Identification of key genes in spontaneous cerebral hemorrhage and prevention of disease damage: LASSO and SVM regression.

Prevention is more important than treatment, and the incidence of intracerebral hemorrhage can be effectively reduced by intervening on the risk factors of intracerebral hemorrhage. By studying the risk factors of spontaneous intracerebral hemorrhage, we can identify the risk factors to achieve the target of treatment and prevention. Through the use of the Least Absolute Shrinkage and Selection Operator (LASSO) and the Support Vector Machine (SVM), the two essential SICH-related genes, NUAK1 and ERO1L, were eliminated from consideration. A Venn analysis was performed, and based on the two important modules, it found that SICH was related with four critical genes: VCM1, CRNDE, COL6A2, and HSPB6. One gene (NUAK1) was dramatically downregulated in the illness group compared to the control group, whereas three essential genes (ERO1L, VCAM1, and COL6A2) were significantly upregulated in the disease group. In the end, the genes ERO1L, VCAM1, COL6A2, and NUAK1 were shown to be the most important ones for SICH. It is anticipated that these genes will become novel biomarkers as well as targets for the development of new pharmacotherapies for SICH.

Association between fibrinogen/albumin ratio and arterial stiffness in patients with type 2 diabetes: A cross-sectional study.

Background: Fibrinogen albumin ratio (FAR) is significantly correlated with the severity and prognosis of cardiovascular disease (CVD). Arterial stiffness is an early lesion of CVD, but no studies have examined the correlation between arterial stiffness and FAR. This study aimed to examine the relationship between FAR and arterial stiffness in patients with type 2 diabetes (T2D), as measured by brachial-ankle pulse wave velocity (baPWV). Methods: In this cross-sectional investigation, patients with T2D were enrolled between January 2021 and April 2022. In each patient, the levels of fibrinogen and albumin in the serum, and baPWV in the serum were measured. A baPWV greater than 1800 cm/s was utilized to diagnose arterial stiffness. Results: The study included 413 T2D patients. The mean age of these participants was 52.56 ± 11.53 years, 60.8% of them were male, and 18.6% of them had arterial stiffness. There were significant differences in baPWV level and proportion of arterial stiffness (p < .001) between the four subgroups categorized by the FAR quartile. The relationships between the FAR and baPWV and arterial stiffness were significantly favorable in the overall population and subgroups of elderly men and non-elderly men (p < .01), while they were insignificant in subgroups of elderly and non-elderly women (p > .05). To investigate the correlation between the FAR and baPWV, the arterial stiffness and the FAR in male T2D patients, respectively, multivariable logistic regression analysis and multiple linear regression analysis were developed. The lnFAR and lnbaPWV had a significant relationship in the multiple linear regression analysis fully adjusted model. After adjusting for potential covariables, multivariable logistic regression analysis revealed that the FAR was independently associated with arterial stiffness [OR (95% CI), 1.075 (1.031-1.120)]. In addition, receiver operating characteristic analysis indicated that the best FAR cutoff value for detecting arterial stiffness in male T2D patients was 76.67 mg/g. Conclusion: The level of FAR had an independent and positive correlation with baPWV and arterial stiffness in male patients with T2D, but not in female patients.

SphK1-targeted miR-6784 inhibits functions of skin squamous cell carcinoma cells.

Sphingosine kinase 1 (SphK1) is overexpressed in skin squamous cell carcinoma (SCC). It has emerged as a novel therapeutic oncotarget. The current study identified a novel SphK1-targeting microRNA, microRNA-6784 (miR-6784). Here, we show that miR-6784 is located at the cytoplasm of A431 skin SCC cells. It directly binds to SphK1 mRNA. Ectopic overexpression of miR-6784 inhibited SphK1 3'-untranslated region (UTR) luciferase activity and downregulated its expression. Moreover, miR-6784 overexpression caused ceramide accumulation in skin SCC cells. Functional studies in established (A431 and SCC9) and primary skin SCC cells revealed that miR-6784 overexpression inhibited cell viability, proliferation, migration, and invasion. It also simultaneously provoked apoptosis activation. Conversely, miR-6784 silencing by antagomiR-6784 induced SphK1 elevation and augmented A431 cell proliferation, migration, and invasion. miR-6784 overexpression-induced anti-A431 cell activity was inhibited by the expression of an UTR-null SphK1 construct. CRISPR/Cas9-induced SphK1 knockout inhibited A431 cell growth. Importantly, miR-6784 was completely ineffective when treating SphK1-knockout A431 cells. Collectively, miR-6784 silences SphK1 and inhibits skin SCC cell progression.

Association of plasminogen activator inhibitor-1 and vitamin D receptor expression with the risk of keloid disease in a Chinese population.

Keloid disease (KD) is a benign fibroproliferative scarring condition of unknown etiopathogenesis. Plasminogen activator inhibitor-1 (PAI-1) and vitamin D receptor (VDR) have been shown to play important roles in the progression of tissue fibrosis; therefore, both these genes are potential susceptibility genes for KD. We aimed to determine whether the gene expression levels of PAI-1 and VDR are altered in Chinese KD patients. We measured the expression of PAI and VDR in human peripheral blood lymphocytes in 236 patients with keloid and 219 age- and sex-matched healthy controls by quantitative real-time polymerase chain reaction. We found that PAI-1 expression in peripheral blood lymphocytes was significantly higher in patients with KD than in control individuals (p < 0.0001), while VDR expression was significantly lower in KD patients than in control individuals (p < 0.0001). High levels of PAI-1 and low levels of VDR expression were significantly associated with an increased risk for KD. PAI-1 and VDR might play important roles in keloid development. Gene expression levels of PAI-1 and VDR may, therefore, be used as potential markers for the prediction of keloid development after scarring.

Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway.

Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague-Dawley rats received a single dose of 20Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF-pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF-pCREB signaling in non-irradiation group. These results suggest that forced running exercise offers a potentially effective treatment for radiation-induced cognitive deficits.