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1.
J Environ Manage ; 357: 120797, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38574707

RESUMO

Phosphate materials (PMs) combine with phosphate solubilizing bacteria play an essential roles in lead (Pb) immobilization, but their resulting ability to reduce Pb bioavailability may vary depending on PMs used. In this study, Pseudomonas edaphica GAU-665 and three PMs: tricalcium phosphate, calcium phytate and nano-hydroxyapatite were respectively encapsulated into bio-beads by sodium alginate, which immobilization efficiency of Pb2+ were 99.11%, 97.76% and 99.02% at initial Pb2+ concentration of 200 mg L-1, respectively. The Pb2+ immobilization performance of bio-beads under different conditions and their organic acids secreted were examined. Most Pb2+ was immobilized by bio-beads through combined functions of adsorption, precipitation, ion exchange and biomineralization, accompanied by the formation of more stable compounds such as Pb3(PO4)2, Pb5(PO4)3OH and Pb5(PO4)3Cl. Meanwhile, pot experimental results indicated that the inoculation of CPhy (calcium phytate) bio-beads with PSB have highest biomass and root growth of oat (Avena sativa L.) in Pb-stressed compared with CK, which increased the content of chlorophyll b (167.51%) in shoot. In addition, the CPhy bio-beads enhance the peroxidase, catalase activities and reduce the malondialdehyde content to alleviating lead physiological toxicity in oat, which reductions the Pb accumulation in shoot (52.06%) and root (81.04%), and increased the residual fraction of Pb by 165.80% in soil. These findings suggest the bio-beads combined with P. edaphica GAU-665 and calcium phytate is an efficient Pb immobilization material and provided feasible way to improve safety agricultural production and Pb-contaminated soil remediation.

2.
Am J Cancer Res ; 14(3): 1015-1032, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590418

RESUMO

The ERK1/2 pathway is involved in epithelial-mesenchymal transformation and cell cycle of tumor cells in hepatocellular carcinoma (HCC). In the present study, we investigated the involvement of ERK1/2 activation on hepatic stellate cells (HSCs). We identified ERK1/2 phosphorylation in activated HSCs of HCC samples. We found that tumor cells promoted the migration and invasion capacity of HSCs by activating ERK1/2 phosphorylation. Using high throughput transcriptome sequencing analysis, we found that ERK1/2 inhibition altered genes significantly correlated to signaling pathways involved in extracellular matrix remodeling. We screened genes and demonstrated that the ERK1/2 inhibition-related gene set significantly correlated to cancer-associated fibroblast infiltration in TCGA HCC tumor samples. Moreover, inhibition of ERK1/2 suppressed tumor cell-induced enhancement of HSC migration and invasion by regulating expression of fibrosis markers FAP, FN1 and COL1A1. In a tumor cell and HSC splenic co-transplanted xenograft mouse model, inhibition of ERK1/2 suppressed liver tumor formation by downregulating fibrosis, indicating ERK1/2 inhibition suppresses tumor-stromal interactions in vivo. Taken together, our data indicate that inhibition of ERK1/2 in tumor-associated HSCs suppresses tumor-stromal interactions and progression. Furthermore, inhibition of ERK1/2 may be a potential target for HCC treatment.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38591127

RESUMO

Sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) is a widely expressed membrane glycoprotein that acts as an important modulator of lipid metabolism and inflammatory stress. N-glycosylation of SCAP has been suggested to modulate cancer development, but its role in NASH is poorly understood. In this study, the N-glycosylation of SCAP was analyzed by using sequential trypsin proteolysis and glycosidase treatment. The liver cell lines expressing wild-type and N-glycosylation sites mutated SCAP were constructed to investigate the N-glycosylation role of SCAP in regulating inflammation and lipid accumulation as well as the underlying mechanisms. The hepatic SCAP protein levels were significantly increased in C57BL/6J mice fed with western diet and sweet water (WD+SW) and diabetic db/db mice, which exhibited typical liver steatosis and inflammation. In vitro, the enhanced N-glycosylation increased the protein stability of SCAP and hence increased its total protein levels, while the ablation of N-glycosylation significantly decreased SCAP protein stability and alleviated lipid accumulation and inflammation in hepatic cell lines. Mechanistically, the presence of SCAP N-glycosylation increased not only the SREBP1-mediated acetyl-CoA synthetase 2 (ACSS2) transcription but also the AMPK-mediated S659 phosphorylation of ACCS2 protein, causing the enhanced ACSS2 levels in nucleus and hence increasing the histone H3K27 acetylation (H3K27ac), which is a key epigenetic modification associated with NASH. Modulating ACSS2 expression or its location in cytoplasm abolished the effects of SCAP N-glycosylation on H3K27ac and lipid accumulation and inflammation. In conclusion, SCAP N-glycosylation aggravates inflammation and lipid accumulation through enhancing ACSS2-mediated H3K27ac in hepatocytes.

4.
Medicine (Baltimore) ; 103(12): e37509, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518033

RESUMO

Xining is located at the eastern edge of the Qinghai-Tibet Plateau, with an average altitude of >7000 feet (>2000 m). Nalbuphine is a kappa-opioid receptor agonist that can provide analgesia with fewer side effects than other opioid analgesics. This study aimed to evaluate pain control, side effects, and neonatal outcomes from combining nalbuphine with sufentanil and ropivacaine in 600 women during epidural anesthesia while giving birth at a high altitude in Xining, China. A total of 600 parturients receiving epidural labor analgesia were randomly divided into 2 groups, each group 300 parturients. The nalbuphine group received nalbuphine, sufentanil, and ropivacain, the control group only received sufentanil and ropivacain. The analgesic effect was evaluated through the Visual Analogue Scale scores. Neonatal outcomes were mainly evaluated through the Apgar Scores. Compared to the control group, the nalbuphine group showed lower Visual Analogue Scale scores at all time points after analgesia (P < .05). In comparison with the control group, parturients in the nalbuphine group showed lower incidence rates of fever at delivery, 24-hour postpartum bleeding, and pruritus (P < .05). However, between the 2 groups, there were no statistically significant differences in the remaining maternal and infant outcomes and neonatal outcomes (P > .05). Moreover, no adverse effects on neonatal outcomes were observed. The findings from this study support findings from previous studies that nalbuphine provided safe epidural analgesia without significant side effects for the mother and infant, and showed both safety and efficacy when used during labor at high altitude.


Assuntos
Analgesia Epidural , Analgesia Obstétrica , Nalbufina , Feminino , Humanos , Recém-Nascido , Gravidez , Altitude , Analgesia Epidural/efeitos adversos , Analgesia Obstétrica/efeitos adversos , Analgésicos/efeitos adversos , Analgésicos Opioides/efeitos adversos , Anestésicos Locais , Nalbufina/efeitos adversos , Dor/etiologia , Sufentanil/uso terapêutico
5.
J Am Chem Soc ; 146(12): 8780-8786, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38497732

RESUMO

The small RNAs on living cell membranes were recently found to be N-glycosylated and terminated with sialic acids, although the glycosylation sites and potential functions remain unclear. Herein, we designed a second-generation hierarchical coding strategy (HieCo 2) for in situ visualization of cell surface RNA-specific sialylation. After covalently binding DNA codes to sialic acids and then binding a DNA code to a target RNA via sequence specificity, cascade decoding processes were performed with subsequent signal amplification that enabled sensitive in situ visualization of low-abundance Y5 RNA-specific sialic acids on living cell membranes. The proposed strategy unveils the number of glycosylation sites on a single RNA and reveals the binding preference of glycosylated RNAs to different sialic acid binding-immunoglobulin lectin-type receptors, demonstrating a new route for exploration of the glycosylated RNA-related biological and pathological processes.


Assuntos
RNA , Ácidos Siálicos , Glicosilação , RNA/metabolismo , Membrana Celular/metabolismo , Ácidos Siálicos/metabolismo , DNA/metabolismo , Ácido N-Acetilneuramínico/metabolismo
6.
Materials (Basel) ; 17(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38473669

RESUMO

In this paper, the corrosion environment of a railway coal truck was simulated with 1.0%H2SO4 + 3%NaCl solution. The effect of weld toe Tungsten Inert Gas (TIG) remelting on the microstructure and corrosion resistance of welded joints of Q450NQR1 high-strength weathering steel was studied. The results show that the weld toe melts to form a remelting area after TIG remelting. After TIG remelting, the weld geometry was improved, and the stress concentration factor decreased from 1.17 to 1.06 at the weld toe, a decrease of 9.4%. TIG remelting refines the microstructure of the weld toe and improves the corrosion resistance of the welded joint. The surface of the TIG-remelted sample is uniformly corroded with no "deep and narrow" pits after the removal of corrosion products. The weight loss rate and corrosion rate of remelted welds are lower than those of unremelted welds. The structure of corrosion products is loose at the initial stage of corrosion, and the corrosion products are transformed into Fe3O4 and Fe2O3 protective rust layers with a dense structure after 480 h of corrosion. With the extension of corrosion time, the tensile strength and percentage elongation of the specimen decreased linearly. The decreasing rates of tensile strength of remelted and unremelted specimens were 0.09 and 0.11, respectively, and the decreasing rates of elongation after fracture were 0.0061 and 0.0076, respectively.

7.
JAMA Netw Open ; 7(3): e241933, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38470418

RESUMO

Importance: Adolescent major depressive disorder (MDD) is associated with serious adverse implications for brain development and higher rates of self-injury and suicide, raising concerns about its neurobiological mechanisms in clinical neuroscience. However, most previous studies regarding the brain alterations in adolescent MDD focused on single-modal images or analyzed images of different modalities separately, ignoring the potential role of aberrant interactions between brain structure and function in the psychopathology. Objective: To examine alterations of structural and functional connectivity (SC-FC) coupling in adolescent MDD by integrating both diffusion magnetic resonance imaging (MRI) and resting-state functional MRI data. Design, Setting, and Participants: This cross-sectional study recruited participants aged 10 to 18 years from January 2, 2020, to December 28, 2021. Patients with first-episode MDD were recruited from the outpatient psychiatry clinics at The First Affiliated Hospital of Chongqing Medical University. Healthy controls were recruited by local media advertisement from the general population in Chongqing, China. The sample was divided into 5 subgroup pairs according to different environmental stressors and clinical characteristics. Data were analyzed from January 10, 2022, to February 20, 2023. Main Outcomes and Measures: The SC-FC coupling was calculated for each brain region of each participant using whole-brain SC and FC. Primary analyses included the group differences in SC-FC coupling and clinical symptom associations between SC-FC coupling and participants with adolescent MDD and healthy controls. Secondary analyses included differences among 5 types of MDD subgroups: with or without suicide attempt, with or without nonsuicidal self-injury behavior, with or without major life events, with or without childhood trauma, and with or without school bullying. Results: Final analyses examined SC-FC coupling of 168 participants with adolescent MDD (mean [mean absolute deviation (MAD)] age, 16.0 [1.7] years; 124 females [73.8%]) and 101 healthy controls (mean [MAD] age, 15.1 [2.4] years; 61 females [60.4%]). Adolescent MDD showed increased SC-FC coupling in the visual network, default mode network, and insula (Cohen d ranged from 0.365 to 0.581; false discovery rate [FDR]-corrected P < .05). Some subgroup-specific alterations were identified via subgroup analyses, particularly involving parahippocampal coupling decrease in participants with suicide attempt (partial η2 = 0.069; 90% CI, 0.025-0.121; FDR-corrected P = .007) and frontal-limbic coupling increase in participants with major life events (partial η2 ranged from 0.046 to 0.068; FDR-corrected P < .05). Conclusions and Relevance: Results of this cross-sectional study suggest increased SC-FC coupling in adolescent MDD, especially involving hub regions of the default mode network, visual network, and insula. The findings enrich knowledge of the aberrant brain SC-FC coupling in the psychopathology of adolescent MDD, underscoring the vulnerability of frontal-limbic SC-FC coupling to external stressors and the parahippocampal coupling in shaping future-minded behavior.


Assuntos
Experiências Adversas da Infância , Transtorno Depressivo Maior , Feminino , Humanos , Adolescente , Transtorno Depressivo Maior/diagnóstico por imagem , Estudos Transversais , Depressão , Encéfalo/diagnóstico por imagem
8.
Pharmacogenomics J ; 24(2): 8, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485921

RESUMO

BACKGROUND: Tibetan medicine Gaoyuan'an capsule (GYAC) is widely used to prevent pulmonary edema at high altitude, but the specific mechanism has not been explored. In this study, we analyzed the mechanism of GYAC in hypoxia tolerance, and provided a new idea for the prevention and treatment of altitude disease. METHODS: The effective components and corresponding targets of GYAC were screened out by the Chinese herbal medicine network database, and the key targets of hypoxia tolerance were retrieved by Genecards, OMIM and PubMed database. Cytoscape 3.7.2 was used to construct GYAC ingredient-target-hypoxia tolerance-related target network. GO function annotation and KEGG enrichment analysis were performed to predict the pathways in which target genes may be involved, and molecular docking was used to verify the binding ability of the compound to target genes. In vitro, the above results were further verified by molecular experiment. RESULTS: We found that GYAC can improve hypoxia tolerance by regulating various target genes, including IL6, IFNG, etc. The main regulatory pathways were HIF-1 signaling pathway. Molecular docking showed that the affinity between luteolin and target genes (IL6, IFNG) were better. In vitro, we observed that hypoxia can inhibit cell viability and promote apoptosis of H9C2 cell. And hypoxia can promote the expression of LDH. After the addition of luteolin, the decrease of cell viability, the increase of cell apoptosis, LDH release and the decrease of mitochondrial membrane potential were inhibited. Besides, inflammatory related factors (IL-6, IL-10, IL-2, IFNG and VEGFA) expression were also inhibited hypoxic cell models. CONCLUSIONS: The results of network pharmacology and molecular docking showed that luteolin, a monomeric component of GYAC, played a role in hypoxia tolerance through a variety of target genes, such as IL6, IFNG. What's more, we have discovered that luteolin can reduce the inflammatory response in cardiac myocytes, thereby alleviating mitochondrial damage, and ultimately enhancing the hypoxia tolerance of H9C2 cardiomyocytes.


Assuntos
Medicamentos de Ervas Chinesas , Interleucina-6 , Humanos , Simulação de Acoplamento Molecular , Luteolina , Farmacologia em Rede , Hipóxia/tratamento farmacológico , Hipóxia/genética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
9.
Transl Psychiatry ; 14(1): 163, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531835

RESUMO

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are classified as major mental disorders and together account for the second-highest global disease burden, and half of these patients experience symptom onset in adolescence. Several studies have reported both similar and unique features regarding the risk factors and clinical symptoms of these three disorders. However, it is still unclear whether these disorders have similar or unique metabolic characteristics in adolescents. We conducted a metabolomics analysis of plasma samples from adolescent healthy controls (HCs) and patients with MDD, BD, and SCZ. We identified differentially expressed metabolites between patients and HCs. Based on the differentially expressed metabolites, correlation analysis, metabolic pathway analysis, and potential diagnostic biomarker identification were conducted for disorders and HCs. Our results showed significant changes in plasma metabolism between patients with these mental disorders and HCs; the most distinct changes were observed in SCZ patients. Moreover, the metabolic differences in BD patients shared features with those in both MDD and SCZ, although the BD metabolic profile was closer to that of MDD than to SCZ. Additionally, we identified the metabolites responsible for the similar and unique metabolic characteristics in multiple metabolic pathways. The similar significant differences among the three disorders were found in fatty acid, steroid-hormone, purine, nicotinate, glutamate, tryptophan, arginine, and proline metabolism. Interestingly, we found unique characteristics of significantly altered glycolysis, glycerophospholipid, and sphingolipid metabolism in SCZ; lysine, cysteine, and methionine metabolism in MDD and BD; and phenylalanine, tyrosine, and aspartate metabolism in SCZ and BD. Finally, we identified five panels of potential diagnostic biomarkers for MDD-HC, BD-HC, SCZ-HC, MDD-SCZ, and BD-SCZ comparisons. Our findings suggest that metabolic characteristics in plasma vary across psychiatric disorders and that critical metabolites provide new clues regarding molecular mechanisms in these three psychiatric disorders.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Esquizofrenia , Humanos , Adolescente , Transtorno Bipolar/metabolismo , Transtorno Depressivo Maior/metabolismo , Esquizofrenia/metabolismo , Metabolômica , Metaboloma
10.
Clin Nephrol ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38511675

RESUMO

OBJECTIVE: Membranous nephropathy is a leading cause of adult-onset nephrotic syndrome. Peripheral T cells and myeloid-derived suppressor cells (MDSCs) are closely associated with autoimmune diseases, while their exact roles and interaction in these processes are unclear. Here, we studied the roles of T cells, MDSCs, and their subsets in patients with idiopathic membranous nephropathy (IMN). MATERIALS AND METHODS: 35 IMN patients and 30 healthy controls were included in this retrospective study. Flow cytometry was performed to determine the phenotype of human T cells and MDSCs in peripheral blood mononuclear cells (PBMCs). Anti-PLA2R was measured by ELISA. Values ≥ 20 RU/mL were defined as positive and < 14 RU/mL as negative. RESULTS: A higher ratio of CD4/CD8 T cells with a lower proportion of Tregs, a remarkably lower proportion of G-MDSCs (but not M-MDSCs), lower frequency of PD-L2+G-MDSCs, and higher frequency of PD-L1+M-MDSCs were found in IMN patients compared to healthy controls. The ratio of CD4/CD8 T cells was higher, and the frequencies of PD-1+CD4+ T cells, CTLA-4+CD4+ T cells, PD-1+Tregs, and CTLA-4+Tregs were lower in PBMCs of PLA2R-positive IMN patients compared to PLA2R-negative IMN patients. CONCLUSION: Tregs and G-MDSCs were reduced in the circulation of the IMN patients, which may promote understanding of the crucial functions that are mediated by these cells in the pathogenesis of IMN.

11.
Mol Biotechnol ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461180

RESUMO

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disorder with complex causes. Calcium channel blockers have long been used in its treatment. Our study aimed to validate experimental results showing increased calcium ion concentration in PAH patients. We investigated the impact of genes related to calcium channel regulation on PAH development and developed an accurate diagnostic model. Clinical trial data from serum of 18 healthy individuals and 18 patients with PAH were retrospectively analyzed. Concentrations of calcium and potassium ions were determined and compared. Datasets were retrieved, selecting genes associated with calcium ion release. R packages processed the datasets, filtering 174 common genes, and conducting Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Six hub genes were identified, and nomogram and logistic regression prediction models were constructed. Random forest filtered cross genes, and a diagnostic model was developed and validated using an artificial neural network. The 174 intersection genes related to calcium ions showed significant correlations with biological processes, cellular components, and molecular functions. Six key genes were obtained by constructing a protein-protein interaction network. A diagnostic model with high accuracy (> 90%) and diagnostic capability (AUC = 0.98) was established using a neural network algorithm. This study validated the experimental results, identified key genes associated with calcium ions, and developed a highly accurate diagnostic model using a neural network algorithm. These findings provide insights into the role of calcium release genes in PAH and demonstrate the potential of the diagnostic model for clinical application. However, due to limitations in sample size and a lack of prognosis data, the regulatory mechanisms of calcium ions in PAH patients and their impact on the clinical prognosis of PAH patients still need further exploration in the future.

12.
J Psychiatr Res ; 173: 183-191, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38547740

RESUMO

Accumulating evidence reveals the metabolism and neurotransmitter systems are different in major depressive disorder (MDD) between adolescent and adult patients; however, much is still unknown from the gut microbiome perspective. To minimize confounding factors such as geographical location, ethnicity, diet, and drugs, we investigated the gut microbial differences between adolescent and adult male Sprague-Dawley rats. We exposed the adolescent rats to chronic unpredictable mild stress (CUMS) for 3 weeks and assessed their behavior using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). We collected and sequenced fecal samples after the behavioral tests and compared them with our previous data on adult rats. Both adolescent and adult CUMS rats exhibited reduced sucrose preference in SPT, reduced total distance in OFT, and increased immobility time in FST. Moreover, compared to their respective controls, the adolescent CUMS rats had distinct amplicon sequence variants (ASVs) mainly in the Muribaculaceae family, Bacteroidetes phylum, while the adult CUMS rats had those in the Lachnospiraceae family, Firmicutes phylum. In the adolescent group, the Muribaculaceae negatively correlated with FST and positively correlated with SPT and OFT. In the adult group, the different genera in the Lachnospiraceae showed opposite correlations with FST. Furthermore, the adolescent CUMS rats showed disrupted microbial functions, such as "Xenobiotics biodegradation and metabolism" and "Immune system", while the adult CUMS rats did not. These results confirmed the gut microbiota differences between adolescent and adult rats after CUMS modeling and provided new insight into the age-related influence on depression models.

13.
Eur J Surg Oncol ; 50(4): 108242, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460248

RESUMO

BACKGROUND: Preoperative neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is a common approach for treating patients with locally advanced rectal cancer. Nevertheless, the mutational profile and its prognostic impact in surgically resected tumor specimens after nCRT remains to be clarified. METHODS: The comprehensive analysis of mutational landscape was retrospectively conducted by target regions sequencing approach that covered 150 tumor-related genes. Univariate and multivariate logistic regression and Cox regression was used to examine the association of mutation status in genes and pathways with pathological response and prognosis. Data from Memorial Sloan Kettering Cancer Center (MSK) cohort was used for comparison with our results. RESULTS: The top five commonly mutated genes in resected rectal tumor tissue samples following nCRT were TP53 (42%), APC (31%), KRAS (27%), PIK3CA (14%) and FBXW7 (11%). Mutations in the WNT pathway, which was mainly represented by APC mutation, were found to be significantly associated with tumor regression grade (TRG) 3. In our cohort, co-mutations in the receptor tyrosine kinase (RTK)/RAS and WNT pathways were found to be independently associated with reduced risk of recurrent and significantly associated with longer disease-free survival (DFS). In both our cohort and the MSK cohort, co-mutations in the TGF-ß and TP53 pathways were significantly associated with worse DFS. CONCLUSIONS: Resected rectal tumor samples from patients without complete pathological response can be appropriately used to detect mutations. Co-mutations in the TGF-ß and TP53 pathways may provide more prognostic information beyond commonly used clinical factors.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Prognóstico , Estudos Retrospectivos , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Quimiorradioterapia , Neoplasias Retais/genética , Neoplasias Retais/terapia , Mutação , Estadiamento de Neoplasias , Resultado do Tratamento , Proteína Supressora de Tumor p53/genética
14.
Neurochem Res ; 49(5): 1254-1267, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38381246

RESUMO

Fibrotic scars play important roles in tissue reconstruction and functional recovery in the late stage of nervous system injury. However, the mechanisms underlying fibrotic scar formation and regulation remain unclear. Casein kinase II (CK2) is a protein kinase that regulates a variety of cellular functions through the phosphorylation of proteins, including bromodomain-containing protein 4 (BRD4). CK2 and BRD4 participate in fibrosis formation in a variety of tissues. However, whether CK2 affects fibrotic scar formation remains unclear, as do the mechanisms of signal regulation after cerebral ischemic injury. In this study, we assessed whether CK2 could modulate fibrotic scar formation after cerebral ischemic injury through BRD4. Primary meningeal fibroblasts were isolated from neonatal rats and treated with transforming growth factor-ß1 (TGF-ß1), SB431542 (a TGF-ß1 receptor kinase inhibitor) or TBB (a highly potent CK2 inhibitor). Adult SD rats were intraperitoneally injected with TBB to inhibit CK2 after MCAO/R. We found that CK2 expression was increased in vitro in the TGF-ß1-induced fibrosis model and in vivo in the MCAO/R injury model. The TGF-ß1 receptor kinase inhibitor SB431542 decreased CK2 expression in fibroblasts. The CK2 inhibitor TBB reduced the increases in proliferation, migration and activation of fibroblasts caused by TGF-ß1 in vitro, and it inhibited fibrotic scar formation, ameliorated histopathological damage, protected Nissl bodies, decreased infarct volume and alleviated neurological deficits after MCAO/R injury in vivo. Furthermore, CK2 inhibition decreased BRD4 phosphorylation both in vitro and in vivo. The findings of the present study suggested that CK2 may control BRD4 phosphorylation to regulate fibrotic scar formation, to affecting outcomes after ischemic stroke.


Assuntos
Benzamidas , Cicatriz , Dioxóis , AVC Isquêmico , Ratos , Animais , Cicatriz/prevenção & controle , Cicatriz/metabolismo , Cicatriz/patologia , Caseína Quinase II/metabolismo , Fosforilação , Proteínas Nucleares , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fatores de Transcrição/metabolismo , AVC Isquêmico/metabolismo , Ratos Sprague-Dawley , Fibrose , Fibroblastos/metabolismo
15.
Plant Physiol Biochem ; 207: 108413, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38330776

RESUMO

Ethylene responsive factor (ERF) is a plant-specific transcription factor that plays a pivotal regulatory role in various stress responses. Although the genome of tobacco harbors 375 ER F genes, the functional roles of the majority of these genes remain unknown. Expression pattern analysis revealed that NtERF283 was induced by water deficit and salt stresses and mainly expressed in the roots and leaves. Subcellular localization and transcriptional activity assays confirmed that NtERF283 was localized in the nucleus and exhibited transcriptional activity. In comparison to the wild-type (WT), the NtERF283-overexpressing transgenic plants (OE) exhibited enhanced water deficit tolerance, whereas the knockout mutant erf283 displayed contrasting phenotypes. Transcriptional analysis demonstrated that several oxidative stress response genes were significantly altered in OE plants under water deficit conditions. 3,3'-diaminobenzidine (DAB) and nitroblue tetrazolium (NBT) staining showed that erf283 accumulated a higher level of reactive oxygen species (ROS) compared to the WT under water deficit conditions. Conversely, OE plants displayed the least amount of ROS accumulation. Furthermore, the activities of POD and SOD were higher in OE plants and lower in erf283, suggesting that NtERF283 enhanced the capacity to effectively eliminate ROS, consequently enhancing water deficit tolerance in tobacco. These findings strongly indicate the significance of NtERF283 in promoting tobacco water deficit tolerance through the activation of the antioxidant system.


Assuntos
Antioxidantes , Água , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Água/metabolismo , Estresse Oxidativo , Plantas Geneticamente Modificadas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética
16.
Behav Brain Res ; 463: 114890, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38309372

RESUMO

Chronic stress is deemed a significant clinical contributor to depression. The use of animal models of chronic stress can fully reveal the complex pathological mechanisms and their changing trends in the pathogenesis of depression, which is crucial for both disease prevention and therapy. It is also unknown how various forms of stress differ in their impact on animal physiology and behavior. The nucleus accumbens (NAc), an essential brain area for the pathophysiology of depression, and its underlying neural mechanisms remain unclear. Here, we systematically compared transcriptional signatures in the NAc of four chronic stress models in rats: chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS), learned helplessness (LH), chronic restraint stress (CRS). The majority of differentially expressed genes (DEGs) were unique to a single depression model, while the rank-rank hypergeometric overlap analysis showed that the CSDS and CRS models had the greatest overlap, and the CRS and CUMS models had the least. Then, we performed pathway analysis of the differential genes and found that the neuroactive ligand-receptor interaction pathway was significantly enriched not only in the LH, CRS and CSDS stress models, but also significantly enriched in stress genes that were also altered in at least two stress models. Finally, we found three hub genes (Dcx, Tnc and Wdfy4) by constructing co-expression networks for stress genes. In summary, our research has the potential to offer fresh insights into the molecular mechanisms underlying depression induced by different types of stress, highlighting both their similarities and differences. It may provide valuable clues for understanding the pathogenesis of depression.


Assuntos
Núcleo Accumbens , Estresse Psicológico , Ratos , Animais , Núcleo Accumbens/metabolismo , Estresse Psicológico/metabolismo , Encéfalo , Expressão Gênica , Modelos Animais de Doenças , Depressão/metabolismo , Comportamento Animal
17.
Heliyon ; 10(4): e25636, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38384544

RESUMO

Objective: This study investigated the predicting value of the ratio of levator hiatus diameter (LHS) to fetal head circumference (HC) in pregnant women at 37 weeks of gestation in the progression of the second stage of labor and levator ani injury 6 weeks postpartum. Methods: A total of 120 first-time women who gave vaginal delivery at 37 weeks of pregnancy were selected as the subjects in our hospital during March 2021 to March 2022. The subjects were divided into the second stage of labor > 1 h group and the second stage of labor ≤ 1 h group, according to the delivery time of the second stage of labor. According to the 6-week postpartum follow-up ultrasound examination with or without levator ani injury, they were divided into levator ani injury group and no injury group. All primipara women underwent three-dimensional ultrasonography at 37 weeks of gestation, and the resting LHS, Valsalva LHS, fetal HC and the ratio of resting LHS and fetal HC were compared. The correlation between these factors and the length of the second labor stage was analyzed using Pearson correlation analysis. The value of these factors in predicting labor progression and postpartum levator ani injury was assessed by receiver operating characteristic (ROC) curves. Results: The resting LHS, Valsalva LHS and the ratio of resting LHS and fetal HC in the levator ani injury group were lower than these in the no injury group, while fetal HC in the levator ani injury group was higher than that in the no injury group (P < 0.05). The resting LHS, Valsalva LHS and the ratio of resting LHS and fetal HC in the second stage of labor > 1 h group were lower than these in the second stage of labor ≤ 1 h group, while fetal HC in the second stage of labor > 1 h group was higher than that in the second stage of labor ≤ 1 h group (P < 0.05). A significant negative correlation was observed between resting LHS/HC and total labor process (=-0.333, P < 0.01). ROC curve analysis showed that the AUCs of resting LHS, Valsalva LHS, HC, and resting LHS/HC ratio in predicting prolongation of the second stage of labor were 0.741, 0.740, 0.702, and 0.843 respectively. Besides, the AUCs of resting LHS, Valsalva LHS, HC, and resting LHS/HC ratio in predicting the total labor process were 0.657, 0.684, 0.768, and 0.836 respectively. The AUCs of resting LHS, Valsalva LHS, HC, and resting LHS/HC ratio in predicting postpartum levator ani muscle injury were 0.769, 0.773, 0.747, and 0.885 respectively.These results suggested that the ratio of resting LHS and fetal HC may have certain clinical value in predicting levator ani injury in pregnant women. Conclusion: LHS, fetal HC and the ratio of resting LHS and fetal HC are significantly correlated with labor progression and postpartum levator ani injury, which have certain value in predicting labor progress and postpartum levator ani injury. Therein, the ratio of resting LHS and fetal HC has the highest predictive value, and early detection of the ratio of resting LHS and fetal HC is helpful to guide the selection of appropriate delivery mode.

18.
Front Endocrinol (Lausanne) ; 15: 1328404, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370360

RESUMO

Background: The burden of metabolic syndrome (MetS) continues to rise globally and is associated with complications of multiple organ systems. We aimed to identify the association between changes in MetS status and accelerated renal function progression through a regional epidemiological survey in China, thus discovering influence factors with treatable potential. Methods: This study was a population-based survey conducted in 2008 and 2014, assessing a representative sample of 5,225 individuals from rural areas of China. They were divided into four subgroups according to their MetS status in 2008 and 2014 (Never, Previously abnormal, New-onset, and Consistent). Multivariate logistic regression and stratification analysis evaluated the relationship between clinical factors and renal function decline under different MetS statuses. Smooth curve fitting further addressed the role of serum uric acid, illustrating the vital turning point of uric acid levels in the background of renal function deterioration. Results: Of all groups of MetS states, the new-onset MetS showed the most significant eGFR decline, with a 6.66 ± 8.21 mL/min/1.73 m2 decrease over 6 years. The population with newly-onset MetS showed a considerable risk increase in delta eGFR with a beta coefficient of 1.66 (95%CI=1.09-2.23) after necessary correction. In searching for the drivers, the strength of the association was significantly reduced after additional adjustment for uric acid levels (ß=0.91, 95%CI=0.35-1.45). Regarding the turning point, uric acid levels exceeding 426 µmol/L were more significantly associated with the stepped-up deterioration of kidney function for those with new-onset MetS. Conclusion: Metabolic syndrome demonstrated a solid correlation with the progression of renal function, particularly in those with newly-onset MetS status. In addition to the diagnostic components of MetS, hyperuricemia could be used as a marker to identify the high risk of accelerating eGFR decline early. Furthermore, we suggested a potential renal benefit for the newly-onset MetS population when maintaining their serum uric acid level below the criteria for asymptomatic hyperuricemia.


Assuntos
Hiperuricemia , Síndrome Metabólica , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Estudos de Coortes , Ácido Úrico , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Rim
19.
Cell Death Discov ; 10(1): 68, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336777

RESUMO

Embryonic stem cells (ESCs) exhibit unique attributes of boundless self-renewal and pluripotency, making them invaluable for fundamental investigations and clinical endeavors. Previous examinations of microgravity effects on ESC self-renewal and differentiation have predominantly maintained a descriptive nature, constrained by limited experimental opportunities and techniques. In this investigation, we present compelling evidence derived from murine and human ESCs, demonstrating that simulated microgravity (SMG)-induced stress significantly impacts self-renewal and pluripotency through a previously unidentified conserved mechanism. Specifically, SMG induces the upregulation of heat shock protein genes, subsequently enhancing the expression of core pluripotency factors and activating the Wnt and/or LIF/STAT3 signaling pathways, thereby fostering ESC self-renewal. Notably, heightened Wnt pathway activity, facilitated by Tbx3 upregulation, prompts mesoendodermal differentiation in both murine and human ESCs under SMG conditions. Recognizing potential disparities between terrestrial SMG simulations and authentic microgravity, forthcoming space flight experiments are imperative to validate the impact of reduced gravity on ESC self-renewal and differentiation mechanisms.

20.
Sci Rep ; 14(1): 3361, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336909

RESUMO

Based on the whole life cycle theory, the carbon effect of three different sizes of high-standard basic farmland construction projects is measured and analysed. The results show that the carbon emissions generated during the construction of high-standard basic farmland projects and the carbon absorption capacity at the later stage are different for projects of different sizes. The carbon emissions of different scales of high-standard basic farmland projects will increase during the construction stage. The results of carbon effect changes in the later operation and management stage show that the high-standard basic farmland construction projects will help reduce the carbon emissions of the field ecosystem where the farmland is located and increase its carbon sink capacity after the completion of construction, which is more obvious in larger projects. The emission reduction and carbon sequestration capacity of the farmland after remediation are improved to different degrees, which is more conducive to the ecological development of agricultural production and ecological environmental protection in the relevant areas. The study contributes to the green development of farmland, which is of some significance for the sustainable development of agriculture in Tianjin and the whole country.

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