Effect of walnut consumption on markers of endothelial function in adults: A systematic review and meta-analysis of randomized controlled trials.

Findings on the effect of walnut consumption on endothelial function are conflicting. Therefore, the present systematic review and meta-analysis summarized available trials in this regard. A systematic search was performed in online databases including PubMed-Medline, Scopus, and ISI Web of Science up to October 2023. Articles that reported the effect of walnut intake on flow-mediated dilation (FMD), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and stimulus-adjusted response measure (SARM) were included. Random effects models for a weighted mean difference (WMD) or standardized mean difference (SMD) were used to test for the overall effect. Six eligible trials were analyzed (250 participants). Walnut intake significantly increased FMD (WMD: 0.94%, 95% CI: 0.12 to 1.75; p = 0.02). However, meta-analysis could not show any beneficial effect of walnut intake on ICAM-1 (SMD: -0.23, 95% CI: -0.68 to 0.22; p = 0.31), VCAM-1 (SMD: -0.02, 95% CI: -1.38 to 1.34; p = 0.97), and SARM (WMD: 0.01%, 95% CI: -0.01 to 0.04; p = 0.28). In conclusion, the present meta-analysis suggests that walnuts may reduce cardiovascular disease risk by improving FMD. However, further studies should be performed on adults to determine the effect of walnut intake on endothelial function.

The protective effects of quercetin on the physiological responses in malathion-exposed common carp, Cyprinus carpio.

This study aimed to evaluate the protective effects of quercetin on the biochemical parameters, immunity, and growth performance in malathion-exposed common carp, Cyprinus carpio. The methods six experimental groups, including the control group, fish exposed to concentrations of 1.04 and 2.08 mg/l malathion, fish supplemented with quercetin (200 mg/kg diet), and fish treated with quercetin + malathion for 21 days, were considered for the experiment. After the feeding period, in results the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) were significantly decreased in the hepatocyte, while malondialdehyde (MDA) content increased in response to malathion. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and glucose, cortisol, and urea levels significantly increased after exposure to malathion. Exposure of fish to malathion-induced decreases in protease, lysozyme, and alternative complement (ACH50) activities and total immunoglobulin (total Ig) in the mucosa. Changes in other parameters were different depending on malathion concentrations. The supplementation of fish with quercetin had no ameliorating effect on the malathion-related alternations of mucosal lysozyme and protease activities. However, quercetin ameliorated the depressing effects of malathion on biochemical and immunological parameters. Changes in the growth performance and hematological parameters indicated the toxic effect of malathion. In conclusion, quercetin could efficiently reduce the toxic effects of malathion on the biochemical, immune, and hematological parameters of the common carp.

Does CCL19 act as a double-edged sword in cancer development?

Cancer is considered a life-threatening disease, and several factors are involved in its development. Chemokines are small proteins that physiologically exert pivotal roles in lymphoid and non-lymphoid tissues. The imbalance or dysregulation of chemokines has contributed to the development of several diseases, especially cancer. CCL19 is one of the homeostatic chemokines that is abundantly expressed in the thymus and lymph nodes. This chemokine, which primarily regulates immune cell trafficking, is involved in cancer development. Through the induction of anti-tumor immune responses and inhibition of angiogenesis, CCL19 exerts tumor-suppressive functions. In contrast, CCL19 also acts as a tumor-supportive factor by inducing inflammation, cell growth, and metastasis. Moreover, CCL19 dysregulation in several cancers, including colorectal, breast, pancreatic, and lung cancers, has been considered a tumor biomarker for diagnosis and prognosis. Using CCL19-based therapeutic approaches has also been proposed to overcome cancer development. This review will shed more light on the multifarious function of CCL19 in cancer and elucidate its application in diagnosis, prognosis, and even therapy. It is expected that the study of CCL19 in cancer might be promising to broaden our knowledge of cancer development and might introduce novel approaches in cancer management.

A comprehensive review of IL-26 to pave a new way for a profound understanding of the pathobiology of cancer, inflammatory diseases and infections.

Cytokines are considered vital mediators of the immune system. Down- or upregulation of these mediators is linked to several inflammatory and pathologic situations. IL-26 is referred to as an identified member of the IL-10 family and IL-20 subfamily. Due to having a unique cationic structure, IL-26 exerts diverse functions in several diseases. Since IL-26 is mainly secreted from Th17, it is primarily considered a pro-inflammatory cytokine. Upon binding to its receptor complex (IL-10R1/IL-20R2), IL-26 activates multiple signalling mediators, especially STAT1/STAT3. In cancer, IL-26 induces IL-22-producing cells, which consequently decrease cytotoxic T-cell functions and promote tumour growth through activating anti-apoptotic proteins. In hypersensitivity conditions such as rheumatoid arthritis, multiple sclerosis, psoriasis and allergic disease, this cytokine functions primarily as the disease-promoting mediator and might be considered a biomarker for disease prognosis. Although IL-26 exerts antimicrobial function in infections such as hepatitis, tuberculosis and leprosy, it has also been shown that IL-26 might be involved in the pathogenesis and exacerbation of sepsis. Besides, the involvement of IL-26 has been confirmed in other conditions, including graft-versus-host disease and chronic obstructive pulmonary disease. Therefore, due to the multifarious function of this cytokine, it is proposed that the underlying mechanism regarding IL-26 function should be elucidated. Collectively, it is hoped that the examination of IL-26 in several contexts might be promising in predicting disease prognosis and might introduce novel approaches in the treatment of various diseases.

Liposomes: Structure, Biomedical Applications, and Stability Parameters With Emphasis on Cholesterol.

Liposomes are essentially a subtype of nanoparticles comprising a hydrophobic tail and a hydrophilic head constituting a phospholipid membrane. The spherical or multilayered spherical structures of liposomes are highly rich in lipid contents with numerous criteria for their classification, including structural features, structural parameters, and size, synthesis methods, preparation, and drug loading. Despite various liposomal applications, such as drug, vaccine/gene delivery, biosensors fabrication, diagnosis, and food products applications, their use encounters many limitations due to physico-chemical instability as their stability is vigorously affected by the constituting ingredients wherein cholesterol performs a vital role in the stability of the liposomal membrane. It has well established that cholesterol exerts its impact by controlling fluidity, permeability, membrane strength, elasticity and stiffness, transition temperature (Tm), drug retention, phospholipid packing, and plasma stability. Although the undetermined optimum amount of cholesterol for preparing a stable and controlled release vehicle has been the downside, but researchers are still focused on cholesterol as a promising material for the stability of liposomes necessitating explanation for the stability promotion of liposomes. Herein, the prior art pertaining to the liposomal appliances, especially for drug delivery in cancer therapy, and their stability emphasizing the roles of cholesterol.

Mesenchymal Stem/Stromal Cells as a Vehicle for Cytokine Delivery: An Emerging Approach for Tumor Immunotherapy.

Pro-inflammatory cytokines can effectively be used for tumor immunotherapy, affecting every step of the tumor immunity cycle. Thereby, they can restore antigen priming, improve the effector immune cell frequencies in the tumor microenvironment (TME), and eventually strengthen their cytolytic function. A renewed interest in the anticancer competencies of cytokines has resulted in a substantial promotion in the number of trials to address the safety and efficacy of cytokine-based therapeutic options. However, low response rate along with the high toxicity associated with high-dose cytokine for reaching desired therapeutic outcomes negatively affect their clinical utility. Recently, mesenchymal stem/stromal cells (MSCs) due to their pronounced tropism to tumors and also lower immunogenicity have become a promising vehicle for cytokine delivery for human malignancies. MSC-based delivery of the cytokine can lead to the more effective immune cell-induced antitumor response and provide sustained release of target cytokines, as widely evidenced in a myriad of xenograft models. In the current review, we offer a summary of the novel trends in cytokine immunotherapy using MSCs as a potent and encouraging carrier for antitumor cytokines, focusing on the last two decades' animal reports.

Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges.

The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted rapidly evolving attention as a cancer treatment modality because of its competence to selectively eliminate tumor cells without instigating toxicity in vivo. TRAIL has revealed encouraging promise in preclinical reports in animal models as a cancer treatment option; however, the foremost constraint of the TRAIL therapy is the advancement of TRAIL resistance through a myriad of mechanisms in tumor cells. Investigations have documented that improvement of the expression of anti-apoptotic proteins and survival or proliferation involved signaling pathways concurrently suppressing the expression of pro-apoptotic proteins along with down-regulation of expression of TRAILR1 and TRAILR2, also known as death receptor 4 and 5 (DR4/5) are reliable for tumor cells resistance to TRAIL. Therefore, it seems that the development of a therapeutic approach for overcoming TRAIL resistance is of paramount importance. Studies currently have shown that combined treatment with anti-tumor agents, ranging from synthetic agents to natural products, and TRAIL could result in induction of apoptosis in TRAIL-resistant cells. Also, human mesenchymal stem/stromal cells (MSCs) engineered to generate and deliver TRAIL can provide both targeted and continued delivery of this apoptosis-inducing cytokine. Similarly, nanoparticle (NPs)-based TRAIL delivery offers novel platforms to defeat barricades to TRAIL therapeutic delivery. In the current review, we will focus on underlying mechanisms contributed to inducing resistance to TRAIL in tumor cells, and also discuss recent findings concerning the therapeutic efficacy of combined treatment of TRAIL with other antitumor compounds, and also TRAIL-delivery using human MSCs and NPs to overcome tumor cells resistance to TRAIL.

PD-1/PD-L1 blockade: Prospectives for immunotherapy in cancer and autoimmunity.

Immune checkpoint blockade therapy (ICBT) has become a successful cancer treatment approach in the field of cancer immunotherapy. Blockade of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) with monoclonal antibodies have been known as successful examples of cancer immunotherapy in recent years. Although ICBT has been shown to be beneficial in cancers, such benefits have only been seen in a portion of cancer patients. In this regard, enhancing the therapeutic effects of inhibiting PD-1 and PD-L1 and reducing the side effects of this approach can be considered as a potential approach in a successful ICBT. In this review, we have highlighted new viewpoints regarding improving the therapeutic effect of PD-1 and PD-L1 blockades in cancer therapy. Besides, their expression levels as a biomarker with prognostic value, their role in intestinal microbiota modulation, combination therapy, and immune-related side effects (irAEs) have been discussed.

Implementing PSO-ELM Model to Approximate Trolox Equivalent Antioxidant Capacity as One of the Most Important Biological Properties of Food.

In this paper, the Trolox equivalent antioxidant capacity (TEAC) is estimated through a robust machine-learning algorithm known as the Particle Swarm Optimization-based Extreme Learning Machine (PSO-ELM) model. For this purpose, a large dataset from previously published reports was gathered. Various analyses were performed to evaluate the proposed model. The results of the statistical analysis showed that this model can predict the actual values with high accuracy, so that the calculated R 2 and RMSE values were equal to 0.973 and 3.56, respectively. Sensitivity analysis was also performed on the effective input parameters. The leverage technique was also performed to check the accuracy of real data, and the results showed that the majority of data are reliable. This simple yet accurate model can be very powerful in predicting the Trolox equivalent antioxidant capacity values and can be a good alternative to laboratory data.

Arctigenin, an anti-tumor agent; a cutting-edge topic and up-to-the-minute approach in cancer treatment.

Today, herbal-derived compounds are being increasingly studied in cancer treatment. Over the past decade, Arctigenin has been introduced as a bioactive dibenzylbutyrolactone lignan which is found in Chinese herbal medicines. In addition to anti-microbial, anti-inflammatory, immune-modulatory functions, Arctigenin has attracted growing attention due to its anti-tumor capabilities. It has been shown that Arctigenin can induce apoptosis and necrosis and abolish drug resistance in tumor cells by inducing apoptotic signaling pathways, caspases, cell cycle arrest, and the modulating proteasome. Moreover, Arctigenin mediates other anti-tumor functions through several mechanisms. It has been demonstrated that Arctigenin can act as an anti-inflammatory compound to inhibit inflammation in the tumor microenvironment. It also downregulates factors involved in tumor metastasis and angiogenesis, such as matrix metalloproteinases, N-cadherin, TGF-ß, and VEGF. Additionally, Arctigenin, through modulation of MAPK signaling pathways and stress-related proteins, is able to abolish tumor cell growth in nutrient-deprived conditions. Due to the limited solubility of Arctigenin in water, it is suggested that modification of this compound through amino acid esterification can improve its pharmacogenetic properties. Collectively, it is hoped that using Arctigenin or its derivates might introduce new chemotherapeutic approaches in future treatment.

Changes in parameters of biochemical and oxidative stress in university students during and after examinations.

The study aimed to evaluate the parameters of lipid peroxidation and antioxidant protection, biochemical parameters, and cortisol and adrenaline content in the blood of students depending on the effect of exam stress. A total of 135 healthy students (72 female (53.3%) and 63 male (46.7%)) aged from 19 to 21 years (mean age 20.16 ± 0.42 years) of the experimental group underwent detailed medical screening and examination before the inclusion in the study. The control group consisted of 30 healthy students (17 female (56.7%) and 13 male (43.3%)) of corresponding age (mean age 20.23 ± 0.54 years), whose medical examination was performed during breaks in the absence of any stress factors. The blood parameters of the experimental group were investigated 1 h before, 1 h after, and 24 h after the exam. The cortisol content in the blood of experimental group students significantly increased 1.37 times (p < 0.05) an hour before the exam and 1.32 times (p < 0.05) an hour after; adrenalin content in blood increased 1.76 times (p < 0.05) and 1.49 times (p < 0.05), respectively. Compared to the control group, intensification of lipid peroxidation processes with a 1.51-fold (p < 0.05) increase in erythrocyte malonic aldehyde content in blood 1 h before and 1.42-fold (p < 0.05) increase an hour after the exam was observed in students due to the effect of exam stress.. Changes in hormonal homeostasis, activation of lipoperoxidation processes with the development of oxidative stress, and the disintegration of antioxidant protection factors are typical for academic stress in students.

Humoral immune mechanisms involved in protective and pathological immunity during COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is associated with excessive inflammation, as a main reason for severe condition and death. Increased inflammatory cytokines and humoral response to SARS-CoV-2 correlate with COVID-19 immunity and pathogenesis. Importantly, the levels of pro-inflammatory cytokines that increase profoundly in systemic circulation appear as part of the clinical pictures of two overlapping conditions, sepsis and the hemophagocytic syndromes. Both conditions can develop lethal inflammatory responses that lead to tissue damage, however, in many patients hemophagocytic lymphohistiocytosis (HLH) can be differentiated from sepsis. This is a key issue because the life-saving aggressive immunosuppressive treatment, required in the HLH therapy, is absent in sepsis guidelines. This paper aims to describe the pathophysiology and clinical relevance of these distinct entities in the course of COVID-19 that resemble sepsis and further highlights two effector arms of the humoral immune response (inflammatory cytokine and immunoglobulin production) during COVID-19 infection.

Mesenchymal Stem/Stromal Cell-Based Delivery: A Rapidly Evolving Strategy for Cancer Therapy.

Mesenchymal stem/stromal cell (MSC)-based therapy has become an attractive and advanced scientific research area in the context of cancer therapy. This interest is closely linked to the MSC-marked tropism for tumors, suggesting them as a rational and effective vehicle for drug delivery for both hematological and solid malignancies. Nonetheless, the therapeutic application of the MSCs in human tumors is still controversial because of the induction of several signaling pathways largely contributing to tumor progression and metastasis. In spite of some evidence supporting that MSCs may sustain cancer pathogenesis, increasing proofs have indicated the suppressive influences of MSCs on tumor cells. During the last years, a myriad of preclinical and some clinical studies have been carried out or are ongoing to address the safety and efficacy of the MSC-based delivery of therapeutic agents in diverse types of malignancies. A large number of studies have focused on the MSC application as delivery vehicles for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), chemotherapeutic drug such as gemcitabine (GCB), paclitaxel (PTX), and doxorubicin (DOX), prodrugs such as 5-fluorocytosine (5-FC) and ganciclovir (GCV), and immune cell-activating cytokines along with oncolytic virus. In the current review, we evaluate the latest findings rendering the potential of MSCs to be employed as potent gene/drug delivery vehicle for inducing tumor regression with a special focus on the in vivo reports performed during the last two decades.

A deep insight into CRISPR/Cas9 application in CAR-T cell-based tumor immunotherapies.

To date, two chimeric antigen receptors (CAR)-T cell products from autologous T cells have been approved by The United States Food and Drug Administration (FDA). The case-by-case autologous T cell generation setting is largely considered as a pivotal restraining cause for its large-scale clinical use because of the costly and prolonged manufacturing procedure. Further, activated CAR-T cells mainly express immune checkpoint molecules, including CTLA4, PD1, LAG3, abrogating CAR-T anti-tumor activity. In addition, CAR-T cell therapy potently results in some toxicity, such as cytokine releases syndrome (CRS). Therefore, the development of the universal allogeneic T cells with higher anti-tumor effects is of paramount importance. Thus, genome-editing technologies, in particular, clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 are currently being used to establish "off-the-shelf" CAR-T cells with robust resistance to immune cell-suppressive molecules. In fact, that simultaneous ablation of PD-1, T cell receptor alpha constant (TRAC or TCR), and also ß-2 microglobulin (B2M) by CRISPR-Cas9 technique can support the manufacture of universal CAR-T cells with robust resistance to PD-L1. . Indeed, the ablation of ß2M or TARC can severely hinder swift elimination of allogeneic T cells those express foreign HLA-I molecules, and thereby enables the generation of CAR-T cells from allogeneic healthy donors T cells with higher persistence in vivo. Herein, we will deliver a brief overview of the CAR-T cell application in the context of tumor immunotherapy. More importantly, we will discuss recent finding concerning the application of genome editing technologies for preparing universal CAR-T cells or cells that can effectively counter tumor escape, with a special focus on CRISPR-Cas9 technology.

Impact of Impulses on Microstructural Evolution and Mechanical Performance of Al-Mg-Si Alloy Joined by Impulse Friction Stir Welding.

Impulse Friction Stir Welding (IFSW) was utilized to join 6082-T6 alloy plates at various impulse frequencies. A distinctive feature of IFSW is the generation of mechanical impulses that enhances the forging action of the tool, and thereby, alters the weld microstructure. The microstructural evolution in the Stir Zone (SZ) with special focus on the strengthening precipitation behavior, and overall mechanical properties of the IFSW joints have been investigated. It was demonstrated that the strengthening ß″ precipitates reprecipitated in the SZ of the IFSW joints during natural aging. In contrast, no precipitates were found in the SZ of the Friction Stir Welding (FSW) weld. Partial reversion of ß″ after IFSW is supposed to occur due to more developed subgrain network and higher dislocation density introduced by impulses that accelerated precipitation kinetics. Dynamic recrystallisation was facilitated by impulses resulting in a fine, homogeneous structure. There was no significant difference between the microhardness in the SZ, tensile and yield strength of the FSW and IFSW joints. However, the application of impulses demonstrated the smoothing of the hardness reduction in the transition region at the advancing side. The shift of the fracture location from the Heat-Affected Zone (HAZ) by FSW to the SZ as well as higher elongation of the joints by IFSW of lower frequencies could be related to the grain refinement and the change of the grain orientation.

Optical Density Optimization of Malaria Pan Rapid Diagnostic Test Strips for Improved Test Zone Band Intensity.

For the last few decades, the immunochromatographic assay has been used for the rapid detection of biological markers in infectious diseases in humans and animals The assay, also known as lateral flow assay, is utilized for the detection of antigen or antibody in human infectious diseases. There are a series of steps involved in the development of these immuno-chromatographic test kits, from gold nano colloids preparation to nitrocellulose membrane coating (NCM). These tests are mostly used for qualitative assays by a visual interpretation of results. For the interpretation of the results, the color intensity of the test zone is therefore very significant. Herein, the study was performed on a malaria antigen test kit. Several studies have reported the use of gold nanoparticles (AuNPs) with varying diameters and its binding with various concentrations of protein in order to optimize tests. However, none of these studies have reported how to fix (improve) test zone band intensity (color), if different sized AuNPs were synthesized during a reaction and when conjugated equally with same amount of protein. Herein, different AuNPs with average diameter ranging from 10 nm to 50 nm were prepared and conjugated equally with protein concentration of 150 µg/mL with KD = 1.0 × 10-3. Afterwards, the developed kits' test zone band intensity for all different sizes AuNPs was fixed to the same band level (high) by utilization of an ultraviolet-visible spectrophotometer. The study found that the same optical density (OD) has the same test zone band intensity irrespective of AuNP size. This study also illustrates the use of absorption maxima (λ max) techniques to characterize AuNPs and to prevent wastage of protein while developing immunochromatographic test kits.

Development and validation of the quantitative determination procedure of iodine in the iodides form in the kelp thallus by the ionometry method.

INTRODUCTION: Iodine is an important compound in the kelp thallus; it should be determined to control the quality of crude herbal drugs of Laminaria sp. The ionometry method is perspective iodine (in the iodides form) determination method in the crude herbal drugs; it is characterized by the availability and relative cheapness of iodide-selective electrodes and equipment in general. This method provides an effective combination of the determination step with the fast, simple, and safe step of sample preparation. AIM: The current study aims to develop and validate a simple, effective procedure for the quantitative determination of iodine in the form of iodide by ionometry in the kelp thallus (Laminaria sp.). MATERIALS AND METHODS: The determination of iodides was carried out by using the "Ecotest-120" pH meter. "Ekom-I" was used as an ion-selective electrode. Silver chloride electrode "ESR 10101" was used as a reference electrode. RESULTS AND DISCUSSION: The developed procedure has a suitable level of linearity (correlation coefficient = 0.9995%), correctness (variation coefficient = 1.58%), repeatability (variation coefficient = 6.67%), and analytical area (0.03-209.4 µg/mL analyte in the test solution). The procedure allows us to determine iodine in the form of iodides with an accuracy comparable to the accuracy of neutron activation analysis and can be recommended as an alternative to titrimetric methods existing in the world-leading pharmacopoeias.