Osteoclasts and activated macrophages in culture were shown to generate an acidic microenvironment specifically in the attachment zone between the cell and the base of the culture dish. Measurements using pH microelectrodes revealed that osteoclasts, when firmly attached, could achieve a pH fall of about 1 unit min-1 to a limit value of pH 3.0 or less. Activated macrophages produced a slower fall of 0.5-2 pH units h-1 and a limit value of pH 3.6-3.7 was generally detected. The method of activation was relatively unimportant, but where macrophages formed clumps the pH effect was reinforced. Osteoclasts were also examined in situ in osteoporotic bone fragments in rabbit ear chambers, using a combination H+ and Ca2+ double-barrelled electrode. The pH readings reached a lower limit of 4.7 and the calcium concentration rose to a maximum of 40 mM in the erosion sites. In vivo such acid conditions would favor the direct extracellular action of secreted lysosomal proteinases in the degradation of collagen by both cell types.
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Sci Rep
December 2024
Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul, 02447, Korea.
To understand the action mechanism of probiotics against postmenopausal symptoms, we examined the effects of Lactococcus lactis P32 (P) and Bifidobacterium bifidum P45 (P), which suppressed interleukin (IL)-6 and receptor activator of nuclear factor-κB (RANK) ligand (RNAKL) expression in Gardnerella vaginalis (Gv)-stimulated macrophages, on vaginitis, osteoporosis, and depression/cognitive impairment (DC) in mice with vaginally infected Gv, ovariectomy (Ov), or Ov/Gv (oG). Oral administration of P or P decreased Gv-induced DC-like behavior and tumor necrosis factor (TNF)-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, hypothalamus, hippocampus, and colon, while Gv-suppressed bone osteoprotegerin and brain serotonin and brain-derived neurotrophic factor (BDNF) levels increased. They partially shifted vaginal and gut dysbiosis in Gv-infected mice to the gut microbiota composition in normal control mice.
View Article and Find Full Text PDFNat Commun
December 2024
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Marine cyclopianes are a family of diterpenoid with novel carbon skeleton and diverse biological activities. Herein, we report our synthetic and chemical proteomics studies of cyclopiane diterpenes which culminate in the asymmetric total synthesis of conidiogenones C, K and 12β-hydroxy conidiogenone C, and identification of Immunity-related GTPase family M protein 1 (IRGM1) as a cellular target. Our asymmetric synthesis commences from Wieland-Miescher ketone and features a sequential intramolecular Pauson-Khand reaction and gold-catalyzed Nazarov cyclization to rapidly construct the 6-5-5-5 tetracyclic skeleton.
View Article and Find Full Text PDFNPJ Regen Med
December 2024
NHC Key Laboratory of Antibody Technique, Jiangsu Province Engineering Research Center of Antibody Drug, Department of Immunology, Nanjing Medical University, Nanjing, China.
Epidural fibrosis post laminectomy is the leading cause of failed back surgery syndrome. Little is known about the role and mechanisms of adipose tissues in epidural fibrosis. Here, we found that obese patients were more likely to develop epidural fibrosis after spine surgery.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
The potential for mitigating intestinal inflammation through the gut-bone axis in the treatment of osteoporosis is significant. While various gut-derived postbiotics or bacterial metabolites have been created as dietary supplements to prevent or reverse bone loss, their efficacy and safety still need improvement. Herein, a colon-targeted drug delivery system is developed using surface engineering of polyvinyl butyrate nanoparticles by shellac resin to achieve sustained release of postbiotics butyric acid at the colorectal site.
View Article and Find Full Text PDFNat Commun
December 2024
Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3 cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.
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