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1.
Sci Data ; 11(1): 883, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143120

RESUMO

Remote sensing technology has the potential to enhance the lake's large-scale and long-term dynamic monitoring capabilities significantly. High-quality in-situ datasets are essential for improving the accuracy and reliability of remote sensing retrieval of lake ecosystems. This dataset provides satellite-ground synchronized in-situ data on water multi-parameters for typical lakes in China spanning the period between 2020 and 2023. It includes quality-checked water optical parameters (remote sensing reflectance (Rrs), chlorophyll-a (Chl-a), total suspended matter (TSM) and Secchi disk depth (SDD)), and water surface temperature (WST) data. It encompasses 586 sampling points across 18 lakes. The dataset exhibits two significant highlights: Firstly, synchronous observations from multiple satellites are coordinated during the data collection effectively supporting the retrieval and validation of water remote sensing products. Secondly, it encompasses diverse data types, collecting synchronous measurements of Rrs and various parameters. This dataset will continuously update, substantially enhancing regional and global lake monitoring capabilities through satellite remote sensing data.

2.
Can Respir J ; 2024: 9284430, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139502

RESUMO

Introduction: The impaired proliferative capacity of alveolar epithelial cells after injury is an important factor causing epithelial repair dysfunction, leading to the occurrence of idiopathic pulmonary fibrosis (IPF). Alveolar type 2 (AT2) cells as the stem cells of alveolar epithelium participate in the repair process after alveolar injury. Lipocalin-2 (LCN2) participates in multiple processes regulating the pathological process of alveolar epithelial cells, but the mechanisms involved are still unclear. Method: We used a BLM-treated mouse model to characterize the expression of LCN2 in lung fibrosis regions and analyzed the location of LCN2 in alveolar epithelial cells. Moreover, human pulmonary alveolar epithelial cells (HPAEpiCs) were transfected with the LCN2 overexpression plasmid vector in vitro. Recombinant human interleukin-17 (IL-17) protein (rhIL-17) at different concentrations was administered to intervene in HPAEpiCs, observing cell viability and analyzing the concentration-dependent effect of IL-17. Results: LCN2 was increased in the alveolar epithelium post-BLM injury, and highly expressed LCN2 was mainly concentrated on AT2 cells in BLM-injured lungs. Meanwhile, LCN2-overexpressing HPAEpiCs showed impaired cell viability and cell growth. HPAEpiC intervention with rhIL-17 mildly rescued the impaired cell proliferation induced by LCN2 overexpression, and the effect of IL-17 intervention was partially concentration-dependent. Conclusions: The results revealed the reversed effect of IL-17 on the impaired proliferative capacity of the alveolar epithelium induced by LCN2 overexpression. The target alveolar epithelial cells regulated by this process were AT2 cells, providing new clues for alveolar epithelium repair after injury and the treatment of lung injury diseases.


Assuntos
Células Epiteliais Alveolares , Proliferação de Células , Interleucina-17 , Lipocalina-2 , Lipocalina-2/genética , Lipocalina-2/metabolismo , Interleucina-17/metabolismo , Interleucina-17/genética , Animais , Proliferação de Células/genética , Camundongos , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/efeitos dos fármacos , Humanos , Bleomicina/toxicidade , Masculino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
3.
Rev Cardiovasc Med ; 25(6): 210, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39076330

RESUMO

Background: Although pulmonary vein isolation (PVI) remains the mainstream way of atrial fibrillation (AF) ablation. The left atrial posterior wall (LAPW) may contributes to the development of AF as an arrhythmogenic substrate. The efficacy of additional left atrial posterior wall isolation (LAPWI) beyond PVI is in AF patients remains undefined. This study explored the influence of posterior wall isolation (PWI) on clinical outcomes in AF patients. Methods: PubMed, EMBASE, and Cochrane Library databases were searched for studies comparing the outcomes of AF with and without PWI. The efficacy outcomes were recurrence of all atrial arrhythmia (AA), atrial fibrillation (AF), and atrial flutter (AFL)/atrial tachycardia (AT). The safety outcomes were mainly focused on procedural adverse events. Results: A total of 16 studies (7 randomized controlled trials (RCTs), 3 prospective studies and 6 retrospective analyses) with 3340 AF patients were enrolled (1550 patients in PVI with PWI group and 1790 in PVI alone group). 12 studies included persistent atrial fibrillation patients, 3 studies with paroxysmal AF patients and 1 study with paroxysmal AF and persistent AF concurrently. Mean follow-up period was 16.56 months. In AF patients, adjunctive PWI obviously reduced the recurrence of all atrial arrhythmias (risk ratio (RR) 0.78 [95% CI 0.64-0.95], I 2 = 79%, p = 0.01) and the recurrence of AF (RR 0.68 [95% CI 0.53-0.88], I 2 = 75%, p = 0.004); Meanwhile, additional PWI left no impact substantially on lower recurrence of AFL/AT (RR 1.23 [95% CI 0.94-1.60], I 2 = 49%, p = 0.12). The results seemed to be no significant differences in occurrence rate of procedural complications between the PVI only and PWI+PVI (RR 1.19 [95% CI 0.80-1.79], I 2 = 0%, p = 0.39). In subgroup analyses, the benefit of adjunctive PWI compared with PVI only was more distinct in persistent AF group and cryoballoon ablation group. Notably, adjunctive PWI with radiofrequency ablation may induce a slight increase of recurrent AFL/AT compared with PVI only (RR 1.56 [95% CI 1.02-2.39], I 2 = 30%, p = 0.04). Conclusions: Compared with PVI alone, additional PWI to PVI appeared to be associated with decreased recurrence of AF and atrial arrhythmias without an increased occurrence of procedural complications, especially in persistent AF patients. Cryoballoon ablation seemed more suitable for PWI compared with radiofrequency ablation. More RCTs are needed to verify the conclusion.

4.
J Nanobiotechnology ; 22(1): 430, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033108

RESUMO

Immunotherapy exhibits considerable promise for sustained tumor reduction. However, current cancer immunotherapy methods elicit limited responses due to the inadequate immunogenicity exhibited by cancer cells. This obstacle may be addressed using nanoplatforms that can activate synergistic therapies (photodynamic therapy and ferroptosis) in response to the acidic pH of the tumor microenvironment. We previously developed an amphiphilic photosensitizer, SR780, which displays satisfactory photodynamic effects. This photosensitizer is inactivated when bound to Fe3+ (SR780Fe) but is activated upon release in mildly acidic conditions. In this study, M1 macrophage-derived extracellular vesicles (EVs) were fused with REV and SR780Fe-loaded liposomes (REV@SR780Fe@Lip) to form REV@SR780Fe@LEV hybrid nanovesicles. Further modification with the RS17 peptide for tumor targeting enabled a combination of photodynamic therapy, ferroptosis, and cGAS-STING pathway activation, resulting in enhanced antitumor efficacy through a synergistic effect. Upon laser irradiation, REV@SR780Fe@LEV-RS17 demonstrated antitumor effects in 4T1 breast cancer models, including the inhibition of lung and liver metastasis, as well as prevention of tumor recurrence.


Assuntos
Vesículas Extracelulares , Imunoterapia , Macrófagos , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes , Animais , Imunoterapia/métodos , Vesículas Extracelulares/química , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Linhagem Celular Tumoral , Feminino , Lipossomos/química , Concentração de Íons de Hidrogênio , Microambiente Tumoral/efeitos dos fármacos , Humanos , Ferroptose/efeitos dos fármacos , Nanopartículas/química
5.
J Am Heart Assoc ; 13(14): e033619, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38979841

RESUMO

BACKGROUND: Few small-sample studies have quantified the T-wave alternans (TWA) value by 24-hour ambulatory recordings or exercise stress tests in patients with long QT syndrome (LQTS). The cutoff point of TWA ≥47 µV was based on patients with myocardial infarction. In our study, we aimed to (1) evaluate the association of TWA with life-threatening arrhythmic events (LAEs); (2) compare the predictive model of LAEs according to the TWA value measured by 24-hour ambulatory recordings and exercise stress tests; and (3) propose a cutoff point for the high risk of LAEs in patients with LQTS. METHODS AND RESULTS: The study cohort included 110 patients with LQTS referred to our hospital, and the primary outcome was LAEs. Thirty-one patients with LQTS (31/110 [28.2%]) developed LAEs during the following 24 (12-47) months. Peak TWA value quantified from 12 leads by 24-hour ambulatory recordings in patients with LQTS with LAEs (LQTS-LAEs group) was significantly higher than LQTS without LAEs (LQTS-non-LAEs group) (64.0 [42.0-86.0] µV versus 43.0 [36.0-53.0] µV; P<0.01). There was no statistical difference in TWA value measured by exercise stress tests between the 2 groups (69.0 [54.5-127.5] µV versus 68.5 [53.3-99.8] µV; P=0.871). The new cutoff point of the peak TWA value measured by 24-hour ambulatory recordings was 55.5 µV, with a sensitivity of 75.0% and a specificity of 78.6%. A univariate Cox regression analysis revealed that TWA value ≥55.5 µV was a strong predictor of LAEs (hazard ratio [HR], 4.5 [2.1-9.6]; P<0.001]. A multivariate Cox regression analysis indicated that TWA value ≥55.5 µV remained significant (HR, 2.7 [1.1-6.8]; P=0.034). CONCLUSIONS: Peak TWA measured by 24-hour ambulatory recordings was a more favorable risk stratification marker than exercise stress tests for patients with LQTS.


Assuntos
Eletrocardiografia Ambulatorial , Teste de Esforço , Síndrome do QT Longo , Humanos , Feminino , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Masculino , Teste de Esforço/métodos , Medição de Risco/métodos , Adulto , Eletrocardiografia Ambulatorial/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Adulto Jovem , Prognóstico , Fatores de Tempo , Estudos Retrospectivos , Frequência Cardíaca/fisiologia
6.
Front Mol Biosci ; 11: 1301099, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993839

RESUMO

Introduction: Hepatocellular carcinoma (HCC), which is closely associated with chronicinflammation, is the most common liver cancer and primarily involves dysregulated immune responses in the precancerous microenvironment. Currently, most studies have been limited to HCC incidence. However, the immunopathogenic mechanisms underlying precancerous lesions remain unknown. Methods: We obtained single-cell sequencing data (GSE136103) from two nonalcoholic fatty liver disease (NAFLD) cirrhosis samples and five healthy samples. Using pseudo-time analysis, we systematically identified five different T-cell differentiation states. Ten machine-learning algorithms were used in 81 combinations to integrate the frameworks and establish the best T-cell differentiation-related prognostic signature in a multi-cohort bulk transcriptome analysis. Results: LDHA was considered a core gene, and the results were validated using multiple external datasets. In addition, we validated LDHA expression using immunohistochemistry and flow cytometry. Conclusion: LDHA is a crucial marker gene in T cells for the progression of NAFLD cirrhosis to HCC.

7.
J Cardiothorac Surg ; 19(1): 321, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845009

RESUMO

BACKGROUND: Long QT Syndrome (LQTS) and Beckwith-Wiedemann Syndrome (BWS) are complex disorders with unclear origins, underscoring the need for in-depth molecular investigations into their mechanisms. The main aim of this study is to identify the shared key genes between LQTS and BWS, shedding light on potential common molecular pathways underlying these syndromes. METHODS: The LQTS and BWS datasets are available for download from the GEO database. Differential expression genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) was used to detect significant modules and central genes. Gene enrichment analysis was performed. CIBERSORT was used for immune cell infiltration analysis. The predictive protein interaction (PPI) network of core genes was constructed using STRING, and miRNAs regulating central genes were screened using TargetScan. RESULTS: Five hundred DEGs associated with Long QT Syndrome and Beckwith-Wiedemann Syndrome were identified. GSEA analysis revealed enrichment in pathways such as T cell receptor signaling, MAPK signaling, and adrenergic signaling in cardiac myocytes. Immune cell infiltration indicated higher levels of memory B cells and naive CD4 T cells. Four core genes (CD8A, ICOS, CTLA4, LCK) were identified, with CD8A and ICOS showing low expression in the syndromes and high expression in normal samples, suggesting potential inverse regulatory roles. CONCLUSION: The expression of CD8A and ICOS is low in long QT syndrome and Beckwith-Wiedemann syndrome, indicating their potential as key genes in the pathogenesis of these syndromes. The identification of shared key genes between LQTS and BWS provides insights into common molecular mechanisms underlying these disorders, potentially facilitating the development of targeted therapeutic strategies.


Assuntos
Síndrome de Beckwith-Wiedemann , Antígenos CD8 , Proteína Coestimuladora de Linfócitos T Induzíveis , Síndrome do QT Longo , Humanos , Síndrome do QT Longo/genética , Síndrome de Beckwith-Wiedemann/genética , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Antígenos CD8/genética , Antígenos CD8/metabolismo , Perfilação da Expressão Gênica/métodos
8.
BMC Plant Biol ; 24(1): 549, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38872078

RESUMO

Ginseng (Panax ginseng C. A. Mey.) is an important and valuable medicinal plant species used in traditional Chinese medicine, and its metabolite ginsenoside is the primary active ingredient. The FAR1/FHY3 gene family members play critical roles in plant growth and development as well as participate in a variety of physiological processes, including plant development and signaling of hormones. Studies have indicated that methyl jasmonate treatment of ginseng adventitious roots resulted in a significant increase in the content of protopanaxadiol ginsenosides. Therefore, it is highly significant to screen the FAR1/FHY3 gene family members in ginseng and preliminarily investigate their expression patterns in response to methyl jasmonic acid signaling. In this study, we screened and identified the FAR1/FHY3 family genes in the ginseng transcriptome databases. And then, we analyzed their gene structure and phylogeny, chromosomal localization and expression patterns, and promoter cis-acting elements, and made GO functional annotations on the members of this family. After that, we treated the ginseng adventitious roots with 200 mM methyl jasmonate and investigated the trend of the expression of four genes containing the largest number of methyl jasmonate cis-acting elements at different treatment times. All four genes were able to respond to methyl jasmonate, the most significant change was in the PgFAR40 gene. This study provides data support for subsequent studies of this family member in ginseng and provides experimental reference for subsequent validation of the function of this family member under methyl jasmonic acid signaling.


Assuntos
Acetatos , Ciclopentanos , Regulação da Expressão Gênica de Plantas , Família Multigênica , Oxilipinas , Panax , Filogenia , Proteínas de Plantas , Oxilipinas/farmacologia , Ciclopentanos/farmacologia , Panax/genética , Panax/metabolismo , Panax/efeitos dos fármacos , Acetatos/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Perfilação da Expressão Gênica , Genes de Plantas , Ginsenosídeos
9.
Purinergic Signal ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922475

RESUMO

Although multiple purinergic receptors mediate the analgesic effects of acupuncture, it remains unclear whether there is mutual interaction between purinergic receptors to jointly mediate the electroacupuncture inhibition of peripheral sensitization in visceral pain. Visceral hypersensitivity was induced by intracolonic 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rat. The antinociception effect of electroacupuncture on visceral pain was evaluated by morphology, behaviors, neuroelectrophysiology and molecular biology techniques. After labeling the colon-related primary sensory neurons with neural retrograde tracer and employing neuropharmacology, neuroelectrophysiology, and molecular biotechnology, the mechanisms of P2X7R, P2Y1R, and P2X3R in colon-related dorsal root ganglion (DRG) neurons alleviating visceral hypersensitivity of irritable bowel syndrome (IBS) by electroacupuncture at Zusanli and Sanyinjiao acupoints.were elucidated from the perspective of peripheral sensitization. Electroacupuncture significantly inhibited TNBS-induced colonic hypersensitivity in rats with IBS, and Satellite Glial Cells (SGCs) in DRG were found to be involved in electroacupuncture-mediated regulation of the electrophysiological properties of neurons. P2X7R was found to play a pain-inducing role in IBS visceral hypersensitivity by affecting P2X3R, and electroacupuncture exerted an analgesic effect by inhibiting P2X7R activation. P2Y1R was found to play an analgesic role in the process of visceral pain, mediating electroacupuncture to relieve visceral hypersensitivity. P2Y1R relieved visceral pain by inhibiting P2X3R in neurons associated with nociception, with P2X7R identified as upstream of P2Y1R up-regulation by electroacupuncture. Our study suggests that the P2X7R → P2Y1R → P2X3R inhibitory pathway in DRG mediates the inhibition of peripheral sensitization by electroacupuncture in rats with IBS visceral hypersensitivity.

10.
Biochim Biophys Acta Mol Cell Res ; 1871(7): 119766, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38823528

RESUMO

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a bladder syndrome of unknown etiology. Reactive oxygen species (ROS) plays a major role in ferroptosis and bladder dysfunction of IC/BPS, while the role of ferroptosis in IC/BPS progression is still unclear. This study aims to investigate the role and mechanism of ROS-induced ferroptosis in IC/BPS using cell and rat model. METHODS: We collected IC/BPS patient bladder tissue samples and established a LPS-induced IC/BPS rat model (LRM). The level of oxidative stress and ferroptosis in IC/BPS patients and LRM rats was analyzed. Function and regulatory mechanism of ferroptosis in IC/BPS were explored by in vitro and in vivo experiments. RESULTS: The patients with IC/BPS showed mast cells and inflammatory cells infiltration in bladder epithelial tissues. Expression of NRF2 was up-regulated, and GPX4 was decreased in IC/BPS patients compared with normal tissues. IC model cells underwent oxidative stress, which induced ferroptosis. These above results were validated in LRM rat models, and inhibition of ferroptosis ameliorated bladder dysfunction in LRM rats. Wnt/ß-catenin signaling was deactivated in IC/BPS patients and animals, and activation of Wnt/ß-catenin signaling reduced cellular free radical production, thereby inhibited ferroptosis in IC model cells. Mechanistically, the Wnt/ß-catenin signaling pathway inhibited oxidative stress-induced ferroptosis by down-regulating NF-κB, thus contributing to recover IC/BPS both in vitro and in vivo. CONCLUSIONS: We demonstrate for the first time that oxidative stress-induced ferroptosis plays an important role in the pathology of IC/BPS. Mechanistically, the Wnt/ß-catenin signaling suppressed oxidative stress-induced ferroptosis by down-regulating NF-κB to improve bladder injury in IC/BPS.

11.
J Colloid Interface Sci ; 671: 175-183, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38797143

RESUMO

The practical applications of lithium-sulfur (Li-S) batteries have severely been hindered by notorious shuttle effect and sluggish redox kinetics of lithium polysulfide intermediates (LiPSs), which bring about rapid capacity degradation, low coulombic efficiency and poor cycling stability. In this work, 1T-rich MoS2 nanosheets are in-situ developed onto the conductive porous carbon matrix (1T-rich MoS2@PC) as efficient polysulfide promotors for high-performance Li-S batteries. The porous carbon skeleton tightly anchors MoS2 nanosheets to prevent their reaggregation and ensures accessible electrical channels, and at the same time provides a favorable confined space that promotes the generation of 1T-rich MoS2 structure. More importantly, the uniformly distributed metallic 1T-rich MoS2 nanosheets not only affords rich sulfphilic sites and high binding energy for immobilizing LiPSs, but also favors rapid electron transfer and LiPSs conversation kinetics, substantially regulating sulfur chemistry in working cells. Consequently, the Li-S cell assembled with 1T-rich MoS2@PC modified separator delivers a remarkable cycling stability with ultralow capacity decay rate of 0.067% over 500 cycles at 1C. Encouragingly, under harsh conditions (high sulfur loading of 4.78 mg cm-2 and low E/S ratio of 8 µL mg-1), a favorable electrochemical performance can still be demonstrated. This study highlights the profitable design of 1T-rich MoS2/carbon based electrocatalyst for suppressing shuttle effect and promoting catalytic conversation of LiPSs, and has the potential to be applied to in other energy storage systems.

12.
Life Sci ; 348: 122687, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38718856

RESUMO

AIMS: Checkpoint blockade immunotherapy is a promising therapeutic modality that has revolutionized cancer treatment; however, the therapy is only effective on a fraction of patients due to the tumor environment. In tumor immunotherapy, the cGAS-STING pathway is a crucial intracellular immune response pathway. Therefore, this study aimed to develop an immunotherapy strategy based on the cGAS-STING pathway. MATERIALS AND METHODS: The physicochemical properties of the nanoparticles EM@REV@DOX were characterized by TEM, DLS, and WB. Subcutaneous LLC xenograft tumors were used to determine the biodistribution, antitumor efficacy, and immune response. Blood samples and tissues of interest were harvested for hematological analysis and H&E staining. SIGNIFICANCE: Overall, our designed nanovesicles provide a new perspective on tumor immunotherapy by ICD and cGAS-STING pathway, promoting DCs maturation, macrophage polarization, and activating T cells, offering a meaningful strategy for accelerating the clinical development of immunotherapy. KEY FINDINGS: EM@REV@DOX accumulated in the tumor site through EPR and homing targeting effect to release REV and DOX, resulting in DNA damage and finally activating the cGAS-STING pathway, thereby promoting DCs maturation, macrophage polarization, and activating T cells. Additionally, EM@REV@DOX increased the production of pro-inflammatory cytokines (e.g., TNF-α and IFN-ß). As a result, EM@REV@DOX was effective in treating tumor-bearing mice and prolonged their lifespans. When combined with αPD-L1, EM@REV@DOX significantly inhibited distant tumor growth, extended the survival of mice, and prevented long-term postoperative tumor metastasis, exhibiting great potential in antitumor immunotherapy.


Assuntos
Imunoterapia , Proteínas de Membrana , Nanopartículas , Nucleotidiltransferases , Animais , Nucleotidiltransferases/metabolismo , Camundongos , Proteínas de Membrana/metabolismo , Imunoterapia/métodos , Nanopartículas/química , Humanos , Transdução de Sinais , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Feminino , Ensaios Antitumorais Modelo de Xenoenxerto , Morte Celular Imunogênica/efeitos dos fármacos
13.
Aging (Albany NY) ; 16(10): 8980-8997, 2024 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-38814181

RESUMO

Hypertension is a complex disease with unknown causes. Therefore, it's crucial to deeply study its molecular mechanism. The hypertension dataset was obtained from Gene Expression Omnibus data base (GEO), and miRNA regulating central hub genes was screened via weighted gene co-expression network (DEGs) and gene set enrichment (GSEA). Cell experiments validated TSR2's role and the PPAR signaling pathway through western blotting. 500 DEGs were identified for hypertension, mainly enriched in actin cross-linking, insulin signaling, PPAR signaling, and protein localization. Eight hub genes (SEC61G, SRP14, Liy AR, NIP7, SDAD1, POLR1D, DYNLL2, TSR2) were identified. Four hub genes (LYAR, SDAD1, POLR1D, TSR2) exhibited high expression levels in the hypertensive tissue samples, while showing low expression levels in the normal tissue samples. This led us to speculate that they may have relevant regulatory effects on hypertension. When TSR2 was knocked down in the hypertension peripheral blood mononuclear cells (PBMC) model, the critical proteins in the PPAR signaling pathway (FABP, PPAR, PLTP, ME1, SCD1, CYP27, FABP1, OLR1, CPT-1, PGAR, CAP, ADIPO, MMP1, UCP1, ILK, PDK1 UBC AQP7) were downregulated. This also occurred in the hypertension peripheral blood mononuclear cells (PBMC) + TSR2_ OV model. TSR2 is highly expressed in individuals with hypertension and may play a significant role in the development of hypertension through the PPAR signaling pathway. TSR2 could serve as a molecular target for the early diagnosis and precise treatment of hypertension, providing a valuable direction for the mechanism research of this condition.


Assuntos
Hipertensão , Transdução de Sinais , Hipertensão/genética , Hipertensão/metabolismo , Humanos , Transdução de Sinais/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Redes Reguladoras de Genes , Leucócitos Mononucleares/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação da Expressão Gênica
14.
Redox Biol ; 72: 103159, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642501

RESUMO

The changes of inflammation and metabolism are two features in nonalcoholic steatohepatitis (NASH). However, how they interact to regulate NASH progression remains largely unknown. Our works have demonstrated the importance of solute carrier family 7 member 11 (SLC7A11) in inflammation and metabolism. Nevertheless, whether SLC7A11 regulates NASH progression through mediating inflammation and metabolism is unclear. In this study, we found that SLC7A11 expression was increased in liver samples from patients with NASH. Upregulated SLC7A11 level was also detected in two murine NASH models. Functional studies showed that SLC7A11 knockdown or knockout had augmented steatohepatitis with suppression of inflammatory markers in mice. However, overexpression of SLC7A11 dramatically alleviated diet-induced NASH pathogenesis. Mechanically, SLC7A11 decreased reactive oxygen species (ROS) level and promoted α-ketoglutarate (αKG)/prolyl hydroxylase (PHD) activity, which activated AMPK pathway. Furthermore, SLC7A11 impaired expression of NLRP3 inflammasome components through AMPK-mitophagy axis. IL-1ß release through NLRP3 inflammasome recruited myeloid cells and promoted hepatic stellate cells (HSCs) activation, which contributed to the progression of liver injury and fibrosis. Anti-IL-1ß and anakinra might attenuate the hepatic inflammatory response evoked by SLC7A11 knockdown. Moreover, the upregulation of SLC7A11 in NASH was contributed by lipid overload-induced JNK-c-Jun pathway. In conclusions, SLC7A11 acts as a protective factor in controlling the development of NASH. Upregulation of SLC7A11 is protective by regulating oxidation, αKG and energy metabolism, decreasing inflammation and fibrosis.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Cirrose Hepática , Mitofagia , Hepatopatia Gordurosa não Alcoólica , Espécies Reativas de Oxigênio , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Camundongos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/genética , Humanos , Espécies Reativas de Oxigênio/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Ácidos Cetoglutáricos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Masculino , Inflamação/metabolismo , Inflamação/patologia , Inflamação/genética , Fígado/metabolismo , Fígado/patologia , Inflamassomos/metabolismo , Transdução de Sinais , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia
15.
Biomed Pharmacother ; 174: 116567, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583340

RESUMO

Bile acid (BA) receptors (e.g., farnesoid X-activated receptor, muscarinic receptor) are expressed in cardiomyocytes, endothelial cells, and vascular smooth muscle cells, indicating the relevance of BAs to cardiovascular disease (CVD). Hydrophobic BAs are cardiotoxic, while hydrophilic BAs are cardioprotective. For example, fetal cardiac insufficiency in maternal intrahepatic cholestasis during pregnancy, and the degree of fetal cardiac abnormality, is closely related to the level of hydrophobic BAs in maternal blood and infant blood. However, ursodeoxycholic acid (the most hydrophilic BA) can reverse/prevent these detrimental effects of increased levels of hydrophobic BAs on the heart. The gut microbiota (GM) and GM metabolites (especially secondary BAs) have crucial roles in hypertension, atherosclerosis, unstable angina, and heart failure. Herein, we describe the relationship between CVD and the GM at the BA level. We combine the concept of the "microbiota-gut-heart axis" (MGHA) and postulate the role and mechanism of BAs in CVD development. In addition, the strategies for treating CVD with BAs under the MGHA are proposed.


Assuntos
Ácidos e Sais Biliares , Doenças Cardiovasculares , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Ácidos e Sais Biliares/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/microbiologia , Animais
16.
iScience ; 27(4): 109540, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38577099

RESUMO

Chronic inflammation is critical for the initiation and progression of type 2 diabetes mellitus via causing both insulin resistance and pancreatic ß cell dysfunction. miR-155, highly expressed in macrophages, is a master regulator of chronic inflammation. Here we show that blocking a macrophage-derived exosomal miR-155 (MDE-miR-155) mitigates the insulin resistances and glucose intolerances in high-fat-diet (HFD) feeding and type-2 diabetic db/db mice. Lentivirus-based miR-155 sponge decreases the level of miR-155 in the pancreas and improves glucose-stimulated insulin secretion (GSIS) ability of ß cells, thus leading to improvements of insulin sensitivities in the liver and adipose tissues. Mechanistically, miR-155 increases its expression in HFD and db/db islets and is released as exosomes by islet-resident macrophages under metabolic stressed conditions. MDE-miR-155 enters ß cells and causes defects in GSIS function and insulin biosynthesis via the miR-155-PDX1 axis. Our findings offer a treatment strategy for inflammation-associated diabetes via targeting miR-155.

17.
J Opt Soc Am A Opt Image Sci Vis ; 41(2): 349-354, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437349

RESUMO

A simple twin-core D-shape photonic crystal fiber sensor based on surface plasmon resonance (SPR) is designed for the measurement of refractive indices (RI). The twin-core D-shape structure enhances the SPR effect, and the M g F 2-Au dual-layer film narrows the linewidth in the loss spectrum, consequently improving both the sensitivity and figure of merit (FOM). The properties of the sensor are analyzed by the finite element method. In the RI range of 1.32-1.42, the maximum wavelength sensitivity, FOM, and resolution are 62,000 nm/RIU, 1281R I U -1, and 1.61×10-6, respectively.

18.
Omega (Westport) ; : 302228241236981, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438064

RESUMO

This quasi-experimental study investigated the impact of traditional Chinese culture-based life-and-death education on 38 ICU nurses. Participants underwent 14 hours of training, and data were collected before and after the intervention using various questionnaires. Frequency and percentage were used for categorical data; mean and standard deviation for measurement data; and paired-sample t test for comparison of teaching effects before and after the intervention of life-and-death education programs. Results indicated significant improvements in understanding of death, reduced death anxiety, enhanced death coping abilities, and increased search for meaning (p < .05). However, there was no statistically significant change in attitude toward death (p > .05). Life-and-death education rooted in traditional Chinese culture positively influenced ICU nurses, fostering improved death cognition, reduced death anxiety, enhanced coping skills, and a heightened sense of meaning in life. Subsequent research will explore the relationship and distinctions between explicit and implicit death attitudes.

19.
J Colloid Interface Sci ; 663: 697-706, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38432168

RESUMO

The unique superstructures electrode materials are of dominant significance for improving the performance of aqueous zinc-ion batteries (AZIBs). In this work, using nano MIL-96 (Al) as the precursor, a series of the layered (AlO)2OH·VO3 composite superstructures with different morphologies and V-oxide contents were prepared by combining calcination and hydrothermal synthesis. Among which, the HBC650·V4 superstructure is composed of the amorphous Al2O3/C, V-oxide, and the fluffy structure of (AlO)2OH, thus the superstructure can enhance the stability, increase the active center, and shorten Zn2+ diffusion, respectively. It is commendable that, the HBC650·V4 superstructure exhibits a high specific capacity of 180.1 mAh·g-1 after 300 cycles at 0.5 A·g-1. Furthermore, the capacity retention can be as high as 99.6 % after 5000 cycles at a high current density of 5.0 A·g-1, showing superior long cycling stability. Importantly, the in-situ XRD patterns and ex-situ analysis revealed the structural changes and reaction mechanisms of the HBC650·V4 superstructure during Zn2+ insertion/extraction. Therefore, the HBC650·V4 superstructure prepared using Al-MOF exhibits the advanced AZIBs performance. The preparation of nano-MOF into multifunctional superstructures through innovative strategies will be development trend in this field, which opens a new way to design AZIBs cathode materials.

20.
Heliyon ; 10(6): e27521, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38496861

RESUMO

Background: In-stent restenosis (ISR) has become a significant obstacle to interventional therapy for atherosclerotic cardiovascular disease. The optimal percutaneous coronary intervention (PCI) strategy for patients with coronary ISR remains controversial. This network meta-analysis (NMA) was aimed to compare and estimate the effectiveness of different PCI strategies and commercial devices for the treatment of patients with coronary ISR. Methods: In present study, we systematically searched PubMed, Embase, Web of Science, and Cochrane Library from database inception to October 20, 2022, to identify randomized controlled trials. We included studies comparing various PCI strategies for the treatment of any type of coronary ISR. The study was registered with PROSPERO, CRD 42022364308. Results: We included 44 eligible trials including 8479 patients, 39 trials comparing the treatment effects of 10 PCIs, and 5 trials comparing the efficacy between different types of drug-eluting stent (DES) or drug-coated balloon (DCB) devices. Among the PCIs, everolimus-eluting stent was the optimal strategy considering target lesion revascularization (TLR), percent diameter stenosis (%DS), and binary restenosis (BR), and sirolimus-coated balloon was the optimal strategy considering late lumen loss (LLL). In the comparison of commercial devices, the combination strategy excimer laser coronary angioplasty plus SeQuent Please paclitaxel-coated balloon showed promising therapeutic prospects. Conclusions: DCB and DES remain the preferred treatment strategies for coronary ISR, considering both the primary clinical outcome (TLR) and the angiographic outcomes (LLL, BR, %DS). Personalized combination interventions including DCB or DES hold promise as a novel potential treatment pattern for coronary ISR.

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