Cationic Protein Research Articles

Atopic dermatitis in Taiwanese children: The laboratory values that correlate best to the SCORAD index are total IgE and positive Cheddar cheese IgE.

Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease associated with a personal or family history of atopic diseases. Determining the objective severity scoring of AD index (SCORAD) and total immunoglobulin E (IgE) to help to stage the severity (lesions extent and intensity of the lesions and then the itch and sleep disturbance they may cause) of AD in children.In this study, we adopted the SCORAD index, which consists of severity, area, and sleep disturbance, to evaluate the AD status of children up to 18 years old. We examined the blood levels of total serum IgE, white blood cell count/differential count (WBC/DC), eosinophil counts (EC), eosinophil cationic protein (ECP) and specific IgE.A total of 208 children with AD were enrolled in this study. Serum IgE values and a number of specific IgE that are positive significantly different SCORAD index through simple linear regression; however, after multiple linear regression, only IgE values (95% CI: 0.001–0.004, P < .001), total WBC count (95% CI: 0.112–1.736, P = .026), EC (95% CI: 0.045–6.706, P = .047), and specific IgE to Cheddar cheese (95% CI: 1.814–16.731, P = .015) remain different. After applying the Phi coefficient, we found that specific IgE to tuna (r = 0.632), codfish (r = 0.613), and clam (r = 0.613) each had a moderate correlation with specific IgE to Cheddar cheese. The 6 most common allergens were found to be mite (D. Farinae: 65.9%), mite (D. Pterony: 64.9%), house dust (47.6%), cockroach mix (37.0%), shrimp (30.8%), and crab (22.6%). Covariates of SCORAD index, severity, area, and sleep disturbance differed.In this study, we found that total IgE values, specific IgE values, WBC, EC, and specific IgE to Cheddar cheese have significant correlations with SCORAD index in AD of Taiwanese children.

Structural Polymorphism of Single pDNA Condensates Elicited by Cationic Block Polyelectrolytes.

DNA folding is a core phenomenon in genome packaging within a nucleus. Such a phenomenon is induced by polyelectrolyte complexation between anionic DNA and cationic proteins of histones. In this regard, complexes formed between DNA and cationic polyelectrolytes have been investigated as models to gain insight into genome packaging. Upon complexation, DNA undergoes folding to reduce its occupied volume, which often results in multi-complex associated aggregates. However, when cationic copolymers comprising a polycation block and a neutral hydrophilic polymer block are used instead, DNA undergoes folding as a single molecule within a spontaneously formed polyplex micelle (PM), thereby allowing the observation of the higher-order structures that DNA forms. The DNA complex forms polymorphic structures, including globular, rod-shaped, and ring-shaped (toroidal) structures. This review focuses on the polymorphism of DNA, particularly, to elucidate when, how, and why DNA organizes into these structures with cationic copolymers. The interactions between DNA and the copolymers, and the specific nature of DNA in rigidity; i.e., rigid but foldable, play significant roles in the observed polymorphism. Moreover, PMs serve as potential gene vectors for systemic application. The significance of the controlled DNA folding for such an application is addressed briefly in the last part.

Silencing ICAM-1 reduces the adhesion of vascular endothelial cells in mice with immunologic contact urticaria.

Immunologic contact urticaria (ICU) is an immediate response of wheal caused by various contactants in vulnerable individuals, with undefined pathogenesis. In the present study, we aim to explore the effects of intercellular cell adhesion molecule-1 (ICAM-1) gene silencing by RNA inference (RNAi) on vascular endothelial cells (VECs) adhesion molecule expression and cell-cell adhesion in ICU mice. Sixty BALB/c mice were selected, among which 48 mice were used for establishment of ICU models. VECs from normal and ICU mice were grouped into different groups. Expressions of ICAM-1, eosinophilic cationic protein (ECP), total immunologlobulin E (tIgE), L-selectin (CD62L), integrin, alpha L (CD11a) in tissues and cells were evaluate by RT-qPCR and western blotting. Cell proliferation was evaluated by MTT assay and EdU staining and cell adhesive function by cell-cell adhesion assay. Compared with normal mice, ICU mice had increased expressions of ICAM-1, ECP, tIgE, CD62L, and CD11a.ICAM-1 gene silencing decreased expressions of ECP, tIgE, CD62L, and CD11a, enhanced cell proliferation, and more activity in cell adhesion. These findings indicate that RNAi-mediated gene silencing of ICAM-1 may decrease VECs adhesion expression and reduce cell-cell adhesion in mice with ICU.

Baicalin regulates Treg/Th17 cell imbalance by inhibiting autophagy in allergic rhinitis

BackgroundBaicalin has many biological properties such as anti-oxidation and anti-allergy. The current study aimed to explore the effect of Baicalin on allergic rhinitis (AR) and its potential mechanism of action. MethodsPeripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation. Expression levels of Th17 and Treg cells-related proteins in nasal mucosa and peripheral blood cells were detected by real-time quantitative PCR, flow cytometry and Western blot. The mice were randomly divided into Control, ovalbumin (OVA), l-Baicalin, H-Baicalin, DSGC, 3-MA, and H-Baicalin + Rapa groups. Changes of allergic rhinitis conditions and eosinophil infiltration of the mice were detected and scored by Diff-Quik staining, and histological changes were observed by Hematoxylin & Eosin (H&E) staining and Periodate Schiff (PAS) staining. Serological changes, expression levels of interleukin-17A (IL-17A), interleukin-10 (IL-10), eosinophilic cationic protein (ECP) and anti-OVA-specific antibodies were detected by Enzyme-linked immunosorbent assay (ELISA). ResultsClinical case analysis found that AR patients had a Th17/Treg imbalance and activated autophagy, however, Baicalin restored Th17/Treg cell balance and inhibited autophagy in vitro. in vivo experiments demonstrated that Baicalin inhibited OVA-induced allergic nasal symptoms and the activation of autophagy pathway, which was the same as the regulation of 3-MA, while Rapa could weaken the effects of H-baicalin. Moreover, Baicalin reduced the infiltration of different inflammatory cells of the nasal lavage fluid, prevented the damages to epithelial cells, and improved nasal mucosal thickness and mucus secretion. In addition, Baicalin regulated the balance of mouse anti-OVA-specific antibody levels and expressions of Th17/Treg-associated cytokines. ConclusionOur study revealed that Baicalin can be used to treat AR, and the effect is realized through inhibiting autophagy to regulate Th17/Treg cell differentiation.

Study of Interactions between Antigens and Polymeric Adjuvants in Vaccines by Frontal Analysis Continuous Capillary Electrophoresis.

Vaccine adjuvants are used to enhance the immune response induced by antigens that have insufficient immunostimulatory capabilities. The present work aims at developing a frontal analysis continuous capillary electrophoresis (FACCE) methodology for the study of antigen-adjuvant interactions in vaccine products. After method optimization using three cationic model proteins, namely lysozyme, cytochrome c, and ribonuclease A, FACCE was successfully implemented to quantify the free antigen and thus to determine the interaction parameters (stoichiometry and binding constant) between an anionic polymeric adjuvant (polyacrylic acid, SPA09) and a cationic vaccine antigen in development for the treatment for Staphylococcus aureus. The influence of the ionic strength of the medium on the interactions was investigated. A strong dependence of the binding parameters with the ionic strength was observed. The concentration of the polymeric adjuvant was also found to significantly modify the ionic strength of the formulation, the extent of which could be estimated and corrected.

Overcoming negatively charged tissue barriers: Drug delivery using cationic peptides and proteins.

Negatively charged tissues are ubiquitous in the human body and are associated with a number of common diseases yet remain an outstanding challenge for targeted drug delivery. While the anionic proteoglycans are critical for tissue structure and function, they make tissue matrix dense, conferring a high negative fixed charge density (FCD) that makes drug penetration through the tissue deep zones and drug delivery to resident cells extremely challenging. The high negative FCD of these tissues is now being utilized by taking advantage of electrostatic interactions to create positively charged multi-stage delivery methods that can sequentially penetrate through the full thickness of tissues, create a drug depot and target cells. After decades of work on attempting delivery using strong binding interactions, significant advances have recently been made using weak and reversible electrostatic interactions, a characteristic now considered essential to drug penetration and retention in negatively charged tissues. Here we discuss these advances using examples of negatively charged tissues (cartilage, meniscus, tendons and ligaments, nucleus pulposus, vitreous of eye, mucin, skin), and delve into how each of their structures, tissue matrix compositions and high negative FCDs create barriers to drug entry and explore how charge interactions are being used to overcome these barriers. We review work on tissue targeting cationic peptide and protein-based drug delivery, compare and contrast drug delivery designs, and also present examples of technologies that are entering clinical trials. We also present strategies on further enhancing drug retention within diseased tissues of lower FCD by using synergistic effects of short-range binding interactions like hydrophobic and H-bonds that stabilize long-range charge interactions. As electrostatic interactions are incorporated into design of drug delivery materials and used as a strategy to create properties that are reversible, tunable and dynamic, bio-electroceuticals are becoming an exciting new direction of research and clinical work.

Measuring inflammation in patients with allergic rhinitis using different biomarkers

Allergic rhinitis is an inflammatory disease affecting the mucosal lining of the nose of individuals of all ages. The allergen in the air involves‏ attaching by Immunoglobulin E that causes the release of inflammatory chemicals from mast cells. This study aimed to measure the serum level of biomarkers and to determine the correlation between them in mediating activate cell in patients with AR. In this study, blood samples were taken from 88 AR patients and 88 healthy controls (HC) Symptom score was measured using the SNOT-22 questionnaire and blood sample was analyzed for eosinophil counts (B-Eos) using optical flow cytometry, IgE by electrochemiluminescence immunoassay, as well as eosinophilic cationic protein, anti-alpha smooth muscle actin (anti-SMA), cyclooxygenase- 2 (COX-2R), phosphatase and tensin (PTEN) homolog and Tryptase Alpha/Beta 1 (TPSABI) by ELISA. B-Eos, IgE, ECP, anti-SMA, and symptom scores were significantly higher in AR patients than in HC. As a result, we found that there was correlation between B-Eos and ECP (r = 0.66, p = 0.001). There was also a correlation between IgE and symptom score (r=0.64, p=0.01). COX-2 also correlated with symptoms score (r = 0.52, p = 0.04). There was a positive correlation between phosphatase and tensin homolog and TPSAB1 (r = 0.76, p&lt;0.001) and PTEN and ECP (r = 0.53, p = 0.03). In conclusion, we realized that in allergic rhinitis, the airway inflammation was characterized by high numbers of eosinophil, IgE, ECP and anti-SMA. B- Eos, IgE and COX-2 were related to symptom scores. The study highlights the importance of systemic inflammation in AR.

Enhanced apoptotic activity in allergic diseases and its relationship with eosinophil cationic protein, systemic inflammation, and severity of atopic sensitisation

IntroductionThe association between serum soluble apoptotic markers, eosinophil cationic protein (ECP), and inflammatory parameters in allergic diseases has seldom been studied. This study aimed to investigate apoptotic activity in allergic diseases and its relationship with ECP, systemic inflammation, and severity of atopic sensitisation.Material and methodsA total of 125 patients with allergic diseases were investigated by measuring ECP, APO-1, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), allergen-specific immunoglobulin E (sIgE), total IgE (tIgE), and high-sensitivity C-reactive protein (hsCRP) levels.ResultsECP, APO-1, TRAIL, and hsCRP levels were significantly higher in patients with allergic diseases than in healthy individuals. Patients who tested positive for ECP had no significant differences in APO-1 and TRAIL levels compared with those who tested negative for ECP. However, among the patients who tested positive for ECP, those with elevated hsCRP concentrations had significantly higher APO-1 and TRAIL levels than those without elevated hsCRP concentrations (p &lt; 0.001, respectively). APO-1, TRAIL, and ECP levels were significantly higher in patients with inhalant allergy than in those with food allergy. APO-1 and TRAIL were significantly associated with hsCRP but not with tIgE and sIgE scores.ConclusionsApoptotic activity is enhanced in allergic diseases and is more closely linked to concomitant systemic inflammation than to the severity of atopic sensitisation, particularly in patients with inhalant allergy.

HIF1α Deficiency in Dendritic Cells Attenuates Symptoms and Inflammatory Indicators of Allergic Rhinitis in a SIRT1-Dependent Manner

Background: Allergic rhinitis is the most prevalent atopic disorder worldwide. Inflammation is believed to participate in allergic rhinitis. Previous studies indicate that hypoxia-inducible factor (HIF) promotes the development of allergic rhinitis, and dendritic cells are also involved in allergic rhinitis. Methods:We explored the consequences of HIF1α deficiency in dendritic cells on allergic rhinitis. Allergic rhinitis in mice was induced by ovalbumin (OVA). The levels of IgE, leukotriene C4 (LTC4), eosinophil cationic protein (ECP), prostaglandin D2 (PGD2), IFN-γ, IL-2, IL-4, IL-5, IL-10, and IL-13 in serum or nasal lavage fluid (NLF) were detected by ELISA. Inflammatory cells in NLF were counted by hemocytometer. The protein levels of p-ERK1/2, p-p38, p-JNK2, SIRT1, p-IκBα, and p65 were determined by Western blot. Results:HIF1α deficiency in dendritic cells (HIF1α^CD11c–/–) decreased sneezing and nasal rubbing, the production of OVA-specific IgE, LTC4, and ECP in serum and NLF, and the numbers of leukocytes, eosinophils, lymphocytes, and neutrophils in NLF. Th1 cytokines increased, while Th2 cytokines decreased in HIF1a^CD11c–/– mice. SIRT1/NF-κB signaling was inhibited in HIF1α^CD11c–/– mice, while SIRT1 inhibitor administration in HIF1α^CD11c–/– mice attenuated the symptoms and inflammatory indicators of allergic rhinitis. Conclusion:HIF1α deficiency in dendritic cells attenuates symptoms and inflammatory indicators of allergic rhinitis in a SIRT1-dependent manner.

Targeting Biological Polyanions in Blood: Strategies toward the Design of Therapeutics.

In this Review, we highlight well-described and emerging polyanions, and the way these molecules can be targeted in the design of potential therapeutics (synthetic and biologics) with applications in thrombosis and hemostasis. It is important to strike a balance between bleeding and clotting. In thrombosis, unwanted blood clots are formed in the lumen of a blood vessel, obstructing the flow of blood through the circulatory system. Over many years of research, several polyanionic biopolymers that can either impede (anticoagulant) or promote (procoagulant) blood clotting have been identified. Mediators impeding blood clotting, including polyanionic polysaccharides such as heparins and heparin mimics, are widely used as antithrombotics, although they impart adverse complications such as bleeding. Emerging synthetic polycations and well-described cationic proteins that are specifically designed to neutralize the biological activity of heparins to prevent bleeding complications are discussed. On the other hand, there is growing evidence that several polyanions bear a procoagulant nature in blood; polyphosphate (polyP), neutrophil extracellular traps (NETs), extracellular RNA, and cell-free DNA are shown to promote blood clotting. Recent research highlights the use of polycations and enzymes that either inhibit or cleave these procoagulant polyanions and demonstrates the proof-of-concept design of new antithrombotics without bleeding side effects. Additional studies have shown that some of these procoagulant polyanions can be used as a hemostat to prevent bleeding in an emergency. There are significant opportunities for chemists in the design of new inhibitors and agents with improved selectivity toward these biological polyanions, furthering the development of novel therapeutics.

Clinical value of IL-13 and ECP in the serum and sputum of eosinophilic AECOPD patients.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an inevitable trend in the development of the disease and eosinophils (EOS) participate in inflammation process. It is important to explore some relatively simple biomarkers in AECOPD which are useful to recognize the disease. In the present study, 108 hospitalized patients with AECOPD were collected and the levels of IL-13 and ECP in the serum and sputum were measured. The levels of IL-13 and ECP in sputum in the eosinophilic group were higher than those in the noneosinophilic group. Moreover, the noneosinophilic group had a higher rate of rehospitalization due to acute exacerbation during the one-year follow-up. The results show that eosinophils in peripheral blood are a simple, convenient, and inexpensive index for assessing the condition and prognosis of AECOPD patients. IL-13 and ECP are involved in the pathogenesis of eosinophilic AECOPD and may be the new targeted anti-inflammatory therapies.

The Effect of Triamcinolone-Soaked Gelfoam in Patients with Polypoid Mucosal Change after Endoscopic Sinus Surgery

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) recurs frequently after endoscopic sinus surgery (ESS). The aim of study was to evaluate the efficacy of triamcinolone-soaked absorbable gelatin foam (gelfoam) as a treatment for recurred polypoid changes after ESS.Subjects and Method: A total of 35 patients and 57 nasal cavities was retrospectively reviewed. All patients underwent triamcinolone- infused gelfoam packing for 1 week under nasal endoscopic guidance. Endoscopic scores were evaluated at 1 week, 1 month, and 3 months. We analyzed clinical characteristics between success and failure groups.Results: Endoscopic scores were significantly improved after triamcinolone-soaked gelfoam packing, and the effects were maintained at 3-month follow-up (1.85±0.61 vs. 0.82±0.77, p＜0.001). Duration between surgery and gelfoam packing was shorter in the success group compared to the failure group (8.2±6.9 vs. 13.7±8.4 weeks, p=0.033). Serum eosinophil cationic protein and tissue eosinophil counts were significantly higher in the failure group (p=0.025 and p=0.010, respectively).Conclusion: Triamcinolone-soaked gelfoam packing is an effective and safe method for managing recurrent polypoid change in patients with CRSwNP after ESS. Early intervention contributed to a successful result, and eosinophilic inflammation was associated with poor outcomes.

A randomized trial of Lactobacillus rhamnosus IDCC 3201 tyndallizate (RHT3201) for treating atopic dermatitis.

Probiotic therapies, mainly live bacteria, have been proven to be effective in treating atopic dermatitis (AD) with some controversies. Killed probiotics or postbiotics would have immunomodulatory effect in allergic diseases including AD. This study was performed to evaluate the therapeutic effect and safety of tyndallized Lactobacillus rhamnosus (IDCC 3201, isolated from the feces of a Korean breastfed infant, repeated heat-treated and incubated, RHT3201) in children with AD. In a randomized, double-blind, placebo-controlled study, RHT3201 at a dose of 1.0×1010 CPU/d or placebo was given in children (aged 1-12years) with moderate AD for 12weeks. SCORing of AD (SCORAD) scores, allergic inflammatory markers, and safety parameters were evaluated. For evaluating the therapeutic effects of RHT3201, 33 subjects in each group were analyzed. The change of SCORAD total score at 12weeks (primary outcome) from baseline was significantly greater in the RHT3201 group (-13.89±10.05) compared to the control group (-8.37±9.95). Levels of eosinophil cationic protein (ECP) and interleukin (IL)-31 showed tendency to decrease in the RHT3201 group and significant decreases in subgroup analysis in AD for ≥50months. For safety analysis, a total of 100 subjects (50 in the treated group and 50 in the control group) were evaluated, and there were no significant differences in safety parameters between two groups. In children with moderate AD, oral administration of RHT3201 showed the therapeutic effect on AD, the effects in part correlated with decrement of ECP and IL-31, and the effect was more remarkable in subgroup analysis.

Maternal Adherence to a Dairy-free Mediterranean Diet and Symptoms of Colic and Allergy in Exclusively Breastfed Infants: A Randomized-Controlled Study

Abstract Objectives Colic and allergy symptoms are problems encountered in the exclusively-breastfed newborn and are thought to be triggered by inflammatory responses in the gut. Maternal diet, especially cow's milk intake, has been associated with infantile colic and allergies, but no study examined the effect of Mediterranean diet. Thus, this study aims to investigate whether maternal adherence to a dairy-free Mediterranean diet, known for is anti-inflammatory properties, reduces colic and allergy symptoms in exclusively-breastfed infants. Methods Exclusively breastfeeding healthy primiparous women were recruited during their pregnancy third trimester and were randomly assigned to receive an education on dairy-free Mediterranean diet or no education (control group). Mother-infant pairs were followed up for 2 months postpartum and adherence to the diet was confirmed through 24 hour recalls. Data on infant fussing &amp; crying using validated “Daily Crying Diary” (Barr, et al., 1988) and allergy symptoms using validated CDC's “Breastfeeding and Infant Feeding Practices postnatal questionnaire” (Centers for Disease Control and Prevention, 2017) were collected on weeks 2, 4 and 7 postpartum. Infant stool samples were also collected to test for blood, pH, and eosinophil cationic protein as estimates of the degree of inflammation in the gut. Results Preliminary data from 10 mother-infant pairs showed that there was no group differences in the weights of the mothers and infants and number of allergy symptoms throughout the study. Colic (defined by the “Wessel Criteria” as crying episodes that last for &amp;gt;3 hours per day, for ≥3 days per week and for ≥3 weeks) was not observed in any infant. Findings from “Daily Crying Diaries” revealed that maternal adherence to dairy-free Mediterranean diet was associated with significantly lower average daily crying compared to controls (0.28 vs. 1.10 hours/d) in infants. Results on infant stool blood, pH, and eosinophil cationic protein are still pending. Conclusions Maternal adherence to a dairy-free Mediterranean diet did not affect allergy symptoms but decreased fussing and crying in exclusively breastfed infants. Mechanisms of action still remain to be determined. Funding Sources Lebanese American University.

Study of eosinophil cationic protein serum levels in patients with toxocariasis

Introduction: Toxocariasis is a zoonotic helminth infection with difficult diagnosis. Determination of specific IgG antibodies alone does not allow to establish the disease stage and to evaluate the treatment efficacy. Therefore it is necessary to identify additional markers that will assist the diagnosis. The purpose of our study was to identify and monitor eosinophil cationic protein (ECP) levels in patients with toxocariasis confirmed by serology and to compare our data with the literature to determine the relevance of this protein as an indicator for recent infection and the effectiveness of the therapy. Material and methods: ELISA (CUSABIO) commercial kit was used for determination of ECP concentration. Sixty serum samples were studied from individuals previously tested and confirmed for toxocariasis by the presence of specific anti-Toxocara IgG antibodies in ELISA (Toxocara IgG Rbiopharm) and the presence of specific bands in Western blot as confirmatory test (LD BIO). Twenty serum samples from clinically healthy blood donors were used as a control group. Results: The mean concentration of serum ECP in the patients with toxocariasis was significantly higher than in clinically healthy subjects. Seventy-two percent of patients affected by toxicariasis showed increased serum concentration of ECP. However, no statistically significant differences were observed in terms of age (p = 0.451) and sex (p = 0.682) of the patients or clinical form of the disease. ECP levels among patients with visceral toxocariasis were relatively higher (mean 22.99 ng / ml ± 13.16 SD) in comparison to those with ocular involvement (15.60 ng/ml ± 9.92 SD). Correlation between the presence of peripheral eosinophilia and the concentration of serum ECP was not also established. Conclusion: Data from our study give us reason to believe that serum levels of ECP could serve as an additional marker indicating recent infection, especially in patients without marked increase in the blood eosinophils.

Study of eosinophil cationic protein serum levels in patients with toxocariasis

Study of eosinophil cationic protein serum levels in patients with toxocariasis

Tubeimoside I Antagonizes Yoda1-Evoked Piezo1 Channel Activation.

Piezo1, a mechanosensitive Ca2+-permeable non-selective cationic ion channel protein, is involved in a wide range of biological processes and plays crucial roles in vascular development. However, the pharmacology of this protein is in its infancy. Yoda1, the first specific chemical activator of Piezo1 channels, can activate Piezo1 in absence of mechanical stimulation. Hence, we sought to identify inhibitors of Yoda1 from Traditional Chinese Medicine (TCM). Intracellular Ca2+ measurements were conducted in human umbilical vein endothelial cells (HUVECs), HEK 293T cells overexpressing TRPC5 and TRPM2 channels, as well as in CHO K1 cells overexpressing TRPV4 channels. We identified tubeimoside I (TBMS1) as a strong inhibitor of the Yoda1 response and demonstrated its selectivity for the Piezo1 channels. Similarly, Yoda1-induced inhibitory results were obtained in Piezo1 wild-type overexpressed cells, murine liver endothelial cells (MLECs), and macrophages. The physiological responses of TBMS1 were identified by isometric tension, which can inhibit Yoda1 relaxation of aortic rings. Our results demonstrated that TBMS1 can effectively antagonize Yoda1 induced Piezo1 channel activation. This study sheds light on the existence of Yoda1 inhibitors and improves the understanding of vascular pharmacology through Piezo1 channels.

Nekoduojančiųjų RNR reikšmė astmos patogenezei

Astma serga daugiau nei 300 milijonų žmonių visame pasaulyje ir 250 000 kasmet jų miršta, o ligos patogenezė vis dar nėra pakankamai ištirta. Tai itin heterogeninė, lėtinė uždegiminė kvėpavimo takų liga, kuriai būdingi dusulio, švokštimo, kosulio epizodai, pasireiškiantys dėl kvėpavimo takų obstrukcijos ir hiperreaktyvumo. Astmos uždegiminis atsakas apima daugybę skirtingų specializuotų imuninių ląstelių, iš kurių svarbiausi yra eozinofilai. Šios ląstelės patenka į kvėpavimo takus per kraują bei išskiria katijoninius baltymus, citokinus, chemokinus ir lipidų mediatorius, esančius jų citoplazminėse granulėse. Taip pat nustatyta, kad eozinofilai į aplinką gali išskirti ir nekoduojančiąsias ribonukleorūgštis (nkRNR) tarpląstelinių nanopūslelių–egzosomų pagalba. Eozinofilų egzosomose yra supakuojami dideli kiekiai nkRNR, taip šios ribonukleorūgštys (RNR) pernešamos kitoms ląstelėms. Visos RNR, kurių seka nėra tiesiogiai transliuojama į baltymo seką, yra vadinamos nkRNR. Remiantis grandinės nukleotidų skaičiumi, nkRNR skirstomos į trumpąsias ir ilgąsias. Svarbiausios trumposios nkRNR yra mažosios mikro RNR (miRNR), su Piwi baltymais susijusios RNR (piRNR) bei interferuojančios RNR (siRNR), kurios skirtingais keliais, tačiau visos slopina informacinės RNR (iRNR) transliaciją į baltymus. Ilgosios nekoduojančiosios RNR (inkRNR) yra kita nkRNR rūšis, kuriai taip pat tenka svarbus vaidmuo reguliuojant genų raišką. Be to, pastebėta, kad miRNR ir inkRNR gali sąveikauti tarpusavyje ir netiesiogiai kitų mediatorių pagalba reguliuoti viena kitos raišką. Žinoma, kad nkRNR turi skirtingą raiškos profilį, priklausomai nuo ląstelės tipo ir ligos būklės. Įrodyta, kad nkRNR yra susijusios su eozinofilinės astmos patogeneze, o jų raiškos spektras gali suteikti naudingos informacijos apie šios ligos egzistavimą. Kadangi nkRNR kiekis serume yra stabilus ir atsparus kraujyje esančioms ribonukleazėms, ši molekulė gali tapti itin naudingu biožymeniu astmai ir jos fenotipams bei endotipams nustatyti. Šioje apžvalgoje pristatomos nkRNR, didžiausią dėmesį sutelkiant į šiuo metu daugiausia tyrinėjamas miRNR bei inkRNR, jų reguliuojamų genų įtaką astmos patogenezei, įvertinamas šių molekulių tinkamumas ligos diagnostikai.

Eosinophil cationic protein is a potential surrogate marker of allergic contact dermatitis: A single-center, retrospective study of 216 patients

To the Editor: Although patch testing is the gold standard diagnostic test for allergic contact dermatitis, assessing the clinical relevance and differentiating between allergic and irritant contact dermatitis or another intrinsic eczema can be challenging1 because of a lack of reliable diagnostic tools and disease-specific biomarkers to support the diagnosis.

Type 2 inflammation in chronic rhinosinusitis without nasal polyps: Another relevant endotype

Chronic rhinosinusitis without nasal polyps (CRSsNP) is mainly considered a type 1 mediated disease. The role and clinical significance of type 2 immune responses in CRSsNP have not been addressed sufficiently; a recent cluster analysis for CRS described the existence of a subgroup of patients with CRSsNP with a type 2 inflammation. We aimed to characterize the underlying type 2 immune response and its clinical significance in patients with CRSsNP. A total of 240 patients with CRSsNP were endotyped and subdivided on the basis of expression of marker cytokines. Clinical data such as recurrence, comorbid asthma and allergy, and numbers of blood eosinophils and neutrophils were collected from all patients. Aselection of 15 patients was further characterized for the presence of eosinophils, neutrophils, Charcot-Leyden crystals, and eosinophil extracellular traps in the mucosae. A type 2 immune response with increased levels of IL-4, IL-5, eosinophil cationic protein, IgE, and Staphylococcus aureus enterotoxin-specific IgE was observed in 49% of patients with CRSsNP. Those patients showed increased numbers of blood and tissue eosinophils, and they displayed a considerable eosinophilic inflammation associated with eosinophil extracellular trap cell death and Charcot-Leyden crystals. Asignificantly increased prevalence of recurrence and asthma was observed in patients with type 2 CRSsNP compared with in patients with non-type 2 CRSsNP. However, only 4 of 117 patients with type 2 CRSsNP developed nasal polyps within 12 years. This study shows that type 2 immune responses in CRSsNP follow similar patterns but are less pronounced than in chronic rhinosinusitis with nasal polyps. Also CRSsNP with a moderate type 2 immune response showed a considerable eosinophilic inflammation with clinical impact.