Hepato-renal toxicity of low dose metal(oid)s mixture in real-life risk simulation in rats: Effects on Nrf2/HO-1 signalling and redox status.

The understanding that humans are exposed to a low level of toxic metals and metalloids in their lifetime has resulted in a shift in scientific and regulatory perspectives from the traditional evaluation of single metal toxicity to complex mixtures, relevant to real-life exposure. Therefore, the aim of this study was to examine the impact of real-life, 90-days exposure to mixture of toxic metal(oid)s, Cd, Pb, Ni, Cr, As and Hg, on the nuclear factor erythroid 2-related factor 2 and hemoxygenase-1 (Nrf2/HO-1) signalling and redox status by assessing total sulfhydryl groups (SH), glutathione (GSH), superoxide dismutase activity (SOD), malondialdehyde (MDA), and ischemia modified albumin (IMA) in the liver and kidney of Wistar rats. Animals (20 males and 20 females) were randomized in 2 control and 6 treated groups that received by oral gavage mixture of metal(oid)s solutions in doses that reflect blood metal(oid) levels determined in previous human biomonitoring study as benchmark dose (F/M _BMD), median (F/M _MED), and 95th percentile (F/M _95).

Surgical training and capacity development in the South African internship programme.

Medical practitioners in South Africa manage a quadruple burden of disease. Junior doctors, who contribute significantly to the health workforce, must complete 2 years of internship training and 1 year of community service work in state health facilities after graduation to register as an independent medical practitioner. The aim of this article is to give a critical appraisal of the current national internship programme and why it was implemented, and outline suggestions for future changes.

Modulation of NRF2: Biological Dualism in Cancer, Targets and Possible Therapeutic Applications.

The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) system is a master regulator of redox homeostasis and cell adaptation to a variety of exogenous and endogenous stressors. Accumulating evidence from the last decade indicates that the impairment of the redox balance leads to oxidative stress (OS), a common alteration occurring in many human acute and chronic inflammatory diseases, such as cancer, diabetes, neurodegeneration, and metabolic disorders, and aging. Being located at the intersection of crucial signaling pathways, NRF2 can influence several cellular functions, which extend beyond the maintenance of the redox balance and include cellular metabolism, proteostasis, mitochondrial function and inflammation.

Nitro-Oxidative Stress and Mitochondrial Dysfunction in Human Cell Lines Exposed to the Environmental Contaminants PFOA and BPA.

Background: Bisphenol A (BPA) and perfluorooctanoic acid (PFOA) are synthetic compounds widely utilized in industrial activities devoted to the production of daily life plastic, metal products, and packaging from which they are able to migrate to food and water. Due to their persistence in the environment, living organisms are chronically exposed to these pollutants. BPA and PFOA have adverse effects on tissues and organs.

NRF2, a crucial modulator of skin cells protection against vitiligo, psoriasis, and cancer.

The skin represents a physical barrier between the organism and the environment that has evolved to confer protection against biological, chemical, and physical insults. The inner layer, known as dermis, is constituted by connective tissue and different types of immune cells whereas the outer layer, the epidermis, is composed by different layers of keratinocytes and an abundant number of melanocytes, localized in the stratum basale of the epidermis. Oxidative stress is a common alteration of inflammatory skin disorders such as vitiligo, dermatitis, or psoriasis but can also play a causal role in skin carcinogenesis and tumor progression.

NRF2 and Mitochondrial Function in Cancer and Cancer Stem Cells.

The NRF2-KEAP1 system is a fundamental component of the cellular response that controls a great variety of transcriptional targets that are mainly involved in the regulation of redox homeostasis and multiple cytoprotective mechanisms that confer adaptation to the stress conditions. The pleiotropic response orchestrated by NRF2 is particularly relevant in the context of oncogenic activation, wherein this transcription factor acts as a key driver of tumor progression and cancer cells' resistance to treatment. For this reason, NRF2 has emerged as a promising therapeutic target in cancer cells, stimulating extensive research aimed at the identification of natural, as well as chemical, NRF2 inhibitors.

A Delphi study to guide the development of a clinical indicator tool for palliative care in South Africa.

Background:  The South African National Policy Framework and Strategy on Palliative Care (NPFSPC) recommends that when integrating palliative care (PC) into the health system, a PC indicators tool should be used to guide clinicians to recognise a patient who should receive PC. The policy document recommends 'a simple screening tool developed for use in South Africa that would assist healthcare professionals (HCPs) to recognise patients who may have unmet palliative care needs'.

Aim:  This research study sought to develop South African consensus on indicators for PC to assist clinicians to recognise a patient in need of PC.

Guidelines for Perioperative Care in Elective Abdominal and Pelvic Surgery at Primary and Secondary Hospitals in Low-Middle-Income Countries (LMIC's): Enhanced Recovery After Surgery (ERAS) Society Recommendation.

Background: This is the first Enhanced Recovery After Surgery (ERAS®) Society guideline for primary and secondary hospitals in low-middle-income countries (LMIC's) for elective abdominal and gynecologic care.

Methods: The ERAS LMIC Guidelines group was established by the ERAS® Society in collaboration with different representatives of perioperative care from LMIC's. The group consisted of seven members from the ERAS® Society and eight members from LMIC's.

Aspartate metabolism in endothelial cells activates the mTORC1 pathway to initiate translation during angiogenesis.

Angiogenesis, the active formation of new blood vessels from pre-existing ones, is a complex and demanding biological process that plays an important role in physiological as well as pathological settings. Recent evidence supports cell metabolism as a critical regulator of angiogenesis. However, whether and how cell metabolism regulates endothelial growth factor receptor levels and nucleotide synthesis remains elusive.

PFAS Molecules: A Major Concern for the Human Health and the Environment.

Per- and polyfluoroalkyl substances (PFAS) are a group of over 4700 heterogeneous compounds with amphipathic properties and exceptional stability to chemical and thermal degradation. The unique properties of PFAS compounds has been exploited for almost 60 years and has largely contributed to their wide applicability over a vast range of industrial, professional and non-professional uses. However, increasing evidence indicate that these compounds represent also a serious concern for both wildlife and human health as a result of their ubiquitous distribution, their extreme persistence and their bioaccumulative potential.

Joint Cardioprotective Effect of Vitamin C and Other Antioxidants against Reperfusion Injury in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Percutaneous coronary intervention (PCI) has long remained the gold standard therapy to restore coronary blood flow after acute myocardial infarction (AMI). However, this procedure leads to the development of increased production of reactive oxygen species (ROS) that can exacerbate the damage caused by AMI, particularly during the reperfusion phase. Numerous attempts based on antioxidant treatments, aimed to reduce the oxidative injury of cardiac tissue, have failed in achieving an effective therapy for these patients.

Targeting Ferroptosis against Ischemia/Reperfusion Cardiac Injury.

Ischemic heart disease is a leading cause of death worldwide. Primarily, ischemia causes decreased oxygen supply, resulting in damage of the cardiac tissue. Naturally, reoxygenation has been recognized as the treatment of choice to recover blood flow through primary percutaneous coronary intervention.

Regulatory Role of Nrf2 Signaling Pathway in Wound Healing Process.

Wound healing involves a series of cellular events in damaged cells and tissues initiated with hemostasis and finally culminating with the formation of a fibrin clot. However, delay in the normal wound healing process during pathological conditions due to reactive oxygen species, inflammation and immune suppression at the wound site represents a medical challenge. So far, many therapeutic strategies have been developed to improve cellular homeostasis and chronic wounds in order to accelerate wound repair.

The Role of Toxic Metals and Metalloids in Nrf2 Signaling.

Nuclear factor erythroid 2-related factor 2 (Nrf2), an emerging regulator of cellular resistance to oxidants, serves as one of the key defensive factors against a range of pathological processes such as oxidative damage, carcinogenesis, as well as various harmful chemicals, including metals. An increase in human exposure to toxic metals via air, food, and water has been recently observed, which is mainly due to anthropogenic activities. The relationship between environmental exposure to heavy metals, particularly cadmium (Cd), lead (Pb), mercury (Hg), and nickel (Ni), as well as metaloid arsenic (As), and transition metal chromium (Cr), and the development of various human diseases has been extensively investigated.

Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer.

Cancer is one of the most fatal diseases with an increasing incidence and mortality all over the world. Thus, there is an urgent need for novel therapies targeting major cancer-related pathways. Nuclear factor-erythroid 2-related factor 2 (NRF2) and its major negative modulator Kelch-like ECH-associated protein 1 (KEAP1) are main players of the cellular defense mechanisms against internal and external cell stressors.

Involvement of NRF2 in Breast Cancer and Possible Therapeutical Role of Polyphenols and Melatonin.

Oxidative stress is defined as a disturbance in the prooxidant/antioxidant balance in favor of the former and a loss of control over redox signaling processes, leading to potential biomolecular damage. It is involved in the etiology of many diseases, varying from diabetes to neurodegenerative diseases and cancer. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor and reported as one of the most important oxidative stress regulators.

Laparoscopic splenopexy for wandering spleen with absorbable mesh fixation.

Wandering spleen is a rare condition characterised by lack of fixation of the spleen to its usual position in the left upper quadrant. Laparoscopic splenopexy has become the standard of care. Although a number of methods have been described, the use of an absorbable mesh to secure the spleen to the left upper quadrant has been shown to be safe, effective and quick to perform.

Short overview on the relevance of microRNA-reactive oxygen species (ROS) interactions and lipid peroxidation for modulation of oxidative stress-mediated signalling pathways in cancer treatment.

Objectives: Modulation of oxidative stress-mediated signalling pathways is constantly getting more attention as a valuable therapeutic strategy in cancer treatment. Although complexity of redox signalling pathways might represent a major hurdle, the development of advanced -omics technologies allow thorough studies on cancer-specific biology, which is essential to elucidate the impact of these signalling pathways in cancer cells. The scope of our review is to provide updated information about recent developments in cancer treatment.

Inhibition of the NRF2/KEAP1 Axis: A Promising Therapeutic Strategy to Alter Redox Balance of Cancer Cells.

The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (NRF2/KEAP1) pathway is a crucial and highly conserved defensive system that is required to maintain or restore the intracellular homeostasis in response to oxidative, electrophilic, and other types of stress conditions. The tight control of NRF2 function is maintained by a complex network of biological interactions between positive and negative regulators that ultimately ensure context-specific activation, culminating in the NRF2-driven transcription of cytoprotective genes. Recent studies indicate that deregulated NRF2 activation is a frequent event in malignant tumors, wherein it is associated with metabolic reprogramming, increased antioxidant capacity, chemoresistance, and poor clinical outcome.

An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation.

Inflammation is a key driver in many pathological conditions such as allergy, cancer, Alzheimer's disease, and many others, and the current state of available drugs prompted researchers to explore new therapeutic targets. In this context, accumulating evidence indicates that the transcription factor Nrf2 plays a pivotal role controlling the expression of antioxidant genes that ultimately exert anti-inflammatory functions. Nrf2 and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH- associated protein 1 (Keap1), play a central role in the maintenance of intracellular redox homeostasis and regulation of inflammation.

Ellagic Acid-Derived Urolithins as Modulators of Oxidative Stress.

Oxidative stress is a state of excess of prooxidative species relative to the antioxidant defenses (enzymatic and nonenzymatic) in a living organism. The consequence of this imbalance is damage of the major cellular macromolecules (carbohydrates, lipids, proteins, and DNA), which further leads to a gradual loss of tissue and organ function. It has been shown that oxidative stress plays an important role in the pathogenesis of many chronic diseases (cardiovascular, metabolic, and neurodegenerative diseases and cancer) and in the process of aging.

Papillary thyroid carcinoma presenting as miliary nodules on chest roentgenogram in the paediatric setting: A case report.

Introduction: Papillary thyroid carcinoma (PTC) is the most common carcinoma to occur in childhood with a peak incidence between 11-17 years, and typically presents with advanced locoregional disease. Pulmonary metastases are seen in up to 46% of cases and should enter the differential diagnosis of miliary nodules seen on chest roentgenogram, even in regions where tuberculosis is endemic.

Presentation Of Case: An 11-year-old male presented with a short history of cough, shortness of breath and constitutional symptoms.

The NRF2/KEAP1 Axis in the Regulation of Tumor Metabolism: Mechanisms and Therapeutic Perspectives.

The NRF2/KEAP1 pathway is a fundamental signaling cascade that controls multiple cytoprotective responses through the induction of a complex transcriptional program that ultimately renders cancer cells resistant to oxidative, metabolic and therapeutic stress. Interestingly, accumulating evidence in recent years has indicated that metabolic reprogramming is closely interrelated with the regulation of redox homeostasis, suggesting that the disruption of NRF2 signaling might represent a valid therapeutic strategy against a variety of solid and hematologic cancers. These aspects will be the focus of the present review.

Potential Applications of NRF2 Modulators in Cancer Therapy.

The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation.

Surgery for Pheochromocytoma: A Single-Center Review of 60 Cases from South Africa.

Background: There is a paucity of data on the presentation and surgical management of pheochromocytoma in developing nations, particularly in Africa.

Methods: This study was a retrospective review, which included all patients managed by the Groote Schuur Hospital/University of Cape Town Endocrine Surgery unit for pheochromocytoma and abdominal paragangliomas, from January 2002 to June 2019.

Results: Sixty patients were included in the study, of which 33% were male and 67% female.