Molecular imaging has revolutionised the field of biomedical research by providing a non-invasive means to visualise and understand biochemical processes within living organisms. Optical fluorescent imaging in particular allows researchers to gain valuable insights into the dynamic behaviour of a target of interest in real time. Ion channels play a fundamental role in cellular signalling, and they are implicated in diverse pathological conditions, making them an attractive target in the field of molecular imaging.
View Article and Find Full Text PDFComp Biochem Physiol C Toxicol Pharmacol
September 2024
In this study, we report the innovative application of whole-cell patch-clamp electrophysiology in assessing broad-spectrum neutralisation by three different antivenoms, of venoms from the medically significant scorpion genus Centruroides. Envenomations by as many as 21 species from the Centruroides genus result in up to 300,000 envenomations per year in Mexico, which poses significant and potentially life-threatening pathophysiology. We first evaluated the in vitro manifestation of envenomation against two human voltage-gated sodium (hNa) channel subtypes: hNa1.
View Article and Find Full Text PDFIntroduction: Deep learning (DL) models predicting biomarker expression in images of hematoxylin and eosin (H&E)-stained tissues can improve access to multi-marker immunophenotyping, crucial for therapeutic monitoring, biomarker discovery, and personalized treatment development. Conventionally, these models are trained on ground truth cell labels derived from IHC-stained tissue sections adjacent to H&E-stained ones, which might be less accurate than labels from the same section. Although many such DL models have been developed, the impact of ground truth cell label derivation methods on their performance has not been studied.
View Article and Find Full Text PDFDespite the recent advances in understanding the mechanisms of olfaction, no tools are currently available to noninvasively identify loss of smell. Because of the substantial increase in patients presenting with coronavirus disease 2019-related loss of smell, the pandemic has highlighted the urgent need to develop quantitative methods. Our group investigated the use of a novel fluorescent probe named Tsp1a-IR800 as a tool to diagnose loss of smell.
View Article and Find Full Text PDFSurgeries and trauma result in traumatic and iatrogenic nerve damage that can result in a debilitating condition that approximately affects 189 million individuals worldwide. The risk of nerve injury during oncologic surgery is increased due to tumors displacing normal nerve location, blood turbidity, and past surgical procedures, which complicate even an experienced surgeon's ability to precisely locate vital nerves. Unfortunately, there is a glaring absence of contrast agents to assist surgeons in safeguarding vital nerves.
View Article and Find Full Text PDFOur case is an asymptomatic, non-smoking, East Asian woman in her 40s presenting with a solitary pulmonary nodule (SPN). On imaging, the 1.7 cm solid SPN located in the left upper lobe, was rounded in morphology and moderately fluorodeoxyglucose avid.
View Article and Find Full Text PDFCurr Opin Pulm Med
January 2024
Purpose Of Review: Lung cancer is one of the most common malignancies in the whole world, and the pulmonologist is generally the first medical professional to meet the patient and decide what method of tumour sampling is preferable in each specific case. It is imperative for pulmonary physicians to be aware of the intricacies of the diagnostic process, and understand the multiple challenges that are encountered, from the moment the tissue specimen leaves their offices and is sent to the pathology laboratory, until the diagnosis reaches the patient and treating physician.
Recent Findings: The new 2021 WHO classification of thoracic tumours recommended a minimum immunohistochemical (IHC) diagnostic panel for nonsmall cell lung cancer (NSCLC), and following publications of different institutional and country-based guidelines, advocated basic molecular testing for epithelial growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and programmed cell death ligand 1 (PD-L1) to be initiated by the diagnosing pathologist in all cases of biopsy or resection specimens.
Thoracic SMARCA4-deficient undifferentiated tumour (SMARCA4-UT) is an unusual and aggressive tumour. While there are approximately 100 cases of this tumour reported in the literature, there are very few detailed descriptions of its cytomorphologic characteristics, and only rare cases in which primary diagnosis was made on cytologic material. Herein we present a case with a detailed description of the appearance on three specimen types: transbronchial needle aspiration (TBNA) cytology, transbronchial needle biopsy (TBNB) and effusion cytology.
View Article and Find Full Text PDFWe report an innovative approach to producing bacteriochlorins (bacs) via formal cycloaddition by subjecting a porphyrin to a trimolecular reaction. Bacs are near-infrared probes with the intrinsic ability to serve in multimodal imaging. However, despite their ability to fluoresce and chelate metal ions, existing bacs have thus offered limited ability to label biomolecules for target specificity or have lacked chemical purity, limiting their use in bio-imaging.
View Article and Find Full Text PDFChronic pelvic pain (CPP) is the primary symptom of endometriosis patients, but adequate treatments are lacking. Modulation of ion channels expressed by sensory nerves innervating the viscera has shown promise for the treatment of irritable bowel syndrome and overactive bladder. However, similar approaches for endometriosis-associated CPP remain underdeveloped.
View Article and Find Full Text PDFThe sense of smell (olfaction) is one of the most important senses for animals including humans. Despite significant advances in the understanding mechanism of olfaction, currently, there are no objective non-invasive methods that can identify loss of smell. Covid-19-related loss of smell has highlighted the need to develop methods that can identify loss of olfaction.
View Article and Find Full Text PDFα-Conotoxins that target muscle nicotinic acetylcholine receptors (nAChRs) commonly fall into two structural classes, frameworks I and II containing two and three disulfide bonds, respectively. Conotoxin SII is the sole member of the cysteine-rich framework II with ill-defined interactions at the nAChRs. Following directed synthesis of α-SII, NMR analysis revealed a well-defined structure containing a 3-helix frequently employed by framework I α-conotoxins; α-SII acted at the muscle nAChR with half-maximal inhibitory concentrations (IC) of 120 nM (adult) and 370 nM (fetal) though weakly at neuronal nAChRs.
View Article and Find Full Text PDFThe human nociceptor-specific voltage-gated sodium channel 1.7 (hNa1.7) is critical for sensing various types of somatic pain, but it appears not to play a primary role in acute visceral pain.
View Article and Find Full Text PDFBackground: Ischemia-reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the buildup of acidic metabolites results in decreased intracellular and extracellular pH, which can reach as low as 6.0 to 6.
View Article and Find Full Text PDFX-linked hypophosphatemia (XLH) is the most prevalent form of hereditary hypophosphatemic rickets associated with phosphate wasting. However, its diagnosis is often missed, resulting in patients presenting late in the course of the disease when complications such as tertiary hyperparathyroidism and renal failure have already set in. Phosphate and calcitriol replacement, both of which have undesirable consequences of their own, have historically been the main stay of therapy.
View Article and Find Full Text PDFIn 2006, humans with a congenital insensitivity to pain (CIP) were found to lack functional Na 1.7 channels. In the subsequent 15 years there was a rush to develop selective inhibitors of Na 1.
View Article and Find Full Text PDFEpilepsy is characterised by spontaneous recurrent seizures that are caused by an imbalance between neuronal excitability and inhibition. Since ion channels play fundamental roles in the generation and propagation of action potentials as well as neurotransmitter release at a subset of excitatory and inhibitory synapses, their dysfunction has been linked to a wide variety of epilepsies. Indeed, these unique proteins are the major biological targets for antiepileptic drugs.
View Article and Find Full Text PDFBackground: Accidental peripheral nerve injury during surgical intervention results in a broad spectrum of potentially debilitating side effects. Tissue distortion and poor visibility can significantly increase the risk of nerve injury with long-lasting consequences for the patient. We developed and characterized Hs1a-FL, a fluorescent near-infrared molecule for nerve visualization in the operating theater with the aim of helping physicians to visualize nerves during surgery.
View Article and Find Full Text PDFDravet syndrome (DS) is a catastrophic epileptic encephalopathy characterised by childhood-onset polymorphic seizures, multiple neuropsychiatric comorbidities, and increased risk of sudden death. Heterozygous loss-of-function mutations in one allele of SCN1A, the gene encoding the voltage-gated sodium channel 1.1 (Na1.
View Article and Find Full Text PDFVoltage-gated sodium (Na) channels play a fundamental role in normal neurological function, especially via the initiation and propagation of action potentials. The Na1.1 subtype is found in inhibitory interneurons of the brain and it is essential for maintaining a balance between excitation and inhibition in neuronal networks.
View Article and Find Full Text PDFRecently, we and other groups revealed that gain-of-function mutations in the human ether à go-go voltage-gated potassium channel hEAG1 (K10.1) lead to developmental disorders with associated infantile-onset epilepsy. However, the physiological role of hEAG1 in the central nervous system remains elusive.
View Article and Find Full Text PDFDravet syndrome is a catastrophic, pharmacoresistant epileptic encephalopathy. Disease onset occurs in the first year of life, followed by developmental delay with cognitive and behavioral dysfunction and substantially elevated risk of premature death. The majority of affected individuals harbor a loss-of-function mutation in one allele of , which encodes the voltage-gated sodium channel Na1.
View Article and Find Full Text PDFGating modifier toxins (GMTs) are venom-derived peptides isolated from spiders and other venomous creatures and modulate activity of disease-relevant voltage-gated ion channels and are therefore being pursued as therapeutic leads. The amphipathic surface profile of GMTs has prompted the proposal that some GMTs simultaneously bind to the cell membrane and voltage-gated ion channels in a trimolecular complex. Here, we examined whether there is a relationship among spider GMT amphipathicity, membrane binding, and potency or selectivity for voltage-gated sodium (Na) channels.
View Article and Find Full Text PDFVoltage-gated sodium (NaV) channels are responsible for propagating action potentials in excitable cells. NaV1.7 plays a crucial role in the human pain signalling pathway and it is an important therapeutic target for treatment of chronic pain.
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