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A 25-year-old man, who was taking treatment for his poorly controlled asthma, presented with symptoms of cough with expectoration, gradually progressive shortness of breath, fever on and off and diffuse wheeze for 2 years. Chest X-ray revealed hyperinflation of lung field with dense opacification at right upper lobe. High-resolution CT chest showed bilateral patchy consolidation, central bronchiectasis and high-attenuation mucus (HAM) impaction. His blood absolute eosinophil count, total serum IgE level, Aspergillus fumigatus specific IgE and IgG level were 1910, 16760 kU/L, 59.8 kU/L and 147.41 kU/L, respectively. Diagnosis of allergic broncho pulmonary aspergillosis (ABPA) was established according to International Society for Human and Animal Mycology society guidelines. He was started on systemic steroids and doing well after 6 months of follow-up. Our case illustrates HAM, which is a rare but typical radiological feature of ABPA.

Significance: Hydrogen sulfide (H2S), an important regulator of physiology and health, helps resolve inflammation and promotes tissue repair in the gastrointestinal tract. Recent Advances: Gut microbiota live as a multispecies biofilm in close interaction with the upper mucus layer lining the epithelium. The relative abundance, spatial organization, and function of these microorganisms affect a broad range of health outcomes. This article provides a state-of-the-art review of our understanding of the cross talk between H2S, the gut microbiota, and health. H2S can have toxic or therapeutic effects, depending on its concentration and source. When produced at excessive concentrations by local microbiota, H2S may cause mucus disruption and inflammation and contribute to development of cancer. In contrast, low levels of endogenous or exogenous H2S directly stabilize mucus layers, prevent fragmentation and adherence of the microbiota biofilm to the epithelium, inhibit the release of invasive pathobionts, and help resolve inflammation and tissue injury. Although scarce, research findings suggest that dietary H2S obtained from plants or ingestion of the H2S precursor, L-cysteine, may also modulate the abundance and function of microbiota. Critical Issues: A critical issue is the lack of understanding of the metagenomic, transcriptomic, and proteomic alterations that characterize the interactions between H2S and gut microbiota to shape health outcomes. Future Directions: The ambivalent roles of H2S in the gut offer a fertile ground for research on such critical issues. The findings will improve our understanding of how H2S modulates the microbiota to affect body function and will help identify novel therapeutic strategies.

Background & Aims One of the features of ulcerative colitis (UC) is a defect in the protective mucus layer. This has been attributed to a reduced number of goblet cells (GCs). However, it is not known whether abnormal GC mucus secretion also contributes to the reduced mucus layer. Our aims were to investigate whether GC secretion was abnormal in UC and exists as a long-term effect of chronic inflammation. Methods Colonoids were established from intestinal stem cells of healthy subjects (HS) and patients with UC. Colonoids were maintained as undifferentiated (UD) or induced to differentiate (DF) and studied as three-dimensional or monolayers on Transwell filters. Total RNA was extracted for quantitative real-time polymerase chain reaction analysis. Carbachol and prostaglandin E2 mediated mucin stimulation was examined by MUC2 IF/confocal microscopy and transmission electron microscopy. Results Colonoids from UC patients can be propagated over many passages; however, they exhibit a reduced rate of growth and transepithelial electrical resistance compared with HS. Differentiated UC colonoid monolayers form a thin and non-continuous mucus layer. UC colonoids have increased expression of secretory lineage markers ATOH1 and SPDEF, along with MUC2 positive GCs, but failed to secrete mucin in response to the cholinergic agonist carbachol and prostaglandin E2, which caused increased secretion in HS. Exposure to tumor necrosis factor α (5 days) reduced the number of GCs, with a greater percentage decrease in UC colonoids compared with HS. Conclusions Chronic inflammation in UC causes long-term changes in GCs, leading to abnormal mucus secretion. This continued defect in GC mucus secretion may contribute to the recurrence in UC., Graphical abstract

There are various defensive mechanisms in upper respiratory tract mucosal linings such as mechanical and functional barriers. The mechanical barrier of sinonasal mucosa consists of mucus, motile cilia, and respiratory epithelial cells linked by adhesion complexes that include tight junctions. On the other hand, the functional barrier in sinonasal mucosa is dynamic and more complex, being equipped with innate and acquired immune response among resident cells on the epithelia and immunocompetent cells in sinonasal submucosa. Importantly, various types of nasal defensive proteins in human nasal mucosa are responsible for exerting those defensive mechanisms. Those proteins are essential for a defense system against various invading pathogens such as bacteria and viruses and modulate allergic or infective chronic inflammations as well. Those proteins derived from epithelial cells or recruited inflammatory cells are also one of the important key players in the pathogenesis of rhinosinusitis and allergic rhinitis at the epithelial linings of nasal cavity and paranasal sinuses. Those defensive proteins could be classified from constitutional and functional aspects such as surfactants, mucins, antimicrobial peptides, and inflammatory cell-derived enzymes. More widely considered, chemokines, cytokines, and various antibodies can be dealt with as defensive proteins, to provoke cellular interactions against microbial infections or pathogenesis of sinonasal persistent inflammations. In this chapter, the general concept of various types of nasal defensive proteins and its function is introduced, as we focus on surfactants, mucins, and antimicrobial peptides.

Background The mucociliary clearance system driven by beating cilia protects the airways from inhaled microbes and particles. Large particles are cleared by mucus bundles made in submucosal glands by parallel linear polymers of the MUC5B mucins. However, the structural organization and function of the mucus generated in surface goblet cells are poorly understood. Methods The origin and characteristics of different mucus structures were studied on live tissue explants from newborn wild-type (WT), cystic fibrosis transmembrane conductance regulator (CFTR) deficient (CF) piglets and weaned pig airways using video microscopy, Airyscan imaging and electron microscopy. Bronchoscopy was performed in juvenile pigs in vivo. Results We have identified a distinct mucus formation secreted from the surface goblet cells with a diameter less than two micrometer. This type of mucus was named mucus threads. With time mucus threads gathered into larger mucus assemblies, efficiently collecting particles. The previously observed Alcian blue stained mucus bundles were around 10 times thicker than the threads. Together the mucus bundles, mucus assemblies and mucus threads cleared the pig trachea from particles. Conclusions These results demonstrate that normal airway mucus is more complex and has a more variable structural organization and function than was previously understood. These observations emphasize the importance of studying young objects to understand the function of a non-compromised lung.

BACKGROUND Abnormal chloride (Cl- ) transport dehydrates airway surface liquid (ASL) in sinonasal epithelium leading to mucus stasis and chronic rhinosinusitis. As an experimental epithelium, rabbit tissue provides an excellent representation of human sinus disease, and the rabbit sinusitis model is both established and well suited for therapeutic interventions in vivo. Our objective in this study was to evaluate whether ivacaftor reverses the consequences of Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. METHODS Rabbit nasal cavities were assessed for responsiveness to ivacaftor in vivo (by nasal potential difference [NPD] assay). Rabbit nasal epithelial (RNE) cultures were incubated with an ultrafiltrate of P aeruginosa (PAO1 strain) for 4 hours and tested for acquired CFTR dysfunction. Markers of mucociliary function, including airway surface liquid depth (ASL), periciliary liquid depth (PCL), ciliary beat frequency (CBF), and mucociliary transport (MCT), were measured by micro-optical coherence tomography (μOCT) after PAO1 and/or ivacaftor incubation. RESULTS Ivacaftor resulted in a significant mean NPD polarization of 21.8 ± 2.1 mV, which was significantly greater than that seen in the low Cl- control (12.9 ± 1.3; p = 0.01). PAO1 exposure induced a state of acquired CFTR dysfunction in rabbit nasal epithelium as measured by forskolin-stimulated short-circuit current (ISC ) (control, 37.0 ± 1.1 μA/cm2 ; PAO1, 24.4 ± 1.1 μA/cm2 ; p

IntroductionInhaled gene therapy of muco-obstructive lung diseases requires a strategy to achieve therapeutically relevant gene transfer to airway epithelium covered by particularly dehydrated and condensed mucus gel layer. Here, we introduce a synthetic DNA-loaded mucus-penetrating particle (DNA-MPP) capable of providing safe, widespread and robust transgene expression in in vivo and in vitro models of muco-obstructive lung diseases.MethodsWe investigated the ability of DNA-MPP to mediate reporter and/or therapeutic transgene expression in lung airways of a transgenic mouse model of muco-obstructive lung diseases (ie, Scnn1b-Tg) and in air–liquid interface cultures of primary human bronchial epithelial cells harvested from an individual with cystic fibrosis. A plasmid designed to silence epithelial sodium channel (ENaC) hyperactivity, which causes airway surface dehydration and mucus stasis, was intratracheally administered via DNA-MPP to evaluate therapeutic effects in vivo with or without pretreatment with hypertonic saline, a clinically used mucus-rehydrating agent.ResultsDNA-MPP exhibited marked greater reporter transgene expression compared with a mucus-impermeable formulation in in vivo and in vitro models of muco-obstructive lung diseases. DNA-MPP carrying ENaC-silencing plasmids provided efficient downregulation of ENaC and reduction of mucus burden in the lungs of Scnn1b-Tg mice, and synergistic impacts on both gene transfer efficacy and therapeutic effects were achieved when DNA-MPP was adjuvanted with hypertonic saline.DiscussionDNA-MPP constitutes one of the rare gene delivery systems providing therapeutically meaningful gene transfer efficacy in highly relevant in vivo and in vitro models of muco-obstructive lung diseases due to its unique ability to efficiently penetrate airway mucus.

The polymeric immunoglobulin receptor (pIgR) plays an important role in mediating the transcytosis of polymeric immunoglobulins (pIgs) to protect organisms against pathogen invasion. Here, a polyclonal antibody against grass carp (Ctenopharyngodon idellus) recombinant pIgR was developed by immunizing New Zealand white rabbit, and the responses of pIgR, IgM and IgZ were analyzed after bath immunization and intraperitoneal administration with Flavobacterium columnare. The results showed that pIgR transcription level was similar to IgM and IgZ, but pIgR rose much faster and peaked earlier than IgM and IgZ; the pIgR mRNA levels were higher in the skin and spleen for both immunized groups, while IgM and IgZ mRNA expression were higher in skin, gills, and intestines in bath immersion group, or spleen and head kidney in intraperitoneal immunization group. ELISA revealed that the IgM, IgZ and pIgR protein levels were up-regulated in skin mucus, gill mucus, gut mucus and bile, reaching a higher peak level earlier in skin mucus and gill mucus in bath immersion group, but a higher peak level in bile in injection group. Moreover, secretory component molecules were detected in grass carp's skin, gill and intestine mucus and bile, but not in serum, which molecular mass was near the theoretical mass obtained from the sequence of grass carp pIgR. These results demonstrated that bath and intraperitoneal immunization up-regulated pIgR and secretory Ig expression in secretions, which provided more insights into the role of pIgR in immunity and offer insight into ways of protecting teleost against pathogen invasion.

A central goal of microbiome research is to understand the factors that balance gut-associated microbial communities, thereby creating longitudinal and cross-sectional heterogeneity in their composition and density. Whereas the diet dictates taxa dominance, microbial communities are linked intimately to host physiology through digestive and absorptive functions that generate longitudinal heterogeneity in nutrient availability. Additionally, the host differentially controls the access to electron acceptors along the longitudinal axis of the intestine to drive the development of microbial communities that are dominated by facultatively anaerobic bacteria in the small intestine or obligately anaerobic bacteria in the large intestine. By secreting mucus and antimicrobials, the host further constructs microhabitats that generate cross-sectional heterogeneity in the colonic microbiota composition. Here we will review how understanding the host factors involved in generating longitudinal and cross-sectional microbiota heterogeneity helps define physiological states that are characteristic of or appropriate to a homeostatic microbiome.

Exposure to cigarette smoke (CS) is a factor that could delay or worsen the recovery of otitis media (OM) by causing inflammatory swelling of the Eustachian tube (ET). However, despite the suggested relationship, little is known about the association between OM and CS. Therefore, we aimed to evaluate the effects of CS on the development, progression, and recovery of OM, as well as the histological and molecular changes caused by CS exposure, by using a rat model of OM infected with non-typeable Haemophilus influenzae (NTHi). Eighty Sprague–Dawley rats with normal middle ears (MEs) were divided into four groups (n = 20 rats/group): control, CS, OM, and CS + OM. The CS and CS + OM groups were exposed to CS for 2 weeks. The inflammatory reaction to NTHi was more intense and lasted longer in the CS + OM group than in the other groups. Goblet cell proliferation and mucus secretion in the ET were more significant in the CS and CS + OM groups than in the other groups. These findings suggested that because CS directly affects the ET and ME mucosa, bacterial OM can become more severe and may resolve more slowly in the presence of CS exposure rather than in its absence.

Infectious diseases are one of the main causes of social and economical losses in world aquaculture. Senegalese sole (Solea senegalensis) is an important species for aquaculture in southern Europe, whose production is affected by the appearance of bacterial diseases such as photobacteriosis, a septicemia caused by Photobacterium damselae subsp. piscicida (Phdp). The aim of this study was to obtain an oral DNA nanovaccine and to evaluate its efficacy against Phdp in S. senegalensis juveniles. For this purpose, the amplified product corresponding to the protein inosine-5′-monophophate dehydrogenase (IMPDH) from Phdp, was cloned into the expression vector pcDNA™6.2/C-EmGFP-GW obtaining the DNA vaccine named as pPDPimpdh. The correct transcription and protein expression was verified at 48 h post tansfection in HEK293 cells. Chitosan nanoparticles (CS-TPP NPs) were prepared by ionotropic gelation and their features were appropriate for use as oral delivery system. Therefore, pPDPimpdh was protected with chitosan CS-TPP NPs throughout complex coacervation method giving as a result a DNA nanovaccine referred as CS-TPP+pPDPimpdh NPs. Sole juveniles were vaccinated orally with CS-TPP NPs, pPDPimpdh and CS-TPP+pPDPimpdh NPs followed by a challenge with Phdp at 30 days post vaccination (dpv). The relative percentage survival (RPS) for pPDPimpdh vaccinated groups was 6.25%, probably due to its degradation in the digestive tract. RPS value obtained for CS-TPP NPs and CS-TPP+pPDPimpdh NPs was 40% and antibodies were observed in both cases. However, a delay in mortality was observed in sole juveniles vaccinated orally with CS-TPP+pPDPimpdh NPs. In fact, an upregulation of tf, mhcII, cd8a and igm in the posterior gut and c3, hamp1, tf and cd4 in spleen was observed in juveniles vaccinated with CS-TPP+pPDPimpdh NPs. After challenge, a modulation of cd8a and cd4 expression levels in the posterior gut and c3, tf, lyg, cd4, igm and igt expression levels in spleen was observed. Moreover, the concentration of lysozyme in skin mucus significantly increased in fish vaccinated orally with CS-TPP+pPDPimpdh NPs at 11 dpc. These data indicate that oral vaccination with CS-TPP+pPDPimpdh NPs could be acting through the non-specific immune responses as well as the specific humoral and cell mediated immunity and provide the first step toward a development of an oral DNA nanovaccine against Phdp in sole.

To date, the mechanisms of inflammation have been poorly studied in fish of commercial interest, due to the lack of development of appropriate experimental models. The current study evaluated a local inflammation triggered by a polymeric carrageenin mixture (a mucopolysaccharide derived from the red seaweed Chondrus crispus) in the skin of gilthead seabream (Sparus aurata). Fish were injected subcutaneously with phosphate-buffered saline (as control) or λ/κ-carrageenin (1%), and skin samples from the injection sites were collected 1.5, 3 and 6 hr post-injection, processed for inclusion in paraplast and stained with haematoxylin-eosin, Alcian blue or periodic acid-Schiff. Furthermore, immunohistochemistry and expression analyses of several cells' markers and proinflammatory genes were also analysed in samples of the injected sites. Microscopic results indicated an increased number of skin mucus-secreting cells and acidophilic granulocytes in the skin of fish studied at 1.5 hr and 3 hr post-injection with carrageenin, respectively, with respect to the data obtained in control fish. Otherwise, both the gene expression of the non-specific cytotoxic cell marker (granzyme B, grb) and the proinflammatory cytokine (interleukin-1β, il-1β) were up-regulated at 1.5 hr in the skin of fish injected with carrageenin compared with the control fish, whilst the gene expression of acidophilic granulocyte markers (NADPH oxidase subunit Phox22 and Phox40, phox22 and phox40) was up-regulated at 3 and 6 hr in the carrageenin group, compared with the control group. In addition, the gene expression of myeloperoxidase (mpo) was also up-regulated at 6 hr in the skin of fish injected with carrageenin in comparison with control samples. The present results indicate the chronological participation of two important immune cells involved in the resolution of the inflammation in the skin of gilthead seabream.

Mammals have microbes resident in their reproductive tract, some of which can be pathogenic while others may play a role in protecting the tract from infection. Volatile compounds play a role as sex pheromones that attract males for coitus during female estrus or heat. It is likely that these compounds themselves are secondary metabolites of bacterial flora resident in the vagina. In order to substantiate this hypothesis, bacteria were isolated from cervico-vaginal mucus (CVM) of buffalo during various phases of the estrous cycle and identified, using morphological, biochemical and molecular characteristics, as Bacillus during preestrus and diestrus, and as Staphylococcus during all three phases of the estrous cycle. Populations of Staphylococcus differed between different phases of the estrous cycle, the predominant forms being S. warneri (BCVMPE1_1) during preestrus, S. pastueri (BCVME2) during estrus and S. epidermis (BCVMDE3) during diestrus. Mice were used as chemosensors to differentiate the estrus-specific S. pasteuri (BCVME2) from the others. Chemical analysis showed that S. pasteuri (BCVME2) produced acetic, propanoic, isobutyric, butyric, isovaleric and valeric acids. In addition, it was shown that S. pasteuri (BCVME2) volatiles influenced the sexual behaviors, flehmen and mounting, of the bull. Thus, S. pasteuri (BCVME2) is a potential source of vaginal pheromone(s) during estrus in buffalo.

The effect of vitamin D3 (VD3) on gastric ulcers was investigated by evaluating ulcer index, biochemical aggressive, and protective factors. Rats were divided into 4 groups; untreated indomethacin ulcer, VD3 pre-treated + indomethacin ulcer, untreated pyloric-ligation ulcer and VD3 pre-treated + pyloric-ligation ulcer. Treatment with VD3 (400 IU/kg intramuscular) was done daily for 6 days and an hour before ulcers induction. Four hours post-induction, the blood sample was obtained for the determinations of 1,25-dihydroxy vitamin D (1,25-DHCC), Parathyroid Hormone (PTH), and Calcium (Ca). Laparotomy was performed and the stomach was harvested for gastric acidity, ulcer index, and biochemical evaluations. The data were analyzed using statistical tools and the “student t-test” was performed at p

Four male infants with cystic fibrosis and prolonged neonatal jaundice underwent Kasai procedure to relieve biliary obstruction due to apparent biliary atresia. The excised remnants had viscid mucus accumulation in hypoplastic gallbladders and distended peribiliary glands. Main hepatic ducts were narrow and/or malformed. Microscopic differences between the gallbladder and extrahepatic bile ducts in cystic fibrosis and sporadic biliary atresia were unequivocal, despite some histologic overlap; no erosive or fibro-obliterative lesions typical of biliary atresia were seen. Common in liver, biopsies were small duct cholangiopathy with intense focal cholangiolitis and massive accumulation of ceroid pigment within damaged cholangiocytes, and in portal macrophages, portal fibrosis, and unequivocal features of large duct obstruction were inconspicuous compared with biliary atresia. Plugs of bile in small ducts tended to be pale and strongly periodic acid-Schiff-reactive in cystic fibrosis. Distinguishing the liver lesion from that of biliary atresia is challenging but possible. Liver biopsies from 2 additional infants with cystic fibrosis and prolonged jaundice that spontaneously resolved showed a similar small duct cholangiopathy. Small gallbladders and extrahepatic ducts challenge surgical judgment as findings in liver biopsies challenge the pathologist. The decision to perform a Kasai procedure is reasonable when mimicry of biliary atresia is grossly complete. We hypothesize that a disorder of bile volume/flow during development and/or early infancy linked to the CFTR mutation alone or in combination with the stresses of neonatal intensive care causes destructive cholangiolitis and intrahepatic reduction of bile flow with secondary hypoplasia of extrahepatic biliary structures.

Infectious laryngotracheitis (ILT) is an important upper respiratory disease of chickens. Gross and histologic lesions of ILT in chickens are compared to immunohistochemistry to evaluate the diagnostic test sensitivity. A total of 31 separate ILT-confirmed necropsy submissions (12 commercial meat-type flocks, 13 egg-type producers, and 6 backyard flocks) were arbitrarily selected. Each submission ranged from 1 to 18 birds, for a total of 246 chickens. Cases with available formalin-fixed tissues were selected to include a range of bird production types, ages, clinical histories, and severity of macroscopic and histologic lesions. Macroscopic findings in the respiratory tract varied from increased mucus (55.6%) to fibrinonecrotic exudate (20.3%) and hemorrhages in the larynx and trachea (13.0%). Syncytia with intranuclear inclusion bodies were present in the respiratory tract epithelium with or without hemorrhages. Sections of conjunctiva, sinus, larynx, trachea, lung, and air sac were analyzed by immunohistochemistry (IHC) to detect gallid alphaherpesvirus 1 (GaHV-1) antigen. Positive immunolabeling was detected in the cytoplasm and nuclei of syncytia and epithelial cells in 18/22 conjunctivae (82%), 12/13 sinuses (92%), 18/22 larynxes (82%), 23/25 tracheas (92%), 10/21 lungs (57%), and 3/8 air sacs (37%). Of the 34 tissues with no visible syncytia or inclusion bodies, 8 were positive by IHC. In conclusion, IHC was useful to study the viral antigen tissue distribution and support the diagnosis of ILT when the histopathologic interpretation was doubtful.

Helicobacter pylori plays a consequential role in gastric inflammations and ulceration. The cure for the same was researched and identified to be the triple therapy regime. Intensive research in the field also proved that altering the food habits during ulcers will be a major factor in the time period that is required for cure. Fermented foods usage dates back to ancient civilizations, but their role in maintaining gastric health are slowly being uncovered. One such major role reported will be the bacterial check that the probiotics in fermented food do in human gastrointestinal tract. Various species of bacteria present in the fermented products will lead to reduction of the H. Pylori infection in the GI tract.Key teaching pointsMicrobes that are active in fermented foods reduce inflammation and improve histological conditions of ulcers caused due to H. pylori.Microbes such as Lactobacillus that were in fermented products when tested showed inhibitory effects, decreasing infection density and reducing mucus depletion.Lactic fermented products showed a decrease in urease activity and reduces H. pylori adhesion through various organic acid secretions.Organisms in fermented products involve various mechanisms like lowering gut pH, improving immunological responses, scavenging free radicals and so on.Fermented foods have many modulatory effects that help fighting and curing gastric ulcers.

Ivasivka Khrystyna. Dynamics of changes in the structural components of the mucosa and cartilage of the larynx of rats at the end of 42 days of experimental opioid exposure and after 56 days with opioid withdrawal. Journal of Education, Health and Sport. 2021;11(07): 201-218. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2021.11.07.019 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2021.11.07.019 https://zenodo.org/record/5156375 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2021; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 25.06.2021. Revised: 12.07.2021. Accepted: 29.07.2021. UDC: 611. 321 - 018.3⁄. 73: 615.214.24.035.8] .08 Dynamics of changes in the structural components of the mucosa and cartilage of the larynx of rats at the end of 42 days of experimental opioid exposure and after 56 days with opioid withdrawal Khrystyna Ivasivka Danylo Halytsky Lviv National Medical University Applicant of the Department of Normal Anatomy https://orcid.org/0000-0003-4372-225х Abstract In our work we aimed to study the pathomorphological manifestations among the structural components of the laryngeal mucosa and cartilage in the later stages of the experimental opioid effect. This goal was achieved through the use of histological techniques to visualize the structural components of the laryngeal mucosa and cartilage. Histological sections with a thickness of 5 -7 mm were made. Histological specimens were prepared according to conventional methods using the dye hematoxylin, eosin, azan according to the method of Heidenhain, PAS-reaction according to Mc-Manus and Alcian blue according to Steedman. Microscopic examinations and photographing of the preparations were performed using an MBI-1 microscope and a Nicon D 3100 digital camera. At the end of 42 days of experimental exposure, the epithelial layer of the epiglottis was inhomogeneously thickened, with excessive accumulation on its pharyngeal and apical part of the stratum corneum. Individual epitheliocytes of the pharyngeal part of the epiglottis underwent necrotic changes, the horny substance loosened in places. On the pharyngeal surface of the mucous membrane found a small amount of mucus with impurities of erythrocytes. Dyscirculatory processes were also registered in the animals of the experimental group. In particular, dilatation and overflow of erythrocytes of vessels of own plate of a mucous membrane of an epiglottis, and also polymorphonuclear infiltration of own plate of a mucous membrane were observed. Key words: opioid; laryngeal mucosa; laryngeal cartilage; rat; early terms

Asthma is an inflammatory disease that affects many people around the world, especially persons at paediatric age group. The effectiveness of tyrosol, a natural phenolic compound, was examined in the asthma model induced by ovalbumin (OVA). For this purpose, four groups, each consisting of eight rats, were arranged. For 21 days, physiological saline solution was treated to the control group and OVA was treated to the groups of OVA, OVA + dexamethasone (Dexa) and OVA + tyrosol groups, intraperitoneally and through inhalation. Additionally, 0.25 mg/kg Dexa was treated to the OVA + Dexa group and 20 mg/kg tyrosol to the OVA + tyrosol group by oral gavage. Serum, blood, bronchoalveolar lavage fluid (BALF) and lung tissues of the rats were examined. It was observed that MDA level decreased, GSH level and GPx activity increased, and there was no change in CAT activity in lung tissues of the tyrosol treatment groups. It was also observed that NF-κB, TNF-α, IL-4, IL-5, IL-13, IFN-γ and IgE levels decreased compared to the OVA group in lung tissue and serum samples except for serum NF-κB and IL-4. However, no effect on IL-1 β level was observed. In addition, it was determined that tyrosol treatment increased the IL-10 level on both tissue samples. The results of the histopathological investigation of lung tissue showed that tyrosol significantly ameliorated OVA-induced histopathological lesions. Additionally, PAS staining showed that mucus hypersecretion was significantly reduced with the use of tyrosol. In addition, it was determined that the number of eosinophils decreased significantly in blood and BALF samples. The obtained results showed that tyrosol possessed antioxidant and anti-inflammatory features on OVA-induced rats and preserved tissue architecture.

The gastrointestinal tract is constantly exposed to various physical and chemical factors. In the intestine, the contact of bacteria and the epithelium largely depends on mucus, which mainly consists of highly glycosylated mucin-2 secreted by goblet cells in the epithelium. Goblet cells are located along the entire length of the small and large intestine and are responsible for the production and maintenance of a protective layer of mucus through the synthesis and secretion of high-molecular glycoproteins known as mucins. The article presents data on the embryogenesis of the small intestine in general and goblet cells, in particular, a literary review of the role of goblet cells in the morphology of the intestinal tract, the functional aсtivity of their secretion is carried out. Due to the unique nature of this highly polarized exocrine cell, the cellular mechanisms by which goblet cells secrete their products are discussed.

Acute respiratory viral infections remain the most common diseases in the world, accounting for about 90% of all infectious diseases. The possibilities of etiological decoding of ARVI using modern examination methods made it possible to establish an increase in the proportion of rhinovirus infection in the structure of ARVI.The aim of the study in this regard was to study the features of the clinical course of rhinovirus infection in children of different ages in modern conditions. The study included 50 patients with rhinovirus infection of children, among whom 1 2 children (24%) were under 1 year old; 34 children (68%) — 1—3 years old, 4 children (8%) — 3—7 years old. To confirm rhinovirus infection, a study of mucus from the nasopharynx by PCR was carried out.A thorough analysis of the symptom complex of the infection showed that in 1 3 (26%) patients the infectious process was limited to lesions of the upper respiratory tract, in 14 (28%) there were symptoms of acute stenosinglaryngotracheitis, in 1 1 (22%) children developed pneumonia, in 1 2 (24%) — bronchitis, with obstructive syndrome in 1 0 (83.3%) patients in this group.

The human conjunctival epithelial cells (HCEC) line the inner sides of the eyelids and the anterior part of the sclera. They include goblet cells that secret mucus into the tear film that protects the ocular surface. The conjunctival epithelium is subjected to mechano-physical stimuli due to eyelid movement during blinking, during wiping and rubbing the eyes, and when exposed to wind and air currents. We cultured primary HCEC under air–liquid interface (ALI) conditions in custom-designed wells that can be disassembled for installation of the in vitro model in a flow chamber. We exposed the HCEC after ALI culture of 8–10 days to steady and oscillatory airflows. The in vitro model of HCEC was exposed to steady wall shear stresses (sWSS) of 0.5 and 1.0 dyne/cm2 for lengths of 30 and 60 min and to oscillatory wall shear stresses (oWSS) of 0.5 and 0.77 dyne/cm2 amplitudes for a length of 10 min. Cytoskeletal alterations and MUC5AC mucin secretion in response to WSS were investigated using immunohistochemically fluorescent staining and enzyme-linked lectin assay (ELLA), respectively. The results revealed that both exposure times and sWSS values increased the polymerization of F-actin filaments while mucin secretion decreased. However, after a recovery of 24 h in the incubator we observed a decrease of F-actin fibers and mucin secretion only for exposure of 30 min. The length of exposure was more influential on cytoskeletal alterations than the level of sWSS. The very small effect of sWSS on mucin secretion is most likely related to the much smaller amount of goblet cell than in other mucus-secreting tissue. The results for both oWSS amplitudes revealed similar trends regarding F-actin and mucin secretion. Immediately post-exposure we observed an increase in polymerization of F-actin filaments while mucin secretion decreased. However, after 24-h recovery we observed that both F-actin and mucin secretion returned to the same values as for unexposed cultures. The results of this study suggest that WSS should be considered while exploring the physiological characteristics of HCEC.

Yishu Xue,* Wuping Bao,* Yan Zhou,* Qiang Fu, Huijuan Hao, Lei Han, Dongning Yin, Yingying Zhang, Xue Zhang, Min Zhang Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min ZhangDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, People’s Republic of ChinaEmail maggie_zhangmin@163.comBackground: There has been growing evidence of small-airway dysfunction in patients with asthma. Few studies have evaluated the mechanism of small-airway dysfunction in mouse models of asthma.Purpose: We explored the correlation between small-airway spirometric variables and large-airway function or inflammation in different endotypes of asthma.Methods: Ovalbumin (OVA) sensitization/challenge was used to produce a type 2 (T2)-high asthma model, and OVA combined with ozone exposure (OVA + ozone) was used for the T2-low asthma model with increased neutrophils. Spirometry, airway responsiveness, cytokine levels in bronchoalveolar lavage fluid (BALF), and pathological analyses of lung slices stained with hematoxylin-eosin, periodic acid–Schiff, and Masson’s trichrome stain were all determined. Muc5ac expression in lung tissue was evaluated by the reverse transcription-polymerase chain reaction (RT-PCR), and alpha-smooth muscle actin was measured by immunohistochemistry.Results: Inflammatory cells infiltrated the lung tissue and inflammatory cytokines were increased in the BALF of both the OVA and OVA + ozone groups, compared with the control group. Peribronchial hypersecretion and collagen deposition were evident in the models. The OVA + ozone group showed greater neutrophilic infiltration and peribronchial smooth muscle proliferation than the OVA group. Large-airway obstruction, small-airway dysfunction, and airway hyperresponsiveness were confirmed in both models. Small-airway functional variables, such as MMEF (mean midexpiratory flow, average flow from 25 to 75% forced vital capacity [FVC]) and FEF50 (forced expiratory flow at 50% of FVC), were positively correlated with large-airway function and had a stronger negative correlation with airway inflammation, mucus secretion, and responsiveness than large-airway function.Conclusion: Small-airway dysfunction was evident in the two endotypes of asthma and was correlated with severe airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. The small airways may be an important target in asthma treatment, and further research in the role of small-airway variables in the pathogenesis of asthma is warranted.Keywords: small airway, spirometry, airway inflammation, asthma, airway hyperresponsiveness

Background Omega-3 polyunsaturated fatty acids (PUFAs) play beneficial roles in metabolism and health. Little is known about the effects of different doses of omega-3 PUFAs on gut microbiota. Objective In this study, we focus on the effects of different doses of omega-3 PUFAs on gut microbiota and immunity. Design BALB/c mice was first treated with ceftriaxone sodium for 7 days, and then they received saline or different doses of omega-3 PUFAs (30, 60 and 90 mg omega-3 PUFAs) via daily gavage for 21 days. Alterations of cecum microbiota; the tight junction proteins, zonula occludens 3 (ZO3) and occludin, in the ileal wall; serum lipopolysaccharide (LPS); Interleukin-10 (IL-10), interleukin-1β (IL-1β), and Tumour Necrosis Factor α (TNF-α) ; mucus SIgA levels were measured. Results Compared with the ceftriaxone sodium administration group, significant increases in bacterial richness and diversity were observed in the 60- and 90-mg omega-3 PUFA groups, while only a slight increase was observed in the 30-mg omega-3 PUFA group. A higher percentage of several genera, including Lactobacillus, Helicobacter, and Ruminococcus, and a lower percentage of Bacteroides, Clostridium, and Prevotella were observed in the 60- and 90-mg omega-3 PUFA groups when compared with those in the 30-mg group. The expression of ZO3 and occludin proteins increased in 60- and 90-mg omega-3 PUFA groups compared with the natural recovery group. The mucus SIgA and serum IL-10 levels were increased, and serum levels of LPS, IL-1β, and TNF-α were decreased in the 60- and 90-mg omega-3 PUFA groups when compared with those in the ceftriaxone sodium-treated group. Conclusion Different doses of omega-3 PUFAs have different therapeutic effects on the intestinal microbiota. The 60- and 90-mg omega-3 PUFA supplementation had better recovery effects on the gut microbiota and immunity than those of the 30 mg omega-3 PUFAs supplementation.

Goblet cells and the mucus they secrete serve as an important barrier, preventing pathogens from invading the mucosa to cause intestinal inflammation. The perspective regarding goblet cells and mucus has changed, with current evidence suggesting that they are not passive but play a positive role in maintaining intestinal tract immunity and mucosal homeostasis. Goblet cells could obtain luminal antigens, presenting them to the underlying antigen-presenting cells (APCs) that induces adaptive immune responses. Various immunomodulatory factors can promote the differentiation and maturation of goblet cells, and the secretion of mucin. The abnormal proliferation and differentiation of goblet cells, as well as the deficiency synthesis and secretion of mucins, result in intestinal mucosal barrier dysfunction. This review provides an extensive outline of the signaling pathways that regulate goblet cell proliferation and differentiation and control mucins synthesis and secretion to elucidate how altering these pathways affects goblet functionality. Furthermore, the interaction between mucins and goblet cells in intestinal mucosal immunology is described. Therefore, the contribution of goblet cells and mucus in promoting gut defense and homeostasis is illustrated, while clarifying the regulatory mechanisms involved may allow the development of new therapeutic strategies for intestinal disorders.

Due to the COVID-19 pandemic, the general public must comply with health protocols and adopt new habits as this disease spreads through droplets and enters the respiratory tract through the nose and mouth. Meanwhile, water penetration into the nasal cavity (istinsyaq) and out (istintsar) during ablution corresponds to the nasal rinse and gargling methods, which prevents the mechanical and chemical attachment of viruses. This article discusses the role of Islamic-based nasal rinse and gargling in the prevention of COVID-19 infection. Various solutions such as plain water, saline, povidone-iodine, and antiseptics have chemical effects. Gargling and nasal rinse mechanically and chemically wash the mucosal surface in the mouth and nose to prevent the attachment of virus and other pathogens. Mechanically, the difference in concentration causes water to move outside the cell by osmosis, reducing mucus secretion and releasing the virus. Meanwhile, a chemical mechanism occurs when the free iodine in povidone-iodine oxidizes fatty acids and damages the virus cell walls and the respiratory chain of cytosolic enzymes, hence preventing inflammation of the host cell. However, the choice of liquid type, concentration, duration, and frequency of use still need to be considered to prevent side effects. © 2021, Sanglah General Hospital. All rights reserved.

Background The pathological diagnosis and follow-up analysis of gastric mucosal biopsy have been paid much attention, and some scholars have proposed the pathological diagnosis of 12 kinds of lesions and accompanying pathological diagnosis, which is of great significance for the treatment of precision gastric diseases, the improvement of the early diagnosis rate of gastric cancer, and the reduction of missed diagnosis rate and misdiagnosis rate. Aim To perform a histopathological classification and follow-up analysis of chronic atrophic gastritis (CAG). Methods A total of 2248 CAG tissue samples were collected, and data of their clinical characteristics were also gathered. Based on these samples, the expression levels of Mucin 1 (MUC1), MUC2, MUC5AC, and MUC6 in CAG tissue were tested by immunohistochemical assay. Moreover, we followed these patients for up to four years. The difference between different stages of gastroscopic biopsy was observed. Results Through observation, it is believed that CAG should be divided into four types, simple type, hyperplasia type, intestinal metaplasia (IM) type, and intraepithelial neoplasia (IEN) type. Simple CAG accounted for 9.1% (205/2248), which was more common in elderly people over 60 years old. The main change was that the lamina propria glands were reduced in size and number. Hyperplastic CAG accounted for 29.1% (654/2248), mostly occurring between 40 and 60 years old. The main change was that the lamina propria glands were atrophy accompanied by glandular hyperplasia and slight expansion of the glands. IM CAG accounted for 50.4% (1132/2248), most of which increased with age, and were more common in those over 50 years. The atrophy of the lamina propria glands was accompanied by significant IM, and the mucus containing sialic acid or sulfate was distinguished according to the nature of the mucus. The IEN type CAG accounted for 11.4% (257/2248), which developed from the previous types, with severe gland atrophy and reduced mucus secretion, and is an important precancerous lesion. Conclusion The histological typing of CAG is convenient to understand the property of lesion, determine the follow-up time, and guide the clinical treatment.

Aim. To evaluate the features of pharynx tonsils mucous membrane colonization by pathogenic and opportunistic microorganisms using electron microscopic examination of pharynx palatine tonsils epithelium in patients with infectious mononucleosis and acute streptococcal tonsillitis. Materials and Methods. Two patients, i.e. a patient P. (12 years old) with a confirmed diagnosis of infectious mononucleosis, and patient A. (8 years old) with acute streptococcal tonsillitis diagnosis were examined. A bacteriological examination of mucus and epithelium scraping from the surface of the pharyngeal tonsils was conducted. Tissue samples were examined in the electron microscopy laboratory of the Lviv National University. Results and Discussion. 36 tonsils epithelial tissue micro preparations of patient A. and 41 micro preparations of patient P. were studied. Streptococcus pyogenes, Str. pneumoniae, Str. viridans, Сandida albicans, as well as non-pathogenic bacteria, Diphtheroides sp., Neisseria sp., and Corynebacterium spp. were identified as result of the bacteriological examination of mucus from the surface of the pharyngeal tonsils of the patient P.. Staph. aureus, Str. Viridans, and Str. pneumoniae were identified during a bacteriological examination of the patient A. Eosinophils with a two-segmented nucleus, specific granularity, phagocytosed spherical bacteria in the cytoplasm were detected during the histological examination of the materials taken from the surface of the patient with acute tonsillitis tonsils. Research shows that bacteria accumulate not only in the structure of extracellular detritus. Numerous bacteria accumulations were found in the cytoplasm of the epithelial cells in the patient with infectious mononucleosis also. The cell's shape resembles a bunch of grapes. Conclusions. The electron microscopic examination showed differences in the coccal flora localization. The extracellular localization of bacteria in the patient with acute bacterial tonsillitis, and intraepithelial presence of the bacteria in the patient with tonsillitis during infectious mononucleosis were found.

Mucosal surfaces lining the internal tracts of the body are vulnerable to damage by exogenous factors mostly through air and food intake [1–4]. A thin layer of mucus gel lines the various mucosae, regulates access of exogenous factors into the underlying epithelia, and protects against its desiccation [1]. Crude mucus consists of mucins, nonmucin proteins, lipids, water (95–97%) and cell debris [1,2]. Mucins are a large family of heavily glycosylated proteins of high molecular weight (0.5–20 MDa), which are either membrane-bound or secreted as gel-forming and nongel-forming, depending on their ability to polymerize and crosslink into a gel [1]. Their genes have been mapped on several chromosomes across the human genome [3]. Crude saliva, its purified mucins [4] and mucins purified from breast milk [5] inhibit HIV-1 in in-vitro assays. The cervix produces ∼60 mg of mucus per day, the viscosity of which changes periodically with fluctuating levels of oestrogen and progesterone [6], thus regulating access of the spermatozoa into the uterus. Mucus is receptive or resistant during the oestrogen-dominant or progesterone-dominant phases, respectively, with the latter phase blocking access into the uterus [7]. Antimicrobials in the cervical mucus strengthen its barrier functions against invading pathogens [8,9], whereas the constant mucus turnover ensures their clearance from the female reproductive tract (FRT) [10]. During the early stages of pregnancy, increasing progesterone levels drive the formation of the cervical mucus plug (CMP) in the cervix, which blocks bacterial entry into the uterus, failure of which may cause life-threatening obstetrical problems [11,12]. The secreted gel-forming mucins -- MUC5AC, MUC5B and MUC6 -- make up the cervical mucus [13,14] and are encoded by a gene cluster (∼500 kb) that is located on chromosome 11p15.5 together with MUC2[1], the expression of which in the cervix is controversial [13]. Lying underneath the cervical mucus layer is a glycocalyx, which is predominantly attributed to the membrane-bound mucins: MUC1, MUC4 and MUC16 [13,14]. They block pathogens from invading the underlying epithelium, and signal underlying immune cells to trigger an immune response against invading pathogens [15,16]. The expression levels of MUC4 and MUC5B transcripts are high in the cervix [17], the latter peaking at mid-cycle [18]. Given the enrichment of the CMPs with antimicrobial factors [8,9,19], we investigated whether the CMP and its mucin components had anti-HIV-1 activity in vitro. We probed samples against a panel of replication-competent SIV and HIV-1 strains in the contexts of cell-free and cell-to-cell infections. We found that the CMPs inhibit HIV-1 more potently than the purified mucins, and exhibit a viral tropism-specific sieve effect and heterogeneity in terms of their antiviral mechanisms and potency, possibly driven by a specific proteomic profile.

This study investigated the acute inflammatory response induced by subcutaneous injection of carrageenin (1%) or phosphate-buffered saline (control) in gilthead seabream (Sparus aurata). Skin mucus, serum, head kidney (HK) and liver were sampled at 1.5, 3 and 6 hr post-injection (p.i.) to determine the immune and antioxidant status of this fish species. The skin mucus of the carrageenin group showed increased superoxide dismutase and peroxidase activities, lysozyme abundance, bactericidal activity against Vibrio anguillarum and Photobacterium damselae, and total immunoglobulins compared with those of the control group. However, the carrageenin-injected fish sampled at 6 hr p.i. showed decreased protease activity in the skin mucus and peroxidase activity in the HK leucocytes compared with the control. Moreover, the carrageenin injection had no effects on the systemic immune system, but it reduced the liver catalase activities at both 3 and 6 hr in the carrageenin group relative to those in the control group. The expression levels of several proinflammatory and cell marker genes in the HK and liver were also determined. In the HK, the expression levels of interleukin-1β and prostaglandin D synthase 1 were upregulated at 1.5 and 3 hr, respectively, in the carrageenin group compared with those in the control group. Contrarily, the expression of the NADPH oxidase subunit phox40 (an acidophilic granulocyte marker) in the carrageenin group at 6 hr was downregulated compared with that in the control group. These results suggested that subcutaneous injection of κ/λ-carrageenin in gilthead seabream triggered an acute skin inflammation characterized by the rapid recruitment of acidophilic granulocytes and the release of humoral mediators into the skin mucus.

Purulent-inflammatory diseases of the upper respiratory tract and ENT organs are an urgent problem of modern clinical medicine. The high prevalence of this pathology is due to the active effect of pathogenic microflora on the mucous membrane of the respiratory tract, the increasing role of opportunistic and atypical microorganisms in the genesis of infection of the upper respiratory tract, as well as disorders in the mucociliary clearance. Limitations in the mobility of cilia of ciliated cells, as well as their partial or complete absence, a change in the composition of mucous secretions and a slowdown in the speed of mucus movement are the mechanisms that determine the possibility of an acute inflammation focus on the mucous membrane of the upper respiratory tract, and also increase the risk of developing chronic inflammatory diseases of the ENT organs. The accumulated data on the peculiarities of the existence of microbial biocenoses in the human body, as well as the steady widespread growth of the problem of antibiotic resistance, dictate the need to search for new solutions in the treatment of purulent-inflammatory pathology of the ENT organs. A well-established principle of therapy for such conditions is the topical use of combined drugs that combine mucolytic and antibacterial components that actively affect the main links in the pathogenesis of acute and chronic inflammation of the upper respiratory tract. These tasks are most effectively solved by the drug, which contains the mucolytic N-acetylcysteine, which potentiates the effect of another component – the antibiotic thiamphenicol. An important aspect in favor of choosing this drug as a monotherapy or combination therapy for purulent-inflammatory diseases of the upper respiratory tract is a convenient form of release for aerosol administration.

BACKGROUND Chronic rhinosinusitis (CRS) is characterized by significant accumulation and thickening of mucus in the sinonasal cavities. One contributor of aberrant mucus production and impaired mucociliary clearance (MCC) is altered function of the sinonasal submucosal glands (SMGs), yet contributions of SMGs to upper airway disease initiation and progression remain unknown. The objective of this study was to characterize the morphology and secretory cell identities of the nasal septum SMGs in both healthy and CRS adults. METHODS Biopsies from adult participants with CRS without nasal polyps (CRSsNP, n = 4), CRS with nasal polyps (CRSwNP, n = 8), and non-CRS controls (n = 14) were collected from the posterior septum. Glandular morphology and mucus markers were investigated using histological techniques and high-resolution confocal microscopy. RESULTS Analysis revealed a significant decrease in gland density in the posterior septum of CRSsNP (28% ± 6.15%) and CRSwNP (23% ± 3.09%) compared to control participants (53% ± 1.59%, p

Highlights • The NSI subepithelial glands in dromedaries had unique anatomical features. • Their ultrastructural features are typical for APUD cells. • They may have the structures required for synthesis of active peptides, amines and chemical mediators., The nasal septal island (NSI) is a sensory patch of neuroepithelium located within the soft tissue of the nasal septum in dromedaries. The island has unique anatomical features, including the specialized subepithelial glands. The aim of the present study was to describe the microscopic features and ultrastructure of these subepithelial glands and to speculate the possible functions. A total of 10 camel heads were used for the study. Unlike the serous and mucous airway glands, the NSI glands’ ultrastructural features were typical for cells of the (Amine Precursor Uptake and Decarboxylation, APUD) system. These features were included, membrane bound secretory vesicles of varying electron density, smooth endoplasmic reticulum in the form of vesicles; electron dense mitochondria, abundant rough endoplasmic reticulum and free ribosomes. Alcian-PAS identifiable mucus granules were not observed, except for few clusters of cells, located at the luminal surface. The probable functions were discussed on basis of cellular morphology and context. In a conclusion, the NSI subepithelial glands in dromedaries had unique anatomical structures, and as many other APUD cells, they had the machinery required for synthesis of a variable number of biologically active peptides, amines and chemical mediators.

Cystic fibrosis (CF) is a progressive autosomal recessive genetic disease that principally affects the respiratory and digestive systems. It is a chronic disease that has no cure. Symptoms often include chronic cough, lung infections, and shortness of breath. Children with cystic fibrosis present failure to thrive as manifested by low weight and height for age. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (cftr) gene that codes for a cell membrane protein of epithelial tissues and affects multiple organ systems in the human body. Mutations on the CFTR causes dysfunctional electrolyte regulation affecting intracellular water content. Defective CFTR function in airways produce a dehydrated and sticky mucus that leads the establishment of bacterial chronic infection that ultimate decrease the lung function. During the first decade of life, affected individuals are colonized principally by non typable Haemophilus influenzae and Staphylococcus aureus. During the second decade, Pseudomonas aeruginosa becomes the most dominant pathogen and persists throughout the remainder of their lives. In this work, we describe the mechanisms used by P. aeruginosa to adapt and persist in lungs of individuals with cystic fibrosis.

Aim. To evaluate the features of pharynx tonsils mucous membrane colonization by pathogenic and opportunistic microorganisms by using the pharynx palatine tonsils epithelium electron microscopic examination of the patients with infectious mononucleosis and acute streptococcal tonsillitis. Materials and methods. Two patients – patient P., 12 years old with a confirmed diagnosis of infectious mononucleosis and patient A., 8 years old with confirmed acute streptococcal tonsillitis. The patients were taken a bacteriological examination of the mucus and epithelium scraping from the surface of the pharyngeal tonsils. Tissue samples were examined in the electron microscopy laboratory of the Lviv National University. Results and discussion. 36 tonsils epithelial tissue micro preparations of patient A. and 41 micro preparations of patient P. were studied. Streptococcus pyogenes, Str. pneumoniae, Str. viridans, Сandida albicans, as well as non-pathogenic bacteria: Diphtheroides sp., Neisseria sp., Corynebacterium spp. were identified as result of the patient P. bacteriological examination of mucus from the surface of the pharyngeal tonsils. Staph. aureus, Str. viridans, Str. pneumoniae were identified during a bacteriological examination of patient A. Eosinophils with a two-segmented nucleus, specific granularity, phagocytosed spherical bacteria in the cytoplasm were detected during the histological examination of the materials taken from the surface of the patient’s tonsils with acute tonsillitis. Research showed that bacteria were accumulated not only in the structure of extracellular detritus. Numerous bacteria accumulations were also found in the cytoplasm of the epithelial cells in the patient with infectious mononucleosis. The cell's shape looked like a bunch of grapes. Conclusions. The electron microscopic examination showed differences in the coccal flora localization: the extracellular localization of bacteria in the patient with acute bacterial tonsillitis and intraepithelial presence of the bacteria in the patient with tonsillitis during infectious mononucleosis were found.

This is well established fact that the exposure of pesticide leads to the significant physiological and histological changes in aquatic fauna. Therefore, ecotoxicology and histopathology have become the important areas of research for scientists, now a days. In order to investigate histopathological effects of synthetic pyrethroids, Skin, Liver, kidney, gills, and spleen of Channa gachua were examined after exposure to sublethal and acute concentration of melathion (0.8 and 1.6 mg/L) for 20 days. Fishes showed degenerative, necrotic changes and congestion of blood vessels in gill filament. Severe degeneration in secondary gill lamellae, separation of gill filament from basement membrane, proliferation of mucus cells and atrophy of gill filament were seen. Hyperplasia was found as an increased number of epithelial cells at the distal or basal portions of kidney. Few nephrons had obstructed glomerular capillary and detachment of the tubular epithelium with the surrounding tissue. Necrosis was present in hematopoietic tissue, glomerular cells, and tubular cells. Melanomacrophage centers (MMC) were scattered throughout liver and spleen. Exudates and necrosis in the splenic white pulp were observed. The liver had a low number of necrotic hepatocytes and enlarged hepatic perisinusoidal areas containing eosinophilic material. Vacuolar dystrophy of hepatocytes and hypertrophy of hepatocytes were also observed. Fish showed serious skin lesions but did not show any behavioural abnormality as compared to controlled group. Their histological recovery was also examined for next 30 days. These changes which observed during exposure were reversed after 30 days of recovery period.

The present study elucidates further on clinical, gross, and microscopic pathologies induced by single or mixed infections with Trypanosoma evansi and Trypanosoma brucei in sheep. Briefly, the experimental animals were divided into four groups of three animals each. Animals in each group were either infected with T. brucei, T. evansi, mixed (T. brucei and T. evansi), or noninfected. Animals were observed for clinical, gross, and microscopic pathologies for 98 days (14 weeks). The clinical pathologies observed included loss of body condition, pale ocular mucus membrane, rough hair coat, scrotal oedema, scrotal degeneration, emaciation, and death. At necropsy, macroscopic or gross lesions included very pale and anaemic carcass composition, congested and pneumonic lungs with severe haemorrhages, serous atrophy of intestinal and body fats, lymphadenopathy, splenomegaly, and hepatomegaly. Microscopic lesions observed in the testes, spleen, liver, lungs, lymphoid, heart, and brain tissues of infected sheep were varied and included swollen kidney with renal tubular degeneration, the proliferation of lymphocytes at the germinal centers of the spleen, degeneration of the bronchioles, severe testicular degeneration with a reduction in the number of spermatogenic cell layers, degenerated Leydig and Sertoli cells with loss of sperm reserves in the seminiferous lumen, congested liver with sinusoidal spaces and the proliferation of monocytes and lymphocytes. The results indicate that trypanosomosis due to experimental T. brucei, T. evansi, or mixed infections may be an important cause of various grades of tissue and organ pathologies in sheep in trypanosome-endemic areas. Keywords: Trypanosomosis; Clinico-pathological and microscopic features; Trypanosoma brucei; Trypanosoma evansi; Mixed infections; Sheep

A 93-year-old female underwent curative endoscopic submucosal dissection (ESD) for intramucosal gastric cancer (70 mm in diameter) in the antrum. The lesion showed an irregularly villous structure covered with mucus. En bloc resection was performed. The large resected specimen induced a longitudinal laceration on the right wall of the esophagogastric junction (EGJ) during retrieval. Unavoidably, we segmented the specimen in the stomach to facilitate retrieval. Histopathological evaluation of the specimen revealed well-to-moderately differentiated tubular and papillary adenocarcinoma. A new elevated lesion (15 mm in diameter) was found at the gastric side of the EGJ laceration scar 6 months after the first ESD, necessitating a second resection with ESD. Endoscopic, histopathological, and immunohistochemical features of the new lesion resembled those of the antral lesion. We assessed the new lesion as a recurrence of cancer caused by implantation of tumor cells in the mucosal laceration after ESD. We experienced recurrence caused by implantation of tumor cells in a mucosal laceration after curative gastric ESD. Endoscopist should be aware of the risk of implantation after gastric ESD.

The oral mucosa is an effective site for vaccination. However, for oral mucosal vaccines, delivery of the right dose of vaccine is not possible due to the water-rich environment. In this study, the buccal mucosa, which is easy to access using a microneedle array in the oral cavity, was selected as the administration site. The immune responses to the use of microneedles to conventional transmucosal delivery were compared. In addition, the adjuvant effect of the addition of cholera toxin (CT) to the drug formulation was observed. Two kinds of patches were prepared: (1) Ovalbumin (OVA) was dip coated only on the tips of microneedles (C-OVA-MN) and (2) OVA was coated on the surface of a flat disk patch substrate without microneedles (C-OVA-D). The drug delivery properties of C-OVA-MN and C-OVA-D were investigated using fluorescent-labeled OVA (OVA/FITC). Each patch was administered to mice twice, 2 weeks apart, and then antibody titers were measured. A microneedle patch can deliver vaccine into the epithelium of the buccal mucosa in a short period of time compared to transmucosal delivery. A microneedle system of C-OVA-MN showed a high serum IgG titer. In addition, CT triggered CD8+ and CD4+ T cell-mediated immune responses. Through this study, we present the possibility of a new method of vaccination to the buccal mucosa using microneedles and CT adjuvant. Illustration of delivery of vaccine to the oral mucosal epithelium using a microneedle patch: Ovalbumin (OVA)-coated microneedle (C-OVA-MN) consists of tip, step, and coating formulation. Microneedle patch coated with OVA formulation is targeting buccal mucosa, which is easy to access in the oral cavity. OVA is delivered to the buccal epithelium precisely using a microneedle patch, and OVA is delivered by transmucosal route using a disk patch.

Human milk oligosaccharides (HMOs) and milk fat globule membrane (MFGM) are highly abundant in breast milk, and have been shown to exhibit potent immunomodulatory effects. Yet, their role in the gut microbiota modulation in relation to colitis remains understudied. Since the mixtures of fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) perfectly mimic the properties and functions of HMOs, the combination of MFGM, FOS, and GOS (CMFG) has therefore been developed and used in this study. Here, CMFG were pre-fed to mice for three weeks to investigate its preventive effect on dextran sodium sulfate (DSS) induced colitis. Moreover, CMFG-treated and vehicle-treated mice were cohoused to further elucidate the preventive role of the gut microbiota transfer in colitis. At the end of the study, 16S rDNA gene amplicon sequencing, short-chain fatty acids (SCFAs) profiling, transcriptome sequencing, histological analysis, immunofluorescence staining and flow cytometry analysis were conducted. Our results showed that CMFG pre-supplementation alleviated DSS-induced colitis as evidenced by decreased disease activity index (DAI) score, reduced body weight loss, increased colon length and mucin secretion, and ameliorated intestinal damage. Moreover, CMFG reduced macrophages in the colon, resulting in decreased levels of IL-1β, IL-6, IL-8, TNF-α, and MPO in the colon and circulation. Furthermore, CMFG altered the gut microbiota composition and promoted SCFAs production in DSS-induced colitis. Markedly, the cohousing study revealed that transfer of gut microbiota from CMFG-treated mice largely improved the DSS-induced colitis as evidenced by reduced intestinal damage and decreased macrophages infiltration in the colon. Moreover, transfer of the gut microbiota from CMFG-treated mice protected against DSS-induced gut microbiota dysbiosis and promotes SCFAs production, which showed to be associated with colitis amelioration. Collectively, these findings demonstrate the beneficial role of CMFG in the gastrointestinal diseases, and further provide evidence for the rational design of effective prophylactic functional diets in both animals and humans.

The vaginal microbiota has been studied in animal reproduction and fertility, in particular little information of vaginal microbes in reference to bovine reproduction and pheromone production is known. The vaginal mucosa in healthy cow is colonized by an equilibrated and dynamic composition of aerobic, facultative anaerobic and obligate anaerobic microbes. Cervico-vaginal mucus (CVM) composition, viscosity and volume vary with the cyclicity and health status of the reproductive tract. In addition, CVM contains pheromones, volatile compounds, and proteins that attract males for coitus. Commensal microbiota plays a key role in protection of the genital tract from pathogenic microbes by competition effect. In the bovine species, the microbial composition, its abundance and diversity in the female gut, vagina, urine, saliva, and feces, and the associated chemical communication remains poorly documented. The impact of microbes in the reproductive tract of cow, buffalo and certain mammals are discussed in this review. Since the microbial population diversity of CVM is modified during estrus phase it presumes that it may have a role for pheromone production in conspecific. Herein, we would like to critically discuss the current state of knowledge on microbially produced signals in animals and the role of genital and CVM microbiota in estrous cycle and pregnancy.

We discussed about the term intestinal permeability like as the mucosal barrier a single structural and functional conception that includes the layer of mucus, the indigenous microbiota and the epithelium of the mucosa in this publication. Information was presented about the role of the microbiota, the composition of intestinal mucus, epithelial cells and proteins of tight junctions which lead to various metabolic diseases. The complex pathogenetic interactions are formed between the intestinal mucosal barrier, metabolic disorders such as non-alcoholic fatty liver disease and cardiovascular diseases. The complex researches and modification of this interactions will allow to create personalized approaches and to prevent of these diseases.

Asthma is an inflammatory disease of the respiratory system affecting over 300 million people worldwide. Lavandula has been traditionally used to treat inflammatory diseases and has also several medical applications. We aimed to explore the anti-inflammatory effects of Lavandula extract on a murine model of asthma. Twenty-eight Balb/c mice were divided into four groups of seven animals. The negative control group was treated with Phosphate-buffered saline, and the remaining three groups received ovalbumin to induce asthma. Subsequently, two asthmatic groups received budesonide or Lavandula extract. Afterward, the changes in the number of eosinophils, gene expressions, and the levels of interleukins 5, 13, and 33 were quantified in bronchoalveolar lavage fluid (BALF) of animals. Histopathological alterations of goblet cells, mucus secretion, and peribronchial and perivascular inflammations were examined in lung tissues of all animals. Eosinophils count and the levels of interleukins 5, 13, and 33 in BALF specimens were significantly reduced. Hyperplasia of goblet cells, mucus hypersecretion, and peribronchial and perivascular inflammations were inhibited in mice treated with Lavandula compared to asthmatic group. Interestingly, Lavandula was more effective than budesonide in alleviating inflammatory responses of asthma. The present study is the first report of anti-inflammatory and antiasthmatic activities of Lavandula extract in the Balb/c mouse model of ovalbumin-induced asthma. Lavandula antiasthmatic effects were mediated by modulating eosinophil counts, type 2 inflammatory responses, mucus secretion, and histological alterations of the lung due to inflammation, proposing it as a therapeutic modality to attenuate inflammatory complications of asthma.

The effect of dietary grape (Vitis vinifera) seed extract (GSE) on growth performance and mucosal immune parameters in rainbow trout (Oncorhynchus mykiss) fry was studied. Fish (1.3 g mean weight) were randomly distributed in nine tanks (15 fish per tank) and fed diets containing GSE at 0 (control), 100, and 200 mg kg−1for 60 days. The results showed that growth parameters were enhanced in both treatment groups compared to the control group. Histological examination of fish skin showed higher epidermis thickness, goblet cell density, and volume density in the GSE groups compared to the values of the control group. Furthermore, the villus height, goblet cell density, and intraepithelial lymphocytes were increased in the fish intestine in those fish fed GSE, with respect to control fish. Feeding fish with low dose of GSE (100 mg kg−1) up-regulated the expression of some immune-relevant genes, including complement component 3 (C3), lysozyme (Lys), omDB-3, interferon gamma (IFN-γ), and tumor necrosis factor-α (TNF-α) in different mucosal tissues. However, feeding fish the high dose of GSE (200 mg kg−1) mostly enhanced expression of these genes in the skin. Besides, skin mucus of fish fed GSE showed bactericidal activity against Yersinia ruckeri. It was concluded that GSE, especially at 100 mg kg−1, modulates the growth performance and mucosal immunity of rainbow trout.

O sistema digestório tem como função fazer a digestão e absorção de nutrientes de modo a fornecer energia para o crescimento e renovação celular. Esse sistema é constituído pelos seguintes segmentos: boca, faringe, esôfago, estômago, intestino delgado, intestino grosso e canal anal. Os cães estão expostos a vários agentes (bactérias, vírus, parasitos e corpos estranhos) que podem acarretar diversos distúrbios gastrointestinais e provocar alterações patológicas no trato gastrointestinal. Diante disso, o objetivo deste trabalho foi identificar as principais patologias encontradas no estômago e intestino de cães por meio do exame de necropsia. Para tanto, foram avaliadas 83 fichas de necropsias preenchidas entre fevereiro de 2014 e abril de 2016, provenientes das aulas práticas de Patologia Animal da Universidade Presidente Antônio Carlos (UNIPAC), de Uberlândia-MG. Durante o estudo, apuraram-se alterações gastrointestinais em 70 casos do total analisado. Ao final do levantamento, constataram-se como alterações mais frequentes: mucosa espessada e hiperêmica, presença de hemorragia, presença de muco e erosões na mucosa.

Mucus and body temperature serve as the first lines of defense against invading pathogens. When the inhaled particles are deposited in the nose, the respiratory mucus and body temperature potentially impact fungal spore germination and prevent pathogen infections. We hypothesized that respiratory mucus and body temperature impact fungal spore germination. This study aimed to investigate the temporal germination dynamics of allergenic Cladosporium, Aspergillus, and Penicillium spp. in respiratory mucus ex situ and the effect of the temperature (28 °C and 37 °C in the upper and lower respiratory tract, respectively) on fungal germination. Fungal spore germination was inhibited at 37 °C in C. oxysporum and C. cladosporioides, but not A. flavus, A. brunneoviolaceus, A. protuberus, P. citrinum, and P. oxalicum. Aspergillus flavus and A. brunneoviolaceus exhibited a high germination rate in the mucus at 28 °C and 37 °C. This indicated that their germination was not limited in the mucus in the upper or lower respiratory tract, where spores of these fungi can overcome the inhibition of germination as in invasive aspergillosis pathogens. The germination rate of A. protuberus in the mucus was very low at both 28 °C and 37 °C. Spore germination of P. citrinum and P. oxalicum occurred at 37 °C (normal body temperature) but was inhibited by the mucus.

Galectins are a family of proteins that bind β-galactosides and play key roles in a variety of cellular processes including host defence. They have been well studied in hosts but less so in gastrointestinal nematodes. Both host and parasite galectins are present in the gastrointestinal tract following infection. Parasite galectins can both bind antibody, especially highly glycosylated IgE and be bound by antibody. Parasite galectins may act as molecular sponges that soak up antibody. Host galectins promote mast cell degranulation while parasite galectins inhibit degranulation. Host and parasite galectins can also bind mucins and influence mucus viscosity. As the protective response against gastrointestinal nematode infection is partly dependent on IgE mediated mast cell degranulation and mucus, the interactions between host and parasite galectins play key roles in determining the outcome of infection.

Kiwifruit (KF) fiber, a mixture of soluble and insoluble fibers, elicits mucosal changes in the gastrointestinal tract (GIT). This study aimed to define the nature of these changes in mucosal features throughout the GIT of the growing pig in response to semi-synthetic iso-fiber diets containing cellulose (CEL, low GIT luminal functionality) as the sole fiber source (4.5%), or diets where half of the CEL was replaced by either PSY fiber (PSY husk, high GIT luminal functionality) or KF fiber (consumed as intact fruit). Entire male growing pigs (n = 24, 21 kg bodyweight) received the three diets (n = 8) for 42 d. GIT tissues, digesta, and feces were sampled. The partial replacement of CEL increased (P ≤ 0.05) the ileal (KF 22% and PSY 33%) and colonic (PSY 86%) mucus layer thickness, whereas it decreased the rectal crypt depth (KF -26%), and small intestinal (duodenum to ileum) villus length (PSY -17%). The number of duodenal goblet cells was 77% higher (P ≤ 0.05) for KF than CEL. Pigs fed the KF-containing diet had greater (P ≤ 0.05) apparent ileal organic matter digestibility and apparent total tract organic matter digestibility compared with CEL, but the lowest amount of fermented organic matter in the large intestine. In conclusion, partial substitution of CEL with PSY or KF at a constant, practically-relevant dietary fiber intake, affected several measures of GIT functionality with effects being specific to the added fiber.

Background & Aims Patients with ulcerative colitis have low concentrations of the major membrane lipid phosphatidylcholine (PC) in gastrointestinal mucus, suggesting that defects in colonic PC metabolism might be involved in the development of colitis. To determine the precise role that PC plays in colonic barrier function, we examined mice with intestinal epithelial cell (IEC)-specific deletion of the rate-limiting enzyme in the major pathway for PC synthesis: cytidine triphosphate:phosphocholine cytidylyltransferase-α (CTαIKO mice). Methods Colonic tissue of CTαIKO mice and control mice was analyzed by histology, immunofluorescence, electron microscopy, quantitative polymerase chain reaction, Western blot, and thin-layer chromatography. Histopathologic colitis scores were assigned by a pathologist blinded to the experimental groupings. Intestinal permeability was assessed by fluorescein isothiocyanate–dextran gavage and fecal microbial composition was analyzed by sequencing 16s ribosomal RNA amplicons. Subsets of CTαIKO mice and control mice were treated with dietary PC supplementation, antibiotics, or 4-phenylbutyrate. Results Inducible loss of CTα in the intestinal epithelium reduced colonic PC concentrations and resulted in rapid and spontaneous colitis with 100% penetrance in adult mice. Colitis development in CTαIKO mice was traced to a severe and unresolving endoplasmic reticulum stress response in IECs with altered membrane phospholipid composition. This endoplasmic reticulum stress response was linked to the necroptotic death of IECs, leading to excessive loss of goblet cells, formation of a thin mucus barrier, increased intestinal permeability, and infiltration of the epithelium by microbes. Conclusions Maintaining the PC content of IEC membranes protects against colitis development in mice, showing a crucial role for IEC phospholipid equilibrium in colonic homeostasis. SRA accession number: PRJNA562603., Graphical abstract