The effects of pterygomaxillary disjunction in surgically assisted rapid maxillary expansion: A systematic review and meta-analysis.

OBJECTIVE: This study aims to assess the expansive effects of pterygomaxillary disjunction (PMD) in surgically assisted rapid maxillary expansion (SARME) surgery using a meta-analysis approach. MATERIALS AND METHODS: The study conducted a comprehensive literature search across five databases: PubMed, Scopus, Medline, Embase, and Cochrane, adhering to the PRISMA 2020 guidelines. Dental alterations were assessed using either cone-beam computed tomography (CBCT) or dental casts, while skeletal changes were exclusively measured from CBCT scans. We analysed the dentoskeletal changes between PMD +/- groups and conducted a within-group comparison. The primary focus of the results was on the mean differences observed in pre- and post-operative measurements. RESULTS: Dental expansion was larger in the PMD+ group but not statistically significant. Skeletal expansion showed a significantly larger expansion in the posterior region in the PMD+ group (P = .033). Without PMD, anterior palatal expansion was significantly larger (P = .03), and the buccal tipping of posterior teeth was also significantly larger (P = .011) to achieve acceptable dental expansion outcomes. CONCLUSIONS: Both PMD +/- groups of SARME surgery can achieve satisfactory dental expansion outcomes. However, bone expansion and tooth inclination are also important factors that influence orthodontic treatment and post-expansion stability. By reducing the bony resistance with PMD, larger posterior palatal expansion and more parallel bony expansion are observed. In contrast, without PMD, there is smaller palatal expansion and greater tooth inclination in the posterior region. This could potentially lead to compromised periodontal conditions following expansion.

Effects of repetitive transcranial magnetic stimulation combined with music therapy in non-fluent aphasia after stroke: A randomised controlled study.

BACKGROUND: Although existing studies have shown that both repetitive transcranial magnetic stimulation (rTMS) and music therapy have advantages in the treatment of non-fluent aphasia, the efficacy of the combination of these two methods remains to be investigated. AIMS: To investigate the clinical efficacy of low-frequency rTMS combined with music therapy on language function and depression in patients with non-fluent aphasia after stroke. METHODS & PROCEDURES: A single-blind parallel randomised controlled trial was conducted. Sixty patients (mean duration = 93.78 days) with non-fluent aphasia after stroke were randomly divided into a traditional therapy group (n = 20), a music therapy group (n = 20) and a combined therapy group (n = 20, 1 Hz). The language function and depression were evaluated before and 3 weeks after treatment with the Chinese version of the Western Aphasia Battery scale, Boston Diagnostic Aphasia Examination scale and Stroke Aphasic Depression Questionnaire Hospital Version scale. OUTCOMES & RESULTS: The combined therapy group was significantly better in all outcomes than the traditional therapy group and was significantly better in depression than the music therapy group. The music therapy group was significantly better in repetition and depression than the traditional therapy group. Language improvement was positively correlated with depression improvement. For adverse events, only two patients in the combined therapy group showed slight dizziness during rTMS treatment and their symptoms improved after rest. CONCLUSIONS & IMPLICATIONS: Our preliminary randomised controlled study indicates that low-frequency rTMS combined with music therapy is feasible and safe in improving language function and depression in non-fluent aphasia patients after stroke. WHAT THIS PAPER ADDS: What is already known on this subject Repetitive transcranial magnetic stimulation (rTMS) and music therapy respectively have advantages in the treatment of non-fluent aphasia after stroke, but whether the combination of the two methods is more effective is still unknown. What this paper adds to the existing knowledge This is one of the first randomised control trials to investigate whether the clinical efficacy of low-frequency rTMS combined music therapy for non-fluent aphasia is better. The findings show that low-frequency rTMS combined music therapy is superior to traditional therapy in spontaneous speech, auditory comprehension, repetition, naming, aphasia quotient, functional language level and depression, and superior to music therapy in depression, while music therapy is superior to traditional therapy in repetition and depression. What are the potential or actual clinical implications of this work? Low-frequency rTMS combined music therapy may be a better method for treatment of non-fluent aphasia.

Alpha-Lipoic Acid Inhibits Spontaneous Diabetes and Autoimmune Recurrence in Non-Obese Diabetic Mice by Enhancing Differentiation of Regulatory T Cells and Showed Potential for Use in Cell Therapies for the Treatment of Type 1 Diabetes.

Type 1 diabetes (T1D) is caused by the destruction of ß cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective treatment for T1D. However, the survival of islet grafts is often disrupted by recurrent autoimmunity. Alpha-lipoic acid (ALA) has been reported to have immunomodulatory effects and, therefore, may have therapeutic potential in the treatment of T1D. In this study, we investigated the therapeutic potential of ALA in autoimmunity inhibition. We treated non-obese diabetic (NOD) mice with spontaneous diabetes and islet-transplantation mice with ALA. The onset of diabetes was decreased and survival of the islet grafts was extended. The populations of Th1 cells decreased, and regulatory T cells (Tregs) increased in ALA-treated mice. The in vitro Treg differentiation was significantly increased by treatment with ALA. The adoptive transfer of ALA-differentiated Tregs into NOD recipients improved the outcome of the islet grafts. Our results showed that in vivo ALA treatment suppressed spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Tregs. Our study also demonstrated the therapeutic potential of ALA in Treg-based cell therapies and islet transplantation used in the treatment of T1D.

Association between socioeconomic status and severity of oral epithelial dysplasia using a Taiwanese Nationwide Oral Mucosal Screening Program: a retrospective analysis.

BACKGROUND: The study aimed to investigate the association between socioeconomic status and severity of oral epithelial dysplasia (OED) using current data from the Taiwanese Nationwide Oral Mucosal Screening Program (TNOMSP). METHODS: This retrospective analysis was conducted in the Department of Oral and Maxillofacial Surgery at a general hospital in Taipei, Taiwan. A total of 134 participants were analysed from a previous study database of 150 patients. The inclusion criteria included age > 20 years and a history of either tobacco or betel nut use. Background information, including para-habits such as betel and tobacco use, was analysed using the Pearson chi-square (χ2) test; furthermore, the correlation of background information with OED severity was investigated using logistic regression (mild or moderate/severe). RESULTS: High school education level (P < 0.001), poor self-awareness (P = 0.002), current betel use (P < 0.001), and tobacco use (P = 0.003) were highly correlated with moderate- and severe OED (P < 0.05). The odds ratio (OR) of education status above senior high school was 0.03 (95% confidence interval [CI] 0.01-0.15, P < 0.001), while that of junior high school was 1. Current betel chewing (OR 6.57 [95% CI 1.17-37.0], P = 0.033) was significantly associated with OED severity compared with never or ex-use of betel. CONCLUSIONS: We found a strong correlation between the severity of OED and current betel use and low education status. The current study revealed that the socioeconomic status, poor self-awareness, and para-habit history of the patients with OED should be evaluated to identify high-risk individuals using TNOMSP.

Pretreatment body mass index as a prognostic predictor in patients with oral squamous cell carcinoma.

OBJECTIVES: To evaluate whether low body mass index (BMI) is a potential adverse prognostic factor in patients with oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: This cross-sectional study included 320 patients with OSCC who underwent therapeutic surgical treatment in Taiwan. The pretreatment BMI was measured as a common indicator of the pretreatment nutritional status to calculate the overall survival in Kaplan-Meier method. The adverse histopathological features of margin status, depth of invasion (DOI), lymphovascular invasion (LVSI), perineural invasion (PNI), and extranodal extension (ENE) were analyzed using the Cox regression model. RESULTS: Low BMI (underweight), DOI > 5 mm, and ENE were identified as detrimental prognostic factors. On multivariate Cox regression analysis, the low BMI group (odds ratio [OR] = 1.683; 95% confidence interval [95% CI] 1.116-2.539; P = 0.022), DOI > 5 mm (OR = 2.399; 95% CI 1.459-3.943; P = 0.001), and ENE (OR = 2.467; 95% CI 1.540-3.951; P = 0.000) yielded reduced survival rate. CONCLUSIONS: The lower BMI had an important and significant effect on the survival of patients with oral cancer and their surgical outcomes. In addition to the adverse histopathological features, a DOI > 5 mm and positive ENE were also identified as the most important prognostic factors. CLINICAL RELEVANCE: Underweight patients with low BMI, DOI of > 5 mm, and positive ENE should receive more intensive nutritional supplementation and postoperative adjuvant therapy.

Adoptive transfer of DMSO-induced regulatory T cells exhibits a similar preventive effect compared to an in vivo DMSO treatment for chemical-induced experimental encapsulating peritoneal sclerosis in mice.

Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). This disease leads to intestinal obstruction with or without peritonitis. The imbalance between the populations of Th17 and regulatory T (Treg) cells (higher Th17 cells and lower Treg cells) is part of the pathogenesis of EPS formation. We demonstrated that dimethyl sulfoxide (DMSO) effectively inhibited autoimmune diabetes recurrence in the islet transplantation of NOD mice via the induction of the differentiation of Treg cells. In this study, we investigated the therapeutic potential of DMSO in the inhibition of EPS formation by a mouse model. Under DMSO treatment, the thickening of the parietal and visceral peritoneum was significantly reduced. The populations of CD4, CD8, and IFN-γ-producing CD4 and CD8 T cells were decreased. The populations of IL-4-producing CD4 T lymphocytes, IL-10-producing CD4 T lymphocytes, CD4 CD69 T lymphocytes and Treg lymphocytes were increased. The expression levels of the cytokines IFN-γ, IL-17a, TNF-α and IL-23, in ascites, were significantly decreased following the DMSO treatment. Furthermore, the differentiation of Treg cells was induced by DMSO from naïve CD4 T cells in vitro, and these cells were adoptively transferred into the EPS mice and significantly prevented EPS formation, exhibiting a comparable effect to the in vivo DMSO treatment. We also demonstrated that the differentiation of Treg cells by DMSO occurred via the activation of STAT5 by its epigenetic effect, without altering the PI3K-AKT-mTOR or Raf-ERK pathways. Our results demonstrated, for the first time, that in vivo DMSO treatment suppresses EPS formation in a mouse model. Furthermore, the adoptive transfer of Treg cells that were differentiated from naïve CD4 T cells by an in vitro DMSO treatment exhibited a similar effect to the in vivo DMSO treatment for the prevention of EPS formation.

Mouth-opening device as a treatment modality in trismus patients with head and neck cancer and oral submucous fibrosis: a prospective study.

OBJECTIVES: This study investigated the clinical effectiveness of intervention with an open-mouth exercise device designed to facilitate maximal interincisal opening (MIO) and improve quality of life in patients with head and neck (H&N) cancer and oral submucous fibrosis (OSF). MATERIALS AND METHODS: Sixty patients with H&N cancer, OSF, and trismus (MIO < 35 mm) participated in the functional rehabilitation program. An open-mouth exercise device intervention group and conventional group, each consisting of 20 patients, underwent a 12-week training and exercising program and follow-up. For the control group, an additional 20 patients were randomly selected to match the demographic characteristics of the aforementioned two groups. RESULTS: The patients' MIO improvements in the aforementioned three groups were 14.0, 10.5, and 1.3 mm, respectively. CONCLUSION: Results of this study confirm the significant improvement in average mouth-opening range. In addition, according to patient feedback, significant improvements in health-related quality of life and reductions in trismus symptoms occurred in the open-mouth exercise device group. CLINICAL RELEVANCE: This newly designed open-mouth exercise device can facilitate trismus patients with H&N cancer and OSF and improve mouth-opening range and quality of life.

Comparison of the hospitalization period after microvascular reconstruction flap in trismus patients: free anterolateral thigh flap versus free forearm flap.

OBJECTIVES: The primary strategy for treating oral squamous cell carcinoma (OSCC) is therapeutic resection, with the trismus resection defect reconstructed via free flap. The most popular free flaps include the radial forearm free flap (RFFF) and anterolateral thigh free flap (ALT). This study investigated the relationships between the hospitalization period and a variety of surgical outcomes, as well as maximum inter-incisor distance (IID), in trismus patients who chewed betel nuts. MATERIALS AND METHODS: Forty-nine primary OSCC patients who chewed betel nuts and underwent surgical resection and reconstruction between 2010 and 2016 were enrolled in this retrospective study. The data were from a single center in Taiwan. The outcome variable after flap recovery surgery was the duration of postoperative hospitalization. Other factors that were analyzed comprised correlations between hospitalization and a variety of factors, including postoperative inter-incisor distances (IIDs), operative time, gender, and WBC count, upon stratification into two reconstruction groups. RESULTS: The mean postoperative hospitalization duration in the ALT group was 22.9 ± 7.2 days, which was significantly shorter than that in the RFFF group (27.8 ± 7.0 days; p = 0.019). Two-week postoperative IID (ALT group: 16.1 ± 0.8 mm; RFFF group: 7.0 ± 0.6 mm) was inversely related to the duration of hospitalization (p = 0.022, r = - 0.372). CONCLUSIONS: The ALT flap is more effective than the RFFF flap to reduce the length of hospitalization in trismus patients. CLINICAL RELEVANCE: The ALT flap should be considered as a first-line technique in OSCC reconstruction in trismus patient reconstruction.

Comparative evaluation of autofluorescence imaging and histopathological investigation for oral potentially malignant disorders in Taiwan.

OBJECTIVES: Autofluorescence imaging is gaining popularity as an adjunctive test for oral potentially malignant disorders (OPMD). This study evaluated the efficacy of autofluorescence imaging based on the current standard oral mucosal disorder checklist in Taiwan. MATERIALS AND METHODS: In total, 126 patients suspected to have mucosal disorders at the Division of Oral and Maxillofacial Surgery, Tri-Service General Hospital, Taipei, Taiwan, were enrolled. Following a conventional oral examination by using the oral mucosal disorder checklist and an autofluorescence imaging examination, all participants underwent histopathological examination to access epithelial dysplasia. RESULTS: Among 126 patients, 68 patients were diagnosis as having an OPMD and 63 having epithelial dysplasia. Autofluorescence imaging exhibited a sensitivity, specificity, positivity predictive value (PPV), negative predictive value (NPV), and accuracy of 77.94%, 35.42%, 63.10%, 53.13%, and 60.34%, respectively, for OPMD and of 88.89%, 43.86%, 63.64%, 78.13%, and 67.50%, respectively, for epithelial dysplasia. After the exclusion of 48 non-OPMD cases according to the checklist, the sensitivity, specificity, PPV, NPV, and accuracy of autofluorescence imaging became 87.50%, 72.73%, 94.23%, 53.33%, and 85.07%, respectively, for epithelial dysplasia. CONCLUSION: The efficacy of epithelial dysplasia identification and OPMD risk assessment can be increased after the exclusion of the non-OPMD cases through autofluorescence imaging. CLINICAL RELEVANCE: Autofluorescence imaging is a useful adjunct that can assist specialists in assessing OPMD patients prone to dysplasia without compromising patient care.

Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma.

OBJECTIVES: Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals. MATERIAL AND METHODS: We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002-2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. RESULTS: Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004). CONCLUSIONS: Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis. CLINICAL RELEVANCE: LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

Danshen extract circumvents drug resistance and represses cell growth in human oral cancer cells.

BACKGROUND: Danshen is a common traditional Chinese medicine used to treat neoplastic and chronic inflammatory diseases in China. However, the effects of Danshen on human oral cancer cells remain relatively unknown. This study investigated the antiproliferative effects of a Danshen extract on human oral cancer SAS, SCC25, OEC-M1, and KB drug-resistant cell lines and elucidated the possible underlying mechanism. METHODS: We investigated the anticancer potential of the Danshen extract in human oral cancer cell lines and an in vivo oral cancer xenograft mouse model. The expression of apoptosis-related molecules was evaluated through Western blotting, and the concentration of in vivo apoptotic markers was measured using immunohistochemical staining. The antitumor effects of 5-fluorouracil and the Danshen extract were compared. RESULTS: Cell proliferation assays revealed that the Danshen extract strongly inhibited oral cancer cell proliferation. Cell morphology studies revealed that the Danshen extract inhibited the growth of SAS, SCC25, and OEC-M1 cells by inducing apoptosis. The Flow cytometric analysis indicated that the Danshen extract induced cell cycle G0/G1 arrest. Immunoblotting analysis for the expression of active caspase-3 and X-linked inhibitor of apoptosis protein indicated that Danshen extract-induced apoptosis in human oral cancer SAS cells was mediated through the caspase pathway. Moreover, the Danshen extract significantly inhibited growth in the SAS xenograft mouse model. Furthermore, the Danshen extract circumvented drug resistance in KB drug-resistant oral cancer cells. CONCLUSION: The study results suggest that the Danshen extract could be a potential anticancer agent in oral cancer treatment.

Triptolide represses oral cancer cell proliferation, invasion, migration, and angiogenesis in co-inoculation with U937 cells.

OBJECTIVES: Advanced oral cancer is a major public health concern because of a lack of effective prevention and treatment. Triptolide (TPL), a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, has been demonstrated to possess strong anticancer properties. In this study, we investigated whether TPL exerts anticancer effects on the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Human macrophage-like U937 cells were co-inoculated with oral cancer SAS cells in a noncontact transwell coculture system. Cytokine expression was detected using ELISA, and cell proliferation was detected using methylene blue. RNA levels were detected using qPCR. Protein levels were detected using Western blot analysis. In vivo experiments involved using xenografted NOD/SCID mice. RESULTS: Our results demonstrated that TPL inhibited the growth of SAS cells co-inoculated with U937 cells in vitro and in vivo. TPL inhibited the invasion, migration ability, and angiogenesis of SAS cells co-inoculated with U937 cells. Expression of cytokines IL-6, IL-8, and TNF-α was induced by co-inoculation, but TPL repressed their expression. CONCLUSION: TPL suppressed the expression of cytokines IL-6, IL-8, and TNF-α, as well as tumor growth, invasion, migration, and angiogenesis in the co-inoculation of human tongue cancer cells with macrophage-like U937 cells. CLINICAL RELEVANCE: TPL is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating tumor-associated macrophages in a tumor microenvironment of HNSCC.

Buccal Mucosa Elasticity Influences Surgical Margin Determination in Buccal Carcinoma Resection.

PURPOSE: Little is known about whether buccal mucosa elasticity influences the determination of surgical margins for buccal carcinomas. This study investigated whether there is a difference in elasticity of the buccal mucosa in patients with buccal carcinoma compared with controls without the disease. PATIENTS AND METHODS: A case-and-control study comprised of patients with buccal carcinoma and controls without the disease was conducted. In each patient, 2 gutta-percha points were attached to the buccal mucosa horizontally and examined twice by lateral cephalometry, once with the mouth closed and once during maximal mouth opening (MMO). Changes in distance between the gutta-percha points were used as a measurement of buccal elasticity. Information on age, alcohol consumption, betel nut chewing, smoking habits, oral submucosa fibrosis (OSF), temporomandibular joint (TMJ) subluxation, and interincisal distance at MMO (IDMMO) was collected. The results were analyzed using independent-sample and paired-sample t tests. RESULTS: Ten patients with buccal carcinoma and another 11 patients without buccal carcinoma were enrolled in this study. There was a significant increase in magnification percentage in patients with carcinoma (32.35%; P < .001) during MMO. Magnification of the comparison group during MMO measured 51.55%, also a significant increase (P < .001). Betel nut chewing significantly decreased mucosa elasticity; magnification was 29.20% (P = .013). Magnification was significantly higher in patients with TMJ subluxation (54.50%; P = .041) than in the controls. Age, alcohol consumption, smoking, OSF, and IDMMO did not affect buccal mucosa elasticity. CONCLUSIONS: Buccal mucosa elasticity increased considerably at MMO in patients with buccal carcinoma. This elasticity should be taken into account when calculating adequate surgical margins for transoral resection of buccal carcinoma.

Daxx and TCF4 interaction links to oral squamous cell carcinoma growth by promoting cell cycle progression via induction of cyclin D1 expression.

OBJECTIVES: Death domain-associated protein (Daxx) has been recently implicated as a positive factor in ovarian cancer and prostate cancer, but the role of Daxx in oral squamous cell carcinoma (OSCC) has never been addressed. Herein, we investigate the expression and function of Daxx in OSCC. MATERIALS AND METHODS: RT-quantitative PCR, Western blotting, and immunohistochemistry were used to evaluation of the expression of Daxx in human OSCC cell lines and clinical surgical specimens. Short hairpin RNA targeting Daxx was transduced by lentivirus infection to knockdown the expression of Daxx in SAS and SCC25 cell lines, and the influence of this knockdown was evaluated by analyzing the growth and the cell cycle in transduced cells. Immunoprecipitation and sequential chromatin immunoprecipitation-quantitative PCR were used to analyze the associations between Daxx, TCF4, and cyclin D1 promoter. Xenograft tumor model was used to evaluate the in vivo tumorigenicity of Daxx in OSCC. RESULTS: Daxx mRNA and protein expression are elevated in several OSCC cell lines and human OSCC samples in comparison to those in normal tissue. We further find that depletion of Daxx decreases OSCC cell growth activity through G1 cell cycle arrest. Daxx silencing reduces cyclin D1 expression via a Daxx-TCF4 interaction, whereas the Daxx depletion-mediated G1 arrest can be relieved by ectopic expression of cyclin D1. Moreover, we show that in OSCC clinical samples, the expression of Daxx is significantly correlated with that of cyclin D1. CONCLUSION: Our data demonstrate the importance of Daxx in regulation of cyclin D1 expression and provide the first evidence that Daxx exhibits tumor-promoting activity in OSCC. CLINICAL RELEVANCE: Daxx plays an important role in malignant transformation of OSCC and may serves as a target for cancer prevention and treatment.

Dimethyl sulfoxide inhibits spontaneous diabetes and autoimmune recurrence in non-obese diabetic mice by inducing differentiation of regulatory T cells.

Type 1 diabetes mellitus (T1D) is caused by the destruction of insulin-producing ß cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective therapeutic strategy for T1D. However, the survival of islet grafts can be disrupted by recurrent autoimmunity. Dimethyl sulfoxide (DMSO) is a solvent for organic and inorganic substances and an organ-conserving agent used in solid organ transplantations. DMSO also exerts anti-inflammatory, reactive oxygen species scavenger and immunomodulatory effects and therefore exhibits therapeutic potential for the treatment of several human inflammatory diseases. In this study, we investigated the therapeutic potential of DMSO in the inhibition of autoimmunity. We treated an animal model of islet transplantation (NOD mice) with DMSO. The survival of the syngeneic islet grafts was significantly prolonged. The population numbers of CD8, DC and Th1 cells were decreased, and regulatory T (Treg) cell numbers were increased in recipients. The expression levels of IFN-γ and proliferation of T cells were also reduced following DMSO treatment. Furthermore, the differentiation of Treg cells from naive CD4 T cells was significantly increased in the in vitro study. Our results demonstrate for the first time that in vivo DMSO treatment suppresses spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Treg cells.

Enhanced anti-tumor activity of triptolide in combination with irradiation for the treatment of oral cancer.

Advanced oral cancer has a poor prognosis because of the lack of an effective treatment. We explored the efficiency of combined treatment with triptolide and ionizing radiation for treating oral cancer. Human tongue cancer cells were treated with triptolide, ionizing radiation, or triptolide plus ionizing radiation. Cell proliferation, cell cycle arrest, and apoptotic influences were analyzed by FACS and immunohistochemistry. Tumor potency was examined in an in vivo human tongue cancer cells xenograft mouse model. Our results demonstrated that triptolide caused a marked reduction in colony number that was further enhanced with increasing doses of ionizing radiation. Triptolide increased apoptosis and decreased the expression of anti-apoptotic proteins. In vivo, combination treatment synergistically reduced tumor weight and volume possibly via the induction of apoptosis and reduction in anti-apoptotic protein expression. In conclusion, triptolide plus ionizing radiation treatment had synergistic anti-tumor effects, especially in vivo, and may be a promising combined modality therapy for advanced oral cancer.

Hard and Soft Tissue Facial Landmarks for Mandibular Angle Reduction: A Clinical Study.

BACKGROUND: Square faces, which are influenced by genetic factors and structural features, are considered undesirable among the Asian population. Surgical interventions, such as mandibular angle reduction, aim to alter these characteristics, though complications may arise. We aimed to investigate the morphology of the mandibular angle and masseter muscle thickness using computed tomography (CT) and to analyze hard and soft tissue correlations to enhance surgical outcomes for patients with square faces. METHODS: This retrospective clinical study included 100 Taiwanese patients aged 18-50 years. CT was used to analyze key clinical parameters, including bilateral mandibular width, mandibular divergence angle, ramus height, distance from the mandibular angle to the inferior alveolar nerve (IAN), and the thickness of the masseter muscle. RESULTS: Significant correlations were noted between the patients' physical height and weight, mandibular width, ramus height, masseter thickness, and distance from the angle to the IAN. Males exhibited a significantly longer and thicker ramus height (66.48 ± 4.28 mm), greater masseter thickness (15.46 ± 2.35 mm), and greater safety range for mandibular angle reduction surgery (18.35 ± 3.19 mm) (p < 0.00008). Significant correlations were observed among all parameters, except between mandibular width and gonial angle and the distance from the angle to the IAN and between mandibular divergence and masseter muscle thickness (p > 0.1). CONCLUSIONS: Our study highlighted the complex interplay among factors that contribute to square facial morphology. Careful preoperative assessments and customized surgical planning are essential for addressing this multifaceted clinical challenge.

Okanin Inhibits Cell Growth and Induces Apoptosis and Pyroptosis in Oral Cancer.

BACKGROUND: Okanin, a flavonoid compound derived from Bidens pilosa L., has garnered attention for its anti-inflammatory properties. Although Bidens pilosa is commonly used in healthcare products and functional foods, the anticancer potential of okanin, particularly in oral cancer, remains underexplored. This study aims to investigate the effects of okanin on oral cancer cell lines and its potential as a therapeutic agent. METHODS: The study involved assessing the cytotoxic effects of okanin on oral cancer cell lines SAS, SCC25, HSC3, and OEC-M1. The IC50 values were determined using methylene blue assays, and the clonogenic capacity was evaluated through colony formation assays. Flow cytometry was used to analyze cell cycle progression and apoptosis. Caspase-3/7 activity assays and annexin V/7-AAD staining confirmed the induction of apoptosis and pyroptosis. In vivo efficacy was assessed using a SAS xenograft model, and immunohistochemical analysis of xenograft tissue was performed to examine pyroptosis-related markers. RESULTS: Okanin exhibited potent cytotoxic effects with IC50 values of 12.0 ± 0.8, 58.9 ± 18.7, 18.1 ± 5.3, and 43.2 ± 6.2 µM in SAS, SCC25, HSC3, and OEC-M1 cells, respectively. It caused dose- and time-dependent reductions in cell viability and significantly impaired clonogenic capacity. Flow cytometry revealed G2/M cell cycle arrest and increased sub-G1 population, indicating cell cycle disruption and death. Okanin induced both apoptosis and pyroptosis, as confirmed by caspase-3/7 activity and annexin V/7-AAD staining. In vivo, okanin reduced tumor growth and involved pyroptosis-related markers such as CASP1, GSDMC, GSDMD, and GSDME. CONCLUSIONS: Okanin demonstrates significant anticancer potential, particularly in oral cancer, by inducing both apoptosis and pyroptosis. Its efficacy in reducing tumor growth in vivo further supports its potential as a novel therapeutic option. Further mechanistic studies are needed to elucidate the pathways involved in okanin-mediated cell death and to explore its clinical applications.

Allyl Isothiocyanate Suppresses the Proliferation in Oral Squamous Cell Carcinoma via Mediating the KDM8/CCNA1 Axis.

The dysregulated expression of cyclin genes can lead to the uncontrolled proliferation of cancer cells. Histone demethylase Jumonji-C domain-containing protein 5 (KDM8, JMJD5) and cyclin A1 (CCNA1) are pivotal in cell cycle progression. A promising candidate for augmenting cancer treatment is Allyl isothiocyanate (AITC), a natural dietary chemotherapeutic and epigenetic modulator. This study aimed to investigate AITC's impact on the KDM8/CCNA1 axis to elucidate its role in oral squamous cell carcinoma (OSCC) tumorigenesis. The expression of KDM8 and CCNA1 was assessed using a tissue microarray (TMA) immunohistochemistry (IHC) assay. In vitro experiments with OSCC cell lines and in vivo experiments with patient-derived tumor xenograft (PDTX) and SAS subcutaneous xenograft tumor models were conducted to explore AITC's effects on their expression and cell proliferation. The results showed elevated KDM8 and CCNA1 levels in the OSCC patient samples. AITC exhibited inhibitory effects on OSCC tumor growth in vitro and in vivo. Additionally, AITC downregulated KDM8 and CCNA1 expression while inducing histone H3K36me2 expression in oral cancer cells. These findings underscore AITC's remarkable anticancer properties against oral cancer, highlighting its potential as a therapeutic option for oral cancer treatment by disrupting the cell cycle by targeting the KDM8/CCNA1 axis.

Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF-κB.

Triptolide (TPL) inhibits the proliferation of a variety of cancer cells and has been proposed as an effective anticancer agent. In this study, we demonstrate that TPL downregulates HER2 protein expression in oral, ovarian, and breast cancer cells. It suppresses HER2 protein expression in a dose- and time-dependent manner. Transrepression of HER2 promoter activity by TPL is also observed. The interacting site of TPL on the HER2 promoter region is located between -207 and -103 bps, which includes a putative binding site for the transcription factor NF-κB. Previous reports demonstrated that TPL suppresses NF-κB expression. We demonstrate that overexpression of NF-κB rescues TPL-mediated suppression of HER2 promoter activity and protein expression in NIH3T3 cells and ovarian cancer cells, respectively. In addition, TPL downregulates the activated (phosphorylated) forms of HER2, phosphoinositide-3 kinase (PI3K), and serine/threonine-specific protein kinase (Akt). TPL also inhibits tumor growth in a mouse model. Furthermore, TPL suppresses HER2 and Ki-67 expression in xenografted tumors based on an immunohistochemistry (IHC) assay. These findings suggest that TPL transrepresses HER2 and suppresses the downstream PI3K/Akt-signaling pathway. Our study reveals that TPL can inhibit tumor growth and thereby may serve as a potential chemotherapeutic agent.