Current Insights into Molecular Mechanisms and Potential Biomarkers for Treating Radiation-Induced Liver Damage.

Highly conformal delivery of radiation therapy (RT) has revolutionized the treatment landscape for primary and metastatic liver cancers, yet concerns persist regarding radiation-induced liver disease (RILD). Despite advancements, RILD remains a major dose-limiting factor due to the potential damage to normal liver tissues by therapeutic radiation. The toxicity to normal liver tissues is associated with a multitude of physiological and pathological consequences. RILD unfolds as multifaceted processes, intricately linking various responses, such as DNA damage, oxidative stress, inflammation, cellular senescence, fibrosis, and immune reactions, through multiple signaling pathways. The DNA damage caused by ionizing radiation (IR) is a major contributor to the pathogenesis of RILD. Moreover, current treatment options for RILD are limited, with no established biomarker for early detection. RILD diagnosis often occurs at advanced stages, highlighting the critical need for early biomarkers to adjust treatment strategies and prevent liver failure. This review provides an outline of the diverse molecular and cellular mechanisms responsible for the development of RILD and points out all of the available biomarkers for early detection with the aim of helping clinicians decide on advance treatment strategies from a single literature recourse.

Exploring the Relationship Between Diet, Lifestyle and Gut Microbiome in Colorectal Cancer Development: A Recent Update.

Colorectal cancer (CRC) is one of the major causes of cancer-related mortality worldwide. Despite advances in treatment modalities, its prevalence continues to rise, notably among younger populations. Unhealthy dietary habits, sedentary routines, and obesity have been identified as one of the key contributors to the development of colorectal cancer, apart from genetic and epigenetic modifications. Recognizing the profound impact of diet and lifestyle on the intricate gut microbiota ecosystem offers a promising avenue for understanding CRC development and its treatment. Gut dysbiosis, characterized by imbalances favoring harmful microbes over beneficial ones, has emerged as a defining feature of CRC. Changes in diet and lifestyle can profoundly alter the composition of gut microbes and the metabolites they produce, potentially contributing to CRC onset. Focusing on recent evidence, this review discussed various dietary factors, such as high consumption of red and processed meats and low fiber intake, and lifestyle factors, including obesity, lack of physical activity, smoking, and excessive alcohol consumption, that influence the gut microbiome composition and elevate CRC risk.

Mitochondrial dysfunction and its association with age-related disorders.

Aging is a complex process that features a functional decline in many organelles. Various factors influence the aging process, such as chromosomal abnormalities, epigenetic changes, telomere shortening, oxidative stress, and mitochondrial dysfunction. Mitochondrial dysfunction significantly impacts aging because mitochondria regulate cellular energy, oxidative balance, and calcium levels. Mitochondrial integrity is maintained by mitophagy, which helps maintain cellular homeostasis, prevents ROS production, and protects against mtDNA damage. However, increased calcium uptake and oxidative stress can disrupt mitochondrial membrane potential and permeability, leading to the apoptotic cascade. This disruption causes increased production of free radicals, leading to oxidative modification and accumulation of mitochondrial DNA mutations, which contribute to cellular dysfunction and aging. Mitochondrial dysfunction, resulting from structural and functional changes, is linked to age-related degenerative diseases. This review focuses on mitochondrial dysfunction, its implications in aging and age-related disorders, and potential anti-aging strategies through targeting mitochondrial dysfunction.

A brief review on recent advances in diagnostic and therapeutic applications of extracellular vesicles in cardiovascular disease.

Extracellular vesicles (EVs) are important mediators of intercellular communication within the cardiovascular system, playing essential roles in physiological homeostasis and contributing to the pathogenesis of various cardiovascular diseases (CVDs). However, their potential as diagnostic biomarkers and therapeutic agents in rare cardiovascular diseases, such as valvular heart disease (VHD) and cardiomyopathies, remains largely unexplored. This review comprehensively emphasizes recent advancements in extracellular vesicle research, explicitly highlighting their growing significance in diagnosing and potentially treating rare cardiovascular diseases, with a particular focus on valvular heart disease and cardiomyopathies. We highlight the potential of extracellular vesicle-based liquid biopsies as non-invasive tools for early disease detection and risk stratification, showcasing specific extracellular vesicle-associated biomarkers (proteins, microRNAs, lipids) with diagnostic and prognostic value. Furthermore, we discussed the therapeutic promise of extracellular vesicles derived from various sources, including stem cells and engineered extracellular vesicles, for cardiac repair and regeneration through their ability to modulate inflammation, promote angiogenesis, and reduce fibrosis. By integrating the findings and addressing critical knowledge gaps, this review aims to stimulate further research and innovation in extracellular vesicle-based diagnostics and therapeutics of cardiovascular disease.

Evaluation of the synergistic effects of curcumin-resveratrol co-loaded biogenic silica on colorectal cancer cells.

Colorectal cancer (CRC) remains a significant global health concern, being the third most diagnosed cancer in men and the second most diagnosed cancer in women, with alarming mortality rates. Natural phytochemicals have gained prominence among various therapeutic avenues explored due to their diverse biological properties. Curcumin, extracted from turmeric, and resveratrol, a polyphenol found in several plants, have exhibited remarkable anticancer activities. However, their limited solubility and bioavailability hinder their therapeutic efficacy. To enhance the bioavailability of these compounds, nanomaterials work as effective carriers with biogenic silica (BS) attracting major attention owing to their exceptional biocompatibility and high specific surface area. In this study, we developed Curcumin-resveratrol-loaded BS (Cur-Res-BS) and investigated their effects on colorectal cancer cell lines (HCT-116 and Caco-2). Our results demonstrated significant concentration-dependent inhibition of cell viability in HCT-116 cells and revealed a complex interplay of crucial proto-onco or tumor suppressor genes, such as TP53, Bax, Wnt-1, and CTNNB1, which are commonly dysregulated in colorectal cancer. Notably, Cur-Res-BS exhibited a synergistic impact on key signaling pathways related to colorectal carcinogenesis. While these findings are promising, further investigations are essential to comprehensively understand the mechanisms and optimize the therapeutic strategy. Moreover, rigorous safety assessments and in vitro studies mimicking the in vivo environment are imperative before advancing to in vivo experiments, ensuring the potential of Cur-Res-BS as an efficient treatment for CRC.

AEG-1 as a Novel Therapeutic Target in Colon Cancer: A Study from Silencing AEG-1 in BALB/c Mice to Large Data Analysis.

BACKGROUND: Astrocyte elevated gene-1 (AEG-1) is overexpressed in various malignancies. Exostosin-1 (EXT-1), a tumor suppressor, is an intermediate for malignant tumors. Understanding the mechanism behind the interaction between AEG-1 and EXT-1 may provide insights into colon cancer metastasis. METHODS: AOM/DSS was used to induce tumor in BALB/c mice. Using an in vivo-jetPEI transfection reagent, transient transfection of AEG-1 and EXT-1 siRNAs were achieved. Histological scoring, immunohistochemical staining, and gene expression studies were performed from excised tissues. Data from the Cancer Genomic Atlas and GEO databases were obtained to identify the expression status of AEG-1 and itsassociation with the survival. RESULTS: In BALB/c mice, the AOM+DSS treated mice developed necrotic, inflammatory and dysplastic changes in the colon with definite clinical symptoms such as loss of goblet cells, colon shortening, and collagen deposition. Administration of AEG-1 siRNA resulted in a substantial decrease in the disease activity index. Mice treated with EXT-1 siRNA showed diffusely reduced goblet cells. In vivo investigations revealed that PTCH-1 activity was influenced by upstream gene AEG-1, which in turn may affect EXT-1 activity. Data from The Cancer Genomic Atlas and GEO databases confirmed the upregulation of AEG-1 and downregulation of EXT-1 in cancer patients. CONCLUSIONS: This study revealed that AEG-1 silencing might alter EXT-1 expression indirectly through PTCH-1, influencing cell-ECM interactions, and decreasing dysplastic changes, proliferation and invasion.

Understanding the molecular mechanism responsible for developing therapeutic radiation-induced radioresistance of rectal cancer and improving the clinical outcomes of radiotherapy - A review.

Rectal cancer accounts for the second highest cancer-related mortality, which is predominant in Western civilizations. The treatment for rectal cancers includes surgery, radiotherapy, chemotherapy, and immunotherapy. Radiotherapy, specifically external beam radiation therapy, is the most common way to treat rectal cancer because radiation not only limits cancer progression but also significantly reduces the risk of local recurrence. However, therapeutic radiation-induced radioresistance to rectal cancer cells and toxicity to normal tissues are major drawbacks. Therefore, understanding the mechanistic basis of developing radioresistance during and after radiation therapy would provide crucial insight to improve clinical outcomes of radiation therapy for rectal cancer patients. Studies by various groups have shown that radiotherapy-mediated changes in the tumor microenvironment play a crucial role in developing radioresistance. Therapeutic radiation-induced hypoxia and functional alterations in the stromal cells, specifically tumor-associated macrophage (TAM) and cancer-associated fibroblasts (CAF), play a crucial role in developing radioresistance. In addition, signaling pathways, such as - the PI3K/AKT pathway, Wnt/ß-catenin signaling, and the hippo pathway, modulate the radiation responsiveness of cancer cells. Different radiosensitizers, such as small molecules, microRNA, nanomaterials, and natural and chemical sensitizers, are being used to increase the effectiveness of radiotherapy. This review highlights the mechanism responsible for developing radioresistance of rectal cancer following radiotherapy and potential strategies to enhance the effectiveness of radiotherapy for better management of rectal cancer.

A Review on Emerging Techniques for Diagnosis of Colorectal Cancer.

Common detection methods in practice for diagnosing colorectal cancer (CRC) are painful and invasive leading to less participation of individuals for CRC diagnosis. Whereas, improved or enhanced imaging systems and other minimally invasive techniques with shorter detection times deliver greater detail and less discomfort in individuals. Thus, this review is a summary of the diagnostic tests, ranging from the simple potential use in developing a flexible CRC treatment to the patient's potential benefits in receiving less invasive procedures and the advanced treatments that might provide a better assessment for the diagnosis of CRC and reduce the mortality related to CRC.

RhoB expression associated with chemotherapy response and prognosis in colorectal cancer.

PURPOSE: To examine the role of RhoB expression in relation to chemotherapy response, clinical outcomes and associated signaling pathways in colorectal cancer patients. MATERIALS AND METHODS: The study included 5 colon cancer cell lines, zebrafish embryos and 260 colorectal cancer patients treated with 5-fluorouracil (5-FU) and oxaliplatin (OXL). The methods consisted of CRISPR/Cas9, reactive oxygen species (ROS), caspase-3 activity, autophagy flux, in-silico RNA sequencing and immunohistochemistry. Gene expression analysis and pathway analysis were conducted using RNA-seq data. RESULTS: All cancer lines tested, including SW480, SW480-KO13 (RhoB knockout), SW480-KO55 (RhoB knockout), HCT116 and HCT116-OE (RhoB overexpressed), exhibited cytotoxicity to 5-FU and OXL. RhoB knockout cell lines demonstrated significantly reduced migration compared to the control cell lines. Furthermore, RhoB played a role in caspase-3-dependent apoptosis, regulation of ROS production and autophagic flux. The mRNA sequencing data indicated lower expression levels of oncogenes in RhoB knockout cell lines. The zebrafish model bearing SW480-KO showed a light trend toward tumor regression. RhoB expression by immunohistochemistry in patients was increased from normal mucosa to tumor samples. In patients who received chemotherapy, high RhoB expression was related to worse survival compared to low RhoB expression. Furthermore, the molecular docking analysis revealed that OXL had a higher binding affinity for RhoB than 5-FU, with a binding affinity of -7.8 kcal/mol and HADDOCK predicted molecular interactions between RhoB and caspase 3 protein. Gene-set enrichment analysis supported these findings, showing that enrichment of DNA damage response pathway and p53 signaling in RhoB overexpression treatment group, while the RhoB knockout treatment group exhibited enrichment in the negative regulation pathway of cell migration. CONCLUSION: RhoB was negatively associated with chemotherapy response and survival in colorectal cancers. Therefore, RhoB inhibition may enhance chemotherapeutic responses and patient survival.

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two crucial classes of transcripts that belong to the major group of non-coding RNAs (ncRNAs). These RNA molecules have significant influence over diverse molecular processes due to their crucial role as regulators of gene expression. However, the dysregulated expression of these ncRNAs constitutes a fundamental factor in the etiology and progression of a wide variety of multifaceted human diseases, including kidney diseases. In this context, over the past years, compelling evidence has shown that miRNAs and lncRNAs could be prospective targets for the development of next-generation drugs against kidney diseases as they participate in a number of disease-associated processes, such as podocyte and nephron death, renal fibrosis, inflammation, transition from acute kidney injury to chronic kidney disease, renal vascular changes, sepsis, pyroptosis, and apoptosis. Hence, in this current review, we critically analyze the recent findings concerning the therapeutic inferences of miRNAs and lncRNAs in the pathophysiological context of kidney diseases. Additionally, with the aim of driving advances in the formulation of ncRNA-based drugs tailored for the management of kidney diseases, we discuss some of the key challenges and future prospects that should be addressed in forthcoming investigations.

Current Technologies and Future Perspectives in Immunotherapy towards a Clinical Oncology Approach.

Immunotherapy is now established as a potent therapeutic paradigm engendering antitumor immune response against a wide range of malignancies and other diseases by modulating the immune system either through the stimulation or suppression of immune components such as CD4+ T cells, CD8+ T cells, B cells, monocytes, macrophages, dendritic cells, and natural killer cells. By targeting several immune checkpoint inhibitors or blockers (e.g., PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM-3) expressed on the surface of immune cells, several monoclonal antibodies and polyclonal antibodies have been developed and already translated clinically. In addition, natural killer cell-based, dendritic cell-based, and CAR T cell therapies have been also shown to be promising and effective immunotherapeutic approaches. In particular, CAR T cell therapy has benefited from advancements in CRISPR-Cas9 genome editing technology, allowing the generation of several modified CAR T cells with enhanced antitumor immunity. However, the emerging SARS-CoV-2 infection could hijack a patient's immune system by releasing pro-inflammatory interleukins and cytokines such as IL-1ß, IL-2, IL-6, and IL-10, and IFN-γ and TNF-α, respectively, which can further promote neutrophil extravasation and the vasodilation of blood vessels. Despite the significant development of advanced immunotherapeutic technologies, after a certain period of treatment, cancer relapses due to the development of resistance to immunotherapy. Resistance may be primary (where tumor cells do not respond to the treatment), or secondary or acquired immune resistance (where tumor cells develop resistance gradually to ICIs therapy). In this context, this review aims to address the existing immunotherapeutic technologies against cancer and the resistance mechanisms against immunotherapeutic drugs, and explain the impact of COVID-19 on cancer treatment. In addition, we will discuss what will be the future implementation of these strategies against cancer drug resistance. Finally, we will emphasize the practical steps to lay the groundwork for enlightened policy for intervention and resource allocation to care for cancer patients.

A review on metal complexes and its anti-cancer activities: Recent updates from in vivo studies.

Research into cancer therapeutics has uncovered various potential medications based on metal-containing scaffolds after the discovery and clinical applications of cisplatin as an anti-cancer agent. This has resulted in many metallodrugs that can be put into medical applications. These metallodrugs have a wider variety of functions and mechanisms of action than pure organic molecules. Although platinum-based medicines are very efficient anti-cancer agents, they are often accompanied by significant side effects and toxicity and are limited by resistance. Some of the most studied and developed alternatives to platinum-based anti-cancer medications include metallodrugs based on ruthenium, gold, copper, iridium, and osmium, which showed effectiveness against many cancer cell lines. These metal-based medicines represent an exciting new category of potential cancer treatments and sparked a renewed interest in the search for effective anti-cancer therapies. Despite the widespread development of metal complexes touted as powerful and promising in vitro anti-cancer therapeutics, only a small percentage of these compounds have shown their worth in vivo models. Metallodrugs, which are more effective and less toxic than platinum-based drugs and can treat drug-resistant cancer cells, are the focus of this review. Here, we highlighted some of the most recently developed Pt, Ru, Au, Cu, Ir, and Os complexes that have shown significant in vivo antitumor properties between 2017 and 2023.

Fatty Acids and their Proteins in Adipose Tissue Inflammation.

Chronic low-grade adipose tissue inflammation is associated with metabolic disorders. Inflammation results from the intertwined cross-talks of pro-inflammatory and anti-inflammatory pathways in the immune response of adipose tissue. In addition, adipose FABP4 levels and lipid droplet proteins are involved in systemic and tissue inflammation. Dysregulated adipocytes help infiltrate immune cells derived from bone marrow responsible for producing cytokines and chemokines. When adipose tissue expands in excess, adipocyte exhibits increased secretion of adipokines and is implicated in metabolic disturbances due to the release of free fatty acids. This review presents an emerging concept in adipose tissue fat metabolism, fatty acid handling and binding proteins, and lipid droplet proteins and their involvement in inflammatory disorders.

A Review on the Efficacy of Plant-derived Bio-active Compounds Curcumin and Aged Garlic Extract in Modulating Cancer and Age-related Diseases.

Aging is a process characterized by accumulating degenerative changes resulting in the death of an organism. Aging is mediated by various pathways that are directly linked to the individual's lifespan and are shunted for many age-related diseases. Many strategies for alleviating age-related diseases have been studied, which can target cells and molecules. Modern drugs such as Metformin, Rapamycin, and other drugs are used to reduce the effects of age-related diseases. Despite their beneficial activity, they possess some side effects which can limit their applications, mainly in older adults. Natural phytochemicals which have anti-aging activities have been studied by many researchers from a broader aspect and suggested that plant-based compounds can be a possible, direct, and practical way to treat age-related diseases which has enormous anti-aging activity. Also, studies indicated that the synergistic action of phytochemicals might enhance the biological effect rather than the individual or summative effects of natural compounds. Curcumin has an antioxidant property and is an effective scavenger of reactive oxygen species. Curcumin also has a beneficial role in many age-related diseases like diabetes, cardiovascular disease, neurological disorder, and cancer. Aged garlic extracts are also another bioactive component that has high antioxidant properties. Many studies demonstrated aged garlic extract, which has high antioxidant properties, could play a significant role in anti-aging and age-related diseases. The synergistic effect of these compounds can decrease the requirement of doses of a single drug, thus reducing its side effects caused by increased concentration of the single drug.

Impacts of gut microbiota alteration on age-related chronic liver diseases.

The gut microbiome and its metabolites are involved in developing and progressing liver disease. Various liver illnesses, such as non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis C, and hepatocellular carcinoma, are made worse and have worse prognoses with aging. Dysbiosis, which occurs when the symbiosis between the microbiota and the host is disrupted, can significantly negatively impact health. Liver disease is linked to qualitative changes, such as an increase in hazardous bacteria and a decrease in good bacteria, as well as quantitative changes in the overall amount of bacteria (overgrowth). Intestinal gut microbiota and their metabolites may lead to chronic liver disease development through various mechanisms, such as increasing gut permeability, persistent systemic inflammation, production of SCFA, bile acids, and alteration in metabolism. Age-related gut dysbiosis can disrupt the communication between gut microbiota and the host, impacting the host's health and lifespan. With aging, a gradual loss of the ability to maintain homeostasis because of structural alteration and gut dysbiosis leads to the disease progression in end-stage liver disease. Recently chronic liver disease has been identified as a global problem. A large number of patients are receiving liver transplants yearly. Thereby gut microbiome ecology is changing in the patients of the gut due to the changes in pathophysiology during the preoperative stage. The present review summarises the age-associated dysbiosis of gut microbial composition and its contribution to chronic liver disease. This review also provides information about the impact of liver transplant on the gut microbiome and possible disadvantageous effects of alteration in gut microbiota.

The Regulatory Role of MicroRNAs in Obesity and Obesity-Derived Ailments.

Obesity is a condition that is characterized by the presence of excessive adipose tissue in the body. Obesity has become one of the main health concerns worldwide since it can lead to other chronic ailments, such as type 2 diabetes or fatty liver disease, and it could be an aggravating factor in infections. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression and can play an important role in controlling crucial biological processes involved in the onset of obesity, such as lipogenesis, adipogenesis, lipid metabolism, or the regulation of cytokines and chemokines. Moreover, chemical compounds present in food or food packaging can alter miRNA expression and regulate the aforementioned biological mechanisms related to diabetes onset and progression. Furthermore, therapies, such as bariatric surgery and aerobic exercise training, can also influence the expression profile of miRNAs in obesity. Therefore, the present review provides insight into the current research on the role of miRNAs in obesity and obesity-derived ailments, intending to develop novel therapies to effectively manage these disorders.

An Updated Review on Molecular Biomarkers in Diagnosis and Therapy of Colorectal Cancer.

Colorectal cancer is one of the most common cancer types worldwide. Since colorectal cancer takes time to develop, its incidence and mortality can be treated effectively if it is detected in its early stages. As a result, non-invasive or invasive biomarkers play an essential role in the early diagnosis of colorectal cancer. Many experimental studies have been carried out to assess genetic, epigenetic, or protein markers in feces, serum, and tissue. It may be possible to find biomarkers that will help with the diagnosis of colorectal cancer by identifying the genes, RNAs, and/or proteins indicative of cancer growth. Recent advancements in the molecular subtypes of colorectal cancer, DNA methylation, microRNAs, long noncoding RNAs, exosomes, and their involvement in colorectal cancer have led to the discovery of numerous new colorectal cancer biomarkers. In small-scale investigations, most biomarkers appear promising. However, large-scale clinical trials are required to validate their effectiveness before routine clinical implementation. Hence, this review focuses on small-scale investigations and results of big data analysis that may provide an overview of the biomarkers for the diagnosis, therapy, and prognosis of colorectal cancer.

A brief overview of SARS-CoV-2 infection and its management strategies: a recent update.

The COVID-19 pandemic has become a global health crisis, inflicting substantial morbidity and mortality worldwide. A diverse range of symptoms, including fever, cough, dyspnea, and fatigue, characterizes COVID-19. A cytokine surge can exacerbate the disease's severity. This phenomenon involves an increased immune response, marked by the excessive release of inflammatory cytokines like IL-6, IL-8, TNF-α, and IFNγ, leading to tissue damage and organ dysfunction. Efforts to reduce the cytokine surge and its associated complications have garnered significant attention. Standardized management protocols have incorporated treatment strategies, with corticosteroids, chloroquine, and intravenous immunoglobulin taking the forefront. The recent therapeutic intervention has also assisted in novel strategies like repurposing existing medications and the utilization of in vitro drug screening methods to choose effective molecules against viral infections. Beyond acute management, the significance of comprehensive post-COVID-19 management strategies, like remedial measures including nutritional guidance, multidisciplinary care, and follow-up, has become increasingly evident. As the understanding of COVID-19 pathogenesis deepens, it is becoming increasingly evident that a tailored approach to therapy is imperative. This review focuses on effective treatment measures aimed at mitigating COVID-19 severity and highlights the significance of comprehensive COVID-19 management strategies that show promise in the battle against COVID-19.

Applications of nanotechnologies for miRNA-based cancer therapeutics: current advances and future perspectives.

MicroRNAs (miRNAs) are short (18-25 nt), non-coding, widely conserved RNA molecules responsible for regulating gene expression via sequence-specific post-transcriptional mechanisms. Since the human miRNA transcriptome regulates the expression of a number of tumor suppressors and oncogenes, its dysregulation is associated with the clinical onset of different types of cancer. Despite the fact that numerous therapeutic approaches have been designed in recent years to treat cancer, the complexity of the disease manifested by each patient has prevented the development of a highly effective disease management strategy. However, over the past decade, artificial miRNAs (i.e., anti-miRNAs and miRNA mimics) have shown promising results against various cancer types; nevertheless, their targeted delivery could be challenging. Notably, numerous reports have shown that nanotechnology-based delivery of miRNAs can greatly contribute to hindering cancer initiation and development processes, representing an innovative disease-modifying strategy against cancer. Hence, in this review, we evaluate recently developed nanotechnology-based miRNA drug delivery systems for cancer therapeutics and discuss the potential challenges and future directions, such as the promising use of plant-made nanoparticles, phytochemical-mediated modulation of miRNAs, and nanozymes.