Biomolecules & biomedicine最新文献

Cervical cancer poses significant clinical challenges, particularly in advanced stages. This study explores the therapeutic potential of andrographolide (AND), a bioactive compound derived from Andrographis paniculata, in mitigating cervical cancer progression using the chick embryo chorioallantoic membrane patient-derived xenograft (CAM-PDX) model. The model was validated through hematoxylin-eosin (H&E) staining and immunohistochemistry, which confirmed its ability to accurately replicate the histological and molecular characteristics of patient-derived xenografts (PDXs), establishing its reliability for therapeutic screening. A dose of 20 mg/kg AND was selected for further evaluation based on preliminary chorioallantoic membrane (CAM) assay findings. In the CAM-PDX model, AND significantly inhibited tumor growth, primarily by reducing angiogenesis and vessel density. Immunohistochemical analysis revealed that AND downregulated key proteins associated with cancer cell proliferation and survival, including Ki67, B-cell lymphoma 2 (BCL-2), and Erythroblast transformation-specific-related gene (ERG). These results indicate that AND not only disrupts tumor angiogenesis but also induces cell cycle arrest and promotes apoptosis in cervical cancer cells. In summary, this study successfully established a reproducible CAM-PDX model for drug evaluation and highlighted the potential of AND as a promising therapeutic candidate for cervical cancer, warranting further clinical investigation.

Jianpi Yiqi Busui Prescription (JYBP), a traditional Chinese medicine formula (TCM), is used in the treatment of myasthenia gravis (MG). However, its mechanisms of action still require further clarification. In this study, an experimental autoimmune MG (EAMG) rat model was established for research. Changes in body weight, forelimb grip strength, Lennon clinical score, and antifatigue ability of EAMG model rats were recorded to evaluate the effectiveness of JYBP. Flow cytometry was utilized to count Th17, Th1, Th2, and Treg cells in lymphocytes. ELISA and RT-qPCR were used to measure acetylcholine receptor antibody (AChR-Ab) and Th17-related cytokines, including IL-17, IL-21, IL-23, TNF-α, TGF-β, IL-1β, and IL-6. Western blot and immunofluorescence staining were used to detect the expression levels of key proteins and their phosphorylated forms, such as transforming growth factor beta-activated kinase 1 (TAK1), P38 mitogen-activated protein kinase (P38 MAPK), and eukaryotic initiation factor 4E (eIF-4E). The results indicate that JYBP can increase the body weight of EAMG model rats, improve grip strength and antifatigue ability, and reduce the Lennon clinical score and AChR-Ab concentration. Mechanistic studies indicate that JYBP can inhibit the differentiation of CD4+ T cells into Th17 and Th1, promote their differentiation into Th2 and Treg, and regulate the expression of Th17-related cytokines. Further research shows that JYBP can reduce the expression of related proteins in the TAK1/P38 MAPK/eIF-4E signaling pathway. In conclusion, JYBP can alleviate the condition of EAMG model rats, positively affecting MG treatment. The inhibitory effect of JYBP on the differentiation of CD4+ T cells into Th17 may be related to the TAK1/P38 MAPK/eIF-4E signaling pathway.

ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1), a crucial enzyme for tumor-associated sialic acid modification, has been reported to positively correlate with colorectal cancer (CRC) tumorigenesis; however, the underlying mechanism remains unclear. To elucidate the protumor mechanisms of ST6GAL1, we performed transcriptomic and N-glycoproteomic analyses and in vitro assays. We found that ST6GAL1 was significantly upregulated in tumor samples than in matched normal samples by analyzing fresh clinical samples from public databases (mean mRNA expression level: tumor vs. normal samples = 0.002712:0.000966, P < 0.05, n = 22). The in vitro results revealed that ST6GAL1 overexpression promoted CRC cell proliferation, migration, and chemoresistance, which were significantly blocked by its knockdown. Transcriptomic data showed that many genes related to the four modules (proliferation/cell cycle, migration, motility, and epithelial-mesenchymal transition (EMT) were upregulated after ST6GAL1 overexpression but downregulated after ST6GAL1 knockdown. Furthermore, the N-glycoproteome data revealed that 25 substrates that were sialylated upon ST6GAL1 overexpression were related to protumor activity. Importantly, we found that knockdown of lectin galactoside-binding soluble 3-binding protein (LGALS3BP), a newly identified secreted substrate of ST6GAL1, significantly blocked the proliferation, invasion, and chemoresistance of CRC cells induced by ST6GAL1 overexpression. Treatment with sialidases (neuraminidases, NAs) also blocked the protumor activity of ST6GAL1. Thus, ST6GAL1-induced increased sialylation of substrates, such as LGALS3BP and upregulation of protumor genes promote CRC tumorigenesis and chemoresistance, which provides important perspectives and new targets for the treatment of CRC.

This study investigates the safety and underlying mechanisms of fecal microbiota transplantation (FMT) in treating radiation enteritis (RE). A rat model of RE was established with six groups: NC, RT, H-FMT, modified FMT (M-FMT), L-FMT, and BTAC. The therapeutic effects of FMT were assessed using the Disease Activity Index (DAI), histological analysis, and biochemical tests, including ink-propelling, xylitol exclusion, and enzyme-linked immunosorbent assay (ELISA). Gut microbiota alterations and fecal metabolism were analyzed via 16S rDNA sequencing and targeted metabolomics. The results demonstrated that FMT, particularly in the M-FMT group, effectively alleviated RE by reducing DAI scores, histological damage, and inflammatory markers while enhancing enzyme activity, superoxide dismutase (SOD) levels, and intestinal absorption. FMT also modulated gut microbiota composition, increasing beneficial species, such as Blautia wexlerae and Romboutsia timonensis while decreasing Enterococcus ratti. Metabolomics analysis revealed that FMT influenced niacin, nicotinamide, and starch metabolism, with notable changes in pantothenic acid and fatty acid levels. Spearman correlation analysis further indicated that these microbial shifts were associated with improved metabolic profiles. Overall, FMT mitigates RE by regulating gut microbiota and metabolites, with pantothenic acid and fatty acids emerging as potential therapeutic targets. Further research is needed to explore the underlying mechanisms in greater detail.

Children with severe β-thalassemia major (β-TM) are at high risk of developing toxoplasmosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study was to identify the neuroimaging findings of cerebral toxoplasmosis in pediatric patients with β-TM for early diagnosis and treatment of cerebral toxoplasmosis. We performed a retrospective assessment of clinical and neuroimaging data of children with severe β-TM who had cerebral toxoplasmosis after allo-HSCT. Additionally, we reviewed and summarized the literature on cerebral toxoplasmosis in patients with other underlying conditions. This case series identified three children who had severe β-TM and had subsequent cerebral toxoplasmosis after allo-HSCT. In addition, we identified 23 patients from literature who had toxoplasmosis and had underlying conditions other than β-TM. We found that the most common clinical symptom among the patients from our series and the patients from literature was fever upon presentation. We identified the typical neuroimaging findings including brain lesions with ring enhancement and eccentric/central nuclear target-like enhancement, which should facilitate early diagnosis and treatment of cerebral toxoplasmosis.

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. A 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 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 the expressions of METTL14, FOXP1, and miR-34a-5p. 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 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 FOXP1 inhibition, which aggravated endothelial cell damage in the PE cell model.

Multiple studies have been published regarding various nutritional supplements or interventions to improve chronic pain. However, many of these studies emphasized widespread pain and were not specific to the spine. Therefore, the primary objective of this scoping review was to evaluate available evidence related to nutritional supplementation or dietary strategies for spine-related pain. A comprehensive literature search was performed on October 11, 2022, and updated on May 2, 2024. Databases included: MEDLINE (PubMed), Embase, Cochrane Library, Scopus, and Web of Science. Results were limited to those published within the past 10 years, to English-language articles, and excluded animal studies. Of the 2,081 screened articles, 29 were included in the final review. Of these, 26 focused on the low back, one on the neck, and two referred to generalized "back" pain. The largest number of studies were found on vitamins D and B, specifically for low back pain. However, there were conflicting findings for both vitamins; therefore, further research is necessary before these can be confidently recommended to patients suffering from low back pain. Furthermore, this scoping review identified a lack of consistency in study design, population or sample size, and outcome measures among currently published studies with a primary focus on nutritional supplementation or dietary strategies for spine-related pain.

The management of anesthesia in elderly patients undergoing surgery presents unique challenges, particularly in mitigating stress responses and ensuring stability. Etomidate may alleviate adrenocortical and immune stress. This study aims to investigate the anesthetic effects of combined spinal-epidural anesthesia (CSEA) supplemented with etomidate during anorectal surgery in elderly patients. The medical records of 49 cases treated with CSEA and etomidate (ETO group) and 48 cases treated with CSEA alone (control group) were reviewed and analyzed. All patients received ropivacaine hydrochloride for anesthesia, with the ETO group additionally receiving an infusion of etomidate for sedation. Parameters such as arterial blood gas, visual analog scale (VAS), Ramsay sedation scale (RSS), serum cortisol and norepinephrine levels, pro-inflammatory cytokines, and lymphocyte ratios were assessed at different time points. Compared to the control group, the ETO group showed increased mean arterial pressure, decreased heart rate, and elevated arterial SpO2 30 minutes after anesthesia. The ETO group also had higher RSS scores, lower VAS scores, and reduced serum cortisol and norepinephrine levels. Additionally, decreased levels of pro-inflammatory cytokines, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-8, were observed, along with an increase in the regulatory cytokine IL-10. An increased proportion of CD4+ T cells and a higher CD4/CD8 ratio were also noted. This study demonstrates the benefits of using etomidate to mitigate adrenocortical and immune stress in elderly patients undergoing anorectal surgery.

Adipose tissue (AT) is a major metabolic organ, functioning through autocrine, paracrine, and endocrine mechanisms. This study investigated the relationship between adipokine levels and blood cell indices, particularly platelets, in individuals with COVID-19. Another aim was to enhance the understanding of AT's endocrine function during dynamic pathological changes, such as acute viral infections like COVID-19. The study was conducted as a cross-sectional analysis at the University Clinical Center of Vojvodina in 2021 and 2022, including 76 consecutive SARS-CoV-2-positive patients of both sexes. Study parameters were determined from peripheral venous blood samples routinely collected upon hospital admission. The results showed that leptin levels were significantly positively correlated with body mass index (BMI) (ρ = 0.421, P < 0.001) and body fat mass (BFM) (ρ = 0.547, P < 0.001). Simultaneously, a significant negative correlation was observed between adiponectin levels and BMI (ρ = -0.430, P < 0.001). Additionally, a significant positive correlation was found between leptin levels and mean platelet volume (MPV) (ρ = 0.307, P < 0.05), platelet distribution width (PDW) (ρ = 0.325, P < 0.05), and platelet-large cell ratio (P-LCR) (ρ = 0.305, P < 0.05). Leptin's impact on platelet indices was confirmed in both simple and multiple linear regression models, where leptin exhibited a slightly higher beta coefficient than BMI. In contrast, adiponectin levels were negatively correlated with hematocrit (HCT) (ρ = -0.329, P < 0.05). These findings may provide further insight into the previously suspected role of AT in the complex cascade of COVID-19 pathogenesis and platelet activation.

Glioma is one of the most prevalent primary intracranial tumors, and biomarker testing offers a non-invasive modality with high diagnostic efficiency. The aim of this meta-analysis is to evaluate the diagnostic effectiveness of exosomes as biomarkers for glioma. We included 16 studies on exosomes as biomarkers for gliomas. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for 25 biomarkers across these 16 studies were as follows: 82% (95% CI: 0.77-0.86), 91% (95% CI: 0.86-0.94), 9.10 (95% CI: 5.64-14.68), 0.20 (95% CI: 0.16-0.25), 45.94 (95% CI: 25.40-83.09), and 0.92 (95% CI: 0.89-0.94), respectively. Meta-regression indicated that biomarker analysis, biomarker type, and sample size may be sources of heterogeneity. Subgroup analysis suggested that ultracentrifugation (UC) was a better method for extracting exosomes. miRNA and other RNA groups (sncRNA, lncRNA, circRNA) provided higher SEN (0.88 vs. 0.84 vs. 0.78) compared to proteins. This study demonstrates the superior diagnostic efficacy of exosomes as biomarkers for gliomas, with high accuracy in diagnosing gliomas.