Search Results (13)

Topical ophthalmic drug delivery targeting the posterior segment of the eye has become a key area of interest due to its non-invasive nature, safety, ease of application, patient compliance, and cost-effectiveness. However, achievement of effective drug bioavailability in the posterior ocular segment is a significant challenge due to unique ocular barriers, including precorneal factors and anatomical barriers, like the cornea, the conjunctiva, and the sclera. Successful ocular drug delivery systems require increased precorneal residence time and improved corneal penetration to enhance intraocular bioavailability. A promising strategy to overcome these barriers is incorporating drug penetration enhancers (DPEs) into formulations. These compounds facilitate drug delivery by improving permeability across otherwise impermeable or poorly permeable membranes. At the ocular level, they act through three primary mechanisms: breaking tear film stability by interfering with the mucous layer; disrupting membrane components such as phospholipids and proteins; and loosening epithelial cellular junctions. DPEs offer significant potential to improve bioavailability and therapeutic outcomes, particularly for drugs targeting the posterior segment of the eye. This review is focused on analyzing the current literature regarding the use of penetration enhancers in topical ocular drug delivery, highlighting their mechanisms of action and potential to revolutionize ophthalmic treatments. Full article

Chicken yolk immunoglobulin (IgY) is a natural immunologically active antibody extracted from egg yolk and can be used as a natural dietary supplement for the treatment of inflammation and damage to the intestines. In our study, IgY was embedded in a double emulsion (W/O/W; DE) to explore the therapeutic effect of the embedded IgY on Lipopolysaccharide (LPS)-induced jejunal injury in mice. The results showed that W/O/W-embedded IgY as a dietary supplement (IgY + DE) attenuated LPS-induced damage to mouse small intestinal structures and protected the integrity of the jejunal mucosal barrier. IgY + DE increased the amount of related transcription factors (Math1, Spdef, Elf3, and Klf4) and promoted thrush cell differentiation. IgY + DE ameliorated LPS-induced reduction in mucin quantity and markers. It promoted the expression of Muc1 and Muc2 and increased the mRNA expression levels of Muc1, Muc2, Muc3, Muc4, Muc13, and Agr2 (p < 0.05). IgY + DE increased the expression of several glycosyltransferases involved in mucin glycosylation. IgY + DE also neutralized the LPS attack on the expression of jejunal inflammatory factors IL-1β, IL-6, IL-4, and TNF-α. In conclusion, the IgY-embedded double emulsion can be used as a dietary supplement for immunotherapy to prevent LPS-induced jejunal injury in mice. Full article

Microorganisms colonize all barrier tissues and are present on the skin and all mucous membranes from birth. Bacteria have many ways of influencing the host organism, including activation of innate immunity receptors by pathogen-associated molecular patterns and synthesis of various chemical compounds, such as vitamins, short-chain fatty acids, bacteriocins, toxins. Bacteria, using extracellular vesicles, can also introduce high-molecular compounds, such as proteins and nucleic acids, into the cell, regulating the metabolic pathways of the host cells. Epithelial cells and immune cells recognize bacterial bioregulators and, depending on the microenvironment and context, determine the direction and intensity of the immune response. A large number of factors influence the maintenance of symbiotic microflora, the diversity of which protects hosts against pathogen colonization. Reduced bacterial diversity is associated with pathogen dominance and allergic diseases of the skin, gastrointestinal tract, and upper and lower respiratory tract, as seen in atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies, and asthma. Understanding the multifactorial influence of microflora on maintaining health and disease determines the effectiveness of therapy and disease prevention and changes our food preferences and lifestyle to maintain health and active longevity. Full article

Carrageenan is a widely used food additive and is seen as a potential candidate in the pharmaceutical industry. However, there are two faces to carrageenan that allows it to be used positively for therapeutic purposes. Carrageenan can be used to create edible films and for encapsulating drugs, and there is also interest in the use of carrageenan for food printing. Carrageenan is a naturally occurring polysaccharide gum. Depending on the type of carrageenan, it is used in regulating the composition of intestinal microflora, including the increase in the population of Bifidobacterium bacteria. On the other hand, the studies have demonstrated the harmfulness of carrageenan in animal and human models, indicating a direct link between diet and intestinal inflammatory states. Carrageenan changes the intestinal microflora, especially Akkermansia muciniphilia, degrades the mucous barrier and breaks down the mucous barrier, causing an inflammatory reaction. It directly affects epithelial cells by activating the pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway. The mechanism is based on activation of the TLR4 receptor, alterations in macrophage activity, production of proinflammatory cytokines and activation of innate immune pathways. Carrageenan increases the content of Bacteroidetes bacteria, also causing a reduction in the number of short chain fatty acid (SCFA)-producing bacteria. The result is damage to the integrity of the intestinal membrane and reduction of the mucin layer. The group most exposed to the harmful effects of carrageenan are people suffering from intestinal inflammation, including Crohn disease (CD) and ulcerative colitis (UC). Full article

Accumulating evidence shows that the abnormal increase in the mortality of intestinal epithelial cells (IECs) caused by apoptosis, pyroptosis, and necroptosis is closely related to the function of mucous membrane immunity and barrier function in patients with ulcerative colitis (UC). As a procedural death path that integrates the above-mentioned many deaths, the role of PANoptosis in UC has not been clarified. This study aims to explore the characterization of PANoptosis patterns and determine the potential biomarkers and therapeutic targets. We constructed a PANoptosis gene set and revealed significant activation of PANoptosis in UC patients based on multiple transcriptome profiles of intestinal mucosal biopsies from the GEO database. Comprehensive bioinformatics analysis revealed five key genes (ZBP1, AIM2, CASP1/8, IRF1) of PANoptosome with good diagnostic value and were highly correlated with an increase in pro-inflammatory immune cells and factors. In addition, we established a reliable ceRNA regulatory network of PANoptosis and predicted three potential small-molecule drugs sharing calcium channel blockers that were identified, among which flunarizine exhibited the highest correlation with a high binding affinity to the targets. Finally, we used the DSS-induced colitis model to validate our findings. This study identifies key genes of PANoptosis associated with UC development and hypothesizes that IRF1 as a TF promotes PANoptosome multicomponent expression, activates PANoptosis, and then induces IECs excessive death. Full article

Actinomycosis is a rare, chronic, suppurative, and granulomatous bacterial disease. The Actinomyces species exist as normal flora in the oropharynx, gastrointestinal tract, and the female genital tract. They are incapable of penetrating the normal mucous membranes and become pathogenic only when this barrier has been destroyed by trauma, surgery, immunosuppression, or after viscus perforation. We report the first case of an actinomycotic abscess after laparoscopic sleeve gastrectomy. A 29-year-old man underwent a laparoscopic sleeve gastrectomy with no intra-operative complications. On postoperative day 3, the patient had a fever with elevated inflammatory markers. Abdominal computerized tomography (CT) with oral water-soluble contrast media showed no extra-luminal leakage and no fluid collection adjacent to the resected stomach, other than the fluid collection in the right subhepatic space. Percutaneous drainage was attempted, but the procedure failed due to the patient’s thick abdominal wall. After two weeks of weight loss of about 12 kg, percutaneous drainage was successfully performed, and A. odontolyticus was identified through pus culture. After effective abscess drainage and high-dose antibiotics, the patient’s symptoms improved and the abscess pocket disappeared. We reported Actinomyces infection after gastric sleeve surgery. In the case of abscess formation after gastric sleeve surgery caused by actinomycete infection, antibiotic treatment and percutaneous drainage are effective together. Full article

Gastroesophageal reflux disease (GERD) has the highest prevalence among diseases of the digestive system and is characterized by a significant decrease in patients’ quality of life, comparable to arterial hypertension and coronary heart disease. One in every ten cases of reflux esophagitis leads to the formation of Barrett’s esophagus, which is associated with a high risk of esophagus adenocarcinoma. The key factors determining the progression of the disease are the frequency and duration of the reflux of the stomach’s contents. As a result, refluxate, which includes hydrochloric acid, pepsin, and, in the case of concomitant duodeno-gastric reflux, bile acids and lysolecithin, is thrown into the overlying sections of the digestive tract. At the same time, in addition to aggression factors, it is necessary to take into account the state of resistance in the esophageal mucosa to the effects of aggressive refluxate molecules. This review was prepared using systematized data on the protective properties of the esophageal mucosa and modern methods to assess the mucosal barrier in reflux esophagitis. Lesions of the epithelial barrier structure in the esophagus are recognized as the main pathogenetic factor in the development of reflux esophagitis and are a potentially significant therapeutic target in the treatment of GERD and Barrett’s esophagus. This article presents the characteristics of the esophageal mucosal barrier and the protective mechanisms of the esophagus’s mucous membrane in conditions of gastroesophageal reflux. Diagnostic approaches for assessing the course of reflux esophagitis are described for both histological criteria and the possibility of a comprehensive assessment of the state of mucins, tight-junction proteins, and the proliferative activity of the mucosa, including under the conditions of ongoing therapy. Full article

Staphylococci are broadly adaptable and their ability to grow in unique environments has been widely established, but the most common and clinically relevant staphylococcal niche is the skin and mucous membranes of mammals and birds. S. aureus causes severe infections in mammalian tissues and organs, with high morbidities, mortalities, and treatment costs. S. epidermidis is an important human commensal but is also capable of deadly infections. Gold-standard diagnostic methods for staph infections currently rely upon retrieval and characterization of the infectious agent through various culture-based methods. Yet, obtaining a viable bacterial sample for in vitro identification of infection etiology remains a significant barrier in clinical diagnostics. The development of volatile organic compound (VOC) profiles for the detection and identification of pathogens is an area of intensive research, with significant efforts toward establishing breath tests for infections. This review describes the limitations of existing infection diagnostics, reviews the principles and advantages of VOC-based diagnostics, summarizes the analytical tools for VOC discovery and clinical detection, and highlights examples of how VOC biomarkers have been applied to diagnosing human and animal staph infections. Full article

The mucin 1 (MUC1) gene was discovered based on its overexpression in human breast cancers. Subsequent work demonstrated that MUC1 is aberrantly expressed in cancers originating from other diverse organs, including skin and immune cells. These findings supported a role for MUC1 in the adaptation of barrier tissues to infection and environmental stress. Of fundamental importance for this evolutionary adaptation was inclusion of a SEA domain, which catalyzes autoproteolysis of the MUC1 protein and formation of a non-covalent heterodimeric complex. The resulting MUC1 heterodimer is poised at the apical cell membrane to respond to loss of homeostasis. Disruption of the complex releases the MUC1 N-terminal (MUC1-N) subunit into a protective mucous gel. Conversely, the transmembrane C-terminal (MUC1-C) subunit activates a program of lineage plasticity, epigenetic reprogramming and repair. This MUC1-C-activated program apparently evolved for barrier tissues to mount self-regulating proliferative, inflammatory and remodeling responses associated with wound healing. Emerging evidence indicates that MUC1-C underpins inflammatory adaptation of tissue stem cells and immune cells in the barrier niche. This review focuses on how prolonged activation of MUC1-C by chronic inflammation in these niches promotes the cancer stem cell (CSC) state by establishing auto-inductive nodes that drive self-renewal and tumorigenicity. Full article

The oral mucosa is a mechanical barrier against the penetration and colonization of microorganisms. Oral homeostasis is maintained by congenital and adaptive systems in conjunction with normal oral flora and an intact oral mucosa. Components contributing to the defense of the oral cavity include the salivary glands, innate antimicrobial proteins of saliva, plasma proteins, circulating white blood cells, keratinocyte products of the oral mucosa, and gingival crevicular fluid. General disturbances in the level of immunoglobulins in the human body may be manifested as pathological lesions in the oral mucosa. Symptoms of immunoglobulin-related general diseases such as mucous membrane pemphigoid (MMP), pemphigus vulgaris (PV), linear IgA bullous dermatosis (LABD), Epidermolysis Bullosa Aquisita (EBA), and Hyper-IgE syndrome (HIES) may appear in the oral cavity. In this review, authors present selected diseases associated with immunoglobulins in which the lesions appear in the oral cavity. Early detection and treatment of autoimmune diseases, sometimes showing a severe evolution (e.g., PV), allow the control of their dissemination and involvement of skin or other body organs. Immunoglobulin disorders with oral manifestations are not common, but knowledge, differentiation and diagnosis are essential for proper treatment. Full article

The sudden outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic in December 2019 caused crises and health emergencies worldwide. The rapid spread of the virus created an urgent need for the development of an effective vaccine and mass immunization to achieve herd immunity. Efforts of scientific teams at universities and pharmaceutical companies around the world allowed for the development of various types of preparations and made it possible to start the vaccination process. However, it appears that the developed vaccines are not effective enough and do not guarantee long-lasting immunity, especially for new variants of SARS-CoV-2. Considering this problem, it is promising to focus on developing a Coronavirus Disease 2019 (COVID-19) mucosal vaccine. Such a preparation applied directly to the mucous membranes of the upper respiratory tract might provide an immune barrier at the primary point of virus entry into the human body while inducing systemic immunity. A number of such preparations against SARS-CoV-2 are already in various phases of preclinical and clinical trials, and several of them are very close to being accepted for general use, constituting a milestone toward pandemic containment. Full article

The average woman uses 12 different cosmetic products every day, but they can have a negative effect on human health. Therefore, in recent years, consumer preferences have changed towards buying natural or ecological cosmetics free from preservatives or unnecessary dyes. The aim of this work is to discuss the use of dyes, minerals, and vitamins in cosmetics in terms of their safety and impact on human health. These substances are very important in the cosmetics industry. Most of them are of natural origin. Some minerals used in the production of face masks or creams are recommended to work against inflammations such as ulcers and acne. Clay minerals have exceptional qualities, among others, low or no toxicity and high bio-compatibility. However, some of them may be harmful. For example, the safety of using talc has been widely debated in recent years. Cosmetic-grade talc cannot contain detectable fibrous asbestos minerals. Moreover, talc should not be applied to the skin when the epidermal barrier is missing or significantly disrupted. The use of talc in cosmetic products in the European Union is restricted. Vitamins are one of the most commonly used, biologically active, and easily accessible components in cosmetics. For example, provitamin B5 (D-panthenol) is a bioactive substance. In cosmetic preparations, it has a softening, repairing, and anti-inflammatory effect and is responsible for regulating sebum secretion. However, some vitamins may be harmful to human health. For example, the use of skin-whitening cosmetics containing vitamin C causes allergic contact dermatitis, whereas the most common adverse effect of topical use of vitamin A is skin irritation, erythema, and peeling. Dyes, which are used to color cosmetics, do not improve the condition of the skin, hair, or nails. Some of them may be harmful to human health. For example, the dye CI 60730 (Acid Violet 43) is prohibited for use in eye products and cosmetics that have contact with mucous membranes. In conclusion, some of the popular cosmetic ingredients discussed in this paper may exert a negative influence on human health, and many of these harmful effects have been discovered recently. Therefore, there is a need for further studies on the possible negative effects of dyes, minerals, and vitamins used in cosmetic products. Full article

Disruption of the epithelial barrier function has been recently associated with a variety of diseases, mainly at intestinal level, but also affecting the respiratory epithelium and other mucosal barriers. Non-pharmacological approaches such as xyloglucan, with demonstrated protective barrier properties, are proposed as new alternatives for the management of a wide range of diseases, for which mucosal disruption and, particularly, tight junction alterations, is a common characteristic. Xyloglucan, a natural polysaccharide derived from tamarind seeds, possesses a “mucin-like” molecular structure that confers mucoadhesive properties, allowing xyloglucan formulations to act as a barrier capable of reducing bacterial adherence and invasion and to preserve tight junctions and paracellular flux, as observed in different in vitro and in vivo studies. In clinical trials, xyloglucan has been seen to reduce symptoms of gastroenteritis in adults and children, nasal disorders and dry eye syndrome. Similar mucosal protectors containing reticulated proteins have also been useful for the treatment of irritable bowel syndrome and urinary tract infections. The role of xyloglucan in other disorders with mucosal disruption, such as dermatological or other infectious diseases, deserves further research. In conclusion, xyloglucan, endowed with film-forming protective barrier properties, is a safe non-pharmacological alternative for the management of different diseases, such as gastrointestinal and nasal disorders. Full article