Correlation between depression scores and serum NF-ĸB/NLRP3 axis, biotinidase, and HMGB1 after treatment with isotretinoin in patients with acne vulgaris.

BACKGROUND: Acne vulgaris (AV) is an inflammatory skin disorder leading to scars and discomfort, its intensity has major psychological consequences such as depression. AIM: To investigate the effect of isotretinoin (ISO) on NF-κB/NLRP3, biotinidase, and HMGB and correlation with depression. PATIENTS AND METHODS: This was a case-control study that involved two groups. Group 1 is 20 healthy control, and group 2 is 20 patients diagnosed with AV according to Global Acne Grading System (GAGS) and received 20 mg ISO for 2 months. Before and after therapy, the Hamilton Depression Rating Scale (HDRS) was applied to assess each participant's level of depression. Nuclear factor kappa B (NF-ĸB), biotinidase, high mobility group box protein (HMGB1), nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP-3) were measured in serum samples. RESULTS: There was no significant difference in all measured markers of healthy group before and after 2 months. Regarding group 2, there was a statistically significant decrease in all measured markers after 2 months of treatment and significant correlations between GAGS, NF-ĸB, HMGB1, NLRP3, biotinidase, and depression score. CONCLUSION: Increased GAGS, HMGB1, NLRP3, and biotinidase were associated with depression severity in AV patients and ISO treatment significantly reduced these parameters and reduced depressive symptoms.

The vitamin D receptor agonist, calcipotriol, modulates fibrogenic pathways mitigating liver fibrosis in-vivo: An experimental study.

Vitamin D was found to be involved in liver fibrosis modulation through binding to its receptor (VDR) halting many fibrotic pathways. Targeting vitamin D-VDR axis using vitamin D analogs may represent an efficient strategy for liver fibrosis treatment . The study aims at testing the potential ability of the VDR agonist, calcipotriol, to stop fibrosis progression and/or regeneration of hepatocytes in an experimental model of liver fibrosis. Mice (CD-1) were injected with thioacetamide (TAA, 100mg/kg, i.p., 3 times/week) for 8 weeks to induce fibrosis and were treated with calcipotriol (20, 60 or 80µg/kg, i.p., daily) concurrently with TAA during the last 4 weeks. Liver function and oxidative stress biomarkers were measured by the end of the study and hepatic sections were examined for inflammation, necrosis and fibrosis percentage. Additionally, liver contents of collagen-1-alpha-1 (COL1a1), transforming growth factor (TGF)-ß1 and phospho-Smad2 (Ser456/467)/Smad3 (Ser423/425) were measured. Finally, expression of TGF-ß1, tissue inhibitor metalloproteinase (TIMP)-1, Smad2/3 and Smad1/5/9 were scored using immunohistochemistry techniques. Mainly, calcipotriol (80µg/kg) significantly (P<0.001) reduced fibrosis percentage and improved TAA effect on transaminases, alkaline phosphatase, COL1a1 level, malondialdehyde, albumin and reduced glutathione (GSH). It also decreased the profibrogenic cytokine TGF-ß1, TIMP-1, Smad2/3, Smad1/5/9 and phospoSmad2/3 significantly (P<0.01) when compared to TAA group. Calcipotriol attenuates TAA induced liver fibrosis and can stop its progression through limiting stellate cells activity by decreasing TGF-ß1 level and modulating TGF-ß1/Smad signaling pathway. It also can help fibrolysis through decreasing TIMP-1 and restoring the balance between metalloproteinases and their inhibitors.