Mucin Secretion Research Articles

Mucins as Potential Biomarkers for Early Detection of Cancer.

Early detection significantly correlates with improved survival in cancer patients. So far, a limited number of biomarkers have been validated to diagnose cancers at an early stage. Considering the leading cancer types that contribute to more than 50% of deaths in the USA, we discuss the ongoing endeavors toward early detection of lung, breast, ovarian, colon, prostate, liver, and pancreatic cancers to highlight the significance of mucin glycoproteins in cancer diagnosis. As mucin deregulation is one of the earliest events in most epithelial malignancies following oncogenic transformation, these high-molecular-weight glycoproteins are considered potential candidates for biomarker development. The diagnostic potential of mucins is mainly attributed to their deregulated expression, altered glycosylation, splicing, and ability to induce autoantibodies. Secretory and shed mucins are commonly detected in patients' sera, body fluids, and tumor biopsies. For instance, CA125, also called MUC16, is one of the biomarkers implemented for the diagnosis of ovarian cancer and is currently being investigated for other malignancies. Similarly, MUC5AC, a secretory mucin, is a potential biomarker for pancreatic cancer. Moreover, anti-mucin autoantibodies and mucin-packaged exosomes have opened new avenues of biomarker development for early cancer diagnosis. In this review, we discuss the diagnostic potential of mucins in epithelial cancers and provide evidence and a rationale for developing a mucin-based biomarker panel for early cancer detection.

A33 EFFECTS OF THE NEXT GENERATION PROBIOTIC, AKKERMANSIA MUCINIPHILA, ON INTESTINAL INFLAMMATION AND BARRIER FUNCTION

Abstract Background Inflammatory bowel disease (IBD), characterised by chronic intestinal inflammation, is hypothesised to arise from the interplay between susceptibility genes, the immune system, environmental factors, and gut microbiota. Akkermansia muciniphila is a symbiotic bacterium that accounts for 1-5% of the human fecal microbiota. This microbe has been hailed as a next-generation probiotic, principally with regard to its plethora of beneficial host interactions, including the ability to influence mucin secretion and strengthen the intestinal barrier. Purpose Though a clear-cut role and mechanism by which A. muciniphila influences inflammatory conditions is unknown, evidence indicates this microbe is depleted in IBD, suggesting it may have protective effects that are lost in these conditions. Here, we investigate the role and mechanism of A. muciniphila in intestinal inflammation and its influence on intestinal barrier function by utilizing barrier-disrupting models of colitis. Method Across several experimental models of intestinal inflammation including the chemically-induced dextran sulphate sodium (DSS) model, the parasitic-based model of Trichuris muris infection, and the spontaneous Muc2-/- model, A.muciniphila was administered by oral gavage. Disease activity index, macroscopic scoring and histological scoring were all performed to assess the severity of intestinal inflammation. Various pro- and anti-inflammatory cytokines were assessed within colonic tissue using commercially available ELISA kits.To investigate the effects that A. muciniphila has on barrier function in the context of colitis, reverse transcriptase qPCR was used to explore several factors, including several TJPs, AMPs, and mucins. To analyse the composition of the microbiota and changes in diversity with A. muciniphila supplementation, 16S rRNA sequencing of fecal samples was performed. Result(s) Though only minor benefits were derived from this microbe in germ-free mice, in specific pathogen-free (SPF) mice, administration of pasteurized A. muciniphila in a DSS recovery model ameliorated inflammation severity and promoted recovery compared to controls. When gavaged prior to DSS administration, both live and pasteurized A. muciniphila failed to diminish inflammatory markers indicating minimal preventative effects. T. muris-infected SPF mice treated with live A. muciniphila showed increased levels of Th2 and anti-inflammatory cytokines, decreased worm burden, and enhanced levels of the mucin, Muc5ac, compared with those receiving control broth or pasteurized bacteria. Further, both live and pasteurized A. muciniphila ameliorated the severity of inflammation in a mucin 2 deficient (Muc2-/-) mouse model of spontaneous colitis, indicating that these protective effects are Muc2-independent. Conclusion(s) These observations provide us not only with an enhanced understanding of the role A. muciniphila plays in the pathogenesis of intestinal inflammatory conditions but also may fuel novel avenues of treatment for those with IBD. Please acknowledge all funding agencies by checking the applicable boxes below CIHR Disclosure of Interest None Declared

Excessive consumption of mucin by over-colonized Akkermansia muciniphila promotes intestinal barrier damage during malignant intestinal environment.

Gut microbiota disorders damage the intestinal barrier, which causes intestinal disease. Thus, we screened the microbiota with significant changes using an in situ malignant colorectal cancer (CRC) model. Among the colonies with increased abundance, Akkermansia muciniphila (A. muciniphila) is known for its characteristic of breaking down mucin, which is an essential component of the intestinal barrier. The role of A. muciniphila remains controversial. To investigate the effect of excess A. muciniphila on the intestinal barrier, we established an over-colonized A. muciniphila mouse model by administering a live bacterial suspension after disrupting the original gut microbiome with antibiotics. The results showed that over-colonization of A. muciniphila decreased intestinal mucin content. The mRNA and protein expression levels of tight junction proteins also decreased significantly in the over-colonized A. muciniphila mouse model. Our findings reveal that excess colonization by A. muciniphila breaks the dynamic balance between mucin secretion and degradation, reduces the thickness of the intestinal mucus layer, and damages the intestinal barrier, which would eventually aggravate the development of colitis and CRC. These results will raise awareness about the safety of A. muciniphila serving as a probiotic.

Role of a novel mouse mutant of the Galnt2 tm1Lat/tm1Lat gene in otitis media.

Genetic susceptibility is one of the most important causes of otitis media (OM). Mutant Galnt2 homozygote (Galnt2 tm1Lat/tm1Lat) mimics human otitis media in comparable pathology and causes hearing loss. Otitis media is characterized by effusion and dysregulated mucosa proliferation and capillary expansion in the middle ear cavity, which is associated with hearing loss. The mucociliary dysfunction could be seen in the middle ear cavity (MEC) in a patient harboring the disease that develops in severity with age by a scanning electron microscope. Tumor necrosis factor alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), Muc5ac, and Muc5b upregulate the expression in the middle ear, which correlates with inflammation, craniofacial development, and mucin secretion. The mouse model with a mutation in the Galnt2 (Galnt2 tm1Lat/tm1Lat) was explored in this study as a novel model of human otitis media.

Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia.

Colorectal cancer (CRC) is one of the most common human malignancies worldwide. Along with apoptosis and inflammation, autophagy is one of three important mechanisms in CRC. The presence of autophagy/mitophagy in most normal mature intestinal epithelial cells has been confirmed, where it has mainly protective functions against reactive oxygen species (ROS)-induced DNA and protein damage. Autophagy regulates cell proliferation, metabolism, differentiation, secretion of mucins and/or anti-microbial peptides. Abnormal autophagy in intestinal epithelial cells leads to dysbiosis, a decline in local immunity and a decrease in cell secretory function. The insulin-like growth factor (IGF) signaling pathway plays an important role in colorectal carcinogenesis. This is evidenced by the biological activities of IGFs (IGF-1 and IGF-2), IGF-1 receptor type 1 (IGF-1R) and IGF-binding proteins (IGF BPs), which have been reported to regulate cell survival, proliferation, differentiation and apoptosis. Defects in autophagy are found in patients with metabolic syndrome (MetS), inflammatory bowel diseases (IBD) and CRC. In neoplastic cells, the IGF system modulates the autophagy process bidirectionally. In the current era of improving CRC therapies, it seems important to investigate the exact mechanisms not only of apoptosis, but also of autophagy in different populations of tumor microenvironment (TME) cells. The role of the IGF system in autophagy in normal as well as transformed colorectal cells still seems poorly understood. Hence, the aim of the review was to summarize the latest knowledge on the role of the IGF system in the molecular mechanisms of autophagy in the normal colon mucosa and in CRC, taking into account the cellular heterogeneity of the colonic and rectal epithelium.

Mammary mucinous cystadenocarcinoma with long-term follow-up: molecular information and literature review

BackgroundMucinous cystadenocarcinoma (MCA) is a very rare form of breast cancer that was first described in 1998. Only 33 cases of primary MCA, including our present case, have been reported thus far. As a consequence, its molecular features, prognosis and treatment regimen are poorly known. Here, we describe a less common presentation of MCA, detail its molecular features, discuss the major differential diagnosis, and provide a brief review of the literature.Case presentationA 59-year-old woman presented with a breast lump in which mammography showed a well-defined nodule. Core needle biopsy (CNB) revealed several lesions lined by tall columnar cells with stratification and abundant mucinous secretion; excision was recommended for final diagnosis. The resected specimens showed cavities of different sizes without surrounding myoepithelial cells. The cavities were rich in mucus, and the nuclei were located at the base of the cells, containing intracellular mucus. Immunohistochemical analysis revealed that it was triple-negative breast cancer (TNBC). Next-generation sequencing (NGS) revealed pathogenic mutations in the PIK3CA, KRAS, MAP2K4, RB1, KDR, PKHD1, TERT, and TP53 genes. A diagnosis of MCA was rendered. The patient has been followed up for 108 months to date and showed no signs of recurrence or metastasis.ConclusionOur study presents the gene profile of an MCA case with no recurrence or metastatic tendency after 108 months of follow-up, and a review of the literature helps us better understand the clinical, pathologic, and molecular features of this tumor.

Quantification of secretory IgA and mucin excretion and their contributions to total endogenous amino acid losses in roosters that were fasted or precision-fed a nitrogen-free diet or various highly digestible protein sources

The objective of this study was to quantify total secretory IgA (sIgA) and mucin excretion via excreta in roosters fed diets containing highly digestible protein sources and to determine their proportional contributions to total endogenous amino acid (AA) losses. Precision-fed rooster assays with 24 h excreta collections were conducted using conventional White Leghorn roosters (4-8 roosters per treatment). In Experiment 1, roosters were fasted or precision-fed 30 g (crop intubation) of a nitrogen-free (NF) or semi-purified diet containing 10% casein. Roosters in Experiment 2 received a NF or semi-purified diet containing either 10% casein, 17% whole egg, 10% egg white, 9.8% soy protein isolate, 10.2% chicken breast meat, 11.2% spray-dried animal plasma (SDAP), or an AA mixture containing the same AA as casein. A Latin square design was used in Experiment 3, where roosters received NF or semi-purified diets containing either 10% casein, 17% whole egg, or 9.6% of a crystalline AA mixture to evaluate both diet and individual bird effects. In Experiment 1, mucin excretion did not differ (P > 0.05) among treatments; however, total sIgA excretion was lower for fasted birds, intermediate for the NF diet, and highest for casein (P < 0.05). Total endogenous AA losses (proportion of the total) from sIgA were higher for roosters fed casein, whereas mucin contributions were higher for fasted roosters (P < 0.05). In Experiment 2, sIgA excretion did not differ (P > 0.05) among treatments; however, mucin excretion was reduced for NF, whole egg, egg white, and chicken breast compared with casein and SDAP. In Experiment 3, sIgA and mucin excretion did not differ (P > 0.05) among treatments; however, sIgA excretion differed among individual roosters (7-27 mg/24 h; P < 0.05). Overall, fasting reduced sIgA excretion and sIgA and mucin excretion were affected by dietary protein source. Further, roosters excreted a substantial amount of sIgA, and sIgA and mucin were considerable contributors to total endogenous AA losses.

Type 2 Immunity and Its Impact on COVID-19 Infection in the Airways.

Type 2 immune responses are characterized by elevated type 2 cytokines and blood eosinophilia. Emerging evidence suggests that people with chronic type 2 inflammatory lung diseases are not particularly susceptible to SARS-CoV-2 infection. Intriguingly, recent in vitro, ex vivo research demonstrates type 2 cytokines, particularly IL-13, reduce the risk of SARS-CoV-2 infection in the airway epithelium. IL-13 treatment in airway epithelial cells followed by SARS-CoV-2 diminished viral entry, replication, spread, and cell death. IL-13 reduces the expression of the angiotensin-converting enzyme 2 (ACE2) receptor in the airway epithelium and transmembrane serine protease 2 (TMPRSS2), particularly in ciliated cells. It also alters the cellular composition toward a secretory-cell-rich phenotype reducing total ciliated cells and, thus, reducing viral tropism. IL-13 enhances Muc5ac mucin and glycocalyx secretion in the periciliary layer, which acts as a physical barrier to restrict virus attachment. Moreover, type 2 airway immune cells, such as M2 alveolar macrophages, CD4+ tissue-resident memory T cells, and innate lymphoid 2 cells, may also rescue type 2 airways from SARS-CoV-2-induced adverse effects. In this review, we discuss recent findings that demonstrate how type 2 immunity alters immune responses against SARS-CoV-2 and its consequences on COVID-19 pathogenesis.

Inhibition of microRNA-328 Increases Ocular Mucin Expression and Conjunctival Goblet Cells.

We previously reported anti-miR-328 therapy for dry eye disease (DED). Since decreased mucin secretion is a risk factor for DED, we aimed to explore whether anti-miR-328 affects mucin expression and goblet cells. MiR-328 was increased in goblet cells when they were under desiccating stress or treated with benzalkonium chloride (BAC), both of which are risk factors for DED. Based on bioinformatics tool results, miR-328 was predicted to directly target the transcription factor CREB1 that has been known to promote the expression of mucin5AC. The inhibitory effect of miR-328 on CREB1 was confirmed by the transfection assay. A miR-328 binding site on the CREB1 gene was confirmed by the luciferase assay. Furthermore, anti-miR-328 increased CREB1 and mucin5AC in cultured goblet cells according to qPCR, Western blot, and IF staining experiments. Anti-miR-328 increased mucin5AC secretion from the cultured goblet cells based on an ELISA assay for the cultured medium. Finally, impression cytology data revealed anti-miR-328 increased conjunctival goblet cells in the DED rabbits induced by BAC. In conclusion, anti-miR-328 increases CREB1 expression leading to an increase in mucin5AC production and secretion. Furthermore, anti-miR-328 also increases conjunctival goblet cells. These results warrant the further development of anti-miR-328 therapy for DED.

The Milk Active Ingredient, 2'-Fucosyllactose, Inhibits Inflammation and Promotes MUC2 Secretion in LS174T Goblet Cells In Vitro.

In several mice inflammatory models, human milk oligosaccharides (HMOs) were shown to protect the intestinal barrier by promoting mucin secretion and suppressing inflammation. However, the functions of the individual HMOs in enhancing mucin expression in vivo have not been compared, and the related mechanisms are not yet to be clarified. In this study, we investigated the modulatory effects of 2′-fucosyllactose (2′-FL), 3′-sialyllactose (3′-SL), galacto-oligosaccharide (GOS) and lactose (Lac) on goblet cells’ functions in vitro. The appropriate dosage of the four chemicals was assessed in LS174T cells using the CCK-8 method. Then they were supplemented into a homeostasis and inflammatory environment to further investigate their effects under different conditions. Mucin secretion-related genes, including mucin 2 (MUC2), trefoil factor family 3 (TFF3), resistin-like β (RETNLB), carbohydrate sulfotransferase 5 (CHST5) and galactose-3-O-sulfotransferase 2 (GAL3ST2), in LS174T cells were detected using quantitative RT-qPCR. The results showed that 2′-FL (2.5 mg/mL, 72 h) was unable to increase MUC2 secretion in a steady-state condition. Comparatively, it exhibited a greater ability to improve mucin secretion under an inflammatory condition compared with GOS, demonstrated by a significant increase in TFF3 and CHST5 mRNA expression levels (p > 0.05). However, 3′-SL and Lac exhibited no effects on mucin secretion. To further investigate the underlying mechanism via which 2′-FL enhanced goblet cells’ secretion function, the NOD-like receptor family pyrin domain containing 6 (NLRP6) gene, which is closely related to MUC2 secretion, was silenced using the siRNA method. After silencing the NLRP6 gene, the mRNA expression levels of MUC2, TFF3 and CHST5 in the (2′-FL + tumor necrosis factor α (TNF-α) + NLRP6 siRNA) group were significantly decreased compared with the (2′-FL + TNF-α) group (p > 0.05), indicating that NLRP6 was essential for MUC2 expression in goblet cells. We further found that 2′-FL could significantly decrease toll-like receptor 4 (TLR4, p < 0.05), myeloid differential protein-88 (MyD88, p < 0.05) and nuclear factor kappa-B (NF-κB, p < 0.05) levels in LS174T inflammatory cells, even when the NLRP6 was silenced. Altogether, these results indicated that in goblet cells, 2′-FL exerts its function via multiple processes, i.e., by promoting mucin secretion through NLRP6 and suppressing inflammation by inhibiting the TLR4/MyD88/NF-κB pathway.

Secretin alleviates biliary and liver injury during late-stage primary biliary cholangitis via restoration of secretory processes.

Primary biliary cholangitis (PBC) is characterised by ductopenia, ductular reaction, impairment of anion exchanger 2 (AE2) and the 'bicarbonate umbrella'. Ductulo-canalicular junction (DCJ) derangement is hypothesised to promote PBC progression. The secretin (Sct)/secretin receptor (SR) axis regulates cystic fibrosis transmembrane receptor (CFTR) and AE2, thus promoting choleresis. We evaluated the role of Sct/SR signalling on biliary secretory processes and subsequent injury in a late-stage PBC mouse model and human samples. At 32 weeks of age, female and male wild-type and dominant-negative transforming growth factor beta receptor II (late-stage PBC model) mice were treated with Sct for 1 or 8 weeks. Bulk RNA-sequencing was performed in isolated cholangiocytes from mouse models. Biliary Sct/SR/CFTR/AE2 expression and bile bicarbonate levels were reduced in late-stage PBC mouse models and human samples. Sct treatment decreased bile duct loss, ductular reaction, inflammation, and fibrosis in late-stage PBC models. Sct reduced hepatic bile acid levels, modified bile acid composition, and restored the DCJ and 'bicarbonate umbrella'. RNA-sequencing identified that Sct promoted mature epithelial marker expression, specifically anterior grade protein 2 (Agr2). Late-stage PBC models and human samples exhibited reduced biliary mucin 1 levels, which were enhanced by Sct treatment. Loss of Sct/SR signalling in late-stage PBC results in a faulty 'bicarbonate umbrella' and reduced Agr2-mediated mucin production. Sct restores cholangiocyte secretory processes and DCJ formation through enhanced mature cholangiocyte phenotypes and bile duct growth. Sct treatment may be beneficial for individuals with late-stage PBC. Secretin (Sct) regulates biliary proliferation and bicarbonate secretion in cholangiocytes via its receptor, SR, and in mouse models and human samples of late-stage primary biliary cholangitis (PBC), the Sct/SR axis is blunted along with loss of the protective 'bicarbonate umbrella'. We found that both short- and long-term Sct treatment ameliorated ductular reaction, immune cell influx, and liver fibrosis in late-stage PBC mouse models. Importantly, Sct treatment promoted bicarbonate and mucin secretion and hepatic bile acid efflux, thus reducing cholestatic and toxic bile acid-associated injury in late-stage PBC mouse models. Our work perpetuates the hypothesis that PBC pathogenesis hinges on secretory defects, and restoration of secretory processes that promote the 'bicarbonate umbrella' may be important for amelioration of PBC-associated damage.

MUC5AC and MUC5B expression in canine gallbladder mucocele epithelial cells.

Gallbladder mucocele (GBM) is one of the most common gallbladder diseases in dogs. Its pathogenesis has not yet been clarified, but excessive accumulation of a secretory gel-forming mucin, MUC5AC in the gallbladder has been reported. This study aimed to ascertain if MUC5AC overproduction resulted in mucus accumulation in the gallbladder during GBM development. Eleven dogs undergoing cholecystectomy who were pathologically diagnosed with GBM were included, and the expression level of mucins, particularly MUC5AC and MUC5B, in their gallbladder epithelial cells was compared with those in normal gallbladder epithelial cells. On reverse transcription-quantitative polymerase chain reaction screening, there was a significant difference (P<0.05) in the mRNA expression level of MUC1, but not of other mucins including MUC5AC and MUC5B, between mucocele and normal gallbladder epithelial cells. Protein expression levels were also evaluated for MUC5AC and MUC5B using immunohistochemistry. There was little immunoreactivity for MUC5AC, whereas MUC5B showed definitive staining in gallbladder epithelial cells. There was no difference in MUC5AC and MUC5B protein expression levels between mucocele and normal gallbladder epithelial cells. These data suggest that excessive production of mucin, especially MUC5AC and MUC5B, does not occur in canine GBM, and that abnormal mucus excretion, rather than excessive mucus production, may be the cause of GBM development.

Limosilactobacillus reuteri Regulating Intestinal Function: A Review

Probiotics have extensive use in daily life, due to the function of the changing intestinal metabolism and material conversion processes, wherein they remodel the intestinal microbiota, regulate the intestinal function and affect the organism’s health. Limosilactobacillus reuteri (L. reuteri), originally discovered in breast milk and currently reported to be present within the gut of almost all vertebrates and mammals, is an intestinal probiotic with prebiotic efficacy. Most L. reuteri have good intestinal colonization and bacteriocin secretion abilities, which can increase the expression of the mucin (mucoprotein) genes 2 MUC2 and MUC13, which in turn promote the development and maturation of intestinal organoids, and augment mucin secretion. In enteritis patients, L. reuteri downregulates α Tumor necrosis factor-α, (TNF-α), Interleukin-6 (IL-6), IL-8, and IL-12 expression to attenuate inflammation. It also induces the host’s production of immunoglobulin A (IGA), which manipulates the intestinal microbial community, inhibiting the growth of pathogens. L. reuteri has been widely used in daily life. with in-depth studies having been conducted on the prebiotic effects of L. reuteri. However, the complexity of its application in a clinical setting is still unclear because the pathogenesis of various diseases still requires a large amount of data and theoretical support.

Apigenin remodels the gut microbiota to ameliorate ulcerative colitis.

Ulcerative colitis (UC), a chronic non-specific colorectal inflammatory disease with unclear etiology, has long plagued human health. Gut microbiota dysbiosis destroy homeostasis of the colon, which is closely related to ulcerative colitis progress. Apigenin, a flavonoid widely present in celery, has been found to improve ulcerative colitis. However, the potential molecular mechanism of apigenin ameliorating ulcerative colitis through protecting intestinal barrier and regulating gut microbiota remains undefined. Dextran sodium sulfate (DSS)-induced colitis mouse model was conducted to evaluate the effect of apigenin on UC. Disease activity index score of mice, colon tissue pathological, cytokines analysis, intestinal tight junction proteins expression, and colonic content short-chain fatty acids (SCFAs) and 16S rRNA gene sequencing were conducted to reflect the protection of apigenin on UC. The results indicated that apigenin significantly relieved the intestinal pathological injury, increased goblet cells quantity and mucin secretion, promoted anti-inflammatory cytokines IL-10 expression, and inhibited the expression of proinflammatory cytokines, TNF-α, IL-1β, IL-6 and MPO activity of colon tissue. Apigenin increased ZO-1, claudin-1 and occludin expressions to restore the integrity of the intestinal barrier. Moreover, apigenin remodeled the disordered gut microbiota by regulating the abundance of Akkermansia, Turicibacter, Klebsiella, Romboutsia, etc., and its metabolites (SCFAs), attenuating DSS-induced colon injury. We also investigated the effect of apigenin supplementation on potential metabolic pathways of gut microbiota. Apigenin effectively ameliorated DSS-induced UC via balancing gut microbiome to inhibit inflammation and protect gut barrier. With low toxicity and high efficiency, apigenin might serve as a potential therapeutic strategy for the treatment of UC via regulating the interaction and mechanism between host and microorganism.

From the Editor’s Desk…

From the Editor’s Desk…

The role of mast cells in the pathogenesis of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is one of major causes of chronic noncommunicable diseases and mortality worldwide. The roles of macrophages, T-lymphocytes, neutrophils, and other cells in the development of chronic inflammation in this disease are well studied, but more and more researchers have focused on mast cells (MC) in recent years.The aim of this work is to summarize the data of experimental and clinical studies on the possible role of MCs in the pathogenesis of COPD. To this end, the review analyzed data on the relationship between MCs and respiratory function parameters in COPD, as well as the distribution of MCs subpopulations in different parts of the respiratory tract. The involvement of proteases (chymase and tryptase) in the development of inflammatory and fibrotic changes in COPD is discussed. The review presents research findings that indicate the possible involvement of chymase in pulmonary artery remodeling, increased secretion of mucins, and slowing down the airway epithelial repair. The role of MC tryptase in the development of fibrotic changes in the lungs and airways in COPD is also highlighted. A separate section of the review is devoted to chemokines that promote MC migration and their specific receptor. Chemokines play a special role in the development of inflammation in COPD.Conclusion. The available data suggest that MCs play a major role in the pathogenesis of COPD. Because of the inconsistency of some results, further clinical studies in larger cohorts of patients are needed.

The effect of chlorhexidine, povidone‐iodine and betadine antiseptic eye drops on cultured human conjunctival goblet cell survival

AbstractPurpose: To compare the effect of ocular antiseptic treatment in terms of 0.05% aqueous chlorhexidine, 5% povidone‐iodine (PI) and 5% betadine on cell viability and mucin secretion of primary cultured human goblet cells.Methods: Cell viability of primary cultured human goblet cells was analysed using lactate dehydrogenase (LDH) and tetrazolium dye (MTT) colorimetric assays. Expression of mucin was visualized by immunohistochemical staining of MUC5AC.Results: According to the LDH assay, PI and betadine significantly reduced goblet cell survival compared to controls (mean cell survival 23% ± 6 and 23% ± 7, respectively) (p &lt; 0.05), whereas chlorhexidine (mean cell survival 78 ± 17) did not significantly affect goblet cell viability. Similar results were obtained from the MTT assay, where PI and betadine caused a significant loss of goblet cells (mean cell survival 26% ± 12 and 26% ± 13, respectively) (p &lt; 0.05), and chlorhexidine caused a non‐significant loss of goblet cells compared to controls (mean cell survival 79% ± 8).Conclusions: PI and betadine, the most used antiseptic treatments prior to ocular surgery, are significantly more cytotoxic on conjunctival goblet cells compared to chlorhexidine.

Molecular Mechanisms Underlying the Effects of Bimin Kang Mixture on Allergic Rhinitis: Network Pharmacology and RNA Sequencing Analysis.

Allergic rhinitis (AR) is a highly prevalent chronic inflammatory disease of the respiratory tract. Previous studies have demonstrated that Bimin Kang Mixture (BMK) is effective in alleviating AR symptoms and reducing the secretion of inflammatory factors and mucin; however, the precise mechanisms underlying these effects remain unclear. We built target networks for each medication component using a network pharmacology technique and used RNA-seq transcriptome analysis to screen differentially expressed genes (DEGs) for AR patients and control groups. The overlapping targets in the two groups were assessed using PPI networks, GO, and KEGG enrichment analyses. The binding ability of essential components to dock with hub target genes was investigated using molecular docking. Finally, we demonstrate how BMK can treat AR by regulating the NF-κB signaling pathway through animal experiments. Effective targets from network pharmacology were combined with DEGs from RNA-seq, with 20 intersections as key target genes. The construction of the PPI network finally identified 5 hub target genes, and all hub target genes were in the NF-κB signaling pathway. Molecular docking suggests that citric acid, deoxyandrographolide, quercetin, luteolin, and kaempferol are structurally stable and can spontaneously attach to IL-1β, CXCL2, CXCL8, CCL20, and PTGS2 receptors. Animal experiments have shown that BMK inhibits NF-κB transcription factor activation, reduces the expression of proinflammatory cytokines and chemokines IL-1β, CXCL2, IL-8, and COX-2, and exerts anti-inflammatory and anti-allergic effects. BMK by regulating the NF-κB signaling pathway improves inflammatory cell infiltration, regulates mucosal immune balance, and reduces airway hypersensitivity. These findings provide theoretical support for the clinical efficacy of BMK for AR treatment.

The antioxidant and anti-inflammatory effects of Eremina desertorum snail mucin on experimentally induced intestinal inflammation and testicular damage.

Eremina desertorum snail mucin antioxidant and anti-inflammatory effects were investigated against carbon tetrachloride (CCl4)-intestinal inflammation and testes damage. Male albino mice were intraperitoneally injected with 0.5 ml/kg b.wt of 40% CCl4, twice a week for 8 weeks. The treated groups were treated orally with mucin (after 8 weeks of CCl4 intoxication, twice a week for 4 weeks). CCl4 caused significant increases in C-reactive protein, lipid peroxidation, interleukin-2 levels and caspase-3, while decreasing the total proteins levels, activities of catalase, superoxide dismutase, and glutathione reductase contents, testosterone and 17β estradiol levels compared with the control mice. The improvements of these parameters occurred after treatment with E. desertorum mucin, where all the biochemical measurements tended to restore to the normal values. Histopathologically, CCl4 caused ulceration in the columnar mucin secreting cells that lined the ileal mucosa, partial loss of goblet cells, abnormal villous/crypt ratio, and submucosal infiltrate of the inflammatory cells. Also, sections of testis showed alterations in the developmental spermatogenic arrangement of the same seminiferous tubules, with no spermatozoa in the center. Improvements in these architectures occurred after administration of mucin, where sections showed almost normal histological structure. In conclusion, E. desertorum mucin could be used as a supplementary material as it has antioxidant and anti-inflammatory effects; besides it has low cost.

Regulated Restructuring of Mucins During Secretory Granule Maturation In Vivo

Mucins are large, highly glycosylated transmembrane and secreted proteins that line and protect epithelial surfaces. However, the details of mucin biosynthesis and packaging invivo are largely unknown. Here, we demonstrate that multiple distinct mucins undergo intragranular restructuring during secretory granule maturation invivo, forming unique structures that are spatially segregated within the same granule. We further identify temporally-regulated genes that influence mucin restructuring, including those controlling pH (Vha16-1), Ca2+ ions (fwe) and Cl- ions (Clic and ClC-c). Finally, we show that altered mucin glycosylation influences the dimensions of these structures, thereby affecting secretory granule morphology. This study elucidates key steps and factors involved in intragranular, rather than intergranular segregation of mucins through regulated restructuring events during secretory granule maturation. Understanding how multiple distinct mucins are efficiently packaged into and secreted from secretory granules may provide insight into diseases resulting from defects in mucin secretion.