Molecules and Cells最新文献

The sense of taste arises from the detection of chemicals in food by taste buds, the peripheral cellular detectors for taste. Although numerous studies have extensively investigated taste buds, research on neural circuits from primary taste neurons innervating taste buds to the central nervous system has only recently begun owing to recent advancements in neuroscience research tools. This minireview focuses primarily on recent reports utilizing advanced neurogenetic tools across relevant brain regions.

The nonsense-mediated mRNA decay (NMD) pathway and the p53 pathway, linked to tumorgenesis, are also promising targets for cancer treatment. NMD plays an important role in RNA quality control, while the p53 pathway is involved in cancer suppression. However, their individual and combined effects on cervical cancer are poorly understood. In this study, we evaluated the impacts of NMD inhibitor, Mouse double minute 2 homolog (MDM2) inhibitor, and their combination on cell apoptosis, cell cycle, and p53 target genes in human papillomavirus-18-positive HeLa cells. Our findings revealed that XR-2 failed to activate p53 or induce apoptosis in HeLa cells, whereas SMG1 (serine/threonine-protein kinase 1) inhibitor repressed cell proliferation at high concentrations. Notably, the combination of these 2 agents significantly inhibited cell proliferation, arrested the cell cycle, and triggered cell apoptosis. Mechanistically, MDM2 inhibitor and NMD inhibitor likely exert a synergistically through the truncated E6 protein. These results underscore the potential of employing a combination of MDM2 inhibitor and NMD inhibitor as a promising candidate for the clinical treatment of human papillomavirus-infected tumors.

Excessive blood vessel wall thickening, known as intimal hyperplasia, can result from injury or inflammation and increase the risk of vascular diseases. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays key roles in tumor surveillance, autoimmune diseases, and apoptosis; however, its role in vascular stenosis remains controversial. Treatment with recombinant isoleucine zipper hexamerization domain soluble TRAIL (ILz(6):TRAIL) significantly inhibited the progression of neointimal hyperplasia (NH) induced by anastomosis of the carotid artery and jugular vein dose dependently, and adenovirus expressing secretable ILz(6):TRAIL also inhibited NH induced by balloon injury in the femoral artery of rats. This study demonstrated the preventive and partial regressive effects of ILz(6):TRAIL on anastomosis of the carotid artery and jugular vein- or balloon-induced NH.

The coordinated movement of germ layer progenitor cells reaches its peak at the dorsal side, where the Bmp signaling gradient is low, and minimum at the ventral side, where the Bmp gradient is high. This dynamic cell movement is regulated by the interplay of various signaling pathways. The noncanonical Wnt signaling cascade serves as a pivotal regulator of convergence and extension cell movement, facilitated by the activation of small GTPases such as Rho, Rab, and Rac. However, the underlying cause of limited cell movement at the ventral side remains elusive. To explore the functional role of a key regulator in constraining gastrulation cell movement at the ventral side, we investigated the Bmp4-direct target gene, sizzled (szl), to assess its potential role in inhibiting noncanonical Wnt signaling. In our current study, we demonstrated that ectopic expression of szl led to gastrulation defects in a dose-dependent manner without altering cell fate specification. Overexpression of szl resulted in decreased elongation of Activin-treated animal cap and Keller explants. Furthermore, our immunoprecipitation assay unveiled the physical interaction of Szl with noncanonical Wnt ligand proteins (Wnt5 and Wnt11). Additionally, the activation of small GTPases involved in Wnt signaling mediation (RhoA and Rac1) was diminished upon szl overexpression. In summary, our findings suggest that Bmp4 signaling negatively modulates cell movement from the ventral side of the embryo by inducing szl expression during early Xenopus gastrulation.

The actin-based cytoskeleton is considered a fundamental driving force for cell differentiation and development. Destrin (Dstn), a member of the actin-depolymerizing factor family, regulates actin dynamics by treadmilling actin filaments and increasing globular actin pools. However, the specific developmental roles of dstn have yet to be fully elucidated. Here, we investigated the physiological functions of dstn during early embryonic development using Xenopus laevis as an experimental model organism. dstn is expressed in anterior neural tissue and neural plate during Xenopus embryogenesis. Depleting dstn promoted morphants with short body axes and small heads. Moreover, dstn inhibition extended the neural plate region, impairing cell migration and distribution during neurulation. In addition to the neural plate, dstn knockdown perturbed neural crest cell migration. Our data suggest new insights for understanding the roles of actin dynamics in embryonic neural development, simultaneously presenting a new challenge for studying the complex networks governing cell migration involving actin dynamics.

Particulate matter 2.5 (PM_2.5) poses a serious threat to human health and is responsible for respiratory disorders, cardiovascular diseases, and skin disorders. 3-Bromo-4,5-dihydroxybenzaldehyde (3-BDB), abundant in marine red algae, exhibits anti-inflammatory, antioxidant, and antidiabetic activities. In this study, we investigated the protective mechanisms of 3-BDB against PM_2.5-induced cell cycle arrest and autophagy in human keratinocytes. Intracellular reactive oxygen species generation, DNA damage, cell cycle arrest, intracellular Ca²⁺ level, and autophagy activation were tested. 3-BDB was found to restore cell proliferation and viability which were reduced by PM_2.5. Furthermore, 3-BDB reduced PM_2.5-induced reactive oxygen species levels, DNA damage, and attenuated cell cycle arrest. Moreover, 3-BDB ameliorated the PM_2.5-induced increases in cellular Ca²⁺ level and autophagy activation. While PM_2.5 treatment reduced cell growth and viability, these were restored by the treatment with the autophagy inhibitor bafilomycin A1 or 3-BDB. The findings indicate that 3-BDB ameliorates skin cell death caused by PM_2.5 via inhibiting cell cycle arrest and autophagy. Hence, 3-BDB can be exploited as a preventive/therapeutic agent for PM_2.5-induced skin impairment.