Open Medicine最新文献

Ischemic stroke, which accounts for the majority of stroke cases, triggers a complex series of pathophysiological events, prominently characterized by acute oxidative stress due to excessive production of reactive oxygen species (ROS). Oxidative stress plays a crucial role in driving cell death and inflammation in ischemic stroke, making it a significant target for therapeutic intervention. Nanomedicine presents an innovative approach to directly mitigate oxidative damage. This review consolidates existing knowledge on the role of oxidative stress in ischemic stroke and assesses the potential of various ROS-scavenging nanoparticles (NPs) as therapeutic agents. We explore the properties and mechanisms of metal, metal-oxide, and carbon-based NPs, emphasizing their catalytic activity and biocompatibility in scavenging free radicals and facilitating the delivery of therapeutic agents across the blood-brain barrier. Additionally, we address the challenges such as cytotoxicity, immunogenicity, and biodistribution that need to be overcome to translate these nanotechnologies from bench to bedside. The future of NP-based therapies for ischemic stroke holds promise, with the potential to enhance outcomes through targeted modulation of oxidative stress.

Heart failure (HF) is a common cardiovascular disease that is related to systemic inflammation. This study aimed to assess the role of C-reactive protein (CRP) combined with fibrinogen-to-albumin ratio (C-FAR) on the prognosis of all-cause mortality in different types of HF. A total of 1,221 hospitalized HF patients from the First Affiliated Hospital of Kunming Medical University between January 2017 and October 2021 were retrospectively analyzed. Patients were categorized into a low C-FAR group (C-FAR < 0.69) and a high C-FAR group (C-FAR ≥ 0.69) according to the median C-FAR value. We used Kaplan-Meier plots, restricted cubic spline regression, Cox survival analyses, and time-dependent receiver operating characteristic (ROC) analyses to evaluate the prognostic role of C-FAR on all-cause mortality in different types of HF. After excluding patients lost to follow-up and those with missing data, we ultimately included 1,196 patients with HF. The Kaplan-Meier plots showed that HF patients with high C-FAR levels had a significantly greater risk of all-cause mortality. In all four Cox proportional risk models, C-FAR was an independent predictor of all-cause mortality. Based on the ROC curve, the area under the curve (AUC) for C-FAR was greater than the AUC for Lg BNP. In the subgroup analyses, patients had the highest risk of all-cause mortality when FAR ≥ 0.091 and CRP ≥ 7.470. Regardless of the type of HF, C-FAR can be a good predictor of prognosis for all-cause mortality in HF patients, and patients with high C-FAR had a significantly increased risk of death compared to those with low C-FAR.

Background: This study investigated the role and mechanisms of cullin-1 (CUL1) in chronic obstructive pulmonary disease (COPD).

Methods: Cigarette smoke extract (CSE)-treated mouse pulmonary microvascular endothelial cells (mPMECs) and cigarette smoke inhalation (CSI)-stimulated mice were used to construct in vitro and in vivo COPD models, respectively. CUL1 expression was assessed using reverse transcriptase-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry were used to detect cell viability and apoptosis, respectively. We conducted an enzyme-linked immunosorbent assay on mPMECs and bronchoalveolar lavage fluid (BALF) to detect inflammatory factors. Reactive oxygen species, malondialdehyde, and superoxide dismutase were detected using the corresponding kits. The histological characteristics of the lung tissues were determined by hematoxylin and eosin staining.

Results: CUL1 expression was downregulated in COPD. CUL1 overexpression significantly promoted cell viability, reduced cell apoptosis, and inhibited inflammatory responses and oxidative stress in CSE-treated mPMECs. These changes were reversed by the p53 agonist nutlin-3. In addition, CUL1 overexpression significantly relieved COPD in mice, as confirmed by the reduced secretion of inflammatory factors in BALF, inhibited oxidative stress response, and improved lung function.

Conclusion: CUL1 plays a protective role in CSE-treated mPMECs and CSI-stimulated mice by inhibiting the p53 signaling pathway.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are common X-inherited neuromuscular diseases. The genetic diagnosis has been used as the diagnostic choice for DMD/BMD. The study subjects consisted of 37 patients from Southwest China. Peripheral blood was collected for the extraction of genomic DNA. DMD mutation was sequenced using the next-generation sequencing approach. The detected mutation was validated using the multiplex ligation-dependent probe amplification or Sanger sequencing methods. Variation annotation and pathogenicity prediction were performed using the online databases. Pathogenic mutations were identified 3 splicing site, 7 single nucleotide, 1 indel, 23 deletion, and 3 duplication mutations. Novel DMD variants were discovered, including two novel splicing variations (c.1890 + 1G>T; c.1923 + 1G>A), one missense mutation (c.1946G>T), one nonsense mutation (c.7441G>T), one indel mutation (INDEL EX20), and one duplication mutation (DUP EX75-78). The current study provides mutation information of DMD for the genetic diagnosis of DMD/BMD.

Objective: Dysregulation of chondrogenic differentiation is associated with osteoarthritis (OA). The myokine irisin is beneficial in OA treatment; yet, the underlying mechanism is not fully understood. Long noncoding RNAs (lncRNAs) act as important regulators of chondrocyte differentiation. This study was conducted to address the role of lncRNAs in mediating irisin-induced chondrocyte differentiation.

Methods: We investigated the irisin-regulated lncRNA profile change in human mesenchymal stem cells (MSCs) using published whole transcriptome sequencing data. We predicted their potential targets and competitive endogenous RNA (ceRNA) prediction and analyzed their molecular functions using functional enrichment analysis.

Results: More differentially expressed lncRNAs (DElncRNAs) were observed in irisin-treated samples. The top irisin-induced lncRNAs were associated with OA or chondrogenic differentiation, including XIST, PAX8-AS1, CASC15, LINC01618, and DLX6-AS1. The DEGs co-expressed with DElncRNAs were enriched in skeletal system development, extracellular matrix (ECM) organization, cell adhesion, and inflammation associated pathways. Several lncRNAs likely acted as ceRNAs to regulate downstream mRNAs including ROR2 and SORBS1 in in OA or chondrogenic differentiation.

Conclusions: We demonstrate the global regulation of lncRNAs by irisin during chondrogenic differentiation of human MSCs. Further study is required to characterize the key irisin-regulated lncRNAs in chondrogenic differentiation.

Objective: To explore the role of cystic fibrosis transmembrane conduction regulator (CFTR)-Epithelial sodium channel (ENaC) in spinal cord edema after spinal cord injury (SCI) and the related mechanism.

Methods: Lipopolysaccharide (LPS)-treated M1830 astrocytes were applied as the SCI in vitro model. Immunohistochemistry, real-time PCR, and Western blotting were utilized to detect CFTR and ENaC expression. Enzyme-linked immunosorbent assay was used to measure inflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-18. Transmission electron microscope examined ultrastructure changes, while CFTR-172 or Capsazepine treatment assessed their effects on edema and inflammation. Western blot analysis was employed to evaluate the PI3K, p-PI3K, AKT, and p-AKT signaling pathways in treated cells.

Results: LPS-treated M1830 cells exhibited increased levels of CFTR and pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-18, alongside decreased ENaC expression and suppressed p-PI3K/PI3K and p-AKT/AKT levels. Degeneration of the myelin sheath and axons was observed in LPS-treated M1830, while changes in ultrastructural were recovered after adding CFTR-172 or Capsazepine. The level of CFTR, TNF-α, IL-1β, IL-6, and IL-18 was decreased, while the level of ENaC, p-PI3K/PI3K, and p-AKT/AKT was increased obviously in LPS-treated M1830 with CFTR-172, Capsazepine, or IGF-1.

Conclusion: Down-regulation of CFTR and up-regulation of ENaC can attenuate inflammation in SCI by activating the PI3K/AKT signaling pathway, highlighting a new therapeutic approach for SCI treatment. These findings address a critical gap in current SCI treatments and suggest a novel intervention strategy targeting ion channel regulation.

Purpose: This study aimed to investigate the role of microtubule-affinity regulatory protein kinase 1 (MARK1) in hepatocellular carcinoma (HCC) progression, its association with sorafenib sensitivity, and the interplay between MARK1 and POTE Ankyrin domain family member E(POTEE) in HCC cells.

Methods: Quantitative real-time polymerase chain reaction analysis was used to assess MARK1 and POTEE expression in 60 pairs of HCC tissues and cell lines. The correlation between MARK1 levels, clinicopathological features, and patient prognosis was analyzed. Sorafenib-resistant HCC cell models were developed, followed by MARK1 overexpression to evaluate its impact on cell functions. Luciferase reporter assays and rescue experiments were conducted to elucidate the MARK1-POTEE regulatory mechanism.

Results: MARK1 exhibited decreased mRNA expression in HCC tissues and cells, correlating with adverse clinicopathological features and poorer patient survival. Luciferase assays confirmed direct binding between MARK1 and POTEE. Sorafenib treatment increased MARK1 protein levels, reduced POTEE, and inhibited cell proliferation. Overexpressing MARK1 suppressed sorafenib-induced proliferation in resistant cells, while co-overexpression of MARK1 and POTEE reversed this effect.

Conclusion: MARK1 potentially restrains HCC progression and enhances sorafenib resistance by negatively modulating POTEE expression, highlighting its significance as a therapeutic target in HCC treatment.

Objective: To observe the efficacy of respiratory exercise in patients with tuberculous pleurisy (TBP).

Methods: A randomized controlled study was conducted including 146 patients diagnosed with TBP and undergoing pleural effusion drainage in Shandong Public Health Clinical Center from June 2020 to December 2022, and the patients were randomly divided into the control group and the respiratory exercise observation group. Pleural effusion drainage time, the difference of pulmonary function, and the degree of pleural hypertrophy between the two groups at 1 and 3 months after treatment were studied.

Results: Compared with the control group, the pleural effusion drainage time of the observation group was shortened, and there was no significant difference between the two groups in terms of lung function and the degree of pleural hypertrophy at 1 month after treatment, while the lung function indexes and the degree of pleural hypertrophy of the observation group were significantly improved compared with that of the control group at 3 months after treatment.

Conclusion: Respiratory exercise can shorten the drainage time of effusion in patients with TBP, and help to improve lung function and alleviate pleural hypertrophy adhesion.

Objective: This study aimed to clarify the roles and underlying mechanisms of luteolin in the progression of cerebral ischemia/reperfusion injury (CIRI).

Methods: A mouse model of CIRI was established using the middle cerebral artery occlusion (MCAO) method, after which luteolin was administered. Subsequently, neuronal apoptosis and pyroptosis were measured and the brain tissues of each group were subjected to RNA sequencing.

Results: Luteolin alleviated MCAO-induced brain infarction, apoptosis, and pyroptosis. RNA sequencing identified 3,379, 2,777, and 3,933 differentially expressed genes (DEGs) in the MCAO vs sham, MCAO vs MCAO + luteolin, and MCAO + luteolin vs sham groups, respectively. The identified DEGs showed enrichment in multiple processes, including pattern specification, forebrain development, anion transport, leukocyte migration, regulation of cell-cell adhesion, and positive regulation of the response to external stimuli, as well as the calcium, PI3K-AKT, JAK-STAT, NF-kappa B, IL-17, cAMP, cGMP-PKG, and Wnt signaling pathways. In addition, Ccl2 and Angpt2 interacted more with the other top 30 DEGs with high interaction weights. Finally, RT-qPCR results showed that MCAO induction significantly up-regulated the expression of Stoml3, Eomes, and Ms4a15 and down-regulated Nms, Ttr, and Avpr1a; however, luteolin could partially reverse the expression caused by MCAO.

Conclusion: Luteolin can alleviate brain infarction, apoptosis, and pyroptosis in CIRI, and may improve MCAO-induced CIRI by targeting the identified DEGs and their enriched pathways.

Temporal muscle thickness (TMT) serves as an indicator of sarcopenia and holds predictive value for various cancers. This study aims to evaluate the prognostic significance of TMT for high-grade glioma patients. A retrospective review of 172 high-grade glioma patients from January 2015 to December 2022 was conducted. TMT value was measured based on contrast-enhanced T1-weighted magnetic resonance images before surgery. Pearson analysis was used to evaluate potential correlations. Cox regression analysis was performed to evaluate overall survival for high-grade glioma patients. In our study, the cutoff value of TMT was determined as 7.4 mm. TMT value was not a significant prognostic predictor for high-grade glioma patients (hazard ratio [HR]: 1.151, 95% confidence interval [CI]: 0.9299-1.424, p = 0.196). World Health Organization (WHO) VI and high body mass index (BMI) value were significantly associated with poorer survival outcomes (HR: 2.6689, 95% CI: 1.5729-4.528, p < 0.001; HR: 1.120, 95% CI: 1.0356-1.211, p = 0.005). TMT did not show a significant association with other factors (p > 0.05). Notably, age demonstrated a significant difference between the thicker and thinner groups (p = 0.019). Our study revealed that WHO grade and BMI demonstrated significant prognostic value for survival outcomes. Consequently, TMT does not appear to be a significant or applicable predictor in patients with high WHO grades.