The Arsenal of Bioactive Molecules in the Skin Secretion of Urodele Amphibians

Urodele amphibians (∼768 spp.), salamanders and newts, are a rich source of molecules with bioactive properties, especially those isolated from their skin secretions. These include pharmacological attributes, such as antimicrobial, antioxidant, vasoactive, immune system modulation, and dermal wound healing activities. Considering the high demand for new compounds to guide the discovery of new drugs to treat conventional and novel diseases, this review summarizes the characteristics of molecules identified in the skin of urodele amphibians. We describe urodele-derived peptides and alkaloids, with emphasis on their biological activities, which can be considered new scaffolds for the pharmaceutical industry. Although much more attention has been given to anurans, bioactive molecules produced by urodeles have the potential to be used for biotechnological purposes and stand as viable alternatives for the development of therapeutic agents.

Molecular Mechanisms of Possible Action of Phenolic Compounds in COVID-19 Protection and Prevention

The worldwide outbreak of COVID-19 was caused by a pathogenic virus called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Therapies against SARS-CoV-2 target the virus or human cells or the immune system. However, therapies based on specific antibodies, such as vaccines and monoclonal antibodies, may become inefficient enough when the virus changes its antigenicity due to mutations. Polyphenols are the major class of bioactive compounds in nature, exerting diverse health effects based on their direct antioxidant activity and their effects in the modulation of intracellular signaling. There are currently numerous clinical trials investigating the effects of polyphenols in prophylaxis and the treatment of COVID-19, from symptomatic, via moderate and severe COVID-19 treatment, to anti-fibrotic treatment in discharged COVID-19 patients. Antiviral activities of polyphenols and their impact on immune system modulation could serve as a solid basis for developing polyphenol-based natural approaches for preventing and treating COVID-19.

The effect of zinc lozenge on pain, oedema, and trismus after impacted third molar surgery: A prospective randomized, double-blinded, placebo-controlled study

The postoperative sequelae after third molar surgery include pain, swelling and trismus, Zinc acts as anti-inflammatory agent, can promote wound healing, immune system modulation, tissue repair, and significant reduction in the use of analgesics for oral pain. This study was aimed to evaluate the efficacy of oral zinc lozenge given 30 min before surgery on reducing postoperative sequelae.s: We recruited 70 patients, randomly assigned to two groups: Zinc and Control group, groups received 40mg Zinc lozenge, placebo lozenge 30 min before surgery respectively and every 6h till 72h after surgery. Third molar extraction was performed under local anesthesia. After extraction, pain, swelling, and mouth opening in both groups observed till 72h.Preoperative and postoperative measurement of visual analog scale scores for pain, edema, interincisal opening, was analyzed using Student t test or ANOVA, Chi-square or Mann-Whit­ney U test was performed for non-parametric samples. P < 0.05 was considered as statistically significant: The overall incidence of Pain in the Zinc group was 18% compared to 43% in the Control group (P = .003) Incidence of Pain, swelling, and mouth opening at different time intervals 6h, 24h, 48h and 72h were significantly (P >0.05) better in Zinc group oral zinc lozenge administered 30 minutes preoperatively can significantly reduce complications like pain, swelling, and limited mouth opening after third molar extraction.

Extracellular Vesicles: Emerging Players in Plant Defense Against Pathogens

Communication between plants and interacting microorganisms requires functional molecule trafficking, which is essential for host defense and pathogen virulence. Extracellular vesicles (EVs) are single membrane-bound spheres that carry complex cargos, including lipids, proteins, and nucleic acids. They mediate cell-to-cell communication via the transfer of molecules between cells. Plant EVs have been isolated from many plant species and play a prominent role in immune system modulation and plant defense response. Recent studies have shown that plant EVs are emerging players in cross-kingdom regulation and contribute to plant immunity by mediating the trafficking of regulatory small RNA into pathogens, leading to the silencing of pathogen virulence-related genes. This review summarizes the current understanding of plant EV isolation technologies, the role of plant EVs in plant immunity, and the mechanism of plant EV biogenesis, as well as approaches for how these findings can be developed into innovative strategies for crop protection.

Serum 25-Hydroxyvitamin D Concentrations and Atopic Dermatitis in Early Childhood: Findings from the Japan Environment and Children’s Study

Vitamin D (VitD) may affect immune system modulation and result in the development of atopic dermatitis (AD). However, published findings have remained controversial. We investigated the association between early-life 25-hydroxyvitamin D (25(OH)D) levels and AD risk at childhood with a birth cohort. The data were obtained from “the Japan Environment and Children’s Study (JECS)” and “the Sub-Cohort study of JECS” performed with children aged 2 years. “Liquid chromatography-tandem mass spectrometry” was used to measure VitD. The information on AD was obtained from parents’ answers to a questionnaire when their children were aged 3 years. In order to explain the seasonal effects on VitD levels, a deseasonalized continuous variable was further calculated. The logistic regression models were fitted to evaluate the effect of VitD on childhood AD. The study included 4378 children with complete data on VitD and AD. The results from models indicated that low VitD at 2 years was not a risk factor for the development of AD at 3 years, after adjusting for potential confounders. Moreover, there was no U-shape relationship between deseasonalized VitD and childhood AD. Overall, early-life 25(OH)D levels were not link to the increased risk of developing childhood AD.

Involvement of Probiotics and Postbiotics in the Immune System Modulation

Intestinal microbiota interacts with other systems, especially the immune system, which is responsible for protecting the body by recognizing “stranger” (pathogen associated molecular patterns-PAMPs) and “danger” (damage-associated molecular patterns-DAMPs) molecular motifs. In this manner, it plays an important role in the pathogenesis of various diseases and health. Despite the use of probiotics that modulate the intestinal microbiota in providing health benefits and in the treatment of diseases, there are some possible concerns about the possibility of developing adverse effects, especially in people with suppressed immune systems. Since probiotics provide health benefits with bioactive compounds, studies are carried out on the use of products containing non-living probiotic microorganisms (paraprobiotics) and/or their metabolites (postbiotics) instead of probiotic products. It is even reported that these microbial compounds have more immunomodulatory activities than living microorganisms via some possible mechanism and eliminates some disadvantages of probiotics. Considering the increasing use of functional foods in health and disease, further studies are needed with respect to the benefits and advantages of parabiotic and/or postbiotic use in the food and pharmaceutical industry as well as immune system modulation. Although probiotics have been extensive studied for a long time, it seems that postbiotics are promising tools for future research and applications according to the recent literature. This review aimed to evaluate the interaction of probiotics and postbiotics with the immune systems and also their advantages and disadvantages in the area of food-pharmaceutical industry and immune system modulation.

Nutraceuticals and Enteric Glial Cells

Until recently, glia were considered to be a structural support for neurons, however further investigations showed that glial cells are equally as important as neurons. Among many different types of glia, enteric glial cells (EGCs) found in the gastrointestinal tract, have been significantly underestimated, but proved to play an essential role in neuroprotection, immune system modulation and many other functions. They are also said to be remarkably altered in different physiopathological conditions. A nutraceutical is defined as any food substance or part of a food that provides medical or health benefits, including prevention and treatment of the disease. Following the description of these interesting peripheral glial cells and highlighting their role in physiological and pathological changes, this article reviews all the studies on the effects of nutraceuticals as modulators of their functions. Currently there are only a few studies available concerning the effects of nutraceuticals on EGCs. Most of them evaluated molecules with antioxidant properties in systemic conditions, whereas only a few studies have been performed using models of gastrointestinal disorders. Despite the scarcity of studies on the topic, all agree that nutraceuticals have the potential to be an interesting alternative in the prevention and/or treatment of enteric gliopathies (of systemic or local etiology) and their associated gastrointestinal conditions.

In Vitro and In Vivo Anti-Parasitic Activity of Artemisinin Combined With Glucantime and Shark Cartilage Extract on Iranian Strain of Leishmania major (MRHO/IR/75/ER)

Background: The adverse effects and increased resistance of drugs necessities the discovery of novel combination therapy. Objectives: This study aimed to examine the effects of Artemisinin plus glucantime or shark cartilage extract on the Iranian strain of Leishmania major (MRHO/IR/75/ER) in vitro and in vivo. Methods: In in vitro experiments, the effects of drugs and their combination in different concentrations (3.12 - 400 µg/mL) on the promastigotes, amastigotes, and un-infected macrophage cells were evaluated. In in vivo experiments, infected BALB/c mice were used as a cutaneous leishmaniasis model to evaluate the effects of the drugs and their combinations with different routes of administrations (namely Artemisinin: oral, ointment, and intraperitoneal; glucantime: intraperitoneal, intramuscular, intralesional, and subcutaneous; shark cartilage extract: oral) on parasite burden, lesion size, and immune system modulation. Results: The results revealed that Artemisinin and glucantime in combination with shark cartilage extract had greater effects on promastigotes than either Artemisinin or glucantime (P < 0.05), and that the combinations also had high cytotoxic effects on promastigotes and uninfected macrophages (P = 0.001). These combinations had more inhibitory effects on amastigotes and infected macrophages than promastigotes. The lesion sizes and parasite burden in the spleen decreased against the combinations of the drugs in different administrations. It was also noticed that the best combination administration route of Artemisinin and glucantime, as strong inducers of INF-γ and Th1 immune response, were ointment and IM, respectively (P < 0.05). Conclusions: The findings indicate that Artemisinin- glucantime or Artemisinin- Shark cartilage combinations are effective inhibitors of L. major. However, further clinical trials are recommended to evaluate the effects of these combinations in human subjects.

Into the Labyrinth of the Lipocalin α1-Acid Glycoprotein

α1-acid glycoprotein (AGP), also known as Orosomucoid (ORM), belongs to the Lipocalin protein family and it is well-known for being a positive acute-phase protein. AGP is mostly found in plasma, with the liver as main contributor, but it is also expressed in other tissues such as the brain or the adipose tissue. Despite the vast literature on AGP, the physiological functions of the protein remain to be elucidated. A large number of activities mostly related to protection and immune system modulation have been described. Recently created AGP-knockout models have suggested novel physiological roles of AGP, including regulation of metabolism. AGP has an outstanding ability to efficiently bind endogenous and exogenous small molecules that together with the complex and variable glycosylation patterns, determine AGP functions. This review summarizes and discusses the recent findings on AGP structure (including glycans), ligand-binding ability, regulation, and physiological functions of AGP. Moreover, this review explores possible molecular and functional connections between AGP and other members of the Lipocalin protein family.