To examine the effect of salidroside on the expression and activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in bone marrow (BM) of BM depressed anemic mice by immunohistochemistry and gelatin zymography respectively, and to explore its roles in hematopoietic regulation. Immunohistochemistry showed that the expression of MMP-2 and MMP-9 of bone marrow cells (BMCs) was found in each group. Compared with control group, the expression of MMP-2 and MMP-9 was obviously increased in the model group, low-dose, middle-dose and high-dose salidroside. At day 4 after treatment of radiation and chemotherapy, the peak of the expression of MMP-2 and MMP-9 was found in middle-dose salidroside . At day 8 after treatment of radiation and chemotherapy, the peak of the expression of MMP-2 and MMP-9 was found in low-dose and middle-dose salidroside respectively. Gelatin zymography revealed that 66 kD proMMP-2, 62 kD MMP-2, 86 kD MMP-9 and 94 kD proMMP-9 were detected in control group, and the activity of MMP-9 was stronger among them. After treatment of radiation and chemotherapy, the activity of gelatinases of hemopoietic microenviroment (HM) was obviously decreased, but low-dose, middle-dose and high-dose salidroside could significantly increase the activities of proMMP-9 and MMP-9, attenuate the activity of proMMP-2. These results suggest that salidroside could promote the recovery of hematopoietic function of BM depressed anemic mice by increasing the expression and activity of MMPs, releasing the cytokines from ECM or cell membrane, repairing impaired microvessels of HM and promotion proliferation, migration and differentiation of HSCs.
Anemia, Aplastic ; blood ; enzymology ; Animals ; Bone Marrow ; enzymology ; Glucosides ; pharmacology ; Hematopoiesis ; drug effects ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; metabolism ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; metabolism ; Mice ; Mice, Inbred BALB C ; Phenols ; pharmacology

The important role of TDP-43 proteinopathy in Alzheimer's disease (AD) has been gradually revealed. High proportion of AD patients have TDP-43 proteinopathy on their postmortem diagnosis. Patients with TDP-43 proteinopathy show more sever hippocampal atrophy and cognitive dysfunction, suggesting that TDP-43 proteinopathy can serve as an important target in AD diagnosis and treatment. Evaluation of TDP-43 proteinopathy in vivo would hold great promise in AD diagnosis, drug development and treatment. In this review, we describe the pathological characteristics of TDP-43 proteinopathy in AD, and summarize the recent progress of TDP-43 proteinopathy in the diagnosis and treatment of AD.