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From ideation to real context of use of a digital solution to promote physical and cognitive training for older adults
Age-related trends in trabecular bone scores and bone mineral density in Chinese men with type 2 diabetes mellitus: a cross-sectional study
Spectroscopic aspects of underwater digital holography of plankton
Clinical spectrum of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia in individuals of Korean ancestry
Pipeline for development of acylated peptide based CGRP receptor antagonist with extended half-life for migraine treatment
Exploring target selectivity in designing and identifying PI3Kα inhibitors for triple negative breast cancer with fragment-based and bioisosteric replacement approach
Abstract Triple-negative breast cancer (TNBC) is one of the most fatal malignancies in the world, accounting for 42% of all deaths due to metastasis. The significant development is hindered by the multi-drug resistance and poor patient compliance. PIK3CA gene mutation is one of the important causes of TNBC, which causes dysregulation of the cell cycle and cell proliferation. PI3Kα selective inhibition can decrease the TNBC by a significant level with minimal off-target effects. Novel compounds with high selectivity towards PI3Kα are crucial for treating TNBC. After extensive literature analysis, it was observed that fragment-based drug discovery, combined with structure-based virtual screening and bioisosteric replacement strategy, could provide a novel way for hit-to-lead optimization. The present study focussed on the fragment-based direct linking of 11269 moieties of the ChemDiv fragment library, - to generate novel moieties and further screened them using molecular docking, MMGBSA, and target selectivity analysis. Further, the top 2 moieties – Djh1 and Djh2 were selected after MMGBSA analysis and target selectivity prediction towards kinase. Further induced fit docking (IFD) analysis, DFT analysis, and MD simulation were employed to establish that – Djh1 and Djh2 could act as potential hit molecules for selective inhibition of PI3Kα. Further bioisosteric replacement, docking analysis, and target selectivity analysis were performed with the bioisosteres. The top two bioisosteres of Djh1 – Compound 10, Compound 06 represented excellent efficacy and selectivity towards PI3Kα in the treatment of TNBC after analysis of ADMET analysis. Further, in vitro and in vivo analysis might prove the effectiveness of the hit compounds.
Evaluation of osseointegration of plasma treated polyaryletherketone maxillofacial implants
Abstract Osseointegration is a crucial property of biomaterials used for bone defect repair. While titanium is the gold standard in craniofacial surgeries, various polymeric biomaterials are being explored as alternatives. However, polymeric materials can be bioinert, hindering integration with surrounding tissues. In this investigation, plasma ion immersion implantation (PIII)-treated polyether ether ketone (PEEK) and polyether ketone (PEK) implants were assessed in a sheep maxilla and mandible model. Defects were filled with PIII-treated PEEK and PEK implants, produced through fused filament fabrication (FFF) and selective laser sintering (SLS), respectively. Positive controls were grade 23 titanium implants via selective laser melting, while untreated PEEK implants served as negative controls. Surface analyses using scanning electron microscopy and atomic force microscopy revealed favorable properties. Osseointegration was qualitatively and quantitatively assessed at 8-, 10-, and 12-weeks post-implantation, showing significantly improved outcomes for both PIII-treated PEEK and PEK implants compared to untreated controls. The study suggests PIII treatment enhances FFF-printed PEEK’s osseointegration, and PIII-treated SLS-printed PEK achieves comparable osseointegration to 3D printed titanium. These findings underscore surface modification strategies’ potential for polymeric biomaterials, offering insights into developing alternative implant materials for craniofacial surgeries, with enhanced biocompatibility and osseointegration capabilities for improved clinical outcomes.
Targeted co-delivery nanosystem based on methotrexate, curcumin, and PAMAM dendrimer for improvement of the therapeutic efficacy in cervical cancer
Hierarchical graph-based integration network for propaganda detection in textual news articles on social media
TSC complex decrease the expression of mTOR by regulated miR-199b-3p
Author Correction: Taxonomy and Identification of the Genus Scolopendra in China Using Integrated Methods of External Morphology and Molecular Phylogenetics
Extended spectrum betalactamase and Carbapenemase producing gram negative bacteria from healthcare workers gowns at Debre Berhan Comprehensive Specialized Hospital, Ethiopia
Caprini score combined with thrombotic molecular markers for predicting DVT in patients with traumatic fractures
A nomogram for postoperative pain relief in patients with osteoporotic vertebral compression fracture treated with polymethylmethacrylate bone cement
Synergetic effects of nano-boehmite and Y nano-zeolite on catalytic cracking of residue oil
Exploring novel solitary wave phenomena in Klein–Gordon equation using $$\phi ^{6}$$ model expansion method
Designing of a wide-area power system stabilizer using an exponential distribution optimizer and fuzzy controller considering time delays
Strong immune responses and robust protection following a novel protein in adjuvant tuberculosis vaccine candidate
Abstract BCG remains the only licensed vaccine for tuberculosis (TB), but its efficacy wanes over time. Subunit vaccines, aim to improve BCG immunity and protection, by inducing responses to a few mycobacterial antigens delivered with a specific platform. Since the platform shapes the immune response induced, selecting the right platform has been challenging due to the lack of immune correlates of protection. Recently, the protein-adjuvated subunit vaccine. M72/AS01E, demonstrated 49.7% efficacy in preventing active TB in latently infected adults, indicating that protective immunity through subunit vaccines is possible. In this study we evaluated the immunogenicity and efficacy of the promising mycobacterial antigen PPE15, formulated with five adjuvants developed by the Vaccine Formulation Institute. While all adjuvants were immunogenic, PPE15 with LMQ protected vaccinated mice against an in vivo Mycobacterium tuberculosis challenge, both as a standalone vaccine and as a boost to BCG. Vaccinated mice had enriched lung parenchymal antigen-specific CD4 + CXCR3 + KLRG1− T cells previously associated with TB protection. Heterologous vaccination strategies were also explored by combining intranasal ChAdOx1.PPE15 viral vector, with intramuscular PPE15-LMQ resulting in improved protection compared to individual vaccines. These findings support the progression of this vaccine candidate to the next stages of development.