1.KAT7 promotes chondrocyte senescence by activating the PI3K/AKT/mTOR signaling pathway
Kang Wang ; Ying Li ; Nuo Xu ; Tingting Guo ; Yun Chen ; Xuran Zeng ; Liqi Sun ; Haochen Xu ; Wei Wei ; Shangxue Yan
Acta Universitatis Medicinalis Anhui 2025;60(8):1506-1513
Objective :
To establish an interleukin-1β (Il-1β) induced inflammatory model of rat articular chondro- cytes (ACs) , and to investigate the relationship between the expression of lysine acetyltransferase 7 (KAT7) under inflammatory stimulation and the senescence of ACs.
Methods:
Primary ACs were obtained by digestion of rat knee cartilage with collagenase type Ⅱ and identified. The inflammatory model of ACs was induced by IL-1β . KAT7 was over-expressed or knocked down in ACs by adeno-associated virus infection or small interfering RNA transfection , respectively. A negative control group was set up. Transwell assay was used to detect cell migration ability. Senes- cent cells were stained with senescence-associated β-galactosidase (SA-β-Gal) . Western blot ( WB) was used to detect the protein expression levels of KAT7 , collagen type II (Col Ⅱ ) , matrix metalloproteinase 13 (MMP13) , tumor protein p53 (p53) and cyclin-dependent kinase inhibitor 1A (p21) . The cells of negative control group and KAT7 over-expression group were performed for RNA sequencing , and WB was used to verify the related signaling pathways obtained by Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis.
Results:
Compared with the control group , the SA-β-Gal staining was enhanced , the protein expression of Col Ⅱ decreased , the pro- tein expression of MMP13 and p53 increased , the cell migration ability decreased , and the expression of KAT7 also increased in the ACs of rats after IL-1β stimulation. Compared with the negative control group , the SA-β-Gal stai- ning was enhanced , the protein expression of Col Ⅱ decreased , the protein expression of MMP13 , p53 and p21 in- creased , and the cell migration ability decreased in the KAT7 over-expression group. Compared with the negative control group , the SA-β-Gal staining was weakened , the protein expression of Col Ⅱ increased , the protein expres- sion of MMP13 , p53 and p21 decreased , and the cell migration ability was enhanced in the KAT7 knockdown inflammatory model of ACs. KEGG enrichment analysis showed that phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was activated. Compared with the negative control group , the relative protein ex⁃pression levels of phosphorylated protein kinase B (p⁃AKT)/AKT and phosphorylated mammalian target of rapamy⁃cin (p⁃mTOR)/mTOR in KAT7 over⁃expression group increased. The relative protein expression levels of p ⁃AKT/AKT and p ⁃mTOR/mTOR in KAT7 knockdown cells decreased.
Conclusion
Rat ACs with high expression of KAT7 exhibit senescence and osteoarthritis phenotype , and the mechanism may be related to the activation of PI3K/AKT/mTOR signaling pathway by KAT7.
2.Clinical Research on Bushen Huoxue Prescription in Treating Kidney Deficiency and Blood Stasis Type Primary Osteoporosis
Lin TIAN ; Haochen KANG ; Shuli WANG ; Ge YANG ; Jiangui ZHU
Chinese Journal of Information on Traditional Chinese Medicine 2017;24(9):11-14
Objective To observe the efficacy and safety of Bushen Huoxue Prescription in the treatment of kidney deficiency and blood stasis type primary osteoporosis. Methods Totally 50 patients with kidney deficiency and blood stasis type primary osteoporosis were collected. They were given Bushen Huoxue Prescription granules twice a day, taking with water, for 12 weeks. Before and after treatment, the femoral neck, Ward's area, L1–4 bone mineral density (BMD) were measured. VAS and TCM syndrome integrals were evaluated before and 4, 8 and 12 week of treatment. The level of serum osteocalcin (OC), β-C-terminal telopeptides of type I collagen (β-CTX) and osteoprotegerin (OPG) were detected before and after treatment. Hematuria routine, liver and kidney function were under safety testing before and after treatment. Results Bushen Huoxue Prescription could significantly increase BMD of left femoral neck and Ward's triangle (P=0.001, P=0.044). L1–4 BMD increased, without statistical significance (P=0.172). The total effective rate was 60.870% (28/46) for L1–4 and left femoral neck and 58.696% (27/46) for Ward's triangle. The VAS and TCM syndrome integral decreased significantly 4 weeks treatment compared with that before the treatment (P<0.01), and the scores decreased significantly with the prolongation of treatment time (F=159.690, P<0.001; F=163.970, P<0.001). After 12 weeks, treatment, the total effective rate for TCM syndromes was 78.26% (36/46). Serum levels of OC and β-CTX showed a tendency to increase, while serum levels of OPG showed a tendency to decrease, without statistical significance (P=0.087, P=0.091, P=0.419). There was no serious adverse reaction in hematuria routine and liver and kidney function. Conclusion Bushen Huoxue Prescription has obvious clinical efficacy for kidney deficiency and blood stasis type primary osteoporosis, which can improve the patients' BMD, improve bone metabolism, relive bone pain, with high level of safety.
3.The ankle-brachial index of type 2 diabetes
International Journal of Traditional Chinese Medicine 2010;32(5):439,443-
Objective To study the ankle-brachial index of the diabetic gangrene. Methods ABI of the sixty cases with type 2 diabetes were measured. The results were divided into four groups: normal, gently abnormal moderate abnormal severely abnormal group. Results 30 cases were normal, occupying 50% (P>0.05), gently and moderate abnormal attained 5 cases (8.33%) and 4 cases (6.67%) respectively, and the rests 21cases were severely abnormal, occupying 35% (P>0.05).Conclusion The normal ABI was not always indicating type 2 diabetes without the gangrene or tendency.


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