Effects of extract solution from magnesium alloys supplemented with different compositions of rare earth elements on in vitro epithelial and osteoblast progenitor cells.

Background: Magnesium alloys (Mg-alloys) have gained significant attention in recent years as a potential bioactive material for clinical applications. The incorporation of rare earth elements (REEs) into Mg-alloys has been of particular interest due to their potential to improve both mechanical and biological properties. Although there are diverse results in terms of cytotoxicity and biological effects of REEs, investigating the physiological benefits of Mg-alloys supplemented with REEs will help in the transition from theoretical to practical applications. Methods: In this study, two culture systems were used to evaluate the effects of Mg-alloys containing gadolinium (Gd), dysprosium (Dy), and yttrium (Y): human umbilical vein endothelial cells (HUVEC) and mouse osteoblastic progenitor cells (MC3T3-E1). Different compositions of Mg-alloys were assessed, and the effects of the extract solution on cell proliferation, viability, and specific cell functions were analyzed. Results: Within the range of weight percentages tested, the Mg-REE alloys did not exhibit any significant negative impacts on either cell line. Interestingly, moderate compositions (Mg-1.5Gd-1.5Dy-0.825Y-0.5Zr and Mg-2Gd-2Dy-1.1Y-0.5Zr) demonstrated a tendency to enhance osteoblastic activity and promote the vascularization process in both HUVEC and MC3T3-E1 cell lines. Discussion: The results of this study provide valuable insights into the potential benefits of REE-supplemented Mg-alloys for clinical applications. The observed enhancement in osteoblastic activity and promotion of vascularization processes suggest that optimizing the compositions of REEs in Mg-alloys could lead to the development of novel, more effective bioactive materials. Further investigations are required to understand the underlying mechanisms and to refine the alloy compositions for improved biocompatibility and performance in clinical settings.

DNA methylation of the MAP3K10 gene may participate in the development of intracranial aneurysm.

BACKGROUND: The goal of this study was to explore the association between mitogen-activated protein kinase kinase kinase 10 (MAP3K10) methylation and blood lipid levels and intracranial aneurysm (IA) risk. MATERIALS AND METHODS: A total of 96 age- and sex-matched investigators participated in the assessment of MAP3K10 methylation. Fourteen CpG sites of the MAP3K10 gene were selected for methylated-pyrosequencing. Human brain vascular smooth muscle cell was used to assess the regulatory role of DNA methylation in MAP3K10 gene transcription. RESULTS: MAP3K10 mean methylation was positively correlated with triglyceride (TG, r = 0.388; p = 0.007) in men, but negatively correlated with TG (r = -0.434; p = 0.002) in women. MAP3K10 methylation in patients with IA was significantly lower than that in controls (p < 0.05), and this phenomenon was more significant in women (12 CpG sites presented significance at p < 0.05). MAP3K10 methylation might be a potential predictor of the risk of IA (CpG1, AUC = 0.81, p < 0.001; mean methylation, AUC = 0.69, p = 0.001). The predictive value was also more significant in women (CpG1: AUC = 0.86, p < 0.001; mean methylation: AUC = 0.73, p = 0.006). No significant association was found between DNA methylation and MAP3K10 gene transcription in vitro experiment. CONCLUSION: Patients with IA had lower MAP3K10 methylation levels than healthy controls. MAP3K10 methylation may be a potential predictor of IA risk, particularly in women.

The Effects of the Application of the "One Disease, One Product" Program to Nursing Practice for Patients After the Resection of Pituitary Adenomas Using the Endonasal Transsphenoi.

OBJECTIVE: To explore the application and effect of the "one disease, one product" project to the nursing care of patients who have undergone pituitary tumour surgery using the nasal sphenoid approach. METHODS: This is a prospective research study. In a standard treatment control study, 132 patients undergoing transnasal pituitary tumour surgery were divided into the control group (n = 71) and the observation group (n = 61). The control group was given routine pituitary tumor care, and the "one disease, one product" nursing model was used on the experimental group. The anxiety level of patients, the incidence of postoperative complications, postoperative hospitalization, and levels of satisfaction and capability of group members were measured between the control and experimental groups. RESULTS: There was no difference in the level of anxiety between the 2 groups before admission (P = 0.634). The anxiety level of the patients in the observation group decreased after the "one disease, one product" nursing intervention (P = 0.012), but in the control group, it did not decrease significantly (P = 0.149), and the anxiety level in the control group was significantly higher than in the observation group on day 1 preoperatively (P < 0.001). CONCLUSIONS: "One disease, one product" nursing can reduce the preoperative anxiety and postoperative satisfaction of pituitary adenoma surgery patients through the sphenoid sinus approach. It is worthy of popularization and application in pituitary adenoma resection through the sphenoid sinus approach.

Multiscale Transcriptomic Integration Reveals B-Cell Depletion and T-Cell Mistrafficking in Nasopharyngeal Carcinoma Progression.

Nasopharyngeal carcinoma (NPC), featured by Epstein-Barr virus (EBV) infection and regional epidemiology, is curable when detected early, but highly lethal at an advanced stage. The molecular mechanism of NPC progression toward a clinically uncontrollable stage remains elusive. In this study, we developed a novel computational framework to conduct multiscale transcriptomic analysis during NPC progression. The framework consists of four modules enabling transcriptomic analyses spanning from single-cell, bulk, microenvironment, to cohort scales. The bulk-transcriptomic analysis of 133 NPC or normal samples unraveled leading functional enrichments of cell-cycle acceleration, epithelial-mesenchymal transition, and chemokine-modulated inflammatory response during NPC progression. The chemokine CXCL10 in the NPC microenvironment, discovered by single-cell RNA sequencing data analysis, recruits cytotoxic T cells through interacting with its receptor CXCR3 at early but late stages. This T-cell mistrafficking was featured by the decline of cytotoxic T cells and the increase of regulatory T cells, accompanied with B-cell depletion confirmed by immunohistochemistry staining. The featured immunomodulatory chemokines were commonly upregulated in the majority of cancers associated with viral or bacterial infections.

Study on the effect of shikonin on CD36 expression and phagocytic ability of microglia in the isolated cerebral haemorrhage model.

AIM OF THE STUDY: To investigate the effects of shikonin on CD36 expression and phagocytic ability of microglia, and its protective effect on neurons and the possible mechanism within. MATERIAL AND METHODS: The effects of shikonin on CD36 expression and phagocytic ability of microglia were detected by Western blot method, and cerebral haemorrhage was isolated by flow cytometry in the experiment. The protective effect of neurons was observed through neuron-microglia co-culture technique. Meanwhile, the effect of hydrogen peroxide on the expression of catalase was detected, and the concentration of hydrogen peroxide was measured in the isolated cerebral haemorrhage model. The t test was used to compare data between 2 groups, and one-way ANOVA was applied to multiple sets of data. RESULTS: Compared with the control group, the CD36 expression and phagocytic ability of microglia was increased by shikonin in the isolated cerebral haemorrhage model, while inflammatory factors such as tumour necrosis factor a (TNF-a) and interleukin 1b (IL-1b) attenuated the effects of the drug. The amount of neuron apoptosis/necrosis was significantly reduced by the drug, while the expression of catalase in microglia was increased, but the secretion of hydrogen peroxide was decreased in the neuron-microglia co-culture system. CONCLUSIONS: Shikonin can enhance the CD36 expression and the ability to phagocytose erythrocyte of microglia. Simultaneously, shikonin performs protective effects on neuronal cells and promotes the absorption of haematoma. Therefore, shikonin is probably an innovative medicine to treat cerebral haemorrhage.

Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms.

DNA methylation at the gene promoter region is reportedly involved in the development of intracranial aneurysm (IA). This study aims to investigate the methylation levels of polypyrimidine tract-binding protein 1 (PTBP1) in IA, as well as its potential to predict IA. Forty-eight patients with IA and 48 age- and sex-matched healthy controls were recruited into this study. Methylation levels of CpG sites were determined via bisulfite pyrosequencing. The PTBP1 levels in the blood were determined using a real-time quantitative reverse transcription-polymerase chain reaction test. Significant differences were found between IAs and controls in CpG1 (p = 0.001), CpG2 (p < 0.001), CpG3 (p = 0.037), CpG4 (p = 0.003), CpG5 (p = 0.006), CpG6 (p = 0.02), and mean methylation (p < 0.001). The mRNA level of PTBP1 in the blood was much lower in IAs compared with controls (p = 0.002), and the PTBP1 expression was significantly associated with DNA methylation promoter levels in individuals (r = -0.73, p < 0.0001). In addition, stratification analysis comparing smokers and non-smokers revealed that tobacco smokers had significantly higher levels of DNA methylation in PTBP1 than non-smokers (p = 0.002). However, no statistical difference in PTBP1 methylation was found between ruptured and unruptured IA groups (p > 0.05). The ROC analyses of curves revealed that PTBP1 methylation may be a predictor of IA regardless of sex (both sexes, area under curve (AUC) = 0.78, p < 0.0001; male, AUC = 0.76, p = 0.002; female, AUC = 0.79, p < 0.0001). These findings suggest that long-term tobacco smoke exposure led to DNA methylation in the promoter region of the PTBP1 gene, which further decreased PTBP1 gene expression and participated in the pathogenesis of IA. The methylation of PTBP1 may be a potential predictive marker for the occurrence of IA.

Inhibition of Dectin-1 Ameliorates Neuroinflammation by Regulating Microglia/Macrophage Phenotype After Intracerebral Hemorrhage in Mice.

Polarization of microglia/macrophages toward the pro-inflammatory phenotype is an important contributor to neuroinflammation after intracerebral hemorrhage (ICH). Dectin-1 is a pattern recognition receptor that has been reported to play a key role in regulating neuroinflammation in ischemic stroke and spinal cord injury. However, the role and mechanism of action of Dectin-1 after ICH remains unclear. In this study, we investigated the effect of Dectin-1 on modulating the microglia/macrophage phenotype and neuroinflammation and the possible underlying mechanism after ICH. We found that Dectin-1 expression increased after ICH, and was mainly localized in microglia/macrophages. Neutrophil infiltration and microglia/macrophage polarization toward the pro-inflammatory phenotype increased after ICH. However, treatment with a Dectin-1 inhibitor reversed these phenomena and induced a shift the anti-inflammatory phenotype in microglia/macrophages; this resulted in alleviation of neurological dysfunction and facilitated hematoma clearance after ICH. We also found that Dectin-1 crosstalks with the downstream pro-inflammatory pathway, Card9/NF-κB, by activating spleen tyrosine kinase (Syk) both in vivo and in vitro. In conclusion, our data suggest that Dectin-1 is involved in the microglia/macrophage polarization and functional recovery after ICH, and that this mechanism, at least in part, may contribute to the involvement of the Syk/Card9/NF-kB pathway.

Association of CDKN2B-AS1 rs1333049 with Brain Diseases: A Case-control Study and a Meta-analysis.

OBJECTIVE: CDKN2B-AS1 polymorphisms were shown to associate with the risk of stroke in European. The goal of this study was to evaluate the contribution of CDKN2B-AS1 rs1333049 to the risk of hemorrhagic stroke (HS) and brain tumor (BT) in Han Chinese. METHODS: A total of 142 HSs, 115 BTs, and 494 controls were included in the current association study. The genotyping test was performed using the melting temperature shift method. RESULTS: We failed to validate the association of CDKN2B-AS1 rs1333049 with the risk of brain disease. Significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p=0.027), high-density lipoprotein cholesterol (HDL-C) (p＜0.001) and total cholesterol (TC) (p＜0.001) were found in HSs in the genotype GG/GC carriers, but not the genotype CC carriers (p＞0.05). The meta-analysis of 10 studies among 133,993 individuals concluded that rs1333049 of CDKN2B-AS1 gene was likely to increase a 16% incidence rate of cerebrovascular disease (CD) among various populations (odds ratio 1.16, 95% confidence interval 1.08-1.25; p＜0.0001, random-effect method). CONCLUSION: Our case-control study identified rs1333049 genotypes showed different association with the concentration of the LDL-C, HDL-C and TC in the HS patients. Meta-analysis supported the association between rs1333049 and CD risk in various populations, although we were unable to observe association between rs1333049 and the risk of HSs in Han Chinese.

Sex-dichotomous effects of NOS1AP promoter DNA methylation on intracranial aneurysm and brain arteriovenous malformation.

The goal of this study was to investigate the contribution of NOS1AP-promoter DNA methylation to the risk of intracranial aneurysm (IA) and brain arteriovenous malformation (BAVM) in a Han Chinese population. A total of 48 patients with IAs, 22 patients with BAVMs, and 26 control individuals were enrolled in the study. DNA methylation was tested using bisulfite pyrosequencing technology. We detected significantly higher DNA methylation levels in BAVM patients than in IA patients based on the multiple testing correction (CpG4-5 methylation: 5.86±1.04% vs. 4.37±2.64%, P=0.006). In women, CpG4-5 methylation levels were much lower in IA patients (3.64±1.97%) than in BAVM patients (6.11±1.20%, P<0.0001). However, in men, CpG1-3 methylation levels were much higher in the controls (6.92±0.78%) than in BAVM patients (5.99±0.70%, P=0.008). Additionally, there was a gender-based difference in CpG1 methylation within the controls (men vs. women: 5.75±0.50% vs. 4.99±0.53%, P=0.003) and BAVM patients (men vs. women: 4.70±0.74% vs. 5.50±0.87%, P=0.026). A subgroup analysis revealed significantly higher CpG3 methylation in patients who smoked than in those who did not (P=0.041). Our results suggested that gender modulated the interaction between NOS1AP promoter DNA methylation in IA and BAVM patients. Our results also confirmed that regular tobacco smoking was associated with increased NOS1AP methylation in humans. Additional studies with larger sample sizes are required to replicate and extend these findings.

Endoscopic endonasal transsphenoidal surgery for treating pituitary adenoma via a sub-septum mucosa approach.

A novel sub-suptum mucusa approach was used to investigate the surgical method via an endonasal sub-septum-mucosa approach to pituitary adenoma under endoscopy. In this work, we aim to ensure the quality of operation and to reduce the operation trauma and complications. By endoscopy, the nasal mucosa was incised in the nasal septum, and all mucosal flaps were retained, a sub-septum-mucosa surgical corridor was made where the endoscope was used in the mucosa cavity for operation and to remove the pituitary adenoma. 52 patients (28 women, mean age 46.76 years) underwent endoscopic endonasal transsphenoidal sub-septum-mucosa approach for treating pituitary adenoma. 46 patients (88.5%) underwent gross total removal (GTR) for the tumor; 6 patients (11.5%) went through partial tumor removal (PTR). After operation, all nasal mucosa was retained, no complications such as nasal bleeding, loss of sense of smell or cerebrospinal fluid rhinorrhea. Our results showed that treating pituitary adenoma using endonasal transsphenoidal surgeries by keeping nasal mucosa under neuroendoscopy tend to have smaller trauma. This novel method more advanced since it provides a clear operation field, a flexible transformation of operation modes and leads to less postoperative complications.

Association study of BUD13-ZNF259 gene rs964184 polymorphism and hemorrhagic stroke risk.

We aimed to evaluate the association of rs964184 of BUD13-ZNF259 gene with the risk of hemorrhagic stroke (HS). A total of 138 HS cases and 587 controls were recruited for the association of rs964184 of BUD13-ZNF259 gene with the risk of HS. Tm shift PCR was used for genotyping. We were unable to find the association of rs964184 of BUD13-ZNF259 gene with the risk of HS (P>0.05). Significant difference was found in the TG level among the three genotypes (CC: 1.51±1.02; CG: 1.68±1.10; GG: 1.90±1.11, P=0.036). The TG level showed strong correlation with rs964184 genotypes (P=0.010, correlation=0.101). Significantly higher TC, HDL-C, and LDL-C levels were observed in the case group. And no difference was found in the TG, ApoA-I, ApoB. Our case-control study supported the significant association between rs964184 genotype and the blood TG concentration, although we were unable to find association between BUD13-ZNF259 rs964184 and the risk of HS in Han Chinese.

PPARD rs2016520 polymorphism and circulating lipid levels connect with brain diseases in Han Chinese and suggest sex-dependent effects.

The PPARD polymorphisms were shown to be associated with circulating lipoprotein metabolism in various diseases. We aimed to check the contribution of PPARD rs2016520 and lipid concentration to the risk of intracerebral hemorrhages (ICH) and brain tumors (BT) in Han Chinese. A total of 864 participants were included in the case-control study. The melting temperature shift (Tm-shift) method was used for rs2016520 genotyping. Under the recessive model, PPARD rs2016520 was shown to be associated with the risk of ICH (P=0.029, odds ratio (OR)=2.72), specifically in males (P=0.045, OR=3.98). Additionally, we also found that the levels of TC and LDL-C were significantly higher in participants with brain diseases than in the controls (TC: P<0.0001; LDL-C: P<0.0001). Significantly higher HDL-C and lower ApoA-I levels were observed in the male patients with brain diseases (HDL-C: P<0.0001; ApoA-I: P=0.008), in contrast of a higher TG level in female ICH (P=0.023). Subsequent interaction analysis between PPARD rs2016520 and lipoprotein metabolism showed that the LDL-C level was positively correlated with ICH in the rs2016520-AA carriers (P<0.0001), but not in the other genotype carriers (AG or GG, P=0.300). Our results showed that PPARD rs2016520 displayed a strong relationship with ICH risk in the male Han Chinese. The TC and LDL-C levels were positively higher in the patients with brain diseases than in the controls. The levels of TG, HDL-C and ApoA-I were shown to affect brain disease in a gender-dependent model. The genotype rs2016520-AA showed significant interaction with the circulating LDL-C levels in ICH.