作者: Yağlı, Ömer Emre ; Topal, Ahmet Sancar ; Ovalı, Gülgün Yılmaz ; Tuncer, Cansu ; Özdemir, Habib ; Temiz, Cüneyt ; Baş, Gülçin ; Onur, Ece ; Yılmaz, Şemsi Güliz ; Eminoğlu, Emin Mehmet

ABSTRACTStudy DesignProspective biochemical study of comparison of A Disintegrin and Metalloproteinase with Thrombospondin motifs‐4 (ADAMTS‐4) and A Disintegrin and Metalloproteinase with Thrombospondin motifs 5 (ADAMTS5) levels in preoperative and postoperative venous blood, as well as in disc tissue obtained during surgery, in patients undergoing surgery for intervertebral disc disease, with enzyme levels in venous blood from a control group.ObjectiveTo compare the levels of ADAMTS‐4 and ADAMTS‐5 between patients with degenerative intervertebral discs and a healthy control group, aiming to identify biomarkers associated with intervertebral disc degeneration.LiteratureAlthough numerous studies have investigated the relationship between ADAMTS‐4 and ADAMTS‐5 enzymes and degeneration in experimental rat models and human tissues, no study has correlated their serum levels with intervertebral disc degeneration.Method and MaterialsVenous blood samples were obtained preoperatively and postoperatively from 41 patients (age: 42 ± 9.7 years, range 20–63) diagnosed with intervertebral disc disease. The affected disc levels were L4‐L5 in 22 patients and L5‐S1 in 19 patients. These patients were selected based on surgical indications due to radicular pain that persisted after an adequate course of conservative management, without any non‐neurological deficit. Disc tissue samples were also obtained during surgery. Additionally, venous blood samples were collected from a control group with no diagnosed diseases, and lumbar MRIs of the control group showed no significant signs of degeneration. ADAMTS‐4 and ADAMTS‐5 levels were measured using the ELISA method on samples obtained after centrifugation of the collected blood and tissue specimens.ResultsThe level of ADAMTS‐4 in patient serum was found to be lower compared to the control group, while the level of ADAMTS‐5 was higher in the patient serum and lower in the control group.ConclusionElevated levels of ADAMTS‐5 in the blood may be associated with intervertebral disc degeneration.

2024-12-01·IUBMB Life

Neuroprotective effects of resveratrol through modulation of PI3K/Akt/GSK‐3β pathway and metalloproteases

Article

作者: Ozpak, Lütfiye ; Bağca, Bakiye Göker

AbstractTo analyze the expressional changes in the PI3K/Akt/GSK‐3β pathway and metalloprotease in the cellular Alzheimer's Disease (AD) model with the effect of antioxidant resveratrol. Neuron‐like cells were obtained by a two‐step method of neuronal differentiation by using a combination of retinoic acid (RA) and brain‐derived factor (BDNF) exposure. Then, the application of the amyloid beta peptide 25–35 (Aβ25‐35) to the cell culture mimicked the environmental toxicity observed in AD. Afterward, cell viability and apoptosis assays were performed to determine whether the resveratrol exerts a cytotoxic and apoptotic effect. Finally, the expressional changes in genes in the cellular AD model with the effect of resveratrol were analyzed by Real‐Time PCR. The analysis in silico was assessed using the STRING V12.0 database in each group. Apoptosis data findings were decreased by 1.5‐fold and 2.5‐fold respectively by Differentiated+Resveratrol (RES) and RES when compared to control but no significant difference was observed between RES and AD model groups. Real‐time PCR analysis results revealed PI3K (3.38‐fold), AKT (3.95‐fold), and RELN (1.99‐fold) expressions were significantly higher (p < .001), and also GSK‐3β, TAU, ADAMTS‐4, ADAMTS‐5, and TIMP‐3 gene expression levels were significantly downregulated (2.53‐, 1.79‐, 2.85‐, 4.09‐, and 6.62‐fold, respectively) in the Differentiated+Aβ + RES groups compared to the Differentiated+Aβ group (p < .001). Network analysis shows the functional enrichment of 23 Alzheimer‐related GO terms in the Wnt signaling, proteolysis, and extracellular matrix organization pathways. Resveratrol has inhibited GSK‐3β by activating the PI3K/Akt insulin pathway in a neurotoxic environment. In addition, TAU, RELN, metalloproteases, and their inhibitors associated with Alzheimer's pathology have been regulated supporting the neuroprotective effect of resveratrol.

2024-11-20·Nan fang yi ke da xue xue bao = Journal of Southern Medical University

[Tougu Xiaotong Capsule alleviates cartilage degeneration in mice with knee osteoarthritis by modulating Nav1.7].

Article

作者: Lan, S ; Lin, Y ; Chen, Y ; Lu, S ; Li, C ; Lin, Q ; Fu, C

OBJECTIVETo investigate the mechanism by which Tougu Xiaotong Capsule (TGXTC) alleviates chondrocyte degeneration in knee osteoarthritis (KOA).METHODSThirty 2-month-old C57BL/6 mouse models of KOA established using the Hulth method were randomized into model group, TGXTC group, and diclofenac sodium group and received treatment with saline, TGXTC (368 mg/kg), and diclofenac sodium (10 mg/kg) by gavage, respectively, with another 10 untreated mice as the blank control group. All interventions were administered 6 times a week for 4 weeks. After the treatments, structural changes in the cartilage tissue were observed with morphological staining, and Nav1.7 mRNA expression and the protein expression levels of Nav1.7, MMP-3, ADAMTS-5, and COX-2 were detected using RT-qPCR and Western blotting. Fluorescence in situ hybridization (FISH) was used to detect Nav1.7 expression in the chondrocytes. In cultured KOA chondrocytes, the effect of TGXTC and lentivirus-mediated Nav1.7 knockdown on MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, and COX-2 protein expressions were assessed with Western blotting.RESULTSIn KOA mice treatments with TGXTC and diclofenac sodium both significantly alleviated structural damage of the cartilage layer, reduced Nav1.7 protein and mRNA expressions and lowered the expressions of MMP-3, ADAMTS-5, and COX-2 proteins in the cartilage tissues. FISH results indicated that TGXTC treatment significantly reduced IL-1β -induced Nav1.7 expression in the chondrocytes. In Nav1.7 knockdown experiment, Nav1.7 levels were significantly lower in IL-1β+sh-Nav1.7 group than in IL-1β group, and also lower in IL-1β+TGXTC group than in IL-1β+sh-Nav1.7+TGXTC group. TGXTC treatment significantly inhibited IL-1β-induced elevation of MMP-3, MMP-13, ADAMTS-4, ADAMTS-5 and COX-2 protein expressions in the chondrocytes, but its effects were strongly weakened by Nav1.7 knockdown.CONCLUSIONTGXTC alleviates extracellular matrix metabolic disorder in KOA chondrocytes by regulating Nav1.7, thereby mitigating chondrocyte degeneration in KOA mice.

分析

对领域进行一次全面的分析。

或

查看完整样例数据

来和芽仔聊天吧

立即开始免费试用!

智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。

立即开始数据试用!

智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。