Neuronal injury in glaucoma persists despite effective intraocular pressure (IOP) control, necessitating neuroprotective strategies for retinal ganglion cells (RGCs). In this study, we investigated the neuroprotective role of the γ-hydroxybutyrate analog HOCPCA in a glaucoma model, focusing on its effects on CaMKII signaling, oxidative stress, and neuroinflammatory responses. Retinal tissue from high IOP animal models was analyzed via proteomics. In vitro mouse retinal explants were subjected to elevated pressure and oxidative stress, followed by HOCPCA treatment. HOCPCA significantly mitigated the RGC loss induced by oxidative stress and elevated pressure, preserving neuronal function. It restored CaMKIIα and β levels, preserving RGC integrity, while also modulating oxidative stress and neuroinflammatory responses. These findings suggest that HOCPCA, through its interaction with CaMKII, holds promise as a neuroprotective therapy for glaucoma.
Animals ; Retinal Ganglion Cells/metabolism* ; Glaucoma/pathology* ; Oxidative Stress/drug effects* ; Neuroprotective Agents/pharmacology* ; Mice ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotection/drug effects* ; Male ; Intraocular Pressure/drug effects*

BACKGROUND:Although aromatase inhibitors significantly improve the clinical benefit of patients with hormone receptor-positive breast cancer,its associated adverse event-osteoporosis seriously affects the quality of life of patients.Huangqi Bushen Huoxue Decoction can effectively prevent the occurrence of aromatase inhibitor-induced osteoporosis,but its mechanism of action is unclear.OBJECTIVE:To investigate the effects of Huangqi Bushen Huoxue Decoction on osteoclast activity in a mouse model of osteoporosis induced by aromatase inhibitors and relevant mechanisms.METHODS:Sixty 8-week-old female C57BL/6J mice were randomly divided into sham operation group,model group,high-,medium-and low-dose Huangqi Bushen Huoxue Decoction,and positive control group,with 10 mice in each group.Bilateral ovaries were removed to establish postmenopausal animal models in all the groups except for the sham operation group.After 1 week of recovery,letrozole was injected subcutaneously to establish postmenopausal osteoporosis models via subcutaneous injection of letrozole(an aromatase inhibitor).The high-,medium-and low-dose Huangqi Bushen Huoxue Decoction groups were intragastrically given 19.24,9.62 and 4.81 g/kg/d Huangqi Bushen Huoxue Decoction(once a day),respectively.The positive control group was given alendronate 5mg/kg once a week.After 3 months of administration,Micro-CT was used to detect tibial bone mineral density and bone microstructure.Hematoxylin-eosin staining and tartrate-resistant acid phosphatase staining of the femur were performed.Immunohistochemistry was used to detect the protein expression of receptor activator of nuclear factor-κB ligand and osteoprotectin in the femur.ELISA was used to detect the serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,the model group showed a significant decrease in bone mineral density,sparse and fractured trabecular morphology,and a significant increase in serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,indicating that the model of aromatase inhibitor-induced osteoporosis was successfully constructed.(2)Compared with the model group,the high-,medium-,and low-dose Huangqi Bushen Huoxue Decoction groups showed significant improvement in bone mineral density and bone microstructure,thickening and densification of trabecular morphology,significantly decreased serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,a decrease in the number of osteoclasts and the expression of receptor activator of nuclear factor-κB ligand proteins,and an increase in the expression of osteoprotegerin.To conclude,Huangqi Bushen Huoxue Decoction may regulate the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin signaling pathway,inhibit osteoclast activity,improve trabecular morphology and bone microstructure,and increase bone mineral density,thus preventing the occurrence and development of aromatase inhibitor-induced osteoporosis.

BACKGROUND:Although aromatase inhibitors significantly improve the clinical benefit of patients with hormone receptor-positive breast cancer,its associated adverse event-osteoporosis seriously affects the quality of life of patients.Huangqi Bushen Huoxue Decoction can effectively prevent the occurrence of aromatase inhibitor-induced osteoporosis,but its mechanism of action is unclear.OBJECTIVE:To investigate the effects of Huangqi Bushen Huoxue Decoction on osteoclast activity in a mouse model of osteoporosis induced by aromatase inhibitors and relevant mechanisms.METHODS:Sixty 8-week-old female C57BL/6J mice were randomly divided into sham operation group,model group,high-,medium-and low-dose Huangqi Bushen Huoxue Decoction,and positive control group,with 10 mice in each group.Bilateral ovaries were removed to establish postmenopausal animal models in all the groups except for the sham operation group.After 1 week of recovery,letrozole was injected subcutaneously to establish postmenopausal osteoporosis models via subcutaneous injection of letrozole(an aromatase inhibitor).The high-,medium-and low-dose Huangqi Bushen Huoxue Decoction groups were intragastrically given 19.24,9.62 and 4.81 g/kg/d Huangqi Bushen Huoxue Decoction(once a day),respectively.The positive control group was given alendronate 5mg/kg once a week.After 3 months of administration,Micro-CT was used to detect tibial bone mineral density and bone microstructure.Hematoxylin-eosin staining and tartrate-resistant acid phosphatase staining of the femur were performed.Immunohistochemistry was used to detect the protein expression of receptor activator of nuclear factor-κB ligand and osteoprotectin in the femur.ELISA was used to detect the serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,the model group showed a significant decrease in bone mineral density,sparse and fractured trabecular morphology,and a significant increase in serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,indicating that the model of aromatase inhibitor-induced osteoporosis was successfully constructed.(2)Compared with the model group,the high-,medium-,and low-dose Huangqi Bushen Huoxue Decoction groups showed significant improvement in bone mineral density and bone microstructure,thickening and densification of trabecular morphology,significantly decreased serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,a decrease in the number of osteoclasts and the expression of receptor activator of nuclear factor-κB ligand proteins,and an increase in the expression of osteoprotegerin.To conclude,Huangqi Bushen Huoxue Decoction may regulate the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin signaling pathway,inhibit osteoclast activity,improve trabecular morphology and bone microstructure,and increase bone mineral density,thus preventing the occurrence and development of aromatase inhibitor-induced osteoporosis.

The antibacterial activity and mechanism of the antimicrobial peptide mutant Cbf-14-2 against NDM-1 carrying recombinant bacteria (E.coli BL21 (DE3)-NDM-1) was investigated in this study.The minimum inhibitory concentration (MIC),minimum bactericidal concentration (MBC) and killing curves (KCs) in vitro were determined by the broth microdilution method.Mice septicemia model was established by interaperitotoneal injection of E.coli BL21 (DE3)-NDM-1 to evaluate the antibacterial activity of this peptide in vivo.Results showed that Cbf-14-2 exhibited a potent antibacterial activity with MIC of 16 μg/mL and killed almost all recombinant bacteria within 120 min.Meanwhile,it significantly improved the survival rate of infected mice up to 70％ with the decreasing of bacterial load in mice lung,liver,spleen and kidney.This powerful clearance ability of Cbf-14-2 against bacteria mainly related to its enhanced membrane penetration ability through neutralizing the negative charges and disrupting the integrity of the bacterial cell membrane.Therefore,Cbf-14-2 is expected to be a potential antimicrobial agent for the treatment of infection induced by multi-drug resistant bacteria,especially for the NDM-1carrying bacteria.

Objective:To determine the content of cyclohexane, ethyl acetate, methanol, methylene chloride and trichloromethane in rupatadine fumarate by headspace gaschromatography. Methods:A DB-WAXETRR capillary column(30 m × 0. 32 mm,0. 25 μm)was used and the carrier gas was nitrogen. The detector was an FID and the inlet temperature was 200℃ . The column temperature program was with the initial temperature of 35℃,maintained 10 min,and then risen to 220℃ with the rate of 20℃·min -1 ,and maintained 5 min. Results:Cyclohexane,ethyl acetate,methanol,methylene chloride and trichloromethane showed a good linear relationship within the range of 77. 590 1- 698. 310 9 μg·ml -1(r = 0. 999 7),102. 166 6- 919. 499 4 μg· ml -1(r = 0. 999 8),62. 744 7- 564. 703 2μg·ml -1(r = 0. 999 9),12. 011 2- 108. 101 1 μg·ml-1(r = 0. 999 6)and 1. 262 8-11. 365 6 μg·ml -1(r = 0. 999 6). The average recovery was 103. 9% ,103. 5% ,104. 9% ,107. 1% and 103. 4% and RSD was 2. 3% ,2. 6% ,3. 1% ,2. 8% and 4. 5%(n = 9),respectively. The five residual solvents were not detected out in rupatadine fumarate. Conclusion:The method is stable,simple,sensitive and accurate,and can be used for the determination of residual solvents in rupatadine fumarate.

Objective To investigate the health behavior level of elderly patients with coronary heart disease (CHD) in order to instruct nurses how to give health education to them. Methods By con-venient sampling, 71 elderly patients with CHD in four hospitals in Wuhan were surveyed with the ques-tionnaire of health promoting lifestyle profile Ⅱ of FANG Heng-ying. The investigation results were ana-lysed. Results The findings showed that mean total score of health behavior of elderly patients with CHD obtained from the questionnaire was only 2.40,the level of health behavior was low. There were statistically significant differences among scores of elderly patients with CHD at different levels of family income and at different occupations before retirement. Conclusions The general level of health behavior of elderly pa-tients with CHD was low, especially in the aspect of health responsibility. Moreover, Patients with lower family income, peasants, and as a worker before retirement have lower health behavior level. This survey suggests that nurses should enhance the health education of the elderly patients with CHD, especially the poor and elderly farmer patients with CHD to improve their health behavior level.