Effects of low-frequency magnetic field on solubility, structural and functional properties of soy 11S globulin.

BACKGROUND: Soy 11S globulin has high thermal stability, limiting its application in the production of low-temperature gel foods. In this study, the low-frequency magnetic field (LF-MF, 5 mT) treatment (time, 30, 60, 90, and 120 min) was used to improve the solubility, conformation, physicochemical properties, surface characteristics, and gel properties of soy 11S globulin. RESULTS: Compared with the native soy 11S globulin, the sulfhydryl content, emulsifying capacity, gel strength, water-holding capacity, and absolute zeta potential values significantly increased (P < 0.05) after LF-MF treatment. The LF-MF treatment induced the unfolding of the protein structure and the fracture of disulfide bonds. The variations in solubility, foaming properties, viscosity, surface hydrophobicity, and rheological properties were closely related to the conformational changes of soy 11S globulin, with the optimum LF-MF modification time being 90 min. CONCLUSION: LF-MF treatment is an effective method to improve various functional properties of native soy 11S globulin, and this study provides a reference for the development of plant-based proteins in the food industry. © 2024 Society of Chemical Industry.

Vision transformer-based weakly supervised histopathological image analysis of primary brain tumors.

Diagnosis of primary brain tumors relies heavily on histopathology. Although various computational pathology methods have been developed for automated diagnosis of primary brain tumors, they usually require neuropathologists' annotation of region of interests or selection of image patches on whole-slide images (WSI). We developed an end-to-end Vision Transformer (ViT) - based deep learning architecture for brain tumor WSI analysis, yielding a highly interpretable deep-learning model, ViT-WSI. Based on the principle of weakly supervised machine learning, ViT-WSI accomplishes the task of major primary brain tumor type and subtype classification. Using a systematic gradient-based attribution analysis procedure, ViT-WSI can discover diagnostic histopathological features for primary brain tumors. Furthermore, we demonstrated that ViT-WSI has high predictive power of inferring the status of three diagnostic glioma molecular markers, IDH1 mutation, p53 mutation, and MGMT methylation, directly from H&E-stained histopathological images, with patient level AUC scores of 0.960, 0.874, and 0.845, respectively.

Changes in Gel Characteristics, Rheological Properties, and Water Migration of PSE Meat Myofibrillar Proteins with Different Amounts of Sodium Bicarbonate.

The changes in the gel and rheological properties and water-holding capacity of PSE meat myofibrillar proteins with different amounts of sodium bicarbonate (SC, 0−0.6/100 g) were studied. Compared to the PSE meat myofibrillar proteins with 0/100 g SC, the texture properties and cooking yield significantly increased (p < 0.05) with increasing SC; meanwhile, adding SC caused the gel color to darken. All samples had similar curves with three phases, and the storage modulus (G') values significantly increased with the increasing SC. The thermal stability of the PSE meat myofibrillar proteins was enhanced, and the G' value at 80 °C increased with the increasing SC. Because water was bound more tightly to the protein matrix, the initial relaxation times of T21 and T22 shortened, the peak ratio of P21 significantly increased (p < 0.05), and the P22 significantly decreased (p < 0.05), which implied that the mobility of the water was reduced. Overall, SC could improve the thermal stability of the PSE meat myofibrillar proteins and increase the water-holding capacity and textural properties of the cooked PSE meat myofibrillar protein gels.

RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux.

The natural product pectolinarigenin exerts anti-inflammatory activity and anti-tumor effects, and exhibits different biological functions, particularly in autophagy and cell cycle regulation. However, the antineoplastic effect of pectolinarigenin on glioblastoma (GBM) remains unclear. In the present study, we found that pectolinarigenin inhibits glioblastoma proliferation, increases autophagic flux, and induces cell cycle arrest by inhibiting ribonucleotide reductase subunit M2 (RRM2), which can be reversed by RRM2 overexpression plasmid. Additionally, pectolinarigenin promoted RRM2 protein degradation via autolysosome-dependent pathway by increasing autophagic flow. RRM2 knockdown promoted the degradation of CDK1 protein through autolysosome-dependent pathway by increasing autophagic flow, thereby inhibiting the proliferation of glioblastoma by inducing G2/M phase cell cycle arrest. Clinical data analysis revealed that RRM2 expression in glioma patients was inversely correlated with the overall survival. Collectively, pectolinarigenin promoted the degradation of CDK1 protein dependent on autolysosomal pathway through increasing autophagic flux by inhibiting RRM2, thereby inhibiting the proliferation of glioblastoma cells by inducing G2/M phase cell cycle arrest, and RRM2 may be a potential therapeutic target and a prognosis and predictive biomarker in GBM patients.

Interfering with hyaluronic acid metabolism suppresses glioma cell proliferation by regulating autophagy.

The tumor microenvironment plays an important role in tumor progression. Hyaluronic acid (HA), an important component of the extracellular matrix in the tumor microenvironment, abnormally accumulates in a variety of tumors. However, the role of abnormal HA accumulation in glioma remains unclear. The present study indicated that HA, hyaluronic acid synthase 3 (HAS3), and a receptor of HA named CD44 were expressed at high levels in human glioma tissues and negatively correlated with the prognosis of patients with glioma. Silencing HAS3 expression or blocking CD44 inhibited glioma cell proliferation in vitro and in vivo. The underlying mechanism was attributed to the inhibition of autophagy flux and maintaining glioma cell cycle arrest in G1 phase. More importantly, 4-methylumbelliferone (4-MU), a small competitive inhibitor of Uridine diphosphate (UDP) with the ability to penetrate the blood-brain barrier (BBB), also inhibited glioma cell proliferation in vitro and in vivo. Thus, approaches that interfere with HA metabolism by altering the expression of HAS3 and CD44 and the administration of 4-MU potentially represent effective strategies for glioma treatment.

The increasing expression of GPX7 related to the malignant clinical features leading to poor prognosis of glioma patients.

BACKGROUND: Glioma is the most common malignant brain tumor in adults. The standard treatment scheme of glioma is surgical resection combined alternative radio- and chemotherapy. However, the outcome of glioma patients was unsatisfied. Here, we aimed to explore the molecular and biological function characteristics of GPX7 in glioma. METHODS: The multidimensional data of glioma samples were downloaded from Chinese Glioma Genome Atlas (CGGA). RT-qPCR method was used to identify the expression status of GPX7. Kaplan-Meier curves and Cox regression analysis were used to explore the prognostic value of GPX7. Gene Set Enrichment Analysis (GSEA) was applied to investigate the GPX7-related functions in glioma. RESULTS: The results indicated that the expression of GPX7 in glioma was higher compared to that in normal brain tissue. Univariate and multivariate Cox regression analyses confirmed that the expression value of GPX7 was an independent prognostic factor in glioma. The GSEA analysis showed that GPX7 was significantly enriched in the cell cycle pathway, ECM pathway, focal adhesion pathway, and toll-like receptor pathway. CONCLUSIONS: The GPX7 was recommended as an independent risk factor for patients diagnosed with glioma for the first time and GPX7 could be potentially used as the therapy target in future. Furthermore, we attempted to explore a potential biomarker for improving the diagnosis and prognosis of patients with glioma.

The predictive role of the neutrophil-lymphocyte ratio in the prognosis of adult patients with stroke.

Our study aimed to determine the effect of the neutrophil-lymphocyte ratio on the prognosis of adult patients with acute stroke. We searched the Web of Science, PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases and selected all of the potentially eligible studies. From the included studies, we extracted characteristics such as the stroke type and acquisition time until routine blood collection and the odds ratios across studies. The 95% confidence intervals and odds ratios were pooled to calculate the effect size for the neutrophil-lymphocyte ratio in acute stroke patients. We defined poor function outcomes according to the modified Rankin Scale ≥ 3 or Glasgow Outcome Scale< 3.Thirteen studies with 4443 patients were included in our analysis, including 7 ischemic and 6 hemorrhagic stroke studies. The pooled odds ratios for poor functional outcome at 3 months with a higher neutrophil-lymphocyte ratio in acute ischemic and hemorrhagic patients were 1.689 (95% CI = 1.184-2.409, p < 0.001) and 1.125 (95% CI = 1.022-1.239, p < 0.001), respectively, and the overall pooled odds ratio for poor functional outcome following stroke was 1.257 (95% CI = 1.146-1.379, p < 0.001). At the same time, the overall combined odds ratio for death at 3 months was 1.632 (95% CI = 1.155-2.306, p < 0.001).The neutrophil-lymphocyte ratio, an easily calculated marker, plays a predictive role in the short-term outcomes of adult patients (mean age ≥ 50 years) following acute ischemic and hemorrhagic stroke.

Identification of hub genes and small-molecule compounds in medulloblastoma by integrated bioinformatic analyses.

BACKGROUND: Medulloblastoma (MB) is the most common intracranial malignant tumor in children. The genes and pathways involved in the pathogenesis of MB are relatively unknown. We aimed to identify potential biomarkers and small-molecule drugs for MB. METHODS: Gene expression profile data sets were obtained from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were identified using the Limma package in R. Functional annotation, and cell signaling pathway analysis of DEGs was carried out using DAVID and Kobas. A protein-protein interaction network was generated using STRING. Potential small-molecule drugs were identified using CMap. RESULT: We identified 104 DEGs (29 upregulated; 75 downregulated). Gene ontology analysis showed enrichment in the mitotic cell cycle, cell cycle, spindle, and DNA binding. Cell signaling pathway analysis identified cell cycle, HIF-1 signaling pathway, and phospholipase D signaling pathway as key pathways. SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were the prominent hub genes and their expression level were verified by RT-qPCR. Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB. The five hub genes may be targets for diagnosis and treatment of MB, and the small-molecule compounds are promising drugs for effective treatment of MB. CONCLUSION: In this study we obtained five hub genes of MB, SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were confirmed as hub genes. Meanwhile, Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB.

Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis.

BACKGROUND: Because of the complex mechanisms of injury, conventional surgical treatment and early blood pressure control does not significantly reduce mortality or improve patient prognosis in cases of intracerebral hemorrhage (ICH). We aimed to identify the hub genes associated with intracerebral hemorrhage, to act as therapeutic targets, and to identify potential small-molecule compounds for treating ICH. METHODS: The GSE24265 dataset, consisting of data from four perihematomal brain tissues and seven contralateral brain tissues, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs) in ICH, with a fold change (FC) value of (|log2FC|) > 2 and a P-value of <0.05 set as cut-offs. The functional annotation of DEGs was performed using Gene Ontology (GO) resources, and the cell signaling pathway analysis of DEGs was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), with a P-value of <0.05 set as the cut-off. We constructed a protein-protein interaction (PPI) network to clarify the interrelationships between the different DEGs and to select the hub genes with significant interactions. Next, the DEGs were analyzed using the CMap tool to identify small-molecule compounds with potential therapeutic effects. Finally, we verified the expression levels of the hub genes by RT-qPCR on the rat ICH model. RESULT: A total of 59 up-regulated genes and eight down-regulated genes associated with ICH were identified. The biological functions of DEGs associated with ICH are mainly involved in the inflammatory response, chemokine activity, and immune response. The KEGG analysis identified several pathways significantly associated with ICH, including but not limited to HIF-1, TNF, toll-like receptor, cytokine-cytokine receptor interaction, and chemokine molecules. A PPI network consisting of 57 nodes and 373 edges was constructed using STRING, and 10 hub genes were identified with Cytoscape software. These hub genes are closely related to secondary brain injury induced by ICH. RT-qPCR results showed that the expression of ten hub genes was significantly increased in the rat model of ICH. In addition, a CMap analysis of three small-molecule compounds revealed their therapeutic potential. CONCLUSION: In this study we obtained ten hub genes, such as IL6, TLR2, CXCL1, TIMP1, PLAUR, SERPINE1, SELE, CCL4, CCL20, and CD163, which play an important role in the pathology of ICH. At the same time, the ten hub genes obtained through PPI network analysis were verified in the rat model of ICH. In addition, we obtained three small molecule compounds that will have therapeutic effects on ICH, including Hecogenin, Lidocaine, and NU-1025.