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Identification of the therapeutic potential of novel TIGIT/PVR interaction blockers based advanced computational techniques and experimental validation.

Biophys Chem

December 2024

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address:

The inhibition of the TIGIT/PVR interaction demonstrates considerable anticancer properties by enhancing the cytotoxic activity of natural killer (NK) and CD8+ T cells. However, the development of small molecule inhibitors that target TIGIT is currently limited. In this study, small molecules with the capacity to bind TIGIT and block the TIGIT/PVR interaction were screened through an advanced computational process, subsequently confirmed by blocking assays.

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Sanguinarine suppresses oral squamous cell carcinoma progression by targeting the PKM2/TFEB aix to inhibit autophagic flux.

Phytomedicine

December 2024

Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China; Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai 200011, China. Electronic address:

Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies. However, there is no effective treatment for OSCC.

Purpose: This study aimed to identify a natural compound with significant efficacy against OSCC and elucidate its primary mechanism of action.

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The FIKK protein family, encompassing 21 serine-threonine protein kinases, is a distinctive cluster exclusive to the Apicomplexa phylum. Predominantly located in which is a malarial parasite, with a solitary gene identified in a distinct apicomplexan species, this family derives its nomenclature from - phenylalanine, isoleucine, lysine, lysine (FIKK), a conserved amino acid motif. Integral to the parasite's life cycle and consequential to malaria pathogenesis, the absence of orthologous proteins in eukaryotic organisms designates it as a promising antimalarial drug target.

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Building a modular and multi-cellular virtual twin of the synovial joint in Rheumatoid Arthritis.

NPJ Digit Med

December 2024

GenHotel, Laboratoire Européen de Recherche Pour La Polyarthrite Rhumatoïde, University Paris-Saclay, University Evry, Evry, France.

Rheumatoid arthritis is a complex disease marked by joint pain, stiffness, swelling, and chronic synovitis, arising from the dysregulated interaction between synoviocytes and immune cells. Its unclear etiology makes finding a cure challenging. The concept of digital twins, used in engineering, can be applied to healthcare to improve diagnosis and treatment for complex diseases like rheumatoid arthritis.

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The development of phosphorylation-suppressing inhibitors targeting Signal Transducer and Activator of Transcription 3 (STAT3) represents a promising therapeutic strategy for non-small cell lung cancer (NSCLC). In this study, a generative model was developed using transfer learning and virtual screening, leveraging a comprehensive dataset of STAT3 inhibitors to explore the chemical space for novel candidates. This approach yielded a chemically diverse library of compounds, which were prioritized through molecular docking and molecular dynamics (MD) simulations.

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