Targeting Lipid Peroxidation for Cancer Treatment

grant number RTI2018-093864-B-I00Cancer is one of the highest prevalent diseases in humans. The chances of surviving cancer and its prognosis are very dependent on the affected tissue, body location, and stage at which the disease is diagnosed. Researchers and pharmaceutical companies worldwide are pursuing many attempts to look for compounds to treat this malignancy. Most of the current strategies to fight cancer implicate the use of compounds acting on DNA damage checkpoints, non-receptor tyrosine kinases activities, regulators of the hedgehog signaling pathways, and metabolic adaptations placed in cancer. In the last decade, the finding of a lipid peroxidation increase linked to 15-lipoxygenases isoform 1 (15-LOX-1) activity stimulation has been found in specific successful treatments against cancer. This discovery contrasts with the production of other lipid oxidation signatures generated by stimulation of other lipoxygenases such as 5-LOX and 12-LOX, and cyclooxygenase (COX-2) activities, which have been suggested as cancer biomarkers and which inhibitors present anti-tumoral and antiproliferative activities. These findings support the previously proposed role of lipid hydroperoxides and their metabolites as cancer cell mediators. Depletion or promotion of lipid peroxidation is generally related to a specific production source associated with a cancer stage or tissue in which cancer originates. This review highlights the potential therapeutical use of chemical derivatives to stimulate or block specific cellular routes to generate lipid hydroperoxides to treat this disease.publishersversionpublishe

The Use of Flavylium Salts as Dynamic Inhibitor Moieties for Human Cb5R

Authors would like to acknowledge the Biochemistry Department in the Faculty of Medicine at the Universidad Autónoma de Madrid for the equipment and support for some of the required reagent purchases. FCT/MCTES is also acknowledged for supporting the National Portuguese NMR Network (ROTEIRO/0031/2013-PINFRA/22161/2016, co-financed by FEDER through COMPETE 2020, POCI, PORL. We thank José Paulo da Silva for the HRMS-ESI analysis. Publisher Copyright: © 2022 by the authors.Cytochrome b5 reductase (Cb5R) is a flavoprotein that participates in the reduction of multiple biological redox partners. Co-localization of this protein with nitric oxide sources has been observed in neurons. In addition, the generation of superoxide anion radical by Cb5R has been observed. A search for specific inhibitors of Cb5R to understand the role of this protein in these new functions has been initiated. Previous studies have shown the ability of different flavonoids to inhibit Cb5R. Anthocyanins are a subgroup of flavonoids responsible for most red and blue colors found in flowers and fruits. Although usually represented by the flavylium cation form, these species are only stable at rather acidic pH values (pH ≤ 1). At higher pH values, the flavylium cation is involved in a dynamic reaction network comprising different neutral species with the potential ability to inhibit the activities of Cb5R. This study aims to provide insights into the molecular mechanism of interaction between flavonoids and Cb5R using flavylium salts as dynamic inhibitors. The outcome of this study might lead to the design of improved specific enzyme inhibitors in the future.publishersversionpublishe

Classifications of Pineapple using Deep Learning

A pineapple is a tropical plant with eatable leafy foods most monetarily critical plant in the family Bromeliaceous. The pineapple is native to South America, where it has been developed for a long time. The acquaintance of the pineapple with Europe in the seventeenth century made it a critical social symbol of extravagance. Since the 1820s, pineapple has been industrially filled in nurseries and numerous tropical manors. Further, it is the third most significant tropical natural product in world creation. In the twentieth century, Hawaii was a prevailing maker of pineapples, particularly for the US, be that as it may, by 2016, Costa Rica, Brazil, and the Philippines represented almost 33% of the world's creation of pineapples. In this paper, machine learning based approach is presented for identifying type pineapple with a dataset that contains 1,311images use 946 images for training, 197 images for validation and 168 images for testing. A deep learning technique that extensively applied to image recognition was used. use 70% from image for training and 30% from image for validation. Our trained model achieved an accuracy of 100% on a heldout test set

Papaya Maturity Classifications using Deep Convolutional Neural Networks

Papaya is a tropical fruit with a green cover, yellow pulp, and a taste between mango and cantaloupe, having commercial importance because of its high nutritive and medicinal value. The process of sorting papaya fruit based on maturely is one of the processes that greatly determine the mature of papaya fruit that will be sold to consumers. The manual grading of papaya fruit based on human visual perception is time-consuming and destructive. The objective of this paper is to the status classification of papaya fruits if it's mature or partially matured or unmatured. A deep learning technique that was extensively applied to image recognition was used. The trained model achieved an accuracy of 100% on a held-out test set, demonstrating the feasibility of this approach. Classification model of VGG16 achieved a 100% accuracy and 112 seconds of training time

Extraperitoneal urine leak after renal transplantation: the role of radionuclide imaging and the value of accompanying SPECT/CT - a case report

<p>Abstract</p> <p>Background</p> <p>The differentiation of the nature of a fluid collection as a complication of kidney transplantation is important for management and treatment planning. Early and delayed radionuclide renography can play an important role in the evaluation of a urine leak. However, it is sometimes limited in the evaluation of the exact location and extent of a urine leak.</p> <p>Case Presentation</p> <p>A 71-year-old male who had sudden anuria, scrotal swelling and elevated creatinine level after cadaveric renal transplantation performed Tc-99 m MAG3 renography to evaluate the renal function, followed by an ultrasound which was unremarkable. An extensive urine leak was evident on the planar images. However, an exact location of the urine leak was unknown. Accompanying SPECT/CT images confirmed a urine leak extending from the lower aspect of the transplant kidney to the floor of the pelvic cavity, presacral region and the scrotum via right inguinal canal as well as to the right abdominal wall.</p> <p>Conclusions</p> <p>Renal scintigraphy is very useful to detect a urine leak after renal transplantation. However, planar imaging is sometimes limited in evaluating the anatomical location and extent of a urine leak accurately. In that case accompanying SPECT/CT images are very helpful and valuable to evaluate the anatomical relationships exactly.</p

Cytochrome c stimulates the superoxide anion production by cytochrome b5 reductase in neuronal synaptic plasma membrane vesicles

info:eu-repo/grantAgreement/FCT/5876/147258/PT Work financed by Grants FCT/MEC (UID/Multi/04378/2013). POCI-01-0145-FEDER-007728 and BFU2014-53641-P of the Spanish Ministerio de Economia y Competitividad co-financed by FEDER.authorsversionpublishe

Loss of Caveolin-1 Accelerates Neurodegeneration and Aging

The aged brain exhibits a loss in gray matter and a decrease in spines and synaptic densities that may represent a sequela for neurodegenerative diseases such as Alzheimer's. Membrane/lipid rafts (MLR), discrete regions of the plasmalemma enriched in cholesterol, glycosphingolipids, and sphingomyelin, are essential for the development and stabilization of synapses. Caveolin-1 (Cav-1), a cholesterol binding protein organizes synaptic signaling components within MLR. It is unknown whether loss of synapses is dependent on an age-related loss of Cav-1 expression and whether this has implications for neurodegenerative diseases such as Alzheimer's disease.We analyzed brains from young (Yg, 3-6 months), middle age (Md, 12 months), aged (Ag, >18 months), and young Cav-1 KO mice and show that localization of PSD-95, NR2A, NR2B, TrkBR, AMPAR, and Cav-1 to MLR is decreased in aged hippocampi. Young Cav-1 KO mice showed signs of premature neuronal aging and degeneration. Hippocampi synaptosomes from Cav-1 KO mice showed reduced PSD-95, NR2A, NR2B, and Cav-1, an inability to be protected against cerebral ischemia-reperfusion injury compared to young WT mice, increased Aβ, P-Tau, and astrogliosis, decreased cerebrovascular volume compared to young WT mice. As with aged hippocampi, Cav-1 KO brains showed significantly reduced synapses. Neuron-targeted re-expression of Cav-1 in Cav-1 KO neurons in vitro decreased Aβ expression.Therefore, Cav-1 represents a novel control point for healthy neuronal aging and loss of Cav-1 represents a non-mutational model for Alzheimer's disease

Neural protection by naturopathic compounds—an example of tetramethylpyrazine from retina to brain

Given the advantages of being stable in the ambient environment, being permeable to the blood–brain and/or blood–eye barriers and being convenient for administration, naturopathic compounds have growingly become promising therapeutic candidates for neural protection. Extracted from one of the most common Chinese herbal medicines, tetramethylpyrazine (TMP), also designated as ligustrazine, has been suggested to be neuroprotective in the central nervous system as well as the peripheral nerve network. Although the detailed molecular mechanisms of its efficacy for neural protection are understood limitedly, accumulating evidence suggests that antioxidative stress, antagonism for calcium, and suppression of pro-inflammatory factors contribute significantly to its neuroprotection. In animal studies, systemic administration of TMP (subcutaneous injection, 50 mg/kg) significantly blocked neuronal degeneration in hippocampus as well as the other vulnerable regions in brains of Sprague–Dawley rats following kainate-induced prolonged seizures. Results from us and others also demonstrated potent neuroprotective efficacy of TMP for retinal cells and robust benefits for brain in Alzheimer’s disease or other brain injury. These results suggest a promising prospect for TMP to be used as a treatment of specific neurodegenerative diseases. Given the assessment of the distribution, metabolism, excretion, and toxicity information that is already available on most neuroprotective naturopathic compounds such as TMP, it would not take much preclinical data to justify bringing such therapeutic compounds to clinical trials in humans

Fuzzy congruences on groups and rings

We prove that the lattice of fuzzy congruences of a group G (resp. ring R) is isomorphic to the lattice of fuzzy normal subgroups of G (resp. fuzzy ideals of R)