S100/metabolismo , Apoptose/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Masculino , Feminino , AdultoRESUMO
BACKGROUND/AIMS: To distinguish the clinical feature of nanophthalmos (NNO) caused by mutations in protease serine 56 (PRSS56), membrane-type frizzled-related protein (MFRP), myelin regulatory factor (MYRF) and transmembrane protein 98 (TMEM98) and to evaluate the association between angle-closure glaucoma (ACG) and NNO. METHODS: Variants in those four genes were identified through exome sequencing/whole genome sequencing data, and bioinformatic analysis was conducted to identify pathogenic/likely pathogenic (P/LP) variants. This observational study comprehensively summarised ophthalmological data of 67 patients with NNO from 63 families. Ocular parameters from 68 eyes without surgical treatment were subjected to further analysis. RESULTS: Totally, 67 patients from 63 families harboured 57 P/LP variants in the four genes, including 30 in PRSS56 (47.6%), 23 in MFRP (36.5%), 5 in TMEM98 (7.9%) and 5 in MYRF (7.9%). ACG was present in 79.1% of patients. An analysis of ocular parameters from 68 eyes revealed that shorter axial length (AL), lower vitreous-to-AL ratios and severe foveal hypoplasia were associated with variants in PRSS56 and MFRP. Uveal effusion was more common in patients with PRSS56 variants, while retinitis pigmentosa was frequently observed in patients with MFRP variants. Patients with MYRF variants exhibited the thinnest retinal nerve fibre layer thickness. Patients with TMEM98 variants had an earlier average onset age of glaucoma. CONCLUSION: Variants in PRSS56 and MFRP are the most common genetic cause of NNO. ACG is a severe complication frequently observed in these patients. Earlier onset of ACG is observed in patients with dominant NNO, while foveal hypoplasia is more common in patients with recessive disease. Recognising these features is helpful in clinical care and genetic counselling.
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Heterochromatin is generally associated with the nuclear periphery, but how the spatial organization of heterochromatin is regulated to ensure epigenetic silencing remains unclear. Here we found that Sad1, an inner nuclear membrane SUN-family protein in fission yeast, interacts with histone H2A-H2B but not H3-H4. We solved the crystal structure of the histone binding motif (HBM) of Sad1 in complex with H2A-H2B, revealing the intimate contacts between Sad1HBM and H2A-H2B. Structure-based mutagenesis studies revealed that the H2A-H2B-binding activity of Sad1 is required for the dynamic distribution of Sad1 throughout the nuclear envelope (NE). The Sad1-H2A-H2B complex mediates tethering telomeres and the mating-type locus to the NE. This complex is also important for heterochromatin silencing. Mechanistically, H2A-H2B enhances the interaction between Sad1 and HDACs, including Clr3 and Sir2, to maintain epigenetic identity of heterochromatin. Interestingly, our results suggest that Sad1 exhibits the histone-enhanced liquid-liquid phase separation property, which helps recruit heterochromatin factors to the NE. Our results uncover an unexpected role of SUN-family proteins in heterochromatin regulation and suggest a nucleosome-independent role of H2A-H2B in regulating Sad1's functionality.
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Heterocromatina , Histonas , Ligação Proteica , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Heterocromatina/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/química , Histonas/metabolismo , Schizosaccharomyces/metabolismo , Schizosaccharomyces/genética , Telômero/metabolismo , Telômero/genética , Membrana Nuclear/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Cristalografia por Raios XRESUMO
Balanophora harlandii Hook (B. harlandii), a folk medicine, has been traditionally employed to treat traumatic bleeding, gastroenteritis, icteric hepatitis, hemorrhoids, and other conditions. In this work, polysaccharides with anti-inflammatory effects were extracted from B. harlandii and purified. The extraction conditions were optimized, and the properties of one purified neutral fraction, denoted as BHPs-W-S3, were analyzed. BHPs-W-S3 has a molecular weight of 14.1â¯kDa, and its three main monosaccharides are glucose, galactose, and xylose, with a molar ratio of 6.4:1.7:1.1. Its main chain consists of â6)-α-D-Glcp-(1â, â4,6)-α-D-Glcp-(1â, â6)-ß-D-Galp-(1â, â3,6)-ß-D-Galp-(1â, and it has branch chains at the O-4 and/or O-3 positions. In addition, in vitro experiments showed that the polysaccharides from B. harlandi can decrease the phosphorylation level of p65 and IκBα in LPS-induced RAW264.7 cells to reduce the expression of the pro-inflammatory genes such as TNF-α, IL-6, and IL-1ß.
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Anti-Inflamatórios , Polissacarídeos , Camundongos , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Células RAW 264.7 , Peso Molecular , Balanophoraceae/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Inflamação/tratamento farmacológicoRESUMO
BACKGROUND: Burning mouth syndrome is a chronic pain syndrome mainly characterized by an intensive burning sensation of tongue. Previous studies have suggested that saliva/serum biomarkers in burning mouth syndrome might be associated with psychological disorders. The aim of systematic review was to observe whether the biomarkers in serum/saliva could be an alternative method to evaluate the psychological disorders in patients with burning mouth syndrome. MATERIALS AND METHODS: The PubMed, Embase, and Cochrane Library databases were searched for papers published up to March 15, 2023. Risk of bias was measured by using the Newcastle-Ottawa Scale. RevMan was used for meta-analysis. RESULTS: A total of 467 articles were screened, which of 12 studies were included. These studies collected 43 different biomarkers in saliva and 35 in serum. Of these biomarkers, only three (cortisol, α-amylase, and IL-6) were analyzed in two or more studies. Only salivary cortisol levels were significantly higher in the patient group compared to the controls (Mean Difference = 1.39; 95% CI [0.80-1.97]; p < 0.001). Moreover, cortisol might be relevant to psychological scores, especially anxiety. CONCLUSION: Different papers have investigated salivary and serum biomarkers in burning mouth syndrome patients with controversial results. This meta-analysis showed that cortisol levels in saliva may be a potential biomarker to assess the psychological disorders in burning mouth syndrome patients.
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Síndrome da Ardência Bucal , Humanos , Síndrome da Ardência Bucal/diagnóstico , Hidrocortisona/análise , Saliva/química , Biomarcadores/análise , AnsiedadeRESUMO
Many powerful methods have been employed to elucidate the global transcriptomic, proteomic, or metabolic responses to pathogen-infected host cells. However, the host glycome responses to bacterial infection remain largely unexplored, and hence, our understanding of the molecular mechanisms by which bacterial pathogens manipulate the host glycome to favor infection remains incomplete. Here, we address this gap by performing a systematic analysis of the host glycome during infection by the bacterial pathogen Brucella spp. that cause brucellosis. We discover, surprisingly, that a Brucella effector protein (EP) Rhg1 induces global reprogramming of the host cell N-glycome by interacting with components of the oligosaccharide transferase complex that controls N-linked protein glycosylation, and Rhg1 regulates Brucella replication and tissue colonization in a mouse model of brucellosis, demonstrating that Brucella exploits the EP Rhg1 to reprogram the host N-glycome and promote bacterial intracellular parasitism, thereby providing a paradigm for bacterial control of host cell infection.
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Brucella , Brucelose , Animais , Camundongos , Brucella/fisiologia , Proteômica , Brucelose/metabolismo , Retículo Endoplasmático/metabolismoRESUMO
BACKGROUND: Long non-coding RNA (LncRNA) is a type of non-coding RNA that plays an important role in the body and accounts for the majority of RNA, and this non-coding RNA can regulate disease onset and progression with its wide range of functions. LncRNA Xist, also known as the long non-coding RNA X inactive specific transcript, is a member of them. It can regulate the development of organismal diseases by acting downstream on specific target genes. In addition to this, it can also influence disease onset and progression by acting on apoptosis, migration, invasion, and other processes. It has been shown that XIST plays an important role in the development of inflammation. OBJECTIVE: To explore the role played by XIST in inflammation-related diseases and to explore its mechanism of action. METHODS: This paper summarizes and analyzes the role played by XIST in inflammation- related diseases by conducting a search in PubMed. CONCLUSION: In this paper, we summarize the mechanism of action of XIST in different types of inflammation-related diseases and propose new protocols for the future clinical treatment of these diseases.
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As a broad-spectrum and efficient triazole fungicide, difenoconazole is widely used, which not only pollutes the environment but also exerts toxic effects on non-target organisms. The spleen plays an important role in immune protection as an important secondary lymphoid organ in carp. In this study, we assessed the protective impact of silybin as a dietary additive on spleen tissues of carp during exposure to difenoconazole. Sixty carp were separated into four groups for this investigation including control group, difenoconazole group, silybin group, and silybin and difenoconazole group. By hematoxylin-eosin staining, dihydroethidium staining, immunohistochemical staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, quantitative real-time PCR assay, Western blot analysis, biochemical assays, and immune function indicator assays, we found that silybin could prevent difenoconazole-induced spleen tissue damage, oxidative stress, and immune dysfunction, and inhibited apoptosis of carp spleen tissue cells by suppressing the formation of p53-driven caspase-9-apoptotic protease activating factor-1-cytochrome C complex. The results suggested that silybin as a dietary additive could improve spleen tissue damage and immune dysfunction induced by difenoconazole in aquaculture carp.
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Carpas , Dioxolanos , Baço , Animais , Baço/metabolismo , Caspase 9/farmacologia , Proteína Supressora de Tumor p53 , Silibina/farmacologia , Carpas/metabolismo , Citocromos c/metabolismo , Apoptose , Triazóis/farmacologiaRESUMO
Recent scientific studies have highlighted the importance of long-chain noncoding RNAs (lncRNAs) in a variety of metabolic diseases, but the specific functions and mechanisms of lncRNAs in aberrant lipid synthesis associated with aging are unknown. In this work, we inspected the effects of lncRNAs on the lipid metabolism in aging mice, as substantial evidence suggests that aging disturbs lipid metabolism. The results revealed that the expression of lncRNA Gm15232 was significantly elevated in the epididymal white adipose tissue of aging mice compared to adult mice. This upregulation of Gm15232 functioned as a competitive endogenous RNA by inhibiting the expression of miR-192-3p, and the ensuing downregulation of miR-192-3p increased the expression of the glucocorticoid receptor gene, which ultimately stimulated fat synthesis. The upregulation of Gm15232 thus increased lipogenesis through this mechanism. This study reveals a potential target for the treatment of age-related abnormalities of lipid metabolism.
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Lipogênese , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , Regulação para Baixo , Lipogênese/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Regulação para Cima , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismoRESUMO
Emerging pollutants, a category of compounds currently not regulated or inadequately regulated by law, have recently become a focal point of research due to their potential toxic effects on human health. The gut microbiota plays a pivotal role in human health; it is particularly susceptible to disruption and alteration upon exposure to a range of toxic environmental chemicals, including emerging contaminants. The disturbance of the gut microbiome caused by environmental pollutants may represent a mechanism through which environmental chemicals exert their toxic effects, a mechanism that is garnering increasing attention. However, the discussion on the toxic link between emerging pollutants and glucose metabolism remains insufficiently explored. This review aims to establish a connection between emerging pollutants and glucose metabolism through the gut microbiota, delving into the toxic impacts of these pollutants on glucose metabolism and the potential role played by the gut microbiota.
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Flavonoid quercetin (QUE) has biological activities of anti-oxidation, anti-inflammation and anti-apoptosis, however, its protective effects against avermectin (AVM) induced liver toxicity in carp remains unclear. The objective of this research is to explore the biologically potent effects of QUE in AVM-induced hepatotoxicity in carp and its underlying mechanism. Therefore, we established a liver injury model in carp induced by AVM to evaluate QUE against AVM induced liver toxicity in carp. In this investigation, AVM dosage was determined as 2.404 µg/L for both groups, and an experimentation of 30 days duration was carried out. Various methods including hematoxylin and eosin (H&E) staining, biochemical kits, real-time quantitative PCR (qRT-PCR), western blotting, TUNEL, reactive oxygen species (ROS) staining, immunofluorescence (Hoseinifar, et al.,), and oil red O staining were used in this study. Results showed that the growth inhibition of carp was relieved in the QUE treatment group comparing to the AVM group. In the QUE treatment group, there was a significant decrease in the levels of ALT and AST in carp liver tissue. Additionally, the histopathological damage and lipid accumulation were alleviated compared to the AVM group. Moreover, QUE prevented AVM induced decrease in the activities of antioxidant enzymes of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione (GSH), catalase (CAT) and the accumulation of reactive oxygen species (ROS), but reduced accumulation of malondialdehyde (MDA). In addition, the mRNA levels of liver pro-inflammatory factors of tumor necrosis factor-α (TNF-α), interleukin-1ß (iL-1ß), interleukin-6 (iL-6), interleukin-10 (iL-10) and the protein levels of NOD-like receptor protein 3 (NLRP3) inflammasome were significantly down-regulated in the QUE treatment group in comparison to the AVM group. We also found that QUE could affect the expression of Bcl2-associated x (Bax), B-cell lymphoma-2 (Bcl-2), cleaved-cysteinyl aspartate specific proteinase (CCaspase3) key apoptotic proteins and TUNEL-labeled apoptotic hepatocytes by regulating SIRT1/FOXO3a signal pathway. In summary, QUE alleviated the growth inhibition, liver oxidative damage, lipid accumulation, inflammatory response, and apoptosis of carp induced by AVM. QUE is a potential protective agent against liver injury induced by AVM in carp.
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Carpas , Doença Hepática Induzida por Substâncias e Drogas , Ivermectina/análogos & derivados , Poluentes Químicos da Água , Animais , Quercetina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Carpas/metabolismo , Poluentes Químicos da Água/toxicidade , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Glutationa/metabolismo , Apoptose , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , LipídeosRESUMO
BACKGROUND: Insulin resistance (IR) is associated with coronary artery disease (CAD) severity. However, its underlying mechanisms are not fully understood. Therefore, our study aimed to explore the relationship between IR and coronary inflammation and investigate the synergistic and mediating effects of coronary inflammation on the association between IR and CAD severity. METHODS: Consecutive patients with CAD who underwent coronary angiography and coronary computed tomography angiography between April 2018 and March 2023 were enrolled. The triglyceride-glucose index (TyG index) and peri-coronary adipose tissue (PCAT) attenuation around the proximal right coronary artery (RCA) were used to evaluate IR and coronary inflammation, respectively. The correlation between the TyG index and PCAT attenuation was analyzed using linear regression models. Logistic regression models were further used for investigating the correlation of the TyG index and PCAT attenuation with CAD severity. A mediation analysis assessed the correlation between IR and CAD severity mediated by coronary inflammation. RESULTS: A total of 569 participants (mean age, 62 ± 11 years; 67.8% men) were included in the study. PCAT attenuation was positively associated with the TyG index (r = 0.166; P < 0.001). After adjusting for potential confounders, the per standard deviation increment in the TyG index was associated with a 1.791 Hounsfield unit (HU) increase (95% confidence interval [CI], 0.920-2.662 HU; P < 0.001) in the PCAT attenuation. In total, 382 (67.1%) patients had multivessel CAD. The patients in the high-TyG index/high PCAT attenuation group had approximately 3.2 times the odds of multivessel CAD compared with those in the low-TyG index/low PCAT attenuation group (odds ratio, 3.199; 95%CI, 1.826-5.607; P < 0.001). Mediation analysis indicated that PCAT attenuation mediated 31.66% of the correlation between the TyG index and multivessel CAD. CONCLUSIONS: The TyG index positively correlated with PCAT attenuation in patients with CAD. The TyG index and PCAT attenuation showed a synergistic correlation with multivessel CAD. Furthermore, PCAT attenuation partially mediated the relationship between the TyG index and CAD severity. Controlling inflammation in patients with high IR and coronary inflammation may provide additional benefits.
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Doença da Artéria Coronariana , Resistência à Insulina , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Transversais , Angiografia Coronária/métodos , Glucose , Arritmias Cardíacas , Inflamação/diagnóstico por imagemRESUMO
The biosynthesis of thyroid hormones is essential for brain and neurological development. It requires iodine as a key component but is also influenced by other nutrients. Evidence for the combined nutrient status in relation to thyroid hormones during pregnancy is limited. We aimed to investigate the joint associations of iodine, selenium, zinc, calcium, magnesium and iron with maternal thyroid functions in 489 pregnant women from Hangzhou, China. Serum levels of six essential minerals and thyroid function parameters were measured during the first antenatal visit. Linear regression, quantile g-computation and Bayesian kernel machine regression were used to explore the individual and joint relationships between the six minerals and thyroid hormones. Linear regression analyses revealed that calcium was positively associated with free triiodothyronine (FT3). Zinc was positively associated with free thyroxine (FT4). Iodine was negatively associated with thyroid-stimulating hormone (TSH) and positively associated with FT3 and FT4. The quantile g-computation and BKMR models indicated that the joint nutrient concentration was negatively associated with TSH and positively associated with FT3 and FT4. Among the six minerals, iodine contributed most to thyroid function. The findings suggested that maintaining the appropriate concentration of minerals, either as individuals or a mixture, is important for thyroid health during pregnancy.
Assuntos
Iodo , Selênio , Feminino , Humanos , Gravidez , Gestantes , Cálcio , Teorema de Bayes , Testes de Função Tireóidea , Hormônios Tireóideos , Tireotropina , Zinco , China , TiroxinaRESUMO
Emerging contaminants have been increasingly recognized as critical determinants in global public health outcomes. However, the intricate relationship between these contaminants and glucose metabolism remains to be fully elucidated. The paucity of comprehensive clinical data, coupled with the need for in-depth mechanistic investigations, underscores the urgency to decipher the precise molecular and cellular pathways through which these contaminants potentially mediate the initiation and progression of diabetes mellitus. A profound understanding of the epidemiological impact of these emerging contaminants, as well as the elucidation of the underlying mechanistic pathways, is indispensable for the formulation of evidence-based policy and preventive interventions. This review systematically aggregates contemporary findings from epidemiological investigations and delves into the mechanistic correlates that tether exposure to emerging contaminants, including endocrine disruptors, perfluorinated compounds, microplastics, and antibiotics, to glycemic dysregulation. A nuanced exploration is undertaken focusing on potential dietary sources and the consequential role of the gut microbiome in their toxic effects. This review endeavors to provide a foundational reference for future investigations into the complex interplay between emerging contaminants and diabetes mellitus.