Association between the copper/selenium ratio and the immune response to SARS-CoV-2 infection.

Aim: To assess the association serum levels of selenium (Se) and copper (Cu) with symptoms and IgG immune response to SARS-CoV-2. Patients & methods/materials: Blood samples and nasopharyngeal swabs were obtained from 126 COVID-19 patients with mild and severe symptoms. The serum levels of Cu and Se were measured by atomic-absorption spectrophotometry. Results & conclusion: Mean Se was higher in patients with mild symptoms and IgG nonresponders, whereas mean Cu was higher in patients with severe symptoms and IgG responders. The Cu/Se ratio was lower in patients with no IgG responses to infection and mild symptoms versus IgG responders with severe symptoms. These results suggest the Cu/Se ratio as a nutritional biomarker of severity and IgG immune response in COVID-19 patients.

The association between the strong immune response to infections and trace elements such as copper (Cu) and selenium (Se) is well documented. Se and Cu are changed under infectious conditions. Since SARS-CoV-2 causes inflammation in the body, this study was conducted to evaluate the association between serum levels of Se and Cu changes with the symptoms and immune response to SARS-CoV-2, and then assess the Cu/Se ratio. Blood samples and nasopharyngeal swabs were obtained from 126 SARS-CoV-2 participants with mild and severe clinical symptoms. The SARS-CoV-2 infection and immune response to the virus were confirmed in the laboratory. Next, the Se and Cu serum levels were measured. Finally, we analyzed our findings. The median Se levels were higher in patients with mild symptoms (115 µg/l) in comparison with the severe symptoms group (99 µg/l), and the mean Se levels were higher in immune nonresponders (110.33 ± 3.38 µg/l) in comparison with the immune responders' group (102.42 ± 1.83 µg/l). However, the median Cu was higher in participants with severe symptoms (124 µg/dl) compared with the mild symptoms group (103 µg/dl), and the mean Cu levels were higher in immune responders (112 ± 9.98 µg/dl) in comparison with the immune nonresponders' group (105.1 ± 9.4 µg/dl). The Cu/Se ratio was lower (ratio <1) in participants with no responses to infection and mild symptoms versus responders with severe symptoms. Our results suggest that the Cu/Se ratio may act as a nutritional biomarker of severity and immune response in SARS-CoV-2-infected patients.

Evaluating mRNA expression of tax, B chain of PDGF and PDGF-ß receptors as well as HTLV-I proviral load in ATL patients and healthy carriers.

Adult T-cell leukemia (ATL) is a life-threatening malignant neoplasm of CD4+ T cells resulted from human T-cell leukemia virus type I (HTLV-I). Tax1 protein of HTLV-I can induce malignant proliferation of T-cells by modulating the expression of growth factors such as platelet-derived growth factor (PDGF). Here, we aimed to investigate the proviral load (PVL) of HTLV-I in ATL and also to evaluate the mRNA expression of B chain of PDGF and PDGF-ß receptors in ATL patients and HTLV-I-infected healthy carriers. To this end, peripheral blood mononuclear cells (PBMCs) were isolated by using Ficoll-Histophaque density centrifugation. The mean of HTLV-I PVL in ATL patients (42,759 ± 15,737 copies/104 cells [95% CI, 9557-75962]) was significantly (p = .01) higher than that in healthy carriers (650 ± 107 copies/104 cells [95% CI, 422-879], respectively. The HTLV-I PVL in ATL patients exhibited a significant correlation with PBMC count (R = .495, p = .001). The mRNA expression of Tax, B chain of PDGF, and PDGF-ß receptor genes was significantly higher in healthy carriers than in patients with ATL. In conclusion, the expression of the canonical PDGFß and its receptor, and their correlation with Tax expression cannot be a suitable indicator and/or prognostic factor for progression of ATL in HTLV-I carriers.

The Impact of Immune Cell-derived Exosomes on Immune Response Initiation and Immune System Function.

Exosomes are small extracellular vesicles that pass genetic material between various cells to modulate or alter their biological function. The role of exosomes is to communicate with the target cell for cell-to-cell communication. Their inherent characteristics of exosomes, such as adhesion molecules, allow targeting specifically to the receiving cell. Exosomes are involved in cell to cell communication in the immune system including antigen presentation, natural killer cells (NK cells) and T cell activation/polarisation, immune suppression and various anti-inflammatory processes. In this review, we have described various functions of exosomes secreted by the immune cells in initiating, activating and modulating immune responses; and highlight the distinct roles of exosomal surface proteins and exosomal cargo. Potential applications of exosomes such as distribution vehicles for immunotherapy are also discussed.

Circulating exosomal microRNAs as emerging non-invasive clinical biomarkers in heart failure: Mega bio-roles of a nano bio-particle.

Exosomes are nano-sized extracellular vesicles containing a cell-specific biologically active cargo of proteins and genetic materials. Exosomes are constitutively released from almost all cell-types and affect neighboring or distant cells through a complex intercellular exchange of the genetic information and/or regulation of certain gene expressions that change the function and behavior of recipient cells. Those released into body fluids are the major mediators of intercellular communications. The success of the biological functions of exosomes is highly mediated by the effective transfer of microRNAs (miRs). Exosomes secreted by a damaged or diseased heart can exhibit alterations in the miRs' profile that may reflect the cellular origin and (patho)physiological state, as a "signature" or "fingerprint" of the donor cell. It has been shown that the transportation of cardiac-specific miRs in exosomes can be rapidly detected and measured, holding great potential as biomarkers in heart diseases. Currently, the search for new biomarkers of heart diseases remains a large and increasing enterprise. Notably, circulating exosomal miRs (Exo-miRs) have successfully gained huge interests for their diagnostic and prognostic potentials. The present review highlights circulating Exo-miRs explored for diagnosis/prognosis and outcome prediction in patients with heart failure (HF). To this end, we explain the feasibility of exosomes as clinical biomarkers, discuss the priority of circulating Exo-miRs over non-exosomal ones as a biomarker, and then outline reported circulating Exo-miRs having the biomarker function in HF patients, together with their mechanism of action. In conclusion, circulating Exo-miRs represent emerging diagnostic (Exo-miR-92b-5p, Exo-miR-146a, Exo-miR-181c, and Exo-miR-495) and prognostic (Exo-miR-192, Exo-miR-194, Exo-miR-34a, Exo-miR-425, Exo-miR-744) biomarkers for HF.

Evaluating the mechanism underlying antitumor effect of interleukin 27 on B cells of chronic lymphocytic leukemia patients.

Chronic lymphocyte leukemia (CLL) is a B-cell malignancy resisted to apoptosis. Recently, some studies indicated that cytokines such as interleukin 27 (IL-27) can reduce B-cell proliferation. The aim of this study is to evaluate the mechanism underlying the proapoptotic effect of IL-27 on B cells of patients with CLL in comparison with B cells of normal subjects. The effect of IL-27 on the antitumor activity of natural killer (NK) and T cells was also evaluated. Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with CLL and 15 normal subjects. B cells and PBMCs were cocultured with IL-27 and B cells apoptosis to evaluate proliferation. Both messenger RNA and protein expression of IL-27 and IL-27 receptor were determined using flow cytometry and real-time polymerase chain reaction analysis. To evaluate the apoptotic effect of IL-27 on B cells of patients with CLL, Annexin V-FITC and 7-AAD (BioLegend) fluorescent dyes were used. In addition, the IL-27 effect on activation of T cell and NK cell was determined by determining CD96 molecule expression. IL-27 and IL-27 receptor expression in patients with CLL was significantly lower than that of normal subjects (p < .05). IL-27 enhanced apoptosis of B cells in patients with CLL (p < .05) but this effect was not significantly observed in B cells of normal subjects (p > .05). Consequently, IL-27 reduced the proliferation of B cells and enhanced NK cell activity (p < .05). IL-27, through inducing apoptosis, can exert an inhibitory effect on cancer B cells of CLL patients with minimal effect on normal B cells.

Evaluation of the Anti-Tumor Activity of Niclosamide Nanoliposomes Against Colon Carcinoma.

BACKGROUND AND AIMS: Niclosamide is an established anti-helminthic drug, which has recently been shown to inhibit the growth of various cancer cells. To exploit the potential anti-tumor activity of this drug for systemic use, the problem of low aqueous solubility should be addressed. The present study tested the in vivo anti-tumor effects of a recently developed nanoliposomal preparation of niclosamide in an experimental model of colon carcinoma. METHODS: The cytotoxicity of nanoliposomal niclosamide on CT26 colon carcinoma cells was evaluated using the MTT test. Inhibition of tumor growth was investigated in BALB/c mice bearing CT26 colon carcinoma cells. The animals were randomly divided into 4 groups including: 1) untreated control, 2) liposomal doxorubicin (15 mg/kg; single intravenous dose), 3) liposomal niclosamide (1 mg/kg/twice a week; intravenously for 4 weeks), and 4) free niclosamide (1 mg/kg/twice a week; intravenously for 4 weeks). To study therapeutic efficacy, tumor size and survival were monitored in 2-day intervals for 40 days. RESULTS: In vitro results indicated that nanoliposomal and free niclosamide could exert cytotoxic effects with IC50 values of 4.5 and 2.5 µM, respectively. According to in vivo studies, nanoliposomal niclosamide showed a higher growth inhibitory activity against CT26 colon carcinoma cells compared with free niclosamide as revealed by delayed tumor growth and prolongation of survival. CONCLUSION: Nnaoliposomal encapsulation enhanced anti-tumor properties of niclosamide in an experimental model of colon carcinoma.

Modulatory effects of curcumin on the atherogenic activities of inflammatory monocytes: Evidence from in vitro and animal models of human atherosclerosis.

Atherosclerosis is a complex and long-lasting disorder characterized by chronic inflammation of arteries that leads to the initiation and progression of lipid-rich plaques, in which monocytes/macrophages play the central role in endothelial inflammation and taking up these lipids. Circulating monocytes can adopt a long-term proinflammatory phenotype leading to their atherogenic activities. During atherogenic condition, inflammatory monocytes adhere to the surface of the activated endothelial cells and then transmigrate across the endothelial monolayer into the intima, where they proliferate and differentiate into macrophages and take up the lipoproteins, forming foam cells that derive atherosclerosis progression. Therefore, modulating the atherogenic activities of inflammatory monocytes can provide a valuable therapeutic approach for atherosclerosis prevention and treatment. Curcumin is a naturally occurring polyphenolic compound with numerous pharmacological activities and shows protective effects against atherosclerosis; however, underlying mechanisms are not clearly known yet. In the present review, on the basis of a growing body of evidence, we show that curcumin can exert antiatherosclerotic effect through inhibiting the atherogenic properties of monocytes, including inflammatory cytokine production, adhesion, and transendothelial migration, as well as intracellular cholesterol accumulation.

Nanoliposomal Encapsulation Enhances In Vivo Anti-Tumor Activity of Niclosamide against Melanoma.

BACKGROUND: Niclosamide is an FDA-approved and old anti-helminthic drug used to treat parasitic infections. Recent studies have shown that niclosamide has broad anti-tumor effects relevant to the treatment of cancer. However, this drug has a low aqueous solubility hindering its systemic use. Herein, we report the preparation and characterization of niclosamide nanoliposomes and their in vivo anti-tumor effects. METHODS: Nanoliposomes were prepared using thin-film method and the drug was encapsulated with a remote loading method. The nanoliposomes were investigated by the observation of morphology, analysis of particle size and zeta potential. Additionally, qualitative and quantitative analyses were performed using HPLC. We assessed the in vitro cytotoxicity of the nanoliposomal niclosamide on B16F10 melanoma cells. Inhibition of tumor growth was investigated in C57BL/6 mice bearing B16F0 melanoma cancer. RESULTS: Analytical results indicated that the nanoliposomal system is a homogeneous and stable colloidal dispersion of niclosamide particles. Atomic force microscopy images and particle size analysis revealed that all niclosamide particles had a spherical shape with a diameter of approximately 108nm. According to in vitro and in vivo studies, nanoliposomal niclosamide exhibited a better anti-tumor activity against B16F10 melanoma tumor compared with free niclosamide. CONCLUSION: Nanoliposomal encapsulation enhanced the aqueous solubility of niclosamide and improved its anti-tumor properties.

Potential therapeutic effects of curcumin in gastric cancer.

Despite recent advancements in understanding of the biology of gastric cancer, treatment of patients with advanced gastric cancer remains a major problem. Among different type of phytochemicals, curcumin, a welltable -known phytochemical, has been shown to be a promising cancer chemopreventive agent. Pharmacokinetics, safety, and efficacy of curcumin have been evaluated in several clinical trials against numerous diseases, and for the treatment of human cancer. In the present review, we have collected in vitro and in vivo investigations and studied the chemosensitizing and anticancer effects of curcumin against the gastric cancer cells. In summary, curcumin has been found to have efficient chemosensitizing effect and also inhibits viability, proliferation, and migration of gastric cancer cells mainly via cell cycle arrest and induction of apoptosis by both mitochondrial-dependent and -independent pathways.

The immunomodulatory role of probiotics in allergy therapy.

The increased incidence of allergic disorders may be the result of a relative fall in microbial induction in the intestinal immune system during infancy and early childhood. Probiotics have recently been proposed as viable microorganisms for the prevention and treatment of specific allergic diseases. Different mechanisms have been considered for this probiotic property, such as generation of cytokines from activated pro-T-helper type 1 after bacterial contact. However, the effects of its immunomodulatory potential require validation for clinical applications. This review will focus on the currently available data on the benefits of probiotics in allergy disease.

The novel role of pyrvinium in cancer therapy.

Pyrvinium pamoate (PP) is a quinoline-derived cyanine dye which was officially approved by FDA for its anthelmintic properties and therapeutic function against animal-like protists such as Cryptosporidium parvum and Plasmodium falciparum in the 1950s. In the last 10 years, several studies have shown the novel activity of pyrvinium in tumor therapy. Some investigations have indicated that pyrvinium could delay or inhibit tumor cell proliferation in cancer models including colon, breast, lung and prostate cancer, and some hematological malignancies. In this review, we discuss multiple critical signaling pathways and mechanisms underlying the anticancer effects of PP. In details, pyrvinium acts through the following main mechanisms: (i) energy and autophagy depletion; and (ii) inhibition of Akt and Wnt-ß-catenin-dependent pathways. Interestingly, pyrvinium has also shown potent anti-cancer stem cell activity. The overwhelming insights into the mechanism of anticancer properties of PP can help establishing novel and future anti-tumor treatment strategies.

Enhanced Entrapment and Improved in Vitro Controlled Release of N-Acetyl Cysteine in Hybrid PLGA/Lecithin Nanoparticles Prepared Using a Nanoprecipitation/Self-Assembly Method.

To enhance the in vitro controlled release of N-acetyl cysteine (NAC), hybrid nanoparticles (NPs) consisting of a poly(lactide-co-glycolide) (PLGA) hydrophobic core and a soybean lecithin mono-layer coat were prepared. Hybrid NPs were synthesized using a nanoprecipitation combined with self-assembly method. To characterize prepared NPs, zeta potential, diameter size, surface morphology, disparity, and lipid coating of hybrid NPs were detrmined using dynamic light scattering, scanning electron microscope and Fourier transform infrared spectroscopy techniques. High-performance liquid chromatography was employed to evaluate drug loading yield and encapsulation efficiency and in vitro drug release of prepared NPs. The cytotoxicity of hybrid NPs was assayed on normal L929 alveolar epithelial cells using MTT method. Prepared NPs were found to disperse as individual NPs with a well-defined spherical shape. The hydrodynamic diameter and surface charge of NAC-loaded hybrid NPs were 81.8 ± 1.3 nm and -33.1 ± 2.1 mV, respectively. Drug loading yield and encapsulation efficiency of NAC-loaded hybrid NPs were found to be 38 ± 2.1% and 67 ± 5.7%, respectively. Prepared hybrid NPs showed no significant cytotoxicity against normal alveolar cells. Our data suggest that the hybrid PLGA-lecithin NPs may be An efficient controlled release drug delivery system for NAC. J. Cell. Biochem. 118: 4203-4209, 2017. © 2017 Wiley Periodicals, Inc.