A concise review on miRNAs as regulators of colon cancer stem cells and associated signalling pathways

Despite recent therapy advances and a better understanding of colon cancer biology, it remains one of the major causes of death. The cancer stem cells, associated with the progression, metastasis, and recurrence of colon cancer, play a major role in promoting the development of tumour and are found to be chemo resistant. The stroma of the tumour, which makes up the bulk of the tumour mass, is composed of the tumour microenvironment. With the advent of theranostic and the development of personalised medicine, miRNAs are becoming increasingly important in the context of colon malignancies. A holistic understanding of the regulatory roles of miRNAs in cancer cells and cancer stem cells will allow us to design effective strategies to regulate miRNAs, which could lead to improved clinical translation and creating a potent colon cancer treatment strategy. In this review paper, we briefly discuss the history of miRNA as well as the mechanisms of miRNA and cancer stem cells that contribute to the tumour growth, apoptosis, and advancement of colon cancer. The usefulness of miRNA in colorectal cancer theranostic is further concisely reviewed. We conclude by holding a stance in addressing the prospects and possibilities for miRNA by the disclosure of recent theranostic approaches aimed at eradicating cancer stem cells and enhancing overall cancer treatment outcomes (AU)

Role of Interleukins in Inflammation-Mediated Tumor Immune Microenvironment Modulation in Colorectal Cancer Pathogenesis.

INTRODUCTION: Tumor cells invade and spread through a procedure termed as epithelial-to-mesenchymal cell transition (EMT). EMT is triggered by any alterations in the genes that encode the extracellular matrix (ECM) proteins, the enzymes that break down the ECM, and the activation of the genes that causes the epithelial cell to change into a mesenchymal type. The transcription factors NF-κB, Smads, STAT3, Snail, Zeb, and Twist are activated by inflammatory cytokines, for instance, Tumor Necrosis Factor, Tumor Growth Factors, Interleukin-1, Interleukin-8, and Interleukin-6, which promotes EMT. MATERIALS: The current piece of work has been reviewed from the literature works published in last 10 years on the role interleukins in inflammation-mediated tumor immune microenvironment modulation in colorectal cancer pathogenesis utilizing the databases like Google Scholar, PubMed, Science Direct. RESULTS: Recent studies have demonstrated that pathological situations, such as epithelial malignancies, exhibit EMT characteristics, such as the downregulation of epithelial markers and the overexpression of mesenchymal markers. Several growing evidence have also proved its existence in the human colon during the carcinogenesis of colorectal cancer. Most often, persistent inflammation is thought to be one factor contributing to the initiation of human cancers, such as colorectal cancer (CRC). Therefore, according to epidemiologic and clinical research, people with ulcerative colitis and Crohn's disease have a greater probability of developing CRC. CONCLUSION: A substantial amount of data points to the involvement of the NF-κB system, SMAD/STAT3 signaling cascade, microRNAs, and the Ras-mitogen-activated protein kinase/Snail/Slug in the epithelial-to-mesenchymal transition-mediated development of colorectal malignancies. As a result, EMT is reported to play an active task in the pathogenesis of colorectal cancer, and therapeutic interventions targeting the inflammation-mediated EMT might serve as a novel strategy for treating CRC. The illustration depicts the relationship between interleukins and their receptors as a driver of CRC development and the potential therapeutic targets.

A concise review on miRNAs as regulators of colon cancer stem cells and associated signalling pathways.

Despite recent therapy advances and a better understanding of colon cancer biology, it remains one of the major causes of death. The cancer stem cells, associated with the progression, metastasis, and recurrence of colon cancer, play a major role in promoting the development of tumour and are found to be chemo resistant. The stroma of the tumour, which makes up the bulk of the tumour mass, is composed of the tumour microenvironment. With the advent of theranostic and the development of personalised medicine, miRNAs are becoming increasingly important in the context of colon malignancies. A holistic understanding of the regulatory roles of miRNAs in cancer cells and cancer stem cells will allow us to design effective strategies to regulate miRNAs, which could lead to improved clinical translation and creating a potent colon cancer treatment strategy. In this review paper, we briefly discuss the history of miRNA as well as the mechanisms of miRNA and cancer stem cells that contribute to the tumour growth, apoptosis, and advancement of colon cancer. The usefulness of miRNA in colorectal cancer theranostic is further concisely reviewed. We conclude by holding a stance in addressing the prospects and possibilities for miRNA by the disclosure of recent theranostic approaches aimed at eradicating cancer stem cells and enhancing overall cancer treatment outcomes.

An Updated Review on the Role of Nanoformulated Phytochemicals in Colorectal Cancer.

The most common cancer-related cause of death worldwide is colorectal cancer. It is initiated with the formation of polyps, which further cause the development of colorectal cancer in multistep phases. Colorectal cancer mortality is high despite recent treatment breakthroughs and a greater understanding of its pathophysiology. Stress is one of the major causes of triggering different cellular signalling cascades inside the body and which might turn toward the development of cancer. Naturally occurring plant compounds or phytochemicals are being studied for medical purposes. Phytochemicals' benefits are being analyzed for inflammatory illnesses, liver failure, metabolic disorders, neurodegenerative disorders, and nephropathies. Cancer treatment with fewer side effects and better outcomes has been achieved by combining phytochemicals with chemotherapy. Resveratrol, curcumin, and epigallocatechin-3-gallate have been studied for their chemotherapeutic and chemopreventive potentiality, but hydrophobicity, solubility, poor bioavailability, and target selectivity limit the clinical uses of these compounds. The therapeutic potential is maximized by utilizing nanocarriers such as liposomes, micelles, nanoemulsions, and nanoparticles to increase phytochemical bioavailability and target specificity. This updated literature review discusses the clinical limitations, increased sensitivity, chemopreventive and chemotherapeutic effects, and the clinical limitations of the phytochemicals.

Epigenetic perspectives associated with COVID-19 infection and related cytokine storm: an updated review.

PURPOSE: The COVID-19 pandemic caused by the novel Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has put the world in a medical crisis for the past three years; nearly 6.3 million lives have been diminished due to the virus outbreak. This review aims to update the recent findings on COVID-19 infections from an epigenetic scenario and develop future perspectives of epi-drugs to treat the disease. METHODS: Original research articles and review studies related to COVID-19 were searched and analyzed from the Google Scholar/PubMed/Medline databases mainly between 2019 and 2022 to brief the recent work. RESULTS: Numerous in-depth studies of the mechanisms used by SARS-CoV-2 have been going on to minimize the consequences of the viral outburst. Angiotensin-Converting Enzyme 2 receptors and Transmembrane serine protease 2 facilitate viral entry to the host cells. Upon internalization, it uses the host machinery to replicate viral copies and alter the downstream regulation of the normal cells, causing infection-related morbidities and mortalities. In addition, several epigenetic regulations such as DNA methylation, acetylation, histone modifications, microRNA, and other factors (age, sex, etc.) are responsible for the regulations of viral entry, its immune evasion, and cytokine responses also play a major modulatory role in COVID-19 severity, which has been discussed in detail in this review. CONCLUSION: Findings of epigenetic regulation of viral pathogenicity open a new window for epi-drugs as a possible therapeutical approach against COVID-19.

A Concise Review on the Role of Natural and Synthetically Derived Peptides in Colorectal Cancer.

Colorectal cancer being the second leading cause of cancer-associated deaths has become a significant health concern around the globe. Though there are various cancer treatment approaches, many of them show adverse effects and some compromise the health of cancer patients. Hence, significant efforts are being made for the evolution of a novel biological therapeutic approach with better efficacy and minimal side effects. Current research suggests that the application of peptides in colorectal cancer therapeutics holds the possibility of the emergence of an anticancer reagent. The primary beneficial factors of peptides are their comparatively rapid and easy process of synthesis and the enormous potential for chemical alterations that can be evaluated for designing novel peptides and enhancing the delivery capacity of peptides. Peptides might be utilized as agents with cytotoxic activities or as a carrier of a specific drug or as cytotoxic agents that can efficiently target the tumor cells. Further, peptides can also be used as a tool for diagnostic purposes. The recent analysis aims at developing peptides that have the potential to efficiently target the tumor moieties without harming the nearby normal cells. Additionally, decreasing the adverse effects, and unfolding the other therapeutic properties of potential peptides, are also the subject matter of in-depth analysis. This review provides a concise summary of the function of both natural and synthetically derived peptides in colorectal cancer therapeutics that are recently being evaluated and their potent applications in the clinical field.

Role of ER Stress Mediated Unfolded Protein Responses and ER Stress Inhibitors in the Pathogenesis of Inflammatory Bowel Disease.

Previous investigations have increased the knowledge about the pathological processes of inflammatory bowel diseases. Besides the complex organization of immune reactions, the mucosal epithelial lining has been recognized as a crucial regulator in the commencement and persistence of intestinal inflammation. As the intestinal epithelium is exposed to various environmental factors, the intestinal epithelial cells are confronted with diverse cellular stress conditions. In eukaryotic cells, an imbalance in the endoplasmic reticulum (ER) might cause aggregation of unfolded or misfolded proteins in the lumen of ER, a condition known as endoplasmic reticulum stress. This cellular mechanism stimulates the unfolded protein response (UPR), which elevates the potential of the endoplasmic reticulum protein folding, improves protein production and its maturation, and also stimulates ER-associated protein degradation. Current analyses reported that in the epithelium, the ER stress might cause the pathogenesis of inflammatory bowel disease that affects the synthesis of protein, inducing the apoptosis of the epithelial cell and stimulating the proinflammatory reactions in the gut. There have been significant efforts to develop small molecules or molecular chaperones that will be potent in ameliorating ER stress. The restoration of UPR balance in the endoplasmic reticulum via pharmacological intervention might be a novel therapeutic approach for the treatment of inflammatory bowel diseases (IBDs). This review provides novel insights into the role of chemical chaperone UPR modulators to modify ER stress levels. We further discuss the future directions/challenges in the development of therapeutic strategies for IBDs by targeting the ER stress. Figure depicting the role of endoplasmic reticulum stress-mediated inflammatory bowel disease and the therapeutic role of endoplasmic reticulum stress inhibitors in alleviating the diseased condition.

Current Understanding of Epigenetics Driven Therapeutic Strategies in Colorectal Cancer Management.

Colorectal cancer is known to be the paramount reason for cancer deaths around the globe. It occurs due to the aggregation of epigenetic and genetic alterations in colon epithelial cells that transmute them into adenocarcinomas. Epigenetic mechanisms are interpreted as the changes in expression of the gene which is not associated with the alterations in the principal DNA sequence, while genetic changes involve modifications in oncogenes and tumor suppressor genes. The changes in the epigenetic in colon cancer that transmute colonic epithelial cells include chromatin modifications, microRNA expression, telomere length, and DNA methylation. DNA hypermethylation causes down-regulation and unsuitable expression of specific microRNA which can behave like tumor suppressor genes. Histone modifications can also influence the chromatin remodeling and gene expression, hence performs an eminent function in the silencing of the gene in colon cancer. Moreover, the telomere/telomerase interaction is a prime mechanism to embrace both cellular replicative potential and genomic instability and its malfunction plays a primary role in colon cancer. Deducing the genesis and the function of epigenetic abnormality in colon cancer pathogenesis will lead to potent prevention and therapeutic approach for colon cancer patients. Epigenetic drugs which emphasize the convertible essence of the epigenetic occurrences have accompanied the probability of epigenetic approach as a treatment alternative in colon cancer. Hence, this review is undertaken to critically envelop the recently advanced events in colorectal cancer therapies with a special emphasis on remedies targeting epigenetic modulators and future challenges towards therapeutic interventions.