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1.
Reprod Toxicol ; 129: 108671, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39038764

ABSTRACT

Maternal prenatal hypoxia is an important contributor to intrauterine growth restriction (IUGR), which impedes fetal lung maturation and leads to the development of chronic lung diseases. Although evidence suggests the involvement of pyroptosis in IUGR, the molecular mechanism of pyroptosis is still unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been found to potentially interact with gasdermin D (GSDMD), the key protein responsible for pyroptosis, indicating its crucial role in inhibiting pyroptosis. Therefore, we hypothesized that Nrf2 deficiency is a key molecular responsible for lung pyroptosis in maternal hypoxia-induced IUGR offspring mice. Pregnant WT and Nrf2-/- mice were exposed to hypoxia (10.5 % O2) to mimic IUGR model. We assessed body weight, lung histopathology, pulmonary angiogenesis, oxidative stress levels, as well as mRNA and protein expressions related to inflammation in the 2-week-old offspring. Additionally, we conducted a dual-luciferase reporter assay to confirm the targeting relationship between Nrf2 and GSDMD. Our findings revealed that offspring with maternal hypoxia-induced IUGR exhibited reduced birth weight, catch-up growth delay, and pulmonary dysplasia. Furthermore, we observed impaired nuclear translocation of Nrf2 and increased GSDMD-mediated pyroptosis in these offspring with IUGR. Moreover, the dual-luciferase reporter assay demonstrated that Nrf2 could directly inhibit GSDMD transcription; deficiency of Nrf2 exacerbated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR. Collectively, our findings suggest that Nrf2 deficiency induces GSDMD-mediated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR; thus highlighting the potential therapeutic approach of targeting Nrf2 for treating prenatal hypoxia-induced pulmonary dysplasia in offspring.

2.
Front Cell Infect Microbiol ; 14: 1401963, 2024.
Article in English | MEDLINE | ID: mdl-38803575

ABSTRACT

The understanding of the link between the gut-bone axis is growing yearly, but the mechanisms involved are not yet clear. Our study analyzed the role of Sestrin2 (SESN2)pathway in the gut-bone axis. We established an osteoarthritis (OA) model in Sprague-Dawley (SD) rats using the anterior cruciate ligament transection (ACLT) procedure, followed by a dietary intervention with varying levels of dietary fiber content for 8 weeks. By 16S rRNA sequencing of the gut microbiota, we found that high dietary fiber (HDF) intake could significantly increase the Bacillota-dominant gut microbiota. Meanwhile, enzyme linked immunosorbent assay (ELISA) and histological analysis showed that intervention with HDF could reduce the degree of bone and joint lesions and inflammation. We hypothesize that HDF increased the dominant flora of Bacillota, up-regulated the expression of SESN2 in knee joint, and reduced gut permeability, thereby reducing systemic inflammatory response and the degree of bone and joint lesions. Therefore, the present study confirms that changes in gut microbiota induced by increased dietary fiber intake delayed the onset of OA by promoting up-regulation of SESN2 expression at the knee joint to maintain chondrocyte activity and reduce synovial inflammation.


Subject(s)
Chondrocytes , Dietary Fiber , Disease Models, Animal , Gastrointestinal Microbiome , Osteoarthritis , Rats, Sprague-Dawley , Animals , Chondrocytes/metabolism , Osteoarthritis/microbiology , Osteoarthritis/pathology , Rats , Male , RNA, Ribosomal, 16S/genetics , Knee Joint/microbiology , Knee Joint/pathology
3.
J Anim Sci Biotechnol ; 15(1): 64, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38706000

ABSTRACT

BACKGROUND: The genetic diversity of yak, a key domestic animal on the Qinghai-Tibetan Plateau (QTP), is a vital resource for domestication and breeding efforts. This study presents the first yak pangenome obtained through the de novo assembly of 16 yak genomes. RESULTS: We discovered 290 Mb of nonreference sequences and 504 new genes. Our pangenome-wide presence and absence variation (PAV) analysis revealed 5,120 PAV-related genes, highlighting a wide range of variety-specific genes and genes with varying frequencies across yak populations. Principal component analysis (PCA) based on binary gene PAV data classified yaks into three new groups: wild, domestic, and Jinchuan. Moreover, we proposed a 'two-haplotype genomic hybridization model' for understanding the hybridization patterns among breeds by integrating gene frequency, heterozygosity, and gene PAV data. A gene PAV-GWAS identified a novel gene (BosGru3G009179) that may be associated with the multirib trait in Jinchuan yaks. Furthermore, an integrated transcriptome and pangenome analysis highlighted the significant differences in the expression of core genes and the mutational burden of differentially expressed genes between yaks from high and low altitudes. Transcriptome analysis across multiple species revealed that yaks have the most unique differentially expressed mRNAs and lncRNAs (between high- and low-altitude regions), especially in the heart and lungs, when comparing high- and low-altitude adaptations. CONCLUSIONS: The yak pangenome offers a comprehensive resource and new insights for functional genomic studies, supporting future biological research and breeding strategies.

4.
BMC Med Imaging ; 24(1): 39, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38336622

ABSTRACT

BACKGROUND: Coronary computed tomography angiography stenosis score (CCTA-SS) is a proposed diagnosis score that considers the plaque characteristics, myocardial function, and the diameter reduction rate of the lesions. This study aimed to evaluate the diagnostic performance of the CCTA-SS in seeking coronary artery disease (CAD). METHODS: The 228 patients with suspected CAD who underwent CCTA and invasive coronary angiography (ICA) procedures were under examination. The diagnostic performance was evaluated with the receiver operating curve (ROC) for CCTA-SS in detecting CAD (defined as a diameter reduction of ≥ 50%) and severe CAD (defined as a diameter reduction of ≥ 70%). RESULTS: The area under ROC (AUC) of CCTA-SS was 0.909 (95% CI: 0.864-0.943), which was significantly higher than that of CCTA (AUC: 0.826; 95% CI: 0.771-0.873; P = 0.0352) in diagnosing of CAD with a threshold of 50%. The optimal cutoff point of CCTA-SS was 51% with a sensitivity of 90.66%, specificity of 95.65%, positive predictive value of 98.80%, negative predictive value of 72.13%, and accuracy of 91.67%, whereas the optimal cutoff point of CCTA was 55%, and the corresponding values were 87.36%, 93.48%, 98.15%, 65.15%, and 88.60%, respectively. With a threshold of 70%, the performance of CCTA-SS with an AUC of 0.927 (95% CI: 0.885-0.957) was significantly higher than that of CCTA with an AUC of 0.521 (95% CI: 0.454-0.587) (P < 0.0001). CONCLUSIONS: CCTA-SS significantly improved the diagnostic accuracy of coronary stenosis, including CAD and severe CAD, compared with CCTA.


Subject(s)
Coronary Artery Disease , Coronary Stenosis , Humans , Computed Tomography Angiography/methods , Constriction, Pathologic , Coronary Stenosis/diagnostic imaging , Tomography, X-Ray Computed/methods , Coronary Angiography/methods , Predictive Value of Tests
5.
Exp Lung Res ; 50(1): 25-41, 2024.
Article in English | MEDLINE | ID: mdl-38419581

ABSTRACT

BACKGROUND: The transcriptional repressor B-cell lymphoma 6 (BCL6) has been reported to inhibit inflammation. So far, experimental evidence for the role of BCL6 in bronchopulmonary dysplasia (BPD) is lacking. Our study investigated the roles of BCL6 in the progression of BPD and its downstream mechanisms. METHODS: Hyperoxia or lipopolysaccharide (LPS) was used to mimic the BPD mouse model. To investigate the effects of BCL6 on BPD, recombination adeno-associated virus serotype 9 expressing BCL6 (rAAV9-BCL6) and BCL6 inhibitor FX1 were administered in mice. The pulmonary pathological changes, inflammatory chemokines and NLRP3-related protein were observed. Meanwhile, BCL6 overexpression plasmid was used in human pulmonary microvascular endothelial cells (HPMECs). Cell proliferation, apoptosis, and NLRP3-related protein were detected. RESULTS: Either hyperoxia or LPS suppressed pulmonary BCL6 mRNA expression. rAAV9-BCL6 administration significantly inhibited hyperoxia-induced NLRP3 upregulation and inflammation, attenuated alveolar simplification and dysregulated angiogenesis in BPD mice, which were characterized by decreased mean linear intercept, increased radical alveolar count and alveoli numbers, and the upregulated CD31 expression. Meanwhile, BCL6 overexpression promoted proliferation and angiogenesis, inhibited apoptosis and inflammation in hyperoxia-stimulated HPMECs. Moreover, administration of BCL6 inhibitor FX1 arrested growth and development. FX1-treated BPD mice exhibited exacerbation of alveolar pathological changes and pulmonary vessel permeability, with upregulated mRNA levels of pro-inflammatory cytokines and pro-fibrogenic factors. Furthermore, both rAAV9-BCL6 and FX1 administration exerted a long-lasting effect on hyperoxia-induced lung injury (≥4 wk). CONCLUSIONS: BCL6 inhibits NLRP3-mediated inflammation, attenuates alveolar simplification and dysregulated pulmonary vessel development in hyperoxia-induced BPD mice. Hence, BCL6 may be a target in treating BPD and neonatal diseases.


Subject(s)
Bronchopulmonary Dysplasia , Hyperoxia , Lung Injury , Animals , Humans , Infant, Newborn , Mice , Animals, Newborn , Bronchopulmonary Dysplasia/etiology , Bronchopulmonary Dysplasia/metabolism , Disease Models, Animal , Endothelial Cells/pathology , Hyperoxia/metabolism , Inflammation/metabolism , Lipopolysaccharides/pharmacology , Lung/metabolism , Lung Injury/drug therapy , Lung Injury/etiology , Lung Injury/prevention & control , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Proto-Oncogene Proteins c-bcl-6/metabolism , RNA, Messenger/metabolism
6.
Int Nurs Rev ; 71(1): 13-19, 2024 Mar.
Article in English | MEDLINE | ID: mdl-36708510

ABSTRACT

AIM: This study examined the correlation among turnover intention, emotional intelligence and job burnout in male nurses and determined its influencing factors. BACKGROUND: The number of male nurses has increased in China; however, the turnover rate is very high. Nurses' turnover intention is related to job burnout and emotional intelligence. INTRODUCTION: Recent studies have shown that job burnout and emotional intelligence are related to medical and health institution employees' intention to leave their jobs. It is not clear if the same conclusions can be drawn about male nurses. METHODS: For this cross-sectional study, 627 male nurses were recruited from across China between May and July 2018. Data were collected through an online questionnaire, and Pearson's product-moment correlation coefficient and multiple linear regression were performed to analyse the data. RESULTS: There was a weak negative, moderate positive and moderate negative correlation between turnover intention and emotional intelligence, turnover intention and job burnout, and emotional intelligence and job burnout, respectively. Factors that significantly affected turnover intention among male nurses included job burnout, young age, lack of interest in nursing and working in the emergency department. CONCLUSION: The study revealed the factors that affected male nurses' turnover intention and the relationships between turnover intention, emotional intelligence and job burnout. IMPLICATIONS FOR NURSING MANAGEMENT AND SOCIAL POLICY: Hospital managers should provide necessary help and support to reduce male nurse turnover rates and incorporate emotional intelligence training. The policy should eliminate the unfair college admission practices for students choosing nursing majors, raise the nursing profession's salaries and vigorously develop specialty nursing. In addition, diversified values should be promoted, and stereotypes of male nurses in nursing should be broken.


Subject(s)
Burnout, Professional , Nurses , Nursing Staff, Hospital , Humans , Male , Nurses, Male , Job Satisfaction , Workplace/psychology , Intention , Cross-Sectional Studies , Burnout, Professional/psychology , Personnel Turnover , China , Surveys and Questionnaires , Nursing Staff, Hospital/psychology
7.
MedComm (2020) ; 4(6): e448, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38077250

ABSTRACT

Staphylococcus aureus (SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA-induced ALI (SA-ALI) remains unclear. In this study, serum samples were collected from SA-sepsis patients, and a SA-ALI mouse model was established by grouping WT and Nrf2-/- mice after 6 h of intraperitoneal injection. A cell model simulating SA-ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA-sepsis patients, negatively correlated with the severity of ALI. In SA-ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation-induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA-ALI. The p-Nrf2/total-Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA-treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual-luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA-ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells.

8.
Int Heart J ; 64(6): 1125-1132, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-37967979

ABSTRACT

This study aimed to observe the mechanism and effect of circ_0004771 on cardiomyocyte injury in acute myocardial infarction (AMI). The differences in circ_0004771 expression in the blood of AMI patients and healthy volunteers were observed by Real-Time Quantitative Reverse Transcription-Polymerase Chain Reaction. AMI cell models were constructed by hypoxia/reoxygenation (H/R)-induced injury in human cardiomyocytes (AC16 cells). The changes of circ_0004771 expression in AMI cells were observed. After transfection with the knockdown or overexpression of circ_0004771 vector in AMI cells, Cell Counting Kit-8 (CCK-8) assay and propidium iodide/FITC-Annexin V staining were performed to detect cell proliferation and apoptosis levels, extracellular lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) concentration, and superoxide dismutase (SOD) activity. Expression levels of Mitogen-activated protein kinase (MAPK) signaling pathway-related proteins (p-MEK1/2, MEK1/2, p-ERK1/2, ERK1/2), and endoplasmic reticulum (ER) stress proteins (GRP78 and CHOP-1) were observed in each group of cells by western blot method. The expression level of circ_0004771 was significantly reduced in both clinical samples and cells of AMI. When circ_0004771 was knocked down in AMI cells, it resulted in a decrease in cell proliferation level and significant increase in apoptosis level. The inhibition of circ_0004771 expression caused leakage of LDH in AMI cells, accumulation of intracellular MDA, and inhibition of SOD activity. In addition, the knockdown of circ_0004771 significantly increased the levels of p-MEK1/2, p-ERK1/2, GRP78, and CHOP-1 in H/R-induced AC16 cells. However, the overexpression of circ_0004771 resulted in the opposite result as when circ_0004771 was knocked down. A low level of circ_0004771 in AMI activates the MAPK signaling pathway in cardiomyocytes as well as encourages intracellular oxidative stress and ER stress, thereby inhibiting cell proliferation and promoting apoptosis.


Subject(s)
MicroRNAs , Myocardial Infarction , Humans , Myocytes, Cardiac/metabolism , Mitogen-Activated Protein Kinases/metabolism , Endoplasmic Reticulum Chaperone BiP , Signal Transduction , Myocardial Infarction/metabolism , Apoptosis , Hypoxia/metabolism , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , MicroRNAs/metabolism
9.
Org Lett ; 25(41): 7464-7469, 2023 10 20.
Article in English | MEDLINE | ID: mdl-37800465

ABSTRACT

Fortuneicyclidins A and B are a pair of recently isolated Cephalotaxus alkaloids with an unprecedented rearranged polycyclic skeleton possessing multiple complex stereocenters and functionalization. In this work, highly stereocontrolled asymmetric total syntheses for title alkaloids were outlined. Key features include an underexplored Ir-catalyzed α-allylation of aldehyde to strategically install a vicinal N-substituted quaternary center and a tertiary stereocenter, Heck and RCM reactions to construct the critical polycyclic framework rapidly, two different tandem oxidation-transannular aldol cyclization processes, one through ozonolysis and another via Swern oxidation, to forge the last ring for fortuneicyclidins A and B, respectively. In this approach, the challenging C-2 hydroxyl group can be installed stereospecifically.


Subject(s)
Alkaloids , Harringtonines , Stereoisomerism , Cyclization , Oxidation-Reduction
10.
Clin Respir J ; 17(9): 941-950, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37545476

ABSTRACT

BACKGROUND: We aimed to explore the prognostic differences among T1-4N0-2M0 non-small cell lung cancer (NSCLC) patients with bronchus involvements and to validate the T category of these patients in an external cohort. METHODS: Univariable and multivariable Cox analysis was performed to determine the prognostic factors. Kaplan-Meier method with a log-rank test was used to compare overall survival differences between groups. Propensity score matching method was used to minimize the bias caused by the imbalanced covariates between groups. RESULTS: A total of 169 390 eligible T1-4N0-2M0 NSCLC cases were included. There were 2354, 3367, 1638, 75, 87 585, 42 056, 19 246, and 13 069 cases in the group of superficial tumors of any size with invasive component limited to bronchial wall (T1-bronchus), tumors involving main stem bronchus ≥2 cm from carina (T2-main bronchus [≥2 cm]), tumors involving main stem bronchus <2 cm from carina (T2-main bronchus [<2 cm]), tumors with carina invasion (T4-carina), T1, T2, T3, and T4, respectively. Multivariable Cox analysis indicated that T1-bronchus patients had the best prognosis; T2-main bronchus (≥2 cm) and T2-main bronchus (<2 cm) patients had similar prognosis both in the entire cohort and in several subgroups. Survival curves showed that T1-bronchus and T1 patients had similar survival rates; the survivals of T2-main bronchus patients regardless of the distance from carina were comparable to those of T2 patients, and the survivals of T4-carina patients were also similar to those of T4 patients. CONCLUSIONS: Our results validated and supported the current T category for the patients with bronchus involvements, which might provide certain reference value for the revisions of T category in the next version of the tumor-node-metastasis stage classification.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Bronchi/pathology , Prognosis , Survival Rate , Neoplasm Staging , Retrospective Studies
11.
Org Lett ; 25(41): 7459-7463, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37578250

ABSTRACT

Cephalotine A, a recently isolated Cephalotaxus alkaloid, was first synthesized enantioselectively through three critical reactions. SmI2 -mediated radical cyclization of lactone and aldehyde to forge the final ring system, Chang's iridium-catalyzed C-H amidation to construct pyrrolidone stereoselectively, and Carreria's dual Ir/amine catalyzed allylation to install the vicinal tertiary stereocenters.

12.
Theriogenology ; 209: 141-150, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37393744

ABSTRACT

DNA binding inhibitory factor 3 (ID3) has been shown to have a key role in maintaining proliferation and differentiation. It has been suggested that ID3 may also affect mammalian ovarian function. However, the specific roles and mechanisms are unclear. In this study, the expression level of ID3 in cumulus cells (CCs) was inhibited by siRNA, and the downstream regulatory network of ID3 was uncovered by high-throughput sequencing. The effects of ID3 inhibition on mitochondrial function, progesterone synthesis, and oocyte maturation were further explored. The GO and KEGG analysis results showed that after ID3 inhibition, differentially expressed genes, including StAR, CYP11A1, and HSD3B1, were involved in cholesterol-related processes and progesterone-mediated oocyte maturation. Apoptosis in CC was increased, while the phosphorylation level of ERK1/2 was inhibited. During this process, mitochondrial dynamics and function were disrupted. In addition, the first polar body extrusion rate, ATP production and antioxidation capacity were reduced, which suggested that ID3 inhibition led to poor oocyte maturation and quality. The results will provide a new basis for understanding the biological roles of ID3 as well as cumulus cells.


Subject(s)
Cumulus Cells , Oocytes , Oogenesis , Progesterone , Animals , Cattle , Female , Cumulus Cells/metabolism , Mammals , Mitochondria , Oocytes/physiology , Oogenesis/genetics , Progesterone/pharmacology , Progesterone/metabolism , Inhibitor of Differentiation Proteins/metabolism
13.
Phytomedicine ; 118: 154934, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37393828

ABSTRACT

BACKGROUND: Ischemic stroke is caused by local lesions of the central nervous system and is a severe cerebrovascular disease. A traditional Chinese medicine, Yiqi Tongluo Granule (YQTL), shows valuable therapeutic effects. However, the substances and mechanisms remain unclear. PURPOSE: We combined network pharmacology, multi-omics, and molecular biology to elucidate the mechanisms by which YQTL protects against CIRI. STUDY DESIGN: We innovatively created a combined strategy of network pharmacology, transcriptomics, proteomics and molecular biology to study the active ingredients and mechanisms of YQTL. We performed a network pharmacology study of active ingredients absorbed by the brain to explore the targets, biological processes and pathways of YQTL against CIRI. We also conducted further mechanistic analyses at the gene and protein levels using transcriptomics, proteomics, and molecular biology techniques. RESULTS: YQTL significantly decreased the infarction volume percentage and improved the neurological function of mice with CIRI, inhibited hippocampal neuronal death, and suppressed apoptosis. Fifteen active ingredients of YQTL were detected in the brains of rats. Network pharmacology combined with multi-omics revealed that the 15 ingredients regulated 19 pathways via 82 targets. Further analysis suggested that YQTL protected against CIRI via the PI3K-Akt signaling pathway, MAPK signaling pathway, and cAMP signaling pathway. CONCLUSION: We confirmed that YQTL protected against CIRI by inhibiting nerve cell apoptosis enhanced by the PI3K-Akt signaling pathway.


Subject(s)
Brain Ischemia , Drugs, Chinese Herbal , Reperfusion Injury , Animals , Mice , Rats , Multiomics , Network Pharmacology , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Molecular Biology , Reperfusion Injury/drug therapy , Brain Ischemia/drug therapy , Drugs, Chinese Herbal/pharmacology , Molecular Docking Simulation
14.
Materials (Basel) ; 16(11)2023 May 26.
Article in English | MEDLINE | ID: mdl-37297134

ABSTRACT

Ammonia (NH3) is a highly important industrial chemical used as fuel and fertilizer. The industrial synthesis of NH3 relies heavily on the Haber-Bosch route, which accounts for roughly 1.2% of global annual CO2 emissions. As an alternative route, the electrosynthesis of NH3 from nitrate anion (NO3-) reduction (NO3-RR) has drawn increasing attention, since NO3-RR from wastewater to produce NH3 can not only recycle waste into treasure but also alleviate the adverse effects of excessive NO3- contamination in the environment. This review presents contemporary views on the state of the art in electrocatalytic NO3- reduction over Cu-based nanostructured materials, discusses the merits of electrocatalytic performance, and summarizes current advances in the exploration of this technology using different strategies for nanostructured-material modification. The electrocatalytic mechanism of nitrate reduction is also reviewed here, especially with regard to copper-based catalysts.

15.
Biomedicines ; 11(6)2023 Jun 09.
Article in English | MEDLINE | ID: mdl-37371773

ABSTRACT

The malfunction of vascular smooth muscle cells (VSMCs) is an initiating factor in the pathogenesis of pathological vascular remodeling, including hypertension-related vascular lesions. MicroRNAs (miRNAs) have been implicated in the pathogenesis of VSMC proliferation and migration in numerous cases of cardiovascular remodeling. The evidence for the regulatory role of miR-155-5p in the development of the cardiovascular system has been emerging. However, it was previously unclear whether miR-155-5p participated in the migration of VSMCs under hypertensive conditions. Thus, we aimed to define the exact role and action of miR-155-5p in VSMC migration by hypertension. Here, we detected that the level of miR-155-5p was lower in primary VSMCs from spontaneously hypertensive rats (SHRs). Its overexpression attenuated, while its depletion accelerated, the migration and oxidative damage of VSMCs from SHRs. Our dual-luciferase reporter assay showed that miRNA-155-5p directly targeted the 3'-untranslated region (3'-UTR) of BTB and CNC homology 1 (BACH1). The miR-155-5p mimic inhibited BACH1 upregulation in SHR VSMCs. By contrast, the deletion of miR-155-5p further elevated the upregulation of BACH1 in SHR-derived VSMCs. Importantly, the overexpression of miR-155-5p and knockdown of BACH1 had synergistic effects on the inhibition of VSMCs in hypertension. Collectively, miR-155-5p attenuates VSMC migration and ameliorates vascular remodeling in SHRs, via suppressing BACH1 expression.

16.
Brain Behav ; 13(6): e3014, 2023 06.
Article in English | MEDLINE | ID: mdl-37062885

ABSTRACT

BACKGROUND: Morphological changes of retina in patients with Wilson's disease (WD) can be found by optical coherence tomography (OCT), and such changes had significant differences between neurological forms (NWD) and hepatic forms (HWD) of WD. The aim of this study was to evaluate the relationship between morphological parameters of retina and brain magnetic resonance imaging (MRI) lesions, course of disease, type of disease, and sexuality in WD. METHODS: A total of 46 WD patients and 40 health controls (HC) were recruited in this study. A total of 42 WD patients were divided into different groups according to clinical manifestations, course of disease, sexuality, and brain MRI lesions. We employed the Global Assessment Scale to assess neurological severity of WD patients. All WD patients and HC underwent retinal OCT to assess the thickness of inner limiting membrane (ILM) layer to retinal pigment epithelium layer and inner retina layer (ILM to inner plexiform layer, ILM-IPL). RESULTS: Compared to HWD, NWD had thinner superior parafovea zone (108.07 ± 6.89 vs. 114.40 ± 5.54 µm, p < .01), temporal parafovea zone (97.17 ± 6.65 vs. 103.60 ± 4.53 µm, p < .01), inferior parafovea zone (108.114 ± 7.65 vs. 114.93 ± 5.84 µm, p < .01), and nasal parafovea zone (105.53 ± 8.01 vs. 112.10 ± 5.44 µm, p < .01) in inner retina layer. Course of disease influenced the retina thickness. Male patients had thinner inner retina layer compared to female patients. CONCLUSION: Our results demonstrated that WD had thinner inner retina layer compared to HC, and NWD had thinner inner retina layer compared to HWD. We speculated the thickness of inner retina layer may be a potential useful biomarker for NWD.


Subject(s)
Hepatolenticular Degeneration , Humans , Male , Female , Hepatolenticular Degeneration/diagnostic imaging , Hepatolenticular Degeneration/pathology , Tomography, Optical Coherence/methods , Retina/diagnostic imaging , Retina/pathology
17.
J Hazard Mater ; 454: 131448, 2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37094442

ABSTRACT

The activation of peracetic acid (PAA) by using Fe2+ has been used to degrade emerging micropollutants in water, the slow cycle of Fe3+/Fe2+ however limits the process efficiency, and debates on the dominant reactive species are still ongoing. This study investigated Fe2+-catalyzed PAA under ultraviolet-A (UVA) irradiation toward the degradation of five representative micropollutants (carbamazepine, diclofenac, naproxen, sulfamethoxazole and trimethoprim). The results showed that PAA was efficiently catalyzed by trace Fe2+ (≤ 10 µM) with the synergy of UVA, resulting in more efficient naproxen degradation than that by inorganic peroxides (H2O2/persulfates)-based photo-Fenton processes. Notably, high-valent iron (IV)-oxo complex (FeIVO2+) was identified as the primary reactive species in Fe2+/PAA/UVA process, whereas the generation of organic radicals and hydroxyl radical were quite minimal. As such, remarkable selectivity toward the degradation of multiple micropollutants were observed, which resulted in much faster degradation rates of naproxen and diclofenac than those of carbamazepine, sulfamethoxazole and trimethoprim. Moreover, the critical operating parameters were optimized based on the degradation kinetics of naproxen, and the application potential has been revealed by the efficient naproxen degradation in actual water samples. The findings highlight that the introduction of UVA in the Fe2+/PAA system not only solves the problem of the slow rate of Fe2+ regeneration, but also greatly decreases the iron sludge production by using trace Fe2+, making it attractive for practical application.

18.
BMC Neurol ; 23(1): 89, 2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36855079

ABSTRACT

OBJECTIVE: To analyze and explore the risk factors for neurological symptoms in patients with purely hepatic Wilson's disease (WD) at diagnosis. METHODS: This retrospective study was conducted at the First Affiliated Hospital of the Guangdong Pharmaceutical University on 68 patients with purely hepatic WD aged 20.6 ± 7.2 years. The physical examinations, laboratory tests, color Doppler ultrasound of the liver and spleen, and magnetic resonance imaging (MRI) of the brain were performed. RESULTS: The elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels and 24-h urinary copper level were higher in the purely hepatic WD who developed neurological symptoms (NH-WD) group than those in the purely hepatic WD (H-WD) group. Adherence to low-copper diet, and daily oral doses of penicillamine (PCA) and zinc gluconate (ZG) were lower in the NH-WD group than those in the H-WD group. Logistic regression analysis showed that insufficient doses of PCA and ZG were associated with the development of neurological symptoms in patients with purely hepatic WD at diagnosis. CONCLUSION: The development of neurological symptoms in patients with purely hepatic WD was closely associated with insufficient doses of PCA and ZG, and the inferior efficacy of copper-chelating agents. During the course of anti-copper treatment, the patient's medical status and the efficacy of copper excretion should be closely monitored.


Subject(s)
Hepatolenticular Degeneration , Humans , Brain , Copper , Hepatolenticular Degeneration/complications , Hepatolenticular Degeneration/drug therapy , Penicillamine/therapeutic use , Retrospective Studies , Risk Factors , Zinc/therapeutic use
19.
Genes (Basel) ; 14(2)2023 01 22.
Article in English | MEDLINE | ID: mdl-36833217

ABSTRACT

(1) Background: DNA double strand breaks (DSBs) are the most serious form of DNA damage that affects oocyte maturation and the physiological state of follicles and ovaries. Non-coding RNAs (ncRNAs) play a crucial role in DNA damage and repair. This study aims to analyze and establish the network of ncRNAs when DSB occurs and provide new ideas for next research on the mechanism of cumulus DSB. (2) Methods: Bovine cumulus cells (CCs) were treated with bleomycin (BLM) to construct a DSB model. We detected the changes of the cell cycle, cell viability, and apoptosis to determine the effect of DSBs on cell biology, and further evaluated the relationship between the transcriptome and competitive endogenous RNA (ceRNA) network and DSBs. (3) Results: BLM increased γH2AX positivity in CCs, disrupted the G1/S phase, and decreased cell viability. Totals of 848 mRNAs, 75 long noncoding RNAs (lncRNAs), 68 circular RNAs (circRNAs), and 71 microRNAs (miRNAs) in 78 groups of lncRNA-miRNA-mRNA regulatory networks, 275 groups of circRNA-miRNA-mRNA regulatory networks, and five groups of lncRNA/circRNA-miRNA-mRNA co-expression regulatory networks were related to DSBs. Most differentially expressed ncRNAs were annotated to cell cycle, p53, PI3K-AKT, and WNT signaling pathways. (4) Conclusions: The ceRNA network helps to understand the effects of DNA DSBs activation and remission on the biological function of CCs.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Female , Animals , Cattle , DNA Breaks, Double-Stranded , RNA, Circular/genetics , RNA, Long Noncoding/genetics , Cumulus Cells/metabolism , Phosphatidylinositol 3-Kinases/genetics , MicroRNAs/genetics , RNA, Messenger/genetics , DNA
20.
Inorg Chem ; 62(10): 4043-4047, 2023 Mar 13.
Article in English | MEDLINE | ID: mdl-36847330

ABSTRACT

The assembly of supertetrahedral chalcogenolate clusters (SCCs) and multifunctional organic linkers could lead to the formation of tunable structures and synergistic properties. Two SCC-based assembled materials (SCCAM-1 and -2) constructed by a triangular chromophore ligand, tris(4-pyridylphenyl)amine, were successfully synthesized and characterized. The SCCAMs demonstrate unusually long-lived afterglow at low temperatures (83 K) and efficient activities for the photocatalytic degradation of organic dye in water.

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