Search

Metabolism plays a crucial role in regulating the function of immune cells in both health and disease, with altered metabolism contributing to the pathogenesis of cancer and many inflammatory diseases. The local microenvironment has a profound impact on the metabolism of immune cells. Therefore, immunological and metabolic heterogeneity as well as the spatial organization of cells in tissues should be taken into account when studying immunometabolism. Here, we highlight challenges of investigating metabolic communication. Additionally, we review the capabilities and limitations of current technologies for studying metabolism in inflamed microenvironments, including single‐cell omics techniques, flow cytometry‐based methods (Met‐Flow, single‐cell energetic metabolism by profiling translation inhibition (SCENITH)), cytometry by time of flight (CyTOF), cellular indexing of transcriptomes and epitopes by sequencing (CITE‐Seq), and mass spectrometry imaging. Considering the importance of metabolism in regulating immune cells in diseased states, we also discuss the applications of metabolomics in clinical research, as well as some hurdles to overcome to implement these techniques in standard clinical practice. Finally, we provide a flowchart to assist scientists in designing effective strategies to unravel immunometabolism in disease‐relevant contexts. [ABSTRACT FROM AUTHOR]

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization. This review proposes new strategies that focus on elucidating the mechanisms of natural products and their target proteins, hoping to provide insights into the development of new drugs based on natural products. [Display omitted] [ABSTRACT FROM AUTHOR]

OBJECTIVE: Adrenergic receptors belong to the G protein-coupled receptor family and are one of the important targets of modern drug therapy. Dexmedetomidine (DEX) is a highly selective agonist of alpha2 receptor, a member of the adrenergic receptor family, which are widely found in immune tissues and which mediate the biological behaviour of the inflammatory immune system. This review mainly summarizes the role of DEX in immune tissue and inflammation-related diseases, to provide a theoretical basis for clinical treatment. MATERIALS AND METHODS: We searched the PUBMED, EMBASE, and Cochrane libraries separately to obtain published literature on DEX related to immune tissue and inflammatory diseases. The mesh (dexmedetomidine, microglia, astrocytes, spleen, marrow, lymph nodes) and their corresponding keywords used for the searches, and no time limit for retrieval. The latest search was conducted on July 1, 2022. RESULTS: By reading a lot of relevant literature, we found that DEX reduces the inflammatory response of brain tissue by interfering with microglia and astrocytes. DEX can regulate the expression of CD40 and CD86 markers on the surface of splenocytes and reduce the secretion of inflammatory cytokines by splenocytes. In addition, we found that DEX reduced inflammation-related diseases such as neuroinflammation, myocarditis, liver cirrhosis, osteoarthritis, upper respiratory tract infection, pancreatitis, spinal tuberculosis, pulpitis, colon inflammation and rheumatoid arthritis, and improved prognosis. CONCLUSIONS: DEX has anti-inflammatory and improved prognosis in many inflammatory related diseases and is expected to become a targeted drug for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is often associated with other comorbidities due to chronic inflammation. However, no population-based, longitudinal study has investigated the relationship between CRS and chronic skin inflammation. Objective: To investigate the potential relationship between CRS and chronic skin inflammatory diseases, such as atopic dermatitis (AD), vitiligo, and psoriasis. Methods: A total of 5638 patients with CRS and 11 276 without CRS as a comparison group, were included from the Korean National Health Insurance Service database from 2002–2013. A propensity score matching (1:2) was performed using the nearest neighbor matching method, sociodemographic factors, and enrollment year. The Cox proportional hazards model was used to analyze the hazard ratio of CRS for AD, vitiligo, and psoriasis. Results: Results from this study showed that patients with CRS had no significant risk of the subsequent development of vitiligo or psoriasis compared to patients without CRS. However, we found a significantly higher incidence of AD in CRS patients than in those without CRS. The incidence of AD was 63.59 per 1000 person-years in the CRS group and 45.38 per 1000 person-years in the comparison group. Additionally, young and middle-aged CRS patients were independently associated with a higher incidence of subsequent AD events, but we could not find a significantly higher incidence of AD events in the elderly group. Conclusions: Our findings suggest there are no significant differences in the overall risk of vitiligo and psoriasis events in patients with CRS; however, we detected a higher risk of AD in young and middle-aged CRS patients. Therefore, clinicians should consider the risk of developing AD in specific patients who are newly diagnosed with CRS. [ABSTRACT FROM AUTHOR]

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic. The pulmonary administration of siRNA in an appropriate delivery vector seems promising to treat undruggable lung diseases such as acute lung injury/acute respiratory distress syndrome ALI/ARDS. [Display omitted] [ABSTRACT FROM AUTHOR]

The initiation and development of major inflammatory diseases, i.e. , cancer, vascular inflammation, and some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these diseases, whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo , poor penetration across biological barriers, and rapid clearance by the reticuloendothelial system. Drug delivery strategies are potent to promote their delivery. Herein, we reviewed the potential targets for immunotherapy against the major inflammatory diseases, discussed the biologics and drug delivery systems involved in the immunotherapy, particularly highlighted the approved therapy tactics, and finally offer perspectives in this field. The potential biological drugs and drug delivery systems against the inflammatory diseases, including cancer, atherosclerosis (AS), rheumatoid arthritis (RA), inflammatory bowel diseases (IBD) and pulmonary arterial hypertension (PAH). [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Revista Médica Clínica Las Condes is the property of Editorial Sanchez y Barcelo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The NLRP3 inflammasome is a cytoplasmic multiprotein complex, the assembly of which can be initiated in response to various exogenous or endogenous danger signals. Excessive activation of the NLRP3 inflammasome has been implicated in the pathogenesis of a wide variety of human inflammatory diseases, suggesting that the NLRP3 inflammasome is a potential target for the treatment of these diseases. However, clinical drugs targeting the NLRP3 inflammasome are still not available. Recent data have elucidated the different signaling pathways or events that can control NLRP3 inflammasome activation and have provided some potential compounds with anti-NLRP3 inflammasome activity. Here, we summarize the molecular mechanisms and diseases involved in NLRP3 inflammasome activation and discuss the potential strategies targeting different aspects of the NLRP3 inflammasome and its implications for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Rheumatic diseases are immune-mediated inflammatory multisystem diseases with frequent cardiovascular manifestations including perimyocarditis, valvular disease, coronary artery disease, heart failure with or without preserved ejection fraction, pulmonary hypertension, aneurysms, and thrombosis. Echocardiography, carotid ultrasonography, cardiac computed tomography, cardiac magnetic resonance imaging, and positron emission tomography are valid diagnostic tools for the detection of the cardiovascular complications of the multisystem diseases that frequently determine prognosis. Furthermore, the findings of these methods may offer additive risk stratification in asymptomatic patients over the conventional risk scores used to assess cardiovascular risk in the primary prevention setting. Finally, the imaging methods offer a unique opportunity to monitor the effects of treatment on atherosclerotic lesions, coronary microcirculatory dysfunction, myocardial inflammation and fibrosis. However, studies are needed to investigate whether improvement of imaging markers by treatment or selection of treatment according to its effects on surrogate imaging markers is linked to improved prognosis. • Rheumatic diseases are inflammatory multisystem diseases with cardiovascular complications that determine prognosis. • Cardiovascular imaging modalities may offer additive risk stratification over the conventional risk scores in asymptomatic patients. • Myocardial strain assessment by echocardiography and gadolinium-enhanced cardiac magnetic resonance frequently detects subclinical cardiac dysfunction. • Whether improvement of surrogate imaging markers by treatment is linked to improved prognosis remains to be determined. [ABSTRACT FROM AUTHOR]

L. fermentum participates in immune regulation. Many L. fermentum have demonstrated capacity to promote a Th1 response and participated in the regulation of a series of inflammatory cytokines in inflammatory diseases. Immunomodulatory properties are strain-dependent, and further evidence is needed in order to give to each L. fermentum a specific immune response in the intestinal mucosa. • L. fermentum has an anti-inflammatory effect in diverse inflammatory diseases. • L. fermentum can modulate both innate and adaptive immune processes. • L. fermentum commonly lessened TNF-α and increased IL-10 in inflammatory tissues. • Immunomodulatory properties of L. fermentum are strain-dependent. Lactobacillus fermentum has been used in industrial processes and food fermentation for a long time. Because it is of human origin, non-pathogenic, has high resistance to passing through the intestine, prevents pathogenic insults and promotes the maturation of the immune system, it has been identified as a potential probiotic. L. fermentum has been shown to interact with human immune cells and to modulate specific pathways involved in innate and adaptive immune processes in diverse inflammatory diseases. This review summarizes the immunomodulatory properties and regulatory mechanisms of L. fermentum identified in isolated immune cells, animal models and the human body in recent studies. [ABSTRACT FROM AUTHOR]

Copyright of Pesquisa Veterinaria Brasileira is the property of Colegio Brasileiro de Patologia Animal - CBPA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Blood oxidative stress (BLOS) is the presence of white blood cells and platelets that are generating high levels of reactive oxygen species (ROS). A mathematical model links the level of BLOS or BLOS# and plasma sulfide concentration. An increase in the BLOS# reduces the plasma sulfide concentration. The reported maximum plasma sulfide concentration for defined health conditions were used to calculate the minimum BLOS#. Elevated BLOS generates high plasma concentration of ROS, which triggers multiple responses in the body that protect the host. First, insulin production by the pancreas is inhibited, which results in elevated blood glucose levels. This results in advanced glycation end products (AGE), which thicken the blood vessel wall. Elevated blood glucose levels also increases urination, which reduces the availability of substrates for infectious bacteria. Second, one or more signaling molecules are stimulated to produce vascular hypertrophy resulting in hypertension. Third, the initial stage of atherosclerosis thickens the blood vessel wall while also protecting the inner surface of the blood vessels from localized infection. The first three mechanisms provide added protection against pathogen migration through the blood vessel wall and reduce the cross-sectional area of blood vessels, which increases the retention time (RT) for improved ROS inactivation of pathogens. Fourth, genes expressed in the liver, which are associated with drug oxidation and uptake transport, are inhibited. This inhibition protects the host from any toxins produced by an anaerobic infection. Elevated BLOS also reduces plasma sulfide concentration, which inhibits wound healing and extends aerobic conditions of the wound. The normal induction of BLOS offers a short-term, cascade of several primary mechanisms for secondary defense against anaerobic infection of a wound. Normal induction of BLOS is due to ultra-exogenous sulfide formation (USF) generated by a local anaerobic infection of a wound in the natural environment. The presence of BLOS without infection is indicative of inadvertent dietary induction. Long-term dietary BLOS results in many severe inflammatory diseases and cancers that are common in an ageing population. Glands were identified as more susceptible to cancers caused by long-term dietary BLOS. Variable BLOS levels in patients of clinical trials may also be reducing effectiveness of experimental drugs and causing drug toxicity. If BLOS is confirmed as a secondary defense against infection that is inadvertently triggered by diet, then a large number of common health problems may be treated and managed by apheresis and dietary changes. [ABSTRACT FROM AUTHOR]

Salivary gland disease is managed by a number of specialities. There are three pairs of major salivary glands and several hundred minor salivary glands within the upper aerodigestive tract. Pathology is diverse, including infective, inflammatory and neoplastic diseases. Clinical presentation is usually with a lump within, or swelling of the gland. Investigations combine clinical assessment, fine needle aspiration cytology and radiology. Management is medical or surgical dependent on pathology. Surgical intervention is commonly performed for chronic inflammatory disorders and neoplasms. Management requires a sound knowledge of anatomy and oncologic principles. [ABSTRACT FROM AUTHOR]

Abstract: Salivary gland disease is managed by a number of specialities. There are three pairs of major salivary glands and several hundred minor salivary glands within the upper aerodigestive tract. Pathology is diverse, including infective, inflammatory and neoplastic diseases. Clinical presentation is usually with a lump within, or swelling of the gland. Investigations combine clinical assessment, fine needle aspiration cytology and radiology. Management is medical or surgical dependent on pathology. Surgical intervention is commonly performed for chronic inflammatory disorders and neoplasms. Management requires a sound knowledge of anatomy and oncologic principles. [Copyright &y& Elsevier]

Abstract: The ocular surface, constantly exposed to environmental pathogens, is particularly vulnerable to infection. Hence an advanced immune defence system is essential to protect the eye from microbial attack. Antimicrobial peptides, such as β-defensins, are essential components of the innate immune system and are the first line of defence against invaders of the eye. High concentrations of l-arginine and l-lysine are necessary for the expression of β-defensins. These are supplied by epithelial cells in inflammatory processes. The limiting factor for initiation of β-defensin production is the transport of l-arginine and l-lysine into the cell. This transport is performed to 80% by only one transporter system in the human, the y+-transporter. This group of proteins exclusively transports the cationic amino acids l-arginine, l-lysine and l-ornithine and is also known under the term cationic amino acid transporter proteins (CAT-proteins). Various infections associated with l-arginine deficiency (for example psoriasis, keratoconjuctivitis sicca) are also associated with an increase in β-defensin production. For the first time, preliminary work has shown the expression of human CATs in ocular surface epithelia and tissues of the lacrimal apparatus indicating their relevance for diseases of the ocular surface. In this review, we summarize current knowledge on the human CATs that appear to be integrated in causal regulation cascades of β-defensins, thereby offering novel concepts for therapeutic perspectives. [Copyright &y& Elsevier]

Objectives: Dokhwaljihwang-tang, one of the prescriptions in Four Constitution medicine, has been used to treat neurological disorders. This work was aimed to examine the effect of Dokhwaljihwang-tang on lipopolysaccharide-induced inflammatory cytokine production in peripheral blood mononuclear cells from the lesser yang subjects. Methods: The inflammatory cytokines, interleukin 1 beta, interleukin 4 and tumor necrosis factor were measured using the ELISA. The interleukin 1 beta mRNA expression was evaluated with reverse transcriptase-polymerase chain reaction. The expression level of nuclear factor kappa B was examined by western blotting. Results: Dokhwaljihwang-tang significantly inhibited interleukin 1 beta and interleukin 4 production (p<0.05). When Dokhwaljihwang-tang was pre-treated at the dose of 1 mg/ml, it not only decreased the interleukin 1 beta mRNA expression, but also inhibited the activation of nuclear factor kappa B. Discussion: These results suggest the potential of Dokhwaljihwang-tang as a source of pharmaceutical acupuncture for neuronal inflammatory diseases. [ABSTRACT FROM AUTHOR]

Abstract: Dendritic cells (DCs) are key players in activation of the adaptive immune system by their ability of antigen presentation to and priming of T cells. An increasing body of evidence suggests that DCs may also play an important role in induction of tolerance, predominantly by induction of regulatory T cells (Treg). More recently, data have been published on how Toll-like receptor (TLR) ligands and cytokines affect DC differentiation, and how DC subsets might be involved in immunoregulation and tolerance rather than in T cell activation. The most important features of tolerance-inducing DCs appear to be their maturation state and their cytokine secretion pattern. The following types of tolerance-inducing DCs have been reported: immature DCs (DCsim) or DCs in the steady state (DCsst), DCsIL-10, semi-mature DCsTNF-α, semi-mature DCsIL-6. With this review article we would like to discuss the aforementioned types of tolerogenic DCs with a focus on semi-mature DCsIL-6 and discuss their potential role in maintenance of (hepatic or intestinal) immune homeostasis and inflammatory diseases such as inflammatory bowel disease. [Copyright &y& Elsevier]

Objective: To review the literature on herbal preparations commonly utilized in the treatment of rheumatic indications. Methods: Search of MEDLINE (PubMed) was performed using both the scientific and the common names of herbs. Relevant articles in English were collected from PubMed and reviewed. Results: This review summarizes the efficacy and toxicities of herbal remedies used in complementary and alternative medical (CAM) therapies for rheumatologic conditions, by elucidating the immune pathways through which these preparations have antiinflammatory and/or immunomodulatory activity and providing a scientific basis for their efficacy. Gammalinolenic acid suppresses inflammation by acting as a competitive inhibitor of prostaglandin E2 and leukotrienes (LTs) and by reducing the auto-induction of interleukin1α (IL-1α)-induced pro-IL-1β gene expression. It appears to be efficacious in rheumatoid arthritis (RA) but not for Sjogren’s disease. The antiinflammatory actions of Harpagophytum procumbens is due to its action on eicosanoid biosynthesis and it may have a role in treating low back pain. While in vitro experiments with Tanacetum parthenium found inhibition of the expression of intercellular adhesion molecule-1, tumor necrosis factor alpha (TNF-α), interferon-γ, IκB kinase, and a decrease in T-cell adhesion, to date human studies have not proven it useful in the treatment of RA. Current experience with Tripterygium wilfordii Hook F, Uncaria tomentosa, finds them to be efficacious in the treatment of RA, while Urtica diocia and willow bark extract are effective for osteoarthritis. T. wilfordii Hook F extract inhibits the production of cytokines and other mediators from mononuclear phagocytes by blocking the up-regulation of a number of proinflammatory genes, including TNF-α, cyclooxygenase 2 (COX-2), interferon-γ, IL-2, prostaglandin, and iNOS. Uncaria tomentosa and Urtica diocia both decrease the production of TNF-α. At present there are no human studies on Ocimum spp. in rheumatic diseases. The fixed oil appears to have antihistaminic, antiserotonin, and antiprostaglandin activity. Zingiber officinale inhibits TNF-α, prostaglandin, and leukotriene synthesis and at present has limited efficacy in the treatment of osteoarthritis. Conclusions: Investigation of the mechanism and potential uses of CAM therapies is still in its infancy and many studies done to date are scientifically flawed. Further systematic and scientific inquiry into this topic is necessary to validate or refute the clinical claims made for CAM therapies. An understanding of the mechanism of action of CAM therapies allows physicians to counsel effectively on their proper and improper use, prevent adverse drug-drug interactions, and anticipate or appreciate toxicities. Relevance: The use of CAM therapies is widespread among patients, including those with rheumatic diseases. Herbal medications are often utilized with little to no physician guidance or knowledge. An appreciation of this information will help physicians to counsel patients concerning the utility and toxicities of CAM therapies. An understanding and elucidation of the mechanisms by which CAM therapies may be efficacious can be instrumental in discovering new molecular targets in the treatment of diseases. [Copyright &y& Elsevier]

• Vascular abnormality at inflamed sites facilitates efficient accumulation of red blood cell vesicle (ReV). • Lipids of ReV optimizes cerium oxide crystallization process, leading to smaller size and higher Ce(III) content. • The resulted Ce-ReV shows superior therapeutic outcomes over clinically used drugs in murine colitis model. • Hybridization with mesenchymal stem cell exosomes exerts additional repair benefit for improving the therapeutic outcomes. [Display omitted] Reactive oxygen species (ROS) are key contributors to inflammatory progression and damage. Upon clinical and experimental observation of vascular abnormalities in acute inflammatory diseases, we explore cellular vesicles as templates and carriers to elevate therapeutic performance of nano-antioxidant. Specifically, we develop a mild one-pot approach for in situ growth of cerium oxide (Ce) nanocrystals onto nano-sized red blood cells vesicles (ReVs). Besides excellent biocompatibility, Ce-ReVs have very high ROS-scavenging activity, which is experimentally and theoretically explained by discovering the unique functions of membrane lipids in optimizing Ce nanocrystals with ultrasmall size (~ 3 nm) and ultrahigh Ce(III) content (~ 60.8%). In colitis and acute liver injury models, Ce-ReVs notably enhance accumulation at the inflamed sites and confer strong ROS elimination. Moreover, we upgrade the system by hybridizing ReVs with mesenchymal stem cell-derived exosomes and demonstrate additional repair function of highly damaged tissues, further verifying the satisfactory flexibility and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Fungal volatile organic compounds (VOCs) comprise a group of compounds commonly found in damp or water-damaged indoor places affecting air quality. Indoor fungal pollution is a severe threat to human health, contributing to the onset of allergic diseases. The compound 1-octen-3-ol, known as "mushroom alcohol", is the most abundant VOC and confers the characteristic mold odor. Exposure to 1-octen-3-ol induces inflammatory markers and episodes of allergic rhinitis and conjunctivitis; however, the effects of this compound towards mitochondria are fairly known. The present study aimed to evaluate the effects of 1-octen-3-ol on inflammatory targets and on mitochondrial morphology and bioenergetic rate in D. melanogaster. Drosophilas were exposed by inhalation to 2.5 μL/L and 5 μL/L of 1-octen-3-ol for 24 h. Observation showed a decreasing in the survival and locomotor ability of flies. Superoxide dismutase (SOD) activity was induced whereas Catalase (CAT) activity was inhibited. Analysis of the mitochondria respiration, detected inhibition of complex I and II in the electron transport chain and a decreased bioenergetic rate. Electronic microscopy provided morphological insights of the mitochondrial status in which a disarrangement in mitochondrial cristae profile was observed. 1-Octen-3-ol induced increased activity of caspase 3/7 and ERK phosphorylation. The mRNA relative steady-state levels of p38MAPK and JNK were down-regulated, whereas NF-κB and p53 were up-regulated. In parallel, nitrite levels were induced in relation to the non-exposed group. These findings point to the mitochondria as a crucial target for the toxicity of 1-octen-3-ol in parallel with activation of pro-inflammatory factors and apoptotic signaling pathway cascade. Image 1 • 1-octen-3-ol inhalation causes mortality and locomotor damage in D. melanogaster. • Fungal compound induces mortality and proinflammatory response in fruit flies. • Mitochondrial and respiration dysfunction in drosophilas exposed to 1-octen-3-ol. [ABSTRACT FROM AUTHOR]