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.

Implications of Complement Imbalance in COVID-19: A Molecular Mechanistic Discussion on the Importance of Complement Balance.

Two central questions in COVID-19 treatment which should be considered are: "How does the imbalance of the complement system affect the therapeutic approaches?" and "Do we consider complement inhibitors in therapeutic protocols?". The complement system is a double-edged sword since it may either promote immune responses against COVID-19 or contribute to destructive inflammation in the host. Therefore, it is crucial to regulate this system with complement inhibitors. In this manuscript, we discuss the molecular mechanisms of complement and complement inhibitors in COVID-19 patients. We searched the terms "COVID-19", "Complement", "Complement inhibitor", "SARS-CoV-2", and all complement fragments and inhibitors from 2000 to 2022 in PubMed and google scholar and checked the pathways in "KEGG pathway database". Complement is not well-appreciated in the treatment protocols despite its multiple roles in the disease, and most of the preventive anti-inflammatory therapeutic approaches did not include a complement inhibitor in COVID-19 therapeutic protocols. In this review article, we discussed the most recent studies regarding complement components mediated interventions and the mechanism of these interventions in COVID-19 patients. Since the control of the complement system overactivation is associated with a better prognosis in the initial stages of COVID-19, heparin, anti-thrombin, C1-inhibitor, montelukast, and hydralazine can be effective in the initial stages of this viral infection. Recombinant complement activation (RCA) proteins are more effective in regulating complement compared to terminal pathway therapeutic approaches such as the C3a and C5a inhibitors.

Digging deeper through glucose metabolism and its regulators in cancer and metastasis.

Glucose metabolism enzymes and transporters play major role in cancer development and metastasis. In this study, we discuss glucose metabolism, transporters, receptors, hormones, oncogenes and tumor suppressors which interact with glucose metabolism and we try to discuss their major role in cancer development and cancer metabolism. We try to highlight the. Metabolic changes in cancer and metastasis upregulation of glycolysis is observed in many primary and metastatic cancers and aerobic glycolysis is the most favorable mechanism for glucose metabolism in cancer cells, and it is a kind of evolutionary change. The question that is posed at this juncture is: Can we use aerobic glycolysis phenotype and enzymes beyond this mechanism in estimating cancer prognosis and metastasis? Lactate is a metabolite of glucose metabolism and it is a key player in cancer and metastasis in both normoxic and hypoxic condition so lactate dehydrogenase can be a good prognostic biomarker. Furthermore, monocarboxylic transporter which is the main lactate transporter can be good target in therapeutic studies. Glycolysis enzymes are valuable enzymes in cancer and metastasis diagnosis and can be used as therapeutic targets in cancer treatment. Designing a diagnostic and prognostic profile for cancer metastasis seems to be possible base on glycolysis enzymes and glucose transporters. Also, glucose metabolism enzymes and agents can give us a clear vision in estimating cancer metastasis. We can promote a panel of genes that detect genetic changes in glucose metabolism agents to diagnose cancer metastasis.

A novel infram deletion in MSH6 gene in glioma: Conversation on MSH6 mutations in brain tumors.

OBJECTIVE AND BACKGROUND: Histological and molecular information and biopsy help in the diagnosis of the type and grade of tumors and increase the value of estimation of the biological behavior of tumors. In this study, we focused on a consanguineous Iranian Family with high prevalence of brain tumors in their pedigree and reviewed the literature on MSH6 mutations in brain tumors and the treatment responses focused on Gliomas. METHOD: We chose a family with a high prevalence of brain tumor in their pedigree. We studied the proband's neuroimaging and brain proton magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI), biopsy result, and whole-genome sequencing. RESULT: The neuroimaging and brain proton MRS reported a lesion in the right frontoparietal. The MRI revealed a large enhancible heterogenous mass in the right temporo-fronto-parieto-occipital lobes with involvement of corpus callosum which was suggestive of glioma. The patient revealed a homozygous pattern for a novel 9 base-pare deletion at the 912-914 codon on exon 4 of the MSH6 gene. DISCUSSION: We discuss several studies on MSH6 mutations in brain tumors and we discuss treatment responses in MSH6 mutations and the studies conducted to sensitize chemotherapy and radiotherapy resistance brain tumors to face this subject efficiently. CONCLUSION: Patients should be evaluated for MMR mutation before chemo and radiotherapy, and it is valuable to follow-up these mutations during the treatment too. In temozolomide (TMZ)-resitance cases, it is suggested to use complementary strategies such as using HDACis and a combination of a STAT3 Inhibitor and an mTOR inhibitor, BER inhibition mechanism, and PARP-1 inhibitor.

Chronic myeloid leukemia with complex karyotypes: Prognosis and therapeutic approaches.

OBJECTIVE AND BACKGROUND: Chronic myeloid leukemia (CML) is a neoplastic disease whose genetic and cytogenetic changes play important roles in prognosis and treatment strategies. Philadelphia (Ph) translocation t(9;22)(q34;q11) is a diagnostic and prognostic biomarker in CML. METHODS: Pubmed and Google Scholar databases were searched for English language articles from 1975 to 2017 containing the terms CML; Additional chromosomal abnormalities; Philadelphia translocation; Prognosis; and Treatment. DISCUSSION: Approximately 10-12% of CML patients exhibit additional chromosomal aberrations (ACAs) in chronic phase and blast crisis. ACAs emergence may cause different features in CML patients according to Ph pattern. For instance, deletion of chromosome 9 derivation is associated to patient's bad survival, whereas monosomy 7 develops myeloid dysplastic syndrome (MDS) or acute myeloid leukemia (AML) in CML patients with Ph-negative pattern. And ACAs in Ph-positive CML is considered as a failure in the management of CML with imatinib. CONCLUSION: CML classification using different features such as Ph and ACAs can play a decisive role in the evaluation of treatment responses in patients, for example, CML patients with Ph negative and monosomy 7 develop MDS or CML patient -Y and extra copy of Ph have a good response to tyrosine kinase inhibitors, therefore, classifications according to Ph and ACAs play an important role in choosing better treatment protocols and therapeutic strategies. Karyotype analysis in CML patients with complex karyotype shows unrandom pattern so ACAs can be great clue in medical guidelines.

Strategies to increase cardioprotection through cardioprotective chemokines in chemotherapy-induced cardiotoxicity.

BACKGROUND: Cardiotoxicity is one of the most important side effects of chemotherapy and its management save myocardium from injury and its consequences. AIM: In this review we discuss cardioprotective chemokines and cardioprotective mechanisms and pathways that induce cardioprotection through cardioprotective chemokines. METHOD: We searched English literature articles in Google scholar and PubMed from "1990 to 2018" through using the terms "Cardioprotection; Cardioprotective Chemokine; Chemotherapy Induced Cardiotoxicity; Cardiomyocytes; Cytokine". DISCUSSION: The routine cardioprotective strategies during chemotherapy such as angiotensin-converting enzyme inhibitors and ß-blockers have cardioprotective effects. Cardioprotective mechanisms and strategies can offer the oncologist several methods to protect the cardiac system through using efficient cardioprotective agents. Chemokines such as SDF-1a, IL-6,IL-8,IL-12 and G-CSF are cardioprotective chemokines. Accelerating the cardioprotection through inducing cardioprotective chemokines production can be useful in chemotherapy. CONCLUSION: Stimulating the production of cardioprotective chemokines through the pathways which induce the production of cardioprotective chemokines can work strongly beside the ß-blockers and ACE inhibitors. The ambiguous point in cardioprotective pathways is that JAK2/STAT3 pathway which is linked to IL-6 production pathway, which induce intracellular adhesion molecule-1 in the area of the ischemia in myocardium and this process is not benefit in cardioprotection however IL-6 induce cardiomyocytes regeneration so it enhance our dull vision about IL-6. Finally there are several choices which can increase cardioprotection during the chemotherapy and if we overcome the boundaries in confirming the efficiency of cardioprotective chemokines and the activation of them through using several mechanisms we will break through the difficulties over chemotherapy-induced cardiotoxicity.