Epigenetic and metabolic reprogramming in inflammatory bowel diseases: diagnostic and prognostic biomarkers in colorectal cancer.

BACKGROUND AND AIM: "Inflammatory bowel disease" (IBD) is a chronic, relapsing inflammatory disease of the intestinal tract that typically begins at a young age and might transit to colorectal cancer (CRC). In this manuscript, we discussed the epigenetic and metabolic change to present a extensive view of IBDs transition to CRC. This study discusses the possible biomarkers for evaluating the condition of IBDs patients, especially before the transition to CRC. RESEARCH APPROACH: We searched "PubMed" and "Google Scholar" using the keywords from 2000 to 2022. DISCUSSION: In this manuscript, interesting titles associated with IBD and CRC are discussed to present a broad view regarding the epigenetic and metabolic reprogramming and the biomarkers. CONCLUSION: Epigenetics can be the main reason in IBD transition to CRC, and Hypermethylation of several genes, such as VIM, OSM4, SEPT9, GATA4 and GATA5, NDRG4, BMP3, ITGA4 and plus hypomethylation of LINE1 can be used in IBD and CRC management. Epigenetic, metabolisms and microbiome-derived biomarkers, such as Linoleic acid and 12 hydroxy 8,10-octadecadienoic acid, Serum M2-pyruvate kinase and Six metabolic genes (NAT2, XDH, GPX3, AKR1C4, SPHK and ADCY5) expression are valuable biomarkers for early detection and transition to CRC condition. Some miRs, such as miR-31, miR-139-5p, miR -155, miR-17, miR-223, miR-370-3p, miR-31, miR -106a, miR -135b and miR-320 can be used as biomarkers to estimate IBD transition to CRC condition.

microRNA-382 as a tumor suppressor? Roles in tumorigenesis and clinical significance.

MicroRNAs (miRNAs) are small single-stranded RNAs belonging to a class of non-coding RNAs with an average length of 18-22 nucleotides. Although not able to encode any protein, miRNAs are vastly studied and found to play role in various human physiologic as well as pathological conditions. A huge number of miRNAs have been identified in human cells whose expression is straightly regulated with crucial biological functions, while this number is constantly increasing. miRNAs are particularly studied in cancers, where they either can act with oncogenic function (oncomiRs) or tumor-suppressors role (referred as tumor-suppressor/oncorepressor miRNAs). miR-382 is a well-studied miRNA, which is revealed to play regulatory roles in physiological processes like osteogenic differentiation, hematopoietic stem cell differentiation and normal hematopoiesis, and liver progenitor cell differentiation. Notably, miR-382 deregulation is reported in pathologic conditions, such as renal fibrosis, muscular dystrophies, Rett syndrome, epidural fibrosis, atrial fibrillation, amelogenesis imperfecta, oxidative stress, human immunodeficiency virus (HIV) replication, and various types of cancers. The majority of oncogenesis studies have claimed miR-382 downregulation in cancers and suppressor impact on malignant phenotype of cancer cells in vitro and in vivo, while a few studies suggest opposite findings. Given the putative role of this miRNA in regulation of oncogenesis, assessment of miR-382 expression is suggested in a several clinical investigations as a prognostic/diagnostic biomarker for cancer patients. In this review, we have an overview to recent studies evaluated the role of miR-382 in oncogenesis as well as its clinical potential.

Complete Blood Count Test in Rheumatology: Not Just a Screening Test.

BACKGROUND: Rheumatic disorders are chronic and common diseases, which especially involve connective tissue and may be associated with the damage to vital organs such as heart and kidney. Diagnosis, prognosis, determining the probability of severe complications, monitoring and evaluation of the response to treatment in such patients require specialized, expensive and time-consuming laboratory tests. METHODS: In this review article, we assessed the value of parameters of routine, inexpensive, and available Complete Blood Count (CBC) in detecting disease activity and explaining the prognosis of a number of rheumatic disorders, including systemic lupus erythematosus and rheumatoid arthritis by reviewing the results of searching Google Scholar search engine and PubMed databases over 2000 - 2021. RESULTS: Review of previous articles showed that while traditional Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) tests do not have sufficient specificity to appraise disease activity, CBC derived inflammatory biomarker Neutrophil-to-Lymphocyte Ratio (NLR) is able to assess disease activity and response to treatment in Rheumatoid Arthritis (RA). Also, Mean Platelet Volume (MPV) and NLR can determine the prognosis of renal involvement in Systemic lupus erythematosus (SLE). CONCLUSIONS: Although CBC-based parameters are not completely specific and sensitive to rheumatic disorders, but based on the results of previous studies, these parameters, particularly red cell distribution width (RDW), MPV, NLR and platelet to lymphocyte ratio (PLR) are inflammatory biomarkers with a prognostic role in rheumatic disorders that can also assess activity of the disease.

Co-existence of mutations in myeloproliferative neoplasms and their clinical significance: a prognostic approach.

OBJECTIVE: Myeloproliferative neoplasms (MPNs) are a group of clonal hematopoietic stem cell disorders that may occur after one or more mutations in hematopoietic progenitor cells. In this study, we will review the co-existence of mutations (especially dual mutations) in MPNs and its effect on the prognosis of patients. METHODS: To find relevant published papers, we systematically searched six major international indexing databases, namely PubMed/Medline, EmBase, Cochrane central, ISI web of science, and Scopus from Feb. 2000 until Jan. 2020. We included the following keywords in the analyzes: Myeloproliferative Disorders, Mutation, Co-existence of Mutations, Acute myeloid leukemia. RESULTS: Co-existence of several mutations in MPNs is mainly associated with a poor prognosis compared with the unimutated MPN disorders. There are several effective factors such as sequence of mutations, incidence of mutations in one cell or different cells, mutation, and MPN type. CONCLUSION AND EXPERT COMMENTARY: It seems that monitoring the status of mutations in MPNs and recognizing the co-existence of mutations (especially dual mutations) in order to determine prognosis and possibility of progression to acute form of leukemia can lead to the prediction of prognosis in MPN patients as well as establishment of better and more reliable therapeutic strategies for patients.

CD markers polymorphisms as prognostic biomarkers in hematological malignancies.

The clusters of differentiation (CD) are surface molecules used for immunophenotyping of cells. The expression of CD markers is widely used to classify hematological malignancies, including leukemia and lymphoma. Single nucleotide polymorphisms (SNPs) are crucial genetic changes that can be associated with abnormal expression and function of CD markers. In this paper, we assess the prognostic effect of CD markers' SNPs in hematological malignancies. Materials and methods and relevant literature was identified by a PubMed search (2001-2019) of English language papers using the following terms: 'polymorphism', 'CD marker', 'leukemia', 'lymphoma', 'prognosis', 'CD marker', and 'polymorphism'. Many studies have demonstrated the effects of CD markers' polymorphisms on risk of hematological malignancies. Also, SNPs of CD markers can be related with clinicopathological features, invasiveness, and response to therapy of these disorders. Considering the importance of SNPs in the expressions of CD markers, these genetic changes could be used as potential prognostic biomarkers in hematological malignancies. It is hoped that the evaluation of SNPs in CD markers will enable early diagnosis, prognosis, and detection of response to treatment. However, better understanding of SNPs in CD markers that are involved in hematological malignancies requires further studies on different populations of the worldwide.

Essential thrombocythemia: a hemostatic view of thrombogenic risk factors and prognosis.

Essential thrombocythemia (ET) is a classical myeloproliferative neoplasm that is susceptible to hypercoagulable state due to impaired hemostatic system, so that thrombotic complications are the leading cause of mortality in ET patients. The content used in this article has been obtained by the PubMed database and Google Scholar search engine from English-language articles (2000-2019) using the following keywords: "Essential thrombocythemia," "Thrombosis," "Risk factors" and "Hemostasis. In this neoplasm, the count and activity of cells such as platelets, leukocytes, endothelial cells, as well as erythrocytes are increased, which can increase the risk of thrombosis through rising intercellular interactions, expression of surface markers, and stimulation of platelet aggregation. In addition to these factors, genetic polymorphisms in hematopoietic stem cells (HSCs), including mutations in JAK2, CALR, MPL, or genetic abnormalities in other genes associated with the hemostatic system may be associated with increased risk of thrombotic events. Moreover, disruption of coagulant factors can pave the way for thrombogeneration. Therefore, the identification of markers related to cell activation, genetic abnormalities, or alternation in the coagulant system can be used together as diagnostic and prognostic markers for the occurrence of thrombosis among ET patients. Thus, because thrombotic complications are the main factors of mortality in ET patients, a hemostatic viewpoint and risk assessment of cellular, genetic, and coagulation factors can have prognostic value and contribute to the choice of effective treatment and prevention of thrombosis.

T-Cell Molecular Modulation Responses in Atherosclerosis Anergy.

Atherosclerosis continues to be a major cause of death in patients with cardiovascular diseases. The cooperative role of immunity has been recently considered in atherosclerotic plaque inflammation, especially adaptive immune response by T cells. In this review, we examine the possible role of T cells in atherosclerosis-mediated inflammation and conceivable therapeutic strategies that can ameliorate complications of atherosclerosis. The cytokines secreted by T-lymphocyte subsets, different pathophysiological profiles of microRNAs (miRs), and the growth factor/receptor axis have diverse effects on the inflammatory cycle of atherosclerosis. Manipulation of miRNA expression and prominent growth factor receptors involved in inflammatory cytokine secretion in atherosclerosis can be considered diagnostic biomarkers in the induction of anergy and blockade of atherosclerotic development. This manuscript reviews immunomodulation of T cells responses in atherosclerosis anergy.

Expression of Blood Cells Associated CD Markers and Cardiovascular Diseases: Clinical Applications in Prognosis.

BACKGROUND: Cardiovascular diseases (CVDs) are a major cause of mortality worldwide. The results of various studies have shown that abnormality in the frequency and function of blood cells can be involved in CVD complications. In this review, we have focused on abnormalities in the expression of the CD (cluster of differentiation) markers of blood cells to assess the association of these abnormalities with CVD prognosis. METHODS: We identified the relevant literature through a PubMed search (1990-2018) of English-language articles using the terms "Cardiovascular diseases", "CD markers", "leukocytes", "platelets", and "endothelial cells". RESULTS: There is a variety of mechanisms for the effect of CD-marker expressions on CVDs prognosis, ranging from proinflammatory processes to dysfunctional effects in blood cells. CONCLUSION: Considering the possible effects of CD-marker expression on CVDs prognosis, particularly prognosis of acute myocardial infarction and atherosclerosis, long-term studies in large cohorts are required to identify the prognostic value of CD markers and to target them with appropriate therapeutic agents.

Thrombocytopenia in solid tumors: Prognostic significance.

Solid tumors are a heterogeneous group of malignancies that result from out-of-control proliferation of cells. Thrombocytopenia is a common complication among patients with solid tumors that predispose them to bleeding disorders. The aim of this review article is to investigate the underlying mechanisms of the risk and incidence of thrombocytopenia in solid tumors. It can be argued that thrombocytopenia is a poor prognostic factor in solid tumors that can result from several factors such as polymorphism and mutation in some transcription factors and cytokines involved in megakaryocytic maturation or from the adverse effects of treatment. Therefore, an understanding of the exact mechanism of thrombocytopenia pathogenesis in each stage of solid tumors can help in developing therapeutic strategies to decrease bleeding complications in these malignancies.

Neutropenia and leukemia development: genetic risk factors and prognosis.

Neutropenia is known as a clinical consequence in various genetic disorders and other neutropenia-inducing mutations (NIM) nonmalignant diseases. Leukemia development is now a major concern about the mortality of patients with congenital neutropenia. We searched the PubMed database and Google Scholar engine using English-language article (1980-2019) using the terms 'Neutropenia,' 'Leukemia,' 'Mutation,' and 'Polymorphism.' Patients with neutropenia have leukemia-related genetic abnormalities which are noticeable as mutations and chromosome abnormalities. The presence of mutations in patients with neutropenia can affect the biological function of neutrophils and increase the likelihood of leukemia progression, which can be important in the diagnosis and prognosis of patients. NIM can play an important role in leukemia development via enhancing intracellular signaling, apoptosis inhibition, and effects on transcription factors in patients with neutropenia. Therefore, the detection of genetic risk factors can be useful in prognosis, early diagnosis, and prevention of leukemia development.

Prognostic Significance of CHEK2 Mutation in Progression of Breast Cancer.

Breast cancer (BC) is one of the most common cancers among women; genetic mutations reflect the development of this disease. Mutations in cell signaling factors can be the main cause of BC development. In this study, we focused on mutations in checkpoint kinase 2 (CHEK2) and their impact as a prognostic factor in the pathogenesis of BC. CHEK2 is controlled in cell signaling pathways through the influence of upstream genes. Also, several downstream genes are regulated by CHEK2. In addition, mutations in CHEK2 lead to resistance of BC cells to chemotherapy and metastasis of cancer cells to other parts of the body. Finally, detection of mutations in CHEK2 can be used as a prognostic factor for patient response to treatment and for targeting downstream molecules of CHEK2 that are involved in the proliferation of breast tumor cells. Mutations such as c.1100delC and I157T can distinguish which patients are susceptible to metastasis.

Autophagy regulation and its role in normal and malignant hematopoiesis.

Autophagy, the molecular machinery of self-eating, plays a dual role of a tumor promoter and tumor suppressor. This mechanism affects different clinical responses in cancer cells. Autophagy is targeted for treating patients resistant to chemotherapy or radiation. Limited reports investigate the significance of autophagy in cancer therapy, the regulation of hematopoietic and leukemic stem cells and leukemia formation. In the current review, the role of autophagy is discussed in various stages of hematopoiesis including quiescence, self-renewal, and differentiation.

Prognostic significance of aberrant CD5 expression in B-cell leukemia.

Aberrant expression of CD5 (as a T-cell marker) is seen in some leukemia and lymphoma of B lineage origin. Given that the signaling resulting from the expression of this marker plays an essential role in the development of leukemia and lymphoma, evaluating the expression of this marker is of paramount importance. Therefore, our goal in this study was to investigate the prognostic importance of CD5 expression in B-cell leukemia and lymphoma. We evaluate CD5 expression in normal and leukemic B-cells by identifying relevant literature through a PubMed search (1998-2018) of English language papers using the terms: 'CD5,' 'B-cell,' 'Leukemia,' and 'Lymphoma.' We are doing this thorough comparison of results from CD5 positive and negative cases to make a correct decision about prognostic importance of CD5 expression in these malignancies. In a number of B-cell malignancies, CD5 is expressed in varying degrees. Due to the different origins and characteristics of these malignancies, the results of CD5 expression evaluations are heterogeneous and impossible to generalize. However, CD5 expression is sometimes associated with clinicopathologic findings, more invasive clinical course, and even resistance to treatment (specifically in DLBCL) among CD5- positive patients, which appears to be a function of CD5 signaling and its downstream factors such as STAT3. Depending on the type of malignancy, CD5 expression is associated with good or bad prognosis, which can be used as an auxiliary prognostic factor to assess the clinical course of B-cell malignancies. Moreover, the difference in expression levels of CD5 in a variety of B-cell malignancies allows for differential diagnosis of these malignancies, which can be helpful when diagnosis is difficult.

Flip-flops of natural killer cells in autoimmune diseases versus cancers: Immunologic axis.

Natural killer (NK) cells play an essential role in the immune response to infections, inflammations, and malignancies. Recent studies suggest that NK cell surface receptors and cytokines are the key points of the disease development and protection. We hypothesized that the interactions between NK cell receptors and targeted cells construct an eventual niche, and this niche has an eventual profile in various autoimmune diseases and cancers. The NK cells preactivated with cytokines, such as interleukin-2 (IL-2), IL-12, IL-15, and IL-18 can have higher cytotoxicity; however, the toxic side effect of IL-2 should be considered. The vicissitudes of NK cell profile and its receptors obey the environmental communications and cell interactions. Our vision around the NK cells as an immune axis remained dual, and we still cannot judge the immune responses based on the NK cell flip-flop. A design of eventual niche to monitor the NK cell and targeted cell interaction is needed to strengthen our ability in diagnosis and treatment approaches based on the NK cells. Here, we have reviewed the shifts in the NK cells and their surface receptors in autoimmune diseases, solid tumors, and leukemia, and also discussed the effective chemokines that affect NK cell activation and proliferation. The main aim of this review is to present a broader vision of the NK cell changes in autoimmune disease and cancers.

Complex karyotype in myelodysplastic syndromes: Diagnostic procedure and prognostic susceptibility.

Complex karyotype (CK) is a poor prognosis factor in hematological malignancies. Studies have shown that the presence of CK in myelodysplastic syndrome (MDS) can be associated with MDS progression to acute myeloid leukemia. The goal of this review was to examine the relationship between different types of CK with MDS, as well as its possible role in the deterioration and progression of MDS to leukemia. The content used in this paper has been obtained by a PubMed and Google Scholar search of English language papers (1975-2018) using the terms complex karyotype and myelodysplastic syndromes. A single independent abnormality can be associated with a good prognosis. However, the coexistence of a series of abnormalities can lead to CK, which is associated with the deterioration of MDS and its progression to leukemia. Therefore, CK may be referred to as a prognostic factor in MDS. The detection of independent cytogenetic disorders that altogether can result in CK could be used as a prognostic model for laboratory and clinical use.

Strategies to inhibit arsenic trioxide-induced cardiotoxicity in acute promyelocytic leukemia.

OBJECTIVE: Arsenic trioxide (ATO) is a drug commonly used for the treatment of acute promyelocytic leukemia (APL). Although ATO has been shown to cause significant improvement in patients, it is associated with serious side effects, which sometimes lead to the patient's death. In this review paper, we examine the reports of ATO-induced cardiotoxicity in APL patients and evaluate the strategies to reduce the incidence of such toxicity. METHODS: The key search terms were "arsenic trioxide," "acute promyelocytic leukemia," "cardiotoxicity," "molecular pathway," and "biomarker." RESULTS: Studies have indicated the involvement of several molecular pathways in ATO-induced cardiotoxicity. These pathways increase the production of reactive oxygen species by interfering with intracellular calcium homeostasis as well as impairing the transfer of calcium into endoplasmic reticulum and mitochondria. On the other hand, increasing or decreasing expressions of some microRNAs (miRs) have been shown to play a role in cardiotoxicity. CONCLUSION: Finally, it can be stated that given the essential role of molecular pathways in cardiotoxicity and considering the fact these pathways impair the regulation of miRs expression, identification of molecular pathways involved in ATO-induced cardiotoxicity aimed at targeting miRs could be a new therapeutic strategy to prevent cardiotoxicity.

Role of bone marrow adipocytes in leukemia and chemotherapy challenges.

Adipose tissue (AT) is an extramedullary reservoir of normal hematopoietic stem cells (HSCs). Adipocytes prevent the production of normal HSCs via secretion of inflammatory factors, and adipocyte-derived free fatty acids may contribute to the development and progression of leukemia via providing energy for leukemic cells. In addition, adipocytes are able to metabolize and inactivate therapeutic agents, reducing the concentrations of active drugs in adipocyte-rich microenvironments. The aim of this study was to detect the role of adipocytes in the progression and treatment of leukemia. Relevant literature was identified through a PubMed search (2000-2018) of English-language papers using the following terms: leukemia, adipocyte, leukemic stem cell, chemotherapy, and bone marrow. Findings suggest the striking interplay between leukemic cells and adipocytes to create a unique microenvironment supporting the metabolic demands and survival of leukemic cells. Based on these findings, targeting lipid metabolism of leukemic cells and adipocytes in combination with standard therapeutic agents might present novel treatment options.

HLAs in Autoimmune Diseases: Dependable Diagnostic Biomarkers?

BACKGROUND: The process of antigen presentation to immune cells is an undeniable contributor to the pathogenesis of autoimmune diseases. Different studies have indicated several factors that are related to autoimmunity. Human Leukocyte Antigens (HLAs) are among such factors, which have a key role in autoimmunity because of their involvement in antigen presentation process. METHODS: Relevant English language literature was searched and retrieved from Google Scholar search engine and PubMed database (1996-2018). The following keywords were used: "Human leukocyte antigen", "Behcet's syndrome", "Rheumatoid arthritis", "Systemic lupus erythematosus", "Type 1 diabetes", "Celiac Disease" and "Autoimmunity". RESULTS: There is a strong association between HLA alleles and autoimmune diseases. For instance, HLA-B alleles and Behcet's syndrome are strongly correlated, and systemic lupus erythematosus and Type 1 diabetes are related to HLA-DQA1 and HLA-DQB1, respectively. CONCLUSION: Association between numerous HLA alleles and autoimmune diseases may justify and rationalize their use as biomarkers as well as possible diagnostic laboratory parameters.

Endothelial Cells: From Dysfunction Mechanism to Pharmacological Effect in Cardiovascular Disease.

Endothelial cells (ECs) are the innermost layer of blood vessels that play important roles in homeostasis and vascular function. However, recent evidence suggests that the onset of inflammation and the production of reactive oxygen species impair the function of ECs and are a main factor in the development of cardiovascular disease (CVD). In this study, we investigated the effects of inflammatory markers, oxidative stress, and treatment on ECs in CVD patients. This review article is based on the material obtained from PubMed up to 2018. The key search terms used were "Cardiovascular Disease," "Endothelial Cell Dysfunction," "Inflammation," "Treatment," and "Oxidative Stress." The generation of reactive oxygen species (ROS) as well as reduced nitric oxide (NO) production by ECs impairs the function of blood vessels. Therefore, treatment of CVD patients leads to the expression of transcription factors activating anti-oxidant mechanisms and NO production. In contrast, NO production by inflammatory agents can cause ECs repair due to differentiation of endothelial progenitor cells (EPCs). Therefore, identifying the molecular pathways leading to the differentiation of EPCs through mediation of factors induced by inflammatory factors can be effective in regenerative medicine for ECs repair.

Diagnostic Value of HLA Typing in Pathogenesis of Cardiomyopathy.

Development of cardiomyopathy (CM) is dependent upon several factors. However, the reaction of the immune response against myocardial tissue due to microbial and viral infections plays an important role in this disease. Therefore, the purpose of this study is to investigate the relationship between HLAs and their pathogenic mechanisms in the incidence of CM. Relevant literature was identified by a PubMed search (1989-2017) of English-language papers using the terms "Cardiomyopathy", "Human leukocyte antigen or HLA", "immune response", and "polymorphism". If CM patients are afflicted with viral and microbial infections, HLA class II molecules, which are not expressed on myocardial tissue in normal conditions, are mainly expressed on it. As a result, these HLAs present self- antigens and provoke autoimmune responses against myocardial tissue. On the other hand, the occurrence of polymorphism as well as disrupted expression of miRNAs can affect HLA expression, leading to hypertrophy and fibrosis of cardiac muscle. Finally, it is inferred that the expression evaluation of HLAs as well as identification of polymorphisms in their coding genes can be effective diagnostic factors in the detection of people susceptible to CM.