Ocular Manifestation in Systemic Sclerosis-A Literature Review.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease that affects more than 2 million people worldwide. It manifests through vasculopathy, an abnormal immunological response, and fibrosis leading to dysfunction of the multiple organs. The disease is categorized into two subtypes: limited cutaneous SSc and diffuse cutaneous SSc. Scleroderma can affect vital organs with respiratory, cardiac, renal, ocular, and dermatological complications. The ocular manifestations of the disease can occur in the anterior and posterior segments of the eye. Changes in the anterior segment related to the disease include eyelid skin remodeling, dry eye syndrome, and conjunctival abnormalities. The disease's impact on the posterior segment of the eye mostly causes pathologies in the retinal microcirculatory system and abnormalities in the optic nerve. This review provides detailed insights into ocular complications associated with scleroderma.

Scleroderma and scleroderma-like syndromes.

Systemic sclerosis is a systemic connective tissue disease whose main pathophysiological mechanism is a progressive fibrosis of internal organs and skin leading to thickening and induration. Blood vessels may also be involved. However, systemic scleroderma is not the only disease causing cutaneous sclerosis. There is a group of diseases that mimic scleroderma in their clinical presentation - these are scleroderma-like syndromes. A distinction can be made between syndromes of inflammatory/autoimmune, genetic, metabolic, toxic, drug-induced, occupational, paraneoplastic and syndromes caused by deposition disorders. In the following paper, we have reviewed the literature on scleroderma-like syndromes. We have outlined the factors predisposing to the development of each disease, its pathogenesis, clinical presentation, diagnostic and treatment process and the differences between each syndrome and systemic scleroderma.

Corrigendum: Scleroderma and Scleroderma-like syndromes.

[This corrects the article DOI: 10.3389/fimmu.2024.1351675.].

Retinal Microvasculature in Systemic Sclerosis Patients and the Correlation between Nailfold Capillaroscopic Findings and Optical Coherence Angiography Results.

Background: The comparison of retinal perfusion in the eyes of patients with systemic sclerosis (SSc) and in healthy controls using optical coherence tomography angiography (OCTA). The correlation between nailfold capillaroscopy results and OCTA findings among SSc. Methods: The study enrolled 31 patients with systemic sclerosis and 41 healthy controls. OCTA was performed in both groups to assess the retinal vasculature in the superficial (SCP) and deep (DCP) capillary plexuses and the foveal avascular zone (FAZ) area. Nailfold capillaroscopy (NC) was performed in SSc patients and compared to the FAZ area and the superficial and the deep vessel density. Results: In the SSc group, the parafoveal vessel density in DCP was significantly higher in relation to the mean value (p < 0.0001) and in each quadrant of the macula (p < 0.0001) compared to healthy subjects (p < 0.0001). The patients with early scleroderma patterns in capillaroscopy had a larger superficial and deep FAZ (p = 0.0104, p = 0.0076, respectively) than those with active and late patterns. There was a statistically significant difference in the FAZ when comparing early to active (p < 0.0001) and early to late scleroderma patterns (p < 0.0001). A statistically significant difference was found in the type of interstitial lung disease and the deep FAZ area (p = 0.0484). SSc patients with nonspecific interstitial pneumonia (NSIP) had a larger FAZ than those with usual interstitial pneumonia (UIP) (p = 0.0484). Moreover, NSIP cases had a higher parafoveal mean superficial vessel density than those with UIP (p = 0.0471). Conclusions: Our investigation showed that the peripheral microvascular system correlates with ocular microcirculatory impairment. The results indicate the important role of OCTA in the diagnosis, monitoring, and prognosis of microvascular changes in SSc.

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant attention in the neuroscience and oncological community regarding its neuroimmunomodulatory and oncogenic functions. This review of the literature summarizes and updates contemporary knowledge about PGRN, its associated receptors and signalling pathway involvement in GBM pathogenesis, indicating possible cellular and molecular mechanisms with potential diagnostic, prognostic and therapeutic targets in order to yield successful individual therapeutic strategies. After a review of the literature, we found that there are possible PGRN-targeted therapeutic approaches for implementation in GBM treatment algorithms both in preclinical and future clinical studies. Furthermore, PGRN-targeted therapies exerted their highest efficacy in combination with other established chemotherapeutic agents, such as temozolomide. The results of the analysis suggested that the possible implementation of routine determinations of PGRN and its associated receptors in tumour tissue and biofluids could serve as a diagnostic and prognostic biomarker of GBM. Furthermore, promising preclinical applications of PGRN-related findings should be investigated in clinical studies in order to create new diagnostic and therapeutic algorithms for GBM treatment.

Salidroside: A Promising Agent in Bone Metabolism Modulation.

Rhodiola rosea, a long-lived herbaceous plant from the Crassulaceae group, contains the active compound salidroside, recognized as an adaptogen with significant therapeutic potential for bone metabolism. Salidroside promotes osteoblast proliferation and differentiation by activating critical signaling pathways, including bone morphogenetic protein-2 and adenosine monophosphate-activated protein kinase, essential for bone formation and growth. It enhances osteogenic activity by increasing alkaline phosphatase activity and mineralization markers, while upregulating key regulatory proteins including runt-related transcription factor 2 and osterix. Additionally, salidroside facilitates angiogenesis via the hypoxia-inducible factor 1-alpha and vascular endothelial growth factor pathway, crucial for coupling bone development with vascular support. Its antioxidant properties offer protection against bone loss by reducing oxidative stress and promoting osteogenic differentiation through the nuclear factor erythroid 2-related factor 2 pathway. Salidroside has the capability to counteract the negative effects of glucocorticoids on bone cells and prevents steroid-induced osteonecrosis. Additionally, it exhibits multifaceted anti-inflammatory actions, notably through the inhibition of tumor necrosis factor-alpha and interleukin-6 expression, while enhancing the expression of interleukin-10. This publication presents a comprehensive review of the literature on the impact of salidroside on various aspects of bone tissue metabolism, emphasizing its potential role in the prevention and treatment of osteoporosis and other diseases affecting bone physiology.