Human sclerostin-inspired short peptides reverse osteoporosis and suppress joint degeneration in osteoarthritis via opposing Wnt pathways.

Sclerostin, a key regulator of Wnt/β-catenin signaling, exhibits dual therapeutic potential in bone disorders: its inhibition promotes bone formation in osteoporosis, while its mimicry suppresses aberrant bone growth in osteoarthritis (OA). Using structural insights from NMR studies, we identified two sclerostin-derived peptides: SC-1 (an 18-mer) from loop 2, and SC-3 (a 14-mer) from loop 3. Molecular modeling showed that SC-1 binds to the first ectodomain of LRP6, potentially displacing sclerostin through competitive inhibition to activate Wnt signaling.

Value Addition to Citrus maxima Peels: Extraction and Modification of Naringenin into Hydrazones Derivatives for Anti-Breast Cancer and Osteogenic Activity via In Vitro and In Silico Studies.

This study investigates the value addition of Citrus maxima fruit peels by extracting Naringenin and chemically modifying it into hydrazone derivatives to enhance its anti-cancer and anti-osteoporotic potential. The compounds (2a-f) were synthesised using simple and efficient chemistry. Their pharmacokinetic properties, molecular docking and simulations were evaluated against key hormonal targets, EGFR, ERα, ERβ, HER2 and PR.

Curcumin monoglucuronide protects cartilage from progressive degeneration by blocking MMP-13.

Collagenases (MMP-1, MMP-8, and MMP-13) play significant roles in the pathophysiology of osteoarthritis. Among these proteins, MMP-13 and MMP-8 are known for their catabolic roles in the degradation of the articular cartilage matrix. Using computational studies, we had previously observed that a metabolite of curcumin, Curcumin monoglucuronide (CMG), binds to MMPs involved in cartilage matrix destruction.

Metabolic dysregulation and temporal dynamics of NF-κB-p65/NLRP3, TXNIP, endoplasmic reticulum and mitochondrial stress in silica-induced pulmonary fibrosis in rats.

Silica(SiO)-induced pulmonary fibrosis(PF), a global occupational illness, is characterized by lung dysfunction, inflammation, and extracellular matrix(ECM) deposition. SiO generates PF via several complicated processes, but how they interact in PF initiation and progression is poorly studied. Here, male Sprague-Dawley rats were used to develop PF model by oropharyngeal instillation of SiO(50 mg/ml/rat).

Persistence of Backdoor-Based Watermarks for Neural Networks: A Comprehensive Evaluation.

Deep neural networks (DNNs) have gained considerable traction in recent years due to the unparalleled results they gathered. However, the cost behind training such sophisticated models is resource-intensive, resulting in many to consider DNNs to be intellectual property (IP) to model owners. In this era of cloud computing, high-performance DNNs are often deployed all over the Internet so that people can access them publicly.