PVA enema ameliorates DSS-induced acute colitis in mice.

BACKGROUND: Ulcerative colitis (UC) represents a clinically challenging condition characterized by persistent damage to the colonic epithelial mucosa as the principal pathological feature. Polyvinyl alcohol (PVA) solution, primarily composed of glue, is a biodegradable polymer material that has found utility in the medical field. This research endeavors to investigate the therapeutic potential of PVA water solution in ameliorating UC in mice. METHODS: UC was induced in 48 C57BL/6 mice by administering 2.5% DSS in their diet for 6 days. Mice were treated with different concentrations of PVA (0.1 mg/ml PVA, 0.3 mg/ml PVA, 1 mg/ml PVA, 3 mg/ml PVA, 10 mg/ml PVA) enemas (n = 6). Disease Activity Index (DAI) and histologic score were evaluated for inflammation degree. Furthermore, mouse colon organoids were cultured, which were used to assess the effects of PVA on expansion in vitro. RESULTS: PVA aqueous solutions (1 mg/ml and 3 mg/ml) were able to alleviate the DAI in mice. By DAY 6, there was a significant 3/5-fold decrease in DAI within the 1 mg/ml PVA group (p = 0.02). Histopathology scores demonstrated improvements, while the levels of inflammatory factors in the intestinal mucosal tissue were reduced. Additionally, it was confirmed that PVA could promote the expansion of colonic organoids in vitro. CONCLUSIONS: In summary, our investigation has yielded findings indicating that PVA holds the potential to ameliorate symptoms associated with colitis in murine subjects afflicted by DSS-induced colitis, primarily through its facilitation of intestinal stem cell expansion. This study might provide a new candidate for the clinical treatment of ulcerative colitis.

Gut dysbiosis induced by florfenicol increases susceptibility to Aeromonas hydrophila infection in Zebrafish Danio rerio after the recommended withdrawal period.

OBJECTIVE: Florfenicol (FFC) is a broad-spectrum antibiotic approved by the U.S. Food and Drug Administration to treat both systemic and external bacterial infections in food fish. The objective of this study was to evaluate the effect of FFC-medicated feed on the gut microbiota of Zebrafish Danio danio to determine (1) if the therapeutic dose of FFC-medicated feed induces dysbiosis and (2) if fish with altered gut microbiota were more susceptible to subsequent infection by the common opportunistic fish pathogen Aeromonas hydrophila. METHODS: Zebrafish that were treated with regular and FFC-medicated feeds were artificially challenged with A. hydrophila at the end of the recommended 15-day antibiotic withdrawal period. The gut microbiota of the Zebrafish at different stages was analyzed using 16S ribosomal RNA gene sequencing. RESULT: Our results found that FFC-medicated feed induced disruption of the gut microbiota. Dysbiosis was observed in all treated groups, with a significant increase in bacterial diversity, and was characterized by a remarkable bloom of Proteobacteria and a drastic decline of Mycoplasma and Cetobacterium in treated animals but without noticeable clinical signs or mortalities. In addition, the increase of Proteobacteria was not significantly reduced after the recommended 15-day withdrawal period, and the Zebrafish treated with FFC-medicated feed exhibited a significantly higher mortality rate when they were subsequently challenged with A. hydrophila compared to the control (regular feed) groups. Interestingly, the most dramatic changes in the gut microbiome composition occurred at the transition time between the late stage of the medicated treatment and the beginning of the withdrawal period instead of the time during the Aeromonas infection. CONCLUSION: The administration of FFC-medicated feed at the recommended dose induced gut dysbiosis in Zebrafish, and fish did not recover to the baseline after the recommended withdrawal period. Our findings suggest that the use of antibiotics in fish elicits a response similar to those previously described in mammals and possibly makes the host more susceptible to subsequent infections of opportunistic pathogens. This study using a controlled model system suggests that antibiotics in aquaculture may have long-term effects on the general well-being of the fish.

Trefoil Factor Family: A Troika for Lung Repair and Regeneration.

Tissue damage in the upper and lower airways caused by mechanical abrasion, noxious chemicals, or pathogenic organisms must be followed by rapid restorative processes; otherwise, persistent immunopathology and disease may ensue. This review will discuss evidence for the important role served by trefoil factor (TFF) family members in healthy and diseased airways of humans and rodents. Collectively, these peptides serve to both maintain and restore homeostasis through their regulation of the mucous layer and their control of cell motility, cell differentiation, and immune function in the upper and lower airways. We will also discuss important differences in which trefoil member tracks with homeostasis and disease between humans and mice, which poses a challenge for research in this area. Moreover, we discuss new evidence supporting newly identified receptor binding partners in the leucine-rich repeat and immunoglobulin-like domain-containing NoGo (LINGO) family in mediating the biological effects of TFF proteins in mouse models of epithelial repair and infection. Recent advances in our knowledge regarding TFF peptides suggest that they may be reasonable therapeutic targets in the treatment of upper and lower airway diseases of diverse etiologies. Further work understanding their role in airway homeostasis, repair, and inflammation will benefit from these newly uncovered receptor-ligand interactions.

Human Immunodeficiency Virus (HIV) and Human Cytomegalovirus (HCMV) Coinfection of Infant Tonsil Epithelium May Synergistically Promote both HIV-1 and HCMV Spread and Infection.

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) and human cytomegalovirus (HCMV) may occur during pregnancy, labor, or breastfeeding. These viruses from amniotic fluid, cervicovaginal secretions, and breast milk may simultaneously interact with oropharyngeal and tonsil epithelia; however, the molecular mechanism of HIV-1 and HCMV cotransmission through the oral mucosa and its role in MTCT are poorly understood. To study the molecular mechanism of HIV-1 and HCMV MTCT via oral epithelium, we established polarized infant tonsil epithelial cells and polarized-oriented ex vivo tonsil tissue explants. Using these models, we showed that cell-free HIV-1 and its proteins gp120 and tat induce the disruption of tonsil epithelial tight junctions and increase paracellular permeability, which facilitates HCMV spread within the tonsil mucosa. Inhibition of HIV-1 gp120-induced upregulation of mitogen-activated protein kinase (MAPK) and NF-κB signaling in tonsil epithelial cells, reduces HCMV infection, indicating that HIV-1-activated MAPK and NF-κB signaling may play a critical role in HCMV infection of tonsil epithelium. HCMV infection of tonsil epithelial cells also leads to the disruption of tight junctions and increases paracellular permeability, facilitating HIV-1 paracellular spread into tonsil mucosa. HCMV-promoted paracellular spread of HIV-1 increases its accessibility to tonsil CD4 T lymphocytes, macrophages, and dendritic cells. HIV-1-enhanced HCMV paracellular spread and infection of epithelial cells subsequently leads to the spread of HCMV to tonsil macrophages and dendritic cells. Our findings revealed that HIV-1- and HCMV-induced disruption of infant tonsil epithelial tight junctions promotes MTCT of these viruses through tonsil mucosal epithelium, and therapeutic intervention for both HIV-1 and HCMV infection may substantially reduce their MTCT. IMPORTANCE Most HIV-1 and HCMV MTCT occurs in infancy, and the cotransmission of these viruses may occur via infant oropharyngeal and tonsil epithelia, which are the first biological barriers for viral pathogens. We have shown that HIV-1 and HCMV disrupt epithelial junctions, reducing the barrier functions of epithelia and thus allowing paracellular penetration of both viruses via mucosal epithelia. Subsequently, HCMV infects epithelial cells, macrophages, and dendritic cells, and HIV-1 infects CD4+ lymphocytes, macrophages, and dendritic cells. Infection of these cells in HCMV- and HIV-1-coinfected tonsil tissues is much higher than that by HCMV or HIV-1 infection alone, promoting their MTCT at its initial stages via infant oropharyngeal and tonsil epithelia.

ACE2 and TMPRSS2 in human saliva can adsorb to the oral mucosal epithelium.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily transmitted through droplets. All human tissues with the angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serines 2 (TRMPRSS2) are potential targets of SARS-CoV-2. The role of saliva in SARS-CoV-2 transmission remains obscure. In this study, we attempted to reveal ACE2 and TRMPRSS2 protein expression in human parotid, submandibular, and sublingual glands (three major salivary glands). Then, the binding function of spike protein to ACE2 in three major salivary glands was detected. The expression of ACE2 and TMPRSS2 in human saliva from parotid glands were both examined. Exogenous recombined ACE2 and TMPRSS2 anchoring and fusing to oral mucosal epithelial cells in vitro were also unraveled. ACE2 and TMPRSS2 were found mainly to be expressed in the cytomembrane and cytoplasm of epithelial cells in the serous acinus cells in parotid and submandibular glands. Our research also discovered that the spike protein of SARS-CoV-2 binds to ACE2 in salivary glands in vitro. Furthermore, exogenous ACE2 and TMPRSS2 can anchor and fuse to oral mucosa in vitro. Thus, the expression of ACE2 and TMPRSS2 in human saliva might have implications for SARS-CoV-2 infection.

Labial mucosal epithelium grafting in an ex vivo human donor cornea model.

The purpose of the study was to establish a simple ex vivo corneal re-epithelization model and study the labial mucosal epithelium grafting as a potential approach for ocular surface reconstruction. Four human donor corneal buttons were overstored in a corneal cold storage solution at 4 °C for 32-52 days. Four labial oral mucosa strips were dissected from four patients during fornix reconstruction after they signed informed consent. The substantia propria was trimmed off, and the resulting graft was sutured near the corneal limbus with running sutures (thus forming the tissue construct). Constructs were cultured under the standard conditions with the anterior corneal side outwards. After 3 weeks of culture, constructs were removed, washed, and fixed. Sections were stained with hematoxylin and eosin (HE), anti-keratins 4, 13, 19, and p63. Nuclei were counterstained with Hoechst. After the cultivation, all constructs were integral with the attached graft and non-loosened sutures. The native cells were absent in all donor corneas. Histological evaluation demonstrated that the labial mucosal grafts were attached to the Bowman's membrane (BM), and its cellular outgrowths were found to be transit from the graft to the BM over the anterior surface in all constructs. Cells expressed mucosal epithelial keratins 4, 13, and 19, and several were p63-positive in nuclei. In the study, a simple ex vivo corneal re-epithelization model was successfully established. The model was potent in studying the labial mucosal epithelium grafting as an option for autologous ocular surface reconstruction in patients with bilateral limbal stem cell deficiency.

Anatomical and cellular heterogeneity in the mouse oviduct-its potential roles in reproduction and preimplantation development†.

The oviduct/fallopian tube is a tube-like structure that extends from the uterus to the ovary. It is an essential reproductive organ that provides an environment for internal fertilization and preimplantation development. However, our knowledge of its regional and cellular heterogeneity is still limited. Here, we examined the anatomical complexity of mouse oviducts using modern imaging techniques and fluorescence reporter lines. We found that there are consistent coiling patterns and turning points in the coiled mouse oviduct that serve as reliable landmarks for luminal morphological regionalities. We also found previously unrecognized anatomical structures in the isthmus and uterotubal junction, which likely play roles in reproduction. Furthermore, we demarcated the ampulla-isthmus junction as a distinct region. Taken together, the oviduct mucosal epithelium has highly diverse structures with distinct epithelial cell populations, reflecting its complex functions in reproduction.

Nattokinase crude extract enhances oral mucositis healing.

BACKGROUND: Nattokinase (NK) is a promising alternative in the prevention and treatment of cardiovascular diseases due to its potent fibrinolytic activity. In this study, we investigated the effect of crude nattokinase extract on the healing of acetic acid-induced oral mucositis in mice. METHODS: Bacillus subtilis culture media (BSCM) was isolated into the supernatant, named nattokinase crude extract (NCE), and the pellet was named Bacillus subtilis mass (BSM). An oral mucositis model was established in mice by applying 50% glacial acetic acid to the buccal mucosa. According to the treatment conditions, the mice were divided into BSCM, NCE, BSM and phosphate buffered saline (PBS) groups. The weight of the mice, oral mucositis healing score and histopathological examination were used to evaluate the treatment. RESULTS: Fibrinolytic activities of BSCM, NCE and BSM were approximately 8069, 10,800 and 80 U/ml, respectively. The weight gain of mice in the NCE group was significantly different from the PBS group after three days' treatment (p < 0.05). The oral mucositis score of NCE group was significantly higher than other groups (p < 0.05). The differences in histopathology scores between the NCE and other groups were statistically significant (p < 0.01). CONCLUSIONS: NCE could possess remarkable potential to reduce pain and promote oral mucositis healing with minimal safety concerns. In this study, we first report that NCE from the supernatant of Bacillus subtilis can promote the healing of oral mucositis, which extends the application scope of NK.

Clusterin in the eye: An old dog with new tricks at the ocular surface.

The multifunctional protein clusterin (CLU) was first described in 1983 as a secreted glycoprotein present in ram rete testis fluid that enhanced aggregation ('clustering') of a variety of cells in vitro. It was also independently discovered in a number of other systems. By the early 1990s, CLU was known under many names and its expression had been demonstrated throughout the body, including in the eye. Its homeostatic activities in proteostasis, cytoprotection, and anti-inflammation have been well documented, however its roles in health and disease are still not well understood. CLU is prominent at fluid-tissue interfaces, and in 1996 it was demonstrated to be the most highly expressed transcript in the human cornea, the protein product being localized to the apical layers of the mucosal epithelia of the cornea and conjunctiva. CLU protein is also present in human tears. Using a preclinical mouse model for desiccating stress that mimics human dry eye disease, the authors recently demonstrated that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration in the tears. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to LGALS3 (galectin-3), a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. CLU depletion from the ocular surface epithelia is seen in a variety of inflammatory conditions in humans and mice that lead to squamous metaplasia and a keratinized epithelium. This suggests that CLU might have a specific role in maintaining mucosal epithelial differentiation, an idea that can now be tested using the mouse model for desiccating stress. Most excitingly, the new findings suggest that CLU could serve as a novel biotherapeutic for dry eye disease.

Nasal Packing Materials and Placement Duration on Wound Healing in Nasal Mucosa: An Animal Study.

OBJECTIVE: The histological findings of wound healing depending on different nasal packing materials and replacement periods were lacking. METHODS: Mucosal defects were created in the nasal septum of rabbits and covered with Spongel®, Algoderm®, or Nasopore®, which were cleaned on Day 14. To investigate the effect of replacement durations, Spongel® was removed on Days 3 and 7. All nasal septal specimens were collected on Day 28. Samples without packing material were prepared as controls. Depending on residual packing materials in the regenerated tissue, specimens were classified into the remnant and non-remnant groups, and morphology was compared using epithelium grade score and subepithelial thickness. RESULTS: The epithelium grade score in the Spongel-14d group was lower than that in the other groups (p < 0.05). Subepithelial thickness was higher in the Algoderm-14d and Spongel-14d groups (p < 0.05). Epithelium grade scores were higher and subepithelial thicknesses were lower in the Spongel-3d and -7d groups than in the Spongel-14d group. Epithelium grade score was lower and subepithelial thickness was higher in the remnant group (n = 10) than in the non-remnant group (n = 15; p < 0.05). CONCLUSIONS: Differences in packing materials and placement durations affected wound healing of nasal mucosa. The selection of appropriate packing materials and replacement duration was considered essential for ideal wound healing. LEVEL OF EVIDENCE: NA Laryngoscope, 134:562-568, 2024.

In vitro characterization of cadmium transport across the gastro-intestinal membrane of the fathead minnow (Pimephales promelas) in the presence and absence of microplastics.

There is concern that microplastics can act as a vector for cadmium through adsorption and desorption of free-ionic cadmium. Little is known about the uptake of cadmium following ingestion of cadmium-microplastic complexes. This study used an in vitro gut sac technique to investigate the translocation of cadmium across the gut barrier of fathead minnows following the simulated ingestion of cadmium, microplastics, or their complexed mixture. Microplastics did not cross the gut membrane, nor did microplastics alter the rate of cadmium translocation, which was estimated to be 1.2 ± 0.04 ng Cd / hour. Less cadmium translocated when cadmium-microplastic complexes were injected than the equivalent dose of only cadmium, indicating that the presence of microplastics was protective of dietary cadmium uptake. This work highlights the importance of considering dietary uptake and the role of microplastics acting as a vector for cadmium in aquatic environments and stresses the need to understand how environmental (digestive or ambient) characteristics govern cadmium-microplastic interactions.

Extract of Sophorae flavescentis radix-Cnidii fructus couplet medicines treats vulvovaginal candidiasis by affecting the vaginal mucosal barrier.

Aim: This study investigated the inhibition of extract of Sophorae flavescentis radix-Cnidii fructus couplet medicines (ESCC) on Candida albicans (C. albicans) in vitro and the effect of ESCC on the vaginal mucosal barrier in vivo. Materials & methods: Susceptibility testing was performed with C. albicans SC5314. A vulvovaginal candidiasis mouse model was successfully established. The plate method, Gram staining, hematoxylin and eosin staining and ELISA were used to detect relevant inflammatory indexes: IFN-γ, IL-1 and TNF-α. Quantitative real-time PCR and western blot were used to detect mucosal immune-related factors: MUC1, MUC4, DEFB1 and DEFB2. Results: ESCC was able to inhibit the proliferative activity of C. albicans, and it affected inflammation-related factors and indicators of vaginal mucosal immunity. Conclusion: ESCC showed potential value in the treatment of vulvovaginal candidiasis.

IBD disease-modifying therapies: insights from emerging therapeutics.

Inflammatory bowel disease (IBD) pathogenesis is associated with gut mucosal inflammation, epithelial damage, and dysbiosis leading to a dysregulated gut mucosal barrier. However, the extent and underlying mechanisms remain largely unknown. Current treatment regimens have focused mainly on treating IBD symptoms; however, such treatment strategies do not address mucosal epithelial repair, barrier homeostasis, or intestinal dysbiosis. Although attempts have been made to identify new therapeutic modalities to enhance gut barrier functions, these are at an early developmental stage and have not been wholly successful. We review conventional therapies, the possible relevant role of gut barrier-protecting agents, and biomaterial strategies relating to combination therapies that may pave the way towards developing new therapeutic approaches for IBD.

Molecular Pathogenesis of Human Immunodeficiency Virus-Associated Disease of Oropharyngeal Mucosal Epithelium.

The oropharyngeal mucosal epithelia have a polarized organization, which is critical for maintaining a highly efficient barrier as well as innate immune functions. In human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) disease, the barrier and innate immune functions of the oral mucosa are impaired via a number of mechanisms. The goal of this review was to discuss the molecular mechanisms of HIV/AIDS-associated changes in the oropharyngeal mucosa and their role in promoting HIV transmission and disease pathogenesis, notably the development of opportunistic infections, including human cytomegalovirus, herpes simplex virus, and Epstein-Barr virus. In addition, the significance of adult and newborn/infant oral mucosa in HIV resistance and transmission was analyzed. HIV/AIDS-associated changes in the oropharyngeal mucosal epithelium and their role in promoting human papillomavirus-positive and negative neoplastic malignancy are also discussed.

CO2 Laser for Esthetic Healing of Injuries and Surgical Wounds with Small Parenchymal Defects in Oral Soft Tissues.

A number of studies have recently demonstrated the effectiveness of CO2 laser irradiation for the repair and regeneration of scar tissue from injuries or surgical wounds. However, such studies of the oral mucosa are highly limited. Previous studies using CO2 laser irradiation have indicated that two factors contribute to esthetic healing, namely, artificial scabs, which are a coagulated and carbonized blood layer formed on the wound surface, and photobiomodulation therapy (PBMT) for suppressing wound scarring and promoting wound healing. This review outlines basic research and clinical studies of esthetic healing with the use of a CO2 laser for both artificial scab formation by high-intensity laser therapy and PBMT in the treatment of injuries and surgical wounds with small parenchymal defects in oral soft tissues. The results showed that the wound surface was covered by an artificial scab, enabling the accumulation of blood and the perfusion necessary for tissue regeneration and repair. Subsequent PBMT also downregulated the expression of transformation growth factor-b1, which is involved in tissue scarring, and decreased the appearance of myofibroblasts. Taken together, artificial scabs and PBMT using CO2 lasers contribute to the suppression of scarring in the tissue repair process, leading to favorable esthetic and functional outcomes of wound healing.

Diagnostic Algorithm for Surgical Management of Limbal Stem Cell Deficiency.

BACKGROUND: Limbal stem cell deficiency (LCSD) presents several challenges. Currently, there is no clearly defined systematic approach to LSCD diagnosis that may guide surgical tactics. METHODS: The medical records of 34 patients with LSCD were analyzed. Diagnostic modalities included standard (visometry, tonometry, visual field testing, slit-lamp biomicroscopy with corneal fluorescein staining, Schirmer test 1, ultrasonography) and advanced ophthalmic examination methods such as anterior segment optical coherence tomography, in vivo confocal microscopy, impression cytology, and enzyme-linked immunoassay. RESULTS: Standard ophthalmological examination was sufficient to establish the diagnosis of LSCD in 20 (58.8%) cases, whereas advanced evaluation was needed in 14 (41.2%) cases. Depending on the results, patients with unilateral LSCD were scheduled to undergo glueless simple limbal epithelial transplantation (G-SLET) or simultaneous G-SLET and lamellar keratoplasty. Patients with bilateral LSCD with normal or increased corneal thickness were enrolled in the paralimbal oral mucosa epithelium transplantation (pLOMET) clinical trial. CONCLUSIONS: Based on the diagnostic and surgical data analyzed, the key points in LSCD diagnosis were identified, helping to guide the surgeon in selecting the appropriate surgical procedure. Finally, we proposed a novel step-by-step diagnostic algorithm and original surgical guidelines for the treatment of patients with LSCD.

Pediatric neuropsychiatric syndromes associated with infection and microbiome alterations: clinical findings, possible role of the mucosal epithelium, and strategies for the development of new animal models.

INTRODUCTION: Pediatric obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD) have been associated with respiratory tract infections and alterations in the intestinal microbiome, respectively. Pediatric Acute-onset Neuropsychiatric Syndromes (PANS) refers to the sudden onset of neuropsychiatric symptoms that are triggered by several infectious and non-infectious factors. Studies indicate that inflammation plays an important etiological role in PANS, as well as in ASD associated with gut dysbiosis. AREAS COVERED: The present review provides an overview of clinical studies of PANS and ASD associated with gastrointestinal symptoms, as well as existing strategies for investigating these syndromes in rodent models. The authors highlight similarities between these syndromes that may provide clues to common etiological mechanisms. EXPERT OPINION: Although data from animal models are consistent with an important role for anti-neuronal antibodies in PANS triggered by GAS infection, we lack models for identifying pathophysiological mechanisms of PANS associated with other infectious and noninfectious triggers. The authors propose an animal modeling strategy that incorporates known vulnerability and triggering factors for PANS into the modeling process. This novel strategy should expand our understanding of the pathophysiology of PANS, as well as facilitate the development of new pharmacological treatments for PANS and related syndromes.

Space-making effect for new bone formation by suppressing scar contraction of mucosal epithelium of rat tooth extraction wound using diode laser and CO2 laser treatment.

Background/purpose: As an extraction wound closes, the mucosal epithelium of the tooth extraction wound impedes the space for new bone formation by invading into the extraction socket. Thus, the height of the alveolar crest decreases, causing significant depression of the alveolar mucosa. In this study, we created a rat tooth extraction model and examined the effects of laser irradiation by CO2 and diode on the dynamics of myofibroblast expression through α-SMA, and TGF-ß1. Materials and methods: After tooth extraction of five-week-old male Wistar rats, they were divided into two laser treatment groups (CO2 laser or diode laser was irradiated into tooth extraction socket) and non-laser treatment group (control group). Surrounding tissues, including the extraction socket, were removed at 3, 5, 7, and 21 days after tooth extraction and the expression of α-SMA and TGF-ß1 was verified using immunohistological techniques (6 animals in each group and each period, 72 animals in total). Results: α-SMA-positive cells and TGF-ß1-positive areas were significantly lower in the two laser treatment groups than in the control group. Particularly, the diode group almost had no TGF-ß1-positive areas on the 21st day when healing after tooth extraction was deemed to be completed. Conclusion: Both CO2 and diode laser irradiation of tooth extraction wounds decreases α-SMA-positive cells and TGF-ß1-positive areas. Further, it causes a decrease in myofibroblast expression and suppresses the invasion of mucosal epithelium into the extraction socket. Therefore, laser irradiation may exert a space-making effect for new bone formation and also contribute to socket preservation.

Virus-associated disruption of mucosal epithelial tight junctions and its role in viral transmission and spread.

Oropharyngeal, airway, intestinal, and genital mucosal epithelia are the main portals of entry for the majority of human pathogenic viruses. To initiate systemic infection, viruses must first be transmitted across the mucosal epithelium and then spread across the body. However, mucosal epithelia have well-developed tight junctions, which have a strong barrier function that plays a critical role in preventing the spread and dissemination of viral pathogens. Viruses can overcome these barriers by disrupting the tight junctions of mucosal epithelia, which facilitate paracellular viral penetration and initiate systemic disease. Disruption of tight and adherens junctions may also release the sequestered viral receptors within the junctional areas, and liberation of hidden receptors may facilitate viral infection of mucosal epithelia. This review focuses on possible molecular mechanisms of virus-associated disruption of mucosal epithelial junctions and its role in transmucosal viral transmission and spread.

Elucidating Molecular Interactions of Ten Natural Compounds Targeting E6 HPV High Risk Oncoproteins Using Microsecond Molecular Dynamics Simulations.

BACKGROUND: Cervical cancer is a major public health issue worldwide, occurring in the vast majority of cases (85%) in low-income countries. Human papillomavirus (HPV) mainly infects the mucosal epithelium, and a small portion causes over 600,000 cases every year worldwide at various anatomical spots, mainly leading to anogenital and head and neck. INTRODUCTION: The E6 oncoprotein encoded by cancer-associated alpha HPV can transform epithelial cells into tumorigenic tissue. Therapy for this infection and blocking of the HPV E6 oncoprotein could be provided with cost-effective and abundant natural products which are an exponentially growing topic in the literature. Finding an active natural compound that readily blocks HPV E6 oncoprotein which could be available for developing countries without expensive extraction processes or costly synthetic pathways is of major interest. METHODS: Molecular dynamics simulation was performed using the most up-to-date AMBER protein force field ff14SB and a GPU enabled high performance computing cluster. RESULTS: In this research, we present a study of the binding properties between 10 selected natural compounds that are readily available with two variants of the E6 oncoprotein types (HPV-16 and HPV-18) using 10+ microsecond molecular dynamics simulations. CONCLUSION: Our results suggest that crocetin, ergosterol peroxide and κ-carrageenan natural products bind strongly to both HPV-16 and HPV-18 and could potentially serve as a scaffolding for further drug development.