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Alzheimer’s disease (AD) is a common neurodegenerative disorder without any satisfactory therapeutic approaches. AD is mainly characterized by the deposition of β-amyloid protein (Aβ) and extensive neuronal cell death. Curcumin, with anti-oxidative stress (OS) and cell apoptosis properties, plays essential roles in AD. However, whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, can exert a neuroprotective effect in AD remains to be elucidated.

BACKGROUND: Imbalance between subchondral bone resorption and bone fonnation occurs in osteoarthritis. Our preliminary study has found that the subchondral bone changes precede the articular cartilage changes in knee osteoarthritis rats. OBJECTIVE: To observe the changes of subchondral bone in knee osteoarthritis rats, and to explore the effect of elcatonin on the expression of p38 MAPK and absorption of subchondral bone. METHODS: Female Sprague-Dawley rats, 3 months of age, were randomly divided into three groups: sham operation group (n=6, the adipose tissue of the same size as the ovary was removed without ovariectomy, the bilateral knee joints were opened, but without cruciate ligament injury); model group (n=6, bilateral ovariectomy plus bilateral cruciate ligament injury, no treatment); elcatonin group (n=6, ovariectomy plus cruciate ligament injury, intramuscular injection of 5lU/kg elcatonin, twice weekly). The bone mineral density and p38 protein expression levels in subchondral bone were detected at 12 weeks. The serum levels of C-terminal crosslinking telopeptides of type I collagen, C-terminal crosslinking telopeptides of type II collagen, interleukin-1, interleukin-6 and bone-specific alkaline phosphatase, tartrate resistant acid phosphatase 5b were detected. RESULTS AND CONCLUSION: (1) The bone volume fraction and trabecular bone number in the elcatonin group were significantly higher than those in the model group (P < 0.05), and the trabecular separation in the elcatonin group was lower than that in the model group (P < 0.05). (2) The bone volume fraction, trabecular bone number and trabecular thickness in the model group were lower than those in the sham operation group (P < 0.01 or P < 0.05), and the trabecular separation was higher than that in the sham operation group (P < 0.01). (3) The serum levels of C-tenninal crosslinking telopeptides of type I collagen, C-tenninal crosslinking telopeptides of type II collagen, interleukin-1, interleukin-6 and tartrate resistant acid phosphatase 5b in the elcatonin group was significanUy lower than those the model group (P < 0.05). and the above levels in the model group were significantly higher than those in the sham operation group (P < 0.05). (4) The p38 expression level in subchondral bone in the elcatonin group was significantly lower than that in the model group (P < 0.01 ), and the level in the model group was significantly higher than that in the sham operation group (P < 0.01). (5) These results indicate that elcatonin may inhibit the secretion of osteoarthritis pro-inflammatory factors and subchondral bone resorption by down-regulating the expression level of p38 MAPK. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mitogen-activated protein kinase signaling pathway participates in the differentiation of osteoblasts and osteoclasts, closely related to subchondral bone reconstruction and play a key role in the occurrence and development of osteoarthritis. Bisphosphonates as bone resorption inhibitor is used to treat osteoporosis. OBJECTIVE: To observe the effect of sodium ibandronate on the knee osteoarthritis in rats, and changes of mitogen-activated protein kinase signaling pathway. METHODS: The study was approved by the Laboratory Animal Ethical Committee of the First Affiliated Hospital of South China University. Thirty female Sprague-Dawley rats were randomly divided into sham, model, and treatment groups. The rats in the latter two groups underwent ovariectomy bilaterally, and anterior cruciate ligament resection, and rats in the sham group received the fatty tissue surrounding the ovaries removed only. After 1 week of surgery, the rats in the treatment group were given intraperitoneal injection of 10 µg/kg sodium ibandronate, rats in the model group were injected with normal saline, and the sham group received no intervention. Twelve weeks late, the rats were killed to perform histological examination of cartticular cartilage and Mankin scores were detected. Micro-CT of subchondral bone and quantitative analysis of the bone microstructure were conducted. The protein and mRNA expression levels of extracellular signal regulated protein kinase and c-Jun N-terminal kinase in mitogen-activated protein kinase signaling pathway were measured. RESULTS AND CONCLUSION: (1) The cartilage structure in the model group was significantly damaged, the Mankin score was significantly higher than that in the sham group, and the Mankin score in the treatment group was significantly lower than that in the model group (P < 0.01 ). (2) The bone mineral density, trabecular bone volume ratio, trabecular number in the model group were significantly lower than those in the sham group (P < 0.01), and trabecular separation was higher than that in the sham group (P < 0.01). Compared with the model group, the treatment group had higher bone mineral density, trabecular bone volume ratio, trabecular number, and lower trabecular separation (P < 0.01 ). (3) The mRNA and protein expression levels of extracellular signal regulated protein kinase and c-Jun N-terminal kinase in the model group were significantly higher than those in the sham group (P < 0.05, P < 0.01), and the levels in the treatment group were significantly lower than those in the model group (P < 0.05). (4) To conclude, sodium ibandronate may inhibit subchondral bone loss and articular cartilage degeneration in rat models of osteoarthritis by inhibiting extracellular signal regulated protein kinase and c-Jun N-terminal kinase in mitogen-activated protein kinase signaling pathway. [ABSTRACT FROM AUTHOR]

This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer's disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aβ1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aβ1–42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1. [ABSTRACT FROM AUTHOR]

This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer's disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aβ1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aβ1–42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1. [ABSTRACT FROM AUTHOR]

Objective: To explore the possible relationship between angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Tie-2 and vascular endothelial growth factor (VEGF) and radiation brain injury (RBI) and detect the expressions of VEGF, Ang-1, Ang-2 and Tie-2 in co-cultured endothelial cells and astrocytes after an irradiation of X-ray., Methods: Murine brain microvascular endothelial cells bEnd.3 and astrocytes were co-cultured in a Transwell culture plate and then exposed to X-ray at various doses (5, 10, 20 and 30 Gy) and cultured for 24 hours. The group without radiation acted as a control. Western blot was used to detect the expressions of VEGF, Ang-1, Ang-2 and Tie-2., Results: As compared with the control group, the expression of VEGF increased in 5, 10, 20 and 30 Gy dose groups [(1.71 ± 0.11), (2.03 ± 0.05), (2.20 ± 0.06), (2.19 ± 0.08) vs (1.26 ± 0.10), P < 0.05]; the expression of Ang-1 decreased in 5, 10, 20 and 30 Gy dose groups [(2.27 ± 0.07), (2.28 ± 0.06), (2.01 ± 0.05), (1.54 ± 0.08) vs (2.46 ± 0.04), P < 0.05]; the expression of Tie-2 decreased in 5, 10, 20 and 30 Gy dose groups [(2.40 ± 0.10), (2.47 ± 0.06), (1.05 ± 0.09), (1.00 ± 0.08)vs(4.80 ± 0.07), P < 0.05]; the expression of Ang-2 increased in 5 Gy and 10 Gy dose groups [(2.10 ± 0.07), (2.43 ± 0.08)vs (1.69 ± 0.05), P < 0.05] while decreased in 20 Gy and 30 Gy dose groups [(1.12 ± 0.10), (1.21 ± 0.04)vs(1.69 ± 0.05), P < 0.05]., Conclusion: X-ray could differentially affect the expressions of VEGF, Ang-1, Ang-2 and Tie-2 in co-cultured endothelial cells and astrocytes. And the differential expressions of VEGF, Ang-1, Ang-2 and Tie-2 may be related with microvascular injury in RBI.