Current Issue : October-December Volume : 2026 Issue Number : 4 Articles : 5 Articles
Background: Estrogen deficiency and glucocorticoid exposure are major contributors to osteoporosis. Although menaquinone-7 (MK-7) exhibits osteoprotective effects, whether low-dose supplementation is comparable to high-dose treatment remains unclear. Methods: Female Sprague–Dawley rats were assigned to sham control (SC), ovariectomy plus dexamethasone (OVX+Dex), and OVX+Dex treated with low-dose MK-7 (100 μg/kg) or high-dose MK-7 (20 mg/kg). Bone microarchitecture, histopathology, and serum bone turnover markers were evaluated. Results: OVX+Dex induced marked deterioration of trabecular bone microarchitecture, characterized by reduced bone volume and structural disruption. These changes were accompanied by increased osteoclast activity (cathepsin K), decreased osteogenic and extracellular matrix–related markers (cbfa-1, osteonectin, and biglycan), and downregulation of osteoprotegerin, indicating a pronounced imbalance in bone remodeling. Serum analysis further revealed reduced estradiol levels and alterations in circulating bone turnover markers, consistent with a dysregulated highturnover state. Both low- and high-dose MK-7 significantly improved bone microarchitecture, restored remodeling-related protein expression, and partially normalized serum calcium- regulating hormones and bone turnover markers (all p < 0.05), with no significant differences observed between doses. Conclusions: MK-7 attenuates osteoporosis by restoring the balance between bone resorption and formation. Notably, low-dose MK-7 provides protective effects comparable to high-dose treatment, supporting its potential clinical utility....
Hypoxia during the postnatal period represents a significant risk factor for renal injury in neonates, yet the molecular mechanisms linking oxygen deprivation to kidney damage remain unclear. In this study, we explored whether ferroptosis serves as a key mediator in hypoxia-induced acute kidney injury (AKI). Using a neonatal rat model, we demonstrated that hypoxic exposure disrupts iron homeostasis, leading to iron accumulation and excessive lipid peroxidation in renal tissues. These alterations were associated with marked tubular injury, glomerular damage, and progressive fibrotic remodeling. Importantly, reoxygenation attenuated ferroptosis-related signaling pathways and improved renal structural and functional outcomes, although incomplete recovery was observed in fibrotic changes. Our findings suggest that ferroptosis is not only involved in the initiation of hypoxia-induced renal injury but may also contribute to its progression toward chronic kidney pathology. Targeting ferroptosis and iron metabolism may therefore represent a promising strategy for preventing or treating neonatal hypoxia-related AKI....
Substances released by cardiomyocytes after myocardial infarction (MI) lead to inflammasome assembly. Heart failure (HF) is associated with skeletal muscle inflammation. Methotrexate (MTX) reduces cardiovascular outcomes in chronic inflammation patients. Lipid core nanoparticle-associated MTX (MTX-LDE) attenuated cardiac remodeling in MI rats. We investigated the effects of early MTX-LDE administration on cardiac remodeling and inflammasomes in soleus muscle of MI rats. Wistar rats were separated into Sham, MI, and MI-MTX groups. MTX was initiated 24 h after MI at 1 mg/kg/week intraperitoneally for 10 weeks. Soleus protein expression of NLRP1, NLRP3, NLRC4, ASC, procaspase-1, Caspase-1, pro-IL-1β, and IL-1β was quantified by Western blotting; Nlrp1a, Nlrp3, Nlrc4, Pycard (Asc), Casp1, and Il1b gene expression was assessed by qPCR; and statistical analysis used Student’s t test and ANOVA. Rats with infarction size > 35% total left ventricle (LV) area were included in the study; infarction size did not differ between groups. Echocardiogram showed infarcted groups with LV dilation and dysfunction. Diastolic function was worse in MI-MTX than MI. NLRP1 and NLRC4 protein expression was lower in MI-MTX than Sham. Expression of other proteins and gene expression did not differ between groups. Early MTX-LDE administration reduces NLRP1 and NLRC4 protein expression in soleus muscle without improving cardiac remodeling in rats....
Background/Objectives: Radiotherapy is a cornerstone of head and neck cancer treatment, but it can adversely affect periodontal tissues by impairing vascularity, cellularity, and healing capacity. The present study aimed to histologically and immunohistochemically evaluate radiotherapy-induced changes in periodontal tissues in a rat model of experimental periodontitis, with particular focus on periodontal ligament width (PerioW) and the RANK/RANKL/OPG axis at different healing stages. Methods: Seventy-two male Sprague–Dawley rats were allocated to three groups: irradiation only (Rt), ligature-induced periodontitis only (Pt), and ligature-induced periodontitis followed by irradiation (PtRt). Experimental periodontitis was induced by placing ligatures around the maxillary first molars for two weeks. On the day of ligature removal, the irradiated groups received a single 20 Gy dose to the head and neck region. Animals were euthanized on days 1, 15, and 30 after ligature removal (n = 8/group/time point). Histomorphometric analysis of PerioW was performed on H&E-stained sections, and immunohistochemical staining was used to quantify RANK, RANKL, and OPG expression. Results: On day 1, PerioW did not differ significantly among groups, although the PtRt group had the highest mean. A significant intergroup difference was observed for RANKL, with higher expression in PtRt than in Pt. On day 15, PerioW differed significantly among groups, with the lowest value in Rt and the highest in PtRt; the Rt–PtRt comparison was significant. At this time point, RANK, RANKL, OPG, and the RANKL/OPG ratio showed no significant intergroup differences. On day 30, no significant intergroup differences were found for PerioW or immunohistochemical parameters; however, PtRt continued to show the highest PerioW and OPG values and the lowest RANKL/OPG ratio. Conclusions: Radiotherapy superimposed on periodontitis enhanced early pro-resorptive signaling and delayed structural normalization of periodontal tissues. Although late increases in OPG suggested a compensatory response, this appeared insufficient to fully reverse radiation-associated periodontal alterations. These findings support the importance of controlling periodontal inflammation before radiotherapy to reduce subsequent periodontal tissue damage....
Background and Objectives: This study aimed to evaluate the association between systemic nicotine administration and histological and biochemical repair endpoints in an acetic acid-induced rat oral ulcer model. Materials and Methods: Thirty-six male Wistar rats were assigned to control, oral ulcer + saline, and oral ulcer + nicotine (1 mg/kg/day, s.c.) groups. Oral ulcers were induced with 70% acetic acid. After 15 days, buccal mucosa and plasma samples were collected for histopathological and biochemical analyses. Epithelial thickness and fibrosis were assessed histologically, while malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor-A (VEGF-A), and epidermal growth factor receptor (EGFR) were quantified. Results: Relative to controls, ulcer induction was associated with reduced epithelial thickness and increased fibrosis, MDA, and TNF-α levels. Compared with the oral ulcer + saline group, the nicotine-treated group showed greater epithelial thickness, lower fibrosis, lower MDA and TNF-α levels, and higher VEGF-A and EGFR levels at the study endpoint. No significant difference in VEGF-A was observed between the control and oral ulcer + saline groups. Conclusions: In this acetic acid-induced rat model, systemic nicotine administration was associated with improved endpoint histological and biochemical indices of oral ulcer repair. Because macroscopic wound closure, dose–response relationships, route comparisons, and direct mechanistic experiments were not included, these findings should be interpreted as preliminary preclinical associations rather than evidence of a direct causal effect of nicotine on wound healing....
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