2,243 publications from this institution
Background: Oral squamous cell carcinoma (OSCC) is a highly aggressive neoplasm characterized by grim survival outcomes, despite significant therapeutic advances. Mortality rates (up to 70%) have remained unaltered for decades, predominantly due to profound diagnostic delays. These derive from the asymptomatic nature of the early stages of oral carcinogenesis and the emergence of dysplastic areas in previously benign lesions, acting as the bridge to malignant transformation. Hence, the establishment of reliable salivary biomarkers is crucial for non-invasive OSCC detection, even from the premalignant stage of dysplasia. Based on our previous bioinformatic research identifying stage-specific miRNAs throughout OSCC progression, which yielded miR-34a-5p as the most significant, we aimed to experimentally investigate its role in oral oncogenesis and explore its stage-reflecting biomarker potential for liquid biopsy. Methods: The expression of miR-34a was evaluated using quantitative real-time PCR in saliva samples from 9 patients with oral premalignant dysplastic lesions, 10 patients with OSCC and 10 healthy controls. The diagnostic accuracy of miR-34a expression profiles was assessed using ROC-curve analyses. Results: The expression of salivary miR-34a differed significantly across the studied groups, demonstrating a steep decrease in the presence of epithelial premalignant dysplasia, significant upregulation in OSCC and intermediate levels in normal oral mucosa (p < 0.001). The ROC results indicate strong diagnostic performance for the detection of oral dysplasia (AUC = 0.93; p < 0.001), OSCC (AUC = 0.77; p = 0.01) and excellent accuracy for the discrimination between premalignant and OSCC lesions (AUC = 0.98; p < 0.001). Conclusions: Our findings reveal a state-dependent dysregulation of miR-34a in oral carcinogenesis, suggesting its complex role as a pathogenetic agent that allows for malignant transformation through its diminished expression, and as a secondary reactive mechanism attempting to suppress tumor development. Salivary miR-34a holds great, stage-specific diagnostic potential, thereby reflecting the health state of oral mucosa in real time.
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A bstract : Pro‐inflammatory cytokines, such as interleukin‐1β (IL‐1β, interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNFα), released from inflammatory foci, can activate the hypothalamus to produce corticotrophin‐releasing hormone (CRH) and arginine vasopressin (AVP). These hypothalamic peptides in synergy increase ACTH production by the pituitary gland and hence corticosteroid (CS) secretion by the adrenal cortices. CS dampens inflammation. The pituitary also produces prolactin (PRL), which is pro‐inflammatory, and macrophage inhibitory factor (MIF), which by counteracting the anti‐inflammatory and immunosuppressive effects of CS, is pro‐inflammatory. Lewis rats develop a variety of induced‐autoimmune inflammatory conditions, such as streptococcal cell wall arthritis, whereas the histocompatible F344 Fisher rats are resistant to this condition. Lewis rats have a defective hypothalamic‐pituitary adrenal (HPA) response to a variety of hypothalamic stimuli, but have augmented systemic secretion of AVP. Patients with rheumatoid arthritis (RA) have deficient CS with exaggerated PRL responses to inflammatory stimuli. Within inflammatory foci, CRH is pro‐inflammatory. AVP, which augments autologous mixed lymphocyte reactions, can replace the IL‐2 requirement for γIFN production by T cells via V 1a receptors, and potentiates primary antibody responses, is also pro‐inflammatory. Lewis rats have significantly high plasma levels, hypothalamic content, and in vitro release of AVP in comparison to the inflammatory disease‐resistant Fischer rats. Immunoneutralization of AVP attenuates inflammatory responses. In Sprague‐Dawley rats, AVP potentiates PRL secretion. Preliminary studies in patients with RA have shown that the circulating levels of AVP are significantly increased, which might be a compensatory response to low CS levels or a result of elevated levels of IL‐6 in these patients but could nevertheless contribute to rheumatoid inflammation. A similar observation has been made in patients with ankylosing spondylitis.
This chapter summarizes key requirements and recommendations for design and detailing of reinforced concrete components in regions of high seismic hazard, as put forward by the American Concrete Institute and applied in American practice. It discusses the most important requirements and recommendations applicable to the most ductile building systems. Transverse reinforcement consisting of hoops or stirrups is required over the entire length of a special moment frame beam. Loss of column support can cause collapse or partial collapse of multiple stories. Column transverse reinforcement provides ductility to column sections yielding in flexure and contributes to shear strength. To provide ductility, the transverse reinforcement must provide sufficient lateral restraint to longitudinal bars to delay buckling to larger strains, and must laterally confine the concrete enclosed within the transverse reinforcement. Beam-column joints must satisfy dimensional requirements and shear strength requirements; attention to detailing is needed to ensure that reinforcement congestion is manageable during construction.