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.

Adriamycin-induced cardiomyopathy can serve as a model for diabetic cardiomyopathy – a hypothesis

Diabetic cardiomyopathy is one of the life threatening complications of diabetes. A number of animal models are being used for studying diabetic cardiomyopathy. In laboratory animal models, induction of cardiomyopathy happens in two stages: first being the induction of diabetic condition and the second being the induction of cardiomyopathy by prolonging diabetic condition. It takes a longer time to develop diabetes with the limited success rate for development of cardiomyopathy. Adriamycin is an effective anti-cancer drug limited by its major side-effect cardiomyopathy. A number of features of Adriamycin treatment mimics diabetes. We postulate that Adriamycin-induced cardiomyopathy might be used as a model system to study diabetic cardiomyopathy in rodents since a number of features of both the cardiomyopathies overlap. Left ventricular hypertrophy, systolic and diastolic dysfunction, myofibrillar loss, and fibrosis are hallmarks of both of the cardiomyopathies. At the molecular level, calcium signaling, endoplasmic reticulum stress, advance glycation endproduct activation, mitochondrial dysfunction, inflammation, lipotoxicity and oxidative stress are similar in both the cardiomyopathies. The signature profile of both the cardiomyopathies shares commonalities. In conclusion, we suggest that Adriamycin induced cardiomyopathic animal model can be used for studying diabetic cardiomyopathy and would save time for researchers working on cardiomyopathy developed in rodent using the traditional method

Phytomedicinal therapeutics for male infertility: critical insights and scientific updates.

Infertility is a significant cause of anxiety, depression, and social stigma among couples and families. In such cases, male reproductive factors contribute widely to the extent of 20-70%. Male infertility is a multifactorial disease with several complications contributing to its diagnosis. Although its management encompasses both modern and traditional medicine arenas, the first line of treatment, adopted by most males, focuses on the reasonably successful medicinal plant-based conventional therapies. Phyto-therapeutics, which relies on active ingredients from traditionally known herbs, influences sexual behavior and male fertility factors. The potency of these phyto-actives depends on their preparation methods and forms of consumption, including decoctions, extracts, semi-purified compounds, etc., as inferred from in vitro and in vivo (laboratory animal models and human) studies. The mechanisms of action therein involve the testosterone pathway for stimulation of spermatogenesis, reduction of oxidative stress, inhibition of inflammation, activation of signaling pathways in the testes [extracellular-regulated kinase (ERK)/protein kinase B(PKB)/transformation of growth factor-beta 1(TGF-β1)/nuclear factor kappa-light-chain-enhancer of activated B cells NF-kB signaling pathways] and mediation of sexual behavior. This review critically focuses on the medicinal plants and their potent actives, along with the biochemical and molecular mechanisms that modulate vital pathways associated with the successful management of male infertility. Such intrinsic knowledge will significantly further studies on medicinal plants that improve male reproductive health. [Abstract copyright: © 2022. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.

Polyphenols as Potent Epigenetics Agents for Cancer

Human diseases such as cancer can be caused by aberrant epigenetic regulation. Polyphenols play a major role in mammalian epigenome regulation through mechanisms and proteins that remodel chromatin. In fruits, seeds, and vegetables, as well as food supplements, polyphenols are found. Compounds such as these ones are powerful anticancer agents and antioxidants. Gallic acid, kaempferol, curcumin, quercetin, and resveratrol, among others, have potent anti-tumor effects by helping reverse epigenetic changes associated with oncogene activation and tumor suppressor gene inactivation. The role dietary polyphenols plays in restoring epigenetic alterations in cancer cells with a particular focus on DNA methylation and histone modifications was summarized. We also discussed how these natural compounds modulate gene expression at the epigenetic level and described their molecular targets in cancer. It highlights the potential of polyphenols as an alternative therapeutic approach in cancer since they modulate epigenetic activity

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