A biomimetic nanodrug self-assembled from small molecules for enhanced ferroptosis therapy

The ferroptosis drugs often induce oxidative damage or block antioxidant defense due to the key mechanism of ferroptosis in cancer treatment involved regulating the intracellular redox balance. However, these ferroptosis...

Novel Redox Tests for Maillard Abuse-Induced Redox Imbalance: a Pilot Single Case Paradigm Analyzing Dietary Oxidized-Browned Foods and Their Instant-Influence on Oral-Intestinal, Extracellular, and Intracellular Systemic Oxidative and Reductive Stress and Eventual Association with COVID-19 Sepsis and Other Leading Causes of Morbidity and Mortality Globally

The public health hazards associated with Maillard end-products such as melanoidins and advanced lipoxidation end-products (ALEs) and advanced glycation end-products (AGEs), intermediary Maillard reaction creations, include most of the leading causes of morbidity and mortality globally. At the same time, only a few clinicians understand the intricacies linking redox biophysics and disease to humans and animals, explained here and in companion articles in simple to conceptualize terms. Maillard abuse causes increased systemic oxidative stress (SOS: pE-> pH+), an accelerant to the fatal vascular complications of type 1 diabetes. Maillard abuse-induced SOS (pE-> pH+) is also linked to type 2 diabetes, thyroid disorders, polycystic ovary syndrome, low testosterone, and osteoporosis. Many studies have shed light on exotic, intricate, and pricey markers to test extracellular and intracellular Maillard reaction-induced redox imbalance. And their corresponding influence on soluble and cell receptor signaling and the Maillard-induced redox-based diseases and deaths they cause. Inconclusive and pricey new markers for measuring extracellular and intracellular redox balance and imbalance cost thousands of US Dollars (USD) per in vivo assay. The author presents seven extracellular and intracellular redox markers costing less than 150 USD per in vivo assay, using standard laboratory tests available to medical centers worldwide. A PubMed search revealed no studies testing colas, pizza, burgers, and wings-specific intra-day Maillard-rich food binges on TSH, TG/HDL ratio (THR), VLDL/HDL ratio (VHR), LDL/HDL ratio (LHR), and urine pH+ extracellular redox markers, and neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) intracellular redox indicators. The objective of this pilot single case study is to test the feasibility of replication on a much larger scale. The second objective is to analyze the potential influence or lack of impact of Maillard intermediate and end-products on oral-intestine, corporal extracellular, and intracellular redox biophysics, soluble and cell receptor signaling, immunosuppression, inflammation, and risk for developing one or more of the leading causes of morbidity and mortality worldwide at three targeted intraday-pH+ points. The participant met inclusion criteria and drank acidic tide-inducing Maillard-rich colas to prompt an intra-oral-intestinal and the body’s extracellular systemic oxidative stress (SOS: pE-> pH+)-associated plasma acidic-tide. And had blood drawn for CBC with differential and platelet count, comprehensive metabolic panel, lipid panel, and TSH, and provided a sample for a routine urinalysis after an at-home confirmation of extracellular acidic-tide using ‘Just Fitter pH Test Strips pH 4.5 – pH 9.0.’ In a concerted attempt to reach an at-home urine pH+ strip value of 5.5, the top of the 4.5 to 5.5 urine and 7.35 to 7.38 blood systemic oxidative stress range (SOS: pE-> pH+). Before driving to the lab to give blood and urine samples for CBC with differential, comprehensive metabolic panel, lipid panel, TSH, and routine urinalysis. A similar procedure occurred to consuming mainly alkaline-botanical pizza, peanut butter shake, stronger alkaline tide-inducing acidic bacon double cheeseburgers and twelve fried chicken wings. The move from cola-associated urine pH+ 6 to pizza-associated pH+ 6.5 within the prime systemic energy PSE (pE- = pH+) urine pH+ range increased oral-intestinal, extracellular, and intracellular SOS by a factor of 50. The move from pizza-associated urine pH+ 6.5 to burgers and wings-associated pH+ 7.0 within the systemic reductive stress (SRS: pE-< pH+) urine pH+ range of 6.7 to 7.7, increased oral-intestinal, extracellular, and intracellular SOS (SOS: pE- > pH+) by a massive score of 556. This pilot study warrants reproduction on a larger scale with similarly healthy participants with elevated antioxidant tone. Such Maillard-intense trials require safe inclusionary criteria that limit initial subject sample pools to the equivalent of less than 25% of healthy females and males 8 to 80 years of age within or close to their ideal body mass indices and waist-to-height ratios.

Novel Redox Tests for Maillard Abuse-Induced Redox Imbalance: a Pilot Single Case Paradigm Analyzing Dietary Oxidized-Browned Foods and Their Instant-Influence on Oral-Intestinal, Extracellular, and Intracellular Systemic Oxidative and Reductive Stress and Eventual Association with COVID-19 Sepsis and Other Leading Causes of Morbidity and Mortality Globally

The public health hazards associated with Maillard end-products such as melanoidins and advanced lipoxidation end-products (ALEs) and advanced glycation end-products (AGEs), intermediary Maillard reaction creations, include most of the leading causes of morbidity and mortality globally. At the same time, only a few clinicians understand the intricacies linking redox biophysics and disease to humans and animals, explained here and in companion articles in simple to conceptualize terms. Maillard abuse causes increased systemic oxidative stress (SOS: pE-> pH+), an accelerant to the fatal vascular complications of type 1 diabetes. Maillard abuse-induced SOS (pE-> pH+) is also linked to type 2 diabetes, thyroid disorders, polycystic ovary syndrome, low testosterone, and osteoporosis. Many studies have shed light on exotic, intricate, and pricey markers to test extracellular and intracellular Maillard reaction-induced redox imbalance. And their corresponding influence on soluble and cell receptor signaling and the Maillard-induced redox-based diseases and deaths they cause. Inconclusive and pricey new markers for measuring extracellular and intracellular redox balance and imbalance cost thousands of US Dollars (USD) per in vivo assay. The author presents seven extracellular and intracellular redox markers costing less than 150 USD per in vivo assay, using standard laboratory tests available to medical centers worldwide. A PubMed search revealed no studies testing colas, pizza, burgers, and wings-specific intra-day Maillard-rich food binges on TSH, TG/HDL ratio (THR), VLDL/HDL ratio (VHR), LDL/HDL ratio (LHR), and urine pH+ extracellular redox markers, and neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) intracellular redox indicators. The objective of this pilot single case study is to test the feasibility of replication on a much larger scale. The second objective is to analyze the potential influence or lack of impact of Maillard intermediate and end-products on oral-intestine, corporal extracellular, and intracellular redox biophysics, soluble and cell receptor signaling, immunosuppression, inflammation, and risk for developing one or more of the leading causes of morbidity and mortality worldwide at three targeted intraday-pH+ points. The participant met inclusion criteria and drank acidic tide-inducing Maillard-rich colas to prompt an intra-oral-intestinal and the body’s extracellular systemic oxidative stress (SOS: pE-> pH+)-associated plasma acidic-tide. And had blood drawn for CBC with differential and platelet count, comprehensive metabolic panel, lipid panel, and TSH, and provided a sample for a routine urinalysis after an at-home confirmation of extracellular acidic-tide using ‘Just Fitter pH Test Strips pH 4.5 – pH 9.0.’ In a concerted attempt to reach an at-home urine pH+ strip value of 5.5, the top of the 4.5 to 5.5 urine and 7.35 to 7.38 blood systemic oxidative stress range (SOS: pE-> pH+). Before driving to the lab to give blood and urine samples for CBC with differential, comprehensive metabolic panel, lipid panel, TSH, and routine urinalysis. A similar procedure occurred to consuming mainly alkaline-botanical pizza, peanut butter shake, stronger alkaline tide-inducing acidic bacon double cheeseburgers and twelve fried chicken wings. The move from cola-associated urine pH+ 6 to pizza-associated pH+ 6.5 within the prime systemic energy PSE (pE- = pH+) urine pH+ range increased oral-intestinal, extracellular, and intracellular SOS by a factor of 50. The move from pizza-associated urine pH+ 6.5 to burgers and wings-associated pH+ 7.0 within the systemic reductive stress (SRS: pE-< pH+) urine pH+ range of 6.7 to 7.7, increased oral-intestinal, extracellular, and intracellular SOS (SOS: pE- > pH+) by a massive score of 556. This pilot study warrants reproduction on a larger scale with similarly healthy participants with elevated antioxidant tone. Such Maillard-intense trials require safe inclusionary criteria that limit initial subject sample pools to the equivalent of less than 25% of healthy females and males 8 to 80 years of age within or close to their ideal body mass indices and waist-to-height ratios.

Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology

Chemogenetics refers to experimental systems that dynamically regulate the activity of a recombinant protein by providing or withholding the protein's specific biochemical stimulus. Chemogenetic tools permit precise dynamic control of specific signaling molecules to delineate the roles of those molecules in physiology and disease. Yeast d-amino acid oxidase (DAAO) enables chemogenetic manipulation of intracellular redox balance by generating hydrogen peroxide only in the presence of d-amino acids. Advances in biosensors have allowed the precise quantitation of these signaling molecules. The combination of chemogenetic approaches with biosensor methodologies has opened up new lines of investigation, allowing the analysis of intracellular redox pathways that modulate physiological and pathological cell responses. We anticipate that newly developed transgenic chemogenetic models will permit dynamic modulation of cellular redox balance in diverse cells and tissues and will facilitate the identification and validation of novel therapeutic targets involved in both physiological redox pathways and pathological oxidative stress. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Sixty-Four Hour Changes in Oral-Intestinal, Extracellular, and Intracellular Redox Status After an All-Day Maillard-Coated Food Binge Followed by Two Days of Redox/Digestion-Balanced Culinary Medicine: A Pilot Single Case Analysis

Browned, melanoidin-coated, and Maillard reaction end-product-covered convenience and fast-foods are as addictive as street drugs. And drive overeating, systemic oxidative stress (SOS: pE- > pH+), and systemic reductive stress (SRS: pE- < pH+), overweight, and the leading causes of mortality and morbidity worldwide. Redox/digestion-balanced culinary medicine protocols are absent as healthcare professionals and the people they serve begin to recognize that Maillard abuse disorder is the main obstacle to self-actualization and a long, accomplished, and content energetically ambulatory extended lifespan. A PubMed search revealed no studies exhibiting sixty-four-hour changes in oral-intestinal, extracellular, and intracellular redox status after an all-day Maillard-coated food spree followed by two days of redox/digestion-balanced culinary medicine. The purpose of this single case study is to analyze changes, if any, in oral-intestinal, extracellular, and intracellular redox status after an all-day Maillard-coated binge followed by two days of redox/digestion-balanced culinary medicine and examine the feasibility of more extensive investigations. The participant met inclusion criteria, drank Maillard-rich colas for breakfast, a small pizza, a peanut butter shake for lunch, a double bacon cheeseburger, and a dozen chicken wings for dinner and provided blood and urine samples. The volunteer then underwent redox/digestion-balanced culinary medicine detoxification and provided laboratory samples. TSH, TG/HDL ratio, VLDL/HDL ratio, LDL/HDL ratio, and urine pH+ measured oral-intestinal and extracellular redox status. The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios assessed intracellular redox status. It took sixty-four hours for the participant’s body and mind to neutralize the toxic manifestations of a day-long binge on Maillard reaction intermediate and end-products, melanoidins, advanced glycation end-products (AGEs), and advanced lipoxidation endproducts-coated and containing foods and beverages. More extensive investigations are needed to increase the Maillard abuse detoxification options. Healthcare professionals and the people they serve increasingly recognize that Maillard abuse is the main obstacle to self-actualization and a long, accomplished, and energetically ambulatory lifespan.