Active vitamin D [1,25(OH)2D3—calcitriol] is a secosteroid hormone whose receptor is expressed on all cells of the immune system. Vitamin D has a global anti-inflammatory effect and its role in the management of a SARS-CoV-2 infection has been investigated since the beginning of the COVID-19 pandemic. In this narrative review, the laboratory and clinical results of a vitamin D supplementation have been collected from both open-label and blinded randomized clinical trials. The results are generally in favor of the utility of maintaining the serum concentrations of calcifediol [25(OH)D3] at around 40 ng/mL and of the absolute usefulness of its supplementation in subjects with deficient serum levels. However, two very recent large-scale studies (one open-label, one placebo-controlled) have called into question the contribution of vitamin D to clinical practice in the era of COVID-19 vaccinations. The precise role of a vitamin D supplementation in the anti-COVID-19 armamentarium requires further investigations in light of the breakthrough which has been achieved with mass vaccinations.
From sea shores to the abysses of the deep ocean, marine ecosystems have provided humanity with valuable medicinal resources. The use of marine organisms is discussed in ancient pharmacopoeias of different times and geographic regions and is still deeply rooted in traditional medicine. Thanks to present-day, large-scale bioprospecting and rigorous screening for bioactive metabolites, the ocean is coming back as an untapped resource of natural compounds with therapeutic potential. This renewed interest in marine drugs is propelled by a burgeoning research field investigating the molecular mechanisms by which newly identified compounds intervene in the pathophysiology of human diseases. Of great clinical relevance are molecules endowed with anti-inflammatory and immunomodulatory properties with emerging applications in the management of chronic inflammatory disorders, autoimmune diseases, and cancer. Here, we review the historical development of marine pharmacology in the Eastern and Western worlds and describe the status of marine drug discovery. Finally, we discuss the importance of conducting sustainable exploitation of marine resources through biotechnology.
Rheumatoid arthritis (RA) is an invalidating chronic autoimmune disorder characterized by joint inflammation and progressive bone damage. Dietary intervention is an important component in the treatment of RA to mitigate oxidative stress, a major pathogenic driver of the disease. Alongside traditional sources of antioxidants, microalgae—a diverse group of photosynthetic prokaryotes and eukaryotes—are emerging as anti-inflammatory and immunomodulatory food supplements. Several species accumulate therapeutic metabolites—mainly lipids and pigments—which interfere in the pro-inflammatory pathways involved in RA and other chronic inflammatory conditions. The advancement of the clinical uses of microalgae requires the continuous exploration of phytoplankton biodiversity and chemodiversity, followed by the domestication of wild strains into reliable producers of said metabolites. In addition, the tractability of microalgal genomes offers unprecedented possibilities to establish photosynthetic microbes as light-driven biofactories of heterologous immunotherapeutics. Here, we review the evidence-based anti-inflammatory mechanisms of microalgal metabolites and provide a detailed coverage of the genetic engineering strategies to enhance the yields of endogenous compounds and to develop innovative bioproducts.
Systemic sclerosis (SSc) is connective tissue disease characterised by early microvascular damage and tissue fibrosis. Nailfold videocapillaroscopy (NVC) enables direct assessment of the microangiopathy and classification into "scleroderma patterns", offering potential prognostic value. This systematic review aims to analyse the most updated evidence linking NVC findings with organ-specific involvement in SSc. Uniquely, only longitudinal studies, with centralised reading using the European Alliance of Associations for Rheumatology (EULAR) Study Group on Microcirculation in Rheumatic Diseases consensus framework for nailfold capillaroscopy reporting, and published in the last 10 years were selected. Risk-of-bias assessment was assessed by 3 reviewers using the "QUality In Prognosis Studies" (QUIPS) risk-of-bias tool. In total, 14 manuscripts with low to moderate risk of bias were selected and critically analysed. Reduced capillary density (<7 capillaries/mm) and "Active/Late" scleroderma patterns, consistently predicted disease progression. Low capillary density and both "Active" and "Late" scleroderma patterns were strongly associated with more severe skin fibrosis, digital ulcers and calcinosis, pulmonary (arterial) hypertension and interstitial lung disease. A lowered capillary density further predicted major cardiovascular events and gastrointestinal dysmotility, and linked with subclinical renal vasculopathy. In Early SSc, "Active" or "Late" patterns increased the probability of progression to definite SSc. Finally, reduced capillary density reflects a globally more severe phenotype with worse prognosis. Integrating NVC into routine assessment may enable earlier identification of high-risk patients and promote timely intervention to prevent irreversible organ damage.