The role of fat-soluble vitamins in efferocytosis.

Cell death and the efficient removal of dead cells are two basic mechanisms that maintain homeostasis in multicellular organisms. efferocytosis, which includes four steps recruitment, recognition, binding and signaling, and engulfment. Effectively and quickly removes apoptotic cells from the body. Any alteration in efferocytosis can lead to several diseases, including autoimmune and inflammatory conditions, atherosclerosis, and cancer. A wide range of dietary components affects apoptosis and, subsequently, efferocytosis. Some vitamins, including fat-soluble vitamins, affect different stages of efferocytosis. Among other things, by affecting macrophages, they are effective in the apoptotic cleansing of cells. Also, polyphenols indirectly intervene in efferocytosis through their effect on apoptosis. Considering that there are limited articles on the effect of nutrition on efferocytosis, in this article we will examine the effect of some dietary components on efferocytosis.

Efferocytosis: a double-edged sword in microbial immunity.

Efferocytosis is characterized as the rapid and efficient process by which dying or dead cells are removed. This type of clearance is initiated via "find-me" signals, and then, carries on by "eat-me" and "don't-eat-me" ones. Efferocytosis has a critical role to play in tissue homeostasis and innate immunity. However, some evidence suggests it as a double-edged sword in microbial immunity. In other words, some pathogens have degraded efferocytosis by employing efferocytic mechanisms to bypass innate immune detection and promote infection, despite the function of this process for the control and clearance of pathogens. In this review, the efferocytosis mechanisms from the recognition of dying cells to phagocytic engulfment are initially presented, and then, its diverse roles in inflammation and immunity are highlighted. In this case, much focus is also laid on some bacterial, viral, and parasitic infections caused by Mycobacterium tuberculosis (M. tb), Mycobacterium marinum (M. marinum), Listeria monocytogenes (L. monocytogenes), Chlamydia pneumoniae (CP), Klebsiella pneumoniae (KP), Influenza A virus (IAV), human immunodeficiency virus (HIV), and Leishmania, respectively.

Cell membrane biomimetic nanoparticles in drug delivery.

Despite the efficiency of nanoparticle (NP) therapy, in vivo investigations have shown that it does not perform as well as in vitro. In this case, NP confronts many defensive hurdles once they enter the body. The delivery of NP to sick tissue is inhibited by these immune-mediated clearance mechanisms. Hence, using a cell membrane to hide NP for active distribution offers up a new path for focused treatment. These NPs are better able to reach the disease's target location, leading to enhanced therapeutic efficacy. In this emerging class of drug delivery vehicles, the inherent relation between the NPs and the biological components obtained from the human body was utilized, which mimic the properties and activities of native cells. This new technology has shown the viability of using biomimicry to evade immune system-provided biological barriers, with an emphasis on restricting clearance from the body before reaching its intended target. Furthermore, by providing signaling cues and transplanted biological components that favorably change the intrinsic immune response at the disease site, the NPs would be capable interacting with immune cells regarding the biomimetic method. Thus, we aimed to provide a current landscape and future trends of biomimetic NPs in drug delivery.

Macrophage efferocytosis in health and disease.

Creating cellular homeostasis within a defined tissue typically relates to the processes of apoptosis and efferocytosis. A great example here is cell debris that must be removed to prevent unwanted inflammatory responses and then reduce autoimmunity. In view of that, defective efferocytosis is often assumed to be responsible for the improper clearance of apoptotic cells (ACs). This predicament triggers off inflammation and even results in disease development. Any disruption of phagocytic receptors, molecules as bridging groups, or signaling routes can also inhibit macrophage efferocytosis and lead to the impaired clearance of the apoptotic body. In this line, macrophages as professional phagocytic cells take the lead in the efferocytosis process. As well, insufficiency in macrophage efferocytosis facilitates the spread of a wide variety of diseases, including neurodegenerative diseases, kidney problems, types of cancer, asthma, and the like. Establishing the functions of macrophages in this respect can be thus useful in the treatment of many diseases. Against this background, this review aimed to recapitulate the knowledge about the mechanisms related to macrophage polarization under physiological or pathological conditions, and shed light on its interaction with efferocytosis.

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.

Potential diagnostic and prognostic of efferocytosis-related unwanted soluble receptors/ligands as new non-invasive biomarkers in disorders: a review.

Efferocytosis is the process by which apoptotic cells are removed without inflammation to maintain tissue homeostasis, prevent unwanted inflammatory responses, and inhibit autoimmune responses. Coordination of efferocytosis occurs via many surfaces and chemotactic molecules and adaptors. Recently, soluble positive or negative mediators of efferocytosis, have been more noticeable as non-invasive valuable biomarkers in prognosis and targeted therapy. These soluble factors can be detected in different bodily fluids, such as serum, plasma, and urine as a non-invasive method. There are lots of studies that have tried to show the importance of receptors and ligands in disorders; while a few studies tried to indicate the importance of soluble forms of receptors/ligands and their clinical aspects as a systemic compound and shedding of targets related to efferocytosis. Some of these soluble forms also can be as sensitive as specific biomarkers for certain diseases compared with routine biomarkers, such as soluble circulatory Lectin-like oxidized low-density lipoprotein receptor-1 vs. troponin T in the acute coronary syndrome. Thus, this review tried to gain more understanding about efferocytosis-related unwanted soluble receptors/ligands, their roles, the clinical significance, and potential for diagnosis, and prognosis related to different diseases.

Effect of diabetes on efferocytosis process.

Diabetes is a complex of genetic, metabolic, and autoimmune disorders that are characterized by hyperglycemia. Elevated apoptotic cell count following defective clearance of dead cells that can cause chronic inflammation is a hallmark of the diabetic wound. Effective dead cell clearance is a prerequisite for rapid inflammation resolution and successful recovery. Efferocytosis is a multistep process in which phagocytes engulf the dead cells. Cell body elimination is of great significance in disease and homeostasis. Recent research has clarified that diabetic wounds have an enhanced load of the apoptotic cell, which is partly attributed to the dysfunction of macrophages in apoptotic clearance at the site of the diabetic wounds. In the current work, we highlight the pathways implicated in efferocytosis, from the diagnosis of apoptotic cells to the phagocytic swallowing and the homeostatic resolution, and explain the possible pathophysiological episodes occurring when the proceeding is abrogated. Also, we describe the last development in the management of inflammation in diabetes wound and future directions of surveillance.

Liposomes: Ideal drug delivery systems in breast cancer.

Breast cancer (BC) has been recognized as the most common type of cancer in females across the world, accounting for 12% of each cancer case. In this sense, better diagnosis and screening have been thus far proven to contribute to higher survival rates. Moreover, traditional (or standard) chemotherapy is still known as one of the several prominent therapeutic options available, though it suffers from unsuitable cell selectivity, severe consequences, as well as resistance. In this regard, nanobased drug delivery systems (DDSs) are likely to provide promising grounds for BC treatment. Liposomes are accordingly effective nanosystems, having the benefits of multiple formulations verified to treat different diseases. Such systems possess specific features, including smaller size, biodegradability, hydrophobic/hydrophilic characteristics, biocompatibility, lower toxicity, as well as immunogenicity, which can all lead to considerable efficacy in treating various types of cancer. As chemotherapy uses drugs to target tumors, generates higher drug concentrations in tumors, which can provide for their slow release, and enhances drug stability, it can be improved via liposomes in DDSs for BC treatment. Therefore, the present study aims to review the existing issues regarding BC treatment and discuss liposome-based targeting in order to overcome barriers to conventional drug therapy.

The role of efferocytosis in neuro-degenerative diseases.

Efferocytosis has a critical role in maintaining tissues and organs' homeostasis by removing apoptotic cells. It is essential for human health, and disturbances in efferocytosis may result indifferent illnesses. In case of inadequate clearance of the dead cells, the content in the cells would be released. In fact, it induces some damages to the tissue and leads to the prolonged inflammation, so unsuitable phagocytosis of the apoptotic cells is involved in occurrence as well as expansion of numerous human chronic inflammatory diseases. Studies have shown age dependence of the neuro-degenerative diseases, which are largely due to the neuro-inflammation and the loss of neurons and thus cause the brain's functional disorders. Efferocytosis is coupled to anti-inflammatory responses that contribute to the elimination of the dying neurons in neuro-degenerative diseases, so its disruption may make a risk factor in numerous human chronic inflammatory diseases such as multiple sclerosis, Alzheimer's disease, glioblastoma, and Rett syndrome. This study is a review of the efferocytosis molecular pathways and their role in neuro-degenerative diseases in order to discover a new treatment option to cure patients.

Genetics of Familial Combined Hyperlipidemia (FCHL) Disorder: An Update.

Familial combined hyperlipidemia (FCHL) is one of the most common familial lipoprotein disorders of the lipoproteins, with a prevalence of 0.5% to 2% in different populations. About 10% of these patients suffer from cardiovascular disease and this number is increased by up to 11.3% in the young survivors of myocardial infarction and by 40% among all the survivors of myocardial infarction. Although initially thought to be that FCHL has an inheritance pattern of monogenic, the disease's etiology is still not fully understood and it appears that FCHL has a complex pattern related to genetic variants, environmental factors, and lifestyles. Two strategies have been used to identify its complex genetic background: candidate gene and the linkage approach, which have yielded an extensive list of genes associated with FCHL with a variable degree of scientific evidence. Until now, more than 30 different genetic variants have been identified related to FCHL. In this study, we aimed to review the individual genes that have been described in FCHL and how these genes and variants can be related to the current concept of metabolic pathways resulting in familial combined hyperlipidemia.

Shedding more light on the role of Midkine in hepatocellular carcinoma: New perspectives on diagnosis and therapy.

One of the most common malignant tumors is hepatocellular carcinoma (HCC). Progression of HCC mainly results from highly complex molecular and pathological pathways. Midkine (MDK) is a growth factor that impacts viability, migration, and other cell activities. Since MDK has been involved in the inflammatory responses, it has been claimed that MDK has a crucial role in HCC. MDK acts as an anti-apoptotic factor, which mediates tumor cell viability. In addition, MDK blocks anoikis to promote metastasis. There is also evidence that MDK is involved in angiogenesis. It has been shown that the application of anti-MDK approaches might be promising in the treatment of HCC. Besides, due to the elevated expression in HCC, MDK has been proposed as a biomarker in the prognosis and diagnosis of HCC. In this review, we will discuss the role of MDK in HCC. It is hoped that the development of new strategies concerning MDK-based therapies will be promising in HCC management.

The regulation of CD47-SIRPα signaling axis by microRNAs in combination with conventional cytotoxic drugs together with the help of nano-delivery: a choice for therapy?

CD47, a member of the immunoglobulin superfamily, is an important "Don't Eat-Me" signal in phagocytosis process [clearance of apoptotic cells] as well as a regulator of the adaptive immune response. The lower level of CD47 on the cell surface leads to the clearance of apoptotic cells. Dysregulation of CD47 plays a critical role in the development of disorders, particularly cancers. In cancers, recognition of CD47 overexpression on the surface of cancer cells by its receptor, SIRPα on the phagocytic cells, inhibits phagocytosis of cancer cells. Thus, blocking of CD47-SIRPα signaling axis might be as a promising therapeutic target, which promotes phagocytosis of cancer cells, antigen-presenting cell function as well as adaptive T cell-mediated anti-cancer immunity. In this respect, it has been reported that CD47 expression can be regulated by microRNAs (miRNAs). MiRNAs can regulate phagocytosis of macrophages apoptotic process, drug resistance, relapse of disease, radio-sensitivity, and suppress cell proliferation, migration, and invasion through post-transcriptional regulation of CD47-SIRPα signaling axis. Moreover, the regulation of CD47 expression by miRNAs and combination with conventional cytotoxic drugs together with the help of nano-delivery represent a valuable opportunity for effective cancer treatment. In this review, we review studies that evaluate the role of miRNAs in the regulation of CD47-SIRPα in disorders to achieve a novel preventive, diagnostic, and therapeutic strategy.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Also, kindly confirm the details in the metadata are correct. Confirmed.Journal standard instruction requires a structured abstract; however, none was provided. Please supply an Abstract with subsections..Not confirmed. This is a review article. According to submission guidelines: "The abstract should be presented divided into subheadings (unless it is a mini or full review article)". Kindly check and confirm whether the corresponding authors and mail ID are correctly identified. Confirmed.

The significant role of a functional polymorphism in the NF-κB1 gene in breast cancer: evidence from an Iranian cohort.

Aims: Breast cancer (BC) is one of the most common cancers among women. The influence of genetic variations on BC risk has been thus far assessed via genome-wide association studies. NF-κB has been recognized as a major player in BC progression. In this study, the association between rs28362491 and BC was evaluated in a population from northeastern Iran. Materials & methods: This study was conducted on 476 patients with BC and 524 healthy controls. The genotyping method used was an amplification-refractory mutation system. Results: The INS/DEL genotype conferred a statistically significant increased risk in patients in comparison with controls. Additionally, in the recessive model, INS/INS + INS/DEL versus DEL/DEL was statistically significant (OR = 0.34; 95% CI: 0.12-0.96; p = 0.042). Conclusion: This study found that rs28362491, as a susceptibility genetic factor, may affect BC risk in the Iranian population.

LncRNAs as putative biomarkers and therapeutic targets for Parkinson's disease.

Parkinson's disease (PD) is known as one of the most common degenerative disorders related to the damage of the central nervous system (CNS). This brain disorder is also characterized by the formation of Lewy bodies in the cytoplasm of the dopaminergic neurons in the substantia nigra pars compacta (SNc), which consequently leads to motor and non-motor symptoms. With regard to the growing trend in the number of cases with PD and its effects on individuals, families, and communities, immediate treatments together with diagnostic methods are required. In this respect, long non-coding ribonucleic acids (lncRNAs) represent a large class of ncRNAs with more than 200 nucleotides in length, playing key roles in some important processes including gene expression, cell differentiation, genomic imprinting, apoptosis, and cell cycle. They are highly expressed in the CNS and previous studies have further reported that the expression profile of lncRNAs is disrupted in human diseases such as neurodegenerative disorders. Since the levels of some lncRNAs change over time in the brains of patients with PD, a number of previous studies have examined their potentials as biomarkers for this brain disorder. Therefore, the main purpose of this study was to review the advances in the related literature on lncRNAs as diagnostic, therapeutic, and prognostic biomarkers for PD.

The Effect of Cigarette Smoke Exposure on Efferocytosis in Chronic Obstructive Pulmonary Disease; Molecular Mechanisms and Treatment Opportunities.

Cigarette smoking-related inflammation, cellular stresses, and tissue destruction play a key role in lung disease, such as chronic obstructive pulmonary disease (COPD). Notably, augmented apoptosis and impaired clearance of apoptotic cells, efferocytosis, contribute to the chronic inflammatory response and tissue destruction in patients with COPD. Of note, exposure to cigarette smoke can impair alveolar macrophages efferocytosis activity, which leads to secondary necrosis formation and tissue inflammation. A better understanding of the processes behind the effect of cigarette smoke on efferocytosis concerning lung disorders can help to design more efficient treatment approaches and also delay the development of lung disease, such as COPD. To this end, we aimed to seek mechanisms underlying the impairing effect of cigarette smoke on macrophages-mediated efferocytosis in COPD. Further, available therapeutic opportunities for restoring efferocytosis activity and ameliorating respiratory tract inflammation in smokers with COPD were also discussed.

CD47 in the Brain and Neurodegeneration: An Update on the Role in Neuroinflammatory Pathways.

CD47 is a receptor belonging to the immunoglobulin (Ig) superfamily and broadly expressed on cell membranes. Through interactions with ligands such as SIRPα, TSP-1, integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), CD47 regulates numerous functions like cell adhesion, proliferation, apoptosis, migration, homeostasis, and the immune system. In this aspect, previous research has shown that CD47 modulates phagocytosis via macrophages, the transmigration of neutrophils, and the activation of T-cells, dendritic cells, and B-cells. Moreover, several studies have reported the increased expression of the CD47 receptor in a variety of diseases, including acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), bladder cancer, acute myeloid leukemia (AML), Gaucher disease, Multiple Sclerosis and stroke among others. The ubiquitous expression of the CD47 cell receptor on most resident cells of the CNS has previously been established through different methodologies. However, there is little information concerning its precise functions in the development of different neurodegenerative pathologies in the CNS. Consequently, further research pertaining to the specific functions and roles of CD47 and SIRP is required prior to its exploitation as a druggable approach for the targeting of various neurodegenerative diseases that affect the human population. The present review attempts to summarize the role of both CD47 and SIRP and their therapeutic potential in neurodegenerative disorders.

Interface between Resolvins and Efferocytosis in Health and Disease.

Acute inflammation resolution acts as a vital process for active host response, tissue support, and homeostasis maintenance, during which resolvin D (RvD) and E (RvE) as mediators derived from omega-3 polyunsaturated fatty acids display specific and stereoselective anti-inflammations like restricting neutrophil infiltration and pro-resolving activities. On the other side of the coin, potent macrophage-mediated apoptotic cell clearance, namely efferocytosis, is essential for successful inflammation resolution. Further studies mentioned a linkage between efferocytosis and resolvins. For instance, resolvin D1 (RvD1), which is endogenously formed from docosahexaenoic acid within the inflammation resolution, thereby provoking efferocytosis. There is still limited information regarding the mechanism of action of RvD1-related efferocytosis enhancement at the molecular level. The current review article was conducted to explore recent data on how the efferocytosis process and resolvins relate to each other during the inflammation resolution in illness and health. Understanding different aspects of this connection sheds light on new curative approaches for medical conditions caused by defective efferocytosis and disrupted inflammation resolution.

The potential role and mechanism of circRNAs in Ferroptosis: A comprehensive review.

Cell death encompasses various mechanisms, including necrosis and apoptosis. Ferroptosis, a unique form of regulated cell death, emerged as a non-apoptotic process reliant on iron and reactive oxygen species (ROS). Distinguishing itself from other forms of cell death, ferroptosis exhibits distinct morphological, biochemical, and genetic features. Circular RNAs (circRNAs), a novel class of RNA molecules, play crucial regulatory roles in ferroptosis-mediated pathways and cellular processes. With their circular structure and stability, circRNAs function as microRNA sponges and participate in protein regulation, offering diverse mechanisms for cellular control. Accumulating evidence indicates that circRNAs are key players in diseases associated with ferroptosis, presenting opportunities for diagnostic and therapeutic applications. This study explores the regulatory roles of circRNAs in ferroptosis and their potential in diseases such as cancer, neurological disorders, and cardiovascular diseases. By investigating the relationship between circRNAs and ferroptosis, this research provides new insights into the diagnosis, treatment, and prognosis of ferroptosis-related diseases. Furthermore, the therapeutic implications of targeting circRNAs in cancer treatment and the modulation of ferroptosis pathways demonstrate the potential of circRNAs as diagnostic markers and therapeutic targets. Overall, understanding the involvement of circRNAs in regulating ferroptosis opens up new avenues for advancements in disease management.

Clearing the Path: Exploring Apoptotic Cell Clearance in Inflammatory and Autoimmune Disorders for Therapeutic Advancements.

Inflammatory and autoimmune disorders, characterized by dysregulated immune responses leading to tissue damage and chronic inflammation, present significant health challenges. This review uniquely focuses on efferocytosis-the phagocyte-mediated clearance of apoptotic cells-and its pivotal role in these disorders. We delve into the intricate mechanisms of efferocytosis' four stages and their implications in disease pathogenesis, distinguishing our study from previous literature. Our findings highlight impaired efferocytosis in conditions like atherosclerosis and asthma, proposing its targeting as a novel therapeutic strategy. We discuss the therapeutic potential of efferocytosis in modulating immune responses and resolving inflammation, offering a new perspective in treating inflammatory disorders.

Efferocytosis and metabolic syndrome: a narrative review.

Metabolic syndrome (MetS), which is distinguished by the simultaneous presence of hyperglycemia, dyslipidemia, hypertension, and central obesity, is a critical risk factor for cardiovascular disease (CVDs), mortality, and illness burden. Eliminating about one million cells per second in the human body, apoptosis conserves homeostasis and regulates the life cycle of organisms. In the physiological condition, the apoptotic cells internalize to the phagocytes by a multistep process named efferocytosis. Any impairment in the clearance of these apoptotic cells results in conditions related to chronic inflammation, such as obesity, diabetes, and dyslipidemia. On the other hand, insulin resistance and MetS can disturb the efferocytosis process. Since no study investigated the relationship between efferocytosis and MetS, we decided to explore the different steps of efferocytosis and describe how inefficient dead cell clearance is associated with the progression of MetS.