Anderson-Fabry disease (AFD) is a rare genetic disease with X-linked transmission characterized by a defect in the enzyme alpha-galactosidase A, which impairs glycosphingolipid metabolism and leads to an excessive storage of globotriaosylceramide (Gb3) within lysosomes. AFD involves renal, cardiac, vascular, and nervous systems and is mainly observed in male patients with onset in childhood, although cardiac manifestation is often shown in adults. AFD cardiomyopathy is caused by the accumulation of Gb3 within myocytes first showed by left ventricular hypertrophy and diastolic dysfunction, leading to restrictive cardiomyopathy and systolic heart failure with biventricular involvement. The diagnosis of AFD cardiomyopathy may be insidious in the first stages and requires accurate differential diagnosis with other cardiomyopathies with hypertrophic phenotype. However, it is fundamental to promptly initiate specific therapies that have shown promising results, particularly for early treatment. A careful integration between clinical evaluation, genetic tests, and cardiac imaging is required to diagnose AFD with cardiac involvement. Basic and advanced echocardiography, cardiac magnetic resonance, and nuclear imaging may offer pivotal information for early diagnosis (Graphical Abstract), and the management of these patients is often limited to centres with high expertise in the field. This clinical consensus statement, developed by experts from the European Society of Cardiology (ESC) Working Group on Myocardial and Pericardial Diseases and the European Association of Cardiovascular Imaging of the ESC, aims to provide practical advice for all clinicians regarding the use of multimodality imaging to simplify the diagnostic evaluation, prognostic stratification, and management of cardiac involvement in AFD.
- Klíčová slova
- Anderson–Fabry disease, diagnosis, imaging, left ventricular hypertrophy, treatment,
- MeSH
- časná diagnóza MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- dospělí MeSH
- echokardiografie metody normy MeSH
- Fabryho nemoc * diagnostické zobrazování terapie MeSH
- konsensus MeSH
- lidé MeSH
- multimodální zobrazování * metody normy MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
Behavioral sensitization is a phenomenon occurring after repeated administration of various psychotropic substances and it is characterized by gradually increasing response to the particular drug. It has been described for majority of addictive substances including amphetamines. It is considered to reinstate drug-seeking behaviour and plays important role in the processes associated with drug abuse and addiction. There are published reports, particularly on preclinical level, that N-acetylcysteine (NAC) may affect addictive properties of different classes of drugs (e.g., cocaine, heroin, alcohol, cannabinoids, nicotine). Since the lack of information on possible effects of NAC on amphetamine derivatives we decided to test possible influence of this substance on behavioral sensitization to methamphetamine (MET) in the mouse open field test. Our results have shown a decreased acute stimulatory effect of MET caused by NAC and moreover, there was a non-significant trend of attenuated development of behavioral sensitization to MET after simultaneous long-term administration of MET and NAC. This suppression of MET stimulatory effects therefore suggested on the preclinical level possible promising efficacy of NAC on addictive properties associated with MET similarly as it was demonstrated by other authors in association with cocaine or heroin. Key words: N-acetylcysteine, Methamphetamine, Behavioral sensitization.
- MeSH
- acetylcystein * farmakologie aplikace a dávkování MeSH
- chování zvířat * účinky léků MeSH
- methamfetamin * farmakologie aplikace a dávkování MeSH
- myši MeSH
- stimulanty centrálního nervového systému * farmakologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acetylcystein * MeSH
- methamfetamin * MeSH
- stimulanty centrálního nervového systému * MeSH
This study investigates the association between serum glutathione (GSH) and malondialdehyde (MDA) levels and early neurological deficits and short-term outcomes in individuals with acute cerebral infarction (ACI). The study included 114 patients with ACI within 48 hours of symptom onset, between January and August 2023, alongside 96 healthy individuals as a control group. Neurological deficits were assessed using the National Institute of Health Stroke Scale (NIHSS), classifying deficits as mild (<5) or moderate to severe (>/=5). Associations between GSH and MDA levels with early neurological deficits were analyzed. Short-term prognosis, assessed three months post-discharge using the Modified Rankin Scale (mRS), was examined in relation to GSH and MDA levels in patients with ACI. Independent predictors of neurological deficits and short-term outcomes were identified through binary logistic regression analysis. Compared to the control group, patients with ACI had higher rates of hypertension, diabetes, smoking, and alcohol consumption. Additionally, elevated levels of MDA, glycated hemoglobin, triglycerides, C-reactive protein (CRP), and D-dimer levels were observed, whereas GSH and high-density lipoprotein (HDL) levels were lower. Among those with moderate to severe ACI, levels of CRP, MDA, triglycerides, low-density lipoprotein (LDL), uric acid, and D-dimer levels were higher compared to mild ACI, while HDL and GSH levels were significantly lower. Low serum GSH levels and elevated MDA levels are associated with early neurological deficits and short-term prognosis in ACI, serving as independent risk factors for adverse prognosis. The combined assessment of MDA, infarct volume, and LDL provides enhanced predictive value for adverse prognosis in patients with ACI. Keywords: Acute cerebral infarction, Malondialdehyde, Neurological deficits, Serum glutathione, Short-term prognosis.
- MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- cerebrální infarkt * krev diagnóza komplikace MeSH
- glutathion * krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- malondialdehyd * krev MeSH
- nemoci nervového systému * krev diagnóza etiologie MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- glutathion * MeSH
- malondialdehyd * MeSH
Stroke and cerebral ischemia/reperfusion (IR) injury are severe conditions characterized by impaired blood flow to the brain, leading to tissue infarction and neurological impairments. Panax notoginseng saponins (PNS) have displayed various beneficial effects in alleviating cerebrovascular disorders. This study aimed to investigate the neuroprotective capacity of PNS in a rat model of middle cerebral artery occlusion (MCAO)-induced cerebral IR injury, focusing specifically on understanding the involvement of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in mediating this protective effect. Male Sprague-Dawley rats (n=45, weighing 250-280g and aged 12 weeks) were utilized in this experiment. Cerebral IR injury was induced by subjecting the rats to 30 minutes of MCAO followed by 24 hours of reperfusion. Prior to the surgery, PNS (120mg/kg) was administered once daily via gavage for 14 days. The evaluation measures included assessing cerebral infarct volume, neurological function using the Longa method, conducting histopathological analysis, examining the expression of SIRT1, Nrf2, and HO-1 genes and proteins, as well as measuring the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA). Pretreatment with PNS markedly decreased infarct volume, enhanced neurological function, and mitigated histopathological alterations. Additionally, PNS intake resulted in the upregulation of SIRT1, Nrf2, and HO-1 genes and proteins, boosted enzymatic antioxidant activity, and lowered MDA levels, pointing towards a diminution in oxidative stress. The multifaceted antioxidant and neuroprotective properties of PNS underscore its promising role in preserving neuronal function, mitigating oxidative damage, and promoting tissue survival in ischemic conditions. These benefits were associated with the modulation of the SIRT1/Nrf2/HO-1 signaling pathway, emphasizing the therapeutic significance of PNS in addressing cerebral IR injury and related neurological complications. Key words: Ischemia/reperfusion injury, Neuroprotection, Oxidative stress, Panax notoginseng saponins, Stroke.
- MeSH
- faktor 2 související s NF-E2 * metabolismus MeSH
- hemová oxygenasa (decyklizující) MeSH
- infarkt arteria cerebri media farmakoterapie patologie MeSH
- ischemie mozku * metabolismus patologie farmakoterapie MeSH
- krysa rodu Rattus MeSH
- neuroprotektivní látky * farmakologie terapeutické užití MeSH
- Panax notoginseng * chemie MeSH
- potkani Sprague-Dawley MeSH
- reperfuzní poškození * metabolismus prevence a kontrola patologie farmakoterapie MeSH
- saponiny * farmakologie terapeutické užití izolace a purifikace MeSH
- signální transdukce účinky léků MeSH
- sirtuin 1 * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- faktor 2 související s NF-E2 * MeSH
- hemová oxygenasa (decyklizující) MeSH
- Hmox1 protein, rat MeSH Prohlížeč
- neuroprotektivní látky * MeSH
- Nfe2l2 protein, rat MeSH Prohlížeč
- saponiny * MeSH
- Sirt1 protein, rat MeSH Prohlížeč
- sirtuin 1 * MeSH
Subarachnoid hemorrhage (SAH) is a critical neurological emergency and one of the leading causes of stroke. Neuronal demise serves as the primary factor contributing to early brain injury (EBI) following SAH. This study aims to investigate the molecular mechanism underlying Hirudin's impact on EBI after SAH, with a particular focus on pyroptosis. The SAH rat model was established by performing intravascular puncture, followed by the administration of Hirudin and Nod-like receptor protein 3 (NLRP3) agonist Nigericin into the lateral ventricle. The SAH grading, neurological score, brain water content, blood-brain barrier (BBB) permeability, neuronal damage, inflammatory reaction, neuronal death, distribution of microglia marker Iba-1 and expression levels of NLRP3 inflammasomal-related proteins were evaluated at 72 h post-SAH. Hirudin treatment significantly ameliorated neurological scores and attenuated brain edema, BBB permeability, inflammatory response, microglia activation, and pyroptosis in SAH rats. Additionally, Hirudin treatment downregulated the expression levels of NLRP3 inflammasomal- related proteins, such as NLRP3, apoptosis- associated speck-like protein (ASC) and cleaved caspsase-1. However, Nigericin partially counteracted the aforementioned effects of Hirudin, indicating that Hirudin exerted its inhibitory effect on pyroptosis by modulating the NLRP3 inflammasome pathway. The neuroprotective effect of Hirudin on EBI following SAH is attributed its ability to inhibit pyroptosis mediated by NLRP3 inflammasome, suggesting its potential as a promising therapeutic approach for SAH. Keywords: Subarachnoid hemorrhage, Early brain injury, Hirudin, pyroptosis, Nod-like receptor protein 3 (NLRP3) inflammasome.
- MeSH
- hematoencefalická bariéra účinky léků metabolismus MeSH
- hirudiny * farmakologie MeSH
- inflamasomy * metabolismus MeSH
- krysa rodu Rattus MeSH
- poranění mozku * metabolismus farmakoterapie etiologie patologie MeSH
- potkani Sprague-Dawley MeSH
- protein NLRP3 * metabolismus MeSH
- pyroptóza * účinky léků fyziologie MeSH
- subarachnoidální krvácení * metabolismus farmakoterapie komplikace patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- hirudiny * MeSH
- inflamasomy * MeSH
- Nlrp3 protein, rat MeSH Prohlížeč
- protein NLRP3 * MeSH
This study systematically evaluated the therapeutic effects of podophyllotoxin in a DSS-induced mouse model of ulcerative colitis. A total of 374 podophyllotoxin-related targets were identified through database screening, and by intersecting them with 1,741 UC-related targets, 120 potential therapeutic targets were obtained. Subsequent GO and KEGG enrichment analyses revealed that these targets are primarily involved in biological processes such as the positive regulation of protein kinase B signaling, cellular response to lipopolysaccharide, and inflammatory responses, with significant enrichment in key pathways like the PI3K-Akt signaling pathway. Molecular docking results indicated that podophyllotoxin has strong binding activity with several targets related to inflammation and signal transduction. Animal experiments further validated the significant therapeutic effects of podophyllotoxin in the DSS-induced ulcerative colitis mouse model. Particularly at high doses, podophyllotoxin effectively alleviated ulcerative colitis symptoms, reduced pathological damage to colonic tissues, and enhanced intestinal barrier function. Additionally, podophyllotoxin significantly lowered the levels of inflammatory cytokines (TNF-?, IL-1?, IL-6) in the serum and colonic tissues of ulcerative colitis model mice and improved oxidative stress status. More importantly, podophyllotoxin effectively restored the impaired intestinal mucosal barrier function by enhancing the expression of tight junction proteins such as ZO-1 and occludin. Finally, the study revealed that podophyllotoxin may alleviate ulcerative colitis symptoms and promote colonic tissue repair by activating the PI3K/AKT signaling pathway. These findings provide strong experimental evidence for the potential use of podophyllotoxin as a therapeutic agent for ulcerative colitis and offer valuable insights for the future development of ulcerative colitis treatment strategies targeting the PI3K/AKT pathway. Key words: Podophyllotoxin, Ulcerative Colitis, Inflammation, PI3K/AKT.
- MeSH
- fosfatidylinositol-3-kinasy * metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- podofylotoxin * farmakologie terapeutické užití MeSH
- protoonkogenní proteiny c-akt * metabolismus MeSH
- signální transdukce účinky léků MeSH
- simulace molekulového dockingu MeSH
- síran dextranu toxicita MeSH
- ulcerózní kolitida * farmakoterapie chemicky indukované metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfatidylinositol-3-kinasy * MeSH
- podofylotoxin * MeSH
- protoonkogenní proteiny c-akt * MeSH
- síran dextranu MeSH
Fanconi anemia (FA) and ferroptosis both affect tumor-related processes. However, few studies have reported on genetic associations between FA and ferroptosis. Our study evaluated the usefulness of genes related to ferroptosis in predicting and diagnosing FA. Transcriptome sequencing data were collected from 11 normal participants and 21 patients with FA. Differential gene analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) analysis, gene correlation analysis, protein-protein interaction network analysis, qRT-PCR, and pan-cancer analysis were performed. The pan-cancer analysis was carried out based on data obtained from the GTEx and TCGA databases. Two hundred ninety-eight differentially expressed genes were detected based on the comparison of FA patients and normal participants, among which four critical non-FA genes, MAD2L1, ASPM, PCNA, and TOP2A, were identified. Among the ferroptosis-related genes, five genes, including CDKN1A, EMC2, FDFT1, HSPB1, and MT1G, were identified as being associated with FA, and the areas under the curve (AUC) of these five ferroptosis-related genes were 0.907, 0.640, 0.902, 0.840, and 0.929, respectively. The AUC for the diagnosis of FA reached 1.000 when the five ferroptosis-related genes were used in combination. In addition, the expressions of CDKN1A, EMC2, FDFT1, and HSPB1 were associated with the prognosis of multiple cancers (P<0.05). The five ferroptosis-related genes CDKN1A, EMC2, FDFT1, HSPB1, and MT1G exhibited excellent predictive effects for the diagnosis of FA.
Cell communication systems based on polypeptide ligands use transmembrane receptors to transmit signals across the plasma membrane. In their biogenesis, receptors depend on the endoplasmic reticulum (ER)-Golgi system for folding, maturation, transport and localization to the cell surface. ER stress, caused by protein overproduction and misfolding, is a well-known pathology in neurodegeneration, cancer and numerous other diseases. How ER stress affects cell communication via transmembrane receptors is largely unknown. In disease models of multiple myeloma, chronic lymphocytic leukemia and osteogenesis imperfecta, we show that ER stress leads to loss of the mature transmembrane receptors FGFR3, ROR1, FGFR1, LRP6, FZD5 and PTH1R at the cell surface, resulting in impaired downstream signaling. This is caused by downregulation of receptor production and increased intracellular retention of immature receptor forms. Reduction of ER stress by treatment of cells with the chemical chaperone tauroursodeoxycholic acid or by expression of the chaperone protein BiP resulted in restoration of receptor maturation and signaling. We show a previously unappreciated pathological effect of ER stress; impaired cellular communication due to altered receptor processing. Our findings have implications for disease mechanisms related to ER stress and are particularly important when receptor-based pharmacological approaches are used for treatment.
- Klíčová slova
- ER, Endoplasmic reticulum, Impaired, Receptor, Signaling, Stress, Transmembrane,
- MeSH
- chaperon endoplazmatického retikula BiP MeSH
- kyselina taurochenodeoxycholová farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- receptory buněčného povrchu * metabolismus MeSH
- signální transdukce * účinky léků MeSH
- stres endoplazmatického retikula * účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chaperon endoplazmatického retikula BiP MeSH
- kyselina taurochenodeoxycholová MeSH
- receptory buněčného povrchu * MeSH
- ursodoxicoltaurine MeSH Prohlížeč
In this study, we present the development of an advanced multivariable sensing platform that combines a flexible extended-gate organic thin-film transistor (ExG-OTFT) with a surface plasmon resonance (SPR) readout of its sensing surface. This device architecture overcomes the limitations of prior combined SPR and field-effect transistor (FET)-based systems, thanks to the spatial separation of the sensing surface from the transistor body, and the implementation of a pseudo-reference electrode, which significantly improves the system reliability. We demonstrate the potential of this solution through the simultaneous electrical and optical detection of layer-by-layer formation of polyelectrolyte multilayers in real-time. While the SPR-based transduction is sensitive to local refractive index changes associated with a mass uptake on the sensing surface, the electronic transduction provides complementary information about collective charge carrier distribution. The ExG-OTFT architecture ensures compatibility with commercially available SPR instrumentation, enabling straightforward upgrades to SPR/FET functionality with minimal modifications. More interestingly, we introduce a flexible SPR/FET sensor, offering a scalable, robust and cost-effective solution (thanks to the use of convenient printing techniques for the fabrication of the organic FET) for multivariable sensing applications across diverse fields to advance the next generation of sensing platforms.
- Klíčová slova
- Extended Gate-OFET, Organic electronic sensors and biosensors, SPR, Simultaneous electronic and optical detection,
- Publikační typ
- časopisecké články MeSH
In the last two decades, a school of thought emerged that perceives male reproductive health, testicular function, and sperm output as a sentry for general, somatic health. Large-scale epidemiologic studies have already linked the reduced sperm count to increased risk of chronic somatic disease (e.g., cancer, cardiovascular, neurological and bone diseases), yet most of these studies have not taken full advantage of advanced andrological analysis. Altered proteostasis, i.e., the disbalance between protein synthesis and turnover, is a common denominator of many diseases, including but not limited to cancer and neurodegenerative diseases. This chapter introduces the concept of cellular proteostasis as a measure of sperm structural and functional integrity and an endpoint of varied impacts on spermiogenesis and sperm maturation, including heritability, general health, lifestyle, and occupational and environmental reprotoxic exposure. Special consideration is given to small molecule protein modifiers, sperm-binding seminal plasma proteins, zinc-interacting proteins, and redox proteins responsible for the maintenance of protein structure and the protection of spermatozoa from oxidative damage. While the main focus is on human male infertility, serious consideration is given to relevant animal models, and in particular to male food animals with extensive records of fertility from artificial insemination services. Altogether, the proteostatic biomarker discovery and validation studies set the stage for the integration of proteomics of sperm proteostasis with genomic and high throughput phenomic approaches to benefit both human and animal reproductive medicine.
- Klíčová slova
- Biomarker, Infertility, Omics, Proteasome, Proteostasis, Seminal plasma, Sperm, Thioredoxin, Ubiquitin,
- MeSH
- fertilita * fyziologie MeSH
- homeostáze proteinů * fyziologie MeSH
- lidé MeSH
- mužská infertilita * metabolismus genetika patologie patofyziologie MeSH
- spermatogeneze * MeSH
- spermie * metabolismus patologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
