Evaluation of the hematological inflammatory parameters in the patients with immune thrombocytopenic purpura: A case-control study.

Background and Aims: Inflammation is one of the immune thrombocytopenic purpura (ITP)'s aggravating elements due to inflammatory cells' function. This study aims to identify and evaluate hematological inflammatory parameters, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin-to-platelet ratio (HPR), in patients with ITP compared to the control group. Methods: We retrospectively analyzed the profile of 190 ITP patients from August 2019 to January 2021 at Imam Reza Hospital of Mashhad, Iran, along with 100 healthy individuals who had no ITP-related clinical or laboratory symptoms. Immune cell counts, NLR, PLR, and HPR were calculated using the complete blood count at the time of diagnosis and after the treatment. The results were analyzed through MedCalc, SPSS software, and the receiver operating characteristic curve. Results: The result showed that white blood cell (WBC) and neutrophil counts were higher in ITP patients (WBC: p: 0.001, neutrophil: p: 0.001), and conversely, platelet and lymphocyte counts were higher in the control group compared to ITP patients (platelets: p: 0.001, lymphocytes: p: 0.001). The indices analysis between the two groups revealed that NLR was significantly increased in ITP patients (p: 0.001), but PLR was significantly reduced in ITP patients (with the mean platelet count of 23.44 ± 35.26 × 109/L) compared to the control group (with the mean platelet count of 234.04 ± 55.88 × 109/L). The HPR index also significantly increased in ITP patients (p: 0.001). Conclusion: An increase in NLR, PLR, and a decrease in HPR can be considered a valuable diagnostic algorithm in patients with ITP.

Molecular Insights into the Relationship Between Platelet Activation and Endothelial Dysfunction: Molecular Approaches and Clinical Practice.

Platelets are one of the coagulation cells. When platelet activation occurs, many mediators are released and affect endothelial cells (ECs) and lead to endothelial dysfunction (ED). ED plays an important role in the pathogenesis of many diseases, including cardiovascular disease (CVD). Platelet are of important factors in ED. The release of mediators by platelets causes the stimulation of inflammatory pathways, oxidative stress, and apoptosis, which ultimately result in ED.On the other hand, platelet activation in CVD patients can be associated with a bad prognosis. Platelet activation can increase the level of markers such as p-selectin in the serum. Also, in this study, we have discussed the role of platelet as a diagnostic factor, as well as its use as a treatment option. In addition, we discussed some of the molecular pathways that are used to target platelet activation.

Evaluation of common protein biomarkers involved in the pathogenesis of respiratory diseases with proteomic methods: A systematic review.

AIM: Respiratory disease (RD) is one of the most common diseases characterized by lung dysfunction. Many diagnostic mechanisms have been used to identify the pathogenic agents of responsible for RD. Among these, proteomics emerges as a valuable diagnostic method for pinpointing the specific proteins involved in RD pathogenesis. Therefore, in this study, for the first time, we examined the protein markers involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, bronchiolitis obliterans (BO), and chemical warfare victims exposed to mustard gas, using the proteomics method as a systematic study. MATERIALS AND METHODS: A systematic search was performed up to September 2023 on several databases, including PubMed, Scopus, ISI Web of Science, and Cochrane. In total, selected 4246 articles were for evaluation according to the criteria. Finally, 119 studies were selected for this systematic review. RESULTS: A total of 13,806 proteins were identified, 6471 in COPD, 1603 in Asthma, 5638 in IPF, three in BO, and 91 in mustard gas exposed victims. Alterations in the expression of these proteins were observed in the respective diseases. After evaluation, the results showed that 31 proteins were found to be shared among all five diseases. CONCLUSION: Although these 31 proteins regulate different factors and molecular pathways in all five diseases, they ultimately lead to the regulation of inflammatory pathways. In other words, the expression of some proteins in COPD and mustard-exposed patients increases inflammatory reactions, while in IPF, they cause lung fibrosis. Asthma, causes allergic reactions due to T-cell differentiation toward Th2.

A computational approach for the identification of key genes and biological pathways of chronic lung diseases: a systems biology approach.

BACKGROUND: Chronic lung diseases are characterized by impaired lung function. Given that many diseases have shared clinical symptoms and pathogenesis, identifying shared pathogenesis can help the design of preventive and therapeutic strategies. This study aimed to evaluate the proteins and pathways of chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and mustard lung disease (MLD). METHODS AND RESULTS: After collecting the data and determining the gene list of each disease, gene expression changes were examined in comparison to healthy individuals. Protein-protein interaction (PPI) and pathway enrichment analysis were used to evaluate genes and shared pathways of the four diseases. There were 22 shared genes, including ACTB, AHSG, ALB, APO, A1, APO C3, FTH1, GAPDH, GC, GSTP1, HP, HSPB1, IGKC, KRT10, KRT9, LCN1, PSMA2, RBP4, 100A8, S100A9, TF, and UBE2N. The major biological pathways in which these genes are involved are inflammatory pathways. Some of these genes activate different pathways in each disease, leading to the induction or inhibition of inflammation. CONCLUSION: Identification of the genes and shared pathways of diseases can contribute to identifying pathogenesis pathways and designing preventive and therapeutic strategies.

Evaluation of Genes and Molecular Pathways Involved in the Progression of Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma: A Systems Biology Approach.

Today, Monoclonal Gammopathy of Undetermined Significance (MGUS) is known as a plasma cell malignancy susceptible to evolving into the life-threatening stage, multiple myeloma (MM), without prominent clinical manifestations. Despite the discovery of advanced therapies and multiple pathogenic markers, the complexity of MM development has made it an incurable malignancy. In this study, the microarray dataset was downloaded from the Gene Expression Omnibus (GEO) database and analyzed using the LIMMA package of R-software to determine differentially expressed genes (DEGs) in MGUS and MM compared to the control samples. Enrichment analysis of DEGs was evaluated using the GeneCodis4 software. Protein-protein interaction (PPI) networks were constructed via the GeneMANIA database, and Cytoscape visualized them. The Molecular Complex Detection (MCODE) plugin from Cytoscape was used to identify the key modules from the PPI network. Afterward, the hub genes were recognized using the cytoHubba plug-in in Cytoscape. Eventually, the correlation between hub-DEGs and MM-specific survival was evaluated via the PrognoScan database. A total of 138 (MM-normal) and 136 (MGUS-normal) DEGs were obtained from the datasets, and 62 common DEGs between MGUS and MM diseases (26 up-regulated and 36 down-regulated genes) were screened out for subsequent analyses. Following enrichment analyses and the PPI network's evaluation, FOS, FOSB, JUN, MAFF, and PPP1R15A involved in the progression of MGUS to MM were detected as the hub genes. The survival analysis revealed that FOS, FOSB, and JUN among hub genes were significantly associated with disease-specific survival (DSS) in MM. Identifying the genes involved in the progression of MGUS to MM can help in the design of preventive strategies as well as the treatment of patients. In addition, their evaluation can be effective in the survival of patients.

Evaluation of MicroRNA as Minimal Residual Disease in Leukemia: Diagnostic and Prognostic Approach: A Review.

Various factors are effective in the development of minimal residual disease (MRD), one of which is MicroRNAs (miRNAs). miRNAs and their dysfunction in gene expression have influential role in the pathogenesis of leukemia. Nowadays, treatments that lead to the suppression or replacement of miRNAs have been developed. Focusing on the role of miRNAs in managing the treatment of leukemia, in this review article we have investigated the miRNAs and signaling pathways involved in the process of apoptosis and cell proliferation, as well as miRNAs with oncogenic function in malignant leukemia cells. Among the studied miRNAs, miR-99a, and miR-181a play an essential role in apoptosis, proliferation and oncogenesis via AKT, MAPK, RAS, and mTOR signaling pathways. miR-223 and miR-125a affect apoptosis and oncogenesis via Wnt/B-catenin, PTEN/PI3K, and STAT5/AKT/ERK/Src signaling pathways. miR-100 also affects both apoptosis and oncogenesis; it acts via IGF1 and mTOR signaling pathways.

The role of exogenous Fibrinogen in cardiac surgery: stop bleeding or induce cardiovascular disease.

The surgical treatment contributes to broad variety of cardiovascular diseases (CVD). Due to many involved factors in preoperative bleeding, it is almost difficult to perform better Haemostatic approach. Fibrinogen is a major blood glycoprotein and a coagulation factor which decreases postoperative bleeding. It has a potential role in platelet activation and bleeding inhibition; it may reflect the inflammatory responses and be related to the endothelial dysfunction. Fibrinogen can act as a pro-inflammatory element via increasing some inflammatory markers including IL-6, tumor necrosis factor-α (TNF-α), monocyte chemo attractant protein (MCP-1), macrophage inflammatory protein-1 (MIP-1a and b), matrix metalloproteinase (MMP-1 and MMP-9) and Toll-like Receptors (TLRs); through activation of these factors, fibrinogen may induce some inflammatory mechanisms such as focal adhesion kinase (FAK), mitogen-activated protein kinases (MAPK) and nuclear factor κB (NF-κB) pathways. It may cause endothelial dysfunction by increasing P and E-selection, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels which activate MAPK and NF-κB pathways. This factor is also associated with increased exocytosed von Willebrand factor (vWF) as well as activation of Rho-GTPase mechanism. All of these data demonstrate the dual role of fibrinogen in cardiac surgeries, bleeding inhibition and CVD. Therefore, identifying the CVD factors is helpful for designing preventive strategies and alternative drugs.

The role of molecular mechanism of Ten-Eleven Translocation2 (TET2) family proteins in pathogenesis of cardiovascular diseases (CVDs).

Cardiovascular disease (CVD) is one of the most common diseases worldwide. The underlying pathogenesis of the disease has not yet been determined, but many factors have been identified. Tet methylcytosine dioxygenase 2 (TET2) is one of the epigenetic factors involved in regulating many genes. Therefore, based on the studies shown, this factor plays an important role in preventing the occurrence of CVD. TET2 has been shown to increase angiogenesis by expressing Robo4. It also increases the activity of Matrix metalloproteinases (MMPs) and stimulates the secretion of Vascular endothelial growth factor angiogenesis. On the other hand, it has been shown that TET2 regulates the expression of several genes and the development of the heart during the embryonic period due to its oxygenating role. TET2 has been shown to regulates the expression of the genes such as Ying Yang1 (YY1), Sox9b, Inhbaa and many other genes that ultimately lead to the differentiation of cardiomyocytes. On the other hand, it has been shown that some Long non coding RNA and MicroRNAs reduce TET2 expression and CVD. Finally, it is concluded that inducing TET2 expression can be a good therapeutic strategy to prevent or improve CVD.

Do exosomes play role in cardiovascular disease development in hematological malignancy?

Exosomes play a role in the pathogenesis and treatment of malignancies as a double-edged sword. Recently, researchers discussed about two new roles, cardiomyocyte function impairment and cardiovascular disease (CVD) genesis. Data were collected from PUBMED at various time points up to the 2019 academic year. The related key words are listed as following; "Arsenic trioxide", "acute promyelocytic leukemia" and "cardio toxicity" and "molecular pathway" and "biomarker". This study has shown that exosomes secreted substances stimulate angiogenesis and cardiomyocytes repairment; cited process depended on the kinds of released substances. Generally, exosomes may involve in the pathogenesis of CVD; although CVD can prevented by identifying the pathways that induce angiogenesis.

Dose HLA-B5, 7, 8, 27, and 51 Antigens Associated to Behcet's disease? A Study in Southwestern Iran.

BACKGROUND: Behcet's disease is a potentially life threatening autoimmune disease with recurrent ulcers and unknown pathogenesis. Gender and human leukocyte antigen-B51 seem to have an effective role in the clinical features of the disease. OBJECTIVE: The aim of this study is to evaluate the frequency of HLA-B5, 7, 8, 27 and 51 in behçet's disease in southwestern Iranian patients who visited the rheumatology clinic and to find the association between these HLA types and the disease. METHODS: 63 patients with behcet's disease participated in this study and peripheral blood samples were collected from them. The expression of each HLA antigen was evaluated by standard lymphocytotoxicity technique. RESULTS: Compared to other studied antigens, the expression of HLA-B5 and HLA-B51 was more prevalent among our patients. According to the results, 25% and 21% of patients were positive for HLA-B5 and HLA-B51, respectively. CONCLUSIONS: HLA-B5 and HLA-B51 are dominant positive HLA antigens among behcet's disease patients in the southwest of Iran; however, we cannot conclude that these antigens are valuable diagnostic or prognostic biomarkers due to our study limitations. We suggest studying the association between HLA-B antigens and inflammation severity in patients to determine the possible prognostic value of HLA-B antigens in Iranian population in the southwest and this region needs more studies in HLA subject among BD patients because of the frequency of BD to evaluate the value of HLA typing in BD prognosis.

STAT5: From Pathogenesis Mechanism to Therapeutic Approach in Acute Leukemia.

BACKGROUND: Based on the results of multiple studies, multiple signaling pathways is a major cause of resistence to chemotherapy in leukemia cells. Signal transducer and activator of transcription 5 (STAT5) is among these factors; it plays an essential role in proliferation of leukemic cells. METHODS: We obtained the materials used in our study via PubMed search from 1996 through 2019. The key search terms included "STAT5," "acute leukemia," "leukemogenesis," and "mutation." RESULTS: On activation, STAT5 not only inhibits apoptosis of leukemic cells via activating the B-cell lymphoma 2 (BCL-2) gene but also inhibits resistance to chemotherapy by enhancing human telomerase reverse transcriptase (hTERT) expression and maintaining telomere length in cells. It has also been shown that a number of mutations in the STAT5 gene and in related genes alter the expression of STAT5. CONCLUSION: The identification of STAT5 and the factors activated in its up- or downstream expression, affecting its function, contribute to better treatments such as targeted therapy rather than chemotherapy, improving the quality of life patients.

Prognostic significance of mutated genes in megakaryocytic disorders.

Megakaryopoiesis is a process during which platelets that play a major role in hemostasis are produced due to differentiation and maturation of megakaryocytic precursors. Several genes, including oncogenes and tumor suppressor genes, play a role in the regulation of this process. This study was conducted to investigate the oncogenes and tumor suppressor genes as well as their mutations during the megakaryopoiesis process, which can lead to megakaryocytic disorders. Relevant literature was identified by a PubMed search (1998-2019) of English language papers using the terms 'Megakaryopoiesis', 'Mutation', 'oncogenes', and 'Tumor Suppressor'. According to investigations, several mutations occur in the genes implicated in megakaryopoiesis, which abnormally induce or inhibit megakaryocyte production, differentiation, and maturation, leading to platelet disorders. GATA-1 is one of the important genes in megakaryopoiesis and its mutations can be considered among the factors involved in the incidence of these disorders. Considering the essential role of these genes (such as GATA- 1) in megakaryopoiesis and the involvement of their mutations in platelet disorders, study and examination of these changes can be a positive step in the diagnosis and prognosis of these diseases.

The effect of lupus disease on the pregnant women and embryos: a retrospective study from 2010 to 2014.

BACKGROUND AND AIMS: Pregnancy in women with systemic lupus erythematosus (SLE) is one of the challenges of recent studies. Women should prevent the onset of relapses with medications before and after pregnancy, and on the other hand, the effect of these medicines considers the health and development of the fetus. In this retrospective study, the effects of anti-phospholipid syndrome and the use of common drugs such as methotrexate, cyclosporine, and azathioprine and their side effects on maternal health and ultimately the development of the fetus have been investigated. MATERIAL AND METHODS: This study is a descriptive and retrospective epidemiologic study that was conducted in 2016 to investigate maternal and fetal complications in SLE patients. We prepared forms of data recording, including age, occupation, and other important information and then analyzed them in SPSS version 22. RESULT: The results showed that the presence of anti-phospholipid syndrome in pregnant women can lead to abnormalities such as preterm, IUGR, abortion, and fetal death (P value 0.0001). It also leads to complications such as nephritis, arthritis, and preeclampsia in the mother (P value 0.003). This study suggests that methotrexate and cyclosporine medications could cause fetal developmental disorders. The P value of cyclosporine was 0.0001 and the P value of methotrexate was 0.001. CONCLUSION: Anti-phospholipid syndrome in women with SLE who intend to become pregnant can disrupt the development of the embryo. The consumption of methotrexate and cyclosporine medications before and during the pregnancy can have irreparable effects on fetal growth. Key Points • Anti-phospholipid syndrome can disrupt the development of the embryo in women with SLE who intend to become pregnant. • Methotrexate and cyclosporine consumption before and during pregnancy can affect fetal growth. • 7 to 33% of patients whose disease had been suppressed and controlled 6 months before pregnancy seams to relapse during the pregnancy. • Taking medications to control the disease during pregnancy plays an important role in the progression of pregnancy and fetus health.

Involvement of Interferon-γ + 874A/T Polymorphism in the Pathogenesis of and Therapeutic Response to Immune Thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by symptoms of thrombocytopenia and bleeding due to production of autoantibodies against platelets. Recently, the occurrence of polymorphisms has been identified as one of the main causes of disease onset. METHODS: To conduct this study, we recruited 140 patients and control individuals with no history of platelet loss. After collection of specimens, the prevalence of interferon-γ polymorphism was evaluated using the allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) technique and confirmed by sequencing techniques. RESULTS: The results showed that the frequency of the AA genotype was higher in the control group, compared with patients with ITP; however, in the acute and chronic groups, the frequency of the AT genotype was higher than that of the AA genotype. We also discovered that there was no significant correlation between platelet counts before and after treatment, nor in its related parameters with interferon (IFN)-γ polymorphism. CONCLUSION: rs2430561 does not seem to have any role in ITP pathogenesis and treatment response.

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.

Protective role of heat shock transcription factor 1 in heart failure: A diagnostic approach.

OBJECTIVE: Nonexpression or expression inhibition of protective factors has been determined in the occurrence of heart failure (HF). Heat shock transcription factor 1 (HSF1) is among such factors, which reduces the incidence of HF by controlling cardiac hypertrophy and fibrosis. In this study, molecular mechanisms for nonexpression of HSF1 in HF patients have been investigated. MATERIALS AND METHODS: This review paper is based on the material obtained via PubMed search of 1996-2018. The key search terms were "heart failure," "heat shock transcription factor 1," "hypertrophy", "fibrosis," and "apoptosis." RESULTS: Although factors such as janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and heat shock proteins (HSPs) may respectively increase and decrease susceptibility to HF, in some circumstances, these factors may unexpectedly prevent HF progression. CONCLUSION: Finally, identification of molecular pathways expressed by various factors could be used to design appropriate treatments or to employ strategies inducing the expression of HSF1 to prevent HF.

T-bet transcription factor in cardiovascular disease: Attenuation or inflammation factor?

T-bet is a major transcription factor increasing inflammatory responses in the immune system. Recently, it has been shown that this factor leads to inflammation in cardiovascular disease (CVD). In this study, we examine the dual role of T-bet in inducing and suppressing inflammatory reactions as well as angiogenesis induction due to inflammatory cytokines in CVD. Relevant literature was identified by a Pubmed search (1992-2018) of English-language papers using the terms "T-bet," "Cardiovascular disease," "Immune response," and "Angiogenesis." Although T-bet causes differentiation of Th1 cells and activation of immune cells such as NK and DC, it suppresses inflammatory responses and replaces damaged vessels with new ones by activating regulatory T-cells and stimulating angiogenesis. It can be stated that T-bet acts as double-edged sword. Therefore, the identification of pathways that can increase the function of T-bet in activating Tregs and inducing angiogenesis might be used as a new therapeutic option in future investigations.

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.

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.

Role of chemokines in metastatic niche: new insights along with a diagnostic and prognostic approach.

Chemokines are cytokines that are involved in the movement of leukocytes and the occurrence of immune responses. It has recently been noted that these cytokines play a role in the movement of cancer cells to different parts of the body and create a suitable environment [i.e. (pre) metastatic niche] for their growth and proliferation. We studied the role of chemokines in the metastasis of cancer cells, as well as their involvement in the proliferation and growth of these cells. Relevant literature was identified by a PubMed search (2005-2017) of English language papers using the terms 'chemokine,' 'metastasis niche,' and 'organotropism.' Based on the nature of cancer cells, the expression of chemokine receptors on these cells leads to metastasis to various organs, which ultimately causes changes in different signaling pathways. Finally, the targeting of chemokines on cancer cells could prevent the metastasis of cancer cells toward different organs.