Misuse of Cardiac Lipid upon Exposure to Toxic Trace Elements—A Focused Review

Funding Information: Ricardo Lagoa acknowledges research support by the Applied Molecular Biosciences Unit-UCIBIO which is financed by national funds from FCT–Foundation for Science and Technology (UIDP/04378/2020 and UIDB/04378/2020). Publisher Copyright: © 2022 by the authors.Heavy metals and metalloids like cadmium, arsenic, mercury, and lead are frequently found in the soil, water, food, and atmosphere; trace amounts can cause serious health issues to the human organism. These toxic trace elements (TTE) affect almost all the organs, mainly the heart, kidney, liver, lungs, and the nervous system, through increased free radical formation, DNA damage, lipid peroxidation, and protein sulfhydryl depletion. This work aims to advance our understanding of the mechanisms behind lipid accumulation via increased free fatty acid levels in circulation due to TTEs. The increased lipid level in the myocardium worsens the heart function. This dysregulation of the lipid metabolism leads to damage in the structure of the myocardium, inclusive fibrosis in cardiac tissue, myocyte apoptosis, and decreased contractility due to mitochondrial dysfunction. Additionally, it is discussed herein how exposure to cadmium decreases the heart rate, contractile tension, the conductivity of the atrioventricular node, and coronary flow rate. Arsenic may induce atherosclerosis by increasing platelet aggregation and reducing fibrinolysis, as exposure interferes with apolipoprotein (Apo) levels, resulting in the rise of the Apo-B/Apo-A1 ratio and an elevated risk of acute cardiovascular events. Concerning mercury and lead, these toxicants can cause hypertension, myocardial infarction, and carotid atherosclerosis, in association with the generation of free radicals and oxidative stress. This review offers a complete overview of the critical factors and biomarkers of lipid and TTE-induced cardiotoxicity useful for developing future protective interventions.publishersversionpublishe

Non-small cell lung carcinoma (NSCLC): Implications on molecular pathology and advances in early diagnostics and therapeutics.

Continuous revision of the histologic and stage-wise classification of lung cancer by the World Health Organization (WHO) provides the foundation for therapeutic advances by promoting molecular targeted and immunotherapies and ensuring accurate diagnosis. Cancer epidemiologic data provide helpful information for cancer prevention, diagnosis, and management, supporting health-care interventions. Global cancer mortality projections from 2016 to 2060 show that cancer will overtake ischemic heart diseases (IHD) as the leading cause of death (18.9 million) immediately after 2030, surpassing non-small cell lung cancer (NSCLC), which accounts for 85 percent of lung cancers. The clinical stage at the diagnosis is the main prognostic factor in NSCLC therapies. Advanced early diagnostic methods are essential as the initial stages of cancer show reduced mortality compared to the advanced stages. Sophisticated approaches to proper histological classification and NSCLC management have improved clinical efficiency. Although immune checkpoint inhibitors (ICIs) and targeted molecular therapies have refined the therapeutic management of late-stage NSCLC, the specificity and sensitivity of cancer biomarkers should be improved by focusing on prospective studies, followed by their use as therapeutic tools. The liquid biopsy candidates such as circulating tumor cells (CTCs), circulating cell-free tumor DNA (cfDNA), tumor educated platelets (TEP), and extracellular vesicles (EVs) possess cancer-derived biomolecules and aid in tracing: driver mutations leading to cancer, acquired resistance caused by various generations of therapeutic agents, refractory disease, prognosis, and surveillance. [Abstract copyright: © 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

Solid-State NMR-Based Metabolomics Imprinting Elucidation in Tissue Metabolites, Metabolites Inhibition, and Metabolic Hub in Zebrafish by Chitosan

In this study, we demonstrated that chitosan-applied zebrafish (Danio rerio) tissue metabolite alteration, metabolic discrimination, and metabolic phenotypic expression occurred. The spectroscopy of solid-state 1H nuclear magnetic resonance (ss 1H-NMR) has been used. Chitosan has no, or low, toxicity and is a biocompatible biomaterial; however, the metabolite mechanisms underlying the biological effect of chitosan are poorly understood. The zebrafish is now one of the most popular ecotoxicology models. Zebrafish were exposed to chitosan concentrations of 0, 50, 100, 200, and 500 mg/L, and the body tissue was subjected to metabolites-targeted profiling. The zebrafish samples were measured via solvent-suppressed and T2-filtered methods with in vivo zebrafish metabolites. The metabolism of glutamate, glutamine, glutathione (GSH), taurine, trimethylamine (TMA), and its N-oxide (TMAO) is also significantly altered. Here, we report the quantification of metabolites and the biological application of chitosan. The metabolomics profile of chitosan in zebrafish has been detected, and the results indicated disturbed amino acid metabolism, the TCA cycle, and glycolysis. Our results demonstrate the potential of comparative metabolite profiling for discovering bioactive metabolites and they highlight the power of chitosan-applied chemical metabolomics to uncover new biological insights

Role of Metabolism and Metabolic Pathways in Prostate Cancer

Prostate cancer (PCa) is the common cause of death in men. The pathophysiological factors contributing to PCa are not well known. PCa cells gain a protective mechanism via abnormal lipid signaling and metabolism. PCa cells modify their metabolism in response to an excessive intake of nutrients to facilitate advancement. Metabolic syndrome (MetS) is inextricably linked to the carcinogenic progression of PCa, which heightens the severity of the disease. It is hypothesized that changes in the metabolism of the mitochondria contribute to the onset of PCa. The studies of particular alterations in the progress of PCa are best accomplished by examining the metabolome of prostate tissue. Due to the inconsistent findings written initially, additional epidemiological research is required to identify whether or not MetS is an aspect of PCa. There is a correlation between several risk factors and the progression of PCa, one of which is MetS. The metabolic symbiosis between PCa cells and the tumor milieu and how this type of crosstalk may aid in the development of PCa is portrayed in this work. This review focuses on in-depth analysis and evaluation of the metabolic changes that occur within PCa, and also aims to assess the effect of metabolic abnormalities on the aggressiveness status and metabolism of PCa

Crosstalk between COVID-19 Infection and Kidney Diseases: A Review on the Metabolomic Approaches

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a respiratory disorder. Various organ injuries have been reported in response to this virus, including kidney injury and, in particular, kidney tubular injury. It has been discovered that infection with the virus does not only cause new kidney disease but also increases treatment difficulty and mortality rates in people with kidney diseases. In individuals hospitalized with COVID-19, urinary metabolites from several metabolic pathways are used to distinguish between patients with acute kidney injury (AKI) and those without. This review summarizes the pathogenesis, pathophysiology, treatment strategies, and role of metabolomics in relation to AKI in COVID-19 patients. Metabolomics is likely to play a greater role in predicting outcomes for patients with kidney disease and COVID-19 with varying levels of severity in the near future as data on metabolic profiles expand rapidly. Here, we also discuss the correlation between COVID-19 and kidney diseases and the available metabolomics approaches

The Cellular and Molecular Immunotherapy in Prostate Cancer

In recent history, immunotherapy has become a viable cancer therapeutic option. However, over many years, its tenets have changed, and it now comprises a range of cancer-focused immunotherapies. Clinical trials are currently looking into monotherapies or combinations of medicines that include immune checkpoint inhibitors (ICI), CART cells, DNA vaccines targeting viruses, and adoptive cellular therapy. According to ongoing studies, the discipline should progress by incorporating patient-tailored immunotherapy, immune checkpoint blockers, other immunotherapeutic medications, hormone therapy, radiotherapy, and chemotherapy. Despite significantly increasing morbidity, immunotherapy can intensify the therapeutic effect and enhance immune responses. The findings for the immunotherapy treatment of advanced prostate cancer (PCa) are compiled in this study, showing that is possible to investigate the current state of immunotherapy, covering new findings, PCa treatment techniques, and research perspectives in the field’s unceasing evolution

A Systematic Role of Metabolomics, Metabolic Pathways, and Chemical Metabolism in Lung Cancer

Lung cancer (LC) is considered as one of the leading causes of cancer-associated mortalities. Cancer cells’ reprogrammed metabolism results in changes in metabolite concentrations, which can be utilized to identify a distinct metabolic pattern or fingerprint for cancer detection or diagnosis. By detecting different metabolic variations in the expression levels of LC patients, this will help and enhance early diagnosis methods as well as new treatment strategies. The majority of patients are identified at advanced stages after undergoing a number of surgical procedures or diagnostic testing, including the invasive procedures. This could be overcome by understanding the mechanism and function of differently regulated metabolites. Significant variations in the metabolites present in the different samples can be analyzed and used as early biomarkers. They could also be used to analyze the specific progression and type as well as stages of cancer type making it easier for the treatment process. The main aim of this review article is to focus on rewired metabolic pathways and the associated metabolite alterations that can be used as diagnostic and therapeutic targets in lung cancer diagnosis as well as treatment strategies

Exploring the Molecular Pathogenesis, Pathogen Association, and Therapeutic Strategies against HPV Infection

The human papillomavirus (HPV), commonly documented as the cause of warts, has gained much interest recently due to its possible links to several types of cancer. HPV infection is discussed in this review from multiple angles, including its virology, epidemiology, etiology, immunology, clinical symptoms, and treatment. Recent breakthroughs in molecular biology have led to the development of new methods for detecting and treating HPV in tissue. There is no cure for HPV, and although vaccines are available to prevent infection with the most common HPV viruses, their utilization is limited. Destruction and excision are the primary treatment modalities. This review sheds light on the epidemiology, molecular pathogenesis, the association of several other pathogens with HPV, the latest treatment strategies available to treat the same, and an overview of the progress made and the obstacles still to be overcome in the fight against HPV infection

Heavy Metal and Metalloid Contamination in Food and Emerging Technologies for Its Detection

Heavy metal and metalloid poisoning in the environment and food has piqued the public’s interest since it poses significant hazards to the ecological system and human health. In food, several metals, including cadmium (Cd), lead (Pb), mercury (Hg), tin (Sn), manganese (Mn), and aluminium (Al), and metalloids, including arsenic (As), antimony (Sb), and selenium (Se), pose a severe threat to human health. It is of utmost importance to detect even minute quantities of these toxic elements and this must be efficiently determined to understand their risk. Several traditional and advanced technologies, including atomic absorption spectrometry (AAS), spectrofluorimetry, inductively coupled plasma spectrometry, e-tongues, electrochemical aptasensors, Raman spectroscopy, and fluorescence sensors, among other techniques, have proven highly beneficial in quantifying even the minute concentrations of heavy metals and metalloids in food and dietary supplements. Hence, this review aims to understand the toxicity of these metals and metalloids in food and to shed light on the emerging technologies for their detection

Exploring the Regulatory Role of ncRNA in NAFLD: A Particular Focus on PPARs

Liver diseases are responsible for global mortality and morbidity and are a significant cause of death worldwide. Consequently, the advancement of new liver disease targets is of great interest. Non-coding RNA (ncRNA), such as microRNA (miRNA) and long ncRNA (lncRNA), has been proven to play a significant role in the pathogenesis of virtually all acute and chronic liver disorders. Recent studies demonstrated the medical applications of miRNA in various phases of hepatic pathology. PPARs play a major role in regulating many signaling pathways involved in various metabolic disorders. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, encompassing a spectrum spanning from mild steatosis to severe non-alcoholic steatohepatitis (NASH). PPARs were found to be one of the major regulators in the progression of NAFLD. There is no recognized treatment for NAFLD, even though numerous clinical trials are now underway. NAFLD is a major risk factor for developing hepatocellular carcinoma (HCC), and its frequency increases as obesity and diabetes become more prevalent. Reprogramming anti-diabetic and anti-obesity drugs is an effective therapy option for NAFLD and NASH. Several studies have also focused on the role of ncRNAs in the pathophysiology of NAFLD. The regulatory effects of these ncRNAs make them a primary target for treatments and as early biomarkers. In this study, the main focus will be to understand the regulation of PPARs through ncRNAs and their role in NAFLD