Microbial Profiles in Oral Lichen Planus: Comparisons with Healthy Controls and Erosive vs. Non-Erosive Subtypes.

Recent studies have begun exploring the potential involvement of microbiota in the pathogenesis of oral lichen planus (OLP), yet comprehensive investigations remain limited. Hence, this study aimed to compare the microbial profiles in saliva samples obtained from patients with OLP against those from healthy controls (HC), along with a comparison between erosive (E) and non-erosive (NE) OLP patients. Saliva samples were collected from 60 OLP patients (E: n = 25, NE: n = 35) and 30 HC individuals. Analysis revealed no significant differences in alpha diversity, as assessed by the Chao1 and Shannon index, across the three groups. However, Bray-Curtis distance analysis indicated a significant disparity in microbiome composition distribution between HC and E-OLP, as well as HC and NE-OLP groups. The six most abundant phyla observed across the groups were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Fusobacteria, and Saccharibacteria (TM7). Notably, OLP groups exhibited a higher prevalence of Bacteroidetes. Prevotella emerged as the predominant genus in the OLP groups, while Capnocytophaga showed a relatively higher prevalence in E-OLP compared to NE-OLP. This study's findings indicate a notable difference in microbiota composition between HC and patients with OLP. Additionally, differences in the microbiome were identified between the E-OLP and NE-OLP groups. The increase in the proportion of certain bacterial species in the oral microbiome suggests that they may exacerbate the inflammatory response and act as antigens for OLP.

A Comparison of the Condyle and Articular Eminence in Asian Juvenile Idiopathic Osteoarthritis Patients with Unilateral and Bilateral TMJ Involvement: A Retrospective Case-Control Study.

This study compared the condylar volume, length, and articular eminence (AE) characteristics of normal individuals to those with unilateral and bilateral juvenile idiopathic osteoarthritis (JOA). The 116 patients were divided into four groups: Control (n = 16), affected condyle of unilateral JOA (Aff-Uni) (n = 36), non-affected condyle of JOA (NonAff-uni) (n = 36), and bilateral JOA (Bilateral) (n = 28). The differences in condyle volume and length and AE were analyzed using ANOVA and Bonferroni post-hoc tests. The results showed that Bilateral had a significantly different condylar volume, especially in the condylar head (p < 0.01), specifically the middle, anterior, and medial parts (p < 0.05). Condylar length also differed among the groups, with differences observed between the control group and the other three groups, as well as between the bilateral group and the other three groups (p < 0.01). AE total volume differed between the control group and Aff-Uni. In the detailed comparison, Aff-Uni and NonAff-Uni were smaller than the control group in the posterior, lateral, and medial sections (p < 0.05). In conclusion, depending on the involvement of unilateral or bilateral JOA, there were differences in condylar volume and AE when compared to the normal control group. Therefore, a prognosis should be evaluated by distinguishing between patients with unilateral and bilateral JOA.

Virus-templated redox nanowire network for enzyme electrode.

Viruses have unique coat proteins that are genetically modifiable. Their surface can serve as a nano-template on which electroactive molecules are immobilized. In this study, we report filamentous bacteriophage as a backbone to which redox mediators are covalently and densely tethered, constructing redox nanowire, i.e. an electron conducting biomaterial. The highly ordered coat proteins of a filamentous bacteriophage provide flexible and biocompatible platform to constitute a biohybrid redox nanowire. Incorporating bacteriophage and redox molecules form an entangled assembly of nanowires enabling facile electron transfer. Electron transfer among the molecular mediators in the entangled assembly originates apparent electron diffusion of which the electron transfer rate is comparable to that observed in conventional redox polymers. Programming peptide terminals suggests further enhancement in electron mediation by increasing redox species mobility. In addition, the redox nanowire film functions as a favorable matrix for enzyme encapsulation. The stability of the enzymes entrapped in this unique matrix is substantially improved.

Establishment of quantitative indicators for an efficient treatment on masticatory muscle pain.

BACKGROUND: Although several studies have investigated effective treatments for masticatory muscle pain (MMP), no unified conclusion has been drawn regarding the effectiveness of these treatments. OBJECTIVES: This study aimed to define quantitative indicators for predicting the outcome of MMP treatment. MATERIALS AND METHODS: In total, patients aged 20-70 years were recruited and divided into the MMP (n = 24) and control (n = 36) groups, based on the presence of MMP according to the Diagnostic Criteria for Temporomandibular Disorders. At pretreatment, the MMP group was assessed using quantitative indicators such as subjective pain levels, pain duration, graded chronic pain scale (GCPS), and perceived stress scale (PSS). Salivary alpha-amylase (sAA) and interleukin-6 (IL-6) levels were analyzed. The masticatory muscle palpation score and the range of mouth opening were measured. At posttreatment, subjective pain levels, mouth opening, and treatment/medication duration were examined. The PSS and sAA levels were assessed in the control group. RESULTS: sAA levels in the MMP group were significantly higher than those in the control group (p < .05). The masseter muscle palpation score (MPS) showed a positive correlation with IL-6 levels (ρ = 0.503, p < .05) and a negative correlation with nonsteroidal anti-inflammatory drug (NSAID) treatment period (ρ = -0.462, p < .05). The temporalis muscle palpation score (TPS) was positively correlated with pain duration and GCPS grade (ρ = 0.483, p < .05, and ρ = 0.445, p < .05, respectively). CONCLUSIONS: Treatment with NSAIDs was effective in the MMP group with high MPS and IL-6 levels, but not in the MMP group with high TPS, pain duration, and GCPS grade.

Prediction of anterior open-bite development after stabilization splint treatment in patients with temporomandibular disorder.

OBJECTIVE: To assess the dentoskeletal factors of patients with temporomandibular disorders (TMDs) that can predict anterior open-bite development after stabilization splint treatment (ST). METHODS: Eighty-seven TMD patients were classified into three groups according to the degree of overbite changes after ST. Statistically significant differences in dental and skeletal measurements before ST among the groups were investigated. RESULTS: Pre-ST dental and skeletal measurements that were significantly different among the groups were upper central incisor (U1) to point A-pogonion (A-Pog), facial height ratio (FHR), A point-nasion-B point angle (ANB), Wits appraisal, ramus height, angle of convexity, and sella to condylion. Among these factors, FHR, ramus height, and sella to condylion had a positive relationship with overbite changes. DISCUSSION: Dentoskeletal factors, i.e., FHR, ramus height, and sella to condylion, can predict anterior open-bite development after ST in TMD patients.

Gene signatures associated with barrier dysfunction and infection in oral lichen planus identified by analysis of transcriptomic data.

Oral lichen planus (OLP) is one of the most prevalent oral mucosal diseases, but there is no cure for OLP yet. The aim of this study was to gain insights into the role of barrier dysfunction and infection in OLP pathogenesis through analysis of transcriptome datasets available in public databases. Two transcriptome datasets were downloaded from the Gene Expression Omnibus database and analyzed as whole and as partial sets after removing outliers. Differentially expressed genes (DEGs) upregulated in the dataset of OLP versus healthy epithelium were significantly enriched in epidermal development, keratinocyte differentiation, keratinization, responses to bacterial infection, and innate immune response. In contrast, the upregulated DEGs in the dataset of the mucosa predominantly reflected chemotaxis of immune cells and inflammatory/immune responses. Forty-three DEGs overlapping in the two datasets were identified after removing outliers from each dataset. The overlapping DEGs included genes associated with hyperkeratosis (upregulated LCE3E and TMEM45A), wound healing (upregulated KRT17, IL36G, TNC, and TGFBI), barrier defects (downregulated FRAS1 and BCL11A), and response to infection (upregulated IL36G, ADAP2, DFNA5, RFTN1, LITAF, and TMEM173). Immunohistochemical examination of IL-36γ, a protein encoded by one of the DEGs IL36G, in control (n = 7) and OLP (n = 25) tissues confirmed the increased expression of IL-36γ in OLP. Collectively, we identified gene signatures associated with hyperkeratosis, wound healing, barrier defects, and response to infection in OLP. IL-36γ, a cytokine involved in both wound repair and antimicrobial defense, may be a possible therapeutic target in OLP.

Correlation between Metal Ions and Cytokines in the Saliva of Patients with Oral Lichenoid Lesions.

PURPOSE: We aimed to investigate the effect of metal ions from oral prostheses (OPs) released into the saliva of patients with oral lichenoid lesions (OLLs). MATERIALS AND METHODS: Subjects (n=183) were divided into four groups according to the presence or absence of OLL and OP. Concentrations of the metal ions titanium, chromium (Cr), cobalt (Co), nickel (Ni), palladium (Pd), silver (Ag), platinum (Pt), gold (Au), and zirconium (Zr) were measured using a laser-ablation microprobe inductively coupled to a plasma mass spectrometer. Saliva levels of interleukin (IL)-6, IL-1ß, IL-8, and tumor necrosis factor-α were detected using an enzyme-linked immunosorbent assay. The reticulation/keratosis, erythema, and ulceration (REU) scoring system was used to assess the severity of OLL. RESULTS: Mean concentrations of IL-6 and IL-8 were statistically higher in OLL patients with OPs. The concentration of Ni was high in OLL groups. The concentrations of Cr, Ni, and Au ions in the saliva were positively correlated with IL-8. REU scores were positively correlated with salivary concentrations of IL-6 and IL-8, as well as with concentrations of Cr, Ni, and Au. CONCLUSION: Increased concentrations of metal ions, especially Ni, in saliva were positively correlated with IL-8 and showed positive correlations with the severity of OLL.

Totally implantable enzymatic biofuel cell and brain stimulator operating in bird through wireless communication.

Animals digest food to fuel brain neurometabolism via cellular respiration. This study demonstrates the combination of a biofuel cell (BFC) and an animal brain stimulator (ABS) implanted in a pigeon. Glucose oxidation and oxygen reduction in an enzymatic BFC supplied electrical power to the ABS. Power from the BFC reached 0.12 mW in vitro and 0.08 mW in vivo using only the natural glucose and oxygen in the pigeon's body. A power management integrated circuit is used to harvest energy from the in vivo BFC at a rate of 28.4 mJ over 10 min, which is sufficient for intermittent neurostimulation.

Local Injection of Growth Hormone for Temporomandibular Joint Osteoarthritis.

PURPOSE: Osteoarthritis (OA) of the temporomandibular joint (TMJ) elicits cartilage and subchondral bone defects. Growth hormone (GH) promotes chondrocyte growth. The aim of this study was to evaluate the efficacy of intra-articular injections of GH to treat TMJ-OA. MATERIALS AND METHODS: Monosodium iodoacetate (MIA) was used to induce OA in the TMJs of rats. After confirming the induction of OA, recombinant human GH was injected into the articular cavities of rats. Concentrations of GH and IGF-1 were measured in the blood and synovial fluid, and OA grades of cartilage and subchondral bone degradation were recorded by histological examination and micro-computed tomography. RESULTS: MIA-induced OA in the rat TMJ upregulated insulin-like growth factor-1 (IGF-1) rather than GH levels. GH and IGF-1 concentrations were increased after local injection of GH, compared with controls. Locally injected GH lowered osteoarthritic scores in the cartilage and subchondral bone of the TMJ. CONCLUSION: Intra-articular injection of GH improved OA scores in rat TMJs in both cartilage and subchondral bone of the condyles without affecting condylar bone growth. These results suggest that intra-articular injection of human GH could be a suitable treatment option for TMJ-OA patients in the future.

Candida Infection Associated with Salivary Gland-A Narrative Review.

Candida species are common global opportunistic pathogens that could repeatedly and chronically cause oral mucosa infection and create an inflammatory environment, leading to organ dysfunction. Oral Candida infections may cause temporary or permanent damage to salivary glands, resulting in the destruction of acinar cells and the formation of scar tissue. Restricted function of the salivary glands leads to discomfort and diseases of the oral mucosa, such as dry mouth and associated infection. This narrative review attempts to summarize the anatomy and function of salivary glands, the associations between Candida and saliva, the effects of Candida infection on salivary glands, and the treatment strategies. Overall, clinicians should proactively manage Candida infections by educating patients on oral hygiene management for vulnerable populations, conducting frequent checks for a timely diagnosis, and providing an effective treatment plan.

Characteristics of patients who perceive dental treatment as a cause of oral mucosal lesions.

This retrospective study aims to investigate the proportion and characteristics of patients who perceive dental treatment (DT) as a cause of oral mucosal lesions (OMLs). A total of 2,302 patients with OMLs visited the Oral Medicine Department of Pusan National University Dental Hospital. The patients were divided into a study group (280 patients who perceived DT as a cause of OMLs) and a control group (300 randomly selected patients). Percentages of DT types, clinical characteristics, and the frequencies of diagnoses and chief complaint (CC) sites were analyzed in both groups. Among the patients with OMLs, 12.2% attributed OMLs to DT. Among the diagnoses, allergic reaction (AR) and traumatic ulcer/irritation (TU) were significantly more frequent in the study group. The DT types most frequently perceived as the cause of OMLs were implants. According to patients, TU and candida occurred most frequently following denture placement (68-79%), whereas oral lichen planus and AR occurred most commonly following implant treatment (52-53%). The gingiva was significantly more frequent as the CC site in the study group than in the control group (P < 0.05 for all outcomes). It is important to inform patients of the potential complications of DT and the importance of regular check-ups.

The Flavonoid Jaceosidin from Artemisia princeps Induces Apoptotic Cell Death and Inhibits the Akt Pathway in Oral Cancer Cells.

Jaceosidin is a single compound from the Japanese mugwort Artemisia princeps, which is used as a food and a traditional medicinal herb. A. princeps extracts and flavonoid components have been shown to have antihyperglycaemic, antioxidant, and anti-inflammatory properties. Although the anticancer properties of these extracts were recently demonstrated, the related mechanisms have not been characterised. In this study, we investigated the effects of jaceosidin in oral squamous cell carcinoma (OSCC) cells and initially showed selective suppression of proliferation (IC50 = 82.1 µM in HSC-3 cells and 97.5 µM in Ca9.22 cells) and accumulation of cells at the sub-G1 stage of the cell cycle. In addition, jaceosidin increased cleavage of caspase-9 and caspase-3 in OSCC cells, although caspase-8 was not detected. In further experiments, jaceosidin downregulated Akt phosphorylation and ectopic activation of Akt blocked the antiproliferative effects of jaceosidin. Finally, we showed that jaceosidin has no effects on HaCaT normal epithelial cell viability, indicating selective chemotherapeutic potential of jaceosidin and that tumour-specific downregulation of Akt increases apoptosis and inhibits growth in OSCC cells.

Concentrations of CTX I, CTX II, DPD, and PYD in the urine as a biomarker for the diagnosis of temporomandibular joint osteoarthritis: A preliminary study.

OBJECTIVES: The aim of this study was to identify a marker for temporomandibular joint (TMJ) osteoarthritis (OA) diagnosis by comparing the concentrations of urinary pyridinoline (PYD), deoxypyridinoline (DPD), and C-terminal telopeptides type I collagen (CTX-I), and CTX-II of TMJ OA patients with those of a non-symptomatic group. METHODS: PYD, DPD, CTX-I, and CTX-II concentrations in the urine of 36 non-symptomatic subjects and 31 TMJ OA subjects were analyzed. RESULTS: The differences for only PYD and DPD were significant. In ROC analysis, PYD and DPD showed higher sensitivity and specificity than CTX-I and CTX-II. PYD and DPD concentrations in urine were significantly increased in TMJ OA patients and can therefore be used as a biomarker in the supplementary clinical diagnosis of TMJ OA. DISCUSSION: The findings suggest that measurement of their concentration can be a supplementary method for clinical diagnosis of TMJ OA.

Novel approaches for bioinformatic analysis of salivary RNA sequencing data for development.

Motivation: Analysis of RNA sequencing (RNA-Seq) data in human saliva is challenging. Lack of standardization and unification of the bioinformatic procedures undermines saliva's diagnostic potential. Thus, it motivated us to perform this study. Results: We applied principal pipelines for bioinformatic analysis of small RNA-Seq data of saliva of 98 healthy Korean volunteers including either direct or indirect mapping of the reads to the human genome using Bowtie1. Analysis of alignments to exogenous genomes by another pipeline revealed that almost all of the reads map to bacterial genomes. Thus, salivary exRNA has fundamental properties that warrant the design of unique additional steps while performing the bioinformatic analysis. Our pipelines can serve as potential guidelines for processing of RNA-Seq data of human saliva. Availability and implementation: Processing and analysis results of the experimental data generated by the exceRpt (v4.6.3) small RNA-seq pipeline (github.gersteinlab.org/exceRpt) are available from exRNA atlas (exrna-atlas.org). Alignment to exogenous genomes and their quantification results were used in this paper for the analyses of small RNAs of exogenous origin. Contact: dtww@ucla.edu.

Pattern analysis of patients with temporomandibular disorders resulting from unilateral mastication due to chronic periodontitis.

PURPOSE: The purpose of the present study was to perform a pattern analysis in patients with temporomandibular disorder (TMD) resulting from unilateral mastication due to chronic periodontitis. METHODS: Thirty participants with signs or symptoms of TMD who engaged in unilateral mastication due to periodontitis-related discomfort (test group) were selected. Another 30 subjects exhibiting signs or symptoms of TMD resulting from unilateral mastication not due to chronic periodontitis (control group) were also recruited. An interview-based questionnaire was administered, and an examination of the temporomandibular joint (TMJ) with determination of periodontal status was performed. RESULTS: The duration of unilateral mastication was significantly longer in the control group than in the test group. There was a significant negative correlation between the duration of unilateral mastication and the Community Periodontal Index score. Using the Research Diagnostic Criteria for TMD (RDC/TMD) axis I algorithms, all the subjects were assigned to 3 main groups. The test group exhibited significantly a higher diagnostic distribution of group III (arthralgia, osteoarthritis, or osteoarthrosis), and in both the test and control groups, the number of diagnoses was larger for the non-chewing side. The control group showed a significantly higher diagnostic distribution of group I (myofacial pain), and in both the test and control groups, the number of diagnoses was larger for the chewing side. CONCLUSIONS: The results of the present study indicate that unilateral mastication due to chronic periodontitis could induce not only pain but also structural TMJ changes if adequate treatment is not administered and supported within a short time from the onset of the condition. Therefore, immediate treatment of chronic periodontitis is recommended to prevent not only the primary progress of periodontal disease, but also secondary TMJ-related problems. Furthermore, subjects who have suffered chronic long-term periodontitis without treatment should be urged to undergo a TMJ examination.

Effect of stabilization splint therapy on glenoid fossa remodeling in temporomandibular joint osteoarthritis.

PURPOSE: The aim of this study was to evaluate, by CBCT superimposition, bone changes (cortical bone intactness, sclerosis and subchondral cyst) in the glenoid fossa related to stabilization splint (SS) therapy for temporomandibular joint osteoarthritis (TMJ OA) patients and to compare the effects for two groups, one that had undergone SS therapy and the other that had not. METHODS: This case-control study included 36 TMJ OA patients, 10 that had undergone SS therapy (the SS group) compared with 26 that had not (the non-SS group). Osseous changes in the glenoid fossa were evaluated based on superimposed CBCT images before and after treatment. RESULTS: Improvements ranging from 57.5 to 100% were achieved in cortical bone integrity, sclerosis, and subchondral cyst for both groups, SS and non-SS. However, there were no statistically significant difference between the two groups (p>0.05). The non-SS group showed a significant decrease in the distances from the point of inflexion and the lowest point of the articular eminence to the reference line (p<0.05). On the other hand, the SS group showed an increase for the point of inflexion. The other measures showed no statistically significant differences in distance before treatment and after treatment, even though the average distance after treatment showed an overall increasing tendency. CONCLUSION: SS therapy relieved excessive loading on the TMJ in the TMD OA patients, who showed, via CBCT superimposition, less bone resorption in the glenoid fossa.

Topical sulfasalazine for unresponsive oral lichen planus.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of topical sulfasalazine in the treatment of oral lichen planus (OLP) resistant to corticosteroid therapy. METHOD AND MATERIALS: Twenty-one unresponsive OLP patients were treated with topical sulfasalazine 3 times a day for 4 weeks. Each patient's symptoms and lesion size were evaluated at the beginning of therapy, and then after 4 weeks to determine the efficacy of topical sulfasalazine. Inflammatory cytokines levels in saliva were measured by ELISA. RESULTS: Seventeen patients (81%) reported improvement of discomfort and 12 patients (57%) had lesions decrease in size over 50%. Patients who had higher levels of IL-1ß and IL-8 were more responsive to topical sulfasalazine therapy. CONCLUSION: Topical sulfasalazine should be considered when OLP does not respond to corticosteroid therapy. Furthermore, high concentrations of IL-1ß and IL-8 in the saliva are useful indicators for the application of topical sulfasalazine in OLP patients refractory to steroid treatment.

The application of neuropathic pain questionnaires in burning mouth syndrome patients.

AIMS: To evaluate and compare the validity of the PainDETECT, DN4, and abbreviated DN4 (DN4i) neuropathic pain questionnaires for primary burning mouth syndrome (BMS), which is a burning sensation in the oral mucosa in the absence of any identifiable organic etiology. METHODS: Eighty-one patients (42 with primary BMS and 39 with nociceptive pain) complaining of a burning sensation and pain in their oral mucosa were enrolled in this study. All of the patients completed the neuropathic pain questionnaires. The sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic (ROC) curve were estimated. Then the relationship between pain intensity and total neuropathic pain score was investigated. Data were analyzed with the chi-square test and independent t test for subjects' baseline characteristic differences, and with Pearson correlation coefficients for the relationship of variables. RESULTS: The mean area under the ROC curves (AUCs) for PainDETECT, DN4, and DN4i were 0.81, 0.79, and 0.81, respectively. There was no statistically significant difference in the AUCs among the questionnaires. PainDETECT, DN4, and DN4i had a lower sensitivity and specificity for BMS compared to previous validation studies. The total scores for PainDETECT, DN4, and DN4i in the primary BMS group were significantly associated with pain intensity. CONCLUSION: Although the results of this study suggest that neuropathic pain questionnaires, such as PainDETECT and DN4, are not ideal principal screening tools for BMS patients, a substantial proportion of neuropathic symptoms in primary BMS patients were identified.

Anti-cancer effects of Kochia scoparia fruit in human breast cancer cells.

BACKGROUND: The fruit of Kochia scoparia Scharder is widely used as a medicinal ingredient for the treatment of dysuria and skin diseases in China, Japan and Korea. Especially, K. scoparia had been used for breast masses and chest and flank pain. OBJECTIVE: To investigate the anti-cancer effect of K. scoparia on breast cancer. MATERIALS AND METHODS: We investigated the anti-cancer effects of K. scoparia, methanol extract (MEKS) in vitro. We examined the effects of MEKS on the proliferation rate, cell cycle arrest, reactive oxygen species (ROS) generation and activation of apoptosis-associated proteins in MDA-MB-231, human breast cancer cells. RESULTS: MTT assay results demonstrated that MEKS decreased the proliferation rates of MDA-MB-231 cells in a dose-dependent manner with an IC50 value of 36.2 µg/ml. MEKS at 25 µg/ml significantly increased the sub-G1 DNA contents of MDA-MB-231 cells to 44.7%, versus untreated cells. In addition, MEKS induced apoptosis by increasing the levels of apoptosis-associated proteins such as cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and cleaved Poly (ADP-ribose) polymerase (PARP). CONCLUSION: These results suggest that MEKS inhibits cell proliferation and induces apoptosis in breast cancer cells and that MEKS may have potential chemotherapeutic value for the treatment of human breast cancer.

Sulfasalazine induces autophagic cell death in oral cancer cells via Akt and ERK pathways.

Sulfasalazine (SSZ) is an anti-inflammatory drug that has been used to treat inflammatory bowel disease and rheumatoid arthritis for decades. Recently, some reports have suggested that SSZ also has anti-cancer properties against human tumors. However, little is known about the effects of SSZ on oral cancer. The aim of this study was to investigate the anti-cancer effects of SSZ in oral squamous cell carcinoma (OSCC) cells and to elucidate the mechanisms involved. The authors investigated the anti-proliferative effect of SSZ using the MTT method in HSC-4 cells (an OSCC cell line). Cell cycle analysis, acidic vesicular organelle (AVO) staining, monodansylcadaverine (MDC) staining and Western blotting were also conducted to investigate the cytotoxic mechanism of SSZ. SSZ significantly inhibited the proliferation of HSC-4 cells in a dose-dependent manner. In addition, SSZ induced autophagic cell death, increased microtubule-associated protein 1 light chain (MAP1- LC; also known as LC) 3-II levels, as well as induced punctate AVO and MDC staining, resulted in autophagic cell death. Furthermore, these observations were accompanied by the inhibition of the Akt pathway and the activation of ERK pathway. These results suggest that SSZ promotes autophagic cell death via Akt and ERK pathways and has chemotherapeutic potential for the treatment of oral cancer.