Three strains of mice bearing the autosomal recessive lpr gene (MRL, C57BL/6, and C3H) that had spontaneously developed a lupus-like disease were studied sequentially for functional natural killer (NK) and natural cytotoxic (NC) cell activity. Natural killing was impaired in spleen and bone marrow cells from all the lpr strains, as well as from the congenic strain MRL--+/+, which develops a late onset lupus-like disease. The NK cell activity was found to be depleted as early as 2 months of age in all lpr strains, and decreased further with age. NK activity was augmentable by Poly I:C and interleukin 2 (IL-2), suggesting that the residual cells can respond to NK modulators. In contrast with NK cell activity, NC activity was not decreased in lpr mice but could be augmented by IL-3-rich supernatants. The spontaneous decrease in NK cell activity was associated with an increased autologous plaque-forming cell (APFC) response to bromelin-treated mouse red blood cells, which is produced primarily by B cells possessing the Ly-1 phenotype (Lyt-1+ B). When NK cell activity was increased by exogenous administration of Poly I:C, the APFC response diminished. Treatment of spleen cells with anti-asialo GM1 prior to Poly I:C treatment resulted in a decreased NK response but increased both APFC and Lyt-1+ B cells. The possible regulation of autoreactivity by NK cells is discussed.
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http://dx.doi.org/10.1111/j.1365-3083.1986.tb03073.x | DOI Listing |
IUBMB Life
January 2025
Precision Medicine Laboratory, School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China.
Triple-negative breast cancer (TNBC) remains a significant global health challenge, emphasizing the need for precise identification of patients with specific therapeutic targets and those at high risk of metastasis. This study aimed to identify novel therapeutic targets for personalized treatment of TNBC patients by elucidating their roles in cell cycle regulation. Using weighted gene co-expression network analysis (WGCNA), we identified 83 hub genes by integrating gene expression profiles with clinical pathological grades.
View Article and Find Full Text PDFPharmacol Res Perspect
February 2025
Department of Pharmaceutical Health Care and Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Doxorubicin (DOXO) has long been used clinically and remains a key drug in cancer therapy. DOXO-induced cardiomyopathy (DICM) is a chronic and fatal complication that severely limits the use of DOXO. However, there are very few therapeutic agents for DICM, and there is an urgent need to identify those that can be used for a larger number of patients.
View Article and Find Full Text PDFLiver Int
February 2025
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Background And Aims: Maternal obesity increases the risk of the paediatric form of metabolic dysfunction-associated steatotic liver disease (MASLD), affecting up to 30% of youth, but the developmental origins remain poorly understood.
Methods: Using a Japanese macaque model, we investigated the impact of maternal Western-style diet (mWSD) or chow diet followed by postweaning WSD (pwWSD) or chow diet focusing on bile acid (BA) homeostasis and hepatic fibrosis in livers from third-trimester fetuses and 3-year-old juvenile offspring.
Results: Juveniles exposed to mWSD had increased hepatic collagen I/III content and stellate cell activation in portal regions.
IUBMB Life
January 2025
Department of Reproductive Medical Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Abnormality of granulosa cells (GCs) is the critical cause of follicular atresia in premature ovarian failure (POF). RIPK3 is highly expressed in GCs derived from atretic follicles. We focus on uncovering how RIPK3 contributes to ovarian GC senescence.
View Article and Find Full Text PDFHead Neck
January 2025
Department of Pathology, All India Institute of Medical Sciences, Rishikesh, India.
Background: To correlate between immunohistochemical expression of tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and natural killer (NK) cells with the AJCC 8th edition TNM staging system and other disease-modifying clinico-pathological variables.
Methods: The representative histology sections of tumor invasive margin (IM) and tumor core (TC) were selected according to the International Immuno-Oncology Biomarker Working Group and were subjected to immunohistochemistry with antibodies for TILs (CD3, CD8, FOXP3), NK Cells (CD57), TAMs (CD68, CD163) and pan-leukocyte marker (CD45). Histo-immuno-density-intensity (HIDI) scoring was calculated as a product of the proportion and intensity of staining.
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