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Osteoporosis is a multifactorial systemic skeletal disease that is characterized by a low bone mineral density (BMD) and the microarchitectural deterioration of bone tissue, leading to bone fragility. The search for new genes that may play an important role in the regulation of bone mass and the development of osteoporosis is ongoing. Recently, it was found that altering the activity of the endothelin-1-converting enzyme encoded by the ECE1 gene may affect bone mineral density (BMD). Another gene involved in the process of osteoblast differentiation and maturation is believed to be PPARG (peroxisome proliferator-activated receptor gamma). This participates in regulating the transformation of stem cells and affects the process of bone formation and resorption. Therefore, we analyzed the association of the ECE1 and PPARG variants with osteopenia and osteoporosis risk in the Polish population. This study included a group (n = 608) of unrelated Polish women (245 individuals with osteoporosis (aged: 57 ± 9), 109 individuals with osteopenia (aged: 53 ± 8) and 254 healthy controls (aged: 54 ± 8)). The real-time PCR technique was used to determine the genetic variants for rs213045 (-338G>T) and rs213046 (-839A>C) of the ECE1 gene and rs1801282 (Pro12Ala, C>G) of the PPARG gene. Analysis of the PPARG rs1801282 variants did not show any association with the risk of osteoporosis and osteopenia. However, in the densitometric results, lower median Z-score values were observed for the T allele compared to the G allele for the rs213045 variant of the ECE1 gene (−1.11 ± 1.07 vs. −0.78 ± 1.21, p = 0.021). Moreover, the TT genotype for the rs213045 variant was more common in women with osteopenia (13.8%, OR = 2.82, p < 0.05) and osteoporosis (7.8%, OR = 1.38, p > 0.05) compared to the control group (5.5%). Additionally, our results suggested that the T allele of rs213045 was more common in women with osteopenia compared to the controls. We further observed that the haplotype containing two major GA alleles of ECE1 (rs213045, rs213046) could reduce the risk of osteopenia in our population. Finally, we found that women with osteoporosis had statistically significantly lower body mass and BMI values compared to the control group. Our results suggest that the ECE1 rs213045 variant may increase the risk of osteopenia. However, the data obtained require confirmation in further studies. Full article

Corneal endothelial cells (CE) are critical for the cornea’s transparency. For severe corneal damage, corneal tissue transplantation is the most promising option for restoring vision. However, CE apoptotic cell death occurs during the storage of donor corneas for transplantation. This study used small interfering (si)RNA-mediated silencing of pro-apoptotic proteins as a novel strategy to protect CE against apoptosis. Therefore, the pro-apoptotic proteins Bax and Bak were silenced in the human corneal endothelial cell line (HCEC-12) by transfection with Accell™siRNA without any adverse effects on cell viability. When apoptosis was induced, e.g., etoposide, the caspase-3 activity and Annexin V-FITC/PI assay indicated a significantly reduced apoptosis rate in Bax+Bak-siRNA transfected HCECs compared to control (w/o siRNA). TUNEL assay in HCECs exposed also significantly lower cell death in Bax+Bak-siRNA (7.5%) compared to control (w/o siRNA: 32.8%). In ex vivo donor corneas, a significant reduction of TUNEL-positive CEs in Bax+Bak-siRNA corneas (8.1%) was detectable compared to control-treated corneas (w/o siRNA: 27.9%). In this study, we demonstrated that suppressing pro-apoptotic siRNA leads to inhibiting CE apoptosis. Gene therapy with siRNA may open a new translational approach for corneal tissue treatment in the eye bank before transplantation, leading to graft protection and prolonged graft survival. Full article

Background: The outcomes of first metatarsal (M1) distal osteotomies in hallux valgus (HV) can be improved, especially for intermetatarsal angle (IMA) correction, which is mainly based on lateral displacement of the M1 head (i.e., translation) through the osteotomy. Conversely, there is a spontaneous reduction in the IMA in first metatarsophalangeal joint (MTP1) arthrodesis. But we do not know whether this can be applied to distal osteotomies. We propose a distal osteotomy, called 3D chevron, which combines supination and varization of the M1 head. This might realign soft tissues around the MTP1, potentially leading to a spontaneous reduction in the IMA by an analogous mechanism to MTP1 fusion. Therefore, our study aimed to assess whether spontaneous reductions in IMAs exist in distal M1 osteotomies in the absence of lateral translations of M1 heads. Methods: A prospective continuous series of 25 3D chevrons was performed. Two groups were formed during surgery. Patients requiring no M1 head lateral displacement were included in the “successful correction without translation” group, and patients requiring M1 head lateral displacement were included in the “failed correction without translation” group. Radiographic analysis was performed preoperatively and at 1 year postoperatively. Results: Twenty-two women and three men, with a mean age of 44.8 ± 14.2 years and a mean body mass index of 22.6 ± 4.1 kg/m², underwent follow-up at one year after surgery. The “successful correction without translation” group was composed of HV with milder deformities (13/25 HVs, median preoperative IMA = 13 (IQR 2)) compared to the “failed correction without translation” group (median IMA = 16 (IQR 2.25) p < 0.001). Spontaneous reductions in IMAs were observed in the “successful correction without translation” group, with a median decrease in the IMA of 6 degrees (CI95%[5.5; 8.0]; p < 0.001) between preoperative and 1-year radiographs. Conclusion: Distal osteotomies allow for spontaneous reduction in the IMA in HV. First metatarsal head translation through an osteotomy should not be considered as the only procedure to correct IMAs in distal osteotomies. Full article