Medicina
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Background and Objectives: Alkaline phosphatase activity, mineralized matrix, and osteogenic-related gene expression have been shown to increase in response to bone morphogenetic protein-9 (BMP-9). In this study, spheroids derived from human gingival stem cells were used to determine the effects of BMP-9 on cell survival, osteogenesis, and mineralization. Materials and Methods: Human gingival stem cells were used to produce spheroids and then grown to concentrations of 0, 0.1, 1, 10, and 100 ng/mL with BMP-9. ⋯ On day 14, the alkaline phosphatase activity in the groups dosed with 0.1, 1, 10, or 100 ng/mL was statistically higher than that in the unloaded control group (p < 0.05). According to qPCR data, the mRNA expression level of RUNX2 with 1 ng/mL dosing was higher on day 7 compared to that of the unloaded control group (p < 0.05). Conclusions: These findings suggest that BMP-9 can be employed to stimulate early osteogenic differentiation in stem cell spheroids.
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Background and Objectives: Damage to normal bone tissue following therapeutic irradiation (IR) represents a significant concern, as IR-induced bone microenvironment disruption can cause bone loss and create a more favorable environment for tumor metastases. The aim of the present study was to explore the cellular regulatory mechanism of IR-induced bone microenvironment disruption to effectively prevent radiotherapy-associated adverse effects in the future. Materials and Methods: In this study, a mouse model of local IR was established via local irradiation of the left hind limb of BALB/c mice with 12 Gy X-rays, and an in vitro osteocyte (OCY) model was established by exposing osteocyte-like MLO-Y4 cells to 2, 4, and 8 Gy irradiation to analyze multicellular biological injuries and cellular senescence. ⋯ Finally, administration of the STING inhibitor C-176 mitigated IR-induced activation of osteoclastogenesis and restraint of osteogenesis, ameliorating the IR-induced biological damage of OCYs, consistent with the inhibition of P-TBK1, RANKL and SOST. Conclusions: The STING-P-TBK1 signaling pathway plays a crucial role in the regulation of the secretion of inflammatory cytokines and osteoclastogenesis potential in IR-induced bone microenvironment disruption. The selective STING antagonist can be used to intervene to block the STING pathway and, thereby, repair IR-induced multicellular biological damage and mitigate the imbalance between osteoclastogenesis and osteoblastgenesis.
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Background and Objectives: Hypercholesterolemia is a main risk-factor leading to ischemic heart disease (IHD). However, among patients with heart failure, the use of lipid lowering drugs in the presence of low cholesterol might be dangerous. This 18-year longitudinal study of patients ≤51 years old investigated the relationship between baseline total cholesterol, low-density lipoprotein cholesterol (LDL-c) and triglyceride levels, and survival among patients with severe HF. ⋯ The association between higher LDL-c levels and lower mortality was most noticeable among patients with heart failure. Conclusion: Longitudinal follow-up found that low LDL-c levels may indicate poorer prognosis among patient with heart failure who are ≤51 years old, similar to elderly heart failure patients. Cholesterol lowering drugs in younger patients with heart failure may increase mortality.
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Background and objectives: Dyslipidemia is one of the most important modifiable risk factors in the pathogenesis of cardiovascular disease in the general population, but its importance in the hemodialysis (HD) population is uncertain. Materials and Methods: This retrospective cohort study includes HD patients hospitalized due to acute coronary syndrome (ACS) in the period 2015-2020 with lipid profile data during ACS. A control group with preserved kidney function was matched. ⋯ Conclusions: Despite comparable lipid profiles and statin treatment before and after ACS hospitalization, mortality rates were significantly higher among HD group. While malnutrition-inflammation markers were associated with survival of dialysis patients after ACS, LDL cholesterol was not. Thus, our study results emphasize that better nutritional status and less inflammation are associated with improved survival among HD patients.
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Background and Objectives: The aim of this study was to investigate under dynamic loading the potential biomechanical benefit of simulated first tarsometatarsal (TMT-1) fusion with low-profile superelastic nitinol staples used as continuous compression implants (CCIs) in two different configurations in comparison to crossed screws and locked plating in a human anatomical model. Materials and Methods: Thirty-two paired human anatomical lower legs were randomized to four groups for TMT-1 treatment via: (1) crossed-screws fixation with two 4.0 mm fully threaded lag screws; (2) plate-and-screw fixation with a 4.0 mm standard fully threaded cortex screw, inserted axially in lag fashion, and a 6-hole TMT-1 Variable-Angle (VA) Fusion Plate 2.4/2.7; (3) CCI fixation with two two-leg staples placed orthogonally to each other; (4) CCI fixation with one two-leg staple and one four-leg staple placed orthogonally to each other. Each specimen was biomechanically tested simulating forefoot weightbearing on the toes and metatarsals. ⋯ No significant differences were detected between the two CCI fixation techniques, as well as between the crossed-screws and plate-and-screw techniques (p ≥ 0.493) for this parameter of interest. Furthermore, displacements at the dorsal and plantar aspects of the TMT-1 joint in unloaded foot condition, together with their amplitudes, did not differ significantly among all pairs of groups (p ≥ 0.224). Conclusions: The low-profile superelastic nitinol staples demonstrate comparable biomechanical performance to established crossed-screws and plate-and-screw techniques applied for fusion of the first tarsometatarsal joint.