Fumonisin B (FB) mycotoxin was intraperitoneally (IP) administered at the No Observed Adverse Effect Level (NOAEL = 0.2 mg/kg BW/day as IP equivalent, "L") and 5-times above ("H") to male rats, in a controlled ("C"), 5-day study (n = 10/group, total n = 30). BW (bodyweight) of H rats decreased after day 4, kidney weight after 5 days. Renal histology revealed tubular epithelial desquamation, tubular dilatation, nuclear swelling, pale chromatin, cell vacuolation and casual karyopycnosis (H). Lipidomic analysis was performed with liquid chromatography - time-of-flight mass spectrometry (LC-TOF). Renal sphinganine (Sa) concentration increased 500 (L) to 1000-fold (H) and Sa-1-P to over 200 and 350-fold, respectively), with FB dose-dependence. Renal triacyclglycerols, diacylglycerols, ceramides and sphingomyelins were depleted, while cholesterol and cholesterol ester concentrations increased. Spearman correlation of free sphingoid bases (Sa, Sa-1-P, sphingosine (So) and So-1-P) was positive with histopathological damage severity, sphingomyelins and ceramides provided negative relationship (-0.78 and -0.8, resp.). Two-way cluster analysis and sparse partial least squares discriminant analysis (sPLS-DA) was used for experimental group classification. Fully effective group separation was achieved for ceramides, sphingomyelins and phosphatidyl-cholines, highlighting molecular species of possible diagnostic value. Lipidomic results highlight possible re-consideration of the NOAEL.
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http://dx.doi.org/10.1016/j.fct.2022.113333 | DOI Listing |
Rheumatol Ther
January 2025
Biosplice Therapeutics, Inc., 9360 Towne Centre Dr, San Diego, CA, 92121, USA.
Introduction: Lorecivivint (LOR), a CDC-like kinase/dual-specificity tyrosine kinase (CLK/DYRK) inhibitor thought to modulate inflammatory and Wnt pathways, is being developed as a potential intra-articular knee osteoarthritis (OA) treatment. The objective of this trial was to evaluate long-term safety of LOR within an observational extension of two phase 2 trials.
Methods: This 60-month, observational extension study (NCT02951026) of a 12-month phase 2a trial (NCT02536833) and 6-month phase 2b trial (NCT03122860) was administratively closed after 36 months as data inferences became limited.
CNS Drugs
January 2025
Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Background: Early neurological deterioration (END) is associated with a poor prognosis in acute ischemic stroke (AIS). Effectively lowering low-density lipoprotein cholesterol (LDL-C) can improve the stability of atherosclerotic plaque and reduce post-stroke inflammation, which may be an effective means to lower the incidence of END. The objective of this study was to determine the preventive effects of evolocumab on END in patients with non-cardiogenic AIS.
View Article and Find Full Text PDFRadiat Oncol
January 2025
Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Kanagawa, Japan.
Introduction: Stage IV non-small cell lung carcinoma (NSCLC) with oligometastases is potentially curable by radical treatment. This study aimed to evaluate the efficacy and safety of chemoradiotherapy (CRT) for thoracic disease, including the primary lesion and lymph node metastases, combined with local consolidative therapy (LCT) for oligometastases.
Methods: This was a multicenter Phase II trial for patients with Stage IV NSCLC with oligometastases for whom CRT for thoracic disease was feasible.
J Cardiothorac Surg
January 2025
Department of Intensive Care Medicine, Hangzhou TCM, Hospital Affiliated to Zhejiang Chinese Medicine University, No.1630, Huanding Road, Shangcheng District, Hangzhou, 310044, China.
Background & Objective: Timely intervention for Acute coronary syndrome (ACS) could effectively reduce the mortality rate of ACS patients. This study aimed to investigate the clinical significance of miR-30c-5p for ACS and to provide a convenient biomarker for diagnosing of ACS.
Methods: Baseline information was collected from a total of 173 subjects (98 ACS subjects and 65 healthy subjects).
BMJ Open
January 2025
Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Introduction: Optimising the micronutrient status of women before and during reproduction confers benefits to them and their offspring. Antenatal multiple micronutrient supplements (MMS), given as a daily tablet with nutrients at ~1 recommended dietary allowance (RDA) or adequate intake (AI) reduces adverse birth outcomes. However, at this dosage, MMS may not fully address micronutrient deficiencies in settings with chronically inadequate diets and infection.
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