Aging is the progressive loss of organ and tissue function over time. Growing older is positively linked to cognitive and biological degeneration such as physical frailty, psychological impairment, ...and cognitive decline. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage. Oxidative stress plays a crucial role in the development of age-related diseases. Emerging research evidence has suggested that antioxidant can control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals and subsequently reduce oxidative stress, improve immune function, and increase healthy longevity. Indeed, oxidation damage is highly dependent on the inherited or acquired defects in enzymes involved in the redox-mediated signaling pathways. Therefore, the role of molecules with antioxidant activity that promote healthy aging and counteract oxidative stress is worth to discuss further. Of particular interest in this article, we highlighted the molecular mechanisms of antioxidants involved in the prevention of age-related diseases. Taken together, a better understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity.
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.
Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for ...regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.
Many types of research have distinctly addressed the efficacy of natural plant metabolites used for human consumption both in cell culture and preclinical animal model systems. However, these in ...vitro and in vivo effects have not been able to be translated for clinical use because of several factors such as inefficient systemic delivery and bioavailability of promising agents that significantly contribute to this disconnection. Over the past decades, extraordinary advances have been made successfully on the development of novel drug delivery systems for encapsulation of plant active metabolites including organic, inorganic and hybrid nanoparticles. The advanced formulas are confirmed to have extraordinary benefits over conventional and previously used systems in the manner of solubility, bioavailability, toxicity, pharmacological activity, stability, distribution, sustained delivery, and both physical and chemical degradation. The current review highlights the development of novel nanocarrier for plant active compounds, their method of preparation, type of active ingredients, and their biomedical applications.
Magnetic iron oxide nanoparticles (Fe3O4 MNPs) 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 Fe3O4 MNPs 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 Fe3O4 MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for leukemia (Jurkat cells), breast cancer (MCF-7 cells), cervical cancer (HeLa cells), and liver cancer (HepG2 cells). The cancer cells were treated with different concentrations of Fe3O4 MNPs, 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±1.1 μg/mL (HepG2), 18.75±2.1 μg/mL (MCF-7), 12.5±1.7 μg/mL (HeLa), and 6.4±2.3 μg/mL (Jurkat) 72 hours 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 Fe3O4 MNP-treated cells at sub-G1 phase, confirming induction of apoptosis by Fe3O4 MNPs. The Fe3O4 MNPs also activated caspase-3 and caspase-9 in a time-response fashion. The nature of the biosynthesis and therapeutic potential of Fe3O4 MNPs could pave the way for further research on the green synthesis of therapeutic agents, particularly in nanomedicine, to assist in the treatment of cancer.
Recently, mesenchymal stem/stromal cells (MSCs) and their widespread biomedical applications have attracted great consideration from the scientific community around the world. However, reports have ...shown that the main populations of the transplanted MSCs are trapped in the liver, spleen, and lung upon administration, highlighting the importance of the development of cell-free therapies. Concerning rising evidence suggesting that the beneficial effects of MSC therapy are closely linked to MSC-released components, predominantly MSC-derived exosomes, the development of an MSC-based cell-free approach is of paramount importance. The exosomes are nano-sized (30-100 nm) lipid bilayer membrane vesicles, which are typically released by MSCs and are found in different body fluids. They include various bioactive molecules, such as messenger RNA (mRNA), microRNAs, proteins, and bioactive lipids, thus showing pronounced therapeutic competence for tissues recovery through the maintenance of their endogenous stem cells, the enhancement of regenerative phenotypic traits, inhibition of apoptosis concomitant with immune modulation, and stimulation of the angiogenesis. Conversely, the specific roles of MSC exosomes in the treatment of various tumors remain challenging. The development and clinical application of novel MSC-based cell-free strategies can be supported by better understanding their mechanisms, classifying the subpopulation of exosomes, enhancing the conditions of cell culture and isolation, and increasing the production of exosomes along with engineering exosomes to deliver drugs and therapeutic molecules to the target sites. In the current review, we deliver a brief overview of MSC-derived exosome biogenesis, composition, and isolation methods and discuss recent investigation regarding the therapeutic potential of MSC exosomes in regenerative medicine accompanied by their double-edged sword role in cancer. Keywords: Mesenchymal stem/stromal cells (MSCs), Exosomes, Regenerative medicine, Cancer, MicroRNAs (miRNAs)
The mastic gum resin has been used in traditional Kurdish medicine for treating various disorders such as topical wound and gastric ulcer. The study designed to evaluate the total polyphenol and ...flavonoid content, free radical scavenging activity, and anticancer effects of mastic gum resin derived from
subspecies kurdica.
Folin -Ciocalteau and the aluminum chloride colorimetric assays were used to determine the total phenol and flavonoid contents in the mastic gum resin respectively. Whereas, DPPH and ABTS+ assays were used to determine the antioxidant activities of mastic gum resin. Regarding anticancer activities, the MTT assay was used to study the effect of mastic gum resin on the proliferation of various cancer cells and the morphological changes were identified after Acridine Orange/Propidium Iodide staining. Flow cytometry was applied to determine the influence of mastic gum resin on the apoptosis rate by Annexin V double staining and to investigate the influence on cell cycle progression. Caspase colorimetric assay was used to estimate the hallmark enzyme of apoptosis, and finally RNA were obtained from COLO205 cells and analyzed by qRT-PCR analyses.
The MTT results showed that the mastic gum resin at concentrations from 0.01 to 100 μM induced death of cancer cells in a dose and time-dependent manner. The mastic gum resin suppressed proliferation of human cancer cells with 72 h IC
value of 15.34 ± 0.21, 11.52 ± 0.18, 8.11 ± 0.23 and 5.2 ± 0.8 μg/mL for bile duct cancer (cholangiocarcinoma) (KMBC), pancreatic carcinoma (PANC-1), gastric adenocarcinoma (CRL-1739), and colonic adenocarcinoma (COLO205) cells, respectively. Normal human colon fibroblast (CCD-18Co) cells were not adversely affected by resin treatment. Flow cytometry showed that the mastic gum resin significantly (
<0.05) arrested COLO205 cell proliferation at the G2/M phase of cell cycle. The resin caused apoptotic morphological changes in COLO205 cells. The apoptotic effect to mastic gum resin was via the mitochondrial as shown by the up-regulation of Bax, down-regulation of Bcl-2 genes, and activation of caspase-9 and -3 activities.
It was confirmed that the antiproliferative efficacy of the resin is positively correlated with its polyphenolic contents, suggesting a causal link related to exudate content of phenolic acid and flavonoids. The results revealed that the mastic gum resin has potential to be developed as an anticancer and antioxidant product due to its high content of polyphenol compounds.
Vitamin D (Vit D) is essential in maintaining calcium homeostasis and other body processes. It has been widely studied how Vit D affects cell cycle pathways and how it affects the development and ...prevention of breast cancer (BC). This study aimed to determine Vit D insufficiency linkage to the development of BC. In this case-control study, 130 women (65 BC patients and 65 healthy controls) aged 20-60 years who visited Shar Hospital Breast Center in Sulaimaniyah, Iraq, from December 2021 to May 2022 were included. Patients were selected after their diagnosis had been verified by breast ultrasound, mammography, and core biopsy. The ELISA test was used to measure the concentrations of serum Vit D and expressed in ng/ml. The results showed that the BC patients had considerably lower serum Vit D levels that were <20 ng/L in 66.1% (n=43) and 43.1% (n=28) in healthy controls. Compared to the control group (20.2±8.7), the mean Vit D level in BC patients was lower (17.8±8.6). A logistic regression test revealed a substantial increase in the risk of BC for low-level Vit D concentrations below 20 ng/L (OR 2.59, 95% CI 1.24-5.38; P=0.009). Vit D is still a significant risk factor for boosting the likelihood of developing BC after age and body mass index (BMI) adjustments (AOR 2.30, 95% CI 1.1-4.86; p=0.03 and AOR 3.67, 95% CI 1.55-8.7; p=0.002 for BC patients and controls, respectively). According to the outcomes of our investigations, we concluded that Vit D insufficiency raises the risk of BC among women in Sulaimaniyah, Iraq.
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.
IL‐26 is an identified member of the IL‐10 family and IL‐20 subfamily which is considered a vital mediator of the immune system. It exerts diverse functions in several diseases, including cancer, infections, and inflammatory diseases. It is hoped that targeting IL‐26 will lead to promising approaches in disease treatment.
Very recently, we postulated that the incorporation of citral into nanostructured lipid carrier (NLC-Citral) improves solubility and delivery of the citral without toxic effects in vivo. Thus, the ...objective of this study is to evaluate anti-cancer effects of NLC-Citral in MDA MB-231 cells in vitro through the Annexin V, cell cycle, JC-1 and fluorometric assays. Additionally, this study is aimed to effects of NLC-Citral in reducing the tumor weight and size in 4T1 induced murine breast cancer model. Results showed that NLC-Citral induced apoptosis and G2/M arrest in MDA MB-231 cells. Furthermore, a prominent anti-metastatic ability of NLC-Citral was demonstrated in vitro using scratch, migration and invasion assays. A significant reduction of migrated and invaded cells was observed in the NLC-Citral treated MDA MB-231 cells. To further evaluate the apoptotic and anti-metastatic mechanism of NLC-Citral at the molecular level, microarray-based gene expression and proteomic profiling were conducted. Based on the result obtained, NLC-Citral was found to regulate several important signaling pathways related to cancer development such as apoptosis, cell cycle, and metastasis signaling pathways. Additionally, gene expression analysis was validated through the targeted RNA sequencing and real-time polymerase chain reaction. In conclusion, the NLC-Citral inhibited the proliferation of breast cancer cells in vitro, majorly through the induction of apoptosis, anti-metastasis, anti-angiogenesis potentials, and reducing the tumor weight and size without altering the therapeutic effects of citral.
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