Search

Introduction: In senile osteoporosis countering the age-mediated bone loss, promotion of osteoblastogenesis and identification of responsible micro-RNA (miR) would be a successful strategy.Material and Methods: miR microarray screening was carried out to identify the suppressed miRs after real time polymerase chain reaction (RT-PCR) analysis in mesenchymal stem cells (MSCs) derived from adult bone marrow during the proliferation to the mineralization stage. The primary calvarial pre-osteoblasts (human) were harvested and received transfection of miR-22's antagomir or agomir in vitro. Bioinformatics study suggested YWHAZ as the favorable target gene. Next, YWHAZ knockdown was studied for its effect on differentiation of osteoblasts. For in vivo studies, ovariectomized or sham mice were injected with miR-22's antagomir for a period of 6 weeks. The stromal cells were isolated in the 6th week for ex vivo experiments.Results: miR-22 was found to be down-regulated in bone marrow derived mesenchymal stem cells. miR-22's antagomir converted the pre-osteoblasts to a more differentiated and mineralized phenotype showing upregulated protein expression of COL1A1, ALP and CBFA1. The miR-22's antagomir suppressed YWHAZ, enhanced stability of CBFA1 and promoted the differentiation of osteoblasts. In vivo, miR-22's antagomir promoted mineralization and osteoblastogenesis, elevated bone strength and reversed the ovariectomy mediated bone loss in sham mice.Conclusions: Inhibition of miR-22 may be a potential target for treating osteoporosis clinically. The findings hence suggest that inhibition of miR-22 may be an effective anabolic therapeutic approach in treating osteoporosis clinically. [ABSTRACT FROM AUTHOR]

Background: The study was conducted to assess differences in overall survival (OS) in patients with non‐small cell lung cancer (NSCLC) receiving different treatment modalities of tyrosine kinase inhibitors (TKIs). Methods: A total of 463 NSCLC patients receiving TKI treatment were included. OS was compared according to treatment timing in all patients, the elderly, and patients positive for EGFR mutations. Results: One hundred and seventy two patients received TKIs as first‐line treatment, 220 as second‐line, and 67 as third‐line. The results between the three groups were not statistically significant: the one, two, and three‐year OS rates were: 55.3%, 22.3%, and 11.3% (first‐line); 59.6%, 27.8%, and 14.9% (second‐line); and 53.8%, 41.3%, and 29.5% (third‐line), respectively (P = 0.095). Results between the three groups of elderly patients were also not statistically significant (P = 0.469). The one and two‐year OS rates in EGFR mutation‐positive patients receiving first‐line treatment were 48% and 17.5%, respectively. The one, two, and three‐year OS rates of patients receiving second‐line treatment were: 54.2%, 30.3%, and 20.2%, respectively. There were no statistically significant differences between the groups with EGFR mutations receiving first‐line or second‐line treatment. Thirteen EGFR mutation‐positive patients received third‐line TKI treatment for a median duration of 7 months. Their one and two‐year OS rates were 69.8% and 58.2%, respectively, which were higher than in the other two groups (P = 0.015). Conclusion: Three lines of TKI therapy can prolong survival in NSCLC patients. Elderly patients can benefit from TKI therapy. EGFR mutation‐positive patients can benefit from second‐line or third‐line TKI therapy. [ABSTRACT FROM AUTHOR]

Highlights: [•] Puerarin decreased up-expression of P2X3 in MI rat SG and DRG. [•] Puerarin inhibited up-ATP currents in DRG neurons after MI. [•] Puerarin decreased blood pressure and heart rate after down-P2X3. [•] Puerarin blocks injury signaling mediated by up-regulated P2X3. [•] Puerarin protected myocardium by blocking P2X3 signaling. [ABSTRACT FROM AUTHOR]

With the development of material science, hydrogels with antibacterial and wound healing properties are becoming common. However, injectable hydrogels with simple synthetic methods, low cost, inherent antibacterial properties, and inherent promoting fibroblast growth are rare. In this paper, a novel injectable hydrogel wound dressing based on carboxymethyl chitosan (CMCS) and polyethylenimine (PEI) was discovered and constructed. Since CMCS is rich in -OH and -COOH and PEI is rich in -NH 2 , the two can interact through strong hydrogen bonds, and it is theoretically feasible to form a gel. By changing their ratio, a series of hydrogels can be obtained by stirring and mixing with 5 wt% CMCS aqueous solution and 5 wt% PEI aqueous solution at volume ratios of 7:3, 5:5, and 3:7. Characterized by morphology, swelling rate, adhesion, rheological properties, antibacterial properties, in vitro biocompatibility, and in vivo animal experiments, the hydrogel has good injectability, biocompatibility, antibacterial ( Staphylococcus aureus : 56.7 × 10 7  CFU/mL in the blank group and 2.5 × 10 7  CFU/mL in the 5/5 CPH group; Escherichia coli : 66.0 × 10 7  CFU/mL in the blank group and 8.5 × 10 7  CFU/mL in the 5/5 CPH group), and certain adhesion (0.71 kPa in the 5/5 CPH group) properties which can promote wound healing (wound healing reached 98.02% within 14 days in the 5/5 CPH group) and repair of cells with broad application prospects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fang, Lin, Fan, Qiu, Zhong, Yang, Yang, Zhang, Feng, Ai, Shi and Wan.)

Introduction: In senile osteoporosis countering the age-mediated bone loss, promotion of osteoblastogenesis and identification of responsible micro-RNA (miR) would be a successful strategy., Material and Methods: miR microarray screening was carried out to identify the suppressed miRs after real time polymerase chain reaction (RT-PCR) analysis in mesenchymal stem cells (MSCs) derived from adult bone marrow during the proliferation to the mineralization stage. The primary calvarial pre-osteoblasts (human) were harvested and received transfection of miR-22's antagomir or agomir in vitro . Bioinformatics study suggested YWHAZ as the favorable target gene. Next, YWHAZ knockdown was studied for its effect on differentiation of osteoblasts. For in vivo studies, ovariectomized or sham mice were injected with miR-22's antagomir for a period of 6 weeks. The stromal cells were isolated in the 6 th week for ex vivo experiments., Results: miR-22 was found to be down-regulated in bone marrow derived mesenchymal stem cells. miR-22's antagomir converted the pre-osteoblasts to a more differentiated and mineralized phenotype showing upregulated protein expression of COL1A1, ALP and CBFA1. The miR-22's antagomir suppressed YWHAZ, enhanced stability of CBFA1 and promoted the differentiation of osteoblasts. In vivo , miR-22's antagomir promoted mineralization and osteoblastogenesis, elevated bone strength and reversed the ovariectomy mediated bone loss in sham mice., Conclusions: Inhibition of miR-22 may be a potential target for treating osteoporosis clinically. The findings hence suggest that inhibition of miR-22 may be an effective anabolic therapeutic approach in treating osteoporosis clinically., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)