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Journal of Asian Natural Products... Jun 2023Two new sesquiterpenoids, named 9,10-dihydroxy-albaflavenone () and 5-hydroxy-albaflavenone () were isolated from . Their structures and absolute configurations were...
Two new sesquiterpenoids, named 9,10-dihydroxy-albaflavenone () and 5-hydroxy-albaflavenone () were isolated from . Their structures and absolute configurations were determined by NMR, ECD and HRESIMS. Compounds and showed anti-inflammatory activity by inhibiting TNF- and NO secretion to varying degrees.
Topics: Basidiomycota; Sesquiterpenes; Tumor Necrosis Factor-alpha
PubMed: 35929891
DOI: 10.1080/10286020.2022.2106223 -
Current Pharmaceutical Design 2017The importance of anti-tumor immunity in the outcome of cancer is now unequivocally established and recent achivements in the field have stimulated the development of... (Review)
Review
The importance of anti-tumor immunity in the outcome of cancer is now unequivocally established and recent achivements in the field have stimulated the development of new immunotherapeutical approaches. In invasive tumors, widespread inflammation promotes invasiveness and concomitantly also inhibits anti-tumor immune responses. We suggest that efficient tumor treatment should target both the malignant cells and the tumor microenvironment. Interleukin-1 (IL-1) is a pro-inflammatory as well as an immunostimulatory cytokine that is abundant in the tumor microenvironment. Manipulation of IL-1 can thus serve as an immunotherapeutical approach to reduce inflammation/immunosuppression and thus enhance anti-tumor immunity. The two major IL-1 agonistic molecules are IL-1α and IL-1β, which bind to the same IL-1 signaling receptor and induce the same array of biological activities. The IL-1 receptor antagonist (IL-Ra) is a physiological inhibitor of IL-1 that binds to its receptor without transmition of activation signals and thus serves as a decoy target. We have demonstrated that IL-1α and IL-1β are different in terms of the producing cells and their compartmentalization and the amount. IL-1α is mainly expressed intracellularly, in the cytosol, in the nucleus or exposed on the cell membrane, however, it is rarely secreted. IL-1β is active only as a secreted molecule that is mainly produced by activated myeloid cells. We have shown different functions of IL-1α and IL-1β in the malignant process. Thus, in its membrane- associated form, IL-1α is mainly immunostimulatory, while IL-1β that is secreted into the tumor microenvironment is mainly pro-inflammatory and promotes tumorigenesis, tumor invasiveness and immunosuppression. These distinct functions of the IL-1 agonistic molecules are mainly manifested in early stages of tumor development and the patterns of their expression dictate the direction of the malignant process. Here, we suggest that IL-1 modulation can serve as an effective mean to tilt the balance between inflammation and immunity in tumor sites, towards the latter. Different agents that neutralize IL-1, mainly the IL-Ra and specific antibodies, exist. They are safe and FDA-approved. The IL-1Ra has been widely and successfully used in patients with Rheumatoid arthritis, autoinflammatory diseases and various other diseases that have an inflammatory component. Here, we provide the rationale and experimental evidence for the use of anti-IL-1 agents in cancer patients, following first line therapy to debulk the major tumor's mass. The considerations and constraints of using anti-IL-1 treatments in cancer are also discussed. We hope that this review will stimulate studies that will fasten the application of IL-1 neutralization at the bedside of cancer patients.
Topics: Animals; Humans; Immunotherapy; Inflammation; Interleukin-1; Interleukin-1alpha; Interleukin-1beta; Neoplasm Invasiveness; Neoplasms; Tumor Microenvironment
PubMed: 28606052
DOI: 10.2174/1381612823666170613080919 -
Critical Reviews in Immunology 2019Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory, disabling arthropathy that severely affects the quality of life. This disease involves several... (Review)
Review
Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory, disabling arthropathy that severely affects the quality of life. This disease involves several proinflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF). IL-1 induces TNF and vice versa, causing joint damage and cartilage degradation. Current antirheumatic drugs may be effective, but they possess many unwanted side effects. In recent years, inhibitors of proinflammatory cytokines have increasingly entered mainstream clinical practice. Recent evidence indicates that IL-37, which has anti-inflammatory properties, is increased in the serum and is released from white blood cells in patients with RA. Mast cells (MCs), stimulated by the neuropeptide substance P (SP) and IL-33, release IL-1β and TNF. Recent evidence indicates that large amounts of IL-1β and TNF can be released from human MCs, which also secrete CXCL8, which promotes migration of immune cells, causing erosion of the bone and cartilage. Treatment with IL-37 can block the MC stimulation and release of inflammatory compounds, attenuating the severity of the disease and/or altering its progression.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Immunity; Immunomodulation; Inflammation; Interleukin-1; Interleukin-1beta; Mast Cells; Tumor Necrosis Factor-alpha
PubMed: 32421968
DOI: 10.1615/CritRevImmunol.2020033176 -
Gastroenterology Jul 2022
Topics: Humans; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 35525321
DOI: 10.1053/j.gastro.2022.04.050 -
Molekuliarnaia Biologiia 2019Skin wound healing is subject to an intricate regulation, involves many cell populations and molecular mediators, and is one of the key mechanisms that ensures the... (Review)
Review
Skin wound healing is subject to an intricate regulation, involves many cell populations and molecular mediators, and is one of the key mechanisms that ensures the barrier functions of the skin and the maintenance of body homeostasis. The efficiency of this process is largely determined by the balance of proinflammatory and proregenerative signals, which are mediated by cytokines. The review summarizes the latest data on the role of proinflammatory cytokines, mainly tumor necrosis factor (TNF), interleukin 6 (IL-6), interleukin 1 (IL-1), and interferons (IFNs), in skin wound healing, including those obtained with the use of genome editing techniques and methods of reverse genetics to establish relevant animal models. The roles that proinflammatory cytokines play at various stages of skin regeneration are discussed for both normal state and systemic pathologies, such as diabetes. Promising approaches to treating poorly healing wounds are summarized.
Topics: Animals; Cytokines; Inflammation Mediators; Interleukin-1; Interleukin-6; Mice; Skin; Tumor Necrosis Factor-alpha; Wound Healing
PubMed: 31661475
DOI: 10.1134/S0026898419050136 -
Journal of Leukocyte Biology Aug 2017IL-1 is a pleiotropic cytokine that controls inflammation, immunity, and hemopoiesis. The major IL-1 agonistic molecules are IL-1α and IL-1β, which bind to IL-1R type... (Review)
Review
IL-1 is a pleiotropic cytokine that controls inflammation, immunity, and hemopoiesis. The major IL-1 agonistic molecules are IL-1α and IL-1β, which bind to IL-1R type I (IL-1R1) and induce similar biologic functions. The IL-1R antagonist (IL-1Ra) is a physiologic inhibitor of IL-1R1 signaling. In the tumor microenvironment, IL-1 is expressed by malignant, stromal, and infiltrating cells and supports tumor invasiveness and progression. We have shown that in the tumor microenvironment, the IL-1 agonistic molecules act different as a result of their local amounts and their compartmentalization within the producing cells. IL-1β is produced mainly by myeloid cells upon inflammatory stimulation and is active as a mature, secreted molecule. The precursor of IL-1α (ProIL-1α) is biologically active; it is constitutively expressed in diverse tissue cells in basal levels, and its expression increases during stress or inflammation. ProIL-1α is mainly located in the cytosol or it is membrane associated. ProIL-1α also translocates into the nucleus and binds to chromatin. ProIL-1α is rarely actively secreted but is released from necrotizing tissues and serves as "alarmin" for initiation of inflammation. In the tumor microenvironment, IL-1β promotes tumorigenesis, tumor invasiveness, and immunosuppression. On the other hand, membrane-associated forms of IL-1α support the development of anti-tumor immunity. In cancer patients, both IL-1 agonistic molecules coexist and interact with each other. Here, we discuss the role of IL-1 agonistic molecules in tumor progression and their potential to serve as targets in anti-tumor immunotherapeutic approaches. Our notion on the optimal conditions for IL-1 manipulation is also discussed.
Topics: Animals; Humans; Immunotherapy; Interleukin-1; Tumor Microenvironment
PubMed: 28522598
DOI: 10.1189/jlb.3MR1216-523R -
Experimental Physiology Dec 2015What is the topic of this review? This review discusses the latest findings on the contribution of inflammation to brain injury, how inflammation is a therapeutic... (Review)
Review
What is the topic of this review? This review discusses the latest findings on the contribution of inflammation to brain injury, how inflammation is a therapeutic target, and details of recent and forthcoming clinical studies. What advances does it highlight? Here we highlight recent advances on the role and regulation of inflammasomes, and the latest clinical progress in targeting inflammation. Acute brain injury is one of the leading causes of mortality and disability worldwide. Despite this, treatments for acute brain injuries are limited, and there remains a massive unmet clinical need. Inflammation has emerged as a major contributor to non-communicable diseases, and there is now substantial and growing evidence that inflammation, driven by the cytokine interleukin-1 (IL-1), worsens acute brain injury. Interleukin-1 is regulated by large, multimolecular complexes called inflammasomes. Here, we discuss the latest research on the regulation of inflammasomes and IL-1 in the brain, preclinical efforts to establish the IL-1 system as a therapeutic target, and the promise of recent and future clinical studies on blocking the action of IL-1 for the treatment of brain injury.
Topics: Animals; Brain; Brain Injuries; Humans; Inflammasomes; Inflammation; Interleukin-1
PubMed: 26096539
DOI: 10.1113/EP085135 -
Journal of Parkinson's Disease 2021Oral microbiota has largely escaped attention in Parkinson's disease (PD), despite its pivotal role in maintaining oral and systemic health.
BACKGROUND
Oral microbiota has largely escaped attention in Parkinson's disease (PD), despite its pivotal role in maintaining oral and systemic health.
OBJECTIVE
The aim of our study was to examine the composition of the oral microbiota and the degree of oral inflammation in PD.
METHODS
Twenty PD patients were compared to 20 healthy controls. Neurological, periodontal and dental examinations were performed as well as dental scaling and gingival crevicular fluid sampling for cytokines measurement (interleukine (IL)-1β, IL-6, IL-1 receptor antagonist (RA), interferon-γ and tumor necrosis factor (TNF)-α). Two months later, oral microbiota was sampled from saliva and subgingival dental plaque. A 16S rRNA gene amplicon sequencing was used to assess bacterial communities.
RESULTS
PD patients were in the early and mid-stage phases of their disease (Hoehn & Yahr 2-2.5). Dental and periodontal parameters did not differ between groups. The levels of IL-1β and IL-1RA were significantly increased in patients compared to controls with a trend for an increased level of TNF-α in patients. Both saliva and subgingival dental plaque microbiota differed between patients and controls. Streptococcus mutans, Kingella oralis, Actinomyces AFQC_s, Veillonella AFUJ_s, Scardovia, Lactobacillaceae, Negativicutes and Firmicutes were more abundant in patients, whereas Treponema KE332528_s, Lachnospiraceae AM420052_s, and phylum SR1 were less abundant.
CONCLUSION
Our findings show that the oral microbiome is altered in early and mid-stage PD. Although PD patients had good dental and periodontal status, local inflammation was already present in the oral cavity. The relationship between oral dysbiosis, inflammation and the pathogenesis of PD requires further study.
Topics: Dental Plaque; Dysbiosis; Humans; Inflammation; Interleukin-1beta; Kingella; Parkinson Disease; RNA, Ribosomal, 16S; Tumor Necrosis Factor-alpha
PubMed: 33646178
DOI: 10.3233/JPD-202459 -
Cold Spring Harbor Perspectives in... Oct 2018The tumor necrosis factor (TNF) cytokine family and the TNF/nerve growth factor (NGF) family of their cognate receptors together control numerous immune functions, as... (Review)
Review
The tumor necrosis factor (TNF) cytokine family and the TNF/nerve growth factor (NGF) family of their cognate receptors together control numerous immune functions, as well as tissue-homeostatic and embryonic-development processes. These diverse functions are dictated by both shared and distinct features of family members, and by interactions of some members with nonfamily ligands and coreceptors. The spectra of their activities are further expanded by the occurrence of the ligands and receptors in both membrane-anchored and soluble forms, by "re-anchoring" of soluble forms to extracellular matrix components, and by signaling initiation via intracellular domains (IDs) of both receptors and ligands. Much has been learned about shared features of the receptors as well as of the ligands; however, we still have only limited knowledge of the mechanistic basis for their functional heterogeneity and for the differences between their functions and those of similarly acting cytokines of other families.
Topics: Animals; Gene Expression Regulation; Humans; Multigene Family; Receptor, Nerve Growth Factor; Tumor Necrosis Factor-alpha
PubMed: 28847899
DOI: 10.1101/cshperspect.a028431 -
F1000Research 2019The landscape of pediatric inflammatory bowel disease is rapidly evolving. The therapeutic advances seen in the adult arena are rapidly being adopted by pediatric... (Review)
Review
The landscape of pediatric inflammatory bowel disease is rapidly evolving. The therapeutic advances seen in the adult arena are rapidly being adopted by pediatric gastroenterologists and evaluated in both controlled trials and real-world experience. Though anti-tumor necrosis factor agents have been the primary therapy over the last decade, recently there has been an expansion of therapeutic targets and alternative mechanism of action drugs with a focus on individualized and personalized therapy. By reviewing epidemiology, pathophysiology, and goals of treatment, we hope to frame the discussion of current and novel therapeutics for the pediatric gastroenterologist. As scientific discovery continues to push the envelope in defining our understanding of pediatric inflammatory bowel disease, the current era of therapeutics gives us hope that a cure may be realized soon.
Topics: Child; Humans; Inflammatory Bowel Diseases; Tumor Necrosis Factor-alpha
PubMed: 31885858
DOI: 10.12688/f1000research.19609.1