Mucin Layer Research Articles

Critical Evaluation of Multifunctional Betaxolol Hydrochloride Nanoformulations for Effective Sustained Intraocular Pressure Reduction.

Glaucoma is a chronic disease that requires long-term adherence to treatment. Topical application of conventional eye drops results in substantial drug loss due to rapid tear turnover, with poor drug bioavailability being a major challenge for efficient glaucoma treatment. We aimed to prepare the anti-glaucoma drug betaxolol hydrochloride (BH) as a novel nano-delivery system that prolonged the retention time at the ocular surface and improved bioavailability. We constructed multifunctional nanoparticles (MMt-BH-HA/CS-ED NPs) by ion cross-linking-solvent evaporation method. The particle size, zeta potential, encapsulation efficiency and drug loading of MMt-BH-HA/CS-ED NPs were physicochemically characterized. The structure of the preparations was characterized by microscopic techniques of SEM, TEM, XPS, XRD, FTIR and TGA, and evaluated for their in vitro release performance as well as adhesion properties. Its safety was investigated using irritation assays of hemolysis experiment, Draize test and histopathology examination. Precorneal retention was examined by in vivo fluorescence tracer method and pharmacokinetics in tear fluid was studied. A model of high IOP successfully induced by injection of compound carbomer solution was used to assess the IOP-lowering efficacy of the formulation, and it was proposed that micro-interactions between the formulation and the tear film would be used to analyze the behavior at the ocular surface. The positively charged MMt-BH-HA/CS-ED NPs were successfully prepared with good two-step release properties, higher viscosity, and slower pre-corneal diffusion rate along with longer precorneal retention time compared to BH solution. The micro-interactions between nanoparticles and tear film converted the drug clearance from being controlled by fast aqueous layer turnover to slow mucin layer turnover, resulting in higher drug concentration on the ocular surface, providing more durable and stable IOP-lowering efficacy. The novel multifunctional MMt-BH-HA/CS-ED NPs can effectively reduce IOP and are suitable for the treatment of chronic disease glaucoma.

Photodynamic Therapy with Nebulized Nanocurcumin on A549 Cells, Model Vessels, Macrophages and Beyond.

This study aimed to determine the damage mechanisms caused by naturally targeted nanoarchaeosomes made of diether lipids from Halorubrum tebenquichense loaded with curcumin (CUR, nATC), which mediated photodynamic therapy (PDT) on A549 cells and on THP-1-macrophages, two cell types found in airway cancers. The effect of nATC- PDT on vessels modeled with a chicken embryo chorioallantoic membrane (CAM), after dropping the formulations on its surface covered with mucins, was also determined. nATCs are known to efficiently trap CUR for at least six months, constituting easy-to-prepare, stable formulations suitable for nebulization. CUR instead, is easily released from carriers such as liposomes made of ordinary phospholipids and cholesterol after a few weeks. Irradiated at 9 J/cm2, nATC (made of archaeolipids: Tween 80: CUR at 1:0.4:0.04 w:w, size 180 ± 40 nm, ζ potential -24 mV, 150 μg CUR/15 mg lipids/mL) was phototoxic (3.7 ± 0.5 μM IC50), on A549 cells after 24 h. The irradiation reduced mitochondrial membrane potential (ΔΨm), ATP levels and lysosomal functionalism, and caused early apoptotic death and late necrosis of A549 cells upon 24 h. nATC induced higher extra and intracellular reactive oxygen species (ROS) than free CUR. nATC-PDT impaired the migration of A549 cells in a wound healing assay, reduced the expression of CD204 in THP-1 macrophages, and induced the highest levels of IL-6 and IL-8, suggesting a switch of macrophage phenotype from pro-tumoral M2 to antitumoral M1. Moreover, nATC reduced the matrix metalloproteinases (MMP), -2 and -9 secretion, by A549 cells with independence of irradiation. Finally, remarkably, upon irradiation at 9 J/cm2 on the superficial vasculature of a CAM covered with mucins, nATC caused the vessels to collapse after 8 h, with no harm on non-irradiated zones. Overall, these results suggest that nebulized nATC blue light-mediated PDT may be selectively deleterious on superficial tumors submerged under a thick mucin layer.

Drug delivery to the brain: In situ gelling formulation enhances carbamazepine diffusion through nasal mucosa models with mucin

The objective of this work was to optimize a thermosensitive in situ gelling formulation to improve intranasal and nose-to-brain delivery of the antiepileptic drug carbamazepine (CBZ). A preliminary procedure of vehicles obtained just mixing different fractions of poloxamer 407 (P407) and poloxamer 188 (P188) revealed preparations with phase transition temperatures, times to gelation and pH values suitable for nasal delivery. Subsequently, the mucoadhesive properties of the most promising formulations were tuned by adding hydroxypropylmethylcellulose types of different viscosity grades, and the effect of the adhesive polymers was evaluated by testing in vitro time and strength of mucoadhesion on specimens of sheep nasal mucosa. The formulation that showed the greatest mucoadhesive potential in vitro, with a time and force of mucoadhesion equal to 1746,75 s and 3.66 × 10-4 N, respectively, was that composed of 22% P407, 5% P188 and 0.8% HPMC low-viscous and it was further investigated for its ability to increase drug solubility and to control the release of the drug. Lastly, the capability of the candidate vehicle to ensure drug permeation across the biomimetic membrane Permeapad®, an artificial phospholipid-based barrier with a stratified architecture, and the same barrier enriched with a mucin layer was verified. The final formulation was characterized by a pH value of 6.0, underwent gelation at 32.33°C in 37.85 s, thus showing all the features required by in situ gelling thermosensitive preparations designed for nasal delivery and, more notably, it conserved the ability to favor drug permeation in the presence of mucin. These findings suggest that the optimized gelling system could be a promising and easy to realize strategy to improve CBZ delivery to the brain exploiting both a direct and indirect pathway.

Resolvin D2 uses multiple Ca2+ -dependent signaling pathways to stimulate mucin secretion in rat and human conjunctival goblet cells.

The mucin layer of the tear film is produced by goblet cells in the conjunctiva to protect the ocular surface and maintain homeostasis. The pro-resolving lipid mediator resolvin D2 (RvD2) biosynthesized from an omega 3 fatty acid actively terminates inflammation and regulates mucin secretion from conjunctival goblet cells. Our objective was to determine which Ca2+ -dependent signaling pathways RvD2 uses to stimulate conjunctival goblet cell function (CGC). We hypothesize that RvD2 activates multiple intracellular Ca2+ signaling pathways to stimulate CGC secretion. Rat and human CGCs were cultured from conjunctival explants. The amount of RvD2 receptor GPR18/DRV2 message and protein were determined. The intracellular concentration of Ca2+ ([Ca2+ ]i ) was measured in CGCs using a fluorescent Ca2+ dye and mucin secretion was determined by measuring protein secretion enzymatically with a lectin. Goblet cells were incubated with signaling pathway inhibitors before stimulation with RvD2 and [Ca2+ ]i or secretion was measured. In rat and human CGCs RvD2 receptor and in rat CGCs IP3 (a molecule that releases Ca2+ from intracellular organelles) receptors 1-3 were detected. In both species of CGC RvD2 increased [Ca2+ ]i similarly to RvD1. In rat CGCs, the increase in [Ca2+ ]i and secretion stimulated by RvD2 was significantly blocked by inhibitors to phospholipase (PL-) C and IP3 -receptor, but not protein kinase C. Increase in [Ca2+ ]i was blocked by the PLD inhibitor, but not the PLA2 inhibitor. Secretion was blocked by PLA2 inhibitor, but not the PLD inhibitor. An inhibitor of the epidermal growth factor receptor blocked the increase in [Ca2+ ]i by RvD2 in both species of CGCs. In CGCs RvD2 activates multiple intracellular signaling pathways that are Ca2+ -dependent, along with one Ca2+ -independent and one cAMP/protein kinase A-dependent pathway. Activation of these pathways stimulate mucin secretion from rat and human CGCs into the tear film contributing to ocular surface homeostasis and health.

The Nutritional Links for Gut Microbial Dysbiosis and its Metabolic and Endocrinal Fallouts

The Human Gut Microbiome: The gastro-intestinal tract, skin and genitals, and various other body organs, harbour large and diverse communities of bacteria, viruses, and other microscopic life. In the human gut, a nutrient-rich environment, reside ~ 100 trillion microbes, the vast majority of which is present in the colon. There inhabit microbial members as residents (autochthonous), while others (allochthonous) are from ingested food, water, and other components of the environment. The adult human gut microbiota is dominated by mainly two bacteria, the Bacteroidetes and Firmicutes, and an archea, Metanobrevibacter smithii. The microbial ecosystems throughout the body interact with the molecular processes, which have been linked to various aspects of human physiology. The understanding about microbiota is evolving and presents as an important research avenue. The Gut Biosphere and Ecosystem: In general, the gut microbial communities depend on their specific enzymes and molecules to utilize available nutrients, cell-surface molecular appendages to attach on to their right habitat, to evade bacteriophages, with ability to deal with immune system and avoid washout and genetic mutability to stay well-adapted. The microbiota influences various biological processes and organ physiology, including gastrointestinal processes, energy metabolism and insulin resistance, and thus influence weight gain, development of diabetes, and aging. The intestinal epithelium actively senses various bacteria and plays an essential role in maintaining host-microbial homeostasis at the mucosal interface. On the other hand, the host factors, such as dietary factors influence the host-microbial and microbial-microbial relationships. Microbiota, Health and Disease States: The evidence from clinical studies and animal models shows a link between the gut microbiome and human health. There exists a bidirectional microbiota–gut–brain communication which modulates brain function and behaviours. The research in mice and humans is beginning to establish a link between the composition of microbes in the gut and immune response to tumor cells. Certain metabolites or antigens presented by members of that microbiome may help uplift the sensitivity of immune system to tumour cells, whereas dysbiosis may lead to the loss of antitumor immunity. On the other hand, the gut microbes harbour enzymes and secrete molecules that can influence drug activation, efficacy, and metabolism. Dietary Constituents and Microbiome: The dietary components influence the gut microbiota. It has been documented that a change in diet can alter the degradative activity of the colonic microbiota in vivo and in a physiologically relevant setting influence the expression of various microbial genes. The complex plant polysaccharides in diet are not digested and enter the colon as a potential food source for the gut microorganisms, which harbour a multitude of genes involved in catabolism of carbohydrates. The reduced availability of dietary polysaccharides and fibre can trigger dysbiosis and degradation of intestinal mucin layer and affect intestinal health. The microbial production of short chain fatty acids and other metabolites has been shown to influence immune system.

Constitution of mucosa‐associated microbiota in the lower digestive tract does not change in early stage of non‐alcoholic fatty liver disease with fecal dysbiosis

Background and AimRegarding the gut–liver axis, fecal dysbiosis is implicated in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). The significance of mucosa‐associated microbiota (MAM, which is present in the mucin layer covering the intestinal mucosa) has not been well explored. We aimed to clarify the characteristics of MAM in patients with NAFLD.MethodsMAM were obtained from seven patients with early‐stage NAFLD and seven controls by colonoscopy in five locations (terminal ileum, cecum, ascending and sigmoid colon, and rectum) using mucosal brushes. The microbial 16S rDNA profiles of the MAM and fecal microbiota of patients in the NAFLD and control groups were analyzed.Resultsα‐diversities of fecal microbiota were decreased in patients with NAFLD (observed species, Shannon index, and Chao1: 174.57 vs 134.86, 5.51 vs 4.65, and 206.34 vs 167.91; P = 0.048, 0.067, and 0.087, respectively), and microbial composition analyses by principal coordinate analysis differed between the fecal microbiota of patients with NAFLD and those of controls (permutational analysis of variance [PERMANOVA] of weighted and unweighted: Pseud‐F: 1.4179/P‐value: 0.05 and Pseud‐F: 2.1497/P‐value: 0.049, respectively). However, α‐diversities or microbial composition of MAM in most parts of the intestine did not differ significantly between the NAFLD and control groups. Unclassified Rikenellaceae, Oscillospira, Odoribacter, unclassified clostridiales, and Holdemania were decreased in the feces of patients with NAFLD (determined by linear discriminant analysis effect size), but five (except Holdemania) of the six genera were not decreased in the MAM of these patients.ConclusionIn early‐stage NAFLD, MAM was uniform and relatively stable throughout the intestine, even when fecal dysbiosis appeared.

Tear Film Stability as a Function of Tunable Mucin Concentration Attached to Supported Lipid Bilayers.

In this work, we describe the development of a tunable, acellular in vitro model of the mucin layer of the human tear film. First, supported lipid bilayers (SLBs) comprised of the phospholipid DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) and biotinyl cap PE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(cap biotinyl)) are created on the surface of a glass dome with radius of curvature comparable to the human eye. Next, biotinylated bovine submaxillary mucins (BSM) are tethered onto the SLB using streptavidin protein. The mucin presentation can be tuned by altering the concentration of biotinylated BSM, which we confirm using fluorescence microscopy. Due to the optically smooth surface that results, this model is compatible with interferometry for monitoring film thickness. Below a certain level of mucin coverage, we observe short model tear film breakup times, mimicking a deficiency in membrane-associated mucins. In contrast, the breakup time is significantly delayed for SLBs with high mucin coverage. Because no differences in mobility or wettability were observed, we hypothesize that higher mucin coverage provides a thicker hydrated layer that can protect against external disturbances to thin film stability. This advance paves the way for a more physiological, interferometry-based in vitro model for investigating tear film breakup.

Stable oral lubrication enhancer obtained from thiolated polyethylene glycol and mucin

Mucins are vital components contributing to the unique lubrication properties of human whole saliva. For patients receiving medication and or treatment such as diabetes or radiotherapy, xerostomia (dry mouth) is a common with numerous and deleterious side effects. Although products exist on the market to relive the symptoms of Xerostomia there remains a drive to formulate a biocompatible lubricant that replicate the functionality offered by the natural biological environment. Herein, a combination of mucin and thiolated polyethylene glycol (PEG-SH) was proposed as a new saliva substitute. Mucin and PEG-SH molecules could form hydrated layers immediately by chemisorption. Meanwhile, the chemical interactions between mucin and PEG-SH molecules also promoted the formation of a mixed layer. All the pre-formed layers could decrease friction and had the potential to decrease wear, especially mucin and PEG-SH mixed layer when compared to mucin only solutions. Further investigations of tribological mechanism implied that the excellent lubrication performance of mixed layer with long effectiveness was contributed to the friction-reducing effect of PEG/mucin molecules and the mucoadhesive property of mucin. The study provides a guide for using mucin as a mucoadhesive agent to stable lubricative polymers with low molecular weight as novel salivary substitutes for lubrication.

Digestion Resistance of Soybean 7S Protein and Its Implications for Reinforcing the Gastric Mucus Barrier.

Previous studies have found that soybean protein, especially soybean 7S protein (β-conglycinin), exhibits digestion resistance, but the mechanism of digestion resistance and its implications for human health are still unclear. Here, we show that the extracted soybean 7S protein contains both oligomer globulins and amyloid aggregates, while the gastric digested soybean 7S protein only contains amyloid aggregates and thus exhibits digestion resistance. An animal experiment shows that un-digestible soybean 7S protein effectively prevents aspirin-induced acute gastric mucosa damage. The impacts of un-digestible soybean 7S protein on gastric mucus barrier properties are investigated using quartz crystal microbalance with dissipation (QCM-D), Langmuir monolayer, and multiple particle tracking (MPT). Results show that these un-digestible protein aggregates can penetrate into gastric mucus, increase the viscosity and compactness of the mucin layer, and reinforce the gastric mucus barrier properties. The findings are helpful to understand that high consumption of non-fermented soybean foods is associated with a decreased risk of gastric cancer.

MUCOADHESIVE PATCHES OF PREGABALIN EFFECTIVE IN THE TREATMENT OF NEUROPATHIC PAIN: A SYSTEMATIC REVIEW

Although the oral pathway is the recommended mode of intake for the majority of medications, it does have some drawbacks i.e., pre-systemic metabolism in the liver, gastrointestinal disturbance, and enzyme degradation. It offers a safe method for administration of medications and easy way to reverse the intake of toxic substances by easy removal of dosage form from oral cavity. This review was designed to critically acknowledge the evaluation parameters, mechanism of cohesion, polymers used in mucoadhesive formulation, main method of preparations (solvent casting & milling), advantages & disadvantages of mucoadhesive patches. This review consists an extensive survey of literature from the Scopus, PubMed, Springer Nature and other international reputed sources. Since the middle of 1980s, the idea of muco-adhesion has acquired extensive interest in drug innovation. Muco-adhesive dosage structures were developed for oral delivery like adhesive unit dosage form, adhesive gels and adhesive patches. The epithelium that forms the internal lining of buccal mucosa is the primary obstruction for the drugs absorption. Muco-adhesion is defined as an interfacial adhesion in which one synthetic mucoadhesive polymer and the other mucin layer (mucosal tissue), are hold together by an attraction force. 'Mucoadhesive’ is defined as an artificial substance being capable of making interaction with mucus membranes and binding them together for extended or delayed periods of time. However, delivering therapeutically for the therapy of both systemic and topical disorders would take a lot more work with these innovative mucoadhesive formulations. In conclusion, it facilitates the target therapy by enriching efficacy or intrinsic activity. Keywords: mucoadhesive patch, solvent-casting, milling, mechanism of muco-adhesion, polymers

Extracts of Periplaneta americana alleviate hepatic fibrosis by affecting hepatic TGF-β and NF-κB expression in rats with pig serum-induced liver fibrosis.

Liver fibrosis is caused by continuous wound healing responses to various harmful stimuli, including viral infection, drugs, alcohol, and autoimmune liver disease. The purpose of this study was to examine the effects of extracts of Periplaneta americana (EPA) in rats with pig serum-induced liver fibrosis to preliminarily assess the antifibrotic effect of EPA. Seventy rats were randomly divided into 7 groups (10 rats in each group): HC, the healthy control group; FC, the fibrotic control group; TL, low-dose EPA treatment group group; TM, medium-dose EPA group; TH, high-dose EPA treatment group; TC1, Panax notoginseng/Salvia mitiorrhiza treatment control group 1; TC2, colchicine treatment control group 2. TC1 and TC2 were used as the positive control to demonstrate the difference between EPA and the effects of other compounds. The liver fibrosis model was induced by intraperitoneal injection of 0.5 mL pig serum twice a week for 13 weeks in all groups except for the HC group. The hepatic fibrosis model was established at the 7th week, and followingly, the corresponding compounds were administered once a day in all groups for 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity was determined in rat blood serum. We also measured liver fibrosis-related serum markers, including hyaluronic acid (HA), mucin layer (LN), type III pre-collagen (PC-III) and type IV collagen (IV-C). Hematoxylin and eosin (H&E) and Masson stainings were used to assess liver morphology and determine the stage of fibrosis. Immunohistochemistry was used to detect the protein expression of NF-κB, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rat liver tissue. Compared with that of the HC group, the liver tissue of the FC group presented obvious liver damage and collagen deposition. The serum levels of ALT, AST, HA, LN, PC-III and IV-C and the expression of NF-κB, α-SMA, TGF-β1 and TIMP-1 in the FC group were significantly higher than those in the HC group, the EPA treatment groups, the TC1 group and the TC2 group (P < 0.01). The levels of serum ALT, AST, HA, LN, PC-III and IV-C and the expression of α-SMA, NF-κB, TGF-β1 and TIMP-1 in the TL, TC1 and TC2 groups were significantly higher than those TM and TH groups (P < 0.05). EPA treatment significantly improved liver function, decreased collagen deposition and reversed the pathological changes related to liver fibrosis. We found that EPA could reduce liver inflammation, suppress liver cell degeneration and necrosis, and reduce the formation of liver fibrous tissue. Its mechanism might be associated with inhibiting the expression of TGF-β1, TIMP-1, NF-κB and α-SMA to block signal transduction pathways in the hepatic fibrosis process. Therefore, EPA, as a traditional Chinese medicine, might be potentially used to prevent and treat hepatic fibrosis in the future. However, further more experiments are necessary to verify its effectiveness and possible signaling pathways.

1357-P: Diabetic Hyperglycemia Impairs Intestinal Barrier Function in the Setting of Diet-Induced Obesity

Proper function of the intestinal barrier plays a crucial role to maintain normal health by selectively absorbing nutrients and keeping out pathogens. Increased gut permeability is a feature of several diseases, including metabolic syndrome, but whether it is a cause or a consequence is unknown. We therefore examined the impact on intestinal barrier function of streptozotocin (STZ) -induced diabetes in C57BL/6J mice that were fed either standard chow or high-fat high-sucrose (HFHS) diet for 13wk. Moderate hyperglycemia was induced by low-dose i.p. STZ injection and 12wk later, intestinal tissues were collected and processed for quantification of colonic mucin and tight junction proteins. In both HFHS- and chow-fed mice, STZ treatment resulted in significantly elevated blood glucose levels compared to vehicle-treated controls (HFHS blood glucose 249.1 mg/dL vs. 157.5 mg/dL, p=0.0008; chow 330.2 mg/dL vs. 139.7mg/dL, p=0.0005) . In HFHS-fed mice, STZ hyperglycemia was associated with reductions of both the colonic mucin layer, as measured by Alcian Blue (AB) staining (percent area 52.6 vs. 62.4, p&amp;lt;0.0001) , and the tight junction protein E-cadherin (percent area 34.7 vs. 55.9, p=0.0029) . In non-obese chow-fed mice, however, STZ-induced hyperglycemia had no significant impact on AB mucin staining or E-cadherin protein abundance. Similarly, levels of colonic mucins and E-cadherin were inversely correlated with blood glucose levels in HFHS-fed mice (AB R2=0.43, p=0.0116; E-cadherin R2=0.30, p=0.0439) , but not in chow-fed mice. We conclude that while the combination of hyperglycemia and diet-induced-obesity is sufficient to impair intestinal barrier function, neither obesity nor diabetes in isolation is sufficient to induce this effect. Our additional finding that the magnitude of colonic dysfunction is correlated with the degree of hyperglycemia implicates excess glucose as a potential driver of obesity-associated impairment of intestinal barrier function. Disclosure K.L.Francis: None. K.M.Alonge: None. S.J.W.Hu: None. B.N.Phan: None. T.P.Doan: None. C.A.Krutzsch: None. Z.Maat: None. J.M.Scarlett: None. M.W.Schwartz: None. Funding National Institutes of Health T32 DK007742

Differences in MUC2 Gene Expression Based on the Clinical Severity of Colitis and the Degree of Histopathological Damage to the Colonic Mucosa in Colitis-induced Rat

BACKGROUND: Inflammatory bowel disease (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by intestinal inflammation and epithelial damage. Impaired mucosal cell barrier function mainly associated with thinning of the mucin layer may be the initial events underlying injury and inflammation in UC. Impaired expression of specific mucins is closely associated with IBD. MUC2 is a gene that produces mucin, which is predominant in the colon in humans and rats. METHODS: This study is an experimental study with a posttest-only design. The sample comprised 16 colitis-induced rats. Induction of colitis was done by giving a solution of dextran sodium sulfate (DSS) 2.5% 1 mL/day orally for 7 days. MUC2 gene expression was measured by rtPCR. The clinical severity of colitis was classified based on the disease activity index (DAI) score. The degree of histopathological damage was classified based on the score of colonic histology observations. The statistical analysis was done by the Shapiro–Wilk normality test and continued with an independent samples t-test. RESULTS: There were differences in MUC2 gene expression in mild and moderate colitis (1.81 vs. 2.99) but the difference was not significant (p &gt; 0.05). MUC2 gene expression also differed in mild and severe histopathological damage degrees (2.32 vs. 2.1) but the difference was not significant (p &gt; 0.05). CONCLUSION: It was concluded in this study that MUC2 gene expression did not have significant differences based on the clinical severity of colitis and the degree of histopathological damage to the colonic mucosa in colitis-induced rats.

Targeting mucin hypersecretion in COVID-19 therapy.

Targeting mucin hypersecretion in COVID-19 therapy.

Greater understanding about the role of mucin proteins in the skin

British Journal of DermatologyVolume 186, Issue 3 p. e116-e116 Plain Language SummaryFree Access Greater understanding about the role of mucin proteins in the skin First published: 07 March 2022 https://doi.org/10.1111/bjd.20990AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Linked Article: Kim and Choi. Br J Dermatol 2022; 186:532–543. The outermost layer of skin, the epidermis, provides a physical barrier of protection from harmful substances and invasion of pathogens such as viruses and bacteria. Part of this skin barrier consists of types of proteins called mucins. Mucins are also found in other organs of the body but less is known about their role in the skin than in other organs. However, we know that mucin can be used as a diagnostic clue in some skin disorders, for example, that there is overexpression of mucin in some skin cancers. In this study, from Korea, we set out to understand more about the role of mucin proteins in the skin. We found that several mucin proteins are expressed in human skin and among these, mucin-like protein 1 (MUCL1) showed high expression and also a clear negative association with melanogenesis (the production of melanin pigments, which determine the colour of our skin and that protect us against ultraviolet radiation damage). As the mucin layer is mostly composed of the amino acids serine and threonine we investigated the relationship of these amino acids with MUCL1. Amino acids are the building blocks of proteins. We found that the amino acid threonine could regulate MUCL1 in melanocytes (the cells producing melanin) and melanoma cells (i.e. cells found in some forms of skin cancers). This study provides a greater understanding about the role of mucins and threonine in skin dysfunction. Volume186, Issue3March 2022Pages e116-e116 RelatedInformation

Human Lactobacillus Biosurfactants as Natural Excipients for Nasal Drug Delivery of Hydrocortisone.

The inclusion of a chemical permeation enhancer in a dosage form is considered an effective approach to improve absorption across the nasal mucosa. Herein we evaluated the possibility of exploiting biosurfactants (BS) produced by Lactobacillus gasseri BC9 as innovative natural excipients to improve nasal delivery of hydrocortisone (HC). BC9-BS ability to improve HC solubility and the BS mucoadhesive potential were investigated using the surfactant at a concentration below and above the critical micelle concentration (CMC). In vitro diffusion studies through the biomimetic membrane PermeaPad® and the same synthetic barrier functionalized with a mucin layer were assessed to determine BC9-BS absorption enhancing properties in the absence and presence of the mucus layer. Lastly, the diffusion study was performed across the sheep nasal mucosa using BC9-BS at a concentration below the CMC. Results showed that BC9-BS was able to interact with the main component of the nasal mucosa, and that it allowed for a greater solubilization and also permeation of the drug when it was employed at a low concentration. Overall, it seems that BC9-BS could be a promising alternative to chemical surfactants in the nasal drug delivery field.

Anti-oxidative and mucin-compensating dual-functional nano eye drops for synergistic treatment of dry eye disease

Oxidative stress plays a central role in dry eye disease (DED), which can destroy the mucin layer on the ocular surface. The currently available eye drops are palliative and short-lived. Thus, a therapy that can continuously scavenge the overexpressed reactive oxygen species (ROS) and promote mucin production in DED is quite necessary. Thus, we have developed a synergistic nanoparticle (NP) that can treat DED by scavenging ROS and promoting mucin production. Mesoporous polydopamine (mPDA) NPs were prepared by one-pot synthesis and loaded with melatonin (Mel) and tavilermide (Tav) (mPDA@Mel-Tav). The mPDA NPs loaded with 20% Mel and 2% Tav showed good cytocompatibility. Mel and Tav were continuously released from mPDA@Mel-Tav NPs, and the release of Mel was slower than that of Tav. The ROS level and apoptosis ratio were decreased in the presence of mPDA@Mel-Tav, indicating the central role of Mel in ROS scavenging and antioxidant effect. Meanwhile, Tav promoted the production of mucins on the ocular surface. The retention time of mPDA was longer than that of normal eye drops. The corneal fluorescence staining score of mice with DED in mPDA@Mel-Tav treatment group was lower than in other treated groups, indicating the good therapeutic effect of mPDA@Mel-Tav in DED. In summary, we synthesized the mPDA@Mel-Tav NP eye drop to achieve a sustained release of Mel and Tav, which could effectively treat DED by scavenging ROS and promoting mucin production. This dual-functional NP represents a promising treatment strategy for DED and other multi-cause diseases.

Schizophyllum commune-derived \u03b2-glucan improves intestinal health demonstrating protective effects against constipation and common metabolic disorders

It has been proven that β-glucan produced by Schizophyllum commune has beneficial effects on obesity, obesity-associated constipation, and colitis conditions; however, the protective effect of the compound on host at basal state is yet to be investigated. C57BL/6 J mice were fed with a normal diet (ND), normal diet supplemented with 3 g/kg (BG_low), and 5 g/kg (BG_high) of β-glucan (BG) for 12 weeks. Body weight, food and water intake and fecal status were monitored weekly. Intestine was stained by Periodic acid–Schiff (PAS) and Alcian Blue to evaluate the mucin layer thickness and goblet cell population. Morphological changes in internal organs and intestinal motility were also assessed, while serum biomarkers for liver injury and glucose level were analyzed. On the other hand, fecal microbiota and associated metabolic activities were also investigated. β-glucan bulked feces, decreased fecal moisture, and proliferated goblet cells resulted in a thickened lubricating mucin layer; however, the intestinal transit rate did not increase. The abundance of beneficial bacteria was increased while the harmful strains was decreased in a dose-dependent manner by the effect of β-glucan. Specific short chain fatty acid (SCFA)-producing strains, such as Roseburia, Ruminococcus, and Bifidobacteria, were selectively increased by β-glucan. In addition, consumption of β-glucan lowered level of obesity-associated biomarkers. Schizophyllum commune β-glucan showed an insignificant change in transit rate in healthy conditions when compared with obesity, despite similar effects on increasing mucus production and bulked feces. Nonetheless, the outcomes proposed protective effects against obesity, diabetes, inflammatory bowel diseases (IBD), and constipation, in which the modification of the gut microbiota by β-glucan is the largest contributor.

Sophorolipid protects against early-weaning syndrome by improving the gut microenvironment in early-weaned piglets

BackgroundIn animals, weaning stress is the first and most critical stress. Weaning can negatively affect the growth performance of animals physically, psychologically, and pathologically. Our previous studies on the HT-29 cell line and early-weaned rats demonstrated that adequate sophorolipid (SPL) supplementation in feed could enhance the mucin-producing and wound healing capacities of the gut defense system by modulating gut microbiota.MethodsWe conducted an experiment with one hundred forty 21-day-old early weaned piglets (L x Y x D). They were allocated into 4 treatment and 7 replications (4 pigs per pen) according to their initial body weight. Body weight and feed intake were measured biweekly during experimental period. After 6 weeks, 28 pigs were randomly selected and sacrificed to collect plasma, jejunum, and cecal content samples.ResultsDietary SPL supplementation at 5 and 10 mg/kg quadratically increased the average daily gain during the experimental period in the treatment groups when compared with the control group. The albumin levels of piglets fed with the SPL supplemented diet were downregulated to the normal range. Moreover, in feed, SPL supplementation at 5 and 10 mg/kg improved jejunal histological indices and gene expression levels related to mucin secretion and local inflammation markers. Consistent with these results, adequate SPL supplementation (5 and 10 mg/kg) increased the population of Prevotella, a beneficial bacterium, and its short-chain fatty acid production in the ceca of piglets.ConclusionsThe occurrence of diarrhea after weaning in piglets could be reduced by feeding a 10 ppm of SPL supplemented diet which improves the gut defense system by improving the microbial population and enhancing mucin layer integrity.

Возможности патогенетической терапии острых кишечных инфекций у детей

Acute gastroenteritis remains one of the relevant health problems causing great economic and social burden both in our country and worldwide. The leading pathogenetic syndromes in gastroenteritis are dehydration, a violation of the qualitative and quantitative composition of the intestinal microbiocenosis, a violation of barrier properties of the intestinal mucosa, and a dysfunction of the apical enzymes of enterocytes. This article presents the main approaches to choosing optimal tactics of pathogenetic therapy, assessing the severity of gastroenteritis dehydration and demonstrates the role of probiotics in therapeutic tactics and the criteria for selecting strains. It was shown that the use of hypo-osmolar solutions in the treatment of dehydration syndrome in children is most appropriate. Complex pathogenetic therapy of gastroenteritis in children should be aimed at correcting the syndromes of dehydration and destabilization of the microbiocenosis system, accelerating the function restoration in apical enzymes of enterocytes, as well as optimizing the protective properties of the mucin layer of the intestinal mucosa. The most reasonable in the treatment of dehydration syndrome in children is the use of hypo-osmolar solutions. Simultaneously with rehydration, enterosorbents and dietary foods may be used to improve the effectiveness of treatment. Probiotic therapy should begin as early as possible and include internationally recommended probiotic strains, among which Lacticaseibacillus rhamnosus GG is one of the most studied and safe and can be successfully used both to relieve the symptoms of gastroenteritis and to prevent their complications. Key words: acute gastroenteritis, dehydration, probiotics, diarrhea, Lacticaseibacillus rhamnosus GG