Search Results (410)

Objectives: This study aims to explore the histological dimensions of the gingiva and the alveolar mucosa and to evaluate their associations with gingival phenotypic parameters, including gingival thickness (GT), keratinized tissue width (KTW), and gingival transparency. Methods: Histological and clinical assessments were performed on 45 healthy volunteers. Gingival and mucosal tissue samples were collected from the mucogingival junction region of one maxillary central incisor. Histomorphometric analysis included measurements of gingival and mucosal thickness, epithelial thickness, connective tissue thickness, epithelial papilla length and density, and keratinization. Clinical parameters included KTW and probe visibility upon insertion into the gingival sulcus. Correlations were statistically analyzed between clinical and histological parameters. Results: Probe visibility showed no significant correlations with any assessed parameter. Histological gingival thickness strongly correlated with gingival connective tissue thickness, moderately with epithelial thickness and papilla length, and weakly with papilla density. Mucosal thickness was strongly associated with connective tissue thickness and moderately with keratinization, but not with other parameters. KTW exhibited weak correlations with epithelial thickness and papilla length. Conclusions: Variability in gingival and mucosal thickness is primarily determined by connective tissue thickness, with a smaller contribution from the epithelium. Increased thickness is associated with longer, sparser epithelial papillae and with a tendency toward higher keratinization. KTW is significantly associated with epithelial thickness and papilla length, underscoring its relevance in gingival phenotype characterization. Full article

Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with low survival rates, especially in advanced stages, despite improved therapies. New developments show that immune checkpoint inhibitors (ICIs) are promising treatment options. A better understanding of immune suppression in OSCC could enable new therapeutic approaches and effective ICI combinations. Methods: The aim of this cross-sectional study was to investigate the significance of the differential expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD28 and their ligands CD80 and CD86 for the diagnosis and treatment of OSCC. To this end, mRNA expression was analysed by RT-PCR and compared in 65 healthy oral mucosa samples (NOM) and 104 OSCC samples. Results: The expression of CTLA-4 (a soluble and membrane-bound isoform) was increased in OSCC by 1.72-fold (p = 0.004) and 6.88-fold (p < 0.001), respectively. There was no significant difference for CD28 (p = 0.283), nor for the soluble isoform of CD86 (p = 0.845). The membrane isoform of CD86 was increased in OSCC by a factor of 1.39 (p = 0.009) and CD80 by 6.11-fold (p < 0.001). Conclusions: The results show a significant association between CTLA-4, CD80 and membrane-bound CD86 expression and diagnosis. They could improve diagnostics in multi-marker approaches and serve as therapeutic targets for ICI strategies. In particular, the data indicate a stronger immunosuppressive role of CD80 compared to CD86 in a tumor tissue context, suggesting the exploration of anti-CTLA-4 and anti-CD80 antibody combinations in animal models. Full article

This scoping review explores the expression patterns and molecular features of sarcoglycans (SGs) in non-muscle organs, challenging the long-standing assumption that their function is confined to skeletal and cardiac muscle. By analyzing evidence from both animal models and human studies, the review highlights the widespread presence of SG subunits in organs, including the nervous system, glands, adipose tissue, oral mucosa, retina, and other structures, with distinct regional and cell-type-specific patterns. Studies on the central nervous system demonstrate a widespread “spot-like” distribution of SG subunits in neurons and glial cells, implicating their involvement in synaptic organization and neurotransmission. Similarly, SGs maintain cellular integrity and homeostasis in glands and adipose tissue. At the same time, the altered expression of SGs is associated with pathological conditions in the gingival epithelium of the oral mucosa. These findings underscore the multifaceted roles of SGs beyond muscle, suggesting that they may contribute to cellular signaling, membrane stability, and neurovascular coupling. However, significant gaps remain regarding SG post-translational modifications and functional implications in non-muscle organs. Future research integrating molecular, cellular, and functional approaches in animal models and human tissues is essential to fully elucidate these roles and explore their potential as therapeutic targets in various diseases. Full article

Background and Objectives: Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide. Genetic and epigenetic changes, especially DNA methylation alterations, are key in CRC development. LINE-1 hypomethylation marks global DNA methylation loss and genomic instability, making it a potential early CRC biomarker. This study investigates the methylation status of LINE-1 in colorectal adenocarcinoma, precancerous lesions (tubular and serrated adenomas), and the surrounding normal mucosa, aiming to elucidate its role as an epigenetic marker in early colorectal tumorigenesis. Materials and Methods: Paired lesion and normal tissue samples from 66 patients were analyzed for LINE-1 methylation at three CpG sites using bisulfite pyrosequencing. Results: Adenocarcinomas and tubular adenomas showed significant hypomethylation, especially at loci A and B, while serrated adenomas exhibited no significant differences. Conclusions: LINE-1 hypomethylation is associated with colorectal tumorigenesis, with distinct patterns observed between tubular and serrated adenomas, indicating distinct pathways forming and progressing specific adenomas. These findings support the potential of LINE-1 methylation as an early epigenetic biomarker for CRC risk stratification and highlight the need for further research into its clinical utility. Full article

Background/Objectives: Keratins form a crucial component of the epithelial cytoskeleton, playing an essential role in maintaining tissue architecture and coordinating key cellular functions. KRT80 is a type II keratin that has emerged as an oncogenic driver in several malignancies, yet its involvement in colorectal cancer (CRC) remains unclear. Here, we investigated the molecular interaction between miR-195-5p, KRT80 expression, and CRC growth. Methods: Potential miR-195-5p binding sites in the KRT80 3′-UTR were identified through the use of integrated bioinformatic analyses, while publicly available datasets confirmed a significant overexpression of KRT80 in CRC tissues compared to normal mucosa. This finding was further validated through the use of mRNA and protein analysis in paired tumor and adjacent normal samples from CRC patients. Results: Functional assays involving CRC cell lines showed that transfection with miR-195-5p mimics led to a significant downregulation of KRT80 expression, reflecting the effects of direct KRT80 silencing by siRNA. Both molecular approaches induced G₁-phase cell cycle arrest, concomitantly with reductions in G₂/M populations. Furthermore, the in vivo delivery of miR-195-5p mimics in a mouse model of colitis-associated CRC resulted in a significant reduction in Krt80 expression in the colon. Conclusions: Collectively, our results reveal that miR-195-5p negatively regulates KRT80 expression, contributing to its tumor-suppressive activity in colorectal cancer and highlighting a molecular mechanism with potential therapeutic relevance. Full article

Background and Objectives: Oral cancer remains a critical global health burden. Oral potentially malignant disorders (OMPDs) such as leukoplakia and oral lichen planus can precede oral squamous cell carcinoma (OSCC). Inflammation, tissue remodeling, and dysregulated signaling pathways are central to malignant transformation. This observational study aimed to evaluate the expression patterns of Maspin, β-catenin, and MMP-14 by immunohistochemistry (IHC) in oral leukoplakia, oral lichen planus, OSCC, and normal mucosa, exploring associations with lesion type, with no prognostic inferences drawn from a single timepoint. Materials and Methods: Biopsy specimens from 67 patients presenting with oral lesions (27 leukoplakia, 22 lichen planus, 18 OSCC), and 10 healthy controls were collected between January 2015 and January 2023. Inclusion criteria were age over 18 years and no other chronic illness, and a histopathologic diagnosis of oral leukoplakia, oral lichen planus or OSCC. Exclusion criteria were smokers, alcohol abuse, and prior head and neck radiotherapy, prior immunosuppressive therapy, systemic inflammatory diseases, absence of histopathological confirmation of the clinical diagnosis, and squamous cell carcinoma of the vermilion. Two pathologists independently scored staining in 10 high-power fields. Normal mucosa served as baseline. Immunohistochemical analysis was conducted using specific antibodies targeting Maspin, β-catenin, and MMP-14. Marker expression was assessed using a semi-quantitative scoring system based on staining intensity and classified into four categories: negative (−), weakly positive (+) for 1–10%, moderately positive (++) for 11–50%, and highly positive (+++) for more than 50%. Results: Maspin showed moderate (++) cytoplasmic/nuclear staining in leukoplakia and lichen planus in 78% of cases and high (+++) in OSCC and stroma in all cases. β-catenin shifted from membranous moderate positivity in 100% of OPMD cases to cytoplasmic/nuclear high positivity in all cases of OSCC. MMP-14 showed positivity (+) in 89% of OPMDs and high positivity (+++) in 100% of OSCC. Conclusions: Maspin, β-catenin, and MMP-14 exhibit distinct expression patterns across lesion types. While Maspin may reflect early tissue remodeling, β-catenin and MMP-14 changes suggest Wnt signaling activation and matrix remodeling in OSCC. Longitudinal studies are needed to establish their predictive value. This observational study refrains from prognostic claims and instead highlights biomarkers for future validation. Full article

Aging affects all tissues in an organism, including the tracheobronchial tree, with structural and functional changes driven by mechanisms such as oxidative stress, cellular senescence, epigenetic modifications, mitochondrial dysfunction, and telomere shortening. Airway aging can be accelerated by intrinsic or extrinsic factors. This review brings together information from the literature on the molecular changes occurring in all layers of the tracheobronchial airway wall. It examines the biomolecular changes associated with aging in the mucosa, submucosa, cartilage, and smooth muscle of the airways. At the mucosal level, aging reduces ciliary function and disrupts mucin homeostasis, impairing mucociliary clearance and contributing to chronic respiratory diseases such as COPD (Chronic Obstructive Pulmonary Disease). Cellular senescence and oxidative stress drive extracellular matrix remodeling and chronic inflammation. Airway cartilage undergoes age-related changes in collagen and fibronectin composition, leading to increased stiffness, while heightened MMP (Matrix Metalloproteinases) activity exacerbates ECM (extracellular matrix) degradation. In airway smooth muscle, aging induces changes in calcium signaling, hypertrophy, and the secretion of pro-inflammatory mediators, further perpetuating airway remodeling. These changes impair respiratory function and increase susceptibility to chronic respiratory conditions in the elderly. By consolidating current knowledge, this review aims to provide a comprehensive overview of the molecular changes occurring in the respiratory tract with aging and to highlight new molecular perspectives for future research on this topic. Full article

Non-Hodgkin lymphomas (NHLs) encompass a diverse group of neoplasms arising from the clonal proliferation of B-cell progenitors, T-cell progenitors, mature B-cells, mature T-cells, and natural killer (NK) cells. These malignancies account for over 90% of lymphoid neoplasms. The link between the gut microbiome and neoplasms has been extensively studied in recent years. Growing evidence suggests that the gut microbiome may be involved not only in the development of the disease, but also in modulating the efficacy of implemented therapies. In this review, we summarize the current knowledge on the potential involvement of the gut microbiome in the development of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mucosa-associated lymphoid tissue (MALT) lymphoma, and NK/T-cell lymphoma, including cutaneous T-cell lymphoma (CTCL). Moreover, we discuss the relationship between gut microbiome changes before and after treatment and their association with treatment outcomes, focusing on chemotherapy and CAR T-cell therapy. Full article

Stress urinary incontinence (SUI) is characterized by the involuntary leakage of urine when bladder pressure exceeds urethral closing pressure during routine activities such as physical exertion, coughing, exercise, or sneezing. SUI is the most prevalent form of urinary incontinence, with a reported prevalence ranging from 10% to 70%, and its incidence increases with age. As the global population continues to age, the prevalence and clinical significance of SUI are expected to rise accordingly. The pathophysiology of SUI is primarily driven by two mechanisms: urethral hypermobility, resulting from compromised supporting structures, and intrinsic urethral sphincter deficiency, characterized by the deterioration of urethral mucosa and muscle tone. Current treatment options for SUI include conservative management strategies, which heavily rely on patient adherence and are associated with high recurrence rates, and surgical interventions, such as sling procedures, which offer effective solutions but are costly and carry the risk of adverse side effects. These limitations highlight the urgent need for more effective and comprehensive treatment modalities. Exosomes, nano-sized (30–150 nm) extracellular vesicles secreted by nearly all cell types, have emerged as a novel therapeutic option due to their regenerative, anti-fibrotic, pro-angiogenic, anti-apoptotic, anti-inflammatory, and anti-hypoxic properties. These biological functions position exosomes as a promising alternative to conventional therapies for SUI. Exosome therapy has the potential to enhance tissue regeneration, restore urethral function, and repair nerve and muscle damage, thereby reducing symptom burden and improving patients’ quality of life. Additionally, exosome-based treatments could offer a less invasive alternative to surgery, potentially decreasing the need for repeated interventions and minimizing complications associated with current procedures. In this literature review, we critically assess the current state of research on the potential use of exosomes in treating SUI, highlighting their therapeutic mechanisms and potential clinical benefits. Full article

The gut microbiota plays an important role in the development of colorectal tumors. However, the underlying mechanisms remain unclear. In this study, we examined the effects of fecal microbiota transplantation (FMT) on azoxymethane (AOM)-induced colorectal tumors in obese mice. We divided the study subjects into the following five groups: high-fat diet (HFD), normal diet (ND), ND+exercise (Ex), HFD+FMT from ND-alone donor (HFD+FMT(ND alone)), and HFD+FMT from ND+Ex donor (HFD+FMT(ND+Ex)). The Ex group performed treadmill exercise for 15 weeks. Thereafter, fecal and colonic mucus samples were extracted for microbiome analysis. The deoxyribonucleic acid sample was collected from the feces and colonic mucosa, and V3–V4 amplicon sequencing analysis of the 16S rRNA gene was performed using MiSeq. The number of polyps was significantly lower in the ND (6.0 ± 1.6) and ND+Ex (1.8 ± 1.3) groups than in the HFD group (11.4 ± 1.5). The ND+Ex group had significantly fewer polyps than the ND group. The HFD+FMT(ND alone) (5.2 ± 0.8) and HFD+FMT(ND+Ex) (2.8 ± 2.6) groups also had significantly fewer polyps than the HFD group. The IL-15 mRNA levels in the colonic tissues were significantly higher in the HFD+FMT(ND alone) group than in the ND group. Fecal ω-muricholic acid concentrations were significantly higher in the HFD+FMT(ND alone) group than in the ND group and in the HFD+FMT(ND+Ex) group than in the ND+Ex group. The ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of Lacyobacillaceae than the HFD group. In the FMT group, Erysipelotrichaceae and Tannerellaceae were significantly less abundant. Compared with the HFD group, the ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of Muribaculaceae and a significantly higher abundance of Lactobacillaceae and Rikenellaceae in common among the ND and ND+Ex groups. The common and significantly less common species were Bacteroidaceae in the FMT group and Lactobacillaceae and Rikenellaceae in the ND alone and ND+Ex groups. Bacteroidaceae and Lachnospiraceae were significantly less common in the FMT group. We found that FMT inhibited AOM-induced colorectal tumorigenesis in obese mice. Furthermore, the fecal concentrations of short-chain fatty acids, bile acids, microbiota, and mucosa-associated microbiota differed between the FMT and diet/EX groups, suggesting that the inhibitory effect of FMT on colorectal tumorigenesis may be due to mechanisms different from those of ND alone and ND+Ex. Full article

Background: Ensuring a minimum peri-implant keratinized mucosa width (PIKM-W) is critical for maintaining dental implant health, as inadequate PIKM-W is associated with increased risks of plaque accumulation, mucosal inflammation, and peri-implantitis. While epithelialized connective tissue grafts (ECTGs) are considered the gold standard for soft tissue augmentation, they often lead to significant patient morbidity. Xenogeneic dermal matrices (XDMs) offer a less invasive alternative, but are prone to shrinkage, particularly in the mandible. The aim of this study was to evaluate a new surgical method to overcome these limitations with the combination of a narrow band of ECTG (autogenous strip graft, ASG) and an XDM to augment the PIKM-W in the posterior mandible. Methods: Twelve patients with a PIKM-W of less than 2 mm in the mandible underwent peri-implant soft tissue augmentation using this combined approach. Changes in the PIKM-W were measured preoperatively; immediately postoperatively; and at 1, 3, 6, 9, and 12 months. Graft remodeling (shrinkage or contraction) and PIKM thickness (PIKM-T) were also evaluated over time. Results: Preoperatively, the mean PIKM-W was 0.39 ± 0.40 mm and the PIKM-T was 1.36 ± 0.43 mm. At 6 months, the mean PIKM-W was 4.93 ± 0.98 mm and the PIKM-T was 2.88 ± 0.80 mm, with shrinkage of 39.2 ± 14.1%. By 12 months, the mean PIKM-W stabilized at 4.58 ± 1.28 mm and the PIKM-T stabilized at 2.83 ± 0.65 mm, with shrinkage of 42.2% ± 16.8%. Conclusions: There were statistically significant differences in clinical parameters between the baseline and 6 and 12 months (p < 0.05). This technique demonstrated the potential for stable augmentation of PIKM-W and PIKM-T over time, with manageable shrinkage. However, further studies with larger sample sizes are needed to confirm its clinical efficacy as an alternative for mandibular keratinized mucosa augmentation around implants. Full article

Background/Objectives: The clinical characteristics of colorectal mucosa-associated lymphoid tissue (MALT) lymphoma remain poorly defined, and there is no standardized treatment for the disease. Therefore, we investigated the clinical characteristics of colorectal MALT lymphoma and its prognosis based on different treatment modalities. Methods: A retrospective analysis was performed on patients diagnosed with colorectal MALT lymphoma from 2003 to 2021 across six hospitals in Korea’s Busan–Ulsan–Gyeongnam area. Macroscopic findings classified all cases into polyposis type, mass-forming type, subepithelial lesion type, and inflammatory type. Results: Fifty-one patients were enrolled. The median age was 59 years, and 27 patients (52.9%) were male. Five patients (9.8%) were stage IV at initial diagnosis. As for the endoscopic type, the polyposis type was the most common (39.2%). There was no statistically significant difference in disease progression according to the endoscopic type (p = 0.813). Three cases of disease progression were confirmed in stage I after treatment, and one of them died due to disease progression. No disease progression was identified in other stages. According to the treatment modality, disease progression was identified in 1 of 16 patients who underwent endoscopic resection and 2 of 16 patients who underwent chemotherapy. There was no disease progression in the observation group. However, there was no statistically significant difference in disease progression according to treatment modality (p = 0.889). Conclusions: Colorectal MALT lymphoma showed good prognosis regardless of the initial stage, endoscopic type, or treatment modality. Full article

Urethral reconstruction remains a challenge. Indeed, the use of oral mucosa, the reference biomaterial for urethroplasty, is associated with two main drawbacks: the limited availability of autologous tissues and potential short- and long-term complications, especially for patients with recurrences or severe anomalies. Therefore, the development of alternative approaches, such as urethral tissue engineering, is necessary. A new type of human urethral substitute devoid of exogenous biomaterials has been reconstructed in vitro. It presented sufficient mechanical strength and had histological and functional properties comparable to native tissues. These reconstructed tissues were implanted in vivo to repair hypospadias induced in tacrolimus-immunosuppressed rabbits via a two-stage urethroplasty. In the first stage, the distal part of the native urethra was removed, and a flat graft was implanted, leaving the urethra open proximally. Twelve weeks later, the graft was tubularized to create a neourethra, reproducing the usual clinical scenario. The results obtained for the experimental group were less effective than for the control group, with a success rate of 50% after excluding the animal affected by unwanted events unrelated to urethroplasty, and it is possible that the animal model or surgical technique used was not suitable and should be modified. Nevertheless, half of the urethral substitutes grafted on rabbits showed successful integration. These self-assembled artificial tissues represent promising substitutes for urethroplasty. Full article

Transmucosal drug products, such as aerosols, films, semisolids, suppositories, and tablets, have been developed for the treatment of various human diseases and conditions. Transmucosal drug absorption is highly influenced by the biological structures of the mucosa and the physiological environment specific to the administration route (e.g., nasal, rectal, and vaginal). Over the last few decades, in vitro permeation testing (IVPT) using animal tissues or in vitro cell cultures have been utilized as a cost-effective and efficient tool for evaluating drug release and permeation behavior, assisting in formulation development and quality control of transmucosal drug delivery systems. This review summarizes the key mucosal permeation barriers associated with representative transmucosal administration routes, as well as considerations for IVPT method development. It highlights various IVPT methods, including vertical diffusion cell, flow-through diffusion cell, Ussing chamber, and transwell systems. Additionally, future perspectives are discussed, such as the use of optical methods to study in vitro drug permeation and the development of in vitro–in vivo correlation (IVIVC) for transmucosal drug development. The potential of IVPT as part of in vitro bioequivalence assessment strategies for locally acting transmucosal drug products is also highlighted. Full article

Introduction: Primary colorectal lymphoma (PCL) is a very rare disease with limited information regarding its macroscopic features. This retrospective descriptive study aims to identify the macroscopic characteristics of PCL and explore treatment trends and outcomes with respect to histopathologic subtypes. Methods: This IRB-approved study from a large academic medical center identified 66 patients with colorectal lymphoma from 1998 to 2022 from a tumor registry. Thirty-four patients met the inclusion criteria of having PCL with available endoscopic data. The macroscopic features of each lesion were identified. Treatment trends and outcomes were examined at the patient level. Data were described using frequency and percentages for categorical characteristics and the median and interquatile range (IQR) for continuous outcomes. Results: A total of 77 PCL lesions were identified. Most were identified on screening or surveillance colonoscopies or colonoscopies performed after abnormal imaging (61.8%). Diffuse large B cell lymphoma (DLBCL) had the highest prevalence (N = 24), followed by follicular lymphoma (n = 21), mantle cell (n = 16), mucosa-associated lymphoid tissue (MALT) (n = 14), then Burkitt’s (n = 2). More mantle cell (93.8%) and follicular (90.5%) lymphomas were sessile. More MALT lymphomas were ulcerated (71.4%). A higher proportion of follicular (76.2%) and mantle cell (71.4%) lymphomas were diminutive (≤5 mm). More MALT (78.6%), DLBCL (75.0%), and Burkitt’s (100%) were large (≥20 mm). More lesions were found in the sigmoid colon (26.0%), followed by the rectum (22.1%), transverse colon (18.2%), cecum (18.2%), descending colon (10.4%), and ascending colon (5.2%). Overall, most underwent immunotherapy (61.3%) and did not have radiation therapy (81.3%), endoscopic resection (75.0%), and surgery (68.8%). Patients with DLBCL demonstrated higher rates of chemotherapy (70.6%), immunotherapy (87.5%), and remission after intervention (52.9%). Conclusions: Primary colorectal lymphomas display distinct macroscopic features and appear in different locations depending on the histopathologic subtype. Most cases are identified at early stages on screening colonoscopies and demonstrate a 75% two-year survival rate. Full article