Search

We have recently shown that the colon is protected by an inner mucus layer that efficiently separates the bacteria in the outer mucus from the epithelial cells. The inner mucus is impervious for bacteria and built by a network formed by the MUC2 mucin. Lack or defects in this inner mucus layer allow bacteria to reach the epithelia, something that triggers colon inflammation.

Mucus from the footsole of the freshwater snail Lymnaea stagnate behaves as a weak, negatively charged ion exchanger. Activities and concentrations of Na, K, Ca, and Cl were measured in mucus dialysed to equilibrium against artificial pond water or physiological saline. Observed activity coefficients (activity/concentration) in mucus were compared with those predicted by the Debye-Huckel theory to interpret the effects of electrostatic forces between the polyelectrolyte ions and small ions. The affinity of mucus for small ions decreased in the series, Ca2+, K+, Na+, Cl−. The extent to which mucus can concentrate cations was measured using three different methods: by titrating the fixed acidic groups with K or Ca and by equilibrium dialysis after which the electrical potential difference was either measured directly or was calculated from the Nernst potential for Na. Ion exchange titration indicated a much smaller exchange capacity than did the other two methods. Kinetics of cation uptake by the snail from dilute media were re-interpreted by considering the enhanced concentrations of cations in the mucus layer. It was shown that the presence of mucus in the unstirred layer adjacent to a transporting epithelium can result in an underestimate of the Michaelis constant (Km) determined from influx measurements.

The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy is diminished by the formation of protein coronas (PCs) when they interact with biological matrices. PCs are broadly implicated in affecting the fate of NPs in vivo and in vitro, yet few studies have investigated PCs formed during interactions of NPs with the epithelial mucosa, especially mucus. In this study, we constructed transferrin modified NPs (Tf-NPs) as a model and explored the mechanisms and effects that epithelial mucosa had on PCs formation and the subsequent impact on the transcellular transport of Tf-NPs. In mucus-secreting cells, Tf-NPs adsorbed more proteins from the mucus layers, which masked, displaced, and dampened the active targeting effects of Tf-NPs, thereby weakening endocytosis and transcellular transport efficiencies. In mucus-free cells, Tf-NPs adsorbed more proteins during intracellular trafficking, which enhanced transcytosis related functions. Inspired by soft coronas and artificial biomimetic membranes, we used mucin as an “active PC” to precoat Tf-NPs (M@Tf-NPs), which limited the negative impacts of “passive PCs” formed during interface with the epithelial mucosa and improved favorable routes of endocytosis. M@Tf-NPs adsorbed more proteins associated with endoplasmic reticulum-Golgi functions, prompting enhanced intracellular transport and exocytosis. In summary, mucus shielded against the absorption of Tf-NPs, but also could be employed as a spear to break through the epithelial mucosa barrier. These findings offer a theoretical foundation and design platform to enhance the efficiency of oral-administered nanomedicines.

Colorectal cancer is one of the most common cancers, and current treatment options include surgery, chemotherapy, and radiation therapy. Most patients undergo surgery, which often requires extensive resection of the colon to prevent recurrence and metastasis of residual malignant tumor cells, leading to postoperative pain and discomfort in daily routines. Although versatile therapeutic patches have been developed to induce tumor apoptosis, achieving both great adhesiveness on the mucus layers of the colon tissue and anti‐cell/tissue adhesion to other surrounding organs remains a challenge. Herein, we report a Janus polysaccharide film comprising two polymers: mussel‐inspired catechol‐conjugated chitosan (Chi‐C) with muco‐adhesiveness, and alginate (Alg) with anti‐adhesion property. The Chi‐C and Alg polymers form a stably entangled bilayer film via electrostatic interactions. The Janus film shows a strong tissue adhesive strength of ∼10 kPa for the Chi‐C layer and weak strength of ∼1 kPa for the Alg layer. Particularly, the Janus film encapsulating an anti‐cancer drug exhibits a directional release profile to the tumor site, which is effective for triggering tumor death in in vivo colorectal tumor resection model. Ultimately, such anti‐cancer material strategies using bilayered structures are promising for advanced tumor therapy. For the patients undergoing the resection surgery of the colon cancer, it is important to minimize the extent of resection and prevent additional infection at the surgical site. Herein, we report a thin Janus film consisting of tissue‐adhesive catechol‐conjugated chitosan and antifouling alginate. The film encapsulating anti‐cancer drugs can inhibit tumor growth when potentially applied onto the surgical site.

Colonic epithelial cells are covered by thick inner and outer mucus layers. The inner mucus layer is free of commensal microbiota, which contributes to the maintenance of gut homeostasis. In the small intestine, molecules critical for prevention of bacterial invasion into epithelia such as Paneth-cell-derived anti-microbial peptides and regenerating islet-derived 3 (RegIII) family proteins have been identified. Although there are mucus layers providing physical barriers against the large number of microbiota present in the large intestine, the mechanisms that separate bacteria and colonic epithelia are not fully elucidated. Here we show that Ly6/PLAUR domain containing 8 (Lypd8) protein prevents flagellated microbiota invading the colonic epithelia in mice. Lypd8, selectively expressed in epithelial cells at the uppermost layer of the large intestinal gland, was secreted into the lumen and bound flagellated bacteria including Proteus mirabilis. In the absence of Lypd8, bacteria were present in the inner mucus layer and many flagellated bacteria invaded epithelia. Lypd8−/−mice were highly sensitive to intestinal inflammation induced by dextran sulfate sodium (DSS). Antibiotic elimination of Gram-negative flagellated bacteria restored the bacterial-free state of the inner mucus layer and ameliorated DSS-induced intestinal inflammation in Lypd8−/−mice. Lypd8 bound to flagella and suppressed motility of flagellated bacteria. Thus, Lypd8 mediates segregation of intestinal bacteria and epithelial cells in the colon to preserve intestinal homeostasis.

Gradients in fluid viscosity characterize microbiomes ranging from mucus layers on marine organisms1and human viscera2,3to biofilms4. Although such environments are widely recognized for their protective effects against pathogens and their ability to influence cell motility2,5, the physical mechanisms regulating cell transport in viscosity gradients remain elusive6–8, primarily due to a lack of quantitative observations. Through microfluidic experiments, we directly observe the transport of model biflagellated microalgae (Chlamydomonas reinhardtii) in controlled viscosity gradients. We show that despite their locally reduced swimming speed, the expected cell accumulation in the viscous region9,10is stifled by a viscophobic turning motility. This deterministic cell rotation—consistent with a flagellar thrust imbalance11,12—reorients the swimmers down the gradient, causing their accumulation in the low-viscosity zones for sufficiently strong gradients. Corroborated by Langevin simulations and a three-point force model of cell propulsion, our results illustrate how the competition between viscophobic turning and viscous slowdown ultimately dictates the fate of population-scale microbial transport in viscosity gradients.

ABSTRACTThe intestinal mucosal barrier, which is composed of epithelial cells and mucus layers secreted by goblet cells and contains commensal bacteria, constitutes the first line of defense against pathogenic gut microbiota. However, homeostasis between the microbiota and mucus layer is easily disrupted by certain factors, resulting in alteration of the gut microbiota and entry of pathogens to the intestinal mucosal barrier. In this review, we describe the structures and functions of the mucus layer, expound several crucial influencing factors, including diet styles, medications and host genetics, and discuss how pathogenic microorganisms interact with the mucus layer and commensal microbiota, with the understanding that unraveling their complex interactions under homeostatic and dysbiosis conditions in the colon would help reveal some underlying pathogenic mechanisms and thus develop new strategies to prevent pathogenic microbiological colonization.

The treatment of gastrointestinal diseases with pharmacological interventions presents several challenges. Ulcerative colitis is a prime cause of inflammation in the colonic region. Individuals with this condition typically have thin mucus layers, making them more susceptible to pathogenic invasions. Integrated biomarkers provide an extensive assessment of disease activity, progression, and response to treatment and offer a more accurate and personalized understanding of the disease, leading to improved diagnosis, targeted therapy, and better patient management. Conventional therapeutic approaches have failed to manage the disease symptoms effectively for many patients, impacting their quality of life significantly. This difficulty mainly arises from the inability of traditional therapies to target and deliver drugs to the colonic site accurately. In this context, targeted carriers are necessary. Smart nanomaterials with responsive properties are being investigated to concentrate therapeutic drugs in inflamed colon areas, including pH-responsive, ROS-responsive, enzyme-responsive, and thermo-responsive nanocarrier systems. The evolution of nanotechnology has enabled the creation of responsive smart nanocarriers, allowing for the controlled release of medications, reducing systemic absorption, and preventing drugs' undesirable distribution to healthy tissues. The latest advancements in responsive nanocarrier systems have given rise to multi-responsive mechanisms, including dual-responsive nanocarriers. These improvements have improved the interplay between biological tissues and smart nanocarriers, resulting in superior targeting and significant cellular intake of therapeutic agents. This article provides insight into current drug delivery systems that use various nanocarriers, highlighting their potential in managing ulcerative colitis and emphasizing the role of diagnostic biomarkers in assessing and optimizing the disease's treatment.

Mucus can effectively protect the exposed mucosal surfaces due to its adhesive and viscoelastic properties. Most foreign particulates are efficiently trapped in mucus layers via steric obstruction and adhesion. Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on their location sites. This article focuses on describing the tenacious mucus barrier properties, the strategies to investigate the interaction of nanoparticles with the mucus as well as the novel developments of mucus penetrating nanoparticles.

We designed a simple coarse-grained model of the glycocalyx layer, or adhesive mucus layer (AML), covered by mucus gel (luminal mucus layer) using a polymer lattice model and stochastic sampling (replica exchange Monte Carlo) for canonical ensemble simulations. We assumed that mucin MUC16 is responsible for the structural properties of the AML. Other mucins that are much smaller in size and less relevant for layer structure formation were not included. We further assumed that the system was in quasi-equilibrium. For systems with surface coverage and concentrations of model mucins mimicking physiological conditions, we determined the equilibrium distribution of inert nanoparticles within the mucus layers using an efficient replica exchange Monte Carlo sampling procedure. The results show that the two mucus layers penetrate each other only marginally, and the bilayer imposes a strong barrier for nanoparticles, with the AML layer playing a crucial role in the mucus barrier.

Fixation is the first step towards preservation of tissues and can impact downstream histological applications. Historically, formalin has been the fixative of choice in both research and clinical settings due to cost, accessibility, and broad applicability. Here, we describe a method for collection of porcine colon, and compare the usage of Carnoy's solution (CS) to a 10% neutral buffered formalin (NBF) in tissue fixation. Consecutive colon samples were collected from 24 four-wk-old piglets and fixed in CS for 45 min or NBF for 24 h. We measured the thickness of the inner mucus layer using Alcian Blue stain and found thicker inner mucus layers in porcine colons fixed with CS as compared to NBF (P < 0.0001). Carnoy's solution-fixed colon exhibited greater bacterial cell counts than NBF-fixed colon (P < 0.0022) after labeling with an eubacterial probe in fluorescent in situ hybridization (FISH). No difference was observed between the mucosal height (P = 0.42) and number of goblet cells (P = 0.66) between the 2 fixatives. From this, we concluded CS is more suitable than NBF for the preservation of the mucus layer and the associated mucosal bacteria in the porcine colon without compromising on overall tissue morphology. This study provides a useful sampling and fixation methodology for histology studies in the porcine gastrointestinal tract, and may be beneficial to microbiota, pathology, and nutrition studies.

Recent research indicates that the progression of Parkinson’s disease can start from neurons of the enteric nervous system, which are in close contact with the gastrointestinal epithelium: α-synuclein molecules can be transferred from these epithelial cells in a prion-like fashion to enteric neurons. Thin mucus layers constitute a defense line against the exposure of noninfected cells to potentially harmful α-synuclein species. We show that—despite its mucoadhesive properties—α-synuclein can translocate across mucin hydrogels, and this process is accompanied by structural rearrangements of the mucin molecules within the gel. Penetration experiments with different α-synuclein variants and synthetic peptides suggest that two binding sites on α-synuclein are required to accomplish this rearrangement of the mucin matrix. Our results support the notion that the translocation of α-synuclein across mucus barriers observed here might be a critical step in the infection of the gastrointestinal epithelium and the development of Parkinson’s disease.

Surface charge is a crucial factor that determines the in vivo behaviors of drug nanocarriers following administration via different routes. However, there is still a lack of comprehensive knowledge of how surface charges affect the in vivo behaviors of particles, especially for oral delivery. In this study, solid lipid nanoparticles (SLNs), as model drug nanocarriers, are modified to bear either anionic, cationic, or net neutral surface charges. The effect of surface charges on oral absorption of intact SLNs was investigated by tracking the in vivo transport of the particles. The fluorescent bioimaging strategy exploits the aggregation-caused quenching property to discriminate the particles. Both in vitro and in vivo lipolysis studies confirm slowed-down lipolysis by anionic charges in comparison with both unmodified and net neutral SLNs but accelerated degradation by cationic charges. The scanning of ex vivo tissues and organs reveals limited absorption of unmodified SLNs into the circulation. Nevertheless, all three types of surface charge modifications are able to enhance the oral absorption of intact SLNs with the fastest and highest absorption observed for net neutral SLNs, possibly owing to promoted mucus penetration. Anionic SLNs, though repulsed by the mucus layer, show the second highest absorption owing to enhanced lymphatic transport. The efficacy of cationic charge modification is less significant due to entrapment and retention in mucus layers as well as increased lability to lipolysis. In conclusion, surface charges may serve as initiators to guide the in vivo behaviors and enhance the oral absorption of intact SLNs.

Inspired by the fact that chitosan is a representative constituent of the ectocellular structure of Cryptococcus neoformansand a typical biomaterial for improving drug oral absorption, we designed an elegant and efficient C. neoformans-targeted drug delivery system via oral administration. A chitosan-binding peptide screened by phage display was used as the targeting moiety, followed by conjugation to the surface of poly(lactic-co-glycolic acid) nanoparticles as the drug carrier, which was then incubated with free chitosan. The noncovalently bound chitosan adheres to mucus layers and significantly enhances penetration of nanoparticles through the oral absorption barrier into circulation and then re-exposed the targeting ligand for later recognition of the fungal pathogen at the site of infection. After loading itraconazole as a model drug, our drug delivery system remarkably cleared lung infections of C. neoformansand increased survival of model mice. Currently, targeted drug delivery is mainly performed intravenously; however, the system described in our study may provide a universal means to facilitate drug targeting to specific tissues and disease sites by oral administration and may be especially powerful in the fight against increasingly severe fungal infections.

1. Using a modified equilibrium dialysis cell the rate of diffusion of butyrate through pig colonic mucus has been compared with that through other gels and unstirred layers. 2. Relative diffusion coefficients were calculated for each layer. Layers of 8% polyacrylamide, and of caecal, mid-colonic and terminal colonic mucus, had coefficients that were 50–60% of the apparent free diffusion coefficient for butyrate, determined using layers made up of Millipore filters alone. 3. The apparent free diffusion coefficients for butyrate (layers of agarose or filters) were 70% of previously determined values in the literature. This discrepancy can be explained by elements of the experimental procedure. 4. All mucus layers differed significantly from layers of 2% agarose and Millipore filters but were not significantly different from layers of 8% polyacrylamide or from each other. 5. Diffusion coefficients for butyrate in the mucus samples correlated with water content and carbohydrate content but had no relationship to protein content. 6. The rate of diffusion of butyrate in colonic mucus layers was significantly reduced when compared with unstirred layers (P < 0.05). Whether this has an effect on the butyrate supply to colonocytes in vitro and whether mucus in colonic disease behaves differently are subjects for further investigation.

Biological barriers significantly limit the delivery efficiency of drug delivery systems, resulting in undesired therapeutic effects. When designing a delivery system with optimized penetration behavior across the biological barriers, mechanical properties, such as deformability, are emerging as important parameters that need to be considered, although they are usually neglected in current research. Herein, a liquid core nanoparticle (LCN) composed of a polymer‐encapsulated edible oil droplet is demonstrated. Owing to the unique structure in which the liquid oil core is encapsulated by a layer of highly hydrophilic and cross‐linked polymer, the LCN exhibits high mechanical softness, making it deformable under external forces. With high deformability, LCNs can effectively penetrate through several important biological barriers including deep tumor tissue, blood–brain barriers, mucus layers, and bacterial biofilms. Moreover, the potential of the LCN as a drug delivery system is also demonstrated by the loading and release of several clinical drugs. With the capability of penetrating biological barriers and delivering drugs, LCN provides a potential platform for disease treatments, particularly for those suffering from inadequate drug penetration. Schematic illustration of liquid core nanoparticle (LCN), which exhibits high deformability, as well as controlled drug loading and release ability. Such a deformable nanoparticle effectively penetrates through several important biological barriers including deep tumor tissue, blood–brain barriers, mucus layer, and bacterial biofilm. Thus, LCN provides a potential platform for disease treatments, especially for those suffering from inadequate drug penetration.

Antimicrobial peptides (AMPs) is a large family of compounds serving as natural antibiotics, widely distributed across the organism, mainly in mucus layers. They are designed to prevent pathogens from colonization. Among them, defensins and cathelicidins could be found. LL-37, the sole human cathelicidin draws particular attention because of its outstanding abilities. In addition to being a broad spectrum antibiotic, LL-37 has potent chemotactic and immunomodulatory properties.

To achieve site-specific delivery of pharmaceuticals, the development of effective mucoadhesive polymers is essential. Thus far, only a few polymers, such as thiolated ones and related variants, have been studied. However, their mucoadhesiveness varies depending on the type of polymer and the degree of chemical functionalization. Furthermore, the chemistry of tethering often requires harsh reaction conditions. Recently, pyrogallol-containing molecules have emerged as good tissue and hemostatic adhesives, but their in vivo mucoadhesive properties have not been demonstrated. Herein, we found that pyrogallol-rich tannic acid (TA) formulated with poly(ethylene glycol) (PEG), named TAPE, exhibits superior mucoadhesive properties. TAPE is prepared by a simple physical mixture of TA and PEG. It remained on esophageal mucus layers for at least several hours (<8 h) after oral feeding. The mucoadhesion originated from intermolecular interaction between the polyphenols of TA and mucin, exhibiting pH dependency. TAPE adhered strongly to mucin in neutral conditions but bound weakly in acidic conditions due to different hydrolysis rates of the ester linkages in TA. Thus, TAPE might be useful as a long-lasting esophageal mucoadhesive composite.

Animals assemble and maintain a diverse but host-specific gut microbial community. In addition to characteristic microbial compositions along the longitudinal axis of the intestines, discrete bacterial communities form in microhabitats, such as the gut lumen, colonic mucus layers and colonic crypts. In this Review, we examine how the spatial distribution of symbiotic bacteria among physical niches in the gut affects the development and maintenance of a resilient microbial ecosystem. We consider novel hypotheses for how nutrient selection, immune activation and other mechanisms control the biogeography of bacteria in the gut, and we discuss the relevance of this spatial heterogeneity to health and disease.

Due to the recent rapid expansion in our understanding of the composition of the gut microflora and the consequences of altering that composition the question of how bacteria colonise mucus layers and interact with components of mucus, such as mucin, is now receiving widespread attention. Using a combination of mucus secreting cells, and a novel mucin microarray platform containing purified native mucins from different sources we recently demonstrated that two gastrointestinal pathogens, Helicobacter pyloriand Campylobacter jejuni, colonise mucus by different mechanisms. This result emphasizes the potential for even closely related bacteria to interact with mucus in divergent ways to establish successful infection. Expanding the use of the mucin arrays described in the study to other microorganisms, both pathogenic and commensal, should lead to the discovery of biologically important motifs in bacterial-host interactions and complement the use of novel in vitro cell models, such as mucus secreting cell lines.

A recent study conducted by researchers at the Shanghai Engineering Research Center of Food Microbiology examined the role of carbohydrate metabolism in the colonization of Lactiplantibacillus plantarum AR113 in vivo. The researchers constructed a ccpA knockout strain of AR113 and found that it had a decrease in maximum biomass and an increase in hysteresis time compared to the wild-type strain. However, the knockout of the ccpA gene did not significantly affect the colonization time of AR113 in the intestine during continuous administration. This research provides valuable insights into the role of carbohydrate metabolism in bacterial colonization time in vivo. [Extracted from the article]

Abstract: One of the standard experimental probes of a viscoelastic material is to measure the response of a layer trapped between parallel surfaces, imposing either periodic stress or strain at one boundary and measuring the other. The relative phase between stress and strain yields solid-like and liquid-like properties, called the storage and loss moduli, respectively, which are then captured over a range of imposed frequencies. Rarely are the full spatial distributions of shear and normal stresses considered, primarily because they cannot be measured except at boundaries and the information was not deemed of particular interest in theoretical studies. Likewise, strain distributions throughout the layer were traditionally ignored except in a classical protocol of Ferry, Adler and Sawyer, based on snapshots of standing shear waves. Recent investigations of thin lung mucus layers exposed to oscillatory stress (breathing) and strain (coordinated cilia), however, suggest that the wide range of healthy conditions and environmental or disease assaults lead to conditions that are quite disparate from the “surface loading” and “gap loading” conditions that characterize classical rheometers. In this article, we extend our previous linear and nonlinear models of boundary stresses in controlled oscillatory strain to the entire layer. To illustrate non-intuitive heterogeneous responses, we characterize experimental conditions and material parameter ranges where the maximum stresses migrate into the channel interior. [Copyright &y& Elsevier]

Mucus layers (McLs) are on the front line of the human defense system that protect us from foreign abiotic/biotic particles (e.g., airborne virus SARS-CoV-2) and lubricates our organs. Recently, the impact of McLs on human health (e.g., nutrient absorption and drug delivery) and diseases (e.g., infections and cancers) has been studied extensively, yet their mechanisms are still not fully understood due to their high variety among organs and individuals. We characterize these variances as the heterogeneity of McLs, which lies in the thickness, composition, and physiology, making the systematic research on the roles of McLs in human health and diseases very challenging. To advance mucosal organoids and develop effective drug delivery systems, a comprehensive understanding of McLs’ heterogeneity and how it impacts mucus physiology is urgently needed. When the role of airway mucus in the penetration and transmission of coronavirus (CoV) is considered, this understanding may also enable a better explanation and prediction of the CoV’s behavior. Hence, in this Review, we summarize the variances of McLs among organs, health conditions, and experimental settings as well as recent advances in experimental measurements, data analysis, and model development for simulations.

The cystic fibrosis (CF) airways have an incompletely characterized defect in innate defense that eventually leads to bacterial infection and airway inflammation. Persistent Pseudomonas aerugionsa infection resulting from defective innate immunity and a bacterial phenotypic switch to a more intractable mucoid form inside the airway are now well established as important components of CF pathogenesis. Broad-based factors leading to chronic infection will be discussed with respect to: bacterial virulence in the context of biofilm formation, quorum sensing machinery and alginate overproduction, and failure of innate lung immunity in CF airways. In addition, a controversial question as to whether inflammation or infection comes first during CF airway disease will be addressed. Finally, a new hypothesis, that P. aeruginosa thrives as biofilms within the thickened anaerobic mucus layers, will be developed.

The histology and ultrastructure of the nidamental glands (glandular oviduct) of 11 species of Nudibranchia are described and compared. Conclusions about functional morphology can be drawn from examination of animals preserved during the process of spawning. Generally speaking, all investigated species possess three structurally and functionally different parts in the nidamental glandular system. The proximal capsule gland forms an inner albuminous layer in the egg capsules, the following membrane gland builts the membrane around the embryo and the albuminous layer and in the distal mucous gland different mucus layers forming the spawn ribbon are successively added.

Loline, an alkaloid produced by Epichloë endophytes in pastoral grass species, is considered non-toxic with suggested antimicrobial and anthelmintic properties. In vivo metabolism of loline suggests ability to reach the abomasum or intestine, and anthelmintic benefit is indicated in vitro when parasites are in either a developmental stage close to the gastric mucus layers or adult stage consuming blood. Therefore, the objective of this project was to investigate the validation of using a loline seed extract as a natural anthelmintic in parasitized lambs. Sixteen Coopworth lambs were individually penned, offered ad-libitum lucerne pellets and water and randomly assigned to 3 treatment groups; CON; no treatment, or treatment with a Festuca pratensis seed extract with (LOL) or without loline (NIL). Lambs were orally infected with 20,0000 L3 Haemonchus contortus on day 0, and 10,000 L3 Teladorsagia circumcincta, and Trichostrongylus colubriformis on day 14. Parasites then matured to determine lolines efficacy on blood feeding adult Haemonchus contortus and L4 mucosal browsers Teladorsagia circumcincta, and Trichostrongylus colubriformis. Loline was orally dosed at 52.5 mg/kg LW starting on day 13, and every other day until slaughter for worm enumeration on day 28. Feed intake and refusals were recorded daily, and fecal samples were taken prior to infection, on loline dose days and at slaughter. Worm and fecal egg counts were transformed to log10and all data were analyzed in Genstat (18thedition). Significance was declared at P < 0.05. Worm burdens of T. circumcincta (P = 0.96), T. colubriformis (P = 0.43), and H. contortus (P = 0.15) were not different between treatments. No treatment difference (P = 0.39) was observed in fecal egg counts, weight gain (P = 0.51), or feed intake (P = 0.18). Average growth efficiency (kg LWG/ kg DM intake) was 0.18 in CON which was less (P = 0.01) than LOL (0.24) or NIL (0.23). In conclusion, limited evidence supported an in vivo anti-parasitic effect of loline.

The article discusses research which suggests that organisms participate in economic decision-making or behavior and cooperation.

A recent study conducted in Gujarat, India, focused on the challenges of delivering therapeutic agents across mucosal barriers in drug delivery. The researchers introduced Mucus-penetrating PEGylated Nanoshuttles (MPNS) as a strategy to overcome these challenges. The MPNSs are engineered with specific surface properties and sizes that allow them to efficiently traverse the mucus barrier without becoming trapped, providing a promising solution for enhanced drug delivery to mucosal tissue. The research was supported by various organizations and has been peer-reviewed. [Extracted from the article]

A recent study from GLA University in Mathura, India, explores the use of nanocarrier systems for targeted therapy and biomarker integration in the treatment of ulcerative colitis. Ulcerative colitis is a gastrointestinal disease that causes inflammation in the colon. Conventional therapies have limitations in effectively managing the symptoms of the disease, and targeted carriers are necessary for accurate drug delivery to the affected area. The advancements in nanotechnology have allowed for the development of smart nanocarriers that can release medications in a controlled manner, improving targeting and cellular intake of therapeutic agents. The study emphasizes the role of diagnostic biomarkers in optimizing the treatment of ulcerative colitis. [Extracted from the article]

The in vitro effect of urea and hydrolysis of urea by urease on mucus H+ permeability is reported here. The effective DHCi values indicate a strong pH dependence for H+ diffusion in both water and mucus layers, with no apparent trend at concentrations between 1 and 50 mM urea. However, the estimated DHCI at near-neutral and alkaline pH are 4- to 10-fold lower through mucus than through aqueous films. Moreover, the pKa values of HCO-3 and NH3 (generated by urease action on urea) had a profound effect on measured DHC1. These in vitro studies suggest that a high local concentration of NH, and HCO-3 within the mucus layer, generated by the action of Helicobacter pylori urease on endogeneous intragastric urea, could greatly accelerate proton flux to the surface epithelium by operation of a buffer shuttle. This results in enhanced H+ permeability, particularly at pKa values of HCO-3, and NH3 and in extreme circumstances it may result in gastric ulcer formation.

A diffusion chamber technique based on time-lag analysis for the estimation of effective diffusion coefficients of radiolabelled macromolecules of varying molecular weights through native mucus gel is reported. For all solutes studied, a reduction in effective diffusion coefficients was observed with a retardation of solute flux in both aqueus and mucus layers. Over the molecular weight range of solutes investigated (126–186 000 Daltons), a consistent effect of molecular weight was evident with regard to the retarding effect of mucus. No apparent or absolute molecular weight cut-off for macromolecular transfer was exhibited. However, at high molecular weights (>30 000 Daltons) the retardation was greatly enhanced. The results confirm that mucus can be regarded as a gel with finite pores, but that it does not constitute an absolute barrier to even high molecular weight solutes.

Helicobacter pylori has been directly linked with active chronic gastritis, peptic ulceration, and gastric adenocarcinoma in humans. Although a substantial portion of the human population is colonized with H. pylori, the patterns of transmission of the organism remain in doubt, and reservoir hosts have not been identified. This study documents the isolation of H. pylori from domestic cats obtained from a commercial vendor. The isolation of H. pylori from these cats was confirmed by morphologic and biochemical evaluations, fatty acid analysis, and 16S rRNA sequence analysis. H. pylori was cultured from 6 cats and organisms compatible in appearance with H. pylori were observed in 15 additional cats by histologic examination. In most animals, H. pylori was present in close proximity to mucosal epithelial cells or in mucus layers of the glandular or surface epithelium. Microscopically, H. pylori-infected cat stomachs contained a mild to severe diffuse lymphoplasmacytic infiltrate with small numbers of neutrophils and eosinophils in the subglandular and gastric mucosae. Lymphoid follicles were also noted, particularly in the antrum, and often displaced glandular mucosal tissue. Thus, the domestic cat may be a potential model for H. pylori disease in humans. Also, the isolation of H. pylori from domestic cats raises the possibility that the organism may be a zoonotic pathogen, with transmission occurring from cats to humans.

This study describes the abundance of multidrug-resistant Vibriosassociated with marine invertebrate hosts from the Andaman Sea, India. Thirty-eight Vibriostrains were isolated from surface mucus layers of coral Porites, Goniastrea, Pocillopora, Fungia, and eggs of spiny lobster (Panulirus penicillatus). Phenotypically, the majority of strains exhibited growth at a wide range of temperatures, salt tolerance, and diverse nutritional requirements. All the strains had more than 97% 16S rRNA sequence similarity with type species of the genus Vibriowhere Vibrio fortis, and Vibrio alginolyticuswere predominant. Multilocus Sequence Analysis (MLSA) using eight housekeeping genes namely ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA,and topAdistributed the strains into 6 reported clades i.e., Harveyi, Ponticus, Nereis, Orientalis, Splendidus,and Mediterraneiwhere nearly half of the total strains represented the clade Harveyi, followed by the clade Splendidus.Likewise, the PFGE profile indicated genomic heterogeneity among the strains resulting in their distribution in five major clusters. Resistance to different antimicrobials was tested following the disc diffusion method where all strains were found susceptible to chloramphenicol (30 µg) and resistant to streptomycin (10 µg), vancomycin (30 µg), sulfamethoxazole-trimethoprim (25 µg). Moreover, the resistant phenotype to other antimicrobials confirmed the abundance of multidrug resistance strains in this marine environment.

Ulcerative colitis causes a big burden to patients due to its complicated treatment and related side effects. Hence, alternative oral dosages are becoming increasingly important for targeted drug delivery, protection from enzymatic conditions and dose reduction to avoid unwanted effects. For this, two different nanoparticle formulations were produced, i.e., non-functionalized negatively charged and poly (ethylenimine) functionalized positively charged fibroin particles. Identified formulations were loaded with rhodamine B and the anti-inflammatory drug α-mangostin. Interactions with the biological barrier and the release behavior were determined. To this end, an in-vitro co-culture model consisting of epithelial (Caco-2) and mucus secreting goblet (HT29-MTX) cells was developed taking into account the mucus layer thickness in the state of ulcerative colitis. Both investigated nanoparticles were non-toxic, colloidal stable for at least 6 months, and showed average particle sizes of approx. 300 nm. Using Caco-2 and HT29-MTX cell ratios of 5:5 and 4:6 resulted in a mucus layer thickness of approx. 15 μm, representing diseased conditions. The negatively charged particles permeated the mucus layers and were internalized by the cells, while their positively charged counterparts were mucoadhesive. The provided data suggest that both nanoparticles represent promising candidates to deliver active drug candidates to the colon at diseased stage.

Biofilm‐associated infections are difficult to treat effectively with antibiotics despite repeated treatments. Polymeric microdevices (microcontainers) have previously been shown to engulf in mucus layers and to provide tunable release. Such devices may overcome the challenge of delivering antibiotics into the biofilm, increasing the local drug concentration and hence improve local bacterial killing. In this work, microcontainers are loaded with the antibiotic, ciprofloxacin hydrochloride, and functionalized with polymeric lids of polyethylene glycol (PEG), chitosan, or Eudragit S100. The PEG lid gives rise to a drug release comparable to uncoated microcontainers showing complete release after 8 h, whereas chitosan and Eudragit S100 lids result in continuous release during the course of 24 h. All antibiotic‐containing microcontainers inhibit planktonic growth of Pseudomonas aeruginosa(PAO1) cells, but the degree of inhibition depends on the coating. Microcontainers with ciprofloxacin hydrochloride kill about three times more biofilm‐associated PAO1 cells compared with a single standard bolus. Moreover, the use of microcontainers in biofilm result in bacterial killing equal to a constant flow of a three times higher concentration of solubilized antibiotics. These studies suggest that microcontainers can be useful for antibiotic delivery in treatment of biofilm‐associated infections, resulting in more effective treatment and reduced use of antibiotics. Treatment of biofilm‐related infections often fails as antibiotics cannot be dosed in concentrations sufficient to eradicate the biofilm. By the use of a versatile drug delivery system, known as microcontainers, the killing of biofilm‐associated PAO1 cells is improved with a factor of three compared to a single standard bolus of antibiotic.

The gastrointestinal tract is covered by a single layer of epithelial cells that, together with the mucus layers, protect the underlying tissue from microbial invasion. The epithelium has one of the highest turnover rates in the body. Using stable isotope labeling, high-resolution mass spectrometry, and computational analysis, we report a comprehensive dataset of the turnover of more than 3,000 and the expression of more than 5,000 intestinal epithelial cell proteins, analyzed under conventional and germ-free conditions across five different segments in mouse intestine. The median protein half-life is shorter in the small intestine than in the colon. Differences in protein turnover rates along the intestinal tract can be explained by distinct physiological and immune-related functions between the small and large intestine. An absence of microbiota results in an approximately 1 day longer protein half-life in germ-free animals.

It is proposed that one of the functions of the mucus layers lining the respiratory tract and gastrointestinal system is the scavenging of highly reactive oxygen-derived species. This would provide anti-oxidant protection to the underlying mucosal epithelial cells.

Numerical simulation based on immersed boundary-lattice Boltzmann method has been employed to study 2D muco-ciliary transport problem. The periciliary liquid (PCL) and mucus layers in this study are considered as the Newtonian and viscoelastic fluid respectively. An Oldroyd-B model is used as the constitutive equations of mucus layer. To simulate accurate effects of the cilia and PCL-mucus interface on the fluid, immersed boundary method is used. Numerical simulations have been performed to investigate the effects of mucus depth on the muco-ciliary clearance at various values of cilia beat frequencies. Our results show that, by increasing mucus depth, which results from air pollution and smoking, mean mucus velocity decreases. But it can be completely modified by increasing cilia beat frequency and the cilia beat frequency has great effect on the muco-ciliary clearance.

According to the news reporters, the research concluded: "These reporters will facilitate studies of P. aeruginosa in biofilms or other contexts relevant to its pathogenesis, such as those found in cystic fibrosis airways. Chalcogens, Cystic Fibrosis, Digestive System Diseases and Conditions, Drugs and Therapies, Gammaproteobacteria, Gram-Negative Aerobic Bacteria, Gram-Negative Aerobic Rods and Cocci, Gram-Negative Bacteria, Health and Medicine, Lung Diseases and Conditions, Pancreatic Diseases and Conditions, Proteobacteria, Pseudomonadaceae, Pseudomonas, Pseudomonas aeruginosa, Respiratory Tract Diseases and Conditions Keywords: Chalcogens; Cystic Fibrosis; Digestive System Diseases and Conditions; Drugs and Therapies; Gammaproteobacteria; Gram-Negative Aerobic Bacteria; Gram-Negative Aerobic Rods and Cocci; Gram-Negative Bacteria; Health and Medicine; Lung Diseases and Conditions; Pancreatic Diseases and Conditions; Proteobacteria; Pseudomonadaceae; Pseudomonas; Pseudomonas aeruginosa; Respiratory Tract Diseases and Conditions EN Chalcogens Cystic Fibrosis Digestive System Diseases and Conditions Drugs and Therapies Gammaproteobacteria Gram-Negative Aerobic Bacteria Gram-Negative Aerobic Rods and Cocci Gram-Negative Bacteria Health and Medicine Lung Diseases and Conditions Pancreatic Diseases and Conditions Proteobacteria Pseudomonadaceae Pseudomonas Pseudomonas aeruginosa Respiratory Tract Diseases and Conditions 3400 3400 1 11/06/23 20231110 NES 231110 2023 NOV 10 (NewsRx) -- By a News Reporter-Staff News Editor at Respiratory Therapeutics Week -- Data detailed on cystic fibrosis have been presented. [Extracted from the article]

An adjustable eye thermal compress assembly comprising: two separate, electrically controllable and individually adjustable thermal treatment units for generating thermal energy to provide a heated or cooled treatment surface for a user's eyelids when worn; and a bridge connecting the two thermal treatment units; wherein each of the thermal treatment units is laterally adjustable relative to the bridge. In some embodiments, the eye thermal compress assembly is used with the user lying face up and the eye thermal compress assembly resting on the user's eyelids. The thermal eye compress assembly of claim 12, further including a battery located within an interior of the thermal eye compress assembly. [Extracted from the article]

Oral delivery of protein drugs is an attractive route of administration due to its convenience for repeated dosing and good patient compliance. However, currently oral protein therapeutics show very low bioavailability mainly due to the existence of hostile gastrointestinal (GI) environments, including mucus layers and intestinal epithelial barriers. Herein, using insulin as a model protein therapeutic, the core–shell nanoparticles with thiolated hyaluronic acid (HA‐SH) coating (NPHA‐SH) are produced utilizing a two‐step flash nanocomplexation process to enhance oral delivery efficiency of insulin. A positively charged nanoparticle core is first generated by electrostatic complexation between insulin and N‐(2‐hydroxypropyl)‐3‐trimethyl ammonium chloride modified chitosan (HTCC), followed by surface coating with HA‐SH. The optimized NPHA‐SHshows an average size of 100 nm with high encapsulation efficiency (91.1%) and loading capacity (38%). In vitro and ex vivo results confirm that NPHA‐SHshows high mucus‐penetration ability, improved intestinal retention and transepithelial transport property due to its thiolated surface and the ability of HA‐SH coating to dissociate from the nanoparticle surface when across the mucosal layer. Oral administration of NPHA‐SHto Type 1 diabetic rats yields high efficacy and an average relative bioavailability of 11.3%. These results demonstrate that the HA‐SH coated core–shell nanoparticles are a promising oral delivery vehicle for protein therapeutics. Uniform core–shell nanoparticleswith a positively charged HTCC/insulin nanocomplex core and a thiolated hyaluronic acid (HA‐SH) coating are engineered with a two‐step flash nanocomplexation (FNC) process to improve intestinal retention, mucus‐penetration ability, and transepithelial transport efficiency, thus collectively enhancing the efficacy and bioavailability of the encapsulated insulin after oral administration.

According to the news reporters, the research concluded: "Thus, maternal diet is a critical long-lasting determinant of offspring microbiota composition, impacting gut health and proneness to obesity and its associated disorders." Keywords: Atlanta; State:Georgia; United States; North and Central America; Bariatrics; Diet and Nutrition; Health and Medicine; Inflammation; Nutrition Disorders; Nutritional and Metabolic Diseases and Conditions; Obesity; Overnutrition EN Atlanta State:Georgia United States North and Central America Bariatrics Diet and Nutrition Health and Medicine Inflammation Nutrition Disorders Nutritional and Metabolic Diseases and Conditions Obesity Overnutrition 4652 4652 1 08/14/23 20230818 NES 230818 2023 AUG 19 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- New research on Nutritional and Metabolic Diseases and Conditions - Obesity is the subject of a report. [Extracted from the article]

The article presents an interview with medical engineer Patricia Yang from the Georgia Institute of Technology. Topics include her introduction to fluid dynamics, or the study of bodily fluids, by researching how long elephants take to urinate at a zoo in Atlanta, Georgia, her research on what causes wombat feces to be square in shape, and her study of the mechanics to stop blood from clotting or the expense of extra blood.

Our news correspondents obtained a quote from the research from Ohio State University: "Medically, biofilms often lead to persistent infections, increased antibiotic resistance, and recurrence of infections. Keywords: Bacterial Infections and Mycoses; Drugs and Therapies; Health and Medicine; Risk and Prevention EN Bacterial Infections and Mycoses Drugs and Therapies Health and Medicine Risk and Prevention 1211 1211 1 06/19/23 20230623 NES 230623 2023 JUN 23 (NewsRx) -- By a News Reporter-Staff News Editor at Drug Week -- Investigators publish new report on bacterial infections and mycoses. [Extracted from the article]

"Additional or alternative aspects of disclosed embodiments pertain to a method for detecting physical characteristics of a multilayered tissue of a subject, the method comprising at least the steps of: "irradiating a multilayered tissue using at least one light sources; "detecting optical properties of light reflected or deflected from the respective multilayered tissue, using at least one optical detector outputting detector-output, the optical properties of the tissue comprising at least polarization of light reflected or deflected from the multilayered tissue; and "determining physical characteristics of the multilayered tissue, based on the optical properties thereof." A method for detecting physical characteristics of a multilayered tissue of a subject, the method comprising at least the steps of: receiving detector-output from at least one optical detector, the detector-output being indicative of optical properties of light reflected or deflected from the respective multilayered tissue; analyzing the received detector-output to determine spectral properties of the multilayered tissue; and determining physical characteristics of the multilayered tissue by using multiple spectral models of the of the multilayered tissue comprising at least: a first model assuming a normal condition of the multilayered tissue and one or more additional models, assuming abnormal conditions of the multilayered tissue, each model being associated with different spectral properties of the multilayered tissue, wherein physical characteristics of the multilayered tissue are determined by hierarchal determination of a best-fit model from the multiple spectral models, based on determination of best-fit of the multilayered tissue to one of the spectral models. [Extracted from the article]

Keywords: Kyoto; Japan; Asia; Dicarboxylic Acids; Food Science; Succinates; Succinic Acid EN Kyoto Japan Asia Dicarboxylic Acids Food Science Succinates Succinic Acid 94 94 1 04/10/23 20230413 NES 230413 2023 APR 13 (NewsRx) -- By a News Reporter-Staff News Editor at Food Weekly News -- New research on Food Science is the subject of a report. Keywords for this news article include: Asia, Kyoto, Japan, Succinates, Food Science, Succinic Acid, Dicarboxylic Acids. [Extracted from the article]

The article provides suggestions for dealing with colic syndrome which is defined as episodes of crying for more than three hours a day. Topics discussed include stomach troubles and flatulence caused by proteins and lactose in milk consumed by baby; views of Dr. Kanav Anand, a consultant paediatrician, on maternal diet which is rich in allergens and proteins; and mechanical changes in the intestines bought about by disturbances in gut microbiota.