Diabetes, periodontitis, and cardiovascular disease: towards equity in diabetes care.

Type 2 diabetes and its associated cardiovascular risk is an escalating epidemic that represents a significant public health burden due to increased morbidity and mortality, disproportionately affecting disadvantaged communities. Poor glycaemic control exacerbates this burden by increasing retinal, renal, and cardiac damage and raising healthcare costs. This predicament underscores the urgent need for research into cost-effective approaches to preventing diabetes complications.

HER2 classification in breast cancer cells: A new explainable machine learning application for immunohistochemistry.

The immunohistochemical (IHC) evaluation of epidermal growth factor 2 (HER2) for the diagnosis of breast cancer is still qualitative with a high degree of inter-observer variability, and thus requires the incorporation of complementary techniques such as fluorescent hybridization (FISH) to resolve the diagnosis. Implementing automatic algorithms to classify IHC biomarkers is crucial for typifying the tumor and deciding on therapy for each patient with better performance. The present study aims to demonstrate that, using an explainable Machine Learning (ML) model for the classification of HER2 photomicrographs, it is possible to determine criteria to improve the value of IHC analysis.

Estrogen, Cognitive Performance, and Functional Imaging Studies: What Are We Missing About Neuroprotection?

Menopause transition can be interpreted as a vulnerable state characterized by estrogen deficiency with detrimental systemic effects as the low-grade chronic inflammation that appears with aging and partly explains age-related disorders as cancer, diabetes mellitus and increased risk of cognitive impairment. Over the course of a lifetime, estrogen produces several beneficial effects in healthy neurological tissues as well as cardioprotective effects, and anti-inflammatory effects. However, clinical evidence on the efficacy of hormone treatment in menopausal women has failed to confirm the benefit reported in observational studies.

Estrogen rapid effects: a window of opportunity for the aging brain?

Estrogen produces several beneficial effects in healthy neurological tissues and exhibits cardioprotective effects. Hormone therapy has been widely used to treat menopausal estrogen deficiency for more than 80 years. Despite high initial expectations of cardioprotective effects, there has been substantial distrust following important randomized clinical trials, such as the Women's Health Initiative.

Optogenetic control of cancer cell survival in ChR2-transfected HeLa cells.

Optogenetics is a molecular biological technique involving transfection of cells with photosensitive proteins and the subsequent study of their biological effects. The aim of this study was to evaluate the effect of blue light on the survival of HeLa cells, transfected with channelrhodopsin-2 (ChR2). HeLa wild-type cells were transfected with a plasmid that contained the gene for ChR2.

TRPV1-Estradiol Stereospecific Relationship Underlies Cell Survival in Oxidative Cell Death.

17β-estradiol is a neuronal survival factor against oxidative stress that triggers its protective effect even in the absence of classical estrogen receptors. The polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channel has been proposed as a steroid receptor implied in tissue protection against oxidative damage. We show here that TRPV1 is sufficient condition for 17β-estradiol to enhance metabolic performance in injured cells.

Intracellular aggregated TRPV1 is associated with lower survival in breast cancer patients.

Background: Breast cancer is a malignant disease that represents an important public health burden. The description of new molecular markers can be important to diagnosis, classification, and treatment. Transient receptor potential vanilloid 1 (TRPV1) polymodal channel is expressed in different neoplastic tissues and cell lines of breast cancer and associated with the regulation of tumor growth, tumor neurogenesis, cancer pain, and malignant progression of cancer.

Proteostasis and Mitochondrial Role on Psychiatric and Neurodegenerative Disorders: Current Perspectives.

Proteostasis involves processes that are fundamental for neural viability. Thus, protein misfolding and the formation of toxic aggregates at neural level, secondary to dysregulation of the conservative mechanisms of proteostasis, are associated with several neuropsychiatric conditions. It has been observed that impaired mitochondrial function due to a dysregulated proteostasis control system, that is, ubiquitin-proteasome system and chaperones, could also have effects on neurodegenerative disorders.

Transient Receptor Potential Vanilloid 1 Expression Mediates Capsaicin-Induced Cell Death.

The transient receptor potential (TRP) ion channel family consists of a broad variety of non-selective cation channels that integrate environmental physicochemical signals for dynamic homeostatic control. Involved in a variety of cellular physiological processes, TRP channels are fundamental to the control of the cell life cycle. TRP channels from the vanilloid (TRPV) family have been directly implicated in cell death.

TRPV1 may increase the effectiveness of estrogen therapy on neuroprotection and neuroregeneration.

Aging induces physical deterioration, loss of the blood brain barrier, neuronal loss-induced mental and neurodegenerative diseases. Hypotalamus-hypophysis-gonad axis aging precedes symptoms of menopause or andropause and is a major determinant of sensory and cognitive integrated function. Sexual steroids support important functions, exert pleiotropic effects in different sensory cells, promote regeneration, plasticity and health of the nervous system.

Keratitis-ichthyosis-deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43.

Mutations in Cx26 gene are found in most cases of human genetic deafness. Some mutations produce syndromic deafness associated with skin disorders, like the Keratitis-Ichthyosis-Deafness syndrome (KID). Because in the human skin connexin 26 (Cx26) is co-expressed with other connexins, like Cx43 and Cx30, and as the KID syndrome is inherited as autosomal dominant condition, it is possible that KID mutations change the way Cx26 interacts with other co-expressed connexins.

Molecular determinants of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) binding to transient receptor potential V1 (TRPV1) channels.

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) has been recognized as an important activator of certain transient receptor potential (TRP) channels. More specifically, TRPV1 is a pain receptor activated by a wide range of stimuli. However, whether or not PI(4,5)P2 is a TRPV1 agonist remains open to debate.

Hydrogen peroxide removes TRPM4 current desensitization conferring increased vulnerability to necrotic cell death.

Necrosis is associated with an increase in plasma membrane permeability, cell swelling, and loss of membrane integrity with subsequent release of cytoplasmic constituents. Severe redox imbalance by overproduction of reactive oxygen species is one of the main causes of necrosis. Here we demonstrate that H(2)O(2) induces a sustained activity of TRPM4, a Ca(2+)-activated, Ca(2+)-impermeant nonselective cation channel resulting in an increased vulnerability to cell death.

Activation of Cl- channels by human chorionic gonadotropin in luteinized granulosa cells of the human ovary modulates progesterone biosynthesis.

Chloride permeability pathways and progesterone (P4) secretion elicited by human chorionic gonadotropin (hCG) in human granulosa cells were studied by electrophysiological techniques and single-cell volume, membrane potential and Ca2+i measurements. Reduction in extracellular Cl(-) and equimolar substitution by the membrane-impermeant anions glutamate or gluconate significantly increased hCG-stimulated P4 accumulation. A similar result was achieved by exposing the cells to hCG in the presence of a hypotonic extracellular solution.

Activation of H2O2-induced VSOR Cl- currents in HTC cells require phospholipase Cgamma1 phosphorylation and Ca2+ mobilisation.

Volume-sensitive outwardly rectifying (VSOR) Cl(-) channels participate in several physiological processes such as regulatory volume decrease, cell cycle regulation, proliferation and apoptosis. Recent evidence points to a significant role of hydrogen peroxide (H(2)O(2)) in VSOR Cl(-) channel activation. The aim of this study was to determine the signalling pathways responsible for H(2)O(2)-induced VSOR Cl(-) channel activation.

Calcium modulates osmosensitive taurine efflux in HeLa cells.

The role of Ca2+ in the signaling transduction pathway involved in osmosensitive taurine efflux in HeLa cells was studied using radiotracer efflux techniques. Taurine efflux induced by extracellular hypotonicity was decreased by 85% by removal of extracellular Ca2+ and simultaneous depletion of intracellular Ca2+ stores with thapsigargin. Extracellular Ca2+ removal, thapsigargin treatment, or addition of Gd3+ all decreased taurine efflux by approximately 50%.

Cell volume regulation in response to hypotonicity is impaired in HeLa cells expressing a protein kinase Calpha mutant lacking kinase activity.

The chloride conductance (G(Cl,swell)) that participates in the regulatory volume decrease process triggered by osmotic swelling in HeLa cells was impaired by removal of extracellular Ca(2+), depletion of intracellular Ca(2+) stores with thapsigargin, or by preloading the cells with BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). Furthermore, overnight exposure to the phorbol ester tetradecanoyl phorbol acetate and acute incubation with inhibitors of the conventional protein kinase C (PKC) isoforms bisindolylmaleimide I and Gö6976 inhibited G(Cl,swell). Treatment of HeLa cells with U73122, a phospholipase C inhibitor, also prevented G(Cl,swell).