Redox pathways in melanoma.

Cases of melanoma are doubling every 12 years, and in stages III and IV, the disease is associated with high mortality rates concomitant with unresectable metastases and therapeutic drug resistance. Despite some advances in treatment success, there is a marked need to understand more about the pathology of the disease. The present review provides an overview of how melanoma cells use and modulate redox pathways to facilitate thiol homeostasis and melanin biosynthesis and describes plausible redox targets that may improve therapeutic approaches in managing malignant disease and metastasis.

Effect of Adding a Program of Contextualized, Personalized, Remote Physical Activity Support to Conventional Cardiac Rehabilitation.

Purpose: The objective of this investigation was to conduct a randomized controlled trial to evaluate whether KiActiv Heart alongside usual care (UC) promotes positive physical activity (PA) change versus UC alone.

Methods: Patients in cardiac rehabilitation (n = 130) undertook an 8-wk intervention with follow-up at wk 8. Both groups attended UC and wore a PA monitor during the intervention.

Value of the surgical pancreatic duct anatomy and associated outcomes in pancreatic cancer.

Introduction: Pancreatic cancer recurrence following surgery is a significant challenge, and personalized surgical care is crucial. Topographical variations in pancreatic duct anatomy are frequent but often underestimated. This study aimed to investigate the potential importance of these variations in outcomes and patient survival after Whipple's procedures.

LymphActiv: A Digital Physical Activity Behavior Intervention for the Treatment of Lymphedema and Lipedema.

Lymphedema and lipedema are debilitating conditions with no proven drug or surgical therapy. Effective treatment requires self-management through movement and compression to reduce limb volume and the incidence of cellulitis. The addition of personalized everyday physical activity (PA) could be transformative, increasing the therapy window to include all waking hours per week and enabling an increased dose of PA.

Adaptive changes in tumor cells in response to reductive stress.

Reductive stress is characterized by an excess of cellular electron donors and can be linked with various human pathologies including cancer. We developed melanoma cell lines resistant to reductive stress agents: rotenone (ROT), n-acetyl-L-cysteine, (NAC), or dithiothreitol (DTT). Resistant cells divided more rapidly and had intracellular homeostatic redox-couple ratios that were shifted towards the reduced state.

Increasing medical student awareness of pathology through a virtual, asynchronous pathology elective.

Faculty from the University of Florida Department of Pathology, Immunology, and Laboratory Medicine developed an asynchronous, fully virtual pathology elective for medical students that emphasizes both foundational pathology concepts as well as the role of pathologists in the broader health system. The program includes ten core modules as well as several selective modules which allows students to tailor their coursework to better align with their desired specialty. After completing each module, students were required to concisely summarize the topic in the form of a 280-character tweet.

Nuclear factor kappa B expression in non-small cell lung cancer.

In this mini-review, we discuss the role of NF-κB, a proinflammatory transcription factor, in the expression of genes involved in inflammation, proliferation, and apoptosis pathways, and link it with prognosis of various human cancers, particularly non-small cell lung cancer (NSCLC). We and others have shown that NF-κB activity can be impacted by post-translational S-glutathionylation through reversible formation of a mixed disulfide bond between its cysteine residues and glutathione (GSH). Clinical data analysis showed that high expression of NF-κB correlated with shorter overall survival (OS) in NSCLC patients, suggesting a tumor promotion function for NF-κB.

Protein disulfide isomerase family mediated redox regulation in cancer.

Protein disulfide isomerase (PDI) and its superfamilies are mainly endoplasmic reticulum (ER) resident proteins with essential roles in maintaining cellular homeostasis, via thiol oxidation/reduction cycles, chaperoning, and isomerization of client proteins. Since PDIs play an important role in ER homeostasis, their upregulation supports cell survival and they are found in a variety of cancer types. Despite the fact that the importance of PDI to tumorigenesis remains to be understood, it is emerging as a new therapeutic target in cancer.

Microsomal glutathione transferase 1 in cancer and the regulation of ferroptosis.

Microsomal glutathione transferase 1 (MGST1) is a member of the MAPEG family (membrane associated proteins in eicosanoid and glutathione metabolism), defined according to enzymatic activities, sequence motifs, and structural properties. MGST1 is a homotrimer which can bind three molecules of glutathione (GSH), with one modified to a thiolate anion displaying one-third-of-sites-reactivity. MGST1 has both glutathione transferase and peroxidase activities.

A role for microsomal glutathione transferase 1 in melanin biosynthesis and melanoma progression.

Recent advancements in the treatment of melanoma are encouraging, but there remains a need to identify additional therapeutic targets. We identify a role for microsomal glutathione transferase 1 (MGST1) in biosynthetic pathways for melanin and as a determinant of tumor progression. Knockdown (KD) of MGST1 depleted midline-localized, pigmented melanocytes in zebrafish embryos, while in both mouse and human melanoma cells, loss of MGST1 resulted in a catalytically dependent, quantitative, and linear depigmentation, associated with diminished conversion of L-dopa to dopachrome (eumelanin precursor).

The Multifaceted Role of Glutathione S-Transferases in Health and Disease.

In humans, the cytosolic glutathione S-transferase (GST) family of proteins is encoded by 16 genes presented in seven different classes. GSTs exhibit remarkable structural similarity with some overlapping functionalities. As a primary function, GSTs play a putative role in Phase II metabolism by protecting living cells against a wide variety of toxic molecules by conjugating them with the tripeptide glutathione.

Iron Fertilization Can Enhance the Mass Production of Copepod, , for Fish Aquaculture.

Copepods are proven nutritious food sources for the mariculture/larviculture industry, however, unreliable methods for mass production of copepods are a major bottleneck. In this study, we modified a previously reported inorganic fertilization method (N: 700 μg L and P: 100 μg L) by the addition of iron (Fe: 10 μg L, using FeSO·7HO) (+Fe treatment) and compared its suitability for copepod culture () to the original method (control). The experiment was conducted outdoors in 1000 L tanks for 15 days.

The Advantages of Inorganic Fertilization for the Mass Production of Copepods as Food for Fish Larvae in Aquaculture.

Copepods are commonly used as live feed for cultured fish larvae, but the current mass production method using organic fertilizers cannot meet the market demand for copepods. We evaluated the feasibility of applying an inorganic fertilization method, which is currently in use in freshwater and marine larviculture, to the mass production of copepods. For 30 days, and with five replicates of each treatment, we made comparative daily measurements of various parameters of (1) copepod cultures fertilized with commercially available condensed fish solubles (organic fertilization) and (2) other cultures in which the concentration of inorganic phosphorus was maintained at 100 μg P L and that of inorganic nitrogen at 700 μg N L (inorganic fertilization).

Extra high superoxide dismutase in host tissue is associated with improving bleaching resistance in "thermal adapted" and -associating coral.

Global warming threatens reef-building corals with large-scale bleaching events; therefore, it is important to discover potential adaptive capabilities for increasing their temperature resistance before it is too late. This study presents two coral species ( and ) surviving on a reef having regular hot water influxes via a nearby nuclear power plant that exhibited completely different bleaching susceptibilities to thermal stress, even though both species shared several so-called "winner" characteristics ( containing , thick tissue, ). During acute heating treatment, algal density did not decline in corals within three days of being directly transferred from 25 to 31 °C; however, the same treatment caused .

Reductive stress in cancer.

Reductive stress is defined as a condition characterized by excess accumulation of reducing equivalents (e.g., NADH, NADPH, GSH), surpassing the activity of endogenous oxidoreductases.

Cisplatin chemotherapy and renal function.

Cisplatin has been a mainstay of cancer chemotherapy since the 1970s. Despite its broad anticancer potential, its clinical use has regularly been constrained by kidney toxicities. This review details those biochemical pathways and metabolic conversions that underlie the kidney toxicities.

Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia.

PFKP (phosphofructokinase, platelet), the major isoform of PFK1 expressed in T cell acute lymphoblastic leukemia (T-ALL), is predominantly expressed in the cytoplasm to carry out its glycolytic function. Our study showed that PFKP is a nucleocytoplasmic shuttling protein with functional nuclear export and nuclear localization sequences (NLSs). Cyclin D3/CDK6 facilitated PFKP nuclear translocation by dimerization and by exposing the NLS of PFKP to induce the interaction between PFKP and importin 9.

Nrf2 inhibition sensitizes breast cancer stem cells to ionizing radiation via suppressing DNA repair.

Radiation is widely used for cancer treatment but the radioresistance properties of cancer stem cells (CSCs) pose a significant challenge to the success of cancer therapy. Nuclear factor erythroid-2-related factor 2 (Nrf2) has emerged as a prominent regulator of cellular antioxidant responses and its over-activation is associated with drug resistant in cancer cells. However, the role of Nrf2 signaling in regulating the response of CSCs to irradiation has yet to be defined.

Risk Stratification of Elderly Patients Undergoing Spinal Surgery Using the Modified Frailty Index.

Study Design: Retrospective cohort.

Objectives: To validate the 11-item modified Frailty Index (mFI) as a perioperative risk stratification tool in elderly patients undergoing spine surgery.

Methods: All consecutive cases of spine surgery in patients aged 65 years or older between July 2016 and June 2018 at a state-wide trauma center were retrospectively reviewed.

Glutathione -Transferase P Influences Redox Homeostasis and Response to Drugs that Induce the Unfolded Protein Response in Zebrafish.

We have created a novel glutathione -transferase 1 () knockout (KO) zebrafish model and used it for comparative analyses of redox homeostasis and response to drugs that cause endoplasmic reticulum (ER) stress and induce the unfolded protein response (UPR). Under basal conditions, KO larvae had higher expression of antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) accompanied by a more reduced larval environment and a status consistent with reductive stress. Compared with wild type, various UPR markers were decreased in KO larvae, but treatment with drugs that induce ER stress caused greater toxicities and increased expression of Nrf2 and UPR markers in KO.

The Role of Spinal Orthoses in Osteoporotic Vertebral Fractures of the Elderly Population (Age 60 Years or Older): Systematic Review.

Study Design: Systematic review.

Objective: Spinal orthoses have been generally used in the management of osteoporotic vertebral fractures in the elderly population with purported positive biomechanical and functional effects. To our knowledge, this is the first systematic review of the literature examining the role of spinal orthoses in osteoporotic elderly patients who sustain low energy trauma vertebral fractures.

Altered redox regulation and S-glutathionylation of BiP contribute to bortezomib resistance in multiple myeloma.

Multiple myeloma (MM) cells have high rates of secretion of proteins rich in disulfide bonds and depend upon compartmentalized redox balance for accurate protein folding. The proteasome inhibitor bortezomib (Btz) is a successful frontline treatment for the disease, but its long-term efficacy is restricted by the acquisition of resistance. We found that MM cell lines resistant to Btz maintain high levels of oxidative stress and are cross resistant to endoplasmic reticulum (ER) stress-inducing agents thapsigargin (ThG), and tunicamycin (TuM).

Spinal Surgery in Patients Aged 80 Years and Older: Risk Stratification Using the Modified Frailty Index.

Study Design: This was an ambispective clinical quality registry study.

Objective: To evaluate utility of 11-variable modified Frailty Index (mFI) in predicting postoperative outcomes among patients ≥80 years undergoing spinal surgery.

Methods: Consecutive patients ≥80 years who underwent spinal surgery between January 1, 2013, and June 30, 2018, were included.