Cascade Of Mediators Research Articles

Varicella-zoster virus-related neurological complications: From infection to immunomodulatory therapies.

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.

Advanced age worsens respiratory function and pulmonary inflammation after burn injury and this correlates with changes in the fecal microbiome in mice.

Cutaneous burn injury in the elderly is associated with poor clinical outcomes and increased pulmonary-related complications. We and others have shown that burn injury triggers a cascade of inflammatory mediators which increase gut permeability and dysbiosis of the fecal microbiota and this is more dramatic in the aged. Since cross-talk between intestinal microbes and the lung, termed the "gut-lung axis," impacts immunity and homeostasis in the airway, we hypothesized that the increased intestinal dysbiosis in age and burn injury may contribute to excessive pulmonary inflammation and poor prognosis after injury. To explore this hypothesis, we used a clinically relevant murine model of burn injury in which young and aged mice are subjected to a 12% total body surface area dorsal scald burn or sham injury. 24 hours after injury, lung function was assessed and lungs and feces were collected for analysis of inflammatory mediators and fecal microbial species. The results show that, when compared to younger mice, burn injury in aged mice triggers a decline in respiratory function and exacerbates pulmonary inflammation. In addition to heightened levels of the neutrophil recruiting chemokine CXCL1, aged mice displayed a profound increase in the pro-inflammatory protein, calprotectin, in the lung after burn injury. Comparison of the fecal microbiome and inflammatory markers in the lung revealed unique, age-dependent, correlation patterns between individual taxa and pulmonary inflammation. Taken together, these findings suggest that the post-burn dysbiosis of the gut flora in aged mice may contribute to the changes in pulmonary inflammatory profiles.

Circulating Autoantibody Profiling Identifies LIMS1 as a Potential Target for Pathogenic Autoimmunity in pathologic Myopia

High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.

Design and Synthesis of Indazole-Indole Hybrid via tert-Butyl Nitrite Mediated Cascade Diazotization/Isomerization/Cyclization.

In this report, a tert-butyl nitrite (TBN)-mediated straightforward metal-free approach has been presented for the synthesis of a diverse range of C-3-substituted indazole-indole hybrids using readily accessible 2-(indolin-3-ylidenemethyl)aniline derivatives. This strategy is proposed to occur via a diazonium salt intermediate that is capable of cascade isomerization and intramolecular C-N bond formation through a 5-endo-dig cyclization to achieve a wide variety of indazole-indole hybrids in good yields.

Suppressive Activity of Boiogito, a Japanese Traditional Kampo Medicine, on Periostin Secretion in Human Fibroblast-Like Synoviocytes In Vitro.

Background Knee osteoarthritis (KOA) is a prevalent degenerative disease that affects the knee joints, particularly among individuals aged over 40 years. It leads to pain, stiffness, and reduced quality of life; affects approximately 300 million individuals worldwide; and is increasing, particularly in developed nations. Although treatments for KOA range from conservative measures to surgical interventions, such as total knee arthroplasty (TKA), the financial burden of TKA in many countries underscores the urgent need for effective conservative therapies. The pathophysiology of KOA involves articular cartilage degeneration, increased subchondral bone turnover, synovitis, and periarticular soft tissue contracture. Abnormal bone turnover, intensified by factors, such as weight gain and knee injury, precedes cartilage degeneration. Synovitis, characterized by inflammation in the synovial tissue, plays a crucial role in perpetuating the disease by triggering a cascade of catabolic and proinflammatory mediators, including cytokines, such as interleukin (IL)-1 beta, tumor necrosis factor-alpha, and IL-13. Periostin, an extracellular matrix protein, is implicated in KOA progression, with its levels increasing with disease severity. Materials & methods In this study, the preventive effect of boiogito (BOT), a traditional herbal medicine, on periostin secretion in human fibroblast-like synoviocytes (hFLS) stimulated by IL-13 was investigated. Synoviocyte Growth Medium and recombinant human IL-13 were used for cell culture and stimulation. BOT was dissolved in phosphate-buffered saline and applied to cell cultures. Periostin secretion and mRNA expression were measured using enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction, respectively. Cell viability was assessed using an MTT assay, and signal transducer and activator of transcription factor 6 (STAT6) phosphorylation was examined using Western blotting. Results IL-13 stimulation of hFLS significantly increased periostin secretion, with levels rising above 20 ng/mL after 72 h of stimulation. Pretreatment with BOT dose-dependently suppressed periostin secretion, with doses of 1,000μg/mL significantly reducing periostin levels. Furthermore, BOT inhibited periostin mRNA expression and STAT6 phosphorylation in IL-13-stimulated hFLS, suggesting its potential in modulating IL-13-mediated inflammatory pathways in KOA. Conclusion This study demonstrated the preventive effect of BOT on periostin secretion in IL-13-stimulated hFLS, highlighting its potential as a therapeutic agent for KOA. By inhibiting periostin production and downstream signaling pathways, BOT may offer a promising conservative treatment option for KOA, addressing the inflammatory cascade implicated in disease progression. Further research is warranted to elucidate the specific herbal components responsible for the therapeutic effects of BOT and to validate its efficacy in clinical settings.

Impact of CytoSorb® on interleukin-6 in cardiac surgery.

Cardiac surgery is known to activate a cascade of inflammatory mediators leading to a systemic inflammatory response. Hemadsorption (HA) devices such as CytoSorb® have been postulated to mitigate an overshooting immune response, which is associated with increased morbidity and mortality, and thus improve outcome. We aimed to investigate the effect of CytoSorb® on interleukin (IL)-6 levels in patients undergoing complex cardiac surgery in comparison to a control group. A total of 56 patients (28 CytoSorb®, 28 control) undergoing acute and elective cardiac surgery between January 2020 and February 2021 at the Department of Cardiac and Vascular Surgery, Clinic Floridsdorf, Vienna, were retrospectively analyzed. The primary endpoint was the difference in IL-6 levels between the CytoSorb® and control group. Secondary endpoint was periprocedural mortality. CytoSorb®, installed in the bypass circuit, had no significant effect on IL-6 levels. IL-6 peaked on the first postoperative day (HA: 775.3 ± 838.4 vs. control: 855.5 ± 1,052.9 pg/ml, p = 0.856). In total, three patients died in the HA group, none in the control (logistic regression model, p = 0.996). Patients with an increased Euroscore II of 7 or more showed a reduced IL-6 response compared to patients with an Euroscore II below 7 (178.3 ± 63.1 pg/ml vs. 908.6 ± 972.6 pg/ml, p-value = 0.00306). No significant reduction of IL-6 levels or periprocedural mortality through intraoperative HA with CytoSorb® in patients undergoing cardiac surgery was observed. However, this study was able to show a reduced immunologic response in patients with a high Euroscore II. The routine application of CytoSorb® in cardiac surgery to reduce inflammatory mediators has to be scrutinized in future prospective randomized studies.

Sensitive detection of cancer biomarker with enzyme-free mediated cascade signal amplification empowered undisturbed dual-mode assay

Cancer is a serious threat to human health, and early identification of cancer biomarkers is crucial for timely treatment. A dual-mode biosensing platform has been developed to identify colon carcinoma suppressor microRNA-199a (miRNA-199a). A biofuel cell is firstly constructed using hybridization chain reaction and catalytic hairpin assembly self-assembly. The anode is a flexible carbon cloth (CP) loaded with glucose oxidase-functionalized molybdenum disulfide nanorods (MoS2 nanorods), and the bio-cathode is made up of double-stranded deoxyribonucleotide chains generated by nucleic acid amplification technology. The linear range of the electrochemical method is 0.1 fM-100 pM, and the limit of detection is 24.1 aM (S/N = 3). The colorimetric method has a linear range of 0.1 fM-10000 pM with detection limit of 34.5 aM (S/N = 3). The combination of MoS2 nanorods, enzyme-free cascade signal amplification technology, and dual-mode detection strategy provides high sensitivity and accuracy, offering a promising method for accurate determination of cancer biomarkers.

Quantifying Phagocytosis by Immunofluorescence and Microscopy.

Phagocytosis is carried out by cells such as macrophages of the immune system, whereby particulates like bacteria and apoptotic bodies are engulfed and sequestered within phagosomes for subsequent degradation. Hence, phagocytosis is important for infection resolution and tissue homeostasis. Aided by the innate and adaptive immune system, the activation of various phagocytic receptors triggers a cascade of downstream signaling mediators that drive actin and plasma membrane remodeling to entrap the bound particulate within the phagosome. Modulation of these molecular players can lead to distinct changes in the capacity and rates of phagocytosis. Here, we present a fluorescence microscopy-based technique to quantify phagocytosis using a macrophage-like cell line. We exemplify the technique through the phagocytosis of antibody-opsonized polystyrene beads and Escherichia coli. This method can be extended to other phagocytes and phagocytic particles.

Clinical Study of non-traumatic causes and management of generalized peritonitis

Background: Peritonitis refers to an inflammatory response of the peritoneum in the abdominal cavity in terms of activation of local mediator cascades by different stimuli. Therefore, bacterial, viral and chemical agents may cause inflammation of the peritoneal layer. Secondary peritonitis is usually due to spillage of gastrointestinal or genitourinary microorganisms into the peritoneal cavity as a result of loss of integrity of the mucosal barrier. Methods: Cross sectional observational study was performed. All patients admitted and treated for perforation secondary to non-traumatic hollow viscus perforation in surgical units of Department of General Surgery, Government Medical College, Nalgonda, Telangana, India, during the period of October 2019 - September 2021. A detailed history was taken and all the patients were subjected to thorough clinical examination. Patients subjected to laparotomy are followed in post-operative period to know the complications, morbidity and mortality rates. General condition at the time of admission was monitored by noting presenting complaints, pulse, BP, respiratory rate, hydration status. Operative findings were recorded. Necessary surgical intervention done is recorded; post operatively patients will be followed up for any complications. Each case will be studied as per the proforma. Results: The most common age group was 40- 60yrs (53.3%) in the present study. Major etiological factor noted is gastric perforation and next is appendicular perforation& duodenal ulcer perforation. In this study pain abdomen was the predominant symptom and was presented in all cases (100%). In this study guarding/rigidity was seen in all cases (100%). Most of the cases had a mean duration of 10-19days of hospital stay. Mortality rate was found to be 16.6%. Conclusion: In our study, youngest age of small intestine perforation was 23years and oldest was 80 years. Most cases had a duration of hospital stay of 10- 19 days. Main presenting complaint was pain abdomen, vomiting, fever and distension of abdomen. Risk factors for perforations were smoking, tobacco, alcohol and NSAIDs.

Anti-Inflammatory Effects of the Iron Chelator, DIBI, in Experimental Acute Lung Injury.

Iron plays a critical role in the immune response to inflammation and infection due to its role in the catalysis of reactive oxygen species (ROS) through the Haber-Weiss and Fenton reactions. However, ROS overproduction can be harmful and damage healthy cells. Therefore, iron chelation represents an innovative pharmacological approach to limit excess ROS formation and the related pro-inflammatory mediator cascades. The present study was designed to investigate the impact of the iron chelator, DIBI, in an experimental model of LPS-induced acute lung injury (ALI). DIBI was administered intraperitoneally in the early and later stages of lung inflammation as determined by histopathological evaluation. We found that lung tissues showed significant injury, as well as increased NF-B p65 activation and significantly elevated levels of various inflammatory mediators (LIX, CXCL2, CCL5, CXCL10, IL-1𝛽, IL-6) 4 h post ALI induction by LPS. Mice treated with DIBI (80 mg/kg) in the early stages (0 to 2 h) after LPS administration demonstrated a significant reduction of the histopathological damage score, reduced levels of NF-B p65 activation, and reduced levels of inflammatory mediators. Intravital microscopy of the pulmonary microcirculation also showed a reduced number of adhering leukocytes and improved capillary perfusion with DIBI administration. Our findings support the conclusion that the iron chelator, DIBI, has beneficial anti-inflammatory effects in experimental ALI.

Tocilizumab overcomes chemotherapy resistance in mesenchymal stem-like breast cancer by negating autocrine IL-1A induction of IL-6

Triple-negative breast cancer (TNBC) patients with mesenchymal stem-like (MSL) subtype have responded poorly to chemotherapy whereas patients with basal-like 1 (BL1) subtype achieved the best clinical response. In order to gain insight into pathways that may contribute to the divergent sensitivity to chemotherapy, we compared the inflammatory profile of the two TNBC subtypes treated with docetaxel. Cellular signaling analysis determined that docetaxel activated MAPK pathway in MSL TNBCs but not BL1 TNBCs. The subsequent MAPK pathway activation in MSL TNBCs led to an IL-1A mediated cascade of autocrine inflammatory mediators including IL-6. Utilizing the humanized IL-6R antibody, tocilizumab, our in vitro and in vivo data show that MSL TNBCs treated with tocilizumab together with chemotherapy results in delayed tumor progression compared to MSL TNBCs treated with docetaxel alone. Our study highlights a molecular subset of TNBC that may be responsive to tocilizumab therapy for potential translational impact.

Discussion of the immunomorphological role of interactions between mast cells and Helicobacter pylori in the gastric mucosa

Helicobacter pylori induced gastritis accounts for 70% of cases in the structure of this pathology. Features of the long-term inflammatory reaction of the mucous membrane are directly related to the mechanisms of bacterial pathogenicity, and features of immunogenesis within narrow limits of the specific tissue microenvironment of organ structures. Mast cells appear to be one of the key players (promoters) in the regulation of the inflammatory mediator cascade and the formation of cytokine-induced expression. Possessing a wide arsenal of biologically active substances, mast cells are able to participate in the formation of the immune response and resistance of the gastric mucosa, modulating both pro- and anti-inflammatory effects. The antigen-presenting features of mast cells are of interest in terms of interaction with H. pylori and induction of mucosa bacterial colonization. The aim of study was to assess the mast cell tryptase profile of the gastric mucosa in the immunopathogenesis of H. pylori-associated inflammation. Material and methods. The study included 19 biopsies of the gastric mucosa with unknown status of H. pylori infection. Microslides were stained with hematoxylin and eosin, and Giemsa's dye for plain microscopy. H. pylori infection of the gastric mucosa was detected using the immunohistochemical method. Using double immunofluorescent labeling, localization of tryptase-positive mast cells and H. pylori strains was detected. Results. In patients infected with H. pylori (n=12), there was a significant increase in the number of tryptase-positive mast cells (177.99±30.55 vs 88.58±11.49; p<0.05) with activation of secretory pathways and release of protease into the extracellular matrix of the gastric mucosa. The quantitative parameters of mast cells in the group of patients with an undetected pathogen and signs of a chronic inflammation of the gastric mucosa were statistically significantly lower than in the group of infected patients. Co-localization of tryptase-positive mast cells and H. pylori strains (with the formation of areas of large free-lying granule accumulation around the glands with pronounced degree of H. pylori contamination) was detected in gastrobiopsy specimens, the fact evidencing their close involvement in the development of inflammatory reactions of the gastric mucosa. Conclusion. The study demonstrated the features of mast cells and H. pylori interaction revealing previously unknown aspects of gastritis pathophysiology. The data obtained contribute a valuable insight to choose a treatment strategy for H. pylori-associated gastritis.

Synthetic Biology-Powered Biosensors Based on Crispr/Cas Mediated Cascade Signal Amplification for Precise Rna Detection

Synthetic Biology-Powered Biosensors Based on Crispr/Cas Mediated Cascade Signal Amplification for Precise Rna Detection

Cover Feature: Ag(I)‐Catalyzed/Acid‐Mediated Cascade Cyclization of ortho‐Alkynylaryl‐1,3‐dicarbonyls to Access Arylnaphthalenelactones and Furanonaphthol Libraries via Aryl‐Disengagement (Chem. Asian J. 1/2022)

The diverging path: The artwork in the cover depicts the use of ortho-alkynylarylketones with a 1,3-dicarbonyl pendant for the synthesis of arylnaphthalenelactone and furanonaphthol libraries. The method utilized a silver catalyst to promote the decarboxylative cyclization in one pot to vastly improve access to arylnaphthalenelactones. For ketone substrates containing a 2-chloro-4,6-dimethoxybenzene substituent, the reaction diverged into the novel oxy-dearylation reaction to form furanonaphthols. The method was general and applicable to a wide range of substrates. More information can be found in the Research Article by Jumreang Tummatorn et al.

Transcutaneous vagal nerve simulation to reduce a systemic inflammatory response syndrome and the associated intestinal failure: study protocol of a prospective, two-armed, sham-controlled, double-blinded trial in healthy subjects (the NeuroSIRS-Study)

PurposeSurgery initiates pro-inflammatory mediator cascades leading to a variably pronounced sterile inflammation (SIRS). SIRS is associated with intestinal paralysis and breakdown of intestinal barrier and might result in abdominal sepsis. Technological progress led to the development of a neurostimulator for transcutaneous auricular vagal nerve stimulation (taVNS), which is associated with a decline in inflammatory parameters and peristalsis improvement in rodents and healthy subjects via activation of the cholinergic anti-inflammatory pathway. Therefore, taVNS might be a strategy for SIRS prophylaxis.MethodsThe NeuroSIRS-Study is a prospective, randomized two-armed, sham-controlled, double-blind clinical trial. The study is registered at DRKS00016892 (09.07.2020). A controlled endotoxemia is used as a SIRS-mimicking model. 2 ng/kg bodyweight lipopolysaccharide (LPS) will be administered after taVNS or sham stimulation. The primary objective is a reduction of clinical symptoms of SIRS after taVNS compared to sham stimulation. Effects of taVNS on release of inflammatory cytokines, intestinal function, and vital parameters will be analyzed.DiscussionTaVNS is well-tolerated, with little to no side effects. Despite not fully mimicking postoperative inflammation, LPS challenge is the most used experimental tool to imitate SIRS and offers standardization and reproducibility. The restriction to healthy male volunteers exerts a certain bias limiting generalizability to the surgical population. Still, this pilot study aims to give first insights into taVNS as a prophylactic treatment in postoperative inflammation to pave the way for further clinical trials in patients at risk for SIRS. This would have major implications for future therapeutic approaches.

Inflammation as a Target for Epilepsy Therapy

Inflammation results from a cascade of inflammatory mediators, with concomitant anti-inflammatory molecules, often due to trauma, ischemia, infection, or an immune process. The inflammatory mediators arise from tissue, or blood circulating cells, and can involve nonspecific innate immunity or antigen-specific adaptive immunity.1-3 In the brain, these mechanisms are mediated through microglia, astrocytes, neurons, and endothelial cells, as well as leukocytes entering the parenchyma through disruption of the blood–brain barrier. Cytokines are polypeptide mediators of inflammation that are released by these cells and interact with various cognate receptors, leading to an array of pathophysiologic effects that contribute to inflammation.4 Chemokines are a specific type of cytokine that attracts leukocyte migration into the parenchymal injury. These multiple pathways mediating inflammation provide many targets for anti-inflammatory therapies.

GaCl3-Mediated Cascade [2 + 4]-Cycloaddition/[4 + 2]-Annulation of Donor-Acceptor Cyclopropanes with Conjugated Dienes: Strategy for the Construction of Benzobicyclo[3.3.1]nonane Skeleton.

Structurally important benzobicyclo[3.3.1]nonane derivatives were synthesized by a gallium trichloride mediated reaction of readily available donor-acceptor cyclopropanes (DACs) with 1,3-dienes as a one-pot cascade ionic [2 + 4]-cycloaddition/Friedel-Crafts-type cyclization process. At the first stage, DACs act as sources of formal gallium 1,2-zwitterionic complexes to give 6-benzylcyclohex-3-ene-1,1-dicarboxylates that are converted under certain conditions in the presence of GaCl3 to give benzobicyclo[3.3.1]nonanes in 30-74% yields. The process is tolerant of varying substituents at different positions of the main framework. Further, potentially useful modifications of benzobicyclo[3.3.1]nonane derivatives are demonstrated. 2-Cyclopropylbutadiene reacts with DAC at higher temperature more deeply with cleavage of three-membered rings in both cyclopropane substrates, and twofold alkylation of the Ph-substituent at ortho- and meta-positions, that leads to a 1,2,7,8,9,10-hexahydro-6H-7,10a-methanocycloocta[cd]indene skeleton. Cyclopropane-1,1-diesters containing a bulky substituent in the ester group react with isoprene in a different way to give bicyclic lactones containing a 2-oxabicyclo[2.2.2]octan-3-one moiety.

The diagnostic significance of PGGT1B in psoriasis.

Psoriasis is a chronic and recurrent inflammatory skin disorder driven by a complex cascade of inflammatory mediators. The present study focused on the potential clinical significance of PGGT1B in psoriasis development. The peripheral blood mononuclear cells (PBMCs) were isolated from 81 psoriasis patients and 84 healthy controls, and the expression levels of PGGT1B in PBMCs were examined by quantitative real-time polymerase chain reaction (RT-qPCR) methods. Furthermore, we tested the relationship between the level of PGGT1B in PBMCs and psoriasis severity. Also, we analyzed the potential significance of PGGT1B in psoriasis diagnosis. Finally, patients with psoriasis were divided into progressive and stable stage groups, and the differential expression of PGGT1B, TNF-α, IL-17, and IFN-γ between different phases were analyzed. PGGT1B was dramatically decreased in the psoriasis patients' PBMCs and negatively correlated with the Psoriasis Area and Severity Index (PASI). Moreover, receiver operating characteristics analysis showed the potential of differentially expressed PGGT1B in terms of distinguishing psoriasis patients from healthy controls. Finally, compared to the patients in the stable phase, PGGT1B was markedly reduced in patients' PBMCs in the progressive stage, while proinflammatory cytokines TNF-α and IL-17 were notably increased. PGGT1B was downregulated in psoriasis patients' PBMCs and may serve as a potential biomarker for the diagnosis and treatment of psoriasis.

P(III)‐Mediated Cascade C‐N/C‐S Bond Formation: A Protocol towards the Synthesis of N,S‐Heterocycles and Spiro Compounds

AbstractA P(III)‐mediated entry towards construction of C−N/C−S bond has been devised. The developed heterocyclization method was exercised for the synthesis of a diverse range of N,S‐heterocycles and related spiro molecules. P(NMe2)3 revealed the maximum efficacies under the aerobic reaction conditions and a spectrum of bis‐nucleophiles, and isothiocyanates were tolerated well to serve the access of manifold immense molecules.magnified image

The Role of Resolvins: EPA and DHA Derivatives Can Be Useful in the Prevention and Treatment of Ischemic Stroke.

Introduction: Most ischemic strokes develop as a result of atherosclerosis, in which inflammation plays a key role. The synthesis cascade of proinflammatory mediators participates in the process induced in the vascular endothelium and platelets. Resolvins are anti-inflammatory mediators originating from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which may improve the prognosis related to atherosclerosis by inhibiting the production of proinflammatory cytokines, limiting neutrophil migration, or positively influencing phagocytosis. Although clinical trials with resolvin in humans after stroke have not been realized, they may soon find application. Aim: The aim of the study was to review the available literature on the scope of the possibilities of the prevention and treatment of stroke with the use of resolvins, EPA and DHA derivatives. Materials and methods: The review features articles published until 31 January 2020. The search for adequate literature was conducted using the keywords: stroke and resolvins. Over 150 articles were found. Studies not written in English, letters to the editor, conference abstracts, and duplicate information were excluded. Results: In several studies using the animal model, the supplementation of resolvin D2 decreased brain damage caused by myocardial infarction, and it reversed the neurological dysfunction of the brain. A decrease in the concentration of proinflammatory cytokines, such as TNF-α, Il-6, and Il-1β, was also observed, as well as a decrease in the scope of brain damage. In the context of stroke in animals, the treatment with resolvin D2 (RvD2) (injection) has a better effect than supplementation with DHA. Conclusions: Resolvins are characterised by strong anti-inflammatory properties. Resolvins improve prognosis and decrease the risk of developing cardiovascular disease, consequently lowering the risk of stroke, and may find application in the treatment of stroke.