Identification of promising small-molecule inhibitors targeting STK17B for cancer therapeutics: molecular docking and molecular dynamics investigations.

Cancer is a complex disease characterized by the uncontrolled growth of abnormal cells, leading to the formation of tumours. STK17B, a member of the DAPK family, has been implicated in various cancers and is considered a potential therapeutic target. However, no drug in the market has been approved for the treatment of STK17 B-associated cancer disease. This research aimed to identify direct inhibitors of STK17B using computational techniques. Ligand-based virtual screening and molecular docking were performed, resulting in the selection of three lead compounds (CID_135698391, CID_135453100, CID_136599608) with superior binding affinities compared to the reference compound dovitinib. While molecular docking simulation revealed specific interactions between the lead compounds and key amino acid residues at the binding pocket of STK17B, molecular dynamics simulations demonstrated that CID_135453100 and CID_136599608 exhibit stable conformations and comparable flexibility to dovitinib. However, CID_135698391 did not perform well using this metric as it displayed poor stability. Overall, small-molecule compounds CID_135453100 and CID_136599608 showed promising binding interactions and stability, suggesting their potential as direct inhibitors of STK17B. These findings could contribute to the exploration of novel therapeutic options targeting STK17B in cancer treatment.Communicated by Ramaswamy H. Sarma.

Computational-based drug design of novel small molecules targeting p53-MDMX interaction.

The regulation of the p53 tumor suppressor pathway is critically dependent on the activity of Murine Double Minute 2 (MDM2) and Murine Double Minute X (MDMX) proteins. In certain types of cancer cells, excessive amount of MDMX can poly-ubiquitinate p53, which can result in its degradation, leading to a subsequent reduction in the levels of this protein. Therefore, the design of small-molecule inhibitors targeting the MDMX-p53 interaction has emerged as a promising strategy for cancer therapy. In this study, we employed computational techniques including pharmacophore modeling and molecular docking to identify three potential small molecule inhibitors (CID_25094615, CID_137634453, and CID_25094344) of the MDMX-p53 interaction from a PubChem database. Molecular dynamics of 100000 ps were conducted to assess the stability of the MDMX-inhibitor complexes. Our results showed that all three compounds exhibit stable binding with MDMX, with significantly lower root mean square deviation (RMSD) and fluctuation (RMSF) values than the control ligand, indicating superior stability. Additionally, the three compounds exhibit stronger intermolecular hydrogen bond (HBOND) interactions compared to the control, suggesting stronger stability. Overall, our findings highlight the potential of these compounds as lead candidates for the development of novel anticancer agents that target the MDMX-p53 interaction.Communicated by Ramaswamy H. Sarma.

The Nigerian health information system policy review of 2014 : the need, content, expectations and progress.

BACKGROUND: Nigeria's national health information system (HIS) data sources are grouped into institutional and population based data that traverse many government institutions. Communication and collaboration between these institutions are limited, fraught with fragmentation and challenges national HIS functionality. OBJECTIVES: The objective of this paper was to share insights from and the implications of a recent review of Nigeria's HIS policy in 2014 that resulted in its substantial revision. We also highlight some subsequent enactments. REVIEW PROCESS AND OUTCOMES: In 2013, Nigeria's Federal Ministry of Health launched an inter-ministerial and multi-departmental review of the National Health Management Information System policy of 2006. The review was guided by World Health Organization's 'Framework and Standards for Country Health Information Systems'. The key finding was a lack of governance mechanisms in the execution of the policy, including an absent data management governance process. The review also found a multiplicity of duplicative, parallel reporting tools and platforms. CONCLUSION: Recommendations for HIS Policy revisions were proposed to and implemented by the Federal Government of Nigeria. The revised HIS policy now provides for a strong framework for the leadership and governance of the HIS with early results.

Development of a master health facility list in Nigeria.

UNLABELLED: Abstract. INTRODUCTION: Routine Health Information Systems (RHIS) are increasingly transitioning to electronic platforms in several developing countries. Establishment of a Master Facility List (MFL) to standardize the allocation of unique identifiers for health facilities can overcome identification issues and support health facility management. The Nigerian Federal Ministry of Health (FMOH) recently developed a MFL, and we present the process and outcome. METHODS: The MFL was developed from the ground up, and includes a state code, a local government area (LGA) code, health facility ownership (public or private), the level of care, and an exclusive LGA level health facility serial number, as part of the unique identifier system in Nigeria. To develop the MFL, the LGAs sent the list of all health facilities in their jurisdiction to the state, which in turn collated for all LGAs under them before sending to the FMOH. At the FMOH, a group of RHIS experts verified the list and identifiers for each state. RESULTS: The national MFL consists of 34,423 health facilities uniquely identified. The list has been published and is available for worldwide access; it is currently used for planning and management of health services in Nigeria. DISCUSSION: Unique identifiers are a basic component of any information system. However, poor planning and execution of implementing this key standard can diminish the success of the RHIS. CONCLUSION: Development and adherence to standards is the hallmark for a national health information infrastructure. Explicit processes and multi-level stakeholder engagement is necessary to ensuring the success of the effort.