Biomolecules & biomedicine最新文献

Heart valve diseases are a prevalent cardiovascular pathology worldwide, affecting nearly 2.5% of the population. Degenerative aortic stenosis is the most common form of heart valve disease. The treatment options include surgical or transcatheter procedures. There are two main categories of valve prostheses available: mechanical heart valves constructed from synthetic materials and bioprosthetic heart valves made from natural biomaterials. The choice of valve type depends on various factors, including the underlying medical condition, suitability for anticoagulation, valve durability, and the patient's age and preferences. Mechanical heart valves have the advantage of long-term durability. However, patients receiving mechanical implants are subjected to lifelong anticoagulation therapy with an increased risk of thromboembolism and bleeding. Natural biomaterials do not require long-term anticoagulation. However, they experience degenerative changes leading to structural valve deterioration that may require reoperation. The purpose of this article is to review the role of natural biological materials used for aortic valve replacement or repair, assess their biomedical and clinical advantages and limitations, and analyze the direction and perspectives of future development.

Preeclampsia (PE) is a pregnancy-related disease characterized by vascular endothelial cell injury. This study aimed to investigate the role of methyltransferase-like protein 14 (METTL14) in vascular endothelial cell injury in PE. The PE cell model was established by treating human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-alpha (TNF-α) in vitro. METTL14 and forkhead box protein 1 (FOXP1) were silenced, and miR-34a-5p was overexpressed in HUVECs to evaluate their effects. HUVEC viability, apoptosis, and the levels of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and endothelin-1 were measured. The N6-methyladenosine (m6A) modification of pri-miR-34a-5p was quantified. The interactions between miR-34a-5p, DiGeorge syndrome critical region 8, and m6A enrichment in miR-34a-5p were analyzed. The relationship between miR-34a-5p and FOXP1 was also verified. The results showed that the expressions of METTL14, FOXP1, and miR-34a-5p were determined. METTL14 expression was elevated in the TNF-α-induced HUVEC injury model. Silencing METTL14 improved HUVEC viability, inhibited apoptosis, and reduced endothelial inflammation. METTL14 promoted miR-34a-5p expression through m6A modification. Overexpression of miR-34a-5p or silencing of FOXP1 reversed the protective effects of METTL14 silencing on cell injury in the PE model. In conclusion, METTL14 mediated m6A modification to promote miR-34a-5p expression, leading to the inhibition of FOXP1 expression, which aggravated endothelial cell damage in the PE cell model.

This study aimed to explore the role of lncRNA MALAT1 (Long non-coding RNAs metastasis-associated lung adenocarcinoma transcript), and its underlying mechanisms in Hypopharyngeal Squamous Cell Carcinoma (HSCC). Quantitative real-time PCR (qRT-PCR) was employed to measure lncRNA MALAT1 expression in HSCC and adjacent non-cancerous tissues, along with the expression of the downstream target mitogen-activated protein kinase kinase 1 (MAP2K1). The independent prognostic significance of lncRNA MALAT1 was assessed using Cox regression analysis. Potential downstream targets of MALAT1 were identified through PRM analysis and validated using the TCGA-HNSC database, Western blotting, and immunohistochemistry. CCK-8, flow cytometry, and Transwell assays were conducted to assess the effects of the lncRNA MALAT1/MAP2K1 axis on FaDu cells. Additionally, a nude mouse xenograft model was used to confirm the role of lncRNA MALAT1/MAP2K1 in tumor growth. LncRNA MALAT1 was significantly upregulated in HSCC tissues and closely associated with poor prognosis. Bioinformatics analysis, including parallel reaction monitoring (PRM) screening and TCGA-HNSC data, identified FERMT2, CSNK2A2, and MAP2K1 as potential downstream targets of MALAT1. Validation through qPCR, Western blotting, and immunohistochemistry confirmed MAP2K1 as a downstream target. In vitro and in vivo experiments demonstrated that inhibiting lncRNA MALAT1 suppressed cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT) by downregulating MAP2K1 expression. Additionally, it induced apoptosis, affected the cell cycle, and inhibited tumor growth. Our study uniquely demonstrates that targeting MALAT1 significantly impedes HSCC progression by downregulating its novel downstream target, MAP2K1, offering new insights into potential therapeutic strategies.

Osteoradionecrosis (ORN) is a severe complication that can arise in patients with nasopharyngeal carcinoma due to the aggressive nature of chemoradiotherapy treatment. The purpose of our study was to assess the utility of the recently introduced CARWL index, which integrates the C-reactive protein-to-albumin ratio (CAR) and significant weight loss (SWL), in predicting the risk of ORN in patients with locoregionally advanced nasopharyngeal cancer (LA-NPC) undergoing concurrent chemoradiotherapy (CCRT). We conducted a retrospective cohort analysis on 304 patients with LA-NPC treated with CCRT. Patients were categorized into CARWL index groups based on CAR (cut-off: 3.0) and SWL (weight loss > 5% over the past six months): CARWL-0 (CAR < 3.0, SWL ≤ 5%), CARWL-1 (CAR < 3.0 with SWL > 5% or CAR ≥ 3.0 with SWL ≤ 5%), and CARWL-2 (CAR ≥ 3.0 and SWL > 5%). The primary endpoint was the incidence of ORN in each CARWL index group. At a median follow-up of 67.2 months, 28 patients (9.2%) developed ORN. The incidence of ORN was 2.1%, 9.4%, and 16.3% in the CARWL-0, CARWL-1, and CARWL-2 groups, respectively (P < 0.001). Multivariate analysis identified smoking status (HR: 2.58, P = 0.034), N-stage (HR: 1.96, P = 0.008), T-stage (HR: 1.84, P = 0.017), pre-CCRT tooth extraction status (HR: 5.81, P < 0.001), post-CCRT tooth extraction status (HR: 6.82, P < 0.001), mandibular V55.8 Gy (HR: 6.12, P < 0.001), and CARWL score (HR: 5.67, P = 0.002) as significant predictors of ORN. The CARWL index is a reliable predictive tool for evaluating the risk of ORN in LA-NPC patients undergoing CCRT. If further validated, its use in clinical settings could aid in the early identification of high-risk patients and enable the implementation of personalized preventive strategies.

Several studies have reported an association between the 9p21 region in the human genome and atherosclerosis. The rs1333049 polymorphism is a single nucleotide polymorphism (SNP) in CDKN2B-AS1, located in the 9p21 region. The aim of our study was to investigate the association between the rs1333049 polymorphism and advanced carotid atherosclerosis, as well as its effect on CDKN2B expression in endarterectomy sequesters. In our case-control study, we included 881 participants, divided into two groups. The case group comprised 308 participants with advanced atherosclerosis of the internal or common carotid artery (stenosis > 75 %) who underwent a revascularization procedure. The control group included 573 participants without hemodynamically significant carotid atherosclerosis. We analyzed the rs1333049 polymorphism using the StepOne real-time polymerase chain reaction (PCR) and TaqMan SNP genotyping assay. We found a statistically significant association according to the co-dominant (P=0.014, OR=3.29, 95% CI: 1.32-8.91, and P=0.015, OR=2.50, 95% CI: 1.22-5.37) and dominant (P=0.006, OR=2.74, 95% CI: 1.36-5.71) models. We performed immunohistochemical analysis of CDKN2B expression on 26 endarterectomy sequesters. The C allele of rs1333049 was associated with a lower numerical area density of CDKN2B-positive cells in atherosclerotic plaques. In conclusion, the C allele of the rs1333049 SNP is associated with an increased risk of developing advanced carotid atherosclerosis and lower CDKN2B expression in the plaques.

Neuroinflammation is associated with the development of postoperative cognitive dysfunction (POCD). Parecoxib has powerful anti-inflammatory and analgesic effects, which may reduce the occurrence of POCD. We hypothesized that parecoxib could reduce the incidence of POCD and relieve postoperative pain without increasing postoperative complications in elderly patients with gastrointestinal cancer. The study analyzed the effect of parecoxib on elderly patients undergoing elective radical resection of gastrointestinal tumors. Patients were divided into the NSAIDs group and the non-NSAIDs group according to whether parecoxib was administered. Demographic and clinical data were collected and compared. The incidence of POCD was set as the primary outcome, and postoperative pain as the secondary outcome. Among the 440 enrolled patients, the POCD incidence rates within 7 days after surgery in the NSAIDs and non-NSAIDs groups were 42.60% and 40.30%, respectively, with no statistically significant difference (P > 0.05). Patients in the NSAIDs group experienced significantly less pain on the first and second days after surgery compared to the non-NSAIDs group (P < 0.05). There were no statistically significant differences in postoperative adverse events between the two groups (P > 0.05). Parecoxib had no significant negative effect on early postoperative cognitive function, effectively alleviating early postoperative acute pain without increasing postoperative complications. The findings have implications for the broader use of parecoxib in postoperative pain management in elderly patients undergoing major surgery.

Tumor budding has been proposed as a potential prognostic marker in various cancers, but its association with survival outcomes in breast cancer (BC) remains unclear. This meta-analysis aimed to clarify the relationship between tumor budding and survival outcomes in patients with BC. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science. Cohort studies examining the association between tumor budding and overall survival (OS) and progression-free survival (PFS) in BC patients were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using a random-effects model to account for potential heterogeneity. Eleven cohort studies, including 2,828 patients, met the inclusion criteria. High tumor budding was significantly associated with poorer OS (HR = 1.89, 95% CI = 1.37-2.60, P < 0.001) and PFS (HR = 1.89, 95% CI = 1.32-2.71, P < 0.001). Subgroup analyses revealed a stronger association in studies where high tumor budding was defined as ≥ 10 buds / high-power field (HPF) compared to those with lower cutoffs. Sensitivity analyses confirmed the robustness of the findings. This meta-analysis demonstrates that high tumor budding is associated with significantly worse OS and PFS in BC patients, underscoring its prognostic significance. These findings suggest tumor budding could be a valuable marker in clinical assessments, and further research is needed to standardize its evaluation criteria in BC.

The Diabetic Foot Ulcer (DFU) is a severe complication that affects approximately 33% of diabetes patients globally, often leading to limb amputation if not detected early. This study introduces an automated approach for identifying and classifying DFU using transfer learning. DFU is typically categorized into ischemic and infection states, which are challenging to distinguish visually. We evaluate the effectiveness of pre-trained Deep Convolutional Neural Network (DCNN) models for autonomous DFU detection. Seven models are compared: EfficientNetB0, DenseNet121, ResNet101, VGG16, MobileNetV2, InceptionV3, and InceptionResNetV2. Additionally, we propose E-DFu-Net, a novel model derived from existing architectures, designed to mitigate overfitting. Experimental results demonstrate that E-DFu-Net achieves remarkable performance, with 97% accuracy in ischemia classification and 92% in infection classification. This advancement enhances current methodologies and aids practitioners in effectively detecting DFU cases.

Inflammation of the central nervous system (CNS) is a common feature of neurological disorders and infections, playing a crucial role in the development of CNS-related conditions. CNS inflammation is primarily regulated by glial cells, with astrocytes being the most abundant type in the mammalian CNS. Numerous studies have demonstrated that astrocytes, as immunocompetent cells, perform diverse and complex functions in both health and disease. Glycosylation, a critical post-translational modification of proteins, regulates numerous biological functions. The expression and activity of glycosyltransferases, the enzymes responsible for glycosylation, are closely associated with the pathogenesis of various diseases. β-1,4-GalTI, a mammalian glycosyltransferase, plays a significant role in cell-cell interactions, adhesion, and migration. Although many studies have focused on β-1,4-GalTI, few have explored its effects on astrocyte function. In this study, we constructed lentiviral vectors for both interference and overexpression of β-1,4-GalTI and discovered that β-1,4-GalTI knockdown inhibited astrocyte migration and proliferation, while its overexpression promoted these processes. Concurrently, β-1,4-GalTI knockdown reduced the expression of TNF-α, IL-1β, and IL-6, whereas overexpression enhanced the expression of these cytokines. These findings suggest that modulating β-1,4-GalTI activity can influence the molecular functions of astrocytes and provide a theoretical foundation for further research into β-1,4-GalTI as a potential therapeutic target in astrocyte-mediated inflammation.

Polyamidoamine (PAMAM) dendrimer nanoparticles are efficient drug delivery vectors with potential clinical applications in nanomedicine. However, PAMAMs can compromise heart function, and strategies to mitigate cardiotoxicity would be beneficial. In this study, we investigated whether the adjunct use of three key cardioprotective agents could prevent the cardiac injury induced by a seventh-generation cationic PAMAM dendrimer (G7). Isolated rat hearts were subjected to ischemia and reperfusion (I/R) injury in the presence or absence of G7 or the cardioprotective agents Losartan, Epidermal Growth Factor (EGF), or S-nitroso-N-acetylpenicillamine (SNAP). I/R injury significantly compromised cardiac function, in terms of left ventricular hemodynamics, contractility, and vascular dynamics, which were markedly improved (p<0.05) by the administration of Losartan, EGF, or SNAP alone, confirming their cardioprotective effects. The administration of G7 significantly worsened cardiac function recovery following I/R(p<0.05). G7-induced impairments in cardiac and vascular dynamics were significantly improved by co-administration of Losartan, EGF, or SNAP. Treatment with G7 also significantly increased cardiac enzyme levels and infarct size, both of which were markedly reduced upon co-infusion of Losartan, EGF, or SNAP (p<0.05). Thus, G7 deteriorates the recovery of cardiac function in isolated hearts subjected to I/R injury, which can be rescued by co-administration of Losartan, EGF, or SNAP. These findings enhance our understanding of the nanotoxicology of PAMAM dendrimers in the mammalian heart and suggest that the adjunct use of cardioprotective agents is an effective strategy for mitigating the cardiotoxicity of these dendrimers and potentially other drug delivery systems.