Probucol protects against brain damage caused by intra-neural pyroptosis in rats with vascular dementia through inhibition of the Syk/Ros pathway.

BACKGROUND: Neuronal injury in chronic cerebral hypoperfusion (CCH) is the main pathogenic factor of vascular dementia (VD). Clinically, there isn't a drug specifically for VD; instead, the majority of medications used to treat Alzheimer's disease (AD) are also used to treat VD. Based on the proven anti-inflammatory and antioxidant effects of Probucol, we hypothesized that it may have therapeutic effects on VD, but more research is required to determine its exact mechanism of action. METHODS: In vivo experiment: We used SD rats and most commonly used bilateral carotid artery occlusion (2-VO) in VD for modeling. After successful modeling, SD rats were given Probucol 3.5 mg/kg/day for 8 weeks to evaluate the therapeutic effect. In vitro experiment: BV-2 microglia of rats were cultured and divided into Control group and Probucol group. Each group was treated with hypoxia-hypoglycemia, hypoxia-hypoglycemia hydrogen peroxide and hypoxia-hypoglycemia hydrogen peroxide Syk inhibitor respectively. RESULTS: The results of immunofluorescence and Western blot showed that Probucol could significantly improve the cognitive impairment induced by CCH, and the neuronal damage was also attenuated. On the one hand, the underlying mechanism of Probucol was to reduce oxidative stress and cell apoptosis of hippocampal neurons by inhibiting the expression of phosphorylated spleen tyrosine kinase (P-Syk); On the other hand, it exerted a protective effect by reducing NLRP3-dependent cell pyroptosis and inhibiting neuroinflammation induced by microglia activation. CONCLUSION: Probucol could reduce oxidative stress and cell apoptosis by inhibiting the Syk/ROS signaling pathway, thereby improving CCH-induced cognitive impairment in vitro and in vivo.

Clinical Characterization of the Expression of Insulin-Like Growth Factor Binding Protein 1 and Tumor Immunosuppression Caused by Ferroptosis of Neutrophils in Non-Small Cell Lung Cancer.

Purpose: The efficacy of immunotherapy for non-small cell lung cancer (NSCLC) is limited owing to cold tumors and drug resistance. Therefore, it is important to identify the molecular mechanisms underlying immune evasion in NSCLC. Spontaneous ferroptosis of neutrophils has been suggested as a key mechanism of immunosuppression in cancer. Insulin-like growth factor binding protein 1 (IGFBP1) plays an important role in immune infiltration in several cancers. However, the role of IGFBP1 in NSCLC is unknown. Therefore, in this study, we aimed to investigate the association of IGFBP1 mRNA expression with infiltration of myeloid-derived suppressor cells and prognosis in NSCLC. Patients and Methods: Retrospective RNA-seq data from 990 patients in the Cancer Genome Atlas (TCGA) database were analyzed in relation to patient clinical characteristics. The Timer2 database was used to assess immune infiltration, and the FerrDb V2 database was used to obtain ferroptosis-related genes. Finally, the results were validated by the proteomic analysis of serum samples collected from six patients with NSCLC and six healthy individuals. Results: IGFBP1 expression was enriched in lung adenocarcinoma samples and positively correlated with the pathological grade of NSCLC. IGFBP1 expression was an independent prognostic factor for the overall survival of patients with NSCLC. In addition, IGFBP1 expression correlated with myeloid-derived suppressor cell infiltration. Notably, Gene Ontology analysis of IGFBP1-related genes revealed that the major molecular functions of their protein products were related to NADP+ 1-oxidoreductase activity. Furthermore, expression levels of multiple ferroptosis suppressor genes positively correlated with IGFBP1 expression. Conclusion: High IGFBP1 expression indicates a poor prognosis in patients with NSCLC, which may be related to tumor immunosuppression caused by neutrophil ferroptosis.

Cell Modeling Based on Bubbles with Weighted Membranes.

Mathematicization for cell modeling provides an effective tool to verify the biological theory, and the existing research mainly focuses on the description of cell structures. This article then addresses the pattern question of cell division or morphogenesis by means of bubble model with weighted membranes. In this study, we show that cell shapes including intersection angles at junction points depend on weights on membranes. For convenience, adhesion and contractile force are considered together as a factor in construction of patterning model. This model is also used to compare with experimental data. And the consistency between our model and experiments is also obtained consequently. This system of differential equations with their boundary conditions theorizes the existing experimental models, and improves the rationality of these models.

A specific subtype of chronic obstructive pulmonary disease classified by forced vital capacity.

BACKGROUND: Forced expiratory volume in one second (FEV1) is widely used in grading the severity of the airflow limitation observed in chronic obstructive pulmonary disease (COPD). However, the characteristics of COPD classified by forced vital capacity (FVC) remain unknown. Hence, the characteristics of pulmonary function test (PFT) and clinical features of COPD patients classified by FVC were investigated. METHODS: COPD patients were classified into three groups by FVC: (I) large consistent FVC (LC-FVC): before bronchodilator (BBD) and after bronchodilator (ABD) FVC ≥80%pred; (II) inconsistent FVC (I-FVC): BBD FVC <80%pred, while ABD FVC ≥80%pred; (III) small consistent FVC (SC-FVC): BBD and ABD FVC <80%pred. The characteristics of pulmonary function and clinical features of 1,329 retrospective patients and 403 prospective patients were analyzed in different FVC subgroups. RESULTS: The percentages of LC-FVC, I-FVC and SC-FVC were 25.4%, 13.8% and 60.9%, respectively in the retrospective cohort, and were 34.0%, 15.6%, 50.4%, respectively in the prospective cohort. For the 1,329 retrospective patients, I-FVC showed the best responsiveness to bronchodilator when compared with those of LC-FVC and SC-FVC, no matter evaluated by FEV1 (0.21 vs. 0.14 vs. 0.10 L, P<0.001) or FVC (0.47 vs. 0.15 vs. 0.23 L, P<0.001), and similar results were found in the 403 prospective patients. Of the 405 retrospective patients who finished lung volume tests, I-FVC and SC-FVC demonstrated higher residual volume than that of LC-FVC (3.43 vs. 3.15 vs. 2.89 L, P<0.05), while I-FVC and LC-FVC showed higher total lung capacity than that of SC-FVC (5.92 vs. 6.06 vs. 5.18 L, P<0.05). In the prospective cohort, LC-FVC and I-FVC experienced more asthma comorbidity than that of SC-FVC (30.7% vs. 30.2% vs. 16.7%, P=0.005); I-FVC group tended to experience more exacerbation events than the other two groups (1.7 vs. 1.2 vs. 1.5, P=0.114). CONCLUSIONS: COPD patients classified by BBD and ABD FVC showed obviously different clinical characteristics, which could assist in distinguishing I-FVC patients who may benefit most from bronchodilators.

An Improved Model of Nonuniform Coleochaete Cell Division.

Cell division is a key biological process in which cells divide forming new daughter cells. In the present study, we investigate continuously how a Coleochaete cell divides by introducing a modified differential equation model in parametric equation form. We discuss both the influence of "dead" cells and the effects of various end-points on the formation of the new cells' boundaries. We find that the boundary condition on the free end-point is different from that on the fixed end-point; the former has a direction perpendicular to the surface. It is also shown that the outer boundaries of new cells are arc-shaped. The numerical experiments and theoretical analyses for this model to construct the outer boundary are given.

The fencing problem and Coleochaete cell division.

The findings in this study suggest that the solution of a boundary value problem for differential equation system can be used to discuss the fencing problem in mathematics and Coleochaete, a green algae, cell division. This differential equation model in parametric expression is used to simulate the two kinds of cell division process, one is for the usual case and the case with a "dead" daughter cell.