A Noncatalytic Cysteine Residue Modulates Cobalamin Reactivity in the Human B Processing Enzyme CblC.

Human CblC catalyzes the indispensable processing of dietary vitamin B by the removal of its β-axial ligand and an either one- or two-electron reduction of its cobalt center to yield cob(II)alamin and cob(I)alamin, respectively. Human CblC possesses five cysteine residues of an unknown function. We hypothesized that Cys149, conserved in mammals, tunes the CblC reactivity.

Macromolecular crowding and bicarbonate enhance the hydrogen peroxide-induced inactivation of glyceraldehyde-3-phosphate dehydrogenase.

The active site Cys residue in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is sensitive to oxidation by hydrogen peroxide (H2O2), with this resulting in enzyme inactivation. This re-routes the carbon flux from glycolysis to the pentose phosphate pathway favoring the formation of NADPH and synthetic intermediates required for antioxidant defense and repair systems. Consequently, GAPDH inactivation serves as a redox switch for metabolic adaptation under conditions of oxidative stress.

Mitochondrial Ca2+-coupled generation of reactive oxygen species, peroxynitrite formation, and endothelial dysfunction in Cantú syndrome.

Cantú syndrome is a multisystem disorder caused by gain-of-function (GOF) mutations in KCNJ8 and ABCC9, the genes encoding the pore-forming inward rectifier Kir6.1 and regulatory sulfonylurea receptor SUR2B subunits, respectively, of vascular ATP-sensitive K+ (KATP) channels. In this study, we investigated changes in the vascular endothelium in mice in which Cantú syndrome-associated Kcnj8 or Abcc9 mutations were knocked in to the endogenous loci.

Production of Peroxymonocarbonate by Steady-State Micromolar HO and Activated Macrophages in the Presence of CO/HCO Evidenced by Boronate Probes.

Peroxymonocarbonate (HCO/HOOCO) is produced by the reversible reaction of CO/HCO with HO ( = 0.33 M, pH 7.0).

Puffing to Persistent Smoking Cessation.

Nicotine e-cigarettes are a safe and effective way to help patients stop smoking.

Peroxynitrite: a multifaceted oxidizing and nitrating metabolite.

Peroxynitrite, a short-lived and reactive oxidant, emerges from the diffusion-controlled reaction between the superoxide radical and nitric oxide. Evidence shows that peroxynitrite is a critical mediator in physiological and pathological processes such as the immune response, inflammation, cancer, neurodegeneration, vascular dysfunction, and aging. The biochemistry of peroxynitrite is multifaceted, involving one- or two-electron oxidations and nitration reactions.

The Prevalence of Tooth Wear and Their Associated Etiologies Among Adult Subjects Visiting Umm Al-Qura University Dental Clinic in Makkah City, Saudi Arabia.

In the past two decades, changing trends in socioeconomic status, dietary habits, and individual lifestyles of individuals have led to the emergence of tooth wear as an oral health problem. The present study aimed to investigate the prevalence and the associated etiologies of tooth wear in a convenience sample of adult patients visiting outpatient clinics of the Faculty of Dentistry at Umm Al-Qura University. This cross-sectional study was conducted on adult patients (18-40 years old) visiting outpatient clinics of the Faculty of Dentistry, Umm Al-Qura University.

Less Is More: Backing off Sliding Scale Insulin for Hospitalized Patients.

In hospitalized patients with type 2 diabetes (T2DM), a less aggressive supplemental insulin regimen is noninferior to a standard, more aggressive, supplemental regimen.

Catalytic Mechanism of Methionine Sulfoxide Reductase A.

The oxidation of Met to methionine sulfoxide (MetSO) by oxidants such as hydrogen peroxide, hypochlorite, or peroxynitrite has profound effects on protein function. This modification can be reversed by methionine sulfoxide reductases (msr). In the context of pathogen infection, the reduction of oxidized proteins gains significance due to microbial oxidative damage generated by the immune system.

Superoxide, nitric oxide and peroxynitrite production by macrophages under different physiological oxygen tensions.

Macrophages count on two O-consuming enzymes to form reactive radical species: NAPDH oxidase 2 (Nox2) and nitric oxide synthase 2 (inducible isoform, iNOS) that produce superoxide radical (O) and nitric oxide (NO), respectively. If formed simultaneously, the diffusion-controlled reaction of O and NO yields peroxynitrite, a potent cytotoxic oxidant. In human tissues and cells, the oxygen partial pressure (pO) normally ranges within 2-14 %, with a typical average pO value for most tissues ca.

The Effect of Fat Intake with Increased Omega-6-to-Omega-3 Polyunsaturated Fatty Acid Ratio in Animal Models of Early and Late Alzheimer's Disease-like Pathogenesis.

This work aims to clarify the effect of dietary polyunsaturated fatty acid (PUFA) intake on the adult brain affected by amyloid pathology. McGill-R-Thy1-APP transgenic (Tg) rat and 5xFAD Tg mouse models that represent earlier or later disease stages were employed. The animals were exposed to a control diet (CD) or an HFD based on corn oil, from young (rats) or adult (mice) ages for 24 or 10 weeks, respectively.

Skin Barrier Function: The Interplay of Physical, Chemical, and Immunologic Properties.

An intact barrier function of the skin is important in maintaining skin health. The regulation of the skin barrier depends on a multitude of molecular and immunological signaling pathways. By examining the regulation of a healthy skin barrier, including maintenance of the acid mantle and appropriate levels of ceramides, dermatologists can better formulate solutions to address issues that are related to a disrupted skin barrier.

4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification.

Background And Aims: Developing novel therapies to battle the global public health burden of heart failure remains challenging. This study investigates the underlying mechanisms and potential treatment for 4-hydroxynonenal (4-HNE) deleterious effects in heart failure.

Methods: Biochemical, functional, and histochemical measurements were applied to identify 4-HNE adducts in rat and human failing hearts.

Photochemically-induced protein tyrosine nitration in vitro and in cellula by 5-methyl-1,4-dinitro-1H-imidazole (DNI): synthesis and biochemical characterization.

The photochemical nitrating agent 5-methyl-1,4-dinitro-1H-imidazole (DNI) has been recently described as an effective tool for nitrating tyrosine residues in proteins under 390 nm irradiation (Long T. et al., 2021).

Is low-dose naltrexone effective in chronic pain management?

YES. Low-dose naltrexone is as effective as amitriptyline in the treatment of painful diabetic neuropathy and has a superior safety profile (strength of recommendation [SOR], B; single randomized controlled trial [RCT]). Low-dose naltrexone significantly reduced pain by 32% in inflammatory conditions and 44% in neuropathic conditions (SOR, B; single retrospective cohort study).

Should you treat prediabetes? It's complicated.

While treatment with metformin or lifestyle modification reduces risk for T2D in patients with prediabetes, neither intervention ultimately offers a mortality benefit.

Dermatologic care of patients with differences of sex development.

Background: Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal, or anatomic sex.

Objective: Dermatologic care is an important component of the multidisciplinary care needed for individuals with DSD. This article discusses the most common primary dermatologic manifestations of DSD in addition to the cutaneous manifestations of hormonal and surgical therapies in individuals with DSD.

A nitroalkene derivative of salicylate alleviates diet-induced obesity by activating creatine metabolism and non-shivering thermogenesis.

Obesity-related type II diabetes (diabesity) has increased global morbidity and mortality dramatically. Previously, the ancient drug salicylate demonstrated promise for the treatment of type II diabetes, but its clinical use was precluded due to high dose requirements. In this study, we present a nitroalkene derivative of salicylate, 5-(2-nitroethenyl)salicylic acid (SANA), a molecule with unprecedented beneficial effects in diet-induced obesity (DIO).

Targeting Some Key Metalloproteinases by Nano-Naringenin and as a Novel Strategy for Treatment of Osteoarthritis in Rats.

Osteoarthritis (OA) represents the highest degenerative disorder. Because cartilage erosion is a common pathological alteration in OA, targeting some key metalloproteinases such as MMP-3, ADAMTS-5 besides their inhibitor TIMP-3 by natural products, could be an effective strategy to protect against osteoarthritis. Forty female Wister rats were categorized into five equal groups.

Does hormone replacement therapy prevent cognitive decline in postmenopausal women?

NO. Hormone replacement therapy (HRT) does not prevent cognitive decline in postmenopausal women-and in fact, it may slightly increase risk (strength of recommendation, A; systematic review, meta-analysis of randomized controlled trials [RCTs], and individual RCT).

Carbon dioxide/bicarbonate is required for sensitive inactivation of mammalian glyceraldehyde-3-phosphate dehydrogenase by hydrogen peroxide.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) contains an active site Cys and is one of the most sensitive cellular enzymes to oxidative inactivation and redox regulation. Here, we show that inactivation by hydrogen peroxide is strongly enhanced in the presence of carbon dioxide/bicarbonate. Inactivation of isolated mammalian GAPDH by HO increased with increasing bicarbonate concentration and was sevenfold faster in 25 mM (physiological) bicarbonate compared with bicarbonate-free buffer of the same pH.

Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides.

Human peroxiredoxin 3 (Prx3) is a thiol-based peroxidase responsible for the reduction of most hydrogen peroxide and peroxynitrite formed in mitochondria. Mitochondrial disfunction can lead to membrane lipoperoxidation, resulting in the formation of lipid-bound fatty acid hydroperoxides (FA-OOHs) which can be released to become free fatty acid hydroperoxides (FA-OOHs). Herein, we report that Prx3 is oxidized and hyperoxidized by FA-OOHs including those derived from arachidonic acid and eicosapentaenoic acid peroxidation at position 15 with remarkably high rate constants of oxidation (>3.