Search

Oxaliplatin (L‐OHP), a third‐generation platinum‐based anti‐tumor drug, finds widespread application in the first‐line treatment of metastatic colorectal cancer. Despite its efficacy, the drug's usage is curtailed by a litany of side effects, with L‐OHP‐induced peripheral neuropathy (OIPN) being the most debilitating. This condition can be classified into varying degrees of severity. Employing serum metabolomics, a high‐sensitivity, high‐throughput technique, holds promise as a method to identify biomarkers for clinical assessment and monitoring of OIPN patients across different severity levels. In our study, we analyzed serum metabolites in patients with different OIPN levels using ultra‐performance liquid chromatography‐high resolution mass spectrometry. By employing statistical analyses and pathway enrichment studies, we aimed to identify potential biomarkers and metabolic pathways. Our findings characterized the serum metabolic profiles of patients with varying OIPN levels. Notably, pathway analysis revealed a significant correlation with lipid metabolism, amino acid metabolism, and energy metabolism. Multivariate statistical analysis and receiver operator characteristic curve evaluation pointed to anhalamine and glycochenodeoxycholic acid as potential biomarkers for OIPN C and A, which suggest that serum metabolomics may serve as a potent tool for exploring the metabolic status of patients suffering from diverse diseases and for discovering novel biomarkers. [ABSTRACT FROM AUTHOR]

Some studies have used diffusion tensor imaging (DTI) to investigate white matter development of the visual pathway in humans and animals after visual deprivation. However, the alterations in the bilateral optic tract after the transection of unilateral optic nerve have not been well explored. In this study, we attempted to investigate the structural integrity of and pathological changes to the bilateral optic tract after transection of the unilateral optic nerve in rats using DTI. Eight healthy male Sprague-Dawley (SD) rats were randomly divided into 2 groups, with 4 in each group. Group A served as a control group. Transection of the unilateral (right) optic nerve was performed in the four rats in group B at seven days after birth to establish the early monocular blind model. Four months after the operation, MnCl 2 was injected into the left eyes of all rats, and MRI examinations were performed 24 h after injection. We detect the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values of the bilateral optic tract in all rats. In a comparison of the ipsilateral optic tract of group B with group A, a significant decrease in FA (P < 0.001) and an increase in RD (P < 0.01) of the left optic tract were found in group B, while no significant difference was found in the right optic tract. In group B, the FA and RD values of the left optic tract were significantly lower (P < 0.01) and significantly higher (P < 0.05), respectively, than those of the right optic tract. Consequently, transection of the right optic nerve can lead to structural integrity damage of and pathological changes to the left optic tract in rats. Some DTI-derived parameters (such as FA and RD) may serve as biomarkers of optic tract degeneration. [ABSTRACT FROM AUTHOR]

The presence of autoantibodies is closely associated with the occurrence and development of cancer. Autoantibodies can be used as biomarkers for early breast cancer diagnosis. However, the relationship between autoantibodies and the prognosis of breast cancer patients remains elusive. This retrospective study aimed to investigate the correlation between the presence of autoantibodies and outcomes in breast cancer patients. This study included a total of 155 patients from People's Hospital of Henan University (Zhengzhou, China) who were diagnosed with breast cancer from January 2017 to December 2021. The enrolled patients' clinicopathological features were collected, and 88 patients were ultimately involved in the analysis. Univariate and multivariate Cox regression analyses were performed to search for the risk factors related to the poor prognosis of breast cancer patients. The association between the presence of autoantibodies and patients' survival was analysed using Kaplan–Meier curves. After screening, there were 38 autoantibody‐positive cases and 50 autoantibody‐negative cases. Breast cancer patients with autoantibody‐positive had a 57% lower risk of death compared with autoantibody‐negative patients. Multivariate Cox regression analysis indicated that the presence of autoantibody could be a potential prognostic predictor for breast cancer, independent of age, histological grade, pathological classification, clinical stage, and the expression levels of hormonal receptors. In addition, autoantibody‐positive breast cancer patients had longer progression‐free survival and overall survival compared with autoantibody‐negative cases. Positive autoantibody was found as an independent biomarker of better prognosis in breast cancer patients, providing a new strategy for the prognostic assessment of breast cancer patients. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to discover differential metabolites and pathways underlying infrequent gout flares (InGF) and frequent gout flares (FrGF) using metabolomics and to establish a predictive model by machine learning (ML) algorithms. Methods: Serum samples from a discovery cohort of 163 patients with InGF and 239 patients with FrGF were analyzed by mass spectrometry–based untargeted metabolomics to profile differential metabolites and explore dysregulated metabolic pathways using pathway enrichment analysis and network propagation–based algorithms. ML algorithms were performed to establish a predictive model based on selected metabolites, which was further optimized by a quantitative targeted metabolomics method and validated in an independent validation cohort with 97 participants with InGF and 139 participants with FrGF. Results: A total of 439 differential metabolites between InGF and FrGF groups were identified. Top dysregulated pathways included carbohydrates, amino acids, bile acids, and nucleotide metabolism. Subnetworks with maximum disturbances in the global metabolic networks featured cross‐talk between purine metabolism and caffeine metabolism, as well as interactions among pathways involving primary bile acid biosynthesis, taurine and hypotaurine metabolism, alanine, aspartate, and glutamate metabolism, suggesting epigenetic modifications and gut microbiome in metabolic alterations underlying InGF and FrGF. Potential metabolite biomarkers were identified using ML‐based multivariable selection and further validated by targeted metabolomics. Area under receiver operating characteristics curve for differentiating InGF and FrGF achieved 0.88 and 0.67 for the discovery and validation cohorts, respectively. Conclusion: Systematic metabolic alterations underlie InGF and FrGF, and distinct profiles are associated with differences in gout flare frequencies. Predictive modeling based on selected metabolites from metabolomics can differentiate InGF and FrGF. [ABSTRACT FROM AUTHOR]

Despite decades of research, the exact pathogenic mechanisms underlying acute mountain sickness (AMS) are still poorly understood. This fact frustrates the search for novel pharmacological prophylaxis for AMS. The prevailing view is that AMS results from an insufficient physiological response to hypoxia and that prophylaxis should aim at stimulating the response. Starting off from the opposite hypothesis that AMS may be caused by an initial excessive response to hypoxia we suggest that directly or indirectly blunting specific parts of the response might provide promising research alternatives. This reasoning is based on the observations that 1) humans, once acclimatized, can climb Mt Everest experiencing arterial partial oxygen pressures (PaO2) as low as 25 mmHg without AMS symptoms, 2) paradoxically AMS usually develops at much higher PaO2 levels, and 3) several biomarkers, suggesting initial activation of specific pathways at such PaO2, are correlated with AMS. Apart from looking for substances that stimulate certain hypoxia triggered effects, such as the ventilatory response to hypoxia, we suggest to also investigate pharmacological means aiming at blunting certain other specific hypoxia activated pathways, or stimulating their agonists, in the quest for better pharmacological prophylaxis for AMS.This article is protected by copyright. All rights reserved. [ABSTRACT FROM AUTHOR]

Highlights: [•] ADAM17 is an important factor in inflammation-associated vascular diseases. [•] ADAM17 is a direct target gene of miR-152. [•] MiR-152 inhibits the proliferation and migration of HUVECs. [•] Serum miR-152 levels are much lower in atherosclerosis patients than in normal individuals. [•] MiR-152 could be used as a diagnostic biomarker or therapeutic target in atherosclerosis. [Copyright &y& Elsevier]

Aims We investigated the usefulness of diffusion tensor tractography ( DTT) for differentiating between histological pathologies and evaluating white matter ( WM) damage resulting from brain tumors. We also sought to categorize the appearance of brain tumor-related WM tract changes. Methods A total of 18 inpatients with intracranial neoplasms were enrolled. MRI examinations were performed at 3 T using an 8-channel phased array coil. DTT was reconstruction from the raw data of diffusion tensor imaging. WM tract-based analysis of the mean diffusivity ( MD), eigenvalues (λ1, λ2, λ3), and fractional anisotropy ( FA) was performed by the manual placement of regions of interest ( ROIs) on the color-coded FA maps using DTIStudio software. The axial diffusivity ( DA, namely λ1) and the tensor shape (Cl, namely (λ1 − λ2)/3 (λ)) were also compared between groups. P values <0.05 were considered statistically significant. Results In cases of low-grade glioma ( LGG), the tracts adjacent to the tumors displayed the highest levels of invasion. Tract disruption was mainly observed in cases of high-grade glioma ( HGG). We found significant differences regarding the FA, MD, DA, and radial diffusivity between ROIs in patients with LGG or HGG. There were also significant differences in DA and tensor shape ( Cl) between patients with LGG and HGG. Conclusion Axial diffusivity and Cl may be useful early markers for differentiating between LGG and HGG. [ABSTRACT FROM AUTHOR]