Ophiopogonin D improves osteointegration of titanium alloy implants under diabetic conditions by inhibition of ROS overproduction via Wnt/ß-catenin signaling pathway.

A high failure rate of titanium implants in diabetic patients has been indicated in clinical evidences. Excessive oxidative stress at the bone-implant interface plays an important role in the impaired osteointegration under diabetic conditions. While the underlying mechanisms remain unknown and the targeted treatments are urgently needed. Ophiopogonin D (OP-D), isolated from Chinese herbal Radix Ophiopogon japonicus, is generally reported to be a potent antioxidant agent. In the present study, we hypothesized that OP-D exerted promotive effects on osteointegration against oxidative stress, and investigated the underlying mechanisms associated with alteration of Wnt/ß-catenin signaling pathway. Rabbit osteoblasts incubated on titanium alloy implant were co-cultured with normal serum (NS), diabetic serum (DS), DS + OP-D, DS + NAC (a potent ROS inhibitor) and DS + OP-D + Dkk1 (a Wnt inhibitor) for examinations of osteoblast behaviors. For in vivo study, titanium alloy implants were implanted into the femoral condyle defects on diabetic rabbits. Results demonstrated that diabetes-induced oxidative stress resulted in osteoblast dysfunctions and apoptotic injury at the bone-implant interface, concomitant with the inactivation of Wnt/ß-catenin signaling. Importantly, OP-D administration attenuated oxidative stress, directly reactivating Wnt/ß-catenin signaling. Osteoblast dysfunctions were thus reversed as evidenced by improved osteoblast adhesion, proliferation and differentiation, and ameliorated apoptotic injury, exerting similar effects to NAC treatment. In addition, the positive effects afforded by OP-D were confirmed by improved osteointegration and oetogenesis within the titanium alloy implants in vivo by Micro-CT and histological analyses. Furthermore, the pro-osteogenic effects of OP-D were almost completely abolished by the Wnt inhibitor Dkk1. These results demonstrated, for the first time, OP-D administration alleviated the damaged osteointegration of titanium alloy implants under diabetic conditions by means of inhibiting oxidative stress via a Wnt/ß-catenin-dependent mechanism. The OP-D administration would become a reliable treatment strategy for implant failure therapy in diabetics due to the optimal anti-oxidative and pro-osteogenic properties.

[Health care and disease prevention in Jiujing Tu (Illustration of moxibustion) of the Dunhuang caves].

Figure four of the Jiujing Tu (Illustration of Moxibustion) of the Dunhuang Caves is the earliest and the most complete recording of treatment for five kinds of strain and seven kinds of impairments in the history of acupuncture and moxibustion. Figure 12 is held as a mystery since it only provided illustrations without indications. Through analysis and approved by clinical experiences, it is held that the two figures are companion illustrations on prevention and treatment of five kinds of strain and seven kinds of impairments as well as health keeping with moxibustion. The point prescriptions in these two figures are defined according to the tri-gram in Yijing (The Book of Change), which allowed the maximization of harmony between the human and the nature. Recovery and health are thus fulfilled through regulation on points at the head, trunk and four extremities of the body. And it is considered to have great significance for promoting the development of the present acupuncture and moxibustion theory since it is effective in both preventing and curing diseases caused by deficient and stagnation conditions such as the wei (flaccidity) syndrome, bi (arthralgia) syndrome, paralysis, dementia, asthma and so on.

[Preliminary study on characteristics of the Illustrations of Moxibustion in Dunhuang Caves in treatment of 5 kinds of strain and 7 kinds of impairments].

The Illustrations of Moxibustion, a remained book in Dunhuang Caves, is available the earliest monograph about moxibustion methods with both pictures and writing since recorded writing. In treatment of 5 kinds of strain and 7 kinds of impairments, point association for correspondence between man and universe was adopted human point distribution according to Jiugong and Bagua; and point association method of viewing the situation as a whole according to humam point distribution on the head, the body and the limbs; it wrote and drew available the earliest naked figures for acupuncture and moxibustion in simple natural materialism; and it is the most reasonable, the most complete explanation of sexual science in Chinese medicine, and is a sample for treatment of 5 kinds of strain and 7 kinds of impairments by ancient physicians stressing moxibustion, with convenient point selection and safety.

[Experience on clinical application of acupoints in the remained book of the Illustrations of Moxibustion in Dunhuang Caves].

The Illustrations of Moxibustion, a remained book in Dunhuang Caves, is now available the earliest monograph of moxibustion methods since having writing in our country. In this paper, the points selected and therapeutic methods in The Illustrations of Moxibustion are used for treatment of typical cases of cerebral palsy, rheumatoid arthritis, diarrhea due to gastroenteritis, impotence, premature, diabetes, asthma and so on to explore characteristics of using points, find out the law, test and verify the actual effect and find guiding values for modern clinic, indicating that The Illustrations of Moxibustion can be applied for treatment and rehabilitation of many kinds of refractory diseases with unique therapeutic effects and practical significance.