• MeSH
• interleukin-6 analýza   krev   MeSH
• kazuistiky jako téma MeSH
• lidé MeSH
• multiorgánové selhání diagnostické zobrazování   diagnóza   klasifikace   patologie   MeSH
• novorozenec s extrémně nízkou porodní hmotností MeSH
• novorozenec MeSH
• syndrom systémové zánětlivé reakce * diagnóza   etiologie   komplikace   MeSH
• ultrasonografie prenatální metody   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• kazuistiky jako téma MeSH
• kritický stav ošetřování   MeSH
• lidé MeSH
• metabolismus MeSH
• novorozenec MeSH
• novorozenecká sepse * diagnóza   etiologie   komplikace   MeSH
• parenterální výživa * metody   MeSH
• Staphylococcus epidermidis patogenita   MeSH
• živiny aplikace a dávkování   klasifikace   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• Publikační typ
• přehledy MeSH

In the previous article, the author demonstrated the close relationship between bloodletting practices in medieval Europe and acupuncture in Traditional Chinese Medicine. This study aimed to explore how acupuncture-based treatment was applied in medieval Europe. The author hypothesizes that the physical stimulation of acupuncture points associated with bloodletting was one of the main methods of pain management at that time. The study examined the indications for phlebotomy as depicted in the original illustration from Practica Medicinalis written by the 15th-century Archbishop of Prague, Sigismundus Albicus, supplemented by two other European medieval medical manuscripts. A total of 76 distinct symptoms (corresponding to 25 bloodletting acupuncture points) from the Practica Medicinalis illustration were assembled into four groups: 1) Pain and inflammation symptoms; 2) Symptoms commonly associated with pain and inflammation; 3) General symptoms affecting various organs and functions; and 4) Conditions unrelated to pain or inflammation. Among the 76 symptoms and 25 acupuncture points, only nine symptoms and a single bloodletting point were not associated with the treatment of pain or inflammation. This suggests that acupuncture-based therapy was an effective method for managing pain and inflammation in the Middle Ages and that such treatment could still be valuable from a modern clinical perspective.

• MeSH
• akupunkturní body * MeSH
• akupunkturní terapie * dějiny   MeSH
• bolest dějiny   MeSH
• dějiny středověku MeSH
• lidé MeSH
• management bolesti * dějiny   metody   MeSH
• zánět * dějiny   terapie   MeSH
• Check Tag
• dějiny středověku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• Geografické názvy
• Evropa MeSH

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging.

• MeSH
• chronická nemoc MeSH
• chronická obstrukční plicní nemoc metabolismus   farmakoterapie   imunologie   MeSH
• lidé MeSH
• metabolické sítě a dráhy * MeSH
• plicní nemoci etiologie   farmakoterapie   metabolismus   imunologie   MeSH
• stárnutí buněk * účinky léků   MeSH
• stárnutí imunologie   metabolismus   MeSH
• zánět metabolismus   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

OBJECTIVE: By exposing mice carrying a deletion of NADPH oxidase isoform 4, NOX4, specifically in pancreatic β cells (βNOX4-/-) to nutrient excess stimulated by a high-fat diet (HFD), this study aimed to elucidate the role of β-cell redox status in the development of meta-inflammation within the diabetic phenotype. METHODS: The authors performed basic phenotyping of βNOX4-/- mice on HFD involving insulin and glycemic analyses, histochemistry of adipocytes, indirect calorimetry, and cytokine analyses. To characterize local inflammation, the study used caspase-1 activity assay, interleukin-1β immunochemistry, and real-time polymerase chain reaction during coculturing of β cells with macrophages. RESULTS: The phenotype of βNOX4-/- mice on HFD was not associated with hyperinsulinemia and hyperglycemia but showed accumulation of excessive lipids in epididymal fat and β cells. Surprisingly, mice showed significantly reduced systemic inflammation. Decreased interleukin-1β protein levels and downregulated NLRP3-inflammasome activity were observed on chronic glucose overload in βNOX4-/- isolated islets and NOX4-silenced INS1-E cells resulting in attenuated proinflammatory polarization of macrophages/monocytes in vitro and in situ and reduced local islet inflammation. CONCLUSIONS: Experimental evidence suggests that NOX4 pro-oxidant activity in β cells is involved in NLRP3-inflammasome activation during chronic nutrient overload and participates in local inflammatory signaling and perhaps toward peripheral tissues, contributing to a diabetic inflammatory phenotype.

• MeSH
• diabetes mellitus * MeSH
• inflamasomy metabolismus   MeSH
• interleukin-1beta metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• NADPH-oxidasa 4 genetika   MeSH
• protein NLRP3 * metabolismus   MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Wound healing represents a complex and evolutionarily conserved process across vertebrates, encompassing a series of life-rescuing events. The healing process runs in three main phases: inflammation, proliferation, and maturation/remodelling. While acute inflammation is indispensable for cleansing the wound, removing infection, and eliminating dead tissue characterised by the prevalence of neutrophils, the proliferation phase is characterised by transition into the inflammatory cell profile, shifting towards the prevalence of macrophages. The proliferation phase involves development of granulation tissue, comprising fibroblasts, activated myofibroblasts, and inflammatory and endothelial cells. Communication among these cellular components occurs through intercellular contacts, extracellular matrix secretion, as well as paracrine production of bioactive factors and proteolytic enzymes. The proliferation phase of healing is intricately regulated by inflammation, particularly interleukin-6. Prolonged inflammation results in dysregulations during the granulation tissue formation and may lead to the development of chronic wounds or hypertrophic/keloid scars. Notably, pathological processes such as autoimmune chronic inflammation, organ fibrosis, the tumour microenvironment, and impaired repair following viral infections notably share morphological and functional similarities with granulation tissue. Consequently, wound healing emerges as a prototype for understanding these diverse pathological processes. The prospect of gaining a comprehensive understanding of wound healing holds the potential to furnish fundamental insights into modulation of the intricate dialogue between cancer cells and non-cancer cells within the cancer ecosystem. This knowledge may pave the way for innovative approaches to cancer diagnostics, disease monitoring, and anticancer therapy.

• MeSH
• autoimunita * MeSH
• hojení ran * imunologie   MeSH
• interleukin-6 * metabolismus   imunologie   MeSH
• lidé MeSH
• nádorové mikroprostředí * imunologie   MeSH
• nádory * imunologie   metabolismus   patologie   MeSH
• stárnutí * imunologie   MeSH
• zánět * imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Úvod: Akutní poškození ledvin (AKI – acute kidney injury) se vyskytuje u kriticky nemocných pacientů s výrazným dopadem na jejich morbiditu a mortalitu. Náhlé snížení renálních funkcí ovlivňuje činnost a funkci jiných orgánů, mezi jinými také střevo navozením střevní dysmikrobie, jež recipročně zhoršuje průběh AKI a může také vést k rozvoji chronické nefropatie. Cíl: Patofyziologie AKI, sepse a střevní dysmikrobie v kritickém stavu pacienta s dopadem na vývoj nemoci a jiné orgánové systémy s možnostmi jejího pozitivního ovlivnění nutričními opatřeními. Závěr: Kriticky nemocní pacienti zejména v septickém stavu komplikovaném AKI jsou náchylní ke komplikacím typu střevní dysmikrobie, sekundární sepse a imunodeficience. Léčba základního onemocnění a jeho komplikací spolu s nutriční podporou napomáhá ke zlepšení klinického stavu této skupiny nemocných.

Introduction: Acute kidney injury (AKI) occurs in critically ill patients with significant impact on their morbidity and mortality. The sudden reduction in renal function affects the function of other organs, comprising the intestine, inducing intestinal dysmicrobia, which reciprocally worsens the course of AKI and may also lead to the development of chronic nephropathy. Purpose: Pathophysiology of AKI, sepsis and intestinal dysmicrobia in a critical patient with impact on the development of the disease and other organ systems with possibilities of its positive influence by nutritional measures. Conclusion: Critically ill patients especially in septic status complicated by AKI are prone to complications such as intestinal dysmicrobia, secondary sepsis and immunodeficiency. Treatment of the underlying disease and its complications along with nutritional support helps to improve the clinical outcome of this group of patients.

• MeSH
• akutní poškození ledvin * komplikace   patofyziologie   MeSH
• dysbióza * etiologie   mikrobiologie   patologie   MeSH
• lidé MeSH
• nutriční podpora MeSH
• péče o pacienty v kritickém stavu MeSH
• podvýživa etiologie   terapie   MeSH
• sepse patologie   MeSH
• septický šok patologie   MeSH
• uremické toxiny škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Systemic treatment with immune combinations is the gold standard for metastatic renal cell carcinoma (mRCC) worldwide. The systemic immune-inflammation index (SII) is a prognostic marker for several types of malignant neoplasms, including mRCC, in the era of tyrosine kinase inhibitor (TKI) treatment. Data regarding the prognostic value of the SII in patients with mRCC treated with immunotherapy are scarce and controversial. METHODS: We retrospectively collected the data of patients with mRCC from 56 centers in 18 countries. SII (Platelet × Neutrophil/Lymphocyte count) was calculated prior to the first systemic treatment and cut-off was defined by a survival receiver operating characteristic (ROC) analysis. The primary objective of our retrospective study was to assess the outcomes of patients treated with first-line immunotherapy. RESULTS: Data from 1034 mRCC patients was collected and included in this analysis. The SII cut-off value was 1265. After a follow-up of 26.7 months, and the overall survival (OS) and progression-free survival (PFS) were 39.8 and 15.7 months, respectively. According to SII (low vs. high), patients with low-SII had longer OS (55.7 vs. 22.2 months, P < .001), better PFS (20.8 vs. 8.5 months, P < .001), and higher overall response rate (52 vs. 37%, P = .033). CONCLUSION: A high SII is associated with poor oncological outcomes in patients with mRCC. SII could be an easily accessible prognostic indicator for use in clinical practice.

• MeSH
• analýza přežití MeSH
• karcinom z renálních buněk * patologie   MeSH
• lidé MeSH
• nádory ledvin * patologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• zánět patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2.

• MeSH
• butyrofiliny * genetika   metabolismus   MeSH
• COVID-19 * genetika   komplikace   imunologie   virologie   MeSH
• dítě MeSH
• genetická predispozice k nemoci MeSH
• heterozygot MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• SARS-CoV-2 * MeSH
• syndrom systémové zánětlivé reakce * genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION AND OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the nasal cavity, penetrates the nasal epithelial cells through the interaction of its spike protein with the host cell receptor angiotensin-converting enzyme 2 (ACE2) and then triggers a cytokine storm. We aimed to assess the biocompatibility of fullerenol nanoparticles C60(OH)40 and ectoine, and to document their effect on the protection of primary human nasal epithelial cells (HNEpCs) against the effects of interaction with the fragment of virus - spike protein. This preliminary research is the first step towards the construction of a intranasal medical device with a protective, mechanical function against SARS-CoV-2 similar to that of personal protective equipment (eg masks). METHODS: We used HNEpCs and the full-length spike protein from SARS-CoV-2 to mimic the first stage of virus infection. We assessed cell viability with the XTT assay and a spectrophotometer. May-Grünwald Giemsa and periodic acid-Schiff staining served to evaluate HNEpC morphology. We assessed reactive oxygen species (ROS) production by using 2',7'-dichlorofluorescin diacetate and commercial kit. Finally, we employed reverse transcription polymerase chain reaction, Western blotting and confocal microscopy to determine the expression of angiotensin-converting enzyme 2 (ACE2) and inflammatory cytokines. RESULTS: There was normal morphology and unchanged viability of HNEpCs after incubation with 10 mg/L C60(OH)40, 0.2% ectoine or their composite for 24 h. The spike protein exerted cytotoxicity via ROS production. Preincubation with the composite protected HNEpCs against the interaction between the spike protein and the host membrane and prevented the production of key cytokines characteristic of severe coronavirus disease 2019, including interleukin 6 and 8, monocyte chemotactic protein 1 and 2, tissue inhibitor of metalloproteinases 2 and macrophage colony-stimulating factor. CONCLUSION: In the future, the combination of fullerenol and ectoine may be used to prevent viral infections as an intranasal medical device for people with reduced immunity and damaged mucous membrane.

• MeSH
• aminokyseliny diaminové MeSH
• angiotensin konvertující enzym 2 metabolismus   MeSH
• COVID-19 * prevence a kontrola   MeSH
• cytokiny metabolismus   MeSH
• epitelové buňky * účinky léků   virologie   MeSH
• fullereny * farmakologie   chemie   MeSH
• glykoprotein S, koronavirus * metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• nanočástice * chemie   MeSH
• nosní sliznice účinky léků   cytologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• SARS-CoV-2 * účinky léků   MeSH
• syndrom uvolnění cytokinů * prevence a kontrola   MeSH
• viabilita buněk * účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH