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Immune Dysfunction in Uremia 2020.

Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failur

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… They found that the NLRP3 inflammasome is not activated by hypervolemia, suggesting that endotoxemia is not a main driver for inflammation in hypervolemic HD patients. 5. …

Exploring the gut microbiome's influence on cancer-associated anemia: Mechanisms, clinical challenges, and innovative therapies.

BackgroundAnemia is a prevalent and challenging complication in patients with hematologic and solid malignancies, which stems from the direct effects of malignancy, treatment-induced toxicities, and systemic inflammation. It affects patients' survival, functional status, and quality of life profoundly. Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia. The gut microbiota, through its intricate interplay with iron metabolism, inflammatory pathways, and immune modulation, may either exacerbate or ameliorate anemia depending

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… Probiotic sepsis, bacteremia, endotoxemia, and infections with multidrug resistant organisms can occur in immunocompromised recipients. Dysregulated immune responses with microbiome-based interventions can manifest in several ways. … Endotoxemia and Gastrointestinal Cancers: Insight into the Mechanisms Underlying a Dangerous Relationship. Microorganisms. 2023;11:267. doi: 10.3390/microorganisms11020267. 118. Kandpal M, Indari O, Baral B, Jakhmola S, Tiwari D, Bhandari V, Pandey RK, Bala K, Sonawane A, Jha HC. …

Длиннокаменистые толстые кислоты как движущие факторы нейроинфламмации в нейродегенерации: механистические связи с липидом пероксидацией, Ферроптозом и митохондриальной дисфункцией.

Фон: Нейродегенеративные заболевания (НИ) рассматриваются главным образом как расстройства, характеризующиеся серьезным иммунометаболическим дисбалансом, характеризующимся текущей нейроинфламмацией и глиальной активацией. Хотя митохондриальная дисфункция и окислительный стресс являются хорошо известными особенностями, метаболические факторы в верхнем течении, связывающие эти патологические процессы, по-прежнему плохо понимаются. Методы: В ходе этого обзора мы изучили недавние доклинические и клинические исследования, в ходе которых были изучены связи между липидным метаболизмом, иммунометаболи

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… Palmitic Acid Modulates Microglial Cell Response to Metabolic Endotoxemia in an In Vitro Study Nutrients 2023 15 3463 10.3390/nu15153463 37571401 PMC10421407 9. Wu C. Lin J. Chen Q. Zhao W. Kawahata I. Cheng A. …

Thrombotic risk in hepatitis C: Interplay between hepatic dysfunction, viral-driven inflammation, and cardiovascular consequences.

Hepatitis C virus (HCV) infection, traditionally regarded as a hepatotropic disease, is increasingly recognized as a systemic condition with significant thrombotic implications. Chronic HCV induces a persistent proinflammatory and prothrombotic state that substantially elevates the risk of both venous and arterial events. Mechanistically, HCV drives endothelial dysfunction, enhances platelet activation, disrupts coagulation and fibrinolytic balance, and promotes immune-mediated vascular injury through cryoglobulinemia and chronic systemic inflammation. Clinical manifestations range from portal

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… Margolis L Anthony DD Lederman MM Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection HIV Med 2016 17 581 589 27187749 10.1111/hiv.12357 PMC4987156 24 Shive CL Kowal CM Desotelle AF Nguyen Y Carbone S Kostadinova L Davitkov P O'Mara M Reihs A Siddiqui H Wilson BM Anthony DD Endotoxemia …

Ось Гут-Брэйна и взаимодействие мозга с помощью микробиома с медицинской точки зрения.

Фон: кишечный микробиом непосредственно влияет на здоровье и активность мозга, что означает, что они тесно связаны между собой. Эта взаимосвязь предполагает наличие связи между микробными диспропорциями и болезнями, такими, как болезнь Альцгеймера, хотя здесь также играют свою роль и многочисленные другие факторы, способствующие этому, такие, как генетика. Кроме того, недавние исследования показали, что цереброспинальная жидкость содержит микробную дезоксирибонуклеиновую кислоту (ДНК), которая может быть истолкована как означающая наличие микробиома в мозгу. Вагустный нерв и центральная нервна

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… Improvement of sleep by resistant dextrin prebiotic in type 2 diabetic women coincides with attenuation of metabolic endotoxemia: Involvement of gut-brain axis J. Sci. Food Agric. 2022 102 5229 5237 10.1002/jsfa.11876 35306660 82. Nikrad N. Farhangi M.A. Fard Tabrizi F.P. Vaezi M. Mahmoudpour A. …

37th International Symposium on Intensive Care and Emergency Medicine (part 1 of 3) : Brussels, Belgium. 21–24 March 2017

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Anti-resorptive therapy in the osteometabolic patient affected by periodontitis. A joint position paper of the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP).

This joint report from the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP) aims for a consensus around the scientific rationale and clinical strategy for the management of osteoporotic patients affected by periodontitis who are undergoing anti-resorptive (AR) therapy to manage the risk of the occurrence of a medication-related osteonecrosis of the jaws (MRONJ). Osteoporosis and periodontitis are chronic diseases with a high prevalence in aging patients, and they share some of the same pathogenetic mechanisms based upon i

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… This phenomenon prolongs bone exposure to a local environment with periodontitis, which is characterized by oxidative stress, endotoxemia and proinflammatory mediators, thus precipitating cellular and molecular toxicity and ultimately the onset of local necrosis [ 40 ]. …

Canine cancer immunotherapy studies: linking mouse and human.

Despite recent major clinical breakthroughs in human cancer immunotherapy including the use of checkpoint inhibitors and engineered T cells, important challenges remain, including determining the sub-populations of patients who will respond and who will experience at times significant toxicities. Although advances in cancer immunotherapy depend on preclinical testing, the majority of in-vivo testing currently relies on genetically identical inbred mouse models which, while offering critical insights regarding efficacy and mechanism of action, also vastly underrepresent the heterogeneity and co

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… For example, a somewhat controversial study by Seok et al. simultaneously analyzed the genetic changes occurring in humans and mice following inflammatory insults such as burns, trauma and endotoxemia. …

Glucocorticoids-based prodrug design: Current strategies and research progress.

Attributing to their broad pharmacological effects encompassing anti-inflammation, antitoxin, and immunosuppression, glucocorticoids (GCs) are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus, nephritis, arthritis, ulcerative colitis, asthma, keratitis, macular edema, and leukemia. However, long-term use often causes undesirable side effects, including metabolic disorders-induced Cushing's syndrome (buffalo back, full moon face, hyperglycemia, etc.), osteoporosis, aggravated infection, psychosis, glaucoma, and cataract. These notorious side e

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… Antibody-drug conjugates anti-CD163-Dex conjugate | Anti-CD163 | Esterase/ Hydrolysis-activated Succinate | Intravenous injection | To treat endotoxemia and nonalcoholic steatohepatitis; Precise targeting to macrophages; The in vivo potency of conjugated Dex was bout 50-fold that of nonconjugated Dex … antibody | Esterase-activated phosphate ester | At cellular level | Precise targeting of immune cells; Allows lower drug doses while achieving superior results. | [111] anti-PRLR- budesonide conjugates | PRLR antibody | Cathepsin B- sensitive linkers | Intraperitoneal injection | To treat LPS-induced endotoxemia …

Impact of Periodontal Host-Modulation Therapies on Oral-Gut Microbiome Axis in Periodontitis Patients with Hematological Diseases: A Narrative Review.

Host-modulating therapies and oral microbiome-targeted approaches are emerging options in periodontal care and are especially relevant for patients undergoing immunotherapy for hematologic malignancies. Immune dysregulation induced by immune checkpoint inhibitors or CAR-T cell therapy may worsen periodontal inflammation and alter the composition and functions of the oral microbiota. Beyond these, other immunomodulatory treatments commonly employed in hematologic malignancies-including monoclonal antibodies (e.g., rituximab, daratumumab), immunomodulatory drugs (e.g., lenalidomide, thalidomide)

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… Inflammatory signals and bacterial metabolites originating in the oral cavity can affect gut barrier integrity and modulate intestinal microbiota composition, promoting systemic immune activation and low-grade endotoxemia [ 18 ]. …

The roles of inflammasomes in cancer.

Inflammation is a key characteristic of all stages of tumor development, including tumor initiation, progression, malignant transformation, invasion, and metastasis. Inflammasomes are an important component of the inflammatory response and an indispensable part of the innate immune system. Inflammasomes regulate the nature of infiltrating immune cells by signaling the secretion of different cytokines and chemokines, thus regulating the anti-tumor immunity of the body. Inflammasome expression patterns vary across different tumor types and stages, playing different roles during tumor progression

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… (Indirect) | Broad-spectrum inhibitor of the ATP-binding cassette transporter and P2X7R | Type2 diabetes Gevokizumab (Xoma 052) | IL-1β | Anti-IL-1β antibody | Diabetes, Osteoarthritis GSK 1070806 | IL-18 | Anti-IL-18 antibody | Diabetes, IBD Ac-YVAD-CHO | Caspase-1 | Caspase-1 inhibitory peptide | Endotoxemia …

Sequential bortezomib and temozolomide treatment promotes immunological responses in glioblastoma patients with positive clinical outcomes: A phase 1B study.

BackgroundGlioblastoma (GBM) is an aggressive malignant brain tumor where median survival is approximately 15 months after best available multimodal treatment. Recurrence is inevitable, largely due to O6 methylguanine DNA methyltransferase (MGMT) that renders the tumors resistant to temozolomide (TMZ). We hypothesized that pretreatment with bortezomib (BTZ) 48 hours prior to TMZ to deplete MGMT levels would be safe and tolerated by patients with recurrent GBM harboring unmethylated MGMT promoter. The secondary objective was to investigate whether 26S proteasome blockade may enhance differentia

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… Proinflammatory effects of IL‐10 during human endotoxemia . J Immunol . 2000 ; 165 : 2783 ‐ 2789 . 10.4049/jimmunol.165.5.2783 10946310 53 Mocellin S , Panelli M , Wang E , et al. IL‐10 stimulatory effects on human NK cells explored by gene profile analysis . …

Myeloid-Derived Suppressor Cells in Sepsis: Pathophysiology, Duality, and Therapeutic Frontiers.

Sepsis-induced immunosuppression, one of the factors contributing to mortality, is closely mediated by myeloid-derived suppressor cells (MDSCs). This review first outlines MDSC biology, describing their origin from pathological emergency myelopoiesis and classification into polymorphonuclear and monocytic subsets. We then discuss their dual role: an early, protective modulation of cytokine storm that later evolves into harmful immunosuppression associated with secondary infections and death. The underlying mechanisms involve L-arginine depletion ( via arginase 1/inducible nitric oxide synthase

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… Myeloid-derived suppressor-like cells as a prognostic marker in critically ill patients: insights from experimental endotoxemia and intensive care patients. Cells . 2024 ; 13 ( 4 ): 314 . 38391927 10.3390/cells13040314 PMC10887109 34. O’Keefe GE Wu Y Mirabadi N . …

Гут Микробиом и мальгический энцефаломилит/хронический синдром утомления (ME/CFS): Понимание механизмов борьбы с заболеваниями.

Myalgic Encephalomyelitis/Chronic Fatige (ME/CFS) — клиническая болезнь, характерная особенность которой заключается в постэкспертальной болезни (PEM). Она может влиять на многие органы и системы, что приводит к серьезному ухудшению качества жизни пациентов. Несмотря на многочисленные постинфекционные, иммунологические, неврологические, метаболические и эндокринные изменения, не существует ни окончательного диагностического маркера, ни утвержденного лечения. Этиология и патофизиология по-прежнему не до конца понимаются; однако появляющиеся данные свидетельствуют о том, что кишечная микробиомия

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… This is known as metabolic endotoxemia, and according to Giloteaux et al., increased endotoxin levels disrupt the epithelial barrier, enter the circulation and activate the inflammatory TLR-4 pathway [ 79 , 104 , 105 ]. …

The potential of mesenchymal stem cells in the management of radiation enteropathy.

Although radiotherapy is effective in managing abdominal and pelvic malignant tumors, radiation enteropathy is still unavoidable. This disease severely affects the quality of life of cancer patients due to some refractory lesions, such as intestinal ischemia, mucositis, ulcer, necrosis or even perforation. Current drugs or prevailing therapies are committed to alleviating the symptoms induced by above lesions. But the efficacies achieved by these interventions are still not satisfactory, because the milieus for tissue regeneration are not distinctly improved. In recent years, regenerative ther

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… prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production Nat Med 2009 15 42 49 19098906 10.1038/nm.1905 PMC2706487 Pils MC Pisano F Fasnacht N Heinrich JM Groebe L Schippers A Monocytes/macrophages and/or neutrophils are the target of IL-10 in the LPS endotoxemia …

Influence of the Mediterranean Diet on Healthy Aging.

The life expectancy of the global population has increased. Aging is a natural physiological process that poses major challenges in an increasingly long-lived and frail population. Several molecular mechanisms are involved in aging. Likewise, the gut microbiota, which is influenced by environmental factors such as diet, plays a crucial role in the modulation of these mechanisms. The Mediterranean diet, as well as the components present in it, offer some proof of this. Achieving healthy aging should be focused on the promotion of healthy lifestyle habits that reduce the development of pathologi

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… Indeed, the review by Cornejo-Pareja et al. concludes that the increase in fat mass in obese patients is not only due to more efficient energy uptake but that the microbiota is involved in changes in endotoxemia, intestinal permeability, insulin resistance, the hormonal environment, the expression of …

Exploring neutrophil extracellular traps: mechanisms of immune regulation and future therapeutic potential.

Neutrophil extracellular traps (NETs) are complex, web-like structures consisting of DNA intertwined with antimicrobial proteins, which neutrophils release upon immune activation. These structures play a crucial role in pathogen elimination, particularly in infectious diseases. However, their involvement in various pathological conditions is multifaceted and context-dependent, while NETs contribute to host defense against infections, they can also exacerbate sterile inflammation, autoimmune disorders, and tumor progression. This review provides a comprehensive analysis of the molecular mechani

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… Sivelestat alleviates atherosclerosis by improving intestinal barrier function and reducing endotoxemia. Front Pharmacol. 2022;13:838688. 10.3389/fphar.2022.838688. 149. Shioya Y, Katakura K, Ohira H. Neutrophil elastase inhibitor suppresses IL-17 based inflammation of murine experimental colitis. …

Oxygen targets in critically ill patients: from pathophysiology to population enrichment strategies.

Oxygen supplementation is widely used to enhance oxygen delivery and to treat or prevent hypoxia; however, it requires careful management to avoid the harmful effects of excessive oxygen exposure. Both hyperoxia (inspiratory oxygen fraction exceeding 0.21) and hyperoxemia (arterial oxygen tension oxygen partial pressure [PaO2] > 100 mmHg) can contribute to lung injury, promote systemic vasoconstriction, and increase the production of reactive oxygen species, which can impair macromolecular and cellular functions. Conversely, in certain situations, hyperoxemia may provide benefits, such as hemo

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… Short-term hyperoxia does not exert immunologic effects during experimental murine and human endotoxemia. Sci Rep. 2015;5:17441. doi: 10.1038/srep17441. 70. Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer. 2011;11:393–410. doi: 10.1038/nrc3064. 71. …

Interleukin-6: obstacles to targeting a complex cytokine in critical illness.

Circulating concentrations of the pleiotropic cytokine interleukin-6 (IL-6) are known to be increased in pro-inflammatory critical care syndromes, such as sepsis and acute respiratory distress syndrome. Elevations in serum IL-6 concentrations in patients with severe COVID-19 have led to renewed interest in the cytokine as a therapeutic target. However, although the pro-inflammatory properties of IL-6 are widely known, the cytokine also has a series of important physiological and anti-inflammatory functions. An adequate understanding of the complex processes by which IL-6 signalling occurs is c

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… Endotoxemia elicits increased circulating β2-IFN/IL-6 in man. J Immunol. 1989;142:2321–2324. 10. Palsson-McDermott EM, O'Neill LA. The Warburg effect then and now: from cancer to inflammatory diseases. BioEssays. 2013;35:965–973. doi: 10.1002/bies.201300084. 11. …

Полигенная природа множественного склероза: генетические варианты, иммунологические модуляции и экологические связи.

Множественный склероз (MS) — изнуряющее воспалительное расстройство центральной нервной системы, характеризующееся обезвоживанием, — в значительной степени зависит от полигенных вариаций. Хотя конкретная причина НР остается неясной, считается, что она возникает в результате сложного взаимодействия генетических и экологических факторов. Последние исследования были сосредоточены на полигенном характере генетических изменений, связанных с риском НР. В настоящем обзоре подчеркивается важнейшая роль этих генетических вариантов в формировании восприимчивости к болезням и их развития. Специфические а

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… In contrast, a gut microbiota imbalance, or dysbiosis, is associated with conditions, like endotoxemia, intestinal or systemic inflammation, and neuroinflammation [ 61 - 63 ]. …