Mucosal Membrane Research Articles

The role of serum albumin in Candida albicans filamentation, germ tube formation, and farnesol sequestration.

Candida albicans is an opportunistic pathogen and colonizer of the human gut and mucosal membranes. C. albicans exhibits morphological plasticity, which is crucial for its fitness within the host and virulence. Morphogenesis in C. albicans is regulated, in part, by its production of farnesol, an autoregulatory molecule that inhibits filamentation. Morphogenesis is also regulated in response to external cues, such as serum, which stimulates hyphal formation by C. albicans. The precise mechanism by which serum stimulates hyphal formation is unknown. The most abundant serum protein is albumin. The binding affinity of albumin for nonpolar, fatty-acid-like molecules suggests that it may interact directly with exogenous farnesol and influence morphogenesis through sequestration of free farnesol. To test this hypothesis, we assessed whether albumin and albumin devoid of fatty acids (i) stimulated farnesol secretion and (ii) influenced the farnesol threshold required to inhibit filamentation. We found that albumin promoted farnesol secretion and filamentation, and the extent of its ability to do so was based on the presence or absence of bound fatty acids. We hypothesize that albumin not bound to fatty acids has the capacity to bind to farnesol and sequester it from C. albicans, encouraging filamentation.IMPORTANCEFor at least 50 years, researchers have wondered about the mechanisms by which serum stimulates germ tube formation (GTF) and hyphal growth in C. albicans. Here, we tested a model (Nickerson et al., Microbiol Mol Biol Rev 88:e00081-22, 2024, https://doi.org/10.1128/mmbr.00081-22) that serum promotes GTF and farnesol synthesis in part by extracting internal farnesol (Fi) from the cells toward the excess binding capacity of the albumins. The data presented here suggests that albumin not bound by fatty acids sequesters free farnesol thereby modulating filamentation and farnesol secretion by altering the equilibrium of internal vs external farnesol. We expect that the influence of secreted farnesol on cell morphology will differ during pathogenesis depending on location within the body, but sequestration of farnesol in the blood could mediate immune cell recruitment and promote hyphal formation.

Identification of new potential inhibitors of pteridine reductase-1 (PTR1) via biophysical and biochemical mechanism-based approaches: Step towards the treatment of Leishmaniasis

Leishmaniasis is a parasitic disease, which spreads from the bite of an infected Phlebotomine fly to human hosts. The disease is characterized by a number of clinical manifestations, such as ulcerative lesions at the site of sandfly bite (cutaneous form), inflammation of mucosal membranes (mucosal leishmaniasis) or the deadly visceral form. This study was aimed to target pteridine reductase-1 (PTR1), a member of short chain dehydrogenases, which accounts for the reduction of conjugated and unconjugated pterins in Leishmania parasite. The ptr1-pET28a+-tev construct was expressed using BL21 (DE3) cells, followed by two tandem purification steps including affinity and gel permeation chromatography. In the next phase, functional studies of PTR1 were performed via screening of an in-house library of 500 compounds. The biochemical-mechanism based assay of PTR1 identified 11 hits that were also found to be non-cytotoxic against human fibroblast cell line (BJ) (except compound 6), and thus further studied via computational technique and saturation transfer difference-nuclear magnetic resonance (STD-NMR) spectroscopy. These high throughput techniques identified six compounds 2, 4, 5, 7, 9, and 11 as active, which were then assessed via in-vitro assay. Among them, compounds 2, 4, and 7 showed substantial leishmanicidal activity, comparable to the standard drug, miltefosine (IC50 value: 31.8 ± 0.2 μM). These results narrowed down the search to 3 compounds as potential leads, with prominent protein-ligand interaction profiles. Hence, the respective compounds can be further assessed for their therapeutic potential against leishmaniasis.

Experimental colitis is comorbid with social interaction deficits and anxiety-like behaviors in mice: mechanistic intuitions into neuroinflammation and Claudin 5 expression in the hippocampus.

Inflammatory bowel disease (IBD) is accompanied by psychiatric disorders, including Schizophrenic-like manifestations. Although incompletely illustrated, intestinal mucosal membrane damage and blood-brain barrier (BBB) penetrability may have significant roles in psychiatric symptoms of IBD. This study aimed to investigate role of the Claudin-5 (CLDN5) (a regulator of the permeability of BBB) and neuroinflammatory response in the comorbid behavioral disorders in experimental colitis in mice. Acetic acid was used to induce colitis in mice. 7 days after induction of colitis, behaviors including social interaction and locomotor activity as well as anxiety-like behaviors were evaluated. Then, the colon was extracted for gross and microscopic evaluations. The expression of CLDN5, TNF-α, IL1β and IL23 was measured by RT-PCR in the colon and hippocampus. Histopathologic evaluations demonstrated mucosal, submucosal, and crypt-related damages in the colon. The negative and positive number of social interactions significantly increased in the colitis group. A considerable increase in locomotor activities (horizontal and vertical components) shown in the colitis group. Mice in colitis group spent less time in the central zone in the open field apparatus. Gene expressions of TNF-α, IL1β, and IL23 increased and CLDN5 decreased in the colitis group. The barrier function of the intestine and brain would be impaired, partially at least, following colitis (as we observed decrease in CLDN5 gene expression). Furthermore, we found that beside inflammatory response in the colon, a neuro-immune response triggered in the hippocampus following colitis. These alterations probably, mediated comorbid behavioral disorders in acetic acid-induced colitis in mice.

Hydroxypropyl methylcellulose stabilized clove oil nanoemulsified orodispersible films: Study of physicochemical properties, release profile, mucosal permeation, and anti-bacterial activity.

Hydroxypropyl methylcellulose (HPMC)-based nanoemulsions for quick dissolving orodispersible (OD) films were prepared to encapsulate clove oil (CO) to harness its anti-bacterial properties. The influence of additives maltodextrin, pectin, and glycerol on the OD films was studied. The nanoemulsion particle size varied from 135 nm to 195 nm. A decrease in tensile strength and, an increase in elongation at break and opacity were observed in OD films compared to neat HPMC film. The AFM images showed an increase in HPMC films' average roughness from 6.95 to 90 nm after adding CO and additives. The additives controlled CO in-vitro release from HPMC following the Higuchi model. The ex-vivo permeation through porcine mucosal membrane was 9-33 % while the permeation coefficient and flux were 0.282-0.879 cm s-1 and 0.191-1.318 μg cm-2 s-1, respectively. The OD films exhibited significant inhibition of Staphylococcus aureus, Streptococcus mutans, and Porphyromonas gingivalis suggesting their therapeutic potential in oral healthcare.

Klebsiella in Wildlife: Clonal Dynamics and Antibiotic Resistance Profiles, a Systematic Review

Klebsiella spp. are a genus of Gram-negative, opportunistic bacteria frequently found in the flora of the mucosal membranes of healthy animals and humans, and in the environment. Species of this group can cause serious infections (meningitis, sepsis, bacteraemia, urinary tract infections, liver damage) and possible death in immunocompromised organisms (and even in immunocompetent ones in the case of hypervirulent K. pneumoniae) that are exposed to them. K. pneumoniae is part of the ESKAPE organisms, and so it is important to understand this genus in terms of multidrug-resistant bacteria and as a carrier of antibiotic resistance mechanisms. As it is a durable bacterium, it survives well even in hostile environments, making it possible to colonize all kinds of habitats, even the mucosal flora of wildlife. This systematic review explores the prevalence of Klebsiella spp. bacteria in wild animals, and the possibility of transmission to humans according to the One Health perspective. The isolates found in this review proved to be resistant to betalactams (blaTEM, blaOXA-48…), aminoglycosides (strAB, aadA2…), fosfomycin, tetracyclines, sulphonamides, trimethoprim, phenicols (catB4), and polymyxins (mcr4).

Interpretation of the key points of Regulation for Diagnosis and Treatment of Non-neonatal Tetanus (2024 Edition)

Non-neonatal tetanus is an acute, specific, toxic disease in patients over 28 days of age, characterized by continuous rigidity and paroxysmal spasms of the skeletal muscles throughout the body caused by the intrusion of Clostridium tetani through skin or mucosal membrane into the body and reproducing in anaerobic environments to produce exotoxins. The mortality rate of severe patients is close to 100% without medical intervention. Even with aggressive comprehensive treatment, the global mortality rate remains at 30%-50%, making it a potentially fatal disease. In order to standardize the diagnosis, treatment and prevention of non-neonatal tetanus, based on "Regulation for Diagnosis and Treatment of Non-Neonatal Tetanus (2019)", experts have revised this regulation according to clinical practice and recent research progress in this field to guide medical institutions in the prevention and control of non-neonatal tetanus. This article interprets the key points and basis for updating the 2024 edition regulation to guide clinical implementation and application.

Comparative Efficacy of Parenteral and Mucosal Recombinant Probiotic Vaccines Against SARS-CoV-2 and S. pneumoniae Infections in Animal Models.

The accumulation of specific IgG antibodies in blood serum is considered a key criterion for the effectiveness of vaccination. For several vaccine-preventable infections, quantitative indicators of the humoral response have been established, which, when reached, provide a high probability of protection against infection. The presence of such a formal correlate of vaccine effectiveness is crucial, for example, in organizing preventive measures and validating newly developed vaccines. However, can effective protection against infection occur when the level of serum antibodies is lower than that provided by parenteral vaccination? Will protection be sufficient if the same vaccine antigen is administered via mucosal membranes without achieving high levels of specific IgG circulating in the blood? In this study, we compared the immunogenicity and protective efficacy of parenteral and mucosal forms of vaccines in experimental animals, targeting infections caused by the SARS-CoV-2 coronavirus and Streptococcus pneumoniae. We investigated the protective properties of a fragment of the coronavirus S1 protein administered intramuscularly with an adjuvant and orally as part of the probiotic strain Enterococcus faecium L3 in a Syrian hamster model. A comparative assessment of the immunogenicity and protective efficacy of a recombinant tandem (PSP) of immunogenic peptides from S. pneumoniae surface proteins, administered either parenterally or orally, was performed in a Balb/c mouse model. Both models demonstrated significant differences in the immunogenicity of parenteral and oral vaccine antigens, but comparable protective efficacy.

One health: the impact of environment, detergents and hygiene on barrier, microbiome and allergy

SummaryA variety of body surfaces, such as skin and mucosal membranes—from the nasopharyngeal area to the lungs, uterus, vaginal area, and digestive tract—contain complex microbial ecosystems that are tailored to the specifics of the respective niche [1].The so-called dysbiosis—a disadvantageous change in the composition of the microbiome—is associated with the pathogenesis of a variety of diseases [2]. Gastrointestinal as well as cardiovascular, metabolic, neurodegenerative, psychological, oncological, and also allergic diseases have been linked to microbial dysbiosis. Susceptibility to allergies can be due to genetic predisposition; in addition, extrinsic factors from today’s lifestyle increasingly contribute to microbiome changes, but also to the disruption of the skin and mucosal barrier and thus to the development of allergies [3].Gisela, a fictional farmer, guides us through this review. She is representative of adults and children of all genders in industrialized countries. During her daily routine, the skin and mucosal microbiome is influenced by a variety of exogenous factors. These include everyday personal hygiene products, detergents for laundry and dishes, food, medication, animal contact, and exposure to various outdoor environments. Gisela’s daily routine will illustrate how the human microbiome and the skin barrier are modified in positive or negative ways, and how this could influence the development of allergies. Furthermore, potential measures for the prevention and management of dysbiosis will be discussed in terms of examples of alternative products and behaviors.

Comparison of post-operative pain in stapled haemorrhoidectomy v/s open haemorrhoidectomy.

Objective: To compare mean post-operative pain in stapled haemorrhoidectomy versus open haemorrhoidectomy. Study Design: Randomized Control Trial. Setting: Department of Surgery, Allied Hospital Faisalabad. Period: 18-04-2021 to 17-10-2021. Methods: There are 94 patients that fill the concert form that agree in this study. The presenting complaints that included such as bleeding per anus ,prolapsed of the mucosal membrane, hardening of stool and itching of rectum that were noted. Complete history was taken and physical examination was done as per rule. There are two groups arranged where patients are divided in this group with a well-mannered numerical method. Patients having the group that labeled as Group A underwent open haemorrhoidectomy that compare with the patients that labelled with as Group B with stapled heamorrhoidectomy. All operations were done by same surgical team .All patients were retained in surgical ward in surgical department of Allied hospital Faisalabad .there are several post-operative therapies were taken for reducing the pain and recommend the analgesic NASIDS in the form of Intravenous rout. In the first post-operative day of treatment I/v Paracetamol were administered for 08 hours. NSAIDS and other pain killers were administered in the form of Diclofenac 50mg for the next five post-operative days. However, these medications were administered in both groups that labeled as Group a and Group B of the patients. Results: Comparison of post-operative pain in both groups shows 2.28+0.45 pain in Group-A and 1.26+0.49 in Group-B, p value is 0.0001. Conclusion: The conclusion that showed post-operative pain is significantly lower in stapled haemorrhoidectomy when compared with open haemorrhoidectomy in 3rd and 4th degree of haemorrhoids.

Reconstruction of deep and perforating corneal defects in dogs-A review (Part II/III): Biomaterials and keratoprosthesis.

The surgical reconstruction of severe corneal ulcers is a common and crucial component of the clinical practice of veterinary ophthalmology. Numerous surgical techniques are used in dogs for corneal reconstruction, and these techniques may be categorized by the material used to repair the corneal lesion. The first part of the present review described procedures that utilize autogenous ocular tissues, homologous donor tissues, and heterologous donor tissues. In this second part of the review, the categories of biomaterials and keratoprosthetics will be summarized. Biomaterials that are reported for use in dogs include amniotic membrane, porcine urinary bladder acellular matrix, porcine small intestinal submucosa, acellular porcine corneal stroma, and other miscellaneous soft tissue and cartilage grafts (e.g., preserved equine renal capsule, autologous omentum, autologous buccal mucosa membrane, bovine pericardium, and homologous peritoneum). Descriptions of keratoprosthesis surgery in dogs are currently limited, but the use of artificial corneal transplants hold promise for dogs with severe, vision-compromising corneal disease that is not amenable to other reconstruction techniques. This review describes the results of experimental studies evaluating these graft materials in dogs, and it will summarize the findings and outcomes of the clinical articles published in each material category. Reporting inconsistencies and areas where additional research is required will be highlighted to help guide future studies in this area. A major aim of this review is to help identify potential subjects that could be evaluated in future investigations and that might lead to refinements in clinical practice.

"Enhancing Oral Drug Absorption: Overcoming Physiological and Pharmaceutical Barriers for Improved Bioavailability".

The oral route stands out as the most commonly used method for drug administration, prized for its non-invasive nature, patient compliance, and easy administration. Several elements influence the absorption of oral medications, including their solubility, permeability across mucosal membranes, and stability within the gastrointestinal (GI) environment. Research has delved into comprehending physicochemical, biochemical, metabolic, and biological obstacles that impact the bioavailability of a drug. To improve oral drug absorption, several pharmaceutical technologies and delivery methods have been studied, including cyclodextrins, micelles, nanocarriers, and lipid-based carriers. This review examines both traditional and innovative drug delivery methods, as well as the physiological and pharmacological barriers influencing medication bioavailability when taken orally. Additionally, it describes the challenges and advancements in developing formulations suitable for oral use.

Vaginal Mucosal Melanoma Cell Activation in Response to Photon or Carbon Ion Irradiation

PurposePrimary gynecological melanomas are uncommon with lower survival rates compared to cutaneous melanomas. Although melanocytes have been identified in a variety of mucosal membranes, little is known about their interactions or roles inside the mucosa layer. Melanin is a common pigment in nature and is endowed with several peculiar chemical, paramagnetic, and semiconductive characteristics. One of its latest explored functions is its interaction with ionizing radiation as a protective mechanism as well as its implication in the metastatic cascade of tumor cells. Materials and MethodsIn this work, we analyzed in vitro the effects of different doses of photon and carbon ion irradiation on dendrite formation, pigmentation, migration, and invasion abilities of human mucosal melanoma cells of the vagina. We evaluated the morphology and melanin production of HMV-II cells exposed to photon and carbon ion beams with single doses between 0.5 and 10 Gy. ResultsOur results showed that irradiation induces dendrite formation or elongation and pigmentation in HMV-II cells in a dose-type-dependent and radiation-type-dependent way but also a decrease in cell motility. ConclusionThe present study describes for the first time an induction of dendritic formation, melanin production, and alterations in migration and invasion abilities by low-linear energy transfer and high-linear energy transfer radiation in human mucosal melanoma cells, suggesting a radioprotective response to further possible exposures increasing the radioresistance of these cells.

323 Advances in using membrane vesicles for studying intestinal functions

Abstract Enterocytes are the major cell lineage of the small intestinal epithelia along the crypt-villus axis in gut mucosa. Enterocytes participate in the gut terminal nutrient digestion and absorption; and have essential roles in nutrient and metabolite recycling and efflux, nutrient and hormonal sensing, interactions with symbiotic microbiome and binding to infectious viruses, thus influencing the host homeostasis and whole-body physiological status. Intestinal membrane vesicles have been widely used for studying various gut functions in the past several decades. Villus enterocytic brush border membrane and the apical membrane vesicles along the crypt-villus axis in gut mucosa can be prepared and isolated by Mg2+- and Ca2+-precipitation and differential centrifugation procedures. Whereas, gut mucosal basolateral membrane vesicles can be prepared, fractionated and differentiated from other intracellular organelles such as the mitochondrial inner membrane by the Percoll gradient ultracentrifugation. Nutrient transport and exchange activities in the membrane vesicles in vitro are conducted often by rapid hand filtration, and in excess, in an automated fast sampling apparatus. Nutrient transport and exchange activity kinetics are derived according to the well-established classic Michaelis-Menten and the tracer inhibitory kinetic models with a simple linear diffusional component. Physiological and biochemical properties associated with various nutrient uptake systems such as pH optimum, requirements for co-transported ions (e.g., Na+, K+, Cl-), transporter affinity and substrate specificity can be effectively investigated in vitro with the membrane vesicles by altering the compositions of uptake buffers and intra-vesicular pre-loading buffers. Some of the fundamental gut functions are established via using the membrane vesicles in different mammalian species. And these include H+-peptide cotransport, Na+-cotransport and Na+-independent systems of hexose uptake across the apical membrane and the low-affinity Na+-independent hexose bidirectional uptake across the basolateral membrane that were characterized in rodents; Na+-dependent cotransport and Na+-independent systems of amino acid (AA) transport across the apical membrane that were revealed in rodents and pigs; as well as the Na+-hexose and AA cotransport and the co-expression of the coronavirus SARS-CoV-2 host epithelial apical membrane binding receptor, i.e., the angiotensin-converting enzyme-2 (ACE2), along the gut crypt-villus axis that were identified in liquid formula-fed piglets. In the post genomic and metagenomic sequencing era, further research efforts need to pursue understanding of expression and various functionality of the gut terminal hydrolases, nutrient transporters, nutrient exchangers, nutrient sensors, substrate and particle receptors, taste receptors, viral binding receptors such as ACE2 and hormonal receptors and their interactions with luminal factors such as nutrient, metabolites, symbiotic bacterial outer membrane vesicles etc., along the longitudinal and crypt-villus axes, through using the mammalian primary enterocytic apical and the basolateral membrane vesicles under various research settings.

The Role of Surface Energy and Wettability in Polymer-Based Drug Delivery Systems: Enhancing Bioadhesion and Drug Release Efficiency

Polymer-based drug delivery systems are pivotal in advancing the precision and efficacy of modern therapeutics. Among the key factors influencing these systems, surface energy and wettability are crucial in determining their interaction with biological tissues and drug release behavior. Surface energy, which governs the adhesive properties of the polymers, plays a significant role in bioadhesion—a critical aspect for drug delivery routes that require prolonged contact with biological surfaces, such as mucosal membranes. Wettability, the extent to which a polymer surface can be wetted by biological fluids, influences both drug loading efficiency and release kinetics. Hydrophilic polymers, characterized by high wettability, typically facilitate rapid drug release, whereas hydrophobic polymers, with low wettability, offer controlled, prolonged release profiles. Additionally, the balance between hydrophilicity and hydrophobicity is essential for optimizing drug-polymer interactions, particularly in systems designed for sustained or targeted drug delivery. Advances in surface modification techniques have enabled precise control over these parameters, allowing for the customization of polymers to meet specific therapeutic requirements. This review discusses the interplay between surface energy, wettability, and drug delivery performance, highlighting how these properties have been manipulated to enhance bioadhesion, drug retention, and release profiles. The review also addresses the challenges in designing polymer wettability, such as maintaining stability, scalability, and regulatory compliance. Finally, it explores emerging trends, including stimuli-responsive polymers and nanotechnology integration, which hold promise for the next generation of drug delivery systems that are more efficient, targeted, and patient-specific, than current systems.

Dietary supplementation of microencapsulated botanicals and organic acids enhances the expression and function of intestine epithelial digestive enzymes and nutrient transporters in broiler chickens

Organic acids and botanicals have shown protective effects on gut barrier and against inflammation in broilers. However, their effects on intestinal digestive enzymes and nutrients transporters expression and functions have not been fully studied. The objective of this study was to understand how a microencapsulated blend of botanicals and organic acids affected intestinal enzyme activities and nutrient transporters expression and functions in broilers. A total of 288 birds were assigned to a commercial control diet or diet supplemented with 500 g/MT (metric ton) of the microencapsulated additive. Growth performance was recorded weekly. At d 21 and d 42, jejunum and ileum were isolated for enzyme (maltase, sucrase, and aminopeptidase) and transporter (SGLT1, GLUT2, GLUT1, EAAT3, B0AT1, and PepT1) analyses. Jejunum specific nutrients (glucose, alanine, and glutamate) transport activities were evaluated by Ussing chamber. Protein expression of nutrient transporters in small intestine were measured in mucosa and brush-border membrane (BBM) samples by western blot. Intestinal gene expression of the transporters was determined by RT-PCR. Statistical analysis was performed using Student's t-test comparing the supplemented diet to the control. The feed efficiency was significantly improved through the study period in the supplemented group (P ≤ 0.05). Significant changes of intestinal histology were shown in both jejunum (P ≤ 0.10) and ileum (P ≤ 0.05) after 21 d of treatment. At d21, jejunal maltase activity was upregulated (P ≤ 0.10). The Ussing chamber transport of glucose and alanine was increased, which was in line with increased gene expression (GLUT2, GLUT1, EAAT3, and B0AT1) (P ≤ 0.10 and P ≤ 0.05, respectively) and BBMV protein levels (B0AT1, P < 0.10). At d21, ileal sucrase and maltase activities were upregulated (P ≤ 0.05). Increased expressions of GLUT1, EAAT3, and B0AT1 were observed in both mRNA and protein levels (P ≤ 0.05). Similar pattern of changes was also shown at d42 of age. Our results suggest that feeding microencapsulated additives improves intestinal nutrient digestion and transporter expression and function in broilers, thereby enhancing feed efficiency.

Clinical Study of Godhuma Yusha (Triticum Aestivum Linn.) in Amlapitta (Gastritis)

Gastritis is a condition that results from inflammation of the gastric mucosal layer characterized by swelling, pain and mucosal membrane irritation of the stomach. Gastritis in Ayurveda can be compared to Amlapitta and consumption of Godhuma in Ayurvedic classics is shown to be very effective. Objectives: To evaluate the study on Godhuma yusha in Amlapitta (gastritis) and assess its effects on Amlapitta (gastritis) Study Design: This was a randomized controlled study with 30 patients divided into two groups. Group A and Group B. Intervention: Group A included 15 patients and was administered 15ml of Godhuma yusha twice daily for a period of 3months. Group B also had 15 patients and was administered placebo 5gm twice daily. All the patients were followed at an interval of 15 days up to 3 months. Results: All the parameters such as Amlodgara, Hritkantadaha, Gourava, Utklesha, Avipaka and Agnimandya showed significant results in both the groups; Group A and Group B after the treatment compared to before treatment with p&lt;0.0001 with more significant results in Group A compared to Group B with statistically significant results (p&lt;0.001). Conclusion: Godhuma Yusha consumption was more effective compared to placebo in the management of Amlapitta.

Docosahexaenoic acid (DHA) alleviates inflammation and damage induced by experimental colitis.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic gastrointestinal disorders associated with significant morbidity and complications. This study investigates the therapeutic potential of docosahexaenoic acid (DHA) in a trinitrobenzene sulfonic acid (TNBS) induced colitis model, focusing on inflammation, oxidative stress, and intestinal membrane permeability. Wistar albino rats were divided into Control, Colitis, and Colitis + DHA groups (n = 8-10/group). The Colitis and Colitis + DHA groups received TNBS intrarectally, while the Control group received saline. DHA (600 mg/kg/day) or saline was administered via gavage for six weeks. Macroscopic and microscopic evaluations of colon tissues were conducted. Parameters including occludin and ZO-1 expressions, myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels were measured in colon tissues. Colitis induction led to significantly higher macroscopic and microscopic damage scores, elevated TOS levels, reduced occludin and ZO-1 intensity, decreased mucosal thickness, and TAS levels compared to the Control group (p < 0.001). DHA administration significantly ameliorated these parameters (p < 0.001). MPO, MDA, TNF-α, and IL-6 levels were elevated in the Colitis group but significantly reduced in the DHA-treated group (p < 0.001 for MPO, MDA; p < 0.05 for TNF-α and IL-6). DHA demonstrated antioxidant and anti-inflammatory effects by reducing reactive oxygen species production, enhancing TAS capacity, preserving GSH content, decreasing proinflammatory cytokine levels, preventing neutrophil infiltration, reducing shedding in colon epithelium, and improving gland structure and mucosal membrane integrity. DHA also upregulated the expressions of occludin and ZO-1, critical for barrier function. Thus, DHA administration may offer a therapeutic strategy or supplement to mitigate colitis-induced adverse effects.

Stress and its impact on the mucosal membranes of the digestive tract: morphological and functional alterations. A review

Studies of morphological changes in the mucous membranes of the digestive tract under stress are highly relevant in medical science and practice. Understanding these changes can be key to developing effective prevention and treatment methods for related problems. It is also important to improve the quality of life of people who are stressed in various areas of life. The literature review examines the physiological changes in the digestive tract under stress. Stress causes a complex effect on the functional state of the digestive system, including changes in blood supply, peristalsis and enzyme production. Such processes can lead to digestive disorders and aggravation of disorders.

Challenges in Diagnosis of Melanoma from the Perspective of a Pathologist

Introduction: Melanoma is an aggressive melanocytic neoplasm with a continuously increasing incidence worldwide. Vast majority of melanoma arises from skin whereas a small subset of melanoma can arise as a primary malignancy of mucosal membranes. Gastrointestinal (GI) melanoma is usually metastatic in origin whereas primary GI melanomas are extremely rare. Anorectal Melanoma comprises of 1/% of all malignant neoplasms of this area. About 70% of these lesions are pigmented whereas 30% of them are amelanotic. Upto 25% of the patients with melanoma develops recurrent disease locally or in regional lymph nodes. Materials And Methods: This is a prospective study conducted in a tertiary care hospital comprising of six cases of Melanoma. We studied the cases according to their age, sex, clinical presentation, site, radiological findings, histopathological findings, immunohistochemical findings and treatment provided. Results: This study comprises of six cases of Melanoma among which five cases are primary one case is recurrent. Among the five primary cases, four cases have GI origin (sigmoid colon, rectum, anal canal) one case originated from skin involving left foot. There is a single case of recurrent MM involving right inguinal lymph nodes with a history of primary MM in the right lower limb. The patients belong to the age group of 6th to 8th decade with male preponderance. Histopathological examination of formalin fixed paraffin tissue sections was done followed by Hematoxylin &amp; Eosin and Immunohistochemical staining which confirmed the diagnosis of Melanoma. Conclusion: Melanoma is an aggressive melanocytic neoplasm that carries a poor prognosis. It commonly involves skin. Its occurrence in GI tract is rare in which primary lesions are exceedingly unusual. Diagnosis and Treatment require multidisciplinary team approach with surgery remaining as a cornerstone of treatment.

Treatment of Epidermolysis Bullosa and Future Directions: A Review.

Epidermolysis bullosa (EB) comprises rare genetic disorders characterized by skin and mucosal membrane blistering induced by mechanical trauma. Molecularly, pathogenic variants affect genes encoding proteins crucial for epidermal-dermal adhesion and stability. Management of severe EB is multidisciplinary, focusing on wound healing support, ensuring that patients thrive, and complication treatment. Despite extensive research over 30years, novel therapeutic approaches face challenges. Gene therapy and protein therapy struggle with efficacy, while regenerative cell-based therapies show limited effects. Drug repurposing to target various pathogenic mechanisms has gained attention, as has in vivo gene therapy with drugs for dystrophic and junctional EB that were recently approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). However, their high cost limits global accessibility. This review examines therapeutic advancements made over the past 5 years, exploiting a systematic literature review and clinical trial data.