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Background and Purpose Experimental Approach Key Results Conclusion and Implications DT‐678 is a novel antiplatelet prodrug, capable of releasing the antiplatelet active metabolite of clopidogrel (AM) upon exposure to glutathione. In this study, we investigated factors responsible for clopidogrel high on‐treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients and evaluated the capacity of DT‐678 to overcome HTPR.A total of 300 consecutive ACS patients naive to P2Y12 receptor inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600‐mg clopidogrel. Platelet reactivity index (PRI) and plasma AM concentrations were determined and grouped according to their CYP2C19 genotypes. DT‐678 was applied ex vivo to whole blood samples to examine its inhibitory effects. To further examine the antiplatelet effectiveness of DT‐678 in vivo, 20 healthy human subjects were recruited in a Phase I clinical trial, and each received a single dose of either 3‐mg DT‐678 or 75‐mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared.Statistical analyses revealed that CYP2C19 genotype, body mass index, hyperuricaemia, and baseline PRI were significantly associated with a higher risk of clopidogrel HTPR in ACS patients. The addition of DT‐678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This observation was further confirmed in healthy volunteers receiving 3 mg of DT‐678.These results suggest that DT‐678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients, demonstrating its potential to improve antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Abstract: Apoptosis is a genetically determined cell suicidal program that plays critical roles in many physiological and pathological processes. In this study, we report the cloning and characterization of a novel human gene, nuclear apoptosis-inducing factor 1 (NAIF1), overexpression of which induces apoptosis in cells. Human NAIF1 is located on chromosome 9q34.11 and encodes 327 amino acids with a homeodomain-like region and two nuclear localization signals at its N-terminal region. NAIF1 is conserved across diverse species, including human, mouse, crab-eating macaque, dog, chicken and frog, and shares no obvious homology to any known genes or proteins. Northern blot analysis revealed wide expression of NAIF1 mRNA throughout human tissues. NAIF1 was predominantly localized in the nucleus. Overexpression of NAIF1 inhibited cell growth and induced apoptosis. Furthermore, NAIF1 transfection caused both decreases in mitochondrial membrane potential and caspase-3 activation. In summary, NAIF1 is a nuclear protein that induces apoptosis when overexpressed. [Copyright &y& Elsevier]

The noninvasive detection technique using serum for large-scale screening is useful for the early diagnosis of gastric cancer (GC). Herein, we employed liquid chromatography mass spectrometry to determine the serum proteome signatures and related pathways in individuals with gastric precancerous (pre-GC) lesions and GC and explore the effect of Helicobacter pylori ( H. pylori ) infection. Differentially expressed proteins in GC and pre-GC compared with non-atrophic gastritis (NAG) group were identified. APOA4, a protein associated with metaplastic differentiation, and COMP, an extracellular matrix protein, were increased in the serum of patients with pre-GC lesions and GC. In addition, several inflammation-associated proteins, such as component C3, were decreased in the GC and pre-GC groups, which highlight a tendency for the inflammatory response to converge at the gastric lesion site during the GC cascade. Moreover, the abundance of proteins associated with oxidant detoxification was higher in the GC group compared with that in the NAG group, and these proteins were also increased in the serum of the H. pylori -positive GC group compared with that in the H. pylori -negative GC patients, reflecting the importance of oxidative stress pathways in H. pylori infection. Collectively, the findings of this study highlight pathways that play important roles in GC progression, and may provide potential diagnostic biomarkers for the detection of pre-GC lesions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gong, Lou, Han, Chen, Zhao, Zhang, Zhang, Xiong, Fu and Ding.)

Maxillofacial bone defects caused by congenital malformations, trauma, tumors, and inflammation can severely affect functions and aesthetics of maxillofacial region. Despite certain successful clinical applications of biomaterial scaffolds, ideal bone regeneration remains a challenge in maxillofacial region due to its irregular shape, complex structure, and unique biological functions. Scaffolds that address multiple needs of maxillofacial bone regeneration are under development to optimize bone regeneration capacity, costs, operational convenience. etc. In this review, we first highlight the special considerations of bone regeneration in maxillofacial region and provide an overview of the biomaterial scaffolds for maxillofacial bone regeneration under clinical examination and their efficacy, which provide basis and directions for future scaffold design. Latest advances of these scaffolds are then discussed, as well as future perspectives and challenges. Deepening our understanding of these scaffolds will help foster better innovations to improve the outcome of maxillofacial bone tissue engineering., (© 2023 The Authors.)

The aim of this study was to identify differently expressed proteins in the presence and absence of EPHX2 gene in mouse hypothalamus using proteomics profiling and bioinformatics analysis. This study was performed on 3 wild type (WT) and 3 EPHX2 gene global knockout (KO) mice (EPHX2(-/-)). Using the nano- electrospray ionization (ESI)-LC-MS/MS detector, we identified 31 over-expressed proteins in WT mouse hypothalamus compared to the KO counterparts. Gene Ontology (GO) annotation in terms of the protein-protein interaction network indicated that cellular metabolic process, protein metabolic process, signaling transduction and protein post-translation biological processes involved in EPHX2(-/-) regulatory network. In addition, signaling pathway enrichment analysis also highlighted chronic neurodegenerative diseases and some other signaling pathways, such as TGF-beta signaling pathway, T cell receptor signaling pathway, ErbB signaling pathway, Neurotrophin signaling pathway and MAPK signaling pathway, were strongly coupled with EPHX2 gene knockout. Further studies into the molecular functions of EPHX2 gene in hypothalamus will help to provide new perspective in neurogenesis.