Renal cyclooxygenase (COX) derived eicosanoids are elevated and lipoxygenase (LOX) products are reduced in the Han:SPRD-Cy rat model of polycystic kidney disease (PKD). Selective COX2 inhibition reduces kidney disease progression, but COX1 levels also are elevated in this model. Since the effect of reducing the products of both COX isoforms and the role of LOX products is not known, weanling normal and diseased Han:SPRD-cy littermates were given either low dose acetylsalicylic acid (ASA), nordihydroguaiaretic (NDGA) or no treatment for eight weeks. Renal eicosanoids were altered in the diseased compared to normal cortex, with COX products being higher and LOX products being lower. ASA reduced COX products, cyst growth and kidney water content, while NDGA reduced LOX products without altering disease progression or kidney function. Hence, a human equivalent ASA dose equal to less than one regular strength aspirin per day slowed disease progression, while further reduction of LOX products did not worsen disease progression.
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http://dx.doi.org/10.1016/j.prostaglandins.2014.10.005 | DOI Listing |
Ann Neurol
January 2025
Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA.
Objective: Approximately 20% of familial cases of amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene encoding superoxide dismutase 1 (SOD1). Epidemiological data have identified traumatic brain injury (TBI) as an exogenous risk factor for ALS; however, the mechanisms by which TBI may worsen SOD1 ALS remain largely undefined.
Methods: We sought to determine whether repetitive TBI (rTBI) accelerates disease onset and progression in the transgenic SOD1 mouse ALS model, and whether loss of the primary regulator of axonal degeneration sterile alpha and TIR motif containing 1 (Sarm1) mitigates the histological and behavioral pathophysiology.
Cancer Commun (Lond)
January 2025
Department of Respiratory and Critical Care Medicine, Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, P. R. China.
Background: The prognosis for non-small cell lung cancer (NSCLC) patients treated with standard platinum-based chemotherapy was suboptimal, with safety concerns. Following encouraging results from a preliminary phase I study, this phase II trial investigated the efficacy and safety of first-line sintilimab and anlotinib in metastatic NSCLC.
Methods: In this open-label, randomized controlled trial (NCT04124731), metastatic NSCLC without epithelial growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or proto-oncogene tyrosine-protein kinase ROS (ROS1) mutations, and previous treatments for metastatic disease were enrolled.
J Alzheimers Dis
January 2025
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: White matter hyperintensities (WMH) are prominent neuroimaging markers of cerebral small vessel disease (CSVD) linked to cognitive decline. Nevertheless, the pathophysiological mechanisms underlying WMH remain unclear.
Objective: This study aimed to assess the structural decoupling index (SDI) as a novel metric for quantifying the brain's hierarchical organization associated with WMH in cognitively normal older adults
Methods: We analyzed data from 112 cognitively normal individuals with varying WMH burdens (43 high WMH burden and 69 low WMH burden).
Mol Med Rep
March 2025
Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China.
Colorectal cancer (CRC) is one of the most common cancers worldwide. With the growing understanding of immune regulation in tumors, the complement system has been recognized as a key regulator of tumor immunity. Traditionally, the complement cascade, considered an evolutionarily conserved defense mechanism against invading pathogens, has been viewed as a crucial inhibitor of tumor progression.
View Article and Find Full Text PDFEndocr Metab Immune Disord Drug Targets
January 2025
Department of Internal Medicine, Division of Nephrology and Hypertension, Faculty of Medicine, Dr. Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia.
Chronic kidney disease (CKD) is a major complication of type 2 diabetes mellitus (T2D), which often leads to diabetic kidney disease (DKD). Traditional therapies, including renin- angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors, are effective in slowing CKD progression. However, these approaches are insufficient to comprehensively inhibit mineralocorticoid receptor (MR) overactivation in the kidneys, which remains a significant driver of inflammation, fibrosis, and oxidative stress.
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