Open Medicine最新文献

Some of the millions of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have developed new sequelae after recovering from the initial disease, termed post-acute sequelae of coronavirus disease 2019 (PASC). One symptom is anxiety, which is likely due to three etiologies: brain structural changes, neuroendocrine disruption, and neurotransmitter alterations. This review provides an overview of the current literature on the pathophysiological pathways linking coronavirus disease 2019 to anxiety, as well as the possible mechanisms of action in which an increasingly scrutinized treatment method, enhanced external counter-pulsation (EECP), is able to alleviate anxiety. SARS-CoV-2 triggers increased inflammatory cytokine production, as well as oxidative stress; these processes contribute to the aforementioned three etiologies. The potential treatment approach of EECP, involving sequenced inflation and deflation of specifically-placed airbags, has become of increasing interest, as it has been found to alleviate PASC-associated anxiety by improving patient cardiovascular function. These functional improvements were achieved by EECP stimulating anti-inflammatory and pro-angiogenic processes, as well as improving endothelial cell function and coronary blood flow, partially via counteracting against the negative effects of SARS-CoV-2 infection on the renin-angiotensin-aldosterone system. Therefore, EECP could promote both psychosomatic and cardiac rehabilitation. Further research, though, is still needed to fully determine its benefits and mechanism of action.

Objectives: This study aims to assess the potential mechanism of rutin to treat triple-negative breast cancer (TNBC) based on network pharmacology followed by in vitro experiments.

Methods: The potential rutin targets were predicted, and the DisGeNET database was used to obtain the disease targets. The intersection targets were identified with Venny 2.1 software, with the String database subsequently used as input to produce the "drug-target-disease" visual network employing Cytoscape 3.7.2. Gene ontology. Kyoto Encyclopaedia of Genes and Genomes analyses were performed for intersection targets, while AutoDock Vina was used for molecular docking and visualization. Cell viability was assessed using the Colorimetric CCK-8 test, and apoptosis was analyzed using PI/Annexin V. The predicted core targets were confirmed by qPCR and western blotting assays.

Results: EGFR, IL6, TNF, and INS were found as the primary targets. The molecular docking analysis revealed the rutin interaction with the core targets. The in vitro results confirmed that rutin inhibited the growth of the MDA-MB-231 cell line. Rutin also induced cell death and decreased the expressions of IL6, TNF, INS, and EGFR.

Conclusion: Rutin's multi-target effects and molecular mechanism for treating TNBC were confirmed through preliminary results. The results provide a theoretical base for rutin's possible function in breast cancer treatment.

Background: Microsatellite instability (MSI) significantly impacts treatment response and outcomes in colon cancer; however, its underlying molecular mechanisms remain unclear. This study aimed to identify prognostic biomarkers by comparing MSI and microsatellite stability (MSS).

Methods: Data from the GSE39582 dataset downloaded from the Gene Expression Omnibus database were analyzed for differentially expressed genes (DEGs) and immune cell infiltration between MSI and MSS. Then, weighted gene co-expression network analysis (WGCNA) was utilized to identify the key modules, and the modules related to immune infiltration phenotypes were considered as the immune-related gene modules, followed by enrichment analysis of immune-related module genes. Prognostic signatures were derived using Cox regression, and their correlation with immune features and clinical features was assessed, followed by a nomogram construction.

Results: A total of 857 DEGs and 14 differential immune cell infiltration between MSI and MSS were obtained. Then, WGCNA identified two immune-related modules comprising 356 genes, namely MEturquoise and MEbrown. Eight signature genes were identified, namely PLK2, VSIG4, LY75, GZMB, GAS1, LIPG, ANG, and AMACR, followed by prognostic model construction. Both training and validation cohorts revealed that these eight signature genes have prognostic value, and the prognostic model showed superior predictive performance for colon cancer prognosis and distinguished the clinical characteristics of colon cancer patients. Notably, VSIG4 among the signature genes correlated significantly with immune infiltration, human leukocyte antigen expression, and immune pathway enrichment. Finally, the constructed nomogram model could significantly predict the prognosis of colorectal cancer.

Conclusion: This study identifies eight prognostic signature genes associated with MSI and immune infiltration in colon cancer, suggesting their potential for predicting prognostic risk.

Background: Atherosclerosis is a lipid-driven inflammatory disease characterized by plaque formation in major arteries. These plaques contain lipid-rich macrophages that accumulate through monocyte recruitment, local macrophage differentiation, and proliferation.

Objective: We identify the macrophage subsets that are closely related to atherosclerosis and reveal the key pathways in the progression of atherosclerotic disease.

Materials and methods: In this study, we characterize the single-cell landscape of atherosclerosis, identifying macrophage subsets closely related to the disease and revealing key pathways in its progression. Using analytical methods like CytoTRACE, Monocle2, Slingshot, and CellChat, we study macrophage differentiation and infer cell trajectory.

Results: The 8,417 macrophages were divided into six subtypes, macrophages: C0 C1QC+ macrophages, C1 SPP1+ macrophages, C2 FCN1+ macrophages, C3 IGKC+ macrophages, C4 FCER1A+ macrophages, C5CALD1+ macrophages. The results of gene set enrichment analysis, Monocle2, and Slingshot suggest that C2 FCN1+ macrophages may play an important role in the progression of atherosclerosis. C2 FCN1+ macrophages interact with endothelial cells via CCL, CXCL, APP, and other pathways to regulate the progression of atherosclerosis.

Conclusion: We identify a key macrophage subgroup (C2 FCN1+ macrophages) associated with atherosclerosis, which interacts with endothelial cells via CCL, CXCL, APP, and other pathways to regulate disease progression.

Rhein is a natural anthraquinone substance extracted from Rheum palmatum L. This study aimed to evaluate Rhein's protective effects against skin wound by in vivo and in vitro models and investigate whether its protective mechanism regulated the PI3K/AKT signaling pathway. The skin wound mice model was established and then treated with Rhein for 10 days. Hematoxylin and eosin staining and Masson's trichrome staining were applied to assess histological changes and collagen maturity in the mice skin wound tissues. Human skin fibroblasts (HSFs) viability, migration, and invasion were detected by Cell counting kit-8 (CCK-8), scratch wound, and transwell assays respectively. Moreover, the protein expression of p-PI3K, PI3K, p-AKT, and AKT were determined by western blot assay. We found that local treatment with Rhein promoted skin wound healing and accelerated collagen maturation, compared with the Model group. In addition, Rhein promoted skin wound healing through accelerated HSF proliferation, migration, and invasion. Furthermore, Rhein remarkably enhanced p-PI3K and p-AKT expression, as well as p-PI3K/PI3K and p-AKT/AKT ratio in skin wound mice and HSF cells, suggesting that Rhein promoted skin wound healing by activating PI3K/AKT signaling pathway. In conclusion, Rhein is a promising agent for promoting wound healing of skin tissues.

[This corrects the article DOI: 10.1515/med-2024-0988.].

[This corrects the article DOI: 10.1515/med-2024-0986.].

Objective: To investigate the relationship between the expression levels of serum forkhead box protein M1(FOXM1) and insulin-like growth factor 2 (IGF2) mRNA in patients with acute respiratory distress syndrome (ARDS) condition and prognosis.

Methods: Ninety patients with ARDS admitted to our hospital were regarded as the ARDS group, according to the prognosis, they were grouped into death group (n = 64) and survival group (n = 126); the control group consisted of 190 healthy individuals.

Results: Compared with the control group, the level of serum FOXM1 mRNA in ARDS group was obviously lower, and the level of IGF2 mRNA was higher. The serum IGF2 mRNA, serum creatinine, inhaled oxygen concentration (FiO₂), and mechanical ventilation time in the death group were higher than those in the control group, and the arterial oxygen partial pressure (PaO₂), FOXM1 mRNA, and oxygenation index (PaO₂/FiO₂) were lower than those in control group. Logistic regression analysis indicated that FOXM1, IGF2, and PaO₂/FiO₂ were significant factors influencing the prognosis and mortality in ARDS patients. Correlation analysis showed that there was a negative correlation between serum FOXM1 and IGF2 mRNA levels in patients with ARDS.

Conclusion: Serum FOXM1 and IGF2 mRNA in patients with ARDS are correlated with the severity and prognosis of ARDS.

Background: Postoperative cognitive dysfunction (POCD) frequently occurs following endovascular therapy for acute ischemic stroke (AIS). Given the complexity of predicting AIS clinically, there is a pressing need to develop a preemptive prediction model and investigate the impact of anesthesia depth on AIS.

Methods: A total of 333 patients diagnosed with AIS were included in the study, comprising individuals with non-POCD (n = 232) or POCD (n = 101). Univariate and multivariate logistic regression analyses were utilized to examine the independent risk factors associated with POCD. A calibration, decision curve analysis, and precision-recall curves were employed to assess the model's goodness of fit.

Results: Multivariate regression analysis identified two inflammatory indicators, high-sensitivity C reactive protein (hs-CRP) and systemic immune inflammatory index (SII), and three brain injury indicators, National Institute of Health Stroke Scale (NIHSS) score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble protein-100 β (S100-β), which were used to construct a nomogram model.

Conclusion: The composite predictive model incorporating NIHSS score, hs-CRP, SII, NT-proBNP, and S100-β demonstrated efficacy in predicting POCD following AIS. Additionally, our results suggest a potential association between depth of anesthesia, cognitive impairment, and inflammatory response in AIS patients.

Selective serotonin reuptake inhibitor correlates with decreased bone mineral density and impedes orthodontic tooth movement. The present study aimed to examine the effects of fluoxetine on osteoclast differentiation and function. Human peripheral blood mononuclear cells (hPBMCs) and murine RAW264.7 cells were cultured with RANKL to stimulate osteoclast differentiation. The resulting multinucleated cells displayed characteristics of mature osteoclasts. Fluoxetine at 0.01-1 μM did not impact cellular viability or oxidative stress. However, 10 μM fluoxetine significantly reduced clonal growth, cell viability, and increased cytotoxicity and lipid peroxidation in RAW 264.7 cells. Further, application of 0.1 μM fluoxetine potently suppressed osteoclast differentiation of both RAW264.7 and hPBMCs, with reduced osteoclast numbers and downregulation of osteoclastic genes matrix metalloproteinase-9, cathepsin K, and integrin β3 at mRNA and protein levels. Fluoxetine also disrupted F-actin ring formation essential for osteoclast resorptive function. Mechanistically, fluoxetine inhibited NF-kB signaling by reducing phosphorylation of pathway members IκBα and p65, preventing IκBα degradation and blocking p65 nuclear translocation. In conclusion, this study demonstrates fluoxetine suppressing osteoclast differentiation in association with disrupting NF-kB activation, providing insight into orthodontic treatment planning for patients taking fluoxetine.