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Abstract: As the World Health Organization (WHO) declared, vaccines prevent an average of 2-3 million deaths yearly from diseases. However, effective prophylactic and therapeutic vaccines have yet to be developed for eradicating the deadliest diseases, viz., types of cancer, malaria, human immunodeficiency virus (HIV), and most serious microbial infections. Furthermore, scores of the existing vaccines have disadvantages, such as failure to completely stimulate the immune system, in vivo instability, high toxicity, need for the cold chain, and multiple administrations. Thus, good vaccine candidates need to be designed to elicit adaptive immune responses. In this line, the integration of sciences along with the use of various technologies has led to the emergence of a new field in vaccine production called biomimetic nanovaccines (BNVs). Given that, nanotechnology can significantly contribute to the design of such vaccines, providing them with enhanced specificity and potency. Nanoparticles (NPs) and biomimetic NPs (BNPs) are now exploited as the main carriers for drug delivery systems, especially BNPs, whose biological mimicry makes them escape the immune system and transport drugs to the desired target. The drug accordingly seeks to camouflage itself with the help of NPs and the membranes taken from cells in the human body, including red blood cells (RBCs), white blood cells (WBCs), platelets, and cancer cells, for more effective and ideal delivery. As BNPs have recently become the center of attention in vaccine design, this review deliberates on the advances in BNVs.

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.

Abstract: Nowadays, many people suffer from Neurological Diseases (NDs), particularly neurodegenerative diseases. Hence, there is an urgent need to discover new and more effective diagnostic and prognostic biomarkers as well as therapeutic strategies for the treatment of NDs. In this context, detecting biomarkers can provide helpful information on various levels of NDs. Up to now, there has been a lot of progress in recognizing these diseases, but they are not completely clear yet. NDs are associated with inflammatory conditions and there are several differences in NDs’ immune biomarkers compared to normal conditions. Among these biomarkers, soluble CD163 (sCD163) levels (as a new biomarker) increase in biofluids, relating to the activation of macrophage/microglia and inflammation levels in NDs. ADAM17/TACE and ADAM10 are the responsible enzymes for producing sCD163 from macrophages. Increased shedding of CD163 is caused by inflammatory stimuli, and a function has been hypothesized for sCD163 in immunological suppression. When the body confronts an inflammation or infection, the concentration of sCD163 drives up. sCD163 is stable and can be easily quantified in the serum. In addition to its role as a biomarker, sCD163 can be a good modulator of adaptive immune suppression after stroke. sCD163, with a long half-life, has been proposed to be a surrogate for some critical markers such as Tumor Necrosis Factor-α (TNF-α). Furthermore, sCD163 production can be regulated by some regents/approaches such as zidovudine, nanotechnology, combination antiretroviral treatment, and aprepitant. Considering the importance of the issue, the critical role of sCD163 in NDs was highlighted for novel diagnostic and prognostic purposes.

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.

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.

Bio-degradable nanoparticles (NPs) have several utilizations as drug delivery vehicles due to their acceptable bio-availability, lower toxicity, potency for encapsulation and controlled release. Moreover, the interaction of the NPs with the macrophages of the reticuloendothelial system (RES) may decrease NPs efficacy for medical purposes. The surface of NPs is conventionally neutralized with the molecules such as poly(ethylene glycol) (PEG), as one of the most widely applied stealth polymers, in order to restrict the NPs clearance through the RES system. In fact, these molecules exhibit resistance to RES clearance and protein adsorption. It is unfortunate that modifying the PEG has some shortcomings, like problems in the synthesis as well as correlation to the immune reaction. The CD47 receptor has been well known as a ‘don’t-eat-me’ molecule on the self-- cells' surface. Therefore, the receptor will inhibit phagocytosis via binding to its ligand that is known as the signal regulatory protein α (SIRP-α). Moreover, the CD47 receptor, as one of the biomimetic substances, or its derivative peptides, have been used recently on the surface of nanoparticles to inhibit phagocytosis and increase the NPs retention time in the blood circulation. Therefore, this review study examined the CD47 receptor and its role in the immune system as well as the use of the CD47 receptor in coating NPs to increase their retention time in the blood circulation.

Brucellosis is considered as the most common bacterial zoonosis in the world. Although the laboratory findings are the most reliable diagnosis today, the current laboratory methods have many limitations. This research aimed to design and evaluate the performance of a novel technique based on the localized surface plasmon resonance (LSPR) to eliminate or reduce existing shortcomings. For this purpose, smooth lipopolysaccharides were extracted from Brucella melitensis and Brucella abortus and fixed on the surface of the gold nanoparticles through covalent interactions. After some optimizing processes, dynamic light scattering was used to characterize the probe. The detection of captured anti-Brucella antibody was performed by measuring the redshift on LSPR peak followed by the determination of cutoff value, which indicated a significant difference between controls and true positive patients (P value

Background: Viral respiratory infections could result in perturbation of the gut microbiota due to a probable cross-talk between lungs and gut microbiota. This can affect pulmonary health and the gastrointestinal system. Objective: This review aimed to discuss the impact of probiotics/prebiotics and supplements on the prevention and treatment of respiratory infections, especially emerging pathogens. Methods: The data were searched in PubMed, Scopus, Google Scholar, Google Patents, and The Lens-Patent using keywords of probiotics and viral respiratory infections in the title, abstract, and keywords. Result: Probiotics consumption could decrease the susceptibility to viral respiratory infections, such as COVID-19 and simultaneously enhance vaccine efficiency in infectious disease prevention through the immune system enhancement. Probiotics improve the gut microbiota and the immune system via regulating the innate system response and production of anti-inflammatory cytokines. Moreover, treatment with probiotics contributes to intestinal homeostasis restitution under antibiotic pressure and decreasing the risk of secondary infections due to viral respiratory infections. Probiotics present varied performances in different conditions; thus, promoting their efficacy through combining with supplements (prebiotics, postbiotics, nutraceuticals, berberine, curcumin, lactoferrin, minerals, and vitamins) is important. Several supplements reported to enhance the probiotics’ efficacy and their mechanisms as well as probiotics- related patents are summarized in this review. Using nanotechnology and microencapsulation techniques can also improve probiotics’ efficiency. Conclusion: Given the global challenge of COVID-19, probiotic/prebiotic and following nutritional guidelines should be regarded seriously. Additionally, their role as an adjuvant in vaccination for immune response augmentation needs attention.

Gastrointestinal cancer (GIC) remains a leading cause of morbidity and mortality worldwide. Unfortunately, these cancers are diagnosed in advanced metastatic stages due to lack of reliable biomarkers that are sufficiently specific and sensitive in early disease. There has been growing evidence that circulating exosomes can be used to diagnose cancer non-invasively with limited risks and side effects. Furthermore, exosomal long non-coding RNAs (lncRNAs) are emerging as a new class of promising biomarkers in cancer. This review provides an overview of the extraction and detection of exosomal lncRNAs with a focus on their potential role in GIC.

Abstract: Treatment of neurological disorders has always been one of the challenges with which scientists are faced due to poor prognosis and symptom overlap, as well as the progress of the disease process. Neurological disorders such as Huntington’s, Parkinson's, Alzheimer's diseases, and Amyotrophic Lateral Sclerosis are very debilitating. Therefore, finding a biomarker is essential for early diagnosis and treatment goals. Recent studies have focused more on molecular factors and gene manipulation to find effective diagnostic and therapeutic biomarkers. Among these factors, microRNAs (miRNAs/miRs) have attracted a lot of attention. On the other hand, a growing correlation between miRNAs and neurological disorders has caused scientists to consider it as a diagnostic and therapeutic target. In this line, the miR-153 is one of the important and highly conserved miRNAs in mice and humans, whose expression level is altered in neurological disorders and also improves neurogenesis. MiR-153 can regulate multiple biological processes by targeting various factors. Furthermore, miR-153 expression also can be regulated by important regulators, such as long non-coding RNAs (e.g., KCNQ1OT1), and some compounds (e.g., Tanshinone IIA), altering the expression of miR-153. Given the growing interest in miR-153 as a biomarker and therapeutic target for neurological diseases as well as the lack of comprehensive investigation of miR-153 function in these disorders, it is necessary to identify the downstream and upstream targets and also it's potential as a therapeutic biomarker target. In this review, we will discuss the critical role of miR-153 in neurological disorders for novel diagnostic and prognostic purposes, and also its role in multi-drug resistance.

Receptor/ligand pair immune checkpoints are inhibitors that regulate immunity as vital "Don't Find-Me" signals to the adaptive immune system, additionally, the essential goals of anti-cancer therapy. Moreover, the immune checkpoints are involved in treatment resistance in cancer therapy. The immune checkpoints as a signal from "self" and their expression on healthy cells prevent phagocytosis. Cells (e.g., senescent and/or apoptotic cells) with low immune checkpoints, such as low CD47 and/or PD-L1, are phagocytosed, which is necessary for tissue integrity and homeostasis maintenance. In other words, cancer cells induce increased CD47 expression in the tumor microenvironment (TME), avoiding their clearance by immune cells. PD-L1 and/or CD47 expression tumors have also been employed as biomarkers to guide cure prospects. Thus, targeting innate and adaptive immune checkpoints might improve the influence of the treatments on tumor cells. However, the CD47 regulation in the TME stands intricate, so much of this process has stayed a riddle. In this line, less attention has been paid to cytokines in TME. Cytokines are significant regulators of tumor immune surveillance, and they do this by controlling the actions of the immune cell. Recently, it has been suggested that different types of cytokines at TME might cooperate with others that contribute to the regulation of CD47 and/or PD-L1.The data were searched in available databases and a Web Search engine (PubMed, Scopus, and Google Scholar) using related keywords in the title, abstract, and keywords.Given the significant role of pro/anti-inflammatory signaling in the TME, we discuss the present understanding of pro/anti-inflammatory signaling implications in "Don't Eat-Me" regulation signals, particularly CD47, in the pathophysiology of cancers and come up with innovative opinions for the clinical transformation and personalized medicine.

Obesity is associated with changes in the resolution of acute inflammation that contribute to the clinical complications. The exact mechanisms underlying unresolved inflammation in obesity are not fully understood. Adipocyte death leads to pro-inflammatory adipose tissue macrophages, stimulating additional adipocyte apoptosis. Thus, a complex and tightly regulated process to inhibit inflammation and maintain homeostasis after adipocyte apoptosis is needed to maintain health. In normal condition, a specialized phagocytic process (efferocytosis) performs this function, clearing necrotic and apoptotic cells (ACs) and controlling inflammation. For efficient and continued efferocytosis, phagocytes must internalize multiple ACs in physiological conditions and handle the excess metabolic burden in adipose tissue. In obesity, this control is lost and can be an important hallmark of the disease. In this regard, the deficiency of efferocytosis leads to delayed resolution of acute inflammation and can result in ongoing inflammation, immune system dysfunction, and insulin resistance in obesity. Hence, efficient clearance of ACs by M2 macrophages could limit long-term inflammation and ensue clinical complications, such as cardiovascular disease and diabetes. This review elaborates upon the molecular mechanisms to identify efferocytosis regulators in obesity, and the mechanisms that can improve efferocytosis and reduce obesity-related complications, such as the use of pharmacological agents and regular exercise.

Efferocytosis (clearance of apoptotic cells by phagocytosis without inducing inflammation and autoimmunity) is an important mechanism in the resolution of inflammatory processes. Efficient efferocytosis inhibits the accumulation of apoptotic cells/debris and maintains homeostasis before the onset of necrosis (secondary necrosis), which promotes inflammation or injury. Moreover, the detection and clearance of apoptotic cells can promote anti-inflammatory responses. Defective efferocytosis is involved in the pathogenesis of several diseases, such as atherosclerosis, chronic inflammation, autoimmunity and cancer. Statins are 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors which exert cholesterol-lowering effects plus multiple pleiotropic properties, such as inhibition of inflammation and macrophage proliferation. Statins exhibit anti-inflammatory properties by reducing both the prenylation of signaling molecules with downregulation of gene expression and the expression of adhesion molecules, as well as the levels of cytokines and chemokines. Additionally, statins suppress the prenylation of GTPases, such as Rac-1, as a positive regulator of efferocytosis, and RhoA, as a negative regulator of efferocytosis. However, statins alter the membrane balance of Rho GTPases in efferocytosis toward Rac-1. Efferocytosis has modifiable targets, which can be exploited for the treatment of several diseases, although limited attention has been given to the mechanisms by which statins regulate efferocytosis and the resulting therapeutic implications. In this review, we will elaborate on the mechanisms underlying the modulation of apoptotic cell clearance by statins, which, in turn, inhibits uncontrolled inflammation and ensuing diseases.

Naturally occurring naphthoquinones (NQs) comprising highly reactive small molecules are the subject of increasing attention due to their promising biological activities such as antioxidant, antimicrobial, apoptosis-inducing activities, and especially anticancer activity. Lapachol, lapachone, and napabucasin belong to the NQs and are in phase II clinical trials for the treatment of many cancers. This review aims to provide a comprehensive and updated overview on the biological activities of several new NQs isolated from different species of plants reported from January 2013 to January 2020, their potential therapeutic applications and their clinical significance.

Abstract: The human microbiome comprises the genomes of the microbiota that live on and within humans, such as protozoa, archaea, eukaryotes, viruses, and most bacteria. Gastrointestinal disorders such as inflammatory bowel disease, colon cancer, celiac disease, and irritable bowel syndrome can all be triggered by a change in gut flora. The alteration of the gut microbiota (also known as "gut dysbiosis") is affected by host genetics, nutrition, antibiotics, and inflammation, and it is associated with the development of inflammatory bowel disease (IBD). Also, intestinal epithelial dysfunction, altered autophagy, and immune hyperactivation are frequently detected in individuals with severe IBD, which may be attributed to impaired miRNA expression functions. While the exact mechanisms of how Gut Microbiota may cause IBD and intestinal epithelial dysfunction are still debated, recent data point toward the possibility that hormones, gender and miRNAs expression are modifiable contributors to IBD. This review summarizes the current evidence for an association between hormones, gender and miRNAs and Gut Microbiota in IBD and discusses potential mechanisms by which gut microbiota may impact IBD. The study also outlines critical unanswered topics that need to be solved to enhance IBD prevention and treatment in people with gut dysbiosis.

MicroRNAs (miRNAs/miRs) are small non-coding RNAs that have a multifunction and play essential roles in gene regulation. Their dysregulation is associated with several human cancers. MiR-153 has a critical role in many biological processes, such as suppressing tumor growth (mostly), responses to treatment, and drug resistance. However, miR-153 in some cancers shows a different role as an oncogene, such as prostate. The miR-153 expression can be regulated by several regulators, such as lncRNAs and circular RNAs. By discovering the target factors for miR-153, it may be possible to approach early diagnosis, reversing drug resistance, and treatment of cancers. This will help choose the precise treatment for the patient and not incur additional costs in treatment. Thus, we attempt to summarize the current situation and potential development prospects about the role of miR-153 in cancers. The miR-153 paly an important role in cancers and can be used for diagnosis and prognosis.

The rapid clearance of apoptotic cells (ACs), known as efferocytosis, prompts the inhibition of inflammatory responses and autoimmunity and maintains homeostatic cell turnover by controlling the release of intracellular contents. The fast clearance of ACs requires professional and nonprofessional phagocytic cells that can accurately and promptly recognize ACs and migrate towards them. Cells undergoing apoptosis alarm their presence by releasing special soluble chemotactic factors, such as lactoferrin, that act as "Find me," "Keep out," or "Stay away" signals to recruit phagocytic cells, such as macrophages or prevent granulocyte migration. Efferocytosis effectively serves to prevent damage-associated molecular pattern release and secondary necrosis and inhibit inflammation/autoimmunity at the very first step. Since less attention has been given to the cross-talk and balance of "Find me" and "Keep out" signals released from ACs in efferocytosis, we set out to investigate the current knowledge of the roles of "Find me" and "Keep out" signals in the efferocytosis process.

MicroRNAs (miRNAs) are non-coding, endogenous, single-stranded, small (21-25 nucleotides) RNAs. Various target genes at the post-transcriptional stage are modulated by miRNAs that are involved in the regulation of a variety of biological processes such as embryonic development, differentiation, proliferation, apoptosis, inflammation, and metabolic homeostasis. Abnormal miRNA expression is strongly associated with the pathogenesis of multiple common human diseases including cardiovascular diseases, cancer, hepatitis, and metabolic diseases.Various signaling pathways including transforming growth factor-β, apoptosis, and Wnt signaling pathways have also been characterized to play an essential role in kidney diseases. Most importantly, miRNA-targeted pharmaceutical manipulation has represented a promising new therapeutic approach against kidney diseases. Furthermore, miRNAs such as miR-30e-5p, miR-98-5p, miR-30d-5p, miR-30a-5p, miR-194-5p, and miR-192-5p may be potentially employed as biomarkers for various human kidney diseases.A significant correlation has also been found between some miRNAs and the clinical markers of renal function like baseline estimated glomerular filtration rate (eGFR). Classification of miRNAs in different genetic renal disorders may promote discoveries in developing innovative therapeutic interventions and treatment tools. Herein, the recent advances in miRNAs associated with renal pathogenesis, emphasizing genetic kidney diseases and development, have been summarized.

The endoplasmic reticulum (ER) is the place where proteins and lipids are biosynthesized and where transmembrane proteins are folded. Both pathological and physiological situations may disturb the function of the ER, resulting in ER stress. Under stress conditions, the cells initiate a defensive procedure known as the unfolded protein response (UPR). Cases of severe stress lead to autophagy and/or the induction of cell apoptosis. Many studies implicate ER stress as a major factor contributing to many diseases. Therefore, the modulation of ER stress pathways has become an attractive therapeutic target. Quercetin is a plant-derived metabolite belonging to the flavonoids class which presents a range of beneficial effects including anti-inflammatory, cardioprotective, anti-oxidant, anti-obesity, anti-carcinogenic, anti-atherosclerotic, anti-diabetic, anti-hypercholesterolemic, and anti-apoptotic activities. Quercetin also has anti-cancer activity, and can be used as an adjuvant to decrease resistance to cancer chemotherapy. Furthermore, the effect of quercetin can be increased with the help of nanotechnology. This review discusses the role of quercetin in the modulation of ER stress (and related diseases) and provides novel evidence for the beneficial use of quercetin in therapy.

Colorectal cancer (CRC) is identified as a life-threatening malignancy. Despite several efforts and proceedings available for CRC therapy, it is still a health concern. Among a vast array of novel therapeutic procedures, employing bispecific antibodies (BsAbs) is currently considered to be a promising approach for cancer therapy. BsAbs, as a large family of molecules designed to realize two distinct epitopes or antigens, can be beneficial microgadgets to target the tumor-associated antigen pairs. On the other hand, applying the immune system's capabilities to attack malignant cells has been proven as a tremendous development in cancer therapeutic projects. The current study has attempted to overview some of the approved BsAbs in CRC therapy and those under clinical trials. For this purpose, reputable scientific search engines and databases, such as PubMed, ScienceDirect, Google Scholar, Scopus, etc., were explored using the keywords ‘bispecific antibodies’, ‘colorectal cancer’, ‘immunotherapy’ and ‘tumor markers’.

In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, children experience mild symptoms compared to adults. However, the precise explanations for this disparity are not clear. Thus, we attempted to identify rational explanations about age-related differences as reported in different studies. Given the incomplete data on SARS-CoV-2, some information has been gathered from other studies of earlier coronavirus or influenza outbreaks. Age-related differences in disease severity are important with regard to diagnosis, prognosis, and treatment of SARS-CoV-2 infections. In addition, these differences impact social distancing needs, since pediatric patients with mild or asymptomatic are likely to play a significant role in disease transmission.

Background A 32-base pair deletion (∆32) in the open reading frame (ORF) of C-C motif chemokine receptor 5 (CCR5) seems to be a protective variant against immune system diseases, especially human immunodeficiency virus type 1 (HIV-1). We aimed to assess the frequency of CCR5∆32 in the healthy Iranian population. Methods In this study, 400 normal samples from Khorasan, northeastern Iran, were randomly selected. The frequency of CCR5∆32 carriers was investigated using PCR analysis. Allele prevalence and the fit to the Hardy-Weinberg equilibrium were analyzed. Results The prevalence of CCR5∆32 in the northeastern population of Iran was 0.016. Four hundred samples were studied, among which one with CCR5∆32/∆32 and 11 with CCR5Wild/∆32 genotype were detected. Conclusion This study was the first investigation for an assessment of the prevalence of CCR5∆32 in northeastern Iran. The low prevalence of CCR5∆32 allele in the Iranian population may result in the increased susceptibility to HIV-1. In addition, this prevalence is the same as that of reported in East Asia, while is lower than that in the Europeans.

Cardiovascular disease (CVD), one of the main mortality causes worldwide is considered to be affected by general oxidative stress and inadequacy antioxidant system. Superoxide dismutase 1 (SOD1), a cytosolic antioxidant enzyme has a key role in neutralizing the excessive prooxidant by scavenging the super oxide anions. SOD1 polymorphic variants exhibit the altered activity properties. In the current study, we are aimed to investigate the association between the SOD1 polymorphism and CVD prevalence. A 6-years case control follow up study was designed to genotype the 526 participants (311 controls and 215 cases) for studying the 50 bp INS/DEL polymorphism at SOD1 promoter gene and analyze their blood lipid profile and anthropometric characteristics. Among the two possible alleles of the SOD1 gene (Wild [W] and Mutant [M]) the meaningful association was detected between the Mutants' frequency and the prevalence of CVD patients (p-value

Introduction Single nucleotide polymorphisms account for most genetic predispositions to breast cancer in the general population. Because of the lack of studies concerning the 2 common polymorphisms in caspase 8 (CASP8), namely rs104548 and rs10931936 in Iranian population, we evaluated the association of these 2 polymorphisms and their haplotypes with breast cancer and molecular profile. Materials and Method Blood samples were collected from 287 breast cancer patients and 490 controls. Genotyping of rs1045485 and rs10931936 was conducted using an amplification refractory mutation system and polymerase chain reaction restriction fragment length polymorphism, respectively. PHASE version 2 (Matthew Stephens) was used to estimate the frequencies of haplotypes. Statistical analysis was performed using SPSS 16.0 (SPSS Inc). Results Although hormone receptors and the molecular profile did not indicate any significant association with different genotypes (P > .05), patients with CC genotype of rs1045485 were more likely to have HER2-positive breast cancer than those with GG genotype (odds ratio [OR], 2.93; 95% confidence interval [CI], 1.0 4-8.26). In addition, CC genotype of D302H was associated with a decreased risk of breast cancer to 48% (OR, 0.52; 95% CI, 0.30-0.90) whereas no significant association was found between rs10931936 and breast cancer. Haplotype analysis indicated C-C haplotype is associated with the decreased risk of breast cancer (OR, 0.69; 95% CI, 0.52-0.91). Conclusion Our data showed a protective effect for CC genotype of rs1045485 variant and C-C haplotype of rs10931936-rs104548 in CASP8 in association with the decrease risk of breast cancer whereas rs10931936 showed no significant association. CASP8 rs1045485 polymorphism might be a candidate genetic marker to evaluate risk of breast cancer. However, further larger studies can confirm such findings.

Efferocytosis, the clearance of apoptotic cells (ACs), is a physiologic, multifaceted and dynamic process and a fundamental mechanism for the preservation of tissue homeostasis by avoiding unwanted inflammation and autoimmune responses through special phagocytic receptors. Defective efferocytosis is associated with several disease states, including cardiovascular disease and impaired immune surveillance, as occurs in cancer and autoimmune disease. A major cause of defective efferocytosis is non-functionality of surface receptors on either the phagocytic cells or the ACs, such as TAM family tyrosine kinase, which turns to a soluble form by cleavage/shedding or alternative splicing. Recently, soluble forms have featured prominently as potential biomarkers, indicative of prognosis and enabling targeted therapy using several commonly employed drugs and inhibitors, such as bleomycin, dexamethasone, statins and some matrix metalloproteinase inhibitors such as TAPI-1 and BB3103. Importantly, to design drug carriers with enhanced circulatory durability, the adaptation of soluble forms of physiological receptors/ligands has been purported. Research has shown that soluble forms are more effective than antibody forms in enabling targeted treatment of certain conditions, such as autoimmune diseases. In this review, we sought to summarize the current knowledge of these soluble products, how they are generated, their interactions, roles, and their potential use as biomarkers in prognosis and treatment related to inflammatory, cardiovascular, and autoimmune diseases.

Breast Cancer is the most frequent neoplasm diagnosed among women worldwide. Genetic background and lifestyle/environment play a significant role in the disease etiology. According to Genome-wide association studies, some single-nucleotide polymorphisms such as 2q35-rs13387042-(G/A) have been introduced to be associated with breast cancer risk and features. In this study, we aimed to evaluate the association between this variant and the risk of breast cancer in a cohort of Iranian women.Demographics and clinical information were collected by interview and using patients' medical records, respectively. DNA was extracted from 506 blood samples, including 184 patients and 322 controls, and genotyping was performed using allele specific-PCR. SPSS v16 was used for statistical analysis.Statistically significant association was observed between AA genotype and disease risk in all patients [pThere is a statistically significant association between 2q35-rs13387042 and breast cancer risk. rs13387042-AA genotype might be a risk-conferring factor for breast cancer development in the Iranian population. However, further consideration is suggested to confirm its role in risk assessment and probable association with other genetic markers.

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.

Cholangiocarcinoma (CCA) is a type of cancer with increasing prevalence around the world that originates from cholangiocytes, the epithelial cells of the bile duct. The tumor begins insidiously and is distinguished by high grade neoplasm, poor outcome, and high risk for recurrence. Liver transplantation has become broadly accepted as a treatment option for CCA. Liver transplantation is expected to play a crucial role as palliative and curative therapy for unresectable hilar CCA and intrahepatic CCA. The purpose of this study was to determine which cases with CCA should be subjected to liver transplantation instead of resection, although reported post-transplant recurrence rate averages approximately 20%. This review also aims to highlight the molecular current frontiers of CCA and directions of liver transplantation for CCA.

Background: CC chemokine receptor 5 (CCR5) is introduced as an immune response modulator. The activity of CCR5 influences breast tumour development in a p53-dependent manner. This study aimed to investigate the frequency of CCR5delta32 and its association with the risk of breast cancer in 1038 blood samples in North East of Iran. Methods: In this case-control study, we genotyped 570 control samples and 468 breast cancer patients by a gel electrophoresis-based gap-polymerase chain reaction (gap-PCR) method Mashhad, Iran. The data were analyzed using the SPSS software. Results: Of 570 controls included, 542 (95.09%) had CCR5delta32 wild/wild (W/W) genotype, 28 samples (4.91%) had CCR5delta32 wild/deletion (W/D) genotype and none of them were CCR5delta32 deletion/deletion (D/D) genotype (0%). While 428 samples of patients (91.45%) had CCR5delta32 W/W genotype, 40 samples (8.55%) had CCR5delta32 W/D and CCR5delta32 D/D homozygous was nil (0%) amongst cases. All samples were in the Hardy–Weinberg equilibrium (P>0.05). According to the allele frequency, D allele, as a risky allele, in the cases was more than the control samples (0.0427 vs 0.0245, respectively) (P=0.0206). Hence, W/D genotype may confer a risk effect (OR=1.77, CI: 1.09-2.90; P=0.0206) compared with WW genotype between case and control groups. Conclusion: There is a statistically significant association between CCR5W/D and breast cancer risk. CCR5 may be regarded as a target for the prevention of breast cancer in certain conditions such as interaction with p53 variants, which remains to be further investigated.

Background Genetic factors play an important role in susceptibility to methamphetamine dependency. In this line, protein that interact with C-kinase-1 (PICK1) and brain-derived neurotrophic factor (BDNF) genes are linked to methamphetamine dependence (substance use disorder). Thus, in a case–control study, we investigated the association between polymorphisms of PICK1 and BDNF genes and methamphetamine dependence in an Iranian population. Methods Total of 235 cases and 204 controls were recruited in a period between 2015 to 2018. The PICK1-rs713729, -rs2076369 and BDNF-rs6265 genotypes were determined via ARMS-PCR assay. Statistical analysis was performed, using SPSS 20.0, PHASE 2.1.1 program as well as SNP Analyzer 2.0. Results In the present study, two polymorphisms including PICK1-rs713729 (OR 1.38 (CI 1.08–1.52; P-value 0.004) in multiplicative and dominant models, and PICK1-rs2076369 (OR 1.31 (CI 1.10–1.56; P-value 0.002) in multiplicative, dominant and co-dominant models were associated with the risk of methamphetamine abuse. Moreover, haplotype analysis showed a significant association of haplotype AG (OR 2.50 (CI 1.50–4.16; P-value 0.0002) in dominant, recessive and co-dominant models, and haplotype TT (OR 0.67 (CI 0.50–0.91; P-value 0.009) in dominant and co-dominant models with the risk of methamphetamine abuse. None of the polymorphisms in this study had a high level of linkage disequilibrium. Conclusion Our findings indicate that the PICK1 gene polymorphism might affect the risk of methamphetamine dependency in our population.

In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, children experience mild symptoms compared to adults. However, the precise explanations for this disparity are not clear. Thus, we attempted to identify rational explanations about age-related differences as reported in different studies. Given the incomplete data on SARS-CoV-2, some information has been gathered from other studies of earlier coronavirus or influenza outbreaks. Age-related differences in disease severity are important with regard to diagnosis, prognosis, and treatment of SARS-CoV-2 infections. In addition, these differences impact social distancing needs, since pediatric patients with mild or asymptomatic are likely to play a significant role in disease transmission.

Introduction Coronavirus disease 2019 (COVID-19) has the characteristics of high transmission, diverse clinical manifestations, and a long incubation period. In addition to infecting the respiratory system, COVID-19 also has adverse effects on the cardiovascular system. COVID-19 causes acute myocardial injuries, as well as chronic damage to the cardiovascular system. Areas covered The present review is aimed at providing current information on COVID-19 and the cardiovascular system. PubMed, Scopus, Science direct, and Google Scholar were searched. Expert opinion It is suggested that heart injury caused by COVID-19 infection might be an important cause of severe clinical phenotypes or adverse events in affected patients. Myocardial damage is closely related to the severity of the disease and even the prognosis in patients with COVID-19. In addition to disorders that are caused by COVID-19 on the cardiovascular system, more protection should be employed for patients with preexisting cardiovascular disease (CVD). Hence, it is very important that once relevant symptoms appear, patients with COVID-19 be rapidly treated to reduce mortality. Thus, early measurements of cardiac damage via biomarkers following hospitalization for COVID-19 infections in a patient with preexisting CVD are recommended, together with careful monitoring of any myocardial injury that might be caused by the infection.Abbreviations: ICU: An intensive care unit; 2019-nCoV: 2019 novel coronavirus; ACEI: ACE inhibitor; ACS: Acute coronary syndrome; ARDS: Acute respiratory distress syndrome; AT1R: Ang II type 1 receptor; ATP: Adenosine triphosphate; ACC: American College of Cardiology; ACE: Angiotensin converting enzyme; Ang II: Angiotensin II; ARB: Angiotensin II receptor blocker; AV block: Atrioventricular block; CAD: Coronary artery disease; CVD: Cardiovascular disease; CT: Computerized tomography; CHF: Congestive heart failure; CHD: Coronary heart disease; CK-MB: Creatine kinase isoenzyme-MB; CRP: C-reactive protein; cTnI: Cardiac troponin I; EAT: Epicardial adipose tissue; ECMO: Extracorporeal membrane oxygenation; FDA: Food and Drug Administration; G-CSF: Granulocyte colony-stimulating factor; HFrEF: HF with a reduced ejection fraction; synhACE2: Human isoform of ACE2; IL: Interleukin; IABP: Intra-aortic balloon counterpulsation; IP10: Interferon γ-induced protein 10 kDa; LPC: Lysophosphatidylcholine; Mas: Mitochondrial assembly receptor; MCP1: Monocyte chemoattractant protein-1; MERS: Middle East respiratory syndrome; MIP1a: macrophage inflammatory protein 1a: MOF: Multiple organ failure; MI: Myocardial infarction; MRI: Magnetic resonance imaging; MYO: Myohe-moglobin; NT-proBNP: N-terminal pro-brain natriuretic peptide; PCPS: Percutaneous cardiopulmonary assistance; rhACE2: Recombinant human ACE2; SARS: Severe acute respiratory syndrome; Th: T helper; RAS: Renin-angiotensin system; TNF-α: Tumor necrosis factor-α; WHO: World Health Organization.