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.

DNA Methylation in Cancer: Epigenetic View of Dietary and Lifestyle Factors.

Background: Alterations in DNA methylation play an important role in cancer development and progression. Dietary nutrients and lifestyle behaviors can influence DNA methylation patterns and thereby modulate cancer risk. Introduction: To comprehensively review available evidence on how dietary and lifestyle factors impact DNA methylation and contribute to carcinogenesis through epigenetic mechanisms. Materials and methods: A literature search was conducted using PubMed to identify relevant studies published between 2005 and 2022 that examined relationships between dietary/lifestyle factors and DNA methylation in cancer. Studies investigating the effects of dietary components (eg, micronutrients, phytochemicals), physical activity, smoking, and obesity on global and gene-specific DNA methylation changes in animal and human cancer models were included. Data on specific dietary/lifestyle exposures, cancer types, DNA methylation targets and underlying mechanisms were extracted. Results: Multiple dietary and lifestyle factors were found to influence DNA methylation patterns through effects on DNA methyltransferase activity, methyl donor availability, and generation of oxidative stress. Altered methylation of specific genes regulating cell proliferation, apoptosis, and inflammation were linked to cancer development and progression. Conclusion: Dietary and lifestyle interventions aimed at modulating DNA methylation have potential for both cancer prevention and treatment through epigenetic mechanisms. Further research is needed to identify actionable targets for nutrition and lifestyle-based epigenetic therapies.

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.

Bioinformatics analysis of microarray data to identify hub genes, as diagnostic biomarker of HELLP syndrome: System biology approach.

BACKGROUND: HELLP syndrome is one of the disorders characterized by hemolysis, increased liver enzymes and decreased platelet count. So far, many molecular pathways and genes have been identified in relation to the pathogenesis of this syndrome; however, the main cause of the incidence and progression of the disease has not been identified. Using the biological system approach is a way to target patients by identifying genes and molecular pathways. In this study, we investigated genes and important molecular factors in the pathogenesis of HELLP syndrome. MATERIAL AND METHODS: In this study, the microarray dataset was downloaded from Gene Expression Omnibus (GEO) database and analyzed using the GEO2R online tool for identifying differentially expressed genes (DEGs). Enrichment analysis of DEGs was evaluated using the Enrichr database. Then, protein-protein interaction (PPI) networks were constructed via the STRING database; they were visualized by Cytoscape. Then the STRING database was used to construct PPI networks. The hub genes were recognized using the cytoHubba. Ultimately, the interaction of the miRNA-hub genes and drug-hub genes were also evaluated. RESULT: After analysis, it was found that some genes with the highest degree of connectivity are involved in the pathogenesis of HELLP syndrome, which are known as the hub genes. These genes are as follows: KIT, JAK2, LEP, EP300, HIST1H4L, HIST1H4F, HIST1H4H, MMP9, THBS2, and ADAMTS3. Has-miR-34a-5p was also most associated with hub genes. CONCLUSION: Finally, it can be said, that the identification of genes and molecular pathways in HELLP syndrome can be helpful in identifying the pathogenesis pathways of the disease, and designing therapeutic targets.

Aspirin exacerbated respiratory disease (AERD): molecular and cellular diagnostic & prognostic approaches.

Aspirin-exacerbated respiratory disease (AERD) is characterized by immune cells dysfunction. This study aimed to investigate the molecular mechanisms involved in AERD pathogenesis. Relevant literatures were identified by a PubMed search (2005-2019) of english language papers using the terms "Aspirin-exacerbated respiratory disease", "Allergic inflammation", "molecular mechanism" and "mutation". According to the significant role of inflammation in AERD development, ILC-2 is known as the most important cell in disease progression. ILC-2 produces cytokines that induce allergic reactions and also cause lipid mediators production, which activates mast cells and basophils, ultimately. Finally, Monoclonal antibody and Aspirin desensitization in patients can be a useful treatment strategy for prevention and treatment.

Correction to: The Molecular Mechanism of Aluminum Phosphide poisoning in Cardiovascular Disease: Pathophysiology and Diagnostic Approach.

The article "The Molecular Mechanism of Aluminum Phosphide poisoning in Cardiovascular Disease: Pathophysiology and Diagnostic Approach", written by Seyed Farzad Hosseini · Mehdi Forouzesh · Mohsen Maleknia · Samira Valiyari · Mahmood Maniati · Azin Samimi, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 25th July 2020 with open access. With the author(s)' decision to step back from Open Choice, the copyright of the article changed on 29th July 2020 to © Springer Science+Business Media, LLC, part of Springer Nature 2020 and the article is forthwith distributed under the terms of copyright. The original article has been corrected.

The Molecular Mechanism of Aluminum Phosphide poisoning in Cardiovascular Disease: Pathophysiology and Diagnostic Approach.

Nowadays, poisoning with metal phosphides, especially aluminum phosphide (ALP), is one of the main health threats in human societies. Patients suffer from significant complications due to this type of poisoning, and the heart is one of the main organs targeted by ALP. Therefore, in this study, we discussed the effect of phosphine on cardiac function. This study is based on data obtained from PubMed, between 2002 and 2020. The key keywords included "Aluminum phosphide," "Oxidative Stress," "Mitochondria," "Cardiovascular disease," and "Treatment." The results showed that ALP produced reactive oxygen species (ROS) due to mitochondrial dysfunction. ROS production leads to red blood cell hemolysis, decreased ATP production, and induction of apoptosis in cardiomyocytes, which eventually results in cardiovascular disease. Since ALP has the most significant effect on cardiomyocytes, the use of appropriate treatment strategies to restore cell function can increase patients' survival.

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.

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.

The HLA-DRB1*11 group-specific allele is a predictor for alloantibody production in the transfusion-dependent thalassemia patients.

BACKGROUND AND OBJECTIVES: Recently, researchers have shown an increased interest in thalassemia for detecting susceptible factors in alloimmunization development. Alloimmunization, especially against Rh and Kell blood, occurs in 30% of thalassemia dependent transfusion (TDT) patients. The aim of this study is to determine the role of HLA-DRB1*11 and HLA-DRB1*13 group-specific alleles in the production of Rh and Kell alloantibodies. MATERIALS AND METHODS: 106 TDT patients were recruited for this study (54 responders and 52 non-responders). Responder patients developed Rh, Kell and/or specificities alloantibodies. HLA genotyping was done with Sequence-Specific Primers (SSP-PCR) and the results were compared between two groups. RESULTS: A significant association was found between anti-K (P=0.021, OR=2.546, 95%CI) and anti-E (P=0.049, OR=2.304, 95%CI) alloantibodies production with DRB1*11, respectively. Development of Anti-K and Anti-E alloantibodies were associated with DRB1*11 (P = 0.021, OR = 2.546, 95%CI) (P = 0.049, OR = 2.304, 95%CI), respectively. Further analysis showed that DRB1*11 is more frequent in multi responders (responder with both Rh and Kell alloantibodies) than mono-responders, 71% Versus 29%. There was not found any association between the DRB1*13 group-specific allele and the production of alloantibodies (P = 0.584, OR = 0.308, 95%CI). CONCLUSIONS: The evidence from this study suggests that detecting the DRB1*11 group-specific allele before starting transfusion can be useful to identify susceptible patients, increase HSCT transplantation compatibility and blood transfusion management.

Deep vein thrombosis: a less noticed complication in hematologic malignancies and immunologic disorders.

Deep vein thrombosis (DVT) is a common complication in hematologic malignancies and immunologic disorders that coagulation and inflammatory factors play a crucial role in its occurrence. The content used in this article has been obtained by PubMed database and Google Scholar search engine of English-language articles (1980-2019) using the "Deep vein thrombosis," "Hematologic malignancies," "Immunologic disorders" and "Treatment." Increased levels of coagulation factors, the presence of genetic disorders, or the use of thrombotic drugs that stimulate coagulation processes are risk factors for the development of DVT in patients with hematologic malignancies. Inflammatory and auto-anti-inflammatory factors, along with coagulant factors, play an essential role in the formation of venous thrombosis in patients with immunological disorders by increasing the recruitment of inflammatory cells and adhesion molecules. Therefore, anti-coagulants in hematologic malignancies and immunosuppressants in immune disorders can reduce the risk of developing DVT by reducing thrombotic and inflammatory activity. Considering the increased risk of DVT due to impaired coagulation and inflammation processes, analysis of coagulation and inflammatory factors have prognostic values in patients with immunologic deficiencies and hematologic malignancies. Evaluation of these factors as diagnostic and prognostic biomarkers in the prediction of thrombotic events could be beneficial in implementing effective treatment strategies for DVT.

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.