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Taurine (Tau) has modulatory effects on inflammatory and oxidative stress biomarkers; however, the results of clinical studies are not comprehensive enough to determine the effect of different durations and doses of Tau supplementation on inflammatory and oxidative stress biomarkers. The current study was conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. For this purpose, PubMed/Medline, Scopus, and Embase databases were systematically searched to obtain the relevant studies published before 30th March 2021. Meta-analysis was performed on controlled clinical trials by using the random-effects method. Non-linear relationship between variables and effect size was performed using dose–response and time–response analyses. The Cochrane Collaboration’s tool was used to evaluate the quality of included studies. Tau supplementation can reduce the levels of malondialdehyde (MDA) (SMD = −1.17 µmol/l; 95% CI: −2.08, − 0.26; P = 0.012) and C-reactive protein (CRP) (SMD = −1.95 mg/l; 95% CI: −3.20, − 0.71; P = 0.002). There have been no significant effects of Tau supplementation on the levels of tumor necrosis factors-alpha (TNF-α) (SMD = −0.18 pg/ml; 95% CI: −0.56, 0.21; P = 0.368), and interleukin-6 (IL-6) (SMD = −0.49 pg/ml; 95% CI: −1.13, 0.16; P = 0.141). Besides, Tau has more alleviating effect on oxidative stress and inflammation on 56 days after supplementation (P

Signal Transducer and Activator of Transcription 3 (STAT3) phosphorylation plays a key role in the transformation and proliferation of breast cancer cells. According to previous studies, STAT3 phosphorylation can be inhibited by curcumin in various cancer cells. Even so, its use is restricted due to low oral bioavailability. This study aimed to enhance curcumin solubility and bioavailability by loading it on Folic Acid-Selenium nanoparticles and determine their effect on STAT3 activation in breast cancer cell line. The synthesized nanoparticles were characterized by Fourier-transform infrared spectroscopy, Dynamic light scattering, and transmission electron microscope. MTT and western blotting methods were applied to determine the viability and protein level of MCF cell line. The size and zeta potential of nanoparticles were found to be about 130 nm and − 45 mV, respectively. The results indicated a reduction of 49.62 ± 1.85% (p

Background: The inhibitory effect of selenium nanoparticles (SeNPs) on cancer cells has been reported in many studies. In this study, the purpose was to compare the in vitro effects of SeNPs and calcium sulfate coated selenium nanoparticles (CaSO4@ SeNPs) on breast cancer cells. Methods: CaSO4@SeNPs and SeNPs were chemically synthesized and characterized with Field Emission Scanning Electron Microscope (FESEM) and energy-dispersive X-ray spectroscopy (EDX). By applying MTT assay, the cytotoxicity effect of both nanomaterials on the 4T1 cancer cells was investigated. Results: While LD50 of SeNPs on 4T1 cancer cells was 80 µg, the LD50 of CaSO4@SeNPs was reported to be only 15 µg. The difference between the inhibition rates obtained for SeNPs and CaSO4@SeNPs was statistically significant (p=0.05). In addition, at higher concentrations (50 µg) of CaSO4@SeNPs, the cytotoxicity was 100% more than SeNPs alone. Conclusion: According to the result of the present work, it can be concluded that de-coration of SeNPs with calcium sulfate leads to an increase in potency by decreasing the effective dose. This effect can be attributed to activation of intrinsic apoptosis signaling and/or pH regulatory properties of CaSO4@SeNPs. However, further studies are still needed to determine the exact corresponding mechanisms of this synergistic effect.

Despite the improvements in endovascular techniques during the last decades, there is still an increase in the prevalence of peripheral artery disease (PAD) with limited practical treatment, which timeline impact of any intervention for critical limb ischemia (CLI) is poor. Most common treatments are not suitable for many patients due to their underlying diseases, including aging and diabetes. On the one hand, there are limitations for current therapies due to the contraindications of some individuals, and on the other hand, there are many side effects caused by common medications, for instance, anticoagulants. Therefore, novel treatment strategies like regenerative medicine, cell-based therapies, Nano-therapy, gene therapy, and targeted therapy, besides other traditional drugs combination therapy for PAD, are newly considered promising therapy. Genetic material encoding for specific proteins concludes with a potential future for developed treatments. Novel approaches for therapeutic angiogenesis directly used the angiogenetic factors originating from key biomolecules such as genes, proteins, or cell-based therapy to induce blood vessel formation in adult tissues to initiate the recovery process in the ischemic limb. As PAD is associated with high mortality and morbidity of patients causing disability, considering the limited treatment choices for these patients, developing new treatment strategies to prevent PAD progression and extending life expectancy, and preventing threatening complications is urgently needed. This review aims to introduce the current and the novel strategies for PAD treatment that lead to new challenges for relief the patient's suffered from the disorder.

Background and purpose: Granulocyte colony-stimulating factor (G-CSF) is routinely used in combination with chemotherapy to battle neutropenia. However, studies suggest that this chemokine may increase the risk of metastasis and malignancy in many cancers. To counteract the adverse effects of G-CSF in cancer, antibodies have been used to block its action. However, antibodies are large and complex molecules which makes their production expensive. Thus in this study, we aim to construct different structure variants of the G-CSF receptor containing different domains and select the best variant that prevents the adverse actions of this chemokine. These novel structures are smaller than antibodies and easier to produce. Experimental approach : Different domains of the G-CSF receptor were designed and cloned into the pET28a expression vector. These recombinant receptor subunits were then expressed in Escherichia coli and purified using standard affinity chromatography techniques. Interaction of recombinant receptor subunits with G-CSF was assessed using enzyme-linked immunosorbent assay and NFS60 cells. Findings / Results: Two recombinant receptor subunits containing D1 + D2 + D3 domains and D2 domain showed the strongest inhibitory activity to G-CSF. Conclusion and implications: These novel recombinant receptor variants could be candidates for further studies in the development of novel therapeutics.

Gastric cancer (GC) is one of the most frequently diagnosed malignancies. Recent studies have highlighted cellular immunotherapy (CI) as a promising approach for treating this disease. Among the CI-based approaches, adoptive cell therapy and dendritic cell-based vaccination are commonly studied in preclinical and clinical trials. Here we review the current evidence on the potentiality of CI in treating GC, the targets for adoptive cell therapy, ongoing clinical trials, constraints and the future outlook. The results suggest that there is a need to identify novel biomarkers that predict which GC patients will most likely respond to these approaches. Also, CI plus chemotherapy or immune checkpoint inhibitors can improve the survival of patients with late-stage GC. Therefore, this approach can be promising for treating these patients.

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.

Vitamin D receptor (VDR) gene polymorphisms are believed to be involved in the obesity pathogenesis. This study summarises the results of research concerning the association between VDR polymorphisms and obesity. For this survey, the records of common databases were searched until November 2019. Four loci of the VDR gene in four case-controlled and 22 cross-sectional studies were assessed and evaluated. In the case-control studies, no significant association was observed between ApaI and FokI polymorphism with obesity risk. TaqI "T" allele in two studies was related to a higher risk of obesity. One investigation found no relationship between BsmI and obesity, while another article suggested that the "b" allele is more frequently found in obese subjects. The results of cross-sectional studies did not lead to consistent findings. Although the previous studies failed to arrive at conclusive findings, the effects of VDR polymorphism on obesity development cannot be ignored.

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.

Summary: Hepatitis B virus (HBV) infection is known as a life-threatening liver infection and leads to chronic liver disease if left untreated. Nevertheless, the prevalence of HBV infection has been reduced by an approved vaccination approach using recombinant Hepatitis B surface Antigen (HBsAg) and Alum, known as the HBV vaccine. Alum can be used as an adjuvant to increase HBsAg immunogenicity as a strong Th2 stimulator. There is a vital need to stimulate Th1 immunity by HBsAg vaccination; however, the present vaccine does not induce a prophylactic immune response in some groups. The main aim of the present study was to induce a Th1 cytokine pattern and stimulate an immune response after HBsAg vaccination. Experimental mice were fed selenium nanoparticles (SeNPs) and were later immunized with 5 μg of Hepatitis B Vaccine. After a period of 30 days, the experimental animals were given two booster doses of SeNPs during their vaccination course. Group one, i.e., the control vaccine group, was only administered the HBsAg vaccine. The two treated groups, Groups 2 and 3, were daily fed different doses of SeNPs (100 μg and 200 μg, respectively) via gavage. Group four was considered the control group and was only given phosphate buffered saline (PBS). Lymphocyte proliferation, IFN-γ and IL-4 levels, total antibody and the isotypes of IgG1, IgG2a, IgG2b, and IgM were measured by Enzyme Linked Immunosorbent Assay (ELISA). The administration of SeNPs and the HBs antigen vaccine affected the lymphocyte proliferation; moreover, the total antibody responses also increased the IFN-γ level and induced a Th1 response. Conclusions: The present study proposed that the administration of SeNPs with a conventional HBs antigen vaccine induces a better immune response with a Th1 bias. Keywords: Selenium nanoparticles, Hepatitis B vaccine, IFN-γ, Th1 immune response

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.

Background: L-tryptophan (L-Trp) is a nutritionally essential amino acid that the body uses to synthesize proteins, niacin (vitamin B3) and serotonin (neurotransmitters). Human and animals depend on plants and microorganisms for its supply. Remarkable increasing demand has caused the development of a wide variety of biotechnological methods for its production which work as well for other amino acids. Objectives: The present work reports on the use of Iranian sugar beet molasses as an inexpensive source of L-serine (precursor) and PLP (cofactor) for the production of L-Trp by Escherichia coli (ATCC 11303). Carbon source and buffered condition are also optimized for L-Trp production by E. coli. Materials and Methods: E. coli (ATCC 11303) was used as the microbial source of tryptophan. Batch fermentation was performed with 8L sugar beet molasses medium. The fermentation was carried out at 37 °C with an agitation speed at 250 rpm. The pH was controlled at 7 with 10 N NaOH. The cells were recovered by centrifugation. A 1g mass of E. coli cells (wet mass) was used as the biocatalyst in the reaction medium (100 cc) containing (in grams/100cc): Molasses/glucose=3.5; Indole=0.2; L-Serine=0.35; PLP=0.005; (NH4)2SO4 =0.5. The reaction medium was incubated on rotatory shaker (180 rpm) for 8 h at 37 °C. The reaction was carried out in KH2PO4-K2HPO4 buffering system (pH = 8, 0.1 M). The detection of produced L-Trp was carried out by the use of chromatography methods (HPLC and TLC), and fluorescence analysis. Results: Consequently, the potassium phosphate buffer system was considered as the suitably buffered reaction medium. The concentration of L-Trp produced in reaction medium was 0.3 mM and 0.12 mM for glucose and molasses (a combination of sugar beet and cane molasses), respectively. Conclusions: our present study shows that sugar beet molasses is a source of PLP and L-Ser; and hence, suggests the general application of the approach to produce L-Trp more economically.