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Overproduction of NLRP3 inflammasome complex is one of the causes of Behcet's disease's (BD) auto-inflammatory nature. The aim of current study was to examine the effect of zinc supplementation on NLRP3 inflammasome expression; as well as clinical manifestations of BD.In this double-blind parallel placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30 mg/day elemental zinc) or placebo groups for 12 weeks. The mRNA expression of NLRP3 and caspase-1 in the leukocytes, serum level of zinc and IL-1β, anthropometric measures, and clinical manifestations of patients were collected at pre- and post-intervention phase. The Iranian Behçet's disease dynamic activity measure (IBDDAM) was scored to measure the treatment effect using the calculation of number needed to treat (NNT). Analysis of covariance was performed to obtain the corresponding effect sizes.Zinc gluconate led to a significant improvement in genital ulcer (P = 0.019). Zinc supplementation decreased NLRP3 and caspase-1 genes expression compared with placebo group (baseline-adjusted P-value = 0.046 for NLRP3 and P-value = 0.003 for caspase-1), even after adjustment for the effect of confounding factors (baseline- and confounders-adjusted P-value = 0.032 for NLRP3 and P-value = 0.004 for caspase-1). Baseline and confounders adjusted effect size demonstrated that zinc was effective in reducing the serum level of IL-1β (P = 0.046). The NNT [95 %CI] for the rate of IBDDAM improvement was 3 [1.7-8.5].Zinc gluconate supplementation (30 mg/day) for a 3-month period can be considered as an adjuvant therapy in alleviating inflammation and genital ulcer among BD patients.

Cancer immunotherapy is more dependent on monoclonal antibodies, proteins, and cells, as therapeutic agents, to attain prominent outcomes. However, cancer immunotherapy's clinical benefits need to be enhanced, as many patients still do not respond well to existing treatments, or their diseases may relapse after temporary control. RNA-based approaches have provided new options for advancing cancer immunotherapy. Moreover, considerable efforts have been made to utilize RNA for vaccine production. RNA vaccines, which encode tumor-associated or specific epitopes, stimulate adaptive immunity. This adaptive immune response is capable of elimination or reduction of tumor burden. It is crucial to develop effective RNA transfer technologies that penetrate the lipid bilayer to reach the cytoplasm for translation into functional proteins. Two important delivery methods include the loading of mRNA into dendritic cells ex vivo; and direct injection of naked RNA with or without a carrier.The latest results of pre-clinical and clinical studies with RNA vaccines in cancer immunotherapy are summarized in this review.RNA vaccines are now in early clinical development with promising safety and efficacy outcomes. Also, the translation capacity and durability of these vaccines can be increased with chemical modifications and sequence engineering.

Malignant melanoma (MM) is an aggressive disease with a rapidly rising incidence due to neoplasm of melanocytes. Molecular targeted therapies have demonstrated lower toxicity and improved overall survival versus conventional therapies of MM. The revealing of mutations in the BRAF/MEK/ERK pathway has led to the development of BRAF inhibitors such as vemurafenib and dabrafenib for the treatment of cutaneous MM. Though, progression of resistance to these agents has prompted attempts to target downstream proteins in this pathway. Trametinib, a MEK1/2 inhibitor, was approved in 2013 for the treatment of BRAF V600E/K mutation-positive unresectable or metastatic cutaneous melanoma patients. Areas covered: The aim of the current review is to present an update on the role of MEK in progressive melanomas and summarize latest results of clinical studies with innovative MEK inhibitors and/or combined approaches with other kinase inhibitors such as BRAF inhibitors in the treatment of MM. Expert opinion: Two combined treatments (i.e. trametinib plus dabrafenib and vemurafenib plus cobimetinib) target two different kinases in the BRAF/MEK/ERK pathway. The simultaneous prohibition of both MEK and BRAF is associated with more durable response rate than BRAF monotherapy and can overcome acquired resistance.

Backgrounds and Aims Selenium nanoparticles (SeNPs) have been reported to exhibit an inhibitory effect on cancer cells. In the present study, we aimed to compare the in vitro and in vivo effects of SeNPs and folic acid surface–coated selenium nanoparticles (FA@SeNPs) on breast cancer. Methods FA@SeNPs and SeNPs were chemically synthesized and characterized with different instrumental techniques. The cytotoxicity of both nanomaterials was evaluated against 4T1 cells. In addition, the intravenous administration effect of these nanomaterials (300 μg/week) on the lifespan and tumor size of cancer-bearing mice was investigated. Results Although the SeNPs showed an antiproliferative effect against the cell line, the cytotoxicity of the FA@SeNPs was higher than that of the SeNPs. A low concentration of FA@SeNPs (25 μg/mL corresponding to 8.75 μg/mL of elemental SeNPs) caused approximately 68% cell mortality. In the in vivo study, the nanomaterials decreased the tumor growth rate in cancerous mice in relation to the control group. FA@SeNPs were more effective than SeNPs. Conclusions The combination of SeNPs and FA has a potent antiproliferative effect against 4T1 cells, significantly increases the lifespan, and prevents tumor growth.

Autophagy pathways are involved in the pathogenesis of some obesity related health problems. As obesity is a nutrient sufficiency condition, autophagy process can be altered in obesity through AMP activated protein kinase (AMPK) inhibition. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) as the main modulator of adipogenesis process can be effective in the regulation of obesity related phenotypes. As well, it has been revealed that PPAR-gamma and its agonists can regulate autophagy in different normal or cancer cells. However, their effects on autophagy modulation in obesity have been investigated in the limited number of studies. In the current comprehensive mechanistic review, we aimed to investigate the possible mechanisms of action of PPAR-gamma on the process of autophagy in obesity through narrating the effects of PPAR-gamma on autophagy in the non-obesity conditions. Moreover, mode of action of PPAR-gamma agonists on autophagy related implications comprehensively reviewed in the various studies. Understanding the different effects of PPAR-gamma agonists on autophagy in obesity can help to develop a new approach to management of obesity.

Prolonged inflammation could be considered as the leading cause of chronic diseases such as cardiovascular disorders, type two diabetes, and obesity. N-acetylcysteine (NAC) is considered an antioxidant. The present meta-analysis aims to determine the efficacy of NAC in alleviating inflammation and oxidative stress. PubMed-Medline, SCOPUS, Web of Science and Embase databases and Google Scholar were searched up to Nov 2019. Random effect analysis was used to perform meta-analysis. Subgroup analyses were carried out to find heterogeneity sources. Meta-regression analysis was used to explore linear relationship between effect size and variables. Trim and fill analysis were performed in case of the presence of publication bias. Quality assessment was performed using Cochrane Collaboration's tool. A total of 28 studies were included in meta-analysis. NAC significantly decreased malondialdehyde (MDA) (SMD = -1.44 μmol/L; 95% CI: -2.05, -0.84; P 0.001), IL-8 (WMD = -2.56 pg/ml; 95% CI: -3.89, -1.23; P 0.001) and homocysteine (WMD = -1.45 pg/ml; 95% CI: -2.74, -0.17; P = 0.027) levels. There were no significant effects of NAC supplementation on CRP (SMD = -0.1 g/L; 95% CI: -0.52, 0.32; P = 0.647), TNF- α (WMD = -0.2 pg/ml; 95% CI: -0.65, 0.25; P = 0.378) and IL-6 (WMD = -0.41 pg/ml; 95% CI: -1.15, 0.32; P = 0.270) levels. However, NAC effects were significant in ameliorating TNF-α and IL-6 using sensitivity analysis. NAC significantly decreased MDA, IL-8, and homocysteine levels. The effects of NAC on amending TNF-α and IL-6 levels were significant after sensitivity analysis. No significant change was observed on CRP levels.

The modification of tumor-associated antigen-based vaccine to elicit a more robust immune response has been addressed in several ways. In the present work, we aimed to investigate the immunomodulatory effect of selenium nanoparticles as an immunoadjuvant in formulation of a tumor-associated antigen-based vaccine in a preventive form. Fortyfive female inbred BALB/c mice five-to-seven weeks old were used and divided into three groups of test and control, each containing fifteen mice. Group one injected by PBS and used as a control. Group two injected by breast tumor cell lysate alone as vaccine. Group three injected by SeNPs with tumor cell lysate as vaccine. All injections were carried out on day fourteen, twentyone and twentyeight of the study. Tumor induction was done at day thirty. Twenty days after tumor induction serum samples were gathered to measure the cytokine assay. Tumor growth and weight of mice as well as delayed type hyper sensitivity (DTH) response were monitored during the study. Results of the present work showed a significant increase in the level of serum IFN-γ, IL-2, IL-12 and decreased TGF-β in SeNPs/vaccine injected mice as well as lower tumor volume, more potent DTH responses and longer survival rate in comparison to control and tumor lysate vaccine. Taken together, it can be deduced from this work that SeNPs can be considered as an adjuvant in vaccine in triggering robust immune response against breast cancer. But further evaluations are still needed to find the best formula for this agent in antitumor vaccines.

Background: Tumor associated antigens can be viably used to enhance host immune response. Objectives: The immunomodulatory effect of biogenic selenium nanoparticles (SeNPs) was compared between treated and untreated mice with crude antigens of 4T1 cells. Materials and Methods: Female inbred BALB/c mice (60) were injected by cancinogenic 4T1 cells causing breast cancer. After 10 days, all tumor bearing mice were divided into 4 groups. Group 1 was daily provided oral PBS and injected by the same buffer after tumor induction and was considered as control. Group 2 received only 100 mg/day SeNPs as an oral supplement for 30 days. Group 3 was only injected with 4T1 cells crude antigens with nil supplementation of SeNPs. Group 4 animals were supplemented 100 mg/day SeNPs for 30 days and simultaneously injected with crude antigens of 4T1 cells. All antigens or PBS injections were introduced at 7, 14 and 28 days following tumor induction. Oral PBS and SeNPs supplementation initiated from the first day of tumor induction and continued up to 30 days. During tumor growth, animal weights and survival rates were monitored and at the end of the study the concentrations of different cytokines and DTH responses were measured. Results: Data clearly showed that the levels of cellular immunomodulatory components (granzyme B, IL-12, IFN-g, and IL-2) significantly increased (P < 0.05) in mice treated with both SeNPs and crude antigens of 4T1 cells in comparison to the other groups. In contrast, the levels of TGF-b in these mice decreased. Conclusions: Although SeNPs showed a noticeable boosting effect for the immune response in mice bearing tumor exposed to crude antigens of 4T1 cells, further complementary studies seem to be inevitable.

Backgrounds and Aims Oral administration of selenium nanoparticles has an immunomodulatory effect on individuals with cancer. In the present study we aimed to compare the cancer preventive effect via administration of different doses of selenium nanoparticles in mice with cancer. Methods Forty 6- to 8-week-old inbred female BALB/c mice were used and divided into four test and control groups; each group contained ten mice. Group 1 (administered PBS) was used as the control and the test groups 2, 3, and 4 were daily administered 50, 100, and 200 μg of selenium nanoparticles, respectively, for 60 days. After 60 days, tumor induction was carried out and 10 days later serum samples were collected to measure the cytokines. Tumor growth and life span of the mice were also monitored during the study. Results The results showed a significant increase in serum IFN-γ and the ratio of IFN-γ/IL-4 in all administered doses compared to control. In addition, in mice that received higher doses of selenium nanoparticles (200 μg/day), lower tumor volume and extended life span were observed compared to control. Administration of selenium nanoparticles in normal mice without tumor challenge caused a nonsignificant increase in cytokine production, indicating that selenium supplementation has no effect on the immune response in the absence of tumor challenge. Conclusions The 200-μg dose of selenium nanoparticles can induce more efficient responses against breast tumors.