Biology and Life Sciences

Abstract: (1) This in vitro study investigated the effect of additional proximal Post-Curing on the microhardness of Class-II resin composite restorations. (2) Methods: Thirty-two extracted human third molars received narrow (N) or wide (W) MO Class-II cavities with cervical margins extending below the cemento-enamel junction. Cavities were restored with Venus Diamond using an adhesive protocol and incremental layering. Specimens were assigned to four groups: N.O, N.OT, W.O, W.OT, representing cavity width (N/W) and curing protocol (O: occlusal light curing only, OT: occlusal plus proximal Post-Curing after matrix band removal). After 7 days of storage in artificial saliva, restorations were sectioned into three vertical planes and Vickers microhardness (HV2/30 s) was measured (3) Results: The highest overall microhardness was observed in Group W.OT (81.35 HV2) whereas Group N.O showed the lowest values (73.14 HV2) (p < 0.05). Proximal Post-Curing significantly increased microhardness, with Group N.OT (78.34 HV2) exceeding both occlusal-only groups (W.O: 74.68 HV2; p<0.05). In all groups, microhardness decreased with increasing restoration depth (p<0.05), although this reduction was less pronounced after Post-Curing. (4) Conclusions: Proximal Post-Curing significantly improves polymerization depth and microhardness of Class-II resin composite restorations and should be considered clinical routine in deep cavities.

Abstract: Somatostatin receptors are being investigated as targets for the treatment of high-risk neuroblas-toma stage 4 (NBS4) due to their overexpression on chromosome 17. The paper investigates a po-tential somatostatin activator (agonist) that could activate the signalling pathways of the SSTR2 receptor, as well as the possibility of binding to two other overexpressed GPCRs on chromosome 17. These latter two receptors are the galanin receptor type 2 (GALR2) and corticotropin-releasing hormone receptor 1 (CRHR1). Using computer-aided technology, including OpenEye Scientific Suite, Samson Suite, Flare Suite, and Discovery Studio Visualizer, eight possible compounds were identified and investigated for their absorption, distribution, metabolism, and excretion (ADME) properties, along with their toxicity using the Predictive Toxicity Estimation Software Tool (T.E.S.T.) and two Web-based tools, DEEP-PK and Swiss ADME. Lastly, the retrosynthesis programs ChemAIRS and Spaya were used to investigate potential synthesis pathways for each of the eight compounds. The results suggest that compound 8 (with an RScore of 1.0), a possible agonist (acti-vator) of SSTR2, CRHR1, and GALR2, can be synthesised; future in vitro and in vivo studies are required to validate these findings.

Abstract: Sphingolipid metabolism has emerged as a regulatory interface between lipid homeostasis, organelle stress, and genome maintenance. Although sphingolipids are essential structural components of cellular membranes, specific metabolites also function as bioactive mediators that shape cellular responses to genotoxic stress. In this review, we examine how canonical and atypical sphingolipid pathways influence the DNA damage response through three mechanistic axes. First, ceramide-centered stress signaling links radiation, chemotherapy, and inflammatory injury to kinase and phosphatase pathways, mitochondrial apoptosis, and checkpoint-associated cell-fate decisions. Second, nuclear sphingolipid metabolism, particularly sphingosine kinase 2-dependent production of sphingosine-1-phosphate, regulates chromatin-associated transcriptional programs through modulation of histone deacetylase activity. Third, persistent sphingolipid imbalance promotes metabolic stress by disrupting lysosomal turnover, mitochondrial function, endoplasmic reticulum homeostasis, and redox balance, thereby increasing endogenous oxidative DNA damage. We also discuss atypical sphingolipids, including 1-deoxysphingolipids generated through altered serine palmitoyltransferase substrate utilization, as emerging mediators of mitochondrial dysfunction and genome instability. Finally, we consider the relevance of these mechanisms to cancer, lysosomal storage disorders, and neurodegenerative diseases, where sphingolipid dysregulation may influence therapeutic responses and disease progression. Together, these findings position sphingolipid metabolism as an integrated regulatory network connecting cellular stress signaling, chromatin regulation, organelle dysfunction, and genome stability.