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Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy.

Chimeric antigen receptors (CARs) have a unique facet of synthetic biology and offer a paradigm shift in personalized medicine as they can use and redirect the patient's immune cells to attack cancer cells. CAR‐natural killer (NK) cells combine the targeted specificity of antigens with the subsequent intracellular signaling ability of the receptors to increase their anti‐cancer functions. Importantly, CAR‐NK cells can be utilized as universal cell‐based therapy without requiring human leukocyte antigen (HLA) matching or earlier contact with tumor‐associated antigens (TAAs). Indeed, CAR‐NK cells can be adapted to recognize various antigens, hold higher proliferation capacity, and in vivo persistence, show improved infiltration into the tumors, and the ability to overcome the resistant tumor microenvironment leading to sustained cytotoxicity against tumors. Accumulating evidence from recent in vivo studies rendering CAR‐NK cell anti‐cancer competencies renewed the attention in the context of cancer immunotherapy, as these redirected effector cells can be used in the development of the “off‐the‐shelf” anti‐cancer immunotherapeutic products. In the current review, we focus on the therapeutic efficacy of CAR‐NK cell therapies for treating various human malignancies, including hematological malignancies and solid tumors, and will discuss the recent findings in this regard, with a special focus on animal studies., In the current review, we focus on the therapeutic efficacy of CAR‐NK cell therapies for treating various human malignancies, including hematological malignancies and solid tumors, and will discuss the recent findings in this regard, with a special focus on animal studies.

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.

Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR), and also the capability to differentiate to multiple cell types including adipocyte, chondrocyte, or osteoblast in vitro depends on culture conditions. However, these distinct properties, including self-renewability, multipotency, and easy accessibility are just one side of the coin; another side is their huge secretome which is comprised of hundreds of mediators, cytokines, and signaling molecules and can effectively modulate the inflammatory responses and control the infiltration process that finally leads to a regulated tissue repair/healing or regeneration process. MSC-mediated immunomodulation is a direct result of a harmonic synergy of MSC-released signaling molecules (i.e., mediators, cytokines, and chemokines), the reaction of immune cells and other target cells to those molecules, and also feedback in the MSC-molecule-target cell axis. These features make MSCs a respectable and eligible therapeutic candidate to be evaluated in immune-mediated disorders, such as graft versus host diseases (GVHD), multiple sclerosis (MS), Crohn’s disease (CD), and osteoarthritis (OA), and even in immune-dysregulating infectious diseases such as the novel coronavirus disease 2019 (COVID-19). This paper discussed the therapeutic applications of MSC secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs were discussed. Besides, the novel discoveries and recent findings on immunomodulatory plasticity of MSCs, clinical applications, and the methods required for their use as an effective therapeutic option in patients with immune-mediated/immune-dysregulating diseases were highlighted.

In recent decades, a new method of cellular immunotherapy was introduced based on engineering and empowering the immune effector cells. In this type of immunotherapy, the immune effector cells are equipped with chimeric antigen receptor (CAR) to specifically target cancer cells. In much of the trials and experiments, CAR-modified T cell immunotherapy has achieved very promising therapeutic results in the treatment of some types of cancers and infectious diseases. However, there are also some considerable drawbacks in the clinical application of CAR-T cells although much effort is in progress to rectify the issues. In some conditions, CAR-T cells initiate over-activated and strong immune responses, therefore, causing unexpected side-effects such as systemic cytokine toxicity (i.e., cytokine release syndrome), neurotoxicity, on-target, off-tumor toxicity, and graft-versus-host disease (GvHD). To overcome these limitations in CAR-T cell immunotherapy, NK cells as an alternative source of immune effector cells have been utilized for CAR-engineering. Natural killer cells are key players of the innate immune system that can destroy virus-infected cells, tumor cells, or other aberrant cells with their efficient recognizing capability. Compared to T cells, CAR-transduced NK cells (CAR-NK) have several advantages, such as safety in clinical use, non-MHC-restricted recognition of tumor cells, and renewable and easy cell sources for their preparation. In this review, we will discuss the recent preclinical and clinical studies, different sources of NK cells, transduction methods, possible limitations and challenges, and clinical considerations.

Background CARs are simulated receptors containing an extracellular single-chain variable fragment (scFv), a transmembrane domain, as well as an intracellular region of immunoreceptor tyrosine-based activation motifs (ITAMs) in association with a co-stimulatory signal. Main body Chimeric antigen receptor (CAR) T cells are genetically engineered T cells to express a receptor for the recognition of the particular surface marker that has given rise to advances in the treatment of blood disorders. The CAR T cells obtain supra-physiological properties and conduct as “living drugs” presenting both immediate and steady effects after expression in T cells surface. But, their efficacy in solid tumor treatment has not yet been supported. The pivotal challenges in the field of solid tumor CAR T cell therapy can be summarized in three major parts: recognition, trafficking, and surviving in the tumor. On the other hand, the immunosuppressive tumor microenvironment (TME) interferes with T cell activity in terms of differentiation and exhaustion, and as a result of the combined use of CARs and checkpoint blockade, as well as the suppression of other inhibitor factors in the microenvironment, very promising results were obtained from the reduction of T cell exhaustion. Conclusion Nowadays, identifying and defeating the mechanisms associated with CAR T cell dysfunction is crucial to establish CAR T cells that can proliferate and lyse tumor cells severely. In this review, we discuss the CAR signaling and efficacy T in solid tumors and evaluate the most significant barriers in this process and describe the most novel therapeutic methods aiming to the acquirement of the promising therapeutic outcome in non-hematologic malignancies.

Angiogenesis is a crucial area in scientific research because it involves many important physiological and pathological processes. Indeed, angiogenesis is critical for normal physiological processes, including wound healing and embryonic development, as well as being a component of many disorders, such as rheumatoid arthritis, obesity, and diabetic retinopathies. Investigations of angiogenic mechanisms require assays that can activate the critical steps of angiogenesis as well as provide a tool for assessing the efficacy of therapeutic agents. Thus, angiogenesis assays are key tools for studying the mechanisms of angiogenesis and identifying the potential therapeutic strategies to modulate neovascularization. However, the regulation of angiogenesis is highly complex and not fully understood. Difficulties in assessing the regulators of angiogenic response have necessitated the development of an alternative approach. In this paper, we review the standard models for the study of tumor angiogenesis on the macroscopic scale that include in vitro, in vivo, and computational models. We also highlight the differences in several modeling approaches and describe key advances in understanding the computational models that contributed to the knowledge base of the field.

Background The links between gut microbiota and obesity are complex and multidirectional. A large number of studies have demonstrated the provoking effect of microbiota as the main environmental factor on the metabolic, and physiology status of its human host, as well as energy harvest. Dietary compounds are a source of energy and metabolites for gut bacteria. Dietary compounds also change the composition of gut microbiota and can influence the production of their metabolites. Impact of intestinal microbiota composition and metabolic interaction, including interaction with dietary components are the key issue in human health and obesity. Scope and approach Gut microecology could help fulfill the gap between obesity and energy intake throughout altering the processing of nutrients and energy storage in the body, revealing diet-related and age-related changes in the human intestinal microbiome and their consequences. Therefore, it is of critical importance in the prevention of obesity to understand how different types of food can influence gut mucosal integrity. Key findings and conclusions The association between gut microbiota and host metabolism could help explain promising therapeutic approaches throughout gut microbiota regulation in preventing and treating obesity.

Tryptophan (Trp) is an amino acid and an essential component of the human diet. It plays a crucial role in many metabolic functions. Clinicians can use Trp levels in the course of diagnosing various metabolic disorders and the symptoms associated with those diseases. Furthermore, supplementation with this amino acid is considered in the treatment of depression and sleep disorders, mainly due to the Trp relationship with the synthesis of serotonin (5-HT) and melatonin. It is also used in helping to resolve cognitive disorders, anxiety, or neurodegenerative diseases. Reduced secretion of serotonin is associated with autism spectrum disorder, obesity, anorexia and bulimia nervosa, and other diseases presenting peripherals symptoms. The literature strongly suggests that Trp has a significant role in the correct functionality of the brain-gut axis and immunology. This information leads to the consideration of Trp as an essential dietary component due to its role in the serotonin pathway. A reduced availability of Trp in diet and nutraceutical supplementation should be considered with greater concern than one might expect. This paper constitutes a review of the more salient aspects gleaned from the current knowledge base about the role of Trp in diseases, associated nutritional disorders, and food science, in general.

As a major neurodevelopmental disorder, Autism Spectrum Disorder (ASD) encompasses deficits in communication and repetitive and restricted interests or behaviors in childhood and adolescence. Its etiology may come from either a genetic, epigenetic, neurological, hormonal, or an environmental cause, generating pathways that often altogether play a synergistic role in the development of ASD pathogenesis. Furthermore, the metabolic origin of ASD should be important as well. A balanced diet consisting of the essential and special nutrients, alongside the recommended caloric intake, is highly recommended to promote growth and development that withstand the physiologic and behavioral challenges experienced by ASD children. In this review paper, we evaluated many studies that show a relationship between ASD and diet to develop a better understanding of the specific effects of the overall diet and the individual nutrients required for this population. This review will add a comprehensive update of knowledge in the field and shed light on the possible nutritional deficiencies, metabolic impairments (particularly in the gut microbiome), and malnutrition in individuals with ASD, which should be recognized in order to maintain the improved socio-behavioral habit and physical health.

Background Breast cancer is the most commonly occurring neoplasm in females, comprising 16% of all female cancers worldwide. Various studies indicate some discrepancies regarding zinc (Zn) levels in various samples of breast cancer patients. Objective The present study evaluated by meta-analysed the published data for Zn levels analyzed in breast tissue, plasma, serum, and hair samples and its relationship with breast cancer. Methods The present meta-analysis included 36 studies, all of which were published in the years between 1984 to 2017 and selected by searching the databases MEDLINE, EMBASE, Cochrane Library, PubMed, Scopus, and the ISI Web of Knowledge. The articles were analyzed, and I² statistics were used to examine heterogeneity. The objective analysis was performed on data from the 36 studies, with total 1699 study subjects and 2009 controls. Results Significant statistical differences overall were observed, based on a random effects model (SMD (95 % CI), −0.78[−1.40, −0.16], P = 0.014). Data from 19 of these studies indicated significant statistical differences between cancerous patients and controls with regard to serum and plasma Zn concentration (SMD [(95 %CI): −1.61(−2.43, −0.79)]. There was a significant statistical difference between the breast tissue and hair as regards Zn status (SMD (95%CI): 2.32(1.42, 3.21)) and (SMD (95v%CI): −1.80(−3.41, −0.20), respectively. Zn concentration levels typically decreased in blood and hair samples of patients with breast cancer, whereas it was elevated in tumor tissues. Conclusions There is a significant relationship between lowered serum Zn concentrations and risk of breast cancer onset or recurrences in women, but because of high heterogeneity, we recommend other primary studies.

Cancer is one of the world's most concerning health problems and poses many challenges in the range of approaches associated with the treatment of cancer. Current understanding of this disease brings to the fore a number of novel therapies that can be useful in the treatment of cancer. Among them, gene and cell therapies have emerged as novel and effective approaches. One of the most important challenges for cancer gene and cell therapies is correct monitoring of the modified genes and cells. In fact, visual tracking of therapeutic cells, immune cells, stem cells and genetic vectors that contain therapeutic genes and the various drugs is important in cancer therapy. Similarly, molecular imaging, such as nanosystems, fluorescence, bioluminescence, positron emission tomography, single photon-emission computed tomography and magnetic resonance imaging, have also been found to be powerful tools in monitoring cancer patients who have received therapeutic cell and gene therapies or drug therapies. In this review, we focus on these therapies and their molecular imaging techniques in treating and monitoring the progress of the therapies on various types of cancer.

Gold nanoparticles were grown onSargassum muticumwater extract (S-GNPs) using the green biosynthetic approach. The nanoparticles were characterized using UV-visible spectroscopy, zeta potential, and transmission electron microscopy (TEM). The resulting S-GNPs were spherical and crystalline with a size of in vitroanticancer activity was demonstrated in human leukemia cell lines. The cancer cells were treated with different concentrations of S-GNPs, and calorimetric (MTT) assay used for the cytotoxicity test, which resulted in an IC50value of 4.22 ± 1.12, 5.71 ± 1.4, 6.55 ± 0.9, and 7.29 ± 1.7 μg/mL for each of the K562, HL-60, Jurkat, and CEM-ss cells, respectively. Thus, the K562 was selected for the next experiments. Furthermore, apoptosis induction was confirmed by Hoechst 33342, annexin V staining, and caspase-3/-9 activity tests. The cell cycle analysis exhibited a significant increase in the accumulation of S-GNPs treated cells at the sub-G1 phase, demonstrating the induction of apoptosis by S-GNPs. The nature of the inhibition of cancer cell growth by S-GNPs could open the way for further research in the design of green synthesis therapeutic agents, particularly in nanomedicine, for the treatment of cancer.

Manganese (Mn) is the fifth most abundant metal on earth. Although it is a well understood essential trace element, in excess, Mn is neurotoxic. Initial toxic symptoms associated with Mn are of psychiatric nature and are clinically defined as locura manganica. Neurological signs of Mn toxicity include dystonia, progressive bradykinesia, and disturbance of gait, slurring, and stuttering of speech with diminished volume. Studies indicate that children who ingested Mn in the drinking water (WMn) at or above a level of 0.241mg/L for a minimum of three years performed more poorly in school as measured by mastery of language, mathematics, and in their overall grade average. The Mn-exposed children also performed more poorly on a battery of neurobehavioral tests. It was also found a significant association between higher WMn and lower cognitive performance, verbal function, and full-scale intelligence quotient (IQ) scores. Young children appear to make up a vulnerable group in exposed populations. Toxicity of WMn is a problem particularly in areas of industrial waste or where Mn is leaching from the soil into public drinking water. Practical and cost-effective approaches are available to remove Mn from drinking water. It is crucial to protect developing brains against Mn toxicity.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotypical patterns of interests and activities. ASD can be extremely costly to society at large and the individuals and families involved, constituting one of the most perplexing challenges in child development and education.

Hassan Othman Hemn,1,2 Muhammad Mustapha Noordin,1 Heshu Sulaiman Rahman,1,2 Hamza Hazilawati,1 Abubakr Zuki,1 Max Stanley Chartrand3 1Department of Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2College of Veterinary Medicine, University of Sulaimani, Sulaimani City, Kurdistan, Republic of Iraq; 3DigiCare, Behavioral Research, Casa Grande, AZ, USAAbstract: Owing to the high incidence of cholesterol-induced cardiovascular disease, particularly atherosclerosis, the current study was designed to investigate the preventive and therapeutic efficacies of dietary zerumbone (ZER) supplementation on the formation and development of atherosclerosis in rabbits fed with a high cholesterol diet. A total of 72 New Zealand white rabbits were divided randomly on two experimental studies carried out 8 weeks apart. The first experiment was designed to investigate the prophylactic efficacy of ZER in preventing early developed atheromatous lesion. The second experimental trial was aimed at investigating the therapeutic effect of ZER in reducing the atherosclerotic lesion progression and establishment. Sudanophilia, histopathological, and ultrastructural changes showed pronounced reduction in the plaque size in ZER-medicated aortas. On the other hand, dietary supplementation of ZER for almost 10 weeks as a prophylactic measure indicated substantially decreasing lipid profile values, and similarly, plaque size in comparison with high-cholesterol non-supplemented rabbits. Furthermore, the results of oxidative stress and antioxidant biomarker evaluation indicated that ZER is a potent antioxidant in suppressing the generation of free radicals in terms of atherosclerosis prevention and treatment. ZER significantly reduced the value of malondialdehyde and augmented the value of superoxide dismutase. In conclusion, our data indicated that dietary supplementation of ZER at doses of 8, 16, and 20 mg/kg alone as a prophylactic measure, and as a supplementary treatment with simvastatin, significantly reduced early plague formation, development, and establishment via significant reduction in serum lipid profile, together with suppression of oxidative damage, and therefore alleviated atherosclerosis lesions.Keywords: zerumbone, antihypercholesterolemic, antioxidant, atherosclerosis, rabbit model

This investigation determined the anticancer properties of zerumbone (ZER) on the human T-cell (Jurkat) line using the MTT assay, microscopic evaluations, flow cytometric analyses, and caspase activity estimations. The results showed that ZER is selectively cytotoxic to Jurkat cells in a dose and time-dependent manner with IC50 of 11.9 ± 0.2, 8.6 ± 0.5 and 5.4 ± 0.4 μg/mL at 24, 48 and 72 hours of treatment, respectively. ZER did not produce an adverse effect on normal human peripheral blood mononuclear cells (PBMC). ZER is not as cytotoxic as doxorubicin, which imposed an inhibitory effect on Jurkat cells with IC50 of 2.1 ± 0.2, 1.8 ± 0.15, 1.5 ± 0.07 μg/mL after 24, 48 and 72 hours treatment, respectively. ZER significantly (P

The aim of this study is to evaluate thein vitrocytotoxic activity and cellular effects of previously prepared ZnO-NPs on murine cancer cell lines using brown seaweed (Sargassum muticum) aqueous extract. Treated cancer cells with ZnO-NPs for 72 hours demonstrated various levels of cytotoxicity based on calculated IC50values using MTT assay as follows: 21.7 ± 1.3 μg/mL (4T1), 17.45 ± 1.1 μg/mL (CRL-1451), 11.75 ± 0.8 μg/mL (CT-26), and 5.6 ± 0.55 μg/mL (WEHI-3B), respectively. On the other hand, ZnO-NPs treatments for 72 hours showed no toxicity against normal mouse fibroblast (3T3) cell line. On the other hand, paclitaxel, which imposed an inhibitory effect on WEHI-3B cells with IC50of 2.25 ± 0.4, 1.17 ± 0.5, and 1.6 ± 0.09 μg/mL after 24, 48, and 72 hours treatment, respectively, was used as positive control. Furthermore, distinct morphological changes were found by utilizing fluorescent dyes; apoptotic population was increased via flowcytometry, while a cell cycle block and stimulation of apoptotic proteins were also observed. Additionally, the present study showed that the caspase activations contributed to ZnO-NPs triggered apoptotic death in WEHI-3 cells. Thus, the nature of biosynthesis and the therapeutic potential of ZnO-NPs could prepare the way for further research on the design of green synthesis therapeutic agents, particularly in nanomedicine, for the treatment of cancer.

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effectin vitrowas evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

Farideh Namvar,1,2 Heshu Sulaiman Rahman,3,4 Rosfarizan Mohamad,1,5 Javad Baharara,2 Mahnaz Mahdavi,6 Elaheh Amini,7 Max Stanley Chartrand,8 Swee Keong Yeap31Institute of Tropical Forestry and Forest Products, Universiti Putra Malaysia, Selangor, Malaysia; 2Research Center for Animal Development Applied Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran; 3Institute of Bioscience, 4Department ofMicrobiology and Pathology, Faculty of Veterinary Medicine, 5Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor, Malaysia; 6Department of Chemistry, Faculty of Science, Islamic Azad University, Shiraz Branch, Shiraz, 7Kharazmi University, Tehran, Iran; 8DigiCare Behavioral Research, Casa Grande, AZ, USAAbstract: Magnetic iron oxide nanoparticles (Fe3O4MNPs) are among the most useful metal nanoparticles for multiple applications across a broad spectrum in the biomedical field, including the diagnosis and treatment of cancer. In previous work, we synthesized and characterized Fe3O4MNPs using a simple, rapid, safe, efficient, one-step green method involving reduction of ferric chloride solution using brown seaweed (Sargassum muticum) aqueous extract containing hydroxyl, carboxyl, and amino functional groups mainly relevant to polysaccharides, which acts as a potential stabilizer and metal reductant agent. The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of these Fe3O4MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for leukemia (Jurkat cells), breast cancer (MCF-7cells), cervical cancer (HeLa cells), and liver cancer (HepG2cells). The cancer cells were treated with different concentrations of Fe3O4MNPs, and an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to test for cytotoxicity, resulting in an inhibitory concentration 50 (IC50)value of 23.83±1.1µg/mL (HepG2), 18.75±2.1µg/mL (MCF-7), 12.5±1.7µg/mL (HeLa), and 6.4±2.3µg/mL (Jurkat) 72hours after treatment. Therefore, Jurkat cells were selected for further investigation. The representative dot plots from flow cytometric analysis of apoptosis showed that the percentages of cells in early apoptosis and late apoptosis were increased. Cell cycle analysis showed a significant increase in accumulation of Fe3O4MNP-treated cells at sub-G1phase, confirming induction of apoptosis by Fe3O4MNPs. The Fe3O4MNPs also activated caspase-3and caspase-9in a time-response fashion. The nature of the biosynthesis and therapeutic potential of Fe3O4MNPs could pave the way for further research on the green synthesis of therapeutic agents, particularly in nanomedicine, to assist in the treatment of cancer. Keywords: green synthesis, seaweed water extract, anticancer effect, apoptosis

This study investigated the anticancer effect of zerumbone (ZER) and zerumbone-loaded nanostructured lipid carrier (ZER-NLC) on the human mammary gland adenocarcinoma (MDA-MB-231) cell line. The effect of ZER and ZER-NLC on MDA-MB-231 cells was determined via electron and fluorescent microscopy and flow cytometry using the Annexin V, cell cycle, and Tdt-mediated dUTP nick-end labeling assays. We demonstrated that ZER and ZER-NLC significantly suppressed the proliferation of MDA-MB-231 cells with an IC50of 5.96 ± 0.13 and 6.01 ± 0.11 μg/mL, respectively. ZER and ZER-NLC arrested MDA-MB-231 cell cycle at the G2/M phase. The induction of apoptosis by ZER and ZER-NLC was via the intrinsic pathway through the release of cytochrome c and activation of caspase-3 and caspase-9. The treatments also caused the downregulation of antiapoptotic Bcl-2, Bcl-xL proteins, and proliferating cell nuclear protein and upregulation of proapoptotic Bax protein. Therefore, loading of ZER into NLC did not compromise the anticancer effects of ZER on MDA-MB-231 cells. In conclusion, ZER-NLC, which increased the bioavailability of ZER, is an effective agent in the treatment of cancers.

Zerumbone (ZER) is a naturally occurring dietary compound, present in many natural foods consumed today. The compound derived from several plant species of the Zingiberaceae family that has been found to possess multiple biomedical properties, such as antiproliferative, antioxidant, anti-inflammatory, and anticancer activities. However, evidence of efficacy is sparse, pointing to the need for a more systematic review for assessing scientific evidence to support therapeutic claims made for ZER and to identify future research needs. This review provides an updated overview of in vitro and in vivo investigations of ZER, its cancer chemopreventive properties, and mechanisms of action. Therapeutic effects of ZER were found to be scientifically plausible and could be explained partially by in vivo and in vitro pharmacological activities. Much of the research outlined in this paper will serve as a foundation to explain ZER anticancer bioactivity, which will open the door for the development of strategies in the treatment of malignancies using ZER.

Underdeveloped recognition systems or predictors for negative consequences related to depression in the older adult put this population at a significant risk for suicide, medical illness, and poor health status. Research concerning strategies for predicting depression in the older adult population has not until recently focused on the possibility of measuring one's EI as a potential predictive factor. To address an aspect of this neglect, the present quantitative correlational study explored to what extent the total Emotional Quotient (EQ) scale score of EI predicted depression. Two self-report measures were utilized: the Geriatric Depression Scale-Short (GDS-Short), and the Bar-On Emotional Quotient Inventory:Short (EQ-i:S). A purposive sample of 128 men and women (ages 65 and older) were recruited from local recreation centers and independent living facilities. To determine the extent to which EQ-i:S scaled score predicted depression, multiple logistic regression analysis was carried out. After accounting for age, education, and anti-depressant use, EQ-i:S scaled score had a statistically significant effect OR=0.94 (0.91, 0.97), p

Heshu Sulaiman Rahman,1–3 Abdullah Rasedee,1,2 Chee Wun How,2 Nazariah Allaudin Zeenathul,1,2 Max Stanley Chartrand,4 Swee Keong Yeap,2 Ahmad Bustamam Abdul,2,5 Sheau Wei Tan,2 Hemn Hassan Othman,1,3 Zahra Ajdari,6 Farideh Namvar,7 Palanisamy Arulselvan,2 Sharida Fakurazi,2,5 Parvaneh Mehrbod,2 Nasibeh Daneshvar,2 Hasina Begum2 1Faculty of Veterinary Medicine, 2Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia; 3Faculty of Veterinary Medicine, University of Sulaimany, Sulaimany City, Northern Iraq; 4DigiCare Behavioral Research, Casa Grande, AZ, USA; 5Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, Malaysia; 6Faculty of Science and Technology, University Kebangsaan Malaysia, Selangor, Malaysia; 7Institute of Tropical Forestry and Forest Products (INTROP), Universiti Putra Malaysia, Selangor, Malaysia Abstract: Cancer nanotherapy is progressing rapidly with the introduction of many innovative drug delivery systems to replace conventional therapy. Although the antitumor activity of zerumbone (ZER) has been reported, there has been no information available on the effect of ZER-loaded nanostructured lipid carrier (NLC) (ZER-NLC) on murine leukemia cells. In this study, the in vitro and in vivo effects of ZER-NLC on murine leukemia induced with WEHI-3B cells were investigated. The results from 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, Hoechst 33342, Annexin V, cell cycle, and caspase activity assays showed that the growth of leukemia cells in vitro was inhibited by ZER-NLC. In addition, outcomes of histopathology, transmission electron microscopy, and Tdt-mediated dUTP nick-end labeling analyses revealed that the number of leukemia cells in the spleen of BALB/c leukemia mice significantly decreased after 4 weeks of oral treatment with various doses of ZER-NLC. Western blotting and reverse-transcription quantitative polymerase chain reaction assays confirmed the antileukemia effects of ZER-NLC. In conclusion, ZER-NLC was shown to induce a mitochondrial-dependent apoptotic pathway in murine leukemia. Loading of ZER in NLC did not compromise the anticancer effect of the compound, suggesting ZER-NLC as a promising and effective delivery system for treatment of cancers. Keywords: zerumbone-loaded nanostructured lipid carrier, leukemia, WEHI-3B cells, BALB/c mice, apoptosis, mitochondrial pathway