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Biology subjects

Babu, G.

Publications and source records attributed to Babu, G..

2 recordsLinked to original sources

Multi Omics Driven Polypharmacology for Osteoarthritis Joint Regeneration

Osteoarthritis (OA) is a common degenerative condition of major joints with no effective cure. Yograj Guggulu (YG) is a well-established polyherbal formulation in Indian traditional medicine for the management of joint disorders. However, its mode of action remains unclear. We integrated multi omics network analysis with a rat model to investigate the effects of oral administration of YG on osteoarthritic joints. YG administration significantly alleviated pain and improved joint function. Imaging and histological analyses reveal that YG protects against structural degeneration in the joint with OA. Proteomic and metabolomic profiling, along with network analysis, uncovered that multiple components of YG alter protein expression in key pathways related to inflammation and cartilage degradation, thus validating the observed clinical effects. The efficacy of YG seems to be the result of the synergistic action of its diverse constituents. Our findings support the use of YG as a multitarget therapy for OA and encourage efforts for the potential repurposing of its active components.

systems biology↗

Melanotransferrin Functions as a Pro-Oncogenic WNT Agonist: A Yin-Yang Relationship in Melanoma with the WNT Antagonist and Metastasis Suppressor, NDRG1

A persistent mystery in the melanoma field has been the function of one of the first melanoma tumor antigens characterized, namely p97 (melanotransferrin; MTf). While MTf expression increases melanoma cell proliferation, migration, and tumorigenesis, the molecular mechanism responsible is unknown. On the other hand, N-myc down-stream regulated gene 1 (NDRG1) is a potent metastasis suppressor and WNT antagonist. Expression of NDRG1 in melanoma cells suggests a role in inhibiting metastasis, with this study investigating MTfs role in oncogenic signaling. We demonstrate MTf acts as a pro-oncogenic WNT agonist, which down-regulates NDRG1, while silencing MTf increases NDRG1 expression. In contrast, silencing NDRG1 increases MTf expression. These observations demonstrate a bidirectional negative feedback loop and "Yin-Yang" relationship between MTf and NDRG1. Mechanistically, MTf was directly associated with the WNT co-receptor, lipoprotein-receptor 6 (LRP6), and increased total LRP6 expression, activated p-LRP6 (Ser1490), {beta}-catenin, and activated {beta}-catenin (Ser552) levels, with MTf expression inducing their nuclear accumulation. Additionally, MTf expression increased downstream WNT targets, namely cyclin D1 and c-Myc, with c-Myc down-regulating NDRG1 expression. Silencing c-Myc prevented the Yin-Yang relationship between NDRG1 and MTf, indicating c-Myc played a key role in their inverse regulation. Melanoma patient specimens demonstrated that a low NDRG1/MTf ratio was significantly (p = 0.008) associated with lower survival and metastasis. Chemotherapeutic agents that up-regulated NDRG1 depressed MTf and nuclear LRP6 and potently inhibited melanoma xenograft growth in vivo. This study demonstrates MTf acts as a WNT agonist, with a Yin-Yang relationship being observed with the WNT antagonist, NDRG1.

cancer biology↗