Epithelial Barrier in the Nasal Mucosa, Related Risk Factors and Diseases.

As the first line of defense against risk factors, the nasal epithelial barrier maintains homeostasis in nasal mucosa. The composition of the epithelial barrier contains physical, chemical, immune, and microbiological barriers. Together, these barriers form the nasal defense against irritations. Risk factors from both internal and external environments can disrupt them. External risk factors contain allergens containing proteases, bacteria, virus, particulate matter, diesel exhaust particles, and cigarette smoke. In the meantime, inflammatory cytokines also increase the load on the barrier. Taking into account the role of the epithelial barrier in the nasal mucosa, some studies focus on the treatment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS) by restoring the epithelial barrier, and some progress has been made. Among the therapeutic approaches, histone deacetylase (HDAC) inhibitor and steroid corticosteroids are considered two of the more studied categories, and their roles in repairing barriers have been demonstrated in AR and CRS. The underlying mechanism of HDAC inhibitor may be related to the transcription factor p63. And the protection of corticosteroids may be associated with the allergic disease susceptibility gene, protocadherin-1. Notably, manipulation of the microbiological barrier also has a positive effect on AR and CRS. Lactococcus and probiotics are two categories that are worth being explored continuously. We here review and discuss the compositions and risk factors of the nasal epithelial barrier. Furthermore, some novel and promising approaches to restore the defective barrier in nasal allergic diseases were mentioned.

Salivary Chemical Barrier Proteins in Oral Squamous Cell Carcinoma-Alterations in the Defense Mechanism of the Oral Cavity.

Oral squamous cell carcinoma (OSCC) is one of the most frequent types of head and neck cancer. Despite the genetic and environmental risk factors, OSCC is also associated with microbial infections and/or dysbiosis. The secreted saliva serves as the chemical barrier of the oral cavity and, since OSCC can alter the protein composition of saliva, our aim was to analyze the effect of OSCC on the salivary chemical barrier proteins. Publicly available datasets regarding the analysis of salivary proteins from patients with OSCC and controls were collected and examined in order to identify differentially expressed chemical barrier proteins. Network analysis and gene ontology (GO) classification of the differentially expressed chemical barrier proteins were performed as well. One hundred and twenty-seven proteins showing different expression pattern between the OSCC and control groups were found. Protein-protein interaction networks of up- and down-regulated proteins were constructed and analyzed. The main hub proteins (IL-6, IL-1B, IL-8, TNF, APOA1, APOA2, APOB, APOC3, APOE, and HP) were identified and the enriched GO terms were examined. Our study highlighted the importance of the chemical barrier of saliva in the development of OSCC.

Postnatal growth retardation is associated with deteriorated intestinal mucosal barrier function using a porcine model.

Individuals with postnatal growth retardation (PGR) are prone to developing chronic diseases. Abnormal development in small intestine is casually implicated in impaired growth. However, the exact mechanism is still implausible. In this present study, PGR piglets (aged 42 days) were employed as a good model to analyze developmental changes in intestinal mucosal barrier function. Our data demonstrated that PGR piglets exhibited impaired jejunal and ileal epithelial villous morphology and permeability, accompanied by decreased cell proliferation ability and increased apoptosis rate. In addition, the expression of tight junction proteins (ZO-1, claudin 1, and occludin) and E-cadherin was markedly inhibited by PGR. The expression of P-glycoprotein was significantly reduced in PGR piglets, as well as decreased activity of lysozyme. Moreover, the mRNA abundance and content of inflammatory cytokines were significantly increased in the intestinal mucosa and plasma of PGR piglets, respectively. PGR also contributed to lower level of sIgA, and higher level of CD68-positive rate, ß-defensins, and protein expression involved p38 MAPK/NF-κB pathway. Furthermore, PGR altered the intestinal microbial community such as decreased genus Alloprevotella and Oscillospira abundances, and led to lower microbial-derived butyrate production, which may be potential targets for treatment. Collectively, our findings indicated that the intestinal mucosal barrier function of PGR piglets could develop the nutritional intervention strategies in prevention and treatment of the intestinal mucosal barrier dysfunction in piglets and humans.

Unraveling the proteomic changes involved in the resistance response of Cajanus platycarpus to herbivory by Helicoverpa armigera.

The pigeonpea wild relative Cajanus platycarpus is resistant to Helicoverpa armigera, one of the major pests responsible for yield losses in Cajanus cajan. Deciphering the molecular mechanism underlying host plant resistance is pertinent to identify proteins that aid in the mitigation of the insect pest. The present study adopted comparative proteomics as a tool to interpret the resistance mechanism(s) in C. platycarpus vis-à-vis C. cajan during continued herbivory (up to 96 h). Over-representation analysis of the differentially expressed proteins implicated a multi-dimensional resistance response accomplished by both physical and chemical barriers in C. platycarpus. While the chemical basis for resistance was depicted by the upregulation of proteins playing a rate limiting role in the phenylpropanoid pathway, the physical basis was provided by the regulation of proteins involved in microtubule assembly and synthesis of lignins. Upregulation of proteins in the polyamine pathway indicated the role of metabolite conjugates to be negatively affecting herbivore growth. Reallocation of resources and diversion of metabolic flux to support the production of secondary metabolites could be the probable approach in the wild relative against herbivory. Our study provided deeper insights into the pod borer resistance mechanism in C. platycarpus for utility in crop improvement. KEY POINTS: • Pod borer resistance in Cajanus platycarpus is multi-dimensional. • Pod borer resistance has been arbitrated to cell wall rigidity and secondary metabolites. • Phenylpropanoid pathway derivatives apparently shaped the plant chemical defense against pod borer.

Modulation of expression and activity of intestinal multidrug resistance-associated protein 2 by xenobiotics.

The multidrug resistance-associated protein 2 (MRP2/ABCC2) is a transporter that belongs to the ATP-binding cassette (ABC) superfamily. In the intestine, it is localized to the apical membrane of the enterocyte and plays a key role in limiting the absorption of xenobiotics incorporated orally. MRP2 may also play a role in systemic clearance of xenobiotics available from the serosal side of the intestine. MRP2 transports a wide range of substrates, mainly organic anions conjugated with glucuronic acid, glutathione and sulfate and its expression can be modulated by xenobiotics at transcriptional- and post-transcriptional levels. Transcriptional regulation is usually mediated by a group of nuclear receptors. The pregnane X receptor (PXR) is a major member of this group. Relevant drugs described to up-regulate intestinal MRP2 via PXR are rifampicin, spironolactone and carbamazepine, among others. The constitutive androstane receptor (CAR, NR1I3) was also reported to modulate MRP2 expression, phenobarbital being a typical activator. Dietary compounds, including micronutrients and other natural products, are also capable of regulating intestinal MRP2 expression transcriptionally. We have given them particular attention since the composition of the food ingested daily is not necessarily supervised and may result in interactions with therapeutic drugs. Post-transcriptional regulation of MRP2 activity by xenobiotics, e.g. as a consequence of inhibitory actions, is also described in this review. Unfortunately, only few studies report on drug-drug or nutrient-drug interactions as a consequence of modulation of intestinal MRP2 activity by xenobiotics. Future clinical studies are expected to identify additional interactions resulting in changes in efficacy or safety of therapeutic drugs.

The silent threat: Nanopolystyrene and chrysene pollutants disrupt the intestinal mucosal barrier, new insights from juvenile Siniperca chuatsi.

The intestinal mucosal barrier-comprising microbial, mechanical, chemical, and immunological barriers-is critical to protection against pathogens and maintenance of host health; however, it remains unclear whether it is affected by environmental contaminants. Therefore, the present study assessed whether exposure to ambient concentrations of nanopolystyrene (NP) and chrysene (CHR)-two ubiquitous environmental pollutants in the aquatic environment-affect the intestinal mucosal barrier in juvenile Siniperca chuatsi. After exposure for 21 days, S. chuatsi exhibited intestinal oxidative stress and imbalance of intestinal microbial homeostasis. NP and/or CHR exposure also disrupted the intestinal mechanical barrier, as evidenced by the altered intestinal epithelial cell morphology, disrupted structure of intercellular tight junctions, and decreased expression of tight junction proteins. Damage to the intestinal chemical barrier manifested as thinning of the mucus layer owing to the loss and damage of goblet cells. Furthermore, the intestinal immunological barrier was impaired as indicated by the loss of intestinal intraepithelial lymphocytes and increase in pro-inflammatory cytokines, chemokines, and immunoglobulins. These findings collectively suggest that the intestinal mucosal barrier was damaged. This study is, to the best of our knowledge, the first to report that exposure to NP and/or CHR at environmentally relevant concentrations disrupts the intestinal mucosal barrier in organisms and highlight the significance of nanoplastic/CHR pollution for intestinal health.

Mechanism of effects of nickel or nickel compounds on intestinal mucosal barrier.

As an important metal in industry, national defense, and production, nickel widely exists in nature and is also a necessary trace element for human beings and animals. Nickel deficiency will affect the growth and development of animals, the contents of related active substances, enzymes and other essential elements in vivo. However, excessive nickel or longer nickel exposure can induce excessive free radicals (reactive oxygen species and reactive nitrogen) in the body, which can lead to a variety of cell damage, apoptosis and canceration, and ultimately pose negative effects on the health of the body. Among them, the intestinal tract, as the largest interface between the body and the external environment, greatly increases the contact probability between nickel or nickel compounds and the intestinal mucosal barrier, thus, the intestinal structure and function are also more vulnerable to nickel damage, leading to a series of related diseases such as enteritis. Therefore, this paper briefly analyzed the damage mechanism of nickel or its compounds to the intestinal tract from the perspective of four intestinal mucosal barriers: mechanical barrier, immune barrier, microbial barrier and chemical barrier, we hope to make a certain theoretical contribution to the further research and the prevention and treatment of nickel related diseases.

Chemical Barrier Proteins in Human Body Fluids.

Chemical barriers are composed of those sites of the human body where potential pathogens can contact the host cells. A chemical barrier is made up by different proteins that are part of the antimicrobial and immunomodulatory protein/peptide (AMP) family. Proteins of the AMP family exert antibacterial, antiviral, and/or antifungal activity and can modulate the immune system. Besides these proteins, a wide range of proteases and protease inhibitors can also be found in the chemical barriers maintaining a proteolytic balance in the host and/or the pathogens. In this review, we aimed to identify the chemical barrier components in nine human body fluids. The interaction networks of the chemical barrier proteins in each examined body fluid were generated as well.

Progress of Studies on Plant-Derived Polysaccharides Affecting Intestinal Barrier Function in Poultry.

As natural bioactive components, plant-derived polysaccharides have many biological functions, such as anti-inflammatory, antioxidant, anticoccidial, and immunity regulation, and have been widely used in poultry production. In this review paper, firstly, the sources and structures of plant-derived polysaccharides are reviewed; secondly, the effects of plant-derived polysaccharides on the intestinal microbiome, permeability, morphology and immune function of poultry are summarized; thirdly, the potential molecular regulation mechanism of plant-derived polysaccharides on the intestinal barrier function of poultry was preliminarily analyzed. The review paper will bring a basis for the scientific utilization of plant-derived polysaccharides in the poultry industry.

Disturbance of ecological habitat distribution driven by a chemical barrier of domestic and agricultural discharges: An experimental approach to test habitat fragmentation.

Contamination is an important factor for determining the pattern of habitat selection by organisms. Since many organisms are able to move from contaminated to more favorable habitats, we aimed to: (i) verify if the contamination along the river Guadalete (Spain) could generate a chemical barrier, restricting the displacement of freshwater shrimps (Atyaephyra desmarestii) and (ii) discriminate the role of the contaminants concerning the preference response by the shrimps. A. desmarestii was experimentally tested in a multi-compartmented, non-forced exposure system, simulating the spatial arrangement of the samples just like their distribution in the environment. Water and sediment samples were chemically characterized by analyses of 98 chemical compounds and 19 inorganic elements. Shrimps selected the less contaminated water and sediment samples, with two marked preference patterns: (i) upstream displacement avoiding the sample located at the point of pollutant discharges and those samples downstream from this point and (ii) fragmentation of the population with spatial isolation of the upstream and downstream populations. The preference was related to the avoidance of artificial sweeteners, flame retardants, fragrances, PAHs, PCBs, pesticides, UV filters and some inorganic elements. The threat of contamination was related to its potential to isolate populations due to the chemical fragmentation of their habitat.

Development of immunochromatographic assays for the detection of imidacloprid in soil chemical barrier.

A soil chemical barrier is the most important and common way to control termites; fast and on-site detection methods are significant tools to verify pesticide content meeting the standard requirements. In this study, conventional and enhanced immunochromatographic assays (ICAs) containing two test lines (TLs) were developed to semi-quantitatively detect imidacloprid in soil chemical barrier, and detection results were quantified by a smart phone. According to the results, the disappearance concentrations of first TL (TL-1) and second TL (TL-2) in an enhanced ICA and conventional ICA were 5 and 20 ng/mL and 20 and 80 ng/mL with the naked eye. The sensitivity of TL-2 was four times that of TL-1 in both ICAs, consistent with the maximum and minimum concentration differences for imidacloprid in Jiangsu province's "the technical regulation of assay and evaluation on chemical soil barrier of termite prevention treatment in buildings". The results of TLs can be used to judge whether the amount of imidacloprid in soil chemical barrier meets the standard. Enhanced and conventional ICAs were available for further quantitative testing with a smart phone, and the limit of detection (LOD) was 0.74 and 3.17 ng/mL, respectively. Moreover, some soil chemical barrier samples from several areas in Wuxi, Jiangsu province, were used to test by ICAs and high-performance liquid chromatography (HPLC), and the results of ICAs correlated well with HPLC.

Metabolic and redox barriers in the skin exposed to drugs and xenobiotics.

INTRODUCTION: Growing exposure of human skin to environmental and occupational hazards, to numerous skin care/beauty products, and to topical drugs led to a biomedical concern regarding sustainability of cutaneous chemical defence that is essential for protection against intoxication. Since skin is the largest extra-hepatic drug/xenobiotic metabolising organ where redox-dependent metabolic pathways prevail, in this review, publications on metabolic processes leading to redox imbalance (oxidative stress) and its autocrine/endocrine impact to cutaneous drug/xenobiotic metabolism were scrutinised. AREAS COVERED: Chemical and photo-chemical skin barriers contain metabolic and redox compartments: their protective and homeostatic functions. The review will examine the striking similarity of adaptive responses to exogenous chemical/photo-chemical stressors and endogenous toxins in cutaneous metabolic and redox system; the role(s) of xenobiotics/drugs and phase II enzymes in the endogenous antioxidant defence and maintenance of redox balance; redox regulation of interactions between metabolic and inflammatory responses in skin cells; skin diseases sharing metabolic and redox problems (contact dermatitis, lupus erythematosus, and vitiligo) EXPERT OPINION: Due to exceptional the redox dependence of cutaneous metabolic pathways and interaction of redox active metabolites/exogenous antioxidants with drug/xenobiotic metabolism, metabolic tests of topical xenobiotics/drugs should be combined with appropriate redox analyses and performed on 3D human skin models.

Chondroitinase ABC plus bone marrow mesenchymal stem cells for repair of spinal cord injury.

As chondroitinase ABC can improve the hostile microenvironment and cell transplantation is proven to be effective after spinal cord injury, we hypothesized that their combination would be a more effective treatment option. At 5 days after T8 spinal cord crush injury, rats were injected with bone marrow mesenchymal stem cell suspension or chondroitinase ABC 1 mm from the edge of spinal cord damage zone. Chondroitinase ABC was first injected, and bone marrow mesenchymal stem cell suspension was injected on the next day in the combination group. At 14 days, the mean Basso, Beattie and Bresnahan score of the rats in the combination group was higher than other groups. Hematoxylin-eosin staining showed that the necrotic area was significantly reduced in the combination group compared with other groups. Glial fibrillary acidic protein-chondroitin sulfate proteoglycan double staining showed that the damage zone of astrocytic scars was significantly reduced without the cavity in the combination group. Glial fibrillary acidic protein/growth associated protein-43 double immunostaining revealed that positive fibers traversed the damage zone in the combination group. These results suggest that the combination of chondroitinase ABC and bone marrow mesenchymal stem cell transplantation contributes to the repair of spinal cord injury.