Abnormal accumulation of collagen fibrils is a hallmark feature of oral submucous fibrosis (OSF). However, the precise characteristics and underlying mechanisms remain unclear, impeding the advancement of potential therapeutic approaches. Here, we observed that collagen I, the main component of the extracellular matrix, first accumulated in the lamina propria and subsequently in the submucosa of OSF specimens as the disease progressed. Using RNA-seq and Immunofluorescence in OSF specimens, we screened the cartilage oligomeric matrix protein (COMP) responsible for the abnormal collagen accumulation. Genetic COMP deficiency reduced arecoline-stimulated collagen I deposition significantly in vivo. In comparison, both COMP and collagen I were upregulated under arecoline stimulation in wild-type mice. Human oral buccal mucosal fibroblasts (hBMFs) also exhibited increased secretion of COMP and collagen I after stimulation in vitro. COMP knockdown in hBMFs downregulates arecoline-stimulated collagen I secretion. We further demonstrated that hBMFs present heterogeneous responses to arecoline stimulation, of which COMP-positive fibroblasts secrete more collagen I. Since COMP is a molecular bridge with Fibril-associated collagens with Interrupted Triple helices (FACIT) in the collagen network, we further screened and identified collagen XIV, a FACIT member, co-localizing with both COMP and collagen I. Collagen XIV expression increased under arecoline stimulation in wild-type mice, whereas it was hardly expressed in the Comp^-/- mice, even with under stimulation. In summary, we found that COMP may mediates abnormal collagen I deposition by functions with collagen XIV during the progression of OSF, suggesting its potential to be targeted in treating OSF.
Oral Submucous Fibrosis/pathology* ; Cartilage Oligomeric Matrix Protein/genetics* ; Animals ; Mice ; Humans ; Fibroblasts/metabolism* ; Collagen Type I/metabolism* ; Arecoline/pharmacology* ; Mouth Mucosa/metabolism* ; Cells, Cultured ; Fluorescent Antibody Technique

As the field of oral pathology has evolved, the nomenclature and classification of oral mucosal diseases with a remarkable risk of malignant transformation have undergone several modifications. In 2005, the World Health Organization (WHO) introduced the concept of oral potentially malignant disorders (OPMDs) as an alternative to the terms for oral precancerous lesions and precancerous conditions. In the consensus report by the WHO Collaborating Center for Oral Cancer of 2021, OPMD is defined as "any oral mucosal abnormality that is associated with a statistically increased risk of developing oral cancer."This definition encompasses a range of conditions, in-cluding oral leukoplakia, oral submucous fibrosis, proliferative verrucous leukoplakia, oral lichen planus, and other lesions. In light of the complex etiology, unclear pathogenesis, and carcinogenesis of OPMDs, early and precise diagnosis and treatment can contribute to the secondary prevention of oral cancer. For this reason, this review, which aims to provide a basis for the precise clinical diagnosis of OPMDs, was performed. Its aim was achieved by reviewing the historical evolution and research progress of the nomenclature, classification, and histopathological diagnostic criteria of OPMDs.
Humans ; Mouth Neoplasms/diagnosis* ; Precancerous Conditions/diagnosis* ; Leukoplakia, Oral/diagnosis* ; Lichen Planus, Oral/pathology* ; Oral Submucous Fibrosis/pathology* ; Mouth Mucosa/pathology* ; World Health Organization

OBJECTIVE: To observe the therapeutic effect of governor vessel moxibustion combined with wenyang yiqi qiwei decoction on erectile dysfunction (ED) with spleen-kidney deficiency and to explore the possible mechanism. METHODS: A total of 130 ED patients with spleen-kidney deficiency were randomized into an observation group (65 cases, 2 cases dropped off) and a control group (65 cases, 3 cases dropped off). The control group was given wenyang yiqi qiwei decoction orally, one dose daily. On the basis of the treatment in the control group, governor vessel moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) in the observation group, 110 min a time, once a day. The treatment of 4 weeks was required in both groups. Before and after treatment, 5-question international index of erectile function (IIEF-5) score, erection quality scale (EQS) score, erectile hardness assessment (EHS) score, TCM syndrome score, serum testosterone (T) level and vascular endothelial function indexes (prostaglandin I2 [PGI2], endothelin-1 [ET-1] and nitric oxide [NO] levels) were observed respectively, and the clinical efficacy was evaluated in both groups. RESULTS: After treatment, the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO were increased compared before treatment (P<0.01), the TCM syndrome scores and serum ET-1 levels were decreased compared before treatment (P<0.01) in the two groups; the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO in the observation group were higher than those in the control group (P<0.01, P<0.05), the TCM syndrome score and serum ET-1 level were lower than those in the control group (P<0.01, P<0.05). The total effective rate was 88.9% (56/63) in the observation group, which was superior to 74.2% (46/62) in the control group (P<0.05). CONCLUSION Governor vessel moxibustion combined with wenyang yiqi qiwei decoction can improve the erectile function and increase the erection hardness and quality in ED patients with spleen-kidney deficiency, its mechanism may relate to improving serum T level and vascular endothelial function.
Humans ; Male ; Administration, Oral ; Drugs, Chinese Herbal/therapeutic use* ; Erectile Dysfunction/therapy* ; Kidney/pathology* ; Kidney Diseases/complications* ; Moxibustion ; Spleen/pathology* ; Splenic Diseases/complications* ; Testosterone/blood* ; Combined Modality Therapy

Atrial Ca²⁺ handling abnormalities, mainly involving the dysfunction of ryanodine receptor (RyR) and sarcoplasmic reticulum Ca²⁺-ATPase (SERCA), play a role in the pathogenesis of atrial fibrillation (AF). Previously, we found that the expression and function of transient receptor potential vanilloid subtype 4 (TRPV4) are upregulated in a sterile pericarditis (SP) rat model of AF, and oral administration of TRPV4 inhibitor GSK2193874 alleviates AF in this animal model. The aim of this study was to investigate whether oral administration of GSK2193874 could alleviate atrial Ca²⁺ handling abnormalities in SP rats. A SP rat model of AF was established by daubing sterile talcum powder on both atria of Sprague-Dawley (SD) rats after a pericardiotomy, to simulate the pathogenesis of postoperative atrial fibrillation (POAF). On the 3rd postoperative day, Ca²⁺ signals of atria were collected in isolated perfused hearts by optical mapping. Ca²⁺ transient duration (CaD), alternan, and the recovery properties of Ca²⁺ transient (CaT) were quantified and analyzed. GSK2193874 treatment reversed the abnormal prolongation of time to peak (determined mainly by RyR activity) and CaD (determined mainly by SERCA activity), as well as the regional heterogeneity of CaD in SP rats. Furthermore, GSK2193874 treatment relieved alternan in SP rats, and reduced its incidence of discordant alternan (DIS-ALT). More importantly, GSK2193874 treatment prevented the reduction of the S2/S1 CaT ratio (determined mainly by RyR refractoriness) in SP rats, and decreased its regional heterogeneity. Taken together, oral administration of TRPV4 inhibitor alleviates Ca²⁺ handling abnormalities in SP rats primarily by blocking the TRPV4-Ca²⁺-RyR pathway, and thus exerts therapeutic effect on POAF.
Administration, Oral ; Animals ; Atrial Fibrillation/etiology* ; Calcium/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericarditis/pathology* ; Rats ; Rats, Sprague-Dawley ; Ryanodine Receptor Calcium Release Channel/pharmacology* ; Sarcoplasmic Reticulum/pathology* ; TRPV Cation Channels

After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient's condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.
Administration, Oral ; COVID-19/virology* ; Drugs, Chinese Herbal/therapeutic use* ; Exudates and Transudates ; Female ; Humans ; Inflammation/etiology* ; Lung/pathology* ; Magnoliopsida ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Pulmonary Fibrosis/etiology* ; SARS-CoV-2

The integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.
Animals ; Carcinoma, Squamous Cell ; pathology ; Cell Transformation, Neoplastic ; pathology ; Mice ; Mouth Mucosa ; Mouth Neoplasms ; pathology ; Oral Submucous Fibrosis ; pathology ; Stem Cells

The study is to investigate effects of andrographolide on experimental autoimmune myocarditis (EAM). Lewis rats were immunized on day 0 with porcine cardiac myosin to establish EAM. The EAM rats were treated with either andrographolide (25, 50, 100 mg/kg/day) or vehicle for 21 days. An antigen-specific splenocytes proliferation assay was performed by using the cells from control rats immunized with cardiac myosin. Survival rates, myocardial pathology and myocardial functional parameters (left ventricle end-diastolic pressure, ± dP/dt and left ventricular internal dimension) of EAM rats received andrographolide were significantly improved. Andrographolide treatment caused an decrease in the infiltration of CD3⁺ and CD14⁺ positive cells in myocardial tissue. Moreover, andrographolide treatment caused a reduction in the plasma levels of tumor necrosis factor-alpha, interleukin-17 (IL-17) and myosin-antibody, and an increase in the level of IL-10 in EAM rats. Oral administration of andrographolide resulted in the decreased expression of p-PI3K, p-Akt without any change of PI3K and Akt. Further results indicate andrographolide significantly inhibited myosin-induced proliferation in splenocytes, and this effect was inhibited by co-treatment of SC79 (Akt activator). Our data indicate andrographolide inhibits development of EAM, and this beneficial effect may be due to powerful anti-inflammatory activity and inhibitory effect on PI3K/Akt pathway.
Administration, Oral ; Animals ; Cardiac Myosins ; Interleukin-10 ; Interleukin-17 ; Models, Animal* ; Myocarditis* ; Pathology ; Plasma ; Rats* ; Survival Rate ; Tumor Necrosis Factor-alpha

In maxillofacial surgery, there is a significant need for the design and fabrication of porous scaffolds with customizable bionic structures and mechanical properties suitable for bone tissue engineering. In this paper, we characterize the porous Ti6Al4V implant, which is one of the most promising and attractive biomedical applications due to the similarity of its modulus to human bones. We describe the mechanical properties of this implant, which we suggest is capable of providing important biological functions for bone tissue regeneration. We characterize a novel bionic design and fabrication process for porous implants. A design concept of "reducing dimensions and designing layer by layer" was used to construct layered slice and rod-connected mesh structure (LSRCMS) implants. Porous LSRCMS implants with different parameters and porosities were fabricated by selective laser melting (SLM). Printed samples were evaluated by microstructure characterization, specific mechanical properties were analyzed by mechanical tests, and finite element analysis was used to digitally calculate the stress characteristics of the LSRCMS under loading forces. Our results show that the samples fabricated by SLM had good structure printing quality with reasonable pore sizes. The porosity, pore size, and strut thickness of manufactured samples ranged from (60.95± 0.27)% to (81.23±0.32)%, (480±28) to (685±31) μm, and (263±28) to (265±28) μm, respectively. The compression results show that the Young's modulus and the yield strength ranged from (2.23±0.03) to (6.36±0.06) GPa and (21.36±0.42) to (122.85±3.85) MPa, respectively. We also show that the Young's modulus and yield strength of the LSRCMS samples can be predicted by the Gibson-Ashby model. Further, we prove the structural stability of our novel design by finite element analysis. Our results illustrate that our novel SLM-fabricated porous Ti6Al4V scaffolds based on an LSRCMS are a promising material for bone implants, and are potentially applicable to the field of bone defect repair.
Alloys ; Bionics ; Bone Substitutes/chemistry* ; Bone and Bones/pathology* ; Compressive Strength ; Elastic Modulus ; Finite Element Analysis ; Humans ; Lasers ; Materials Testing ; Maxillofacial Prosthesis Implantation ; Porosity ; Pressure ; Printing, Three-Dimensional ; Prostheses and Implants ; Prosthesis Design ; Stress, Mechanical ; Surgery, Oral/instrumentation* ; Tissue Engineering/methods* ; Titanium/chemistry*

OBJECTIVE: To evaluate the effectiveness of oral contraceptive pill (OCP) as therapy for endometrial hyperplasia (EH) without atypia in reproductive-aged women compared with oral progestin. METHODS: A retrospective cohort study was carried out in our reproductive center. Consecutive patients diagnosed with infertility and non-atypical EH identified through electronic database who met inclusion criteria (n=309). Patients were assigned to two treatment groups: OCP (n=216) and oral progestin (n=93); clinical and reproductive outcomes were recorded. RESULTS: Reversal of EH to normal endometrium, clinical pregnancy, live birth and miscarriage rate. Women in OCP group were younger, had higher prevalence of Polycystic Ovary Syndrome and other uterine pathology and longer duration of infertility than women in progestin group. Reversal of EH was observed in 93.52% women on OCP and in 86.02% women on progestin (p=0.032; adjusted odds ratio [aOR]= 2.35; 95% confidence interval [CI]=1.06-5.21) after the initial course of treatment for 2 to 6 months. Cyclic OCP (n=184) resulted in better response to treatment compared to continuous OCP (n=32) (95.11% vs. 84.38%; p=0.039; aOR =3.60; 95% CI =1.12-11.55). Clinical pregnancy rate in OCP group was marginally higher than progestin group (87/208, 41.83% vs. 27/90, 30.00%; p=0.054). Miscarriage (25.29% vs. 29.63%; p=0.654) and live birth rate (31.25% vs. 21.11%; p=0.074) were comparable between the groups. CONCLUSION: For the first time we demonstrate that OCP is an effective therapy for non-atypical EH and is associated with higher remission rate compared with oral progestin. Reproductive outcomes are reassuring and comparable between the two groups.
Abortion, Spontaneous ; Cohort Studies ; Contraceptives, Oral, Combined ; Drug Therapy ; Endometrial Hyperplasia ; Endometrium ; Female ; Humans ; Infertility ; Live Birth ; Odds Ratio ; Pathology ; Polycystic Ovary Syndrome ; Pregnancy ; Pregnancy Rate ; Prevalence ; Progestins ; Reproductive History ; Retrospective Studies

PURPOSE: The prevalence of supernumerary teeth has been reported to be between 0.1% and 3.8%. The aim of this study was to determine the prevalence, clinical significance, and associated pathologies of fourth molars based on a retrospective study and a literature review. MATERIALS AND METHODS: A 5-year retrospective prevalence study was conducted at the Department of Oral Diagnosis and Dentomaxillofacial Radiology of Okayama University Hospital, Okayama, Japan. The study involved extracting data from the digital records of patients from January 1, 2013 through December 31, 2017. The sampling frame included all patients who had panoramic radiographs, cone-beam computed tomography (CT), and multislice CT images during the period under review. RESULTS: A total of 26,721 cases were reviewed and 87 fourth molars were identified. The prevalence of fourth molars in the 5-year study at Okayama was calculated as 0.32%. The mean age of patients with a fourth molar was 30.43 years, and the male-to-female ratio was 1:0.98. The vast majority of cases were in the maxilla (92%) and had normal shapes (89.7%); furthermore, 82.8% of cases were unerupted. CONCLUSION: The prevalence of fourth molars in the study population was found to be 0.32%, and fourth molars occurred with approximately equal frequency in males and females. Fourth molars were more common in the maxilla and were predominantly unerupted and small.
Cone-Beam Computed Tomography ; Cross-Sectional Studies ; Diagnosis, Oral ; Female ; Humans ; Japan ; Male ; Maxilla ; Odontogenic Cysts ; Odontoma ; Pathology ; Prevalence ; Retrospective Studies ; Tooth, Supernumerary