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Discogenic low back pain (LBP) is a significant clinical condition arising from degeneration of the intervertebral disc, a common yet complex cause of chronic pain, defined by fissuring in the annulus fibrosus resulting in vascularization of growing granulation tissue and growth of nociceptive nerve fibers along the laceration area. This paper delves into the anatomical and pathophysiological underpinnings of discogenic LBP, emphasizing the role of intervertebral disc degeneration in the onset of pain. The pathogenesis is multifactorial, involving processes like mitochondrial dysfunction, accumulation of advanced glycation end products, and pyroptosis, all contributing to disc degeneration and subsequent pain. Despite its prevalence, diagnosing discogenic LBP is challenging due to the overlapping symptoms with other forms of LBP and the absence of definitive diagnostic criteria. Current diagnostic approaches include clinical evaluations, imaging techniques, and the exploration of potential biomarkers. Treatment strategies range from conservative management, such as physical therapy and pharmacological interventions, to more invasive procedures such as spinal injections and surgery. Emerging therapies targeting molecular pathways involved in disc degeneration are under investigation and hold potential for future clinical application. This paper highlights the necessity of a multidisciplinary approach combining clinical, imaging, and molecular data to enhance the accuracy of diagnosis and the effectiveness of treatment for discogenic LBP, ultimately aiming to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Sortilin has been positively correlated with vascular disorders in humans. No study has yet evaluated the possible direct effect of sortilin on vascular function. We used pharmacological and genetic approaches coupled with study of murine and human samples to unravel the mechanisms recruited by sortilin in the vascular system. Sortilin induced endothelial dysfunction of mesenteric arteries through NADPH oxidase 2 (NOX2) isoform activation, dysfunction that was prevented by knockdown of acid sphingomyelinase (ASMase) or sphingosine kinase 1. In vivo, recombinant sortilin administration induced arterial hypertension in WT mice. In contrast, genetic deletion of sphingosine-1-phosphate receptor 3 (S1P3) and gp91phox/NOX2 resulted in preservation of endothelial function and blood pressure homeostasis after 14 days of systemic sortilin administration. Translating these research findings into the clinical setting, we detected elevated sortilin levels in hypertensive patients with endothelial dysfunction. Furthermore, in a population-based cohort of 270 subjects, we showed increased plasma ASMase activity and increased plasma levels of sortilin, S1P, and soluble NOX2-derived peptide (sNOX2-dp) in hypertensive subjects, and the increase was more pronounced in hypertensive subjects with uncontrolled blood pressure. Our studies reveal what we believe is a previously unrecognized role of sortilin in the impairment of vascular function and in blood pressure homeostasis and suggest the potential of sortilin and its mediators as biomarkers for the prediction of vascular dysfunction and high blood pressure., Introduction Over the past few years, sortilin, a member of the vacuolar protein sorting 10 (VPS10P) family of receptors, has been positively correlated with vascular and metabolic disorders (1). Preclinical [...]

Sleep is essential for overall health, yet various sleep disorders disrupt normal sleep patterns, affecting duration, quality, and timing. This pilot study investigate the impact of a food supplement (SPINOFF®) on both sleep quality and mental well-being in 41 participants (mean age: 45.3 years). Initial assessments revealed sleep disturbances (Pittsburgh Sleep Quality Index—PSQ—mean score: 8.2) and insomnia symptoms (Insomnia Severity Index—ISI— mean score: 12.7). Mental health assessments showed psychological distress (Dass-21 Depression mean score: 4.2, Anxiety mean score: 6.9, Stress mean score: 11.6, Total mean score: 22.7). This study assessed sleep continuity using Awakenings per Night (ApN) via a smartwatch (HELO HEALTH®) and conducted the study in two phases: baseline (T0) and after 30 days of treatment (T1) (Phase A). No placebo-control was used in this study. After 30 days (Phase B), 21 patients were selected for reassessment. Eleven continued treatment for another 30 days (T2), while ten discontinued. Following the intervention, we observed remarkable improvements in sleep quality and mental distress. The SPINOFF® supplement significantly reduced the PSQI scores (22.4%), indicating enhanced sleep quality. Additionally, there was a 19.6% decrease in ISI scores, demonstrating a reduction in insomnia symptoms. Moreover, overall psychological distress decreased by 19.5% signifying improved psychological well-being. In the second phase, participants who continued treatment experienced more substantial improvements, with a mean decrease of 0.8 points in PSQI scores (±0.9) and a mean decrease of 0.9 points in ISI scores. Our findings suggest that the SPINOFF® supplement has the potential to effectively address both sleep disturbances and psychological distress in our study population. [ABSTRACT FROM AUTHOR]

Antibodies are the macromolecules of choice to ensure specific recognition of biomarkers in biological assays. However, they present a range of shortfalls including a relatively high production cost and limited tissue penetration. Peptides are relatively small molecules able to reproduce sequences of highly specific paratopes and, although they have less biospecificity than antibodies, they offer advantages like ease of synthesis, modifications of their amino acid sequences and tagging with fluorophores and other molecules required for detection. This work presents a strategy to design peptide sequences able to recognize the CD44 hyaluronic acid receptor present in the plasmalemma of a range of cells including human bone marrow stromal mesenchymal cells. The protocol of identification of the optimal amino acid sequence was based on the combination of rational design and in silico methodologies. This protocol led to the identification of two peptide sequences which were synthesized and tested on human bone marrow mesenchymal stromal cells (hBM-MSCs) for their ability to ensure specific binding to the CD44 receptor. Of the two peptides, one binds CD44 with sensitivity and selectivity, thus proving its potential to be used as a suitable alternative to this antibody in conventional immunostaining. In the context of regenerative medicine, the availability of this peptide could be harnessed to functionalize tissue engineering scaffolds to anchor stem cells as well as to be integrated into systems such as cell sorters to efficiently isolate MSCs from biological samples including various cell subpopulations. The data here reported can represent a model for developing peptide sequences able to recognize hBM-MSCs and other types of cells and for their integration in a range of biomedical applications. [ABSTRACT FROM AUTHOR]