Multidrug-resistant bacteria are emerging as a global threat, making the search for alternative compounds urgent. Antimicrobial peptides (AMPs) became a promising hotspot due to their distinct action mechanism and possibility to be used as an alternative or complement to traditional antibiotics. However, gaining a better understanding about the relationship between antimicrobial peptides structure and its bioactivity is crucial for the development of next generation of antimicrobial agents. NK-2, derived from mammalian protein NK-lysin, has potent antitumor and bactericidal abilities. As proline was considered to be an effective α-helix breaker due to its restricted conformation, to better comprehend the effects of proline in the structure-activity relationship of NK-2, we constructed two NK-2 analogs. We examined the biological activities of NK-2 and its proline substitution analogs and analyzed the resulting conformational changes. Our results showed that introducing proline into the primary sequence of NK-2 significantly decreased the antitumor, antibacterial, and cytotoxic effects, as well as DNA binding activity by changing the α-helix content. However, α-helical content was not the only determining factor, the position of proline inserted was also critical. This study will allow for clearer insight into the role of proline in structure and bioactivity of NK-2 and provide a foundation for future studies.
IntroductionNeuroligins are postsynaptic cell adhesion molecules that interact with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, accumulating evidence, involving mutation analysis, cellular assays, and mouse models, has suggested that neuroligin (NLGN) mutations affect synapse maturation and function. Previously, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162K (NLGN4X), and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing.MethodsIn this study, we analyzed the functional effect of these missense variations by in vitro experiment via the stable HEK293 cells expressing wild‐type and mutant neuroligin.ResultsWe found that the four mutations did not significantly impair the expression of neuroligin 3 and neuroligin 4X, and also did not measurably inhibit the neurexin 1–neuroligin interaction. These variants might play a modest role in the pathogenesis of autism or might simply be unreported infrequent polymorphisms.ConclusionOur data suggest that these four previously described neuroligin mutations are not primary risk factors for autism.
Cell proliferation and migration play important parts in ovarian cancer progression. BMP9, as one of the members of the TGF-ant array of biological roles, including cell differentiation, proliferation, apoptosis, tumorigenesis, and metabolism. However, the role and mechanism of BMP9 in ovarian cancer progression remains uncertain. We found that the expression of BMP9 was increased in human ovarian cancer cell lines, which induced Notch1 intracellular domain (NICD1) accumulation. And we also found the expression abundance of BMP9 is low in ovarian cancer cells. Thus, we generated recombinant adenoviruses overexpressing BMP9 to perform the research. We found that overexpression of BMP9 promoted ovarian cancer cell proliferative viability, cell cycle progression, cell migration in vitro, and accelerated subcutaneous tumor growth in vivo, which was inhibited by dominant-negative mutant Notch1 recombinant adenoviruses. Besides, we also demonstrated that silencing BMP9 by recombinant adenoviruses inhibited ovarian cancer cell viability and migration in vitro. Additionally, BMP9-induced ovarian cancer cell progression also involved the e levation of HES2, c-Myc, MMP9, and Cyclin D1, as well as repressed expression of p27. Together, these results revealed that BMP9 acts as a promoting factor in ovarian cancer progression, and overexpression of BMP9 promotes ovarian cancer progression and growth via Notch1 signaling.Thereby our research may provide new insight into the pathogenesis of ovarian cancer and BMP9-Notch1 signaling may serve as a novel therapeutic target axis for ovarian cancer treatment.
Recent studies have highlighted the development prospects of magnetic hyperthermia in cancer therapy. A few studies on the application of Fe 3 O 4 nanospheres for the magnetic hyperthermia of gynecological malignancies have achieved certain efficacy, but there was no visible progress currently. In this work, Fe 3 O 4 nanospheres modified with polyetherimide (PEI) and folic acid (FA) were synthesized using a hydrothermal method for possible utility in biocompatible and active tumor-targeting magnetic induction hyperthermia. The PEI-and FA-coated Fe 3 O 4 nanospheres showed high crystallinity, well-dispersed spherical structures and ideal M s value. As a result, the designed Fe 3 O 4 @ PEI@FA nanospheres achieved higher specific absorption rate (SAR) values at 360 kHz and 308 Oe, as well as excellent biocompatibility in Hela, SKOV3, HEC-1-A and NIH3T3 cells. These nanospheres can be used as an optimal heating agent for the magnetic hyperthermia treatment of gynecological cancers. K E Y W O R D S anticancer therapy, Fe 3 O 4 nanospheres, magnetic hyperthermia 1 | INTRODUCTION Cancer is a global scourge responsible for high mortality in the world, causes almost 10.0 million deaths annually (2021), reported by World Health Organization in February 2021 factsheets. 1 Among them,
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