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Exosomes, key components of the tumour microenvironment, can mediate intercellular communication through the delivery of various signalling molecules, including microribonucleic acids (miRNAs), and ultimately participate in regulating the process of tumour development. In this study, we aimed to investigate the reason and mechanism by which exosomal miRNAs derived from gastric cancer cells affect carcinogenesis and metastasis. Among these miRNAs, microRNA-128-3p (miR-128-3p) was highly expressed in serum exosomes isolated from gastric cancer patients, as confirmed by high-throughput sequencing and subsequent experiments. Coculture of gastric cancer-derived exosomes overexpressing miR-128-3p with human umbilical vein endothelial cells (HUVECs) significantly enhanced HUVEC proliferation, migratio n and angiogenesis. Bioinformatics analysis suggested SASH1 as the target gene of miR-128-3p. The dual luciferase assay and Western blot analysis results confirmed that miR-128-3p directly targeted SASH1 to inhibit its expression in HUVECs. Therefore, this study provides preliminary evidence that gastric cancer-derived exosomal miR-128-3p promotes tumour angiogenesis by targeting SASH1, reveals the potential diagnostic and therapeutic value of cancer-derived exosomal miR-128-3p, and provides new insights into the novel molecular mechanisms regulating metastasis. This study provides further information for understanding the role of gastric cancer-derived exosomal miR-128-3p in cancer progression and to discover new therapeutic targets. [ABSTRACT FROM AUTHOR]

Background and purpose: Serum-thymidine kinase 1 (S-TK1) and macrophage inflammatory protein-1α (MIP-1α) are serum tumor markers, and their expression levels in serum are closely associated with disease severity and prognosis of thyroid cancer patient. Therefore, this article aimed to explore clinical value of the expression levels of S-TK1 and MIP-1α in the evaluation of postoperative radioactive 131 I treatment for thyroid carcinoma. Methods: A total of 158 preoperative patients with thyroid cancer and 128 healthy subjects were selected as study group and control group. Serum MIP-1α and S-TK1 levels were compared between the two groups. All patients with malignancy were divided into groups: the successful group (58 cases) and the unsuccessful group (40 cases), the metastasis positive group (20 cases) and the metastasis negative group (78 cases). The levels of serum MIP-1α and S-TK1 were compared, and immunohistochemical staining technique was used to detect the expressions of MIP-1α and S-TK1 in the thyroid tissues of different groups of patients. The factors affecting postoperative outcome were analyzed by single factor and logistic regression analysis. Results: The expression levels of MIP-1α and S-TK1 were significantly higher in the thyroid malignant group than in the benign group and the healthy control group (P ＜ 0.05). Compared with those who were unsuccessful, the serum expression levels of MIP-1α and S-TK1 in the successful group before the 131 I treatment were significantly reduced (P ＜ 0.05). The serum levels of MIP-1α and S-TK1 were significantly higher in the metastasis positive group than in the metastatic negative group (P ＜ 0.05). Immunohistochemical staining results showed that the positive expression rate of MIP-1α protein in the thyroid tissues of the malignant group (70.41%) was significantly higher than in the benign group (18.33%), and the positive expression rate of S-TK1 protein was significantly higher in the malignant group (68.37%) than in the benign group (15.00%) (P ＜ 0.05). Univariate analysis showed that maximum diameter, body mass index (BMI), thyroid-stimulating hormone (TSH), the expression levels of MIP- 1α and S-TK1 had significant effects on the first postoperative 131 I clearing effect in patients with thyroid cancer (P ＜ 0.05). Logistic regression analysis showed the largest diameter of the lesion and the expression levels of TSH, MIP-1α and S-TK1 were independent factors influencing the efficacy of the first postoperative clearing effect (P ＜ 0.05). Conclusion: The expression levels of MIP-1α and S-TK1 are significantly higher in thyroid cancer patients than in healthy people. The expression levels of MIP-1α and S-TK1 are significantly increased after metastasis in thyroid cancer patients, and the maximum diameter of lesion, TSH and the expression levels of MIP-1α and S-TK1 are independent factors affecting the efficacy of the first postoperative clearing effect (P ＜ 0.05).

Background and purpose: Serum-thymidine kinase 1 (S-TK1) and macrophage inflammatory protein-1α (MIP-1α) are serum tumor markers, and their expression levels in serum are closely associated with disease severity and prognosis of thyroid cancer patient. Therefore, this article aimed to explore clinical value of the expression levels of S-TK1 and MIP-1α in the evaluation of postoperative radioactive 131I treatment for thyroid carcinoma. Methods: A total of 158 preoperative patients with thyroid cancer and 128 healthy subjects were selected as study group and control group. Serum MIP-1α and S-TK1 levels were compared between the two groups. All patients with malignancy were divided into groups: the successful group (58 cases) and the unsuccessful group (40 cases), the metastasis positive group (20 cases) and the metastasis negative group (78 cases). The levels of serum MIP-1α and S-TK1 were compared, and immunohistochemical staining technique was used to detect the expressions of MIP-1α and S-TK1 in the thyroid tissues of different groups of patients. The factors affecting postoperative outcome were analyzed by single factor and logistic regression analysis. Results: The expression levels of MIP-1α and S-TK1 were significantly higher in the thyroid malignant group than in the benign group and the healthy control group (P<0.05). Compared with those who were unsuccessful, the serum expression levels of MIP-1α and S-TK1 in the successful group before the 131I treatment were significantly reduced (P<0.05). The serum levels of MIP-1α and S-TK1 were significantly higher in the metastasis positive group than in the metastatic negative group (P<0.05). Immunohistochemical staining results showed that the positive expression rate of MIP-1α protein in the thyroid tissues of the malignant group (70.41%) was significantly higher than in the benign group (18.33%), and the positive expression rate of S-TK1 protein was significantly higher in the malignant group (68.37%) than in the benign group (15.00%) (P<0.05). Univariate analysis showed that maximum diameter, body mass index (BMI), thyroid-stimulating hormone (TSH), the expression levels of MIP-1α and S-TK1 had significant effects on the first postoperative 131I clearing effect in patients with thyroid cancer (P<0.05). Logistic regression analysis showed the largest diameter of the lesion and the expression levels of TSH, MIP-1α and S-TK1 were independent factors influencing the efficacy of the first postoperative clearing effect (P<0.05). Conclusion: The expression levels of MIP-1α and S-TK1 are significantly higher in thyroid cancer patients than in healthy people. The expression levels of MIP-1α and S-TK1 are significantly increased after metastasis in thyroid cancer patients, and the maximum diameter of lesion, TSH and the expression levels of MIP-1α and S-TK1 are independent factors affecting the efficacy of the first postoperative clearing effect (P<0.05). [ABSTRACT FROM AUTHOR]

Background and purpose: Serum-thymidine kinase 1 (S-TK1) and macrophage inflammatory protein-1α (MIP-1α) are serum tumor markers, and their expression levels in serum are closely associated with disease severity and prognosis of thyroid cancer patient. Therefore, this article aimed to explore clinical value of the expression levels of S-TK1 and MIP-1α in the evaluation of postoperative radioactive 131I treatment for thyroid carcinoma. Methods: A total of 158 preoperative patients with thyroid cancer and 128 healthy subjects were selected as study group and control group. Serum MIP-1α and S-TK1 levels were compared between the two groups. All patients with malignancy were divided into groups: the successful group (58 cases) and the unsuccessful group (40 cases), the metastasis positive group (20 cases) and the metastasis negative group (78 cases). The levels of serum MIP-1α and S-TK1 were compared, and immunohistochemical staining technique was used to detect the expressions of MIP-1α and S-TK1 in the thyroid tissues of different groups of patients. The factors affecting postoperative outcome were analyzed by single factor and logistic regression analysis. Results: The expression levels of MIP-1α and S-TK1 were significantly higher in the thyroid malignant group than in the benign group and the healthy control group (P<0.05). Compared with those who were unsuccessful, the serum expression levels of MIP-1α and S-TK1 in the successful group before the 131I treatment were significantly reduced (P<0.05). The serum levels of MIP-1α and S-TK1 were significantly higher in the metastasis positive group than in the metastatic negative group (P<0.05). Immunohistochemical staining results showed that the positive expression rate of MIP-1α protein in the thyroid tissues of the malignant group (70.41%) was significantly higher than in the benign group (18.33%), and the positive expression rate of S-TK1 protein was significantly higher in the malignant group (68.37%) than in the benign group (15.00%) (P<0.05). Univariate analysis showed that maximum diameter, body mass index (BMI), thyroid-stimulating hormone (TSH), the expression levels of MIP-1α and S-TK1 had significant effects on the first postoperative 131I clearing effect in patients with thyroid cancer (P<0.05). Logistic regression analysis showed the largest diameter of the lesion and the expression levels of TSH, MIP-1α and S-TK1 were independent factors influencing the efficacy of the first postoperative clearing effect (P<0.05). Conclusion: The expression levels of MIP-1α and S-TK1 are significantly higher in thyroid cancer patients than in healthy people. The expression levels of MIP-1α and S-TK1 are significantly increased after metastasis in thyroid cancer patients, and the maximum diameter of lesion, TSH and the expression levels of MIP-1α and S-TK1 are independent factors affecting the efficacy of the first postoperative clearing effect (P<0.05). [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to build alternative indices weighing using a measure of fundamental value rather than debt size. The official bond indices built to reflect general price trends are market weighted, meaning that the bonds are weighted by their debt size. The more indebted, the more weight in the index, which mechanically increments the investment risks that are inherent. Those market indices are shown to be return-to-risk inefficient in recent studies compared to indices with alternative weighting schemes. The authors contribute to this growing literature, which mostly focuses on equities, by testing on bonds. Design/methodology/approach – The authors build alternative indices weighing using a measure of fundamental value rather than debt size. The authors have done this for sovereign bonds using gross domestic product (GDP) figures and for corporates taking sales revenues. Findings – The authors find in empirical tests that the fundamental indices build tend to outperform the market-weighted indices. Originality/value – This article builds on two articles by Arnott et al. (2005, 2010), in the Financial Analysts Journal and Journal of Portfolio Management, respectively, and adds value in the sense that – it takes an appreciation-free fundamental measure, – tests on the European as opposed to the US bond markets. [ABSTRACT FROM AUTHOR]

Background: Targeting ferroptosis is an effective approach to mitigate hepatic fibrosis, yet no reports exist on the ferroptosis signature in liver fibrosis. This study aimed to explore ferroptosis characteristics in this disease., Methods: RNAseq data from GSE6764, GSE188604 and Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) were downloaded. Multiple machine learning methods, including Weighted Gene Co-expression Network Analysis (WGCNA), Random Forest (RF) and Support Vector Machine (SVM), were used to identify core genes in liver fibrosis and ferroptosis. WGCNA can pinpoint modules linked to clinical traits, aiding in discovering diagnostic and progression molecules in complex diseases. RF and SVM are often utilized for WGCNA validation to boost result accuracy. Carbon tetrachloride (CCl4) was used to establish a mouse liver fibrosis model to validate core gene expression, which was also assessed in test and validation GEO datasets. Finally, the diagnostic role of the core genes in liver fibrosis and hepatocellular carcinoma (HCC) was also investigated using ROC analysis., Results: Multiple machine learning methods screened nine core genes, including IL1B, GSTZ1, LIFR, SLC25A37, PTGS2, MT1G, HSPB1, ESR1, and PHGDH. In vivo experimental validation, RT-PCR showed ESR1 and GSTZ1 were significantly under-expressed in the liver fibrosis group compared to the normal group. Simultaneously, in GSE6764 and GSE188604, ESR1 and GSTZ1 were also identified as protective genes for liver fibrosis. More in-depth research found that ESR1 and GSTZ1 exhibited a good diagnostic performance both in liver fibrosis and HCC, suggesting that a persistent decrease in ESR1 and GSTZ1 in patients might signal the progression from hepatic fibrosis to HCC., Conclusion: The present study is the first to report the ferroptosis signature in liver fibrosis and identifies two novel biomarkers, ESR1 and GSTZ1, providing new insights for the diagnosis and treatment of liver fibrosis in the future., Competing Interests: This research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Luo et al.)

Objective: The study endeavors to elucidate AE signals associated with zanubrutinib data from the WHO-VigiAccess and FAERS databases. The aim is to furnish robust scientific evidence to inform clinical practice and regulatory decisions., Methods: We meticulously extracted all AE breports tied to zanubrutinib from the both databases, encompassing the period from the drug's market introduction until 30 April 2024. Retrospective quantitative analysis employing ROR, PRR, and BCPNN methodologies were utilized to analysis., Results: The investigation unveiled 1,304 reports from WHO-VigiAccess and 1,141 reports from FAERS related to zanubrutinib. Among the top 30 reported PTs in both databases, those not recorded in the drug label included pyrexia, dizziness, and death. In the FAERS database, signals for zanubrutinib were detected across 19 SOCs. Systems not covered in the drug label included reproductive system and breast disorders, metabolism and nutrition disorders, ear and labyrinth disorders, among others. Unmentioned signals included intestinal perforation, onychoclasis, night sweats, etc., Conclusion: This study confirms common AEs of zanubrutinib and identifies new ones, highlighting the need for careful monitoring and personalized treatment. It also emphasizes the importance of ongoing drug safety surveillance and patient management to maximize therapeutic benefits and minimize risks.

Background: This study aimed to investigate the real-world profile of adverse events (AEs) associated with gepant medications in the clinical treatment of migraines by analyzing data collected from the VigiAccess database and the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. As novel migraine therapies, gepants act by targeting the calcitonin gene-related peptide (CGRP) pathway, demonstrating effective control of migraine attacks and good tolerability. Nonetheless, comprehensive real-world studies on the safety of gepants are still lacking, particularly regarding their safety in large populations, long-term use, and potential adverse reactions in specific groups, which necessitates further empirical research. Leveraging these two international adverse event reporting system databases, we systematically gathered and analyzed reports of AEs related to gepant medications, such as rimegepant. Our focus encompasses but is not limited to severe, new, and rare adverse reactions induced by the drugs, as well as safety issues pertaining to the gastrointestinal, cardiovascular, hepatic, and renal systems. Through descriptive statistical analyses, we assessed the incidence and characteristics of AEs, compared AEs among gepants, and uncovered previously unknown AE information, all with the goal of providing a reference for the selection of clinical treatment regimens and AE monitoring., Methods: By extracting all AE reports concerning "rimegepant", "atogepant", and "ubrogepant" from the VigiAccess and FAERS database since its establishment up to 31 March 2024, a retrospective quantitative analysis was conducted. The reporting odds ratio (ROR) method were used to compare AEs among the three gepants., Results: In the VigiAccess and FAERS databases, 23542 AE reports in total, respectively, were identified as being related to gepant medications. Among gastrointestinal system AEs, rimegepant had the greatest proportion and greatest signal strength; nausea was most severe and had the strongest signal in rimegepant AEs, whereas constipation was most prominent and had the strongest signal in atogepant AEs. In skin and subcutaneous tissue disorders, rash and pruritus were more frequently observed with rimegepant, followed by ubrogepant. Alopecia emerged as a novel AE, being more severe in rimegepant and secondarily in atogepant. Regarding cardiac disorders, the three gepants showed comparable rates of cardiac AEs, yet rimegepant exhibited the strongest AE signal. In musculoskeletal and connective tissue AEs, ubrogepant presented the most positive signals for skeletal muscle AEs. Furthermore, among the rare blood and lymphatic system disorder AEs, rimegepant had the highest number of reports of Raynaud's phenomenon and the strongest signal. The study also revealed that while reports of AEs involving liver diseases were scarce across the three gepants, severe AEs were detected in clinical trials, highlighting the need for continued, enhanced monitoring of liver system AEs through large-scale datasets., Conclusion: Gepant medications exhibit similarities and differences in their safety profiles. Analysis of the two databases indicated the presence of AEs across various systems, including gastrointestinal disorders, skin and subcutaneous tissue diseases, musculoskeletal and connective tissue disorders, organ-specific effects, and liver diseases. However, each drug displays distinct incidences and signal intensities for these AEs. Additionally, the study revealed a rare AE in the form of Raynaud's phenomenon. These findings suggest that during clinical use, individualized medication selection and AE monitoring should be based on the patient's physiological condition and specific characteristics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liang, Liao, Wu, Huang, Liang and Li.)

The conformation of proteins is closely related to their biological functions, and it is affected by many factors, including the type of cations in solution. However, it is difficult to detect the conformational changes of a protein in situ . As a single-molecule sensing technology, nanopores can convert molecular structural information into analyzable current signals within a reasonable time range. Herein, we detect and analyze the effects of two different types of monovalent cations (Na + and Li + ) on a model protein bovine serum albumin (BSA) conformation using SiN x nanopores with different diameters. The quantitative analysis results show that the excluded volume of BSA in LiCl salt solutions is larger than the value in NaCl solution, indicating that Li + is more prone to unfolding the proteins and making them unstable. This study demonstrated that nanopores enable the in situ detection of the structure of proteins at the single-molecule level and provide a new approach for the quantitative analysis of proteins.