Search Results (11)

Narrow band imaging (NBI) magnification endoscopy for the diagnosis of early-stage oral cavity-related cancer and precancerous lesions can recognize oral lesions as brownish areas, and can observe intraepithelial papillary capillary loops (IPCLs) in the mucosa and submucosa to make a qualitative diagnosis of the lesion and highlight the mucosal surface microstructure to facilitate appropriate diagnosis and early treatment. IPCLs are classified from Type 0 to IV: Type 0 is normal mucosa or no blood vessels observed, e.g., in keratinization; Type I is mainly normal mucosa; Type II is mainly inflammatory sites or non-malignant lesions; Type III is mainly precancerous or suspected malignant lesions; and Type IV is cancerous or malignant lesions. NBI magnification endoscopy is a useful noninvasive method for identifying the malignant transformation of oral potentially malignant disorders (OPMDs). Oral lesions classified as IPCL Type II or higher are atypical epithelial or oral squamous cell carcinoma (OSCC); oral biopsy is recommended for early and accurate diagnosis, and is an indicator of the appropriate biopsy site in the follow-up for OPMDs. In the future, the accuracy of NBI magnification endoscopy for malignant transformation of OPMDs and OSCC will be further confirmed. Full article

Zenker’s Diverticulum (ZD) is the most common hypopharyngeal diverticulum; however, it is often underdiagnosed. It results from the herniation of the mucosa and submucosa through Killian’s Triangle. Dysphagia is the primary symptom, occurring in 80–90% of cases. The primary goal of treatment is to transect the cricopharyngeal muscle (CM) and connect the ZD cavity to the esophageal lumen. Traditional treatments include surgical open transcervical diverticulectomy and CM septomyotomy, using rigid or flexible endoscopes. However, surgery is burdened by technical difficulties and not negligible rates of adverse events (AEs). For this reason, endoscopic techniques for ZD treatment have gained traction in recent years. Flexible endoscopic septum division (FESD), introduced nearly 20 years ago, involves a full-thickness incision of the diverticular septum. The advent of third-space endoscopy has led to the application of these techniques to ZD treatment as well. Zenker-POEM (Z-POEM) and, subsequently, Per Oral Endoscopic Septomyotomy (POES) have been developed. Hybrid techniques, such as Peroral Endoscopic Diverticulotomy (POED) and tunneling-free methods, represent additional ZD treatment options. This review outlines the armamentarium of ZD endoscopic management, summarizing the characteristics of these techniques, their benefits and limitations, and highlighting future research directions. Full article

Head and neck squamous-cell carcinoma (HNSCC) is associated with aggressive local invasiveness, being a main reason for its poor prognosis. The exact mechanisms underlying the strong invasive abilities of HNSCC remain to be elucidated. Therefore, there is a need for in vitro models to study the interplay between cancer cells and normal adjacent tissue at the invasive tumor front. To generate oral mucosa tissue models (OMM), primary keratinocytes and fibroblasts from human oral mucosa were isolated and seeded onto a biological scaffold derived from porcine small intestinal submucosa with preserved mucosa. Thereafter, we tested different methods (single tumor cells, tumor cell spots, spheroids) to integrate the human cancer cell line FaDu to generate an invasive three-dimensional model of HNSCC. All models were subjected to morphological analysis by histology and immunohistochemistry. We successfully built OMM tissue models with high in vivo–in vitro correlation. The integration of FaDu cell spots and spheroids into the OMM failed. However, with the integration of single FaDu cells into the OMM, invasive tumor cell clusters developed. Between segments of regular epithelial differentiation of the OMM, these clusters showed a basal membrane penetration and lamina propria infiltration. Primary human fibroblasts and keratinocytes seeded onto a porcine carrier structure are suitable to build an OMM. The HNSCC model with integrated FaDu cells could enable subsequent investigations into cancer cell invasiveness. Full article

ACE inhibitors, sartans, and sacubitril are among the most important drugs for the prevention of cardiovascular mortality and morbidity. At the same time, they are known to cause non-allergic bradykinin-mediated angioedema, a potentially fatal swelling of the mucosa and/or submucosa and deeper skin without signs of urticaria or pruritus, occurring mainly in the head and neck region. In contrast with hereditary angioedema, which is also mediated by bradykinin, angioedema triggered by these drugs is by far the most common subtype of non-allergic angioedema. The molecular mechanisms underlying this type of angioedema, which are discussed here, are not yet sufficiently understood. There are a number of approved drugs for the prevention and treatment of acute attacks of hereditary angioedema. These include inhibitors of bradykinin synthesis that act as kallkrein inhibitors, such as the parenterally applied plasma pool, and recombinant C1 esterase inhibitor, ecallantide, lanadelumab, and the orally available berotralstat, as well as the bradykinin receptor type 2 antagonist icatibant. In contrast, no diagnostic tools, guidelines, or treatments have yet been approved for the diagnosis and treatment of acute non-allergic drug-induced angioedema, although it is more common and can take life-threatening courses. Approved specific drugs and a structured diagnostic workflow are needed for this emergency diagnosis. Full article

Plasma cell mucositis (PCM) is an unusual idiopathic disorder characterized by dense infiltrates of plasma cells in submucosa. Clinical phenotypes of oral plasma cell mucositis (o-PMC) are heterogenous. A systematic review has been conducted, aiming to synthesize the available evidence on o-PCM. Literature search, study design, and data analysis were performed following PRISMA guidelines. The SPIDER and the PICO tools were used to structure the research question. In all, 79 case reports and 19 case series on a total of 158 patients (85 females and 73 males; average age: 44.1 years) were identified. Among oral sites involved, gingiva (65.82%) was the most frequent site. The main clinical phenotype was erythema (99.37%). In relation to symptoms, pain (60.76%) was the most reported. On histological examination, all samples showed a dense inflammatory infiltration with predominant plasma cells. The treatment regimens of o-PCM were summarized in six groups: irritant removal; topical/systemic corticosteroids; topical/systemic immunosuppressants/immunomodulators; surgery and similar treatments; radiotherapy and chemotherapy; other therapies, such as antifungals, antibiotics, and antivirals drugs. This is the first systematic review aimed to synthesize the findings of studies on o-PCM. The lack of universally shared information on etiological factors and the absence of international consensus of pharmacological protocols make o-PCM a diagnostic and therapeutic challenge. Full article

Malvaviscus arboreus is used in traditional Mexican medicine to treat gastrointestinal diseases. Therefore, a mixture of Kaempferol-O-sambubioside and Kaempferol-O-sophoroside (MaSS) isolated from flowers of this species was tested as a preventive treatment on gastric lesions induced with ethanol in rats. MaSS was obtained by chromatographic methods and administered by oral pathway to male Sprague Dawley rats with ethanol-induced gastric lesions. Pretreatment with MaSS at doses of 30, 90, 120, and 180 mg/kg significantly prevents gastric lesions, inhibits the increment in relative stomach weight (%) in gastric IL-6, and also provokes an increment of IL-10 concentration and catalase activity. Finally, MaSS prevented edema in the mucosa and submucosa and diminished microscopic gastric lesions provoked by ethanol. Full article

This study aimed to demonstrate the feasibility of near-infrared (NIR) fluorescence imaging using methylene blue (MB) for detecting oral sentinel lymph nodes (SLNs) in rats and compared MB’s tracer effects with those of indocyanine green (ICG) in SLN mapping. Different concentrations of MB were injected into the rats’ left lingual submucosa to determine the optimal concentration by using a continuous (1 h) MI-1 fluorescence imaging system. To compare the tracer effects of the optimal MB concentration with ICG in oral SLN mapping, MI-1 imaging was continuously monitored for 12 h. The mean signal-to-background ratio (SBR) of the SLNs and SLN fluorescence area fraction were analyzed. SLNs and lymphatic vessels were clearly visible in all rats. The optimal injection dose of MB infected into lingual submucosa for NIR fluorescence imaging was 0.2 mL of 6.68 mM MB. During continuous monitoring for 12 h, the mean SBR of the SLNs was significantly higher in the ICG groups than in the MB groups (p < 0.001). However, the area fraction of SLN fluorescence in the ICG groups increased continuously, owing to strong fluorescent contamination. This study examined the feasibility of detection of draining lymph nodes in the oral cavity of rats using MB NIR fluorescence imaging. MB causes less fluorescent contamination than does ICG, which shows promise for clinical research and application. Full article

Most of the current SARS-CoV-2 vaccines are based on parenteral immunization targeting the S protein. Although protective, such vaccines could be optimized by inducing effective immune responses (neutralizing IgA responses) at the mucosal surfaces, allowing them to block the virus at the earliest stage of the infectious cycle. Herein a recombinant chimeric antigen called LTB-RBD is described, which comprises the B subunit of the heat-labile enterotoxin from E. coli and a segment of the RBD from SARS-CoV-2 (aa 439-504, carrying B and T cell epitopes) from the Wuhan sequence and the variant of concern (VOC)—delta. Since LTB is a mucosal adjuvant, targeting the GM1 receptor at the surface and facilitating antigen translocation to the submucosa, this candidate will help in designing mucosal vaccines (i.e., oral or intranasal formulations). LTB-RBD was produced in E. coli and purified to homogeneity by IMAC and IMAC-anionic exchange chromatography. The yields in terms of pure LTB-RBD were 1.2 mg per liter of culture for the Wuhan sequence and 3.5 mg per liter for the delta variant. The E. coli-made LTB-RBD induced seric IgG responses and IgA responses in the mouth and feces of mice when subcutaneously administered and intestinal and mouth IgA responses when administered nasally. The expression and purification protocols developed for LTB-RBD constitute a robust system to produce vaccine candidates against SARS-CoV-2 and its variants, offering a low-cost production system with no tags and with ease of adaptation to new variants. The E. coli-made LTB-RBD will be the basis for developing mucosal vaccine candidates capable of inducing sterilizing immunity against SARS-CoV-2. Full article

Comparable outcomes were published using a buccal mucosa graft (BMG) from the cheek and a lingual mucosa graft (LMG) from the sublingual area, for urethral augmentation or substitution. To date, no histological comparison between both grafts has been conducted. We histologically assessed BMG and LMG harvested during urethral surgeries, aiming to compare graft properties and vascular support. We conducted a prospective single cohort study, including oral mucosa urethroplasty patients. During surgery, graft dimensions and donor sites were collected, and a 0.5 × 0.5 cm sample was obtained from the prepared graft. Formalin-fixed paraffin-embedded samples were sliced at 4 micrometres (µm) and hematoxylin-eosin stained. Using a telepathology tool, all slides were digitalized and measured from 10× to 40× magnification. In each graft, global and individual layers thicknesses were assessed, including vascular density and area. Descriptive and comparative (parametrical and non-parametrical) statistical analysis occurred. We collected 57 grafts during 33 urethroplasties, with 30 BMG and 22 LMG, finally, included. The mean age was 56.6 (SD 15.2) years, and the mean graft length was 5.8 (SD 1.7) cm and the width was 1.7 (SD 0.4) cm. The median graft thickness was 1598.9 (IQR 1200–2100) µm, the mean epithelium layer was 510.2 (SD 223.7) µm, the median submucosa was 654 (IQR 378–943) µm. the median muscular was 477.6 (IQR 286–772) µm, the median vascular area was 5% (IQR 5–10), and the median adipose tissue area was 5% (IQR 0–20). LMG were significantly longer and narrower than BMG. Total graft thickness was similar between LMG and BMG, but the epithelium and submucosa layers were significantly thinner in LMG. The muscular layer was significantly thicker in LMG. Vascular density and vascular areas were not significantly different between both types of grafts. LMG showed significantly less adipose tissue compared with BMG. Our findings show LMG and BMG for urethroplasty surgeries share the same thickness and blood supply, despite having significantly different graft sizes as well as mucosal and submucosal layers thickness. Full article

Egyptian rousette bats (Rousettus aegyptiacus) are natural reservoir hosts of Marburg virus (MARV), and Ravn virus (RAVV; collectively called marburgviruses) and have been linked to human cases of Marburg virus disease (MVD). We investigated the clinical and pathologic effects of experimental MARV infection in Egyptian rousettes through a serial euthanasia study and found clear evidence of mild but transient disease. Three groups of nine, captive-born, juvenile male bats were inoculated subcutaneously with 10,000 TCID₅₀ of Marburg virus strain Uganda 371Bat2007, a minimally passaged virus originally isolated from a wild Egyptian rousette. Control bats (n = 3) were mock-inoculated. Three animals per day were euthanized at 3, 5–10, 12 and 28 days post-inoculation (DPI); controls were euthanized at 28 DPI. Blood chemistry analyses showed a mild, statistically significant elevation in alanine aminotransferase (ALT) at 3, 6 and 7 DPI. Lymphocyte and monocyte counts were mildly elevated in inoculated bats after 9 DPI. Liver histology revealed small foci of inflammatory infiltrate in infected bats, similar to lesions previously described in wild, naturally-infected bats. Liver lesion severity scores peaked at 7 DPI, and were correlated with both ALT and hepatic viral RNA levels. Immunohistochemical staining detected infrequent viral antigen in liver (3–8 DPI, n = 8), spleen (3–7 DPI, n = 8), skin (inoculation site; 3–12 DPI, n = 20), lymph nodes (3–10 DPI, n = 6), and oral submucosa (8–9 DPI, n = 2). Viral antigen was present in histiocytes, hepatocytes and mesenchymal cells, and in the liver, antigen staining co-localized with inflammatory foci. These results show the first clear evidence of very mild disease caused by a filovirus in a reservoir bat host and provide support for our experimental model of this virus-reservoir host system. Full article

This study was conducted for evaluation of the ability to maintain efficacy and biocompatibility of cross-linked dextran in hydroxypropyl methylcellulose (DiHM) and cross-linked dextran mixed with PMMA in hydroxypropyl methylcellulose (PDiHM), compared with hyaluronic acid (HA) filler. Saline and HA solution was administered in the negative and positive control groups, and DiHM and PDiHM were administered in the test groups (n = 10 in each group). The site of cranial subcutaneous injection was the mid-point of the interpupillary line, and the site of intraoral submucosal injection was the ridge crest 2 mm below the cervical line of the mandibular left incisor. Before and immediately after filler injection, intraoral photos and lateral cephalometric radiographs were taken for analysis and comparison of the effect of the filler on the injection sites. The filler injected areas were converted into sequential size changes (%) of the baseline. Histomorphologic examination was performed after 12 weeks. The smallest value in the filler injected area was observed during the experimental period in the normal saline group (p < 0.001), which was almost absorbed at 4 weeks (7.19% ± 12.72%). The HA group exhibited a steady decrease in sequential size and showed a lower value than the DiHM and PDiHM groups (saline < HA < DHiM, PDHiM, p < 0.001). DiHM and PDiHM tended to increase for the first 4 weeks and later decreased until 12 weeks. In this study on DiHM and PDiHM, there was no histological abnormality in cranial skin and oral mucosa. DiHM and PDiHM filler materials with injection system provide an excellent alternative surgical method for use in oral and craniofacial fields. Full article