The phenol red compound: A potential artifact in pharmacological induction of ferroptosis.

Phenol red (PR) is a commonly used compound in culture media as a pH indicator. However, it is unknown whether this compound can interfere with the pharmacological induction of ferroptosis. Here, using high-content live-cell imaging death analysis, we determined that the presence of PR in the culture medium preconditioned normal and tumor cells to ferroptosis induced by system x inhibition mediated by imidazole ketone erastin (IKE) or GPX4 blockade in response to RSL-3, but had no significant effects against treatment with the endoperoxide FINO.

Cognitive Profile and Cardiovascular Risk Factors in Older Adults with Mild Cognitive Impairment.

The prevalence of cardiovascular risk factors (CVRFs) in the older adults population and their specific impact on their cognitive profiles still requires further research. For this purpose, a cross-sectional study was carried out to describe the presence of CVRFs and their association with cognitive performance in a sample of older adults (65-85 years old) with Mild Cognitive Impairment (MCI). Participants ( = 185) were divided into three groups concerning their cardiovascular risk level determined by the presence of different CVRFs, including Type 2 Diabetes (T2D), dyslipidemia, hypertension, and obesity.

Tanycytes release glucose using the glucose-6-phosphatase system during hypoglycemia to control hypothalamic energy balance.

Objective: The liver releases glucose into the blood using the glucose-6-phosphatase (G6Pase) system, a multiprotein complex located in the endoplasmic reticulum (ER). Here, we show for the first time that the G6Pase system is also expressed in hypothalamic tanycytes, and it is required to regulate energy balance.

Methods: Using automatized qRT-PCR and immunohistochemical analyses, we evaluated the expression of the G6Pase system.

Dehydroascorbic acid sensitizes cancer cells to system x inhibition-induced ferroptosis by promoting lipid droplet peroxidation.

Since the discovery of ferroptosis, it has been postulated that this type of cell death could be utilized in treatments for cancer. Unfortunately, several highly aggressive tumor models are resistant to the pharmacological induction of ferroptosis. However, with the use of combined therapies, it is possible to recover sensitivity to ferroptosis in certain cellular models.

Hyperglycemia increases SCO-spondin and Wnt5a secretion into the cerebrospinal fluid to regulate ependymal cell beating and glucose sensing.

Hyperglycemia increases glucose concentrations in the cerebrospinal fluid (CSF), activating glucose-sensing mechanisms and feeding behavior in the hypothalamus. Here, we discuss how hyperglycemia temporarily modifies ependymal cell ciliary beating to increase hypothalamic glucose sensing. A high level of glucose in the rat CSF stimulates glucose transporter 2 (GLUT2)-positive subcommissural organ (SCO) cells to release SCO-spondin into the dorsal third ventricle.

María Teresa Miras Portugal: a pioneer in the study of purinoceptors in chromaffin cells.

María Teresa Miras Portugal devoted most of her scientific life to the study of purinergic signalling. In an important part of her work, she used a model system: the chromaffin cells of the adrenal medulla. It was in these cells that she identified diadenosine polyphosphates, from which she proceeded to the study of adrenomedullary purinome: nucleotide synthesis and degradation, adenosine transport, nucleotide uptake into chromaffin granules, exocytotic release of nucleotides and autocrine regulation of chromaffin cell function via purinoceptors.

Pharmacological targets for the induction of ferroptosis: Focus on Neuroblastoma and Glioblastoma.

Neuroblastomas are the main extracranial tumors that affect children, while glioblastomas are the most lethal brain tumors, with a median survival time of less than 12 months, and the prognosis of these tumors is poor due to multidrug resistance. Thus, the development of new therapies for the treatment of these types of tumors is urgently needed. In this context, a new type of cell death with strong antitumor potential, called ferroptosis, has recently been described.

Influence of Maternal Diabetes on the Risk of Neurodevelopmental Disorders in Offspring in the Prenatal and Postnatal Periods.

Background: This study aimed to evaluate the influence of maternal diabetes in the risk of neurodevelopmental disorders in offspring in the prenatal and postnatal periods.

Methods: This cohort study included singleton gestational diabetes mellitus (GDM) pregnancies >22 weeks' gestation with live newborns between 1991 and 2008. The control group was randomly selected and matched (1:2) for maternal age, weeks of gestation and birth year.

β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models.

Transient receptor potential melastatin subtype 8 (TRPM8) is a cation channel extensively expressed in sensory neurons and implicated in different painful states. However, the effectiveness of TRPM8 modulators for pain relief is still a matter of discussion, since structurally diverse modulators lead to different results, depending on the animal pain model. In this work, we described the antinociceptive activity of a β-lactam derivative, RGM8-51, showing good TRPM8 antagonist activity, and selectivity against related thermoTRP channels and other pain-mediating receptors.

In vitro inhibition of phosphodiesterase type 4 enhances rat corpus cavernosum nerve-mediated relaxation induced by gasotransmitters.

Aims: Nitric oxide (NO) and hydrogen sulfide (HS) are involved in nerve-mediated corpus cavernosum (CC) relaxation. Expression of phosphodiesterase type 5 (PDE5) and type 4 (PDE4), cyclic guanosine monophosphate (cGMP)- and cyclic adenosine monophosphate (cAMP)-specific, respectively, has been described and PDE5- and PDE4-inhibitors induce cavernous smooth muscle relaxation. Whereas the NO/cGMP signaling pathway is well established in penile erection, the cAMP-mediated mechanism is not fully elucidated.

IQM-PC332, a Novel DREAM Ligand with Antinociceptive Effect on Peripheral Nerve Injury-Induced Pain.

Neuropathic pain is a form of chronic pain arising from damage of the neural cells that sense, transmit or process sensory information. Given its growing prevalence and common refractoriness to conventional analgesics, the development of new drugs with pain relief effects constitutes a prominent clinical need. In this respect, drugs that reduce activity of sensory neurons by modulating ion channels hold the promise to become effective analgesics.

Venous outflow banding for maturation of a percutaneous arteriovenous fistula.

In the present report, we have described venous outflow banding as a technique to assist with maturation of a percutaneous arteriovenous fistula (pAVF) without sacrificing potential target veins for future access. A 47-year-old obese man had undergone pAVF creation between the right ulnar vessels with coil embolization of the brachial vein. Follow-up imaging demonstrated the median cubital vein briskly filling the cephalic and basilic veins.

Novel glycoproteins identify preclinical atherosclerosis among women with previous preeclampsia regardless of type 1 diabetes status.

Background And Aims: Information regarding inflammation and cardiovascular disease (CVD) risk in type 1 diabetes (T1D) or preeclampsia (PE) is scarce. We assessed differences in inflammation markers according to the presence of both conditions and their association with atherosclerosis.

Methods And Results: We recruited 112 women without CVD and last pregnancy ≥5 years previously (n = 28 per group): a)T1D and PE; b)T1D without PE; c)PE without T1D; and d)Controls (without T1D or PE).

SVCT2 Overexpression and Ascorbic Acid Uptake Increase Cortical Neuron Differentiation, Which Is Dependent on Vitamin C Recycling between Neurons and Astrocytes.

During brain development, sodium-vitamin C transporter (SVCT2) has been detected primarily in radial glial cells in situ, with low-to-absent expression in cerebral cortex neuroblasts. However, strong SVCT2 expression is observed during the first postnatal days, resulting in increased intracellular concentration of vitamin C. Hippocampal neurons isolated from SVCT2 knockout mice showed shorter neurites and low clustering of glutamate receptors.

Two Distinct Faces of Vitamin C: AA vs. DHA.

Historically, vitamin C has been associated with many regulatory processes that involve specific signaling pathways. Among the most studied signaling pathways are those involved in the regulation of aging, differentiation, neurotransmission, proliferation, and cell death processes in cancer. This wide variety of regulatory effects is due to the fact that vitamin C has a dual mechanism of action.

Tympanic Membrane Rupture During Stereotaxic Surgery Disturbs the Normal Feeding Behavior in Rats.

Stereotactic surgery is a widely used procedure in neuroscience research to study the brain's regulation of feeding behavior. In line with this notion, this study aims to assess how food consumption and feeding patterns are affected in response to the use of auditory bars that preserve or damage the tympanic membrane during stereotactic surgery. Our previous observations led us to hypothesize that the traumatic tympanic membrane rupture affects food intake and feeding patterns in rats undergoing stereotactic procedures.

Nuclear magnetic resonance-based metabolomic analysis in the assessment of preclinical atherosclerosis in type 1 diabetes and preeclampsia.

Aims: Evaluate the role of plasma metabolomics in atherosclerosis according to the presence of type 1 diabetes (T1D) or previous preeclampsia.

Methods: We recruited 105 women without cardiovascular disease and last pregnancy ≥5 years previously, divided according to the presence of T1D or previous preeclampsia. Preclinical atherosclerosis was defined as the presence of carotid plaque (intima-media thickness ≥1.

Hydrogel-based 3D bioprints repair rat small intestine injuries and integrate into native intestinal tissue.

3D Printing has become a mainstay of industry, with several applications in the medical field. One area that could benefit from 3D printing is intestinal failure due to injury or genetic malformations. We bioprinted cylindrical tubes from rat vascular cells that were sized to form biopatches.

Penicillin G Induces H+, K+-ATPase via a Nitric Oxide-Dependent Mechanism in the Rat Colonic Crypt.

Background/aims: The colonic H, K ATPase (HKA2) is a heterodimeric membrane protein that exchanges luminal K for intracellular H and is involved in maintaining potassium homeostasis. Under homeostatic conditions, the colonic HKA2 remains inactive, since most of the potassium is absorbed by the small intestine. In diarrheal states, potassium is secreted and compensatory potassium absorption becomes necessary.

The Adrenal Medulla Modulates Mechanical Allodynia in a Rat Model of Neuropathic Pain.

We have investigated whether the stress response mediated by the adrenal medulla in rats subjected to chronic constriction injury of the sciatic nerve (CCI) modulates their nocifensive behavior. Treatment with SK29661 (300 mg/kg; intraperitoneal (I.P.

The FGF2-induced tanycyte proliferation involves a connexin 43 hemichannel/purinergic-dependent pathway.

In the adult hypothalamus, the neuronal precursor role is attributed to the radial glia-like cells that line the third-ventricle (3V) wall called tanycytes. Under nutritional cues, including hypercaloric diets, tanycytes proliferate and differentiate into mature neurons that moderate body weight, suggesting that hypothalamic neurogenesis is an adaptive mechanism in response to metabolic changes. Previous studies have shown that the tanycyte glucosensing mechanism depends on connexin-43 hemichannels (Cx43 HCs), purine release, and increased intracellular free calcium ion concentration [(Ca ) ] mediated by purinergic P2Y receptors.

The SEEN comprehensive clinical survey of adult obesity: Executive summary.

Obesity is one of the great challenges in healthcare nowadays with important implications for health so requiring comprehensive management. This document aims to establish practical and evidence-based recommendations for the diagnosis and management of in Spain, from the perspective of the clinical endocrinologist. A position statement has been made that can be consulted at www.

Higher risk of urinary tract infections in renal transplant recipients receiving pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis pneumonia prophylaxis.

Urinary tract infection (UTI) is one of the most common infectious complications among renal transplant patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is routinely used as first-line prophylaxis against Pneumocystis pneumonia (PCP) and other opportunistic infections including UTI. Aerosolized pentamidine is an alternate agent used for PCP prophylaxis; however, it does not provide coverage against uropathogens.

Human Small Intestine Transplantation: Segmental Susceptibility to Ischemia Using Different Preservation Solutions and Conditions.

Background And Aims: Among all transplanted abdominal organs, the small intestine is one of the most ischemia sensitive. Appropriate graft selection, procurement, and preservation are crucial for optimum graft and patient survival. We evaluated ischemic damage in human small intestine grafts under different hypothermic preservation conditions (cold static and continuous perfusion) and solutions: histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW).