Vitamin D Serum Levels in Subjects Tested for SARS-CoV-2: What Are the Differences among Acute, Healed, and Negative COVID-19 Patients? A Multicenter Real-Practice Study.

Vitamin D might play a role in counteracting COVID-19, albeit strong evidence is still lacking in the literature. The present multicenter real-practice study aimed to evaluate the differences of 25(OH)D3 serum levels in adults tested for SARS-CoV-2 (acute COVID-19 patients, subjects healed from COVID-19, and non-infected ones) recruited over a 6-month period (March-September 2021). In a sample of 117 subjects, a statistically significant difference was found, with acute COVID-19 patients demonstrating the lowest levels of serum 25(OH)D3 (9.63 ± 8.70 ng/mL), significantly lower than values reported by no-COVID-19 patients (15.96 ± 5.99 ng/mL, p = 0.0091) and healed COVID-19 patients (11.52 ± 4.90 ng/mL, p > 0.05). Male gender across the three groups displayed unfluctuating 25(OH)D3 levels, hinting at an inability to ensure adequate levels of the active vitamin D3 form (1α,25(OH)2D3). As a secondary endpoint, we assessed the correlation between serum 25(OH)D3 levels and pro-inflammatory cytokine interleukin-6 (IL-6) in patients with extremely low serum 25(OH)D3 levels (<1 ng/mL) and in a subset supplemented with 1α,25(OH)2D3. Although patients with severe hypovitaminosis-D showed no significant increase in IL-6 levels, acute COVID-19 patients manifested high circulating IL-6 at admission (females = 127.64 ± 22.24 pg/mL, males = 139.28 ± 48.95 ng/mL) which dropped drastically after the administration of 1α,25(OH)2D3 (1.84 ± 0.77 pg/mL and 2.65 ± 0.92 ng/mL, respectively). Taken together, these findings suggest that an administration of 1α,25(OH)2D3 might be helpful for treating male patients with an acute COVID-19 infection. Further studies on rapid correction of vitamin D deficiency with fast acting metabolites are warranted in COVID-19 patients.

Biological therapy induces expression changes in Notch pathway in psoriasis.

Psoriasis is a chronic inflammatory skin disease, characterized by hyperproliferation of keratinocytes and by skin infiltration of activated T cells. To date, the pathophysiology of psoriasis has not yet been fully elucidated. The Notch pathway plays a determinant role in cell fate determination, proliferation, differentiation, immune cell development and function. Many biological agents, used in the treatment of psoriasis, include TFN-α inhibitors, such as etanercept, adalimumab, and anti IL-12/IL-23 p40 antibody, such as ustekinumab. This study aimed to determine mRNA expression levels by real-time RT-PCR, and protein expression levels, analysed by Western blot and immunohistochemistry, of some components of the Notch pathway, such as NOTCH1, NOTCH2, JAGGED1, and HES1 after biological treatments in psoriatic patients. mRNA and protein levels of NOTCH1, NOTCH2, JAGGED1 and HES1 were upregulated in skin samples from untreated psoriatic patients compared with normal controls. Biological therapy showed to downregulate differently the protein expression levels of the molecules under study. Our study suggests that Notch pathway components might be a potential therapeutic target against psoriasis.

Nectin like-5 overexpression correlates with the malignant phenotype in cutaneous melanoma.

NECL-5 is involved in regulating cell-cell junctions, in cooperation with cadherins, integrins and platelet-derived growth factor receptor, that are essential for intercellular communication. Its role in malignant transformation was previously described. It has been reported that transformation of melanocytes is associated with altered expression of adhesion molecules suggesting the potential involment of NECL-5 in melanoma development and prognosis. To shed light on this issue, the expression and the role of NECL-5 in melanoma tissues was investigated by bioinformatic and molecular approaches. NECL-5 was up-regulated both at the mRNA and the protein levels in WM35, M14 and A375 cell lines compared with normal melanocytes. A subsequent analysis in primary and metastatic melanoma specimens confirmed "in vitro" findings. NECL-5 overexpression was observed in 53 of 59 (89.8%) and 12 of 12 (100%), primary melanoma and melanoma metastasis, respectively; while, low expression of NECL-5 was detected in 12 of 20 (60%) benign nevi. A significant correlation of NECL-5 overexpression was observed with most of known negative melanoma prognostic factors, including lymph-node involvement (P = 0.009) and thickness (P = 0.004). Intriguingly, by analyzing the large series of melanoma samples in the Xu dataset, we identified the transcription factor YY1 among genes positively correlated with NECL-5 (r = 0.5). The concordant computational and experimental data of the present study indicate that the extent of NECL-5 expression correlates with melanoma progression.