Osteoma in the upper cervical spine: A case report and comprehensive literature review.

INTRODUCTION AND IMPORTANCE: Osteoma is a benign, and usually asymptomatic bone tumor normally found in the skull and facial bones, although it can occasionally occur in the long bones and spine. CASE PRESENTATION: In this article, we present a 49-year-old male patient who experienced progressive neck pain accompanied by left-sided radicular pain symptoms. Clinical investigation using various imaging techniques confirmed a bone-forming lesion located within the C1 vertebrae region. Treatment involved performing hemilaminectomy of C1 along with resection for complete removal of this extradural bone lesion, ultimately achieving symptom relief. Histopathological examination of the resected specimen leads to the diagnosis of osteoma. Along with reporting this case, we conducted a comprehensive literature review of the previously reported spinal osteoma cases. CLINICAL DISCUSSION: Histopathological examination confirmed the diagnosis of osteoma. A comprehensive literature review was conducted, revealing 16 previously reported cases of spinal osteoma. Among these, only one case involved the C1 vertebra and presented similar neurological symptoms. The review underscores the rarity of spinal osteomas and the importance of surgical intervention for symptom relief. CONCLUSION: Spinal osteomas are rare but should be considered in the differential diagnosis of patients presenting with neck pain and radicular symptoms. Surgical removal of the lesion is often necessary for symptom relief, as highlighted by our case and supported by the literature review. This case adds to the limited body of evidence on spinal osteomas and emphasizes the importance of a multidisciplinary approach for optimal patient outcomes.

Association of Demographic, Clinical, and Vaccination Characteristics with COVID-19 Viral Load Assessed by qRT-PCR.

BACKGROUND: The effect of vaccination on the SARS-CoV-2 baseline viral load and clearance during COVID-19 infection is debatable. This study aimed to assess the effects of demographic and vaccination characteristics on the viral load of SARS-CoV-2. METHODS: We included the patients referred for outpatient SARS-CoV-2 qRT-PCR (reverse transcriptase quantitative polymerase chain reaction) test between July and September 2022. Cycle threshold (Ct) data were compared based on the demographic and vaccination characteristics. A generalized linear model was used to determine the factors associated with the SARS-CoV-2 PCR Ct value. RESULTS: Of 657 participants, 390 (59.4%) were symptomatic and 308 (47.1%) were COVID-19 positive. Among 590 individuals with known vaccination status, 358 (60.6%) were booster vaccinated, 193 (32.6%) were fully vaccinated, 13 (2.2%) were partially vaccinated, and 26 (4.4%) were unvaccinated. Most vaccinated patients received inactivated vaccines (70.5%). The median Ct value was 20 [IQR: 18-23.75] with no significant difference between individuals with different vaccination statuses (P value = 0.182). There were significant differences in Ct value in terms of both symptom presence and onset (both P values < 0.001). Our regression model showed that inactivated vaccines (P value = 0.027), mRNA vaccines (P value = 0.037), and the presence and onset of symptoms (both P values < 0.001) were independent factors significantly associated with the viral load. CONCLUSION: The SARS-CoV-2 baseline viral load is unaffected by vaccination status, yet vaccination might accelerate viral clearance. Furthermore, we demonstrated that the presence and onset of symptoms are independent variables substantially associated with the patient's viral load.

A systems pharmacology approach to identify the autophagy-inducing effects of Traditional Persian medicinal plants.

Aging is correlated with several complex diseases, including type 2 diabetes, neurodegeneration diseases, and cancer. Identifying the nature of this correlation and treatment of age-related diseases has been a major subject of both modern and traditional medicine. Traditional Persian Medicine (TPM) embodies many prescriptions for the treatment of ARDs. Given that autophagy plays a critical role in antiaging processes, the present study aimed to examine whether the documented effect of plants used in TPM might be relevant to the induction of autophagy? To this end, the TPM-based medicinal herbs used in the treatment of the ARDs were identified from modern and traditional references. The known phytochemicals of these plants were then examined against literature for evidence of having autophagy inducing effects. As a result, several plants were identified to have multiple active ingredients, which indeed regulate the autophagy or its upstream pathways. In addition, gene set enrichment analysis of the identified targets confirmed the collective contribution of the identified targets in autophagy regulating processes. Also, the protein-protein interaction (PPI) network of the targets was reconstructed. Network centrality analysis of the PPI network identified mTOR as the key network hub. Given the well-documented role of mTOR in inhibiting autophagy, our results hence support the hypothesis that the antiaging mechanism of TPM-based medicines might involve autophagy induction. Chemoinformatics study of the phytochemicals using docking and molecular dynamics simulation identified, among other compounds, the cyclo-trijuglone of Juglans regia L. as a potential ATP-competitive inhibitor of mTOR. Our results hence, provide a basis for the study of TPM-based prescriptions using modern tools in the quest for developing synergistic therapies for ARDs.

AICAR and nicotinamide treatment synergistically augment the proliferation and attenuate senescence-associated changes in mesenchymal stromal cells.

BACKGROUND: Mesenchymal stromal cell (MSC) stemness capacity diminishes over prolonged in vitro culture, which negatively affects their application in regenerative medicine. To slow down the senescence of MSCs, here, we have evaluated the in vitro effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK activator, and nicotinamide (NAM), an activator of sirtuin1 (SIRT1). METHODS: Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10. Cell proliferation, differentiation capacity, level of apoptosis and autophagy, morphological changes, total cellular reactive oxygen species (ROS), and activity of mTORC1 and AMPK were compared among different treatment groups. RESULTS: MSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both. Treatment with AICAR or NAM led to decreased expression of ß-galactosidase, reduced accumulation of dysfunctional lysosomes, and characteristic morphologic features of young MSCs. Furthermore, while NAM administration could significantly reduce the total cellular ROS in aged MSCs, AICAR treatment did not. Moreover, AICAR-treated cells possess a high proliferation capacity; however, they also show the highest level of cellular apoptosis. The observed effects of AICAR and NAM were in light of the attenuated mTORC1 activity and increased AMPK activity and autophagy. CONCLUSIONS: Selective inhibition of mTORC1 by AICAR and NAM boosts autophagy, retains MSCs' self-renewal and multi-lineage differentiation capacity, and postpones senescence-associated changes after prolonged in vitro culture. Additionally, co-administration of AICAR and NAM shows an additive or probably a synergistic effect on cellular senescence.

Aging: A cell source limiting factor in tissue engineering.

Tissue engineering has yet to reach its ideal goal, i.e. creating profitable off-the-shelf tissues and organs, designing scaffolds and three-dimensional tissue architectures that can maintain the blood supply, proper biomaterial selection, and identifying the most efficient cell source for use in cell therapy and tissue engineering. These are still the major challenges in this field. Regarding the identification of the most appropriate cell source, aging as a factor that affects both somatic and stem cells and limits their function and applications is a preventable and, at least to some extents, a reversible phenomenon. Here, we reviewed different stem cell types, namely embryonic stem cells, adult stem cells, induced pluripotent stem cells, and genetically modified stem cells, as well as their sources, i.e. autologous, allogeneic, and xenogeneic sources. Afterward, we approached aging by discussing the functional decline of aged stem cells and different intrinsic and extrinsic factors that are involved in stem cell aging including replicative senescence and Hayflick limit, autophagy, epigenetic changes, miRNAs, mTOR and AMPK pathways, and the role of mitochondria in stem cell senescence. Finally, various interventions for rejuvenation and geroprotection of stem cells are discussed. These interventions can be applied in cell therapy and tissue engineering methods to conquer aging as a limiting factor, both in original cell source and in the in vitro proliferated cells.

Dynamic modeling of signal transduction by mTOR complexes in cancer.

Signal integration has a crucial role in the cell fate decision and dysregulation of the cellular signaling pathways is a primary characteristic of cancer. As a signal integrator, mTOR shows a complex dynamical behavior which determines the cell fate at different cellular processes levels, including cell cycle progression, cell survival, cell death, metabolic reprogramming, and aging. The dynamics of the complex responses to rapamycin in cancer cells have been attributed to its differential time-dependent inhibitory effects on mTORC1 and mTORC2, the two main complexes of mTOR. Two explanations were previously provided for this phenomenon: 1-Rapamycin does not inhibit mTORC2 directly, whereas it prevents mTORC2 formation by sequestering free mTOR protein (Le Chatelier's principle). 2-Components like Phosphatidic Acid (PA) further stabilize mTORC2 compared with mTORC1. To understand the mechanism by which rapamycin differentially inhibits the mTOR complexes in the cancer cells, we present a mathematical model of rapamycin mode of action based on the first explanation, i.e., Le Chatelier's principle. Translating the interactions among components of mTORC1 and mTORC2 into a mathematical model revealed the dynamics of rapamycin action in different doses and time-intervals of rapamycin treatment. This model shows that rapamycin has stronger effects on mTORC1 compared with mTORC2, simply due to its direct interaction with free mTOR and mTORC1, but not mTORC2, without the need to consider other components that might further stabilize mTORC2. Based on our results, even when mTORC2 is less stable compared with mTORC1, it can be less inhibited by rapamycin.

Aging and stem cell therapy: AMPK as an applicable pharmacological target for rejuvenation of aged stem cells and achieving higher efficacy in stem cell therapy.

In recent years, tissue regeneration has become a promising field for developing stem cell-based transplantation therapies for human patients. Adult stem cells are affected by the same aging mechanisms that involve somatic cells. One of the mechanisms involved in cellular aging is hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and disruption of 5' adenosine monophosphate-activated protein kinase (AMPK). Aging of stem cells results in their impaired regenerative capacity and depletion of stem cell pools in adult tissue, which results in lower efficacy of stem cell therapy. By utilizing an effective therapeutic intervention for aged stem cells, stem cell therapy can become more promising for future application. mTORC1 inhibition is a practical approach to preserve the stem cell pool. In this article, we review the dynamic interaction between sirtuin (silent mating type information regulation 2 homolog) 1, AMPK, and mTORC1. We propose that using AMPK activators such as 5-aminoimidazole-4-carboxamide ribonucleotide, A769662, metformin, and oxidized nicotinamide adenine dinucleotide (NAD+) are practical ways to be employed for achieving better optimized results in stem cell-based transplantation therapies.