BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors...BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(ECM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remodeling and the degradation of the ECM.MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions.MMP-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of tumors.Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.AIM To assess the immunohistochemical expression of MMP-9 and MMP-13 in OSCC.METHODS A total of 40 cases with histologically confirmed OSCC by incisional biopsy were included in this cross-sectional retrospective study.The protocols for both MMP-9 and MMP-13 immunohistochemical staining were performed according to the manufacturer’s recommendations along with the normal gingival epithelium as a positive control.All the observations were recorded and Pearson’sχ²test with Fisher exact test was used for statistical analysis.RESULTS Our study showed no significant correlation between MMP-9 and MMP-13 staining intensity and tumor size.The majority of the patients were in advanced TNM stages(III and IV),and showed intense expression of MMP-9 and MMP-13.CONCLUSION The present study suggests that both MMP-9 and MMP-13 play an important and independent role in OSCC progression and invasiveness.Intense expression of MMP-9 and MMP-13,irrespective of histological grade of OSCC,correlates well with TNM stage.Consequently,it is evident that MMP-9 and MMP-13 are important for the invasiveness and progression of tumors.The findings may facilitate the development of new approaches for evaluating lymph node metastases and interventional therapy techniques,hence enhancing the prognosis of patients diagnosed with OSCC.展开更多
Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly inter...Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years.Porphyromonas gingivalis(P.gingivalis)is increasingly considered to be closely related to the development of oral squamous cell carcinoma(OSCC).Nevertheless,the role of P.gingivalis in the stemness of OSCC cells remains uncertain.Herein,we showed that P.gingivalis was positively correlated with CSC markers expression in human OSCC specimens,promoted the stemness and tumorigenicity of OSCC cells,and enhanced tumor formation in nude mice.Mechanistically,P.gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1(SCD1)expression,a key enzyme involved in lipid metabolism,which ultimately resulted in enhanced acquisition of stemness.Moreover,SCD1 suppression attenuated P.gingivalis-induced stemness of OSCC cells,including CSCs markers expression,sphere formation ability,chemoresistance,and tumor growth,in OSCC cells both in vitro and in vivo.Additionally,upregulation of SCD1 in P.gingivalis-infected OSCC cells was associated with the expression of KLF5,and that was modulated by P.gingivalis-activated NOD1 signaling.Taken together,these findings highlight the importance of SCD1-dependent lipid synthesis in P.gingivalis-induced stemness acquisition in OSCC cells,suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.展开更多
BACKGROUND Oral squamous cell carcinoma(OSCC)is a frequent cancer affecting the oral cavity.OSCC is usually preceded by occurrence of precursor lesions,which demonstrate a varying degree of malignant transformation po...BACKGROUND Oral squamous cell carcinoma(OSCC)is a frequent cancer affecting the oral cavity.OSCC is usually preceded by occurrence of precursor lesions,which demonstrate a varying degree of malignant transformation potential.Epithelialmesenchymal transition is a significant biological phenomenon that facilitates tumor growth and metastasis through the involvement of diverse epithelial and mesenchymal proteins.E-cadherin down regulation and over-expression of zincfinger E-box-binding homeobox 1(ZEB1)has been reported in several cancers.AIM To evaluate the role of E-cadherin and ZEB1 in oral leukoplakia and OSCC.METHODS A total of 60 cases i.e.,oral leukoplakia/oral epithelial dysplasia(OED)(n=30)and OSCC(n=30)were included.Immunohistochemistry was performed utilizing two markers:E-cadherin and ZEB1.The Mann-Whitney U test was employed to compare individual markers across the study groups.Spearman’s correlation was done followed by discriminant function analysis.RESULTS Reduction in the expression E-cadherin and altered localization were noted from OED to OSCC.Overexpression of ZEB1 along with cytoplasmic accumulation was noted in OED,with marked expression in OSCC.ZEB1 epithelium intensity and ZEB1 connective tissue percentage contributed to the discriminant function with an accuracy of 85%for the classification of OED from OSCC.CONCLUSION Loss of E-cadherin and up-regulation of ZEB1 from OED to OSCC,predisposes to induction of epithelial-mesenchymal transition.Discriminant formulas are developed to classify cases of OED and OSCC with 85%accuracy.展开更多
Radiochemotherapy-induced oral mucositis(OM)is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy.Erosion and ulcers are the main features of OM that seriously affe...Radiochemotherapy-induced oral mucositis(OM)is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy.Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment.To date,differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties,which has increased the uncertainty of treatment effects.On the basis of current research evidence,this expert consensus outlines risk factors,clinical manifestations,clinical grading,ancillary examinations,diagnostic basis,prevention and treatment strategies and efficacy indicators for OM.In addition to strategies such as basic oral care,antiinflammatory and analgesic agents,anti-infective agents,pro-healing agents,and photobiotherapy recommended in previous guidelines,we also emphasize the role of traditional Chinese medicine in OM prevention and treatment.This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention,diagnosis,and treatment,standardizing clinical practice,reducing OM occurrence,promoting healing,and improving the quality of life of patients.展开更多
Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(P...Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(PTMs),such as phosphorylation,acetylation,methylation,and glycosylation,regulate osteogenic differentiation(OD).These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix.While the molecular mechanisms behind OD are increasingly understood,many questions remain,particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation.Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases.This review summarizes the role of PTMs in the OD of oral-derived stem cells,discusses their clinical applications,and suggests future research directions.展开更多
This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression...This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression pattern in OSCC,and the expression levels of PERs in OSCC patients are correlated with a favorable prognosis.PERs impact the occurrence and development of OSCC through multiple pathways.In the regulation of cell proliferation,they can function not only through cell cycle regultion but also via metabolic pathways.For example,PER1 can interact with receptors for activated C kinase 1(RACK1)and phosphatidylinositol 3-kinase(PI3K)through its PAS domain to inhibit glycolysis and thereby reduce cell proliferation.Regarding the regulation of cell death,PERs mediate various types of cell death in OSCC cells,such as p53-dependent apoptosis,protein kinase B(AKT)/mammalian target of rapamycin(mTOR)dependent autophagy,or hypoxia-inducible factor l-alpha(HIF-1a)mediated ferroptosis.In regulating epithelia-mesenchymal transition(EMT),PERs can lead to the downregulation of EMT related genes,such as zinc finger E-box binding homeobox 1/2(ZEBI/2),twist family BHLH transcription factor 1/2(TWIST1/2),and Vimentin,thereby influencing the migration and invasion capabilities of OSCC cells.In tumor angiogenesis,PERs exert regulatory effects on related factors,such as methionyl aminopeptidase 2(MetAP2)and vascular endothelial growth factor(VEGF).In the tumor immune microenvironment,PERs can inhibit the inhibitor of kappa B kinase(IKK)/nuclear factor kappa B(NF-kB)pathway and programmed cell death ligand 1(PD-L1)expression,thereby enhancing the cytotoxic effect of CD8+T cells on OSCC cells.In-depth studies focusing on elucidating the precise regulatory mechanisms of PERs can facilitate the development of therapeutic strategies targeting PERs,including restoration of PERs expression/activity,targeting PERs-regulated pathways,combination therapies,and chronotherapy.These furnish a theoretical foundation for formulating individualized treatment plans to achieve precise treatment for patients with OSCC.展开更多
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 therap...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.展开更多
Background:Oral cancer remains a significant global health challenge,as it has high morbidity and mortality rates.Current treatments show limited efficacy and have severe side effects,prompting searches for new therap...Background:Oral cancer remains a significant global health challenge,as it has high morbidity and mortality rates.Current treatments show limited efficacy and have severe side effects,prompting searches for new therapeutic agents.SH003,a traditional herbal formulation comprising Astragalus membranaceus,Angelica gigas,and Trichosanthes kirilowii,has demonstrated potential anticancer properties in previous studies.However,its specific efficacy against oral cancer and the role of its key components,particularly Cucurbitacin D,remain underexplored.Methods:The cytotoxic effects of SH003 and its major components—i.e.,Cucurbitacin D,Decursin,Formononetin,and Nodakenin—were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide(MTT),Trypan Blue exclusion,and Lactate Dehydrogenase(LDH)release assays.Cell migration was analyzed via wound healing assays,and apoptosis induction was assessed using cell cycle analysis and caspase activation assays.Epithelial-tomesenchymal transition(EMT)marker expression(E-cadherin and N-cadherin)was measured using Western blotting and Quantitative reverse transcription PCR(qRT-PCR).Results:SH003 significantly reduced cell viability in a dosedependent manner,with YD-8 and YD-9 cells showing greater sensitivity than YD-38 cells.Of the individual compounds,Cucurbitacin D was identified as a key active agent,as it exhibited potent inhibition of cell migration and significant modulation of EMT markers,including the upregulation of E-cadherin and downregulation of N-cadherin.These effects were most pronounced in YD-9 cells.Conclusions:Taken together,these findings suggest that Cucurbitacin D plays a crucial role mediating the anticancer activity of SH003,particularly via the reversal of EMT and the reduction of migratory and invasive potential of oral cancer cells.This study provides valuable insight into the mechanistic basis of SH003,highlighting its potential as a therapeutic agent against oral cancer.Further research,including in vivo studies and clinical trials,is needed to elucidate its precise mechanisms and potential applications against other cancer types.展开更多
Oral squamous cell carcinoma(OSCC)constitutes 90%of oral tumors.Advanced cases severely impair patients'life quality of life due to anatomical location and limited therapies.Conventional treatments often induce dr...Oral squamous cell carcinoma(OSCC)constitutes 90%of oral tumors.Advanced cases severely impair patients'life quality of life due to anatomical location and limited therapies.Conventional treatments often induce drug resistance or recurrence.Patientderived xenograft(PDX)models are widely used to simulate tumor progression and drug responses,serving as translational tools for precision medicine.This study aimed to establish drug-resistant OSCC PDX models.Human OSCC tissues were transplanted into immunodeficient mice and passaged(P1–P2).At P2(tumor volume:40–80 mm^(3)),mice received cisplatin(1 mg/kg,three times/week)with cetuximab(1 mg/kg,weekly),GSK690693(10 mg/kg,five times/week),or rapamycin(4 mg/kg,five times/week).PDX tissues from groups with less-therapeutic response(manifested as larger tumor volumes)were serially passaged to assess treatment efficacy.Tumor tissues with diminished drug sensitivity underwent histopathological analysis and identified stability of their tumor characteristics using hematoxylin–eosin(HE)and immunohistochemical staining after one additional passage and retreatment.Results demonstrated that successive passaging accelerates tumor growth.First-generation treatments showed universal sensitivity.At P2,cisplatin–cetuximab and rapamycin groups remained sensitive,whereas GSK690693 efficacy declined.Continued passaging of GSK690693-treated tumors confirmed resistance,as evidenced by exhibiting enhanced malignant characteristics at histological level.The GSK690693-resistant model was established first,whereas resistant models of other treatment groups were established according to similar protocols.These findings suggest that sequential passaging and drug exposure in PDX models recapitulated clinical tumor evolution,enabling the development of drug-resistant OSCC models.This study can offer methodological insights for precision therapy of OSCC.展开更多
Decorin(DCN)is primarily found in the connective tissues of various parts of the body,including the lungs,kidneys,bone tissue,aorta,and tendons.It is an important component of the extracellular matrix(ECM)and belongs ...Decorin(DCN)is primarily found in the connective tissues of various parts of the body,including the lungs,kidneys,bone tissue,aorta,and tendons.It is an important component of the extracellular matrix(ECM)and belongs to the class I small leucine-rich proteoglycans family.DCN is increasingly attracting attention due to its significant role in tumors,fibrotic diseases,and the regulation of vascular formation.Moreover,its anti-tumor properties have positioned it as a promising biomarker in the fight against cancer.Numerous studies have confirmed that DCN can exert inhibitory effects in various solid tumors,particularly in oral squamous cell carcinoma(OSCC),by activating its downstream pathways through binding with the epidermal growth factor receptor(EGFR)and mesenchymal-epithelial transition(MET)receptor,or by stabilizing and enhancing the expression of the tumor suppressor gene p53 to mediate apoptosis in cancer cells that have undergone mutation.The occurrence of OSCC is a continuous and dynamic process,encompassing the transition from normal mucosa to oral potentially malignant disorders(OPMDs),and further progressing from OPMDs to the malignant transformation into OSCC.We have found that DCN may exhibit a bidirectional effect in the progression of oral mucosal carcinogenesis,showing a trend of initial elevation followed by a decline,which decreases with the differentiation of OSCC.In OPMDs,DCN exhibits high expression and may be associated with malignant transformation,possibly linked to the increased expression of P53 in OPMDs.In OSCC,the expression of DCN is reduced,which can impact OSCC angiogenesis,and inhibit tumor cell proliferation,migration,and invasion capabilities,serving as a potential marker for predicting adverse prognosis in OSCC patients.This article reviews the current research status of DCN,covering its molecular structure,properties,and involvement in the onset and progression of oral mucosal carcinogenesis.It elucidates DCN’s role in this process and aims to offer insights for future investigations into its mechanism of action in oral mucosal carcinogenesis and its potential application in the early diagnosis and treatment of OSCC.展开更多
Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanism...Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC.展开更多
BACKGROUND Odontogenic infection is one of the common infectious diseases in oral and maxillofacial head and neck regions.Clinically,if early odontogenic infections such as acute periapical periodontitis,alveolar absc...BACKGROUND Odontogenic infection is one of the common infectious diseases in oral and maxillofacial head and neck regions.Clinically,if early odontogenic infections such as acute periapical periodontitis,alveolar abscess,and pericoronitis of wisdom teeth are not treated timely,effectively and correctly,the infected tissue may spread up to the skull and brain,down to the thoracic cavity,abdominal cavity and other areas through the natural potential fascial space in the oral and maxillofacial head and neck.Severe multi-space infections are formed and can eventually lead to life-threatening complications(LTCs),such as intracranial infection,pleural effusion,empyema,sepsis and even death.CASE SUMMARY We report a rare case of death in a 41-year-old man with severe odontogenic multi-space infections in the oral and maxillofacial head and neck regions.One week before admission,due to pain in the right lower posterior teeth,the patient placed a cigarette butt dipped in the pesticide"Miehailin"into the"dental cavity"to relieve the pain.Within a week,the infection gradually spread bilaterally to the floor of the mouth,submandibular space,neck,chest,waist,back,temporal and other areas.The patient had difficulty breathing,swallowing and eating,and was transferred to our hospital as an emergency admission.Following admission,oral and maxillofacial surgeons immediately organized consultations with doctors in otolaryngology,thoracic surgery,general surgery,hematology,anesthesia and the intensive care unit to assist with treatment.The patient was treated with the highest level of antibiotics(vancomycin)and extensive abscess incision and drainage in the oral,maxillofacial,head and neck,chest and back regions.Unfortunately,the patient died of septic shock and multiple organ failure on the third day after admission.CONCLUSION Odontogenic infection can cause serious multi-space infections in the oral and maxillofacial head and neck regions,which can result in multiple LTCs.The management and treatment of LTCs such as multi-space infections should be multidisciplinary led by oral and maxillofacial surgeons.展开更多
Objective: To develop a BALB/c mouse model of oral submucous fibrosis(OSF)induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes.Methods: BALB/c mice were randomly assigned to either ...Objective: To develop a BALB/c mouse model of oral submucous fibrosis(OSF)induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes.Methods: BALB/c mice were randomly assigned to either the control(distilled water) or experimental group(arecoline)(n = 40). Eight mice from each group were sacrificed every 4 weeks since 8 weeks post treatment. Changes in histopathologic features, levels of collagen type Ⅰ and collagen type Ⅲ, and angiogenesis were measured.Results: In the 8th week, epithelium atrophy, collagen cumulation and micrangium pathologic changes in the lamina propria were observed in the oral mucosa. In the 20th week, hyaline degeneration of the connective tissues was observed on the tongue and palate mucosa. The angiogenesis and collagen type Ⅰ changed significantly as the diseases advanced(P < 0.05); however, collagen type Ⅲ was not statistically different.Conclusions: An OSF model involving mice can be rapidly induced by drinking a highdose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type Ⅰ.展开更多
Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated wit...Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.展开更多
Objective:To investigate the effect of Phyllanthus emblica(P.emblica) Linn,ethanolic extract on the adhesion of Candida albicans(C.albicans) to human buccal epithelial cells(BECs) and denture acrylic surfaces.Methods:...Objective:To investigate the effect of Phyllanthus emblica(P.emblica) Linn,ethanolic extract on the adhesion of Candida albicans(C.albicans) to human buccal epithelial cells(BECs) and denture acrylic surfaces.Methods:Human BECs and transparent acrylic strips were pretreated with ethanolic extract solution of P.emblica fruits at concentration ranged from 18.7 to 300 mg/mL.After washing BECs and the strips were inoculated with three strains of C.albicans (ATCC 10281 and two clinical isolates)(10~7 cells/mL).Normal saline solution(NSS) and 0.2% chlorhexidine gluconate were used as negative and positive controls,respectively.BECs were harvested on 12μm-polycarbonate filters(Millipore,USA).The membrane filters and the strips were stained with Gram stain.Adherent yeast cells on 100 randomly selected epithelial cells and 20 randomly selected fields on each strip were counted under microscope.The statistical significance was calculated by Kruskal-Wallis and Tukey tests at a significant level of P【0.05. Results:Significant lower numbers of all strains of yeasts adhering to BECs and acrylic strips were observed after exposure to 75-300 mg/mL of plant extract compared with NSS.Conclusions: The present study demonstrates that P.emblica ethanolic extract interferes with the adhesion of C. albicans to BECs and denture acrylic surfaces in vitro.展开更多
As an important component of the tumor microenvironment,cancer-associated fibroblasts(CAFs)secrete energy metabolites to supply energy for tumor progression.Abnormal regulation of long noncoding RNAs(lncRNAs)is though...As an important component of the tumor microenvironment,cancer-associated fibroblasts(CAFs)secrete energy metabolites to supply energy for tumor progression.Abnormal regulation of long noncoding RNAs(lncRNAs)is thought to contribute to glucose metabolism,but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined.In the present study,by using RNA sequencing and bioinformatics analysis,we analyzed the lncRNA/mRNA profiles of normal fibroblasts(NFs)derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma(OSCC).LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs.Using small interfering RNA(siRNA)strategies,we determined that lncRNA H19 knockdown affected proliferation,migration,and glycolysis in oral CAFs.We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway,6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)and miR-675-5p.Furthermore,the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs,as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor.Our study presents a new way to understand glucose metabolism in oral CAFs,theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.展开更多
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 mali...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.展开更多
Objective: To investigate the effect of the roselle calyx extract(RCE)(Hibiscus sabdariffa L.) on the in vitro viability and biofilm formation ability of oral pathogenic bacteria. Methods:RCE was prepared by soaking r...Objective: To investigate the effect of the roselle calyx extract(RCE)(Hibiscus sabdariffa L.) on the in vitro viability and biofilm formation ability of oral pathogenic bacteria. Methods:RCE was prepared by soaking roselle calyx powder with ethyl alcohol for 24 h at room temperature. After centrifugation, the extract was lyophilized. Then, the extract was dissolved in phosphate-buffered saline, the p H was adjusted, and the extract was aseptically filtered. We used Streptococcus mutans, Streptococcus sanguinis, Lactobacillus casei, Actinomyces naeslundii, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis and Prevotella intermedia in this study. The antibacterial activity of the RCE was determined by treating the cells of these bacteria with the extract for 10 or 20 min at room temperature. The minimum inhibitory concentration(MIC) and minimum bactericidal concentration was determined using the micro dilution method, and the effect of the RCE on the ability to form biofilm was determined using a polystyrene micro plate assay. In addition, we used the WST-1 assay to determine the cytotoxicity of the RCE on HGF, Ca9-22 and KB cells. Results: The RCE had antibacterial activity against oral bacteria used in this study. In particular, most significant antibacterial activity was observed against Fusobacterium nucleatum, Prevotella intermedia and Porphyromonas gingivalis. The MIC and minimum bactericidal concentration were 7.2 mg/m L–28.8 mg/m L and 14.4 to >57.6 mg/m L. The RCE had an inhibitory effect on biofilm formation at the MIC and sub-MIC levels. In addition, the RCE had low cytotoxic effects on HGF, Ca9-22 and KB cells. Conclusions: Thus, our results indicate that the RCE may be used for preventing oral diseases.展开更多
文摘BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(ECM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remodeling and the degradation of the ECM.MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions.MMP-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of tumors.Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.AIM To assess the immunohistochemical expression of MMP-9 and MMP-13 in OSCC.METHODS A total of 40 cases with histologically confirmed OSCC by incisional biopsy were included in this cross-sectional retrospective study.The protocols for both MMP-9 and MMP-13 immunohistochemical staining were performed according to the manufacturer’s recommendations along with the normal gingival epithelium as a positive control.All the observations were recorded and Pearson’sχ²test with Fisher exact test was used for statistical analysis.RESULTS Our study showed no significant correlation between MMP-9 and MMP-13 staining intensity and tumor size.The majority of the patients were in advanced TNM stages(III and IV),and showed intense expression of MMP-9 and MMP-13.CONCLUSION The present study suggests that both MMP-9 and MMP-13 play an important and independent role in OSCC progression and invasiveness.Intense expression of MMP-9 and MMP-13,irrespective of histological grade of OSCC,correlates well with TNM stage.Consequently,it is evident that MMP-9 and MMP-13 are important for the invasiveness and progression of tumors.The findings may facilitate the development of new approaches for evaluating lymph node metastases and interventional therapy techniques,hence enhancing the prognosis of patients diagnosed with OSCC.
基金supported by the National Natural Science Foundation of China(grant#82370975 and 82170969)。
文摘Cancer stem cells(CSCs)are widely acknowledged as primary mediators to the initiation and progression of tumors.The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years.Porphyromonas gingivalis(P.gingivalis)is increasingly considered to be closely related to the development of oral squamous cell carcinoma(OSCC).Nevertheless,the role of P.gingivalis in the stemness of OSCC cells remains uncertain.Herein,we showed that P.gingivalis was positively correlated with CSC markers expression in human OSCC specimens,promoted the stemness and tumorigenicity of OSCC cells,and enhanced tumor formation in nude mice.Mechanistically,P.gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1(SCD1)expression,a key enzyme involved in lipid metabolism,which ultimately resulted in enhanced acquisition of stemness.Moreover,SCD1 suppression attenuated P.gingivalis-induced stemness of OSCC cells,including CSCs markers expression,sphere formation ability,chemoresistance,and tumor growth,in OSCC cells both in vitro and in vivo.Additionally,upregulation of SCD1 in P.gingivalis-infected OSCC cells was associated with the expression of KLF5,and that was modulated by P.gingivalis-activated NOD1 signaling.Taken together,these findings highlight the importance of SCD1-dependent lipid synthesis in P.gingivalis-induced stemness acquisition in OSCC cells,suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
文摘BACKGROUND Oral squamous cell carcinoma(OSCC)is a frequent cancer affecting the oral cavity.OSCC is usually preceded by occurrence of precursor lesions,which demonstrate a varying degree of malignant transformation potential.Epithelialmesenchymal transition is a significant biological phenomenon that facilitates tumor growth and metastasis through the involvement of diverse epithelial and mesenchymal proteins.E-cadherin down regulation and over-expression of zincfinger E-box-binding homeobox 1(ZEB1)has been reported in several cancers.AIM To evaluate the role of E-cadherin and ZEB1 in oral leukoplakia and OSCC.METHODS A total of 60 cases i.e.,oral leukoplakia/oral epithelial dysplasia(OED)(n=30)and OSCC(n=30)were included.Immunohistochemistry was performed utilizing two markers:E-cadherin and ZEB1.The Mann-Whitney U test was employed to compare individual markers across the study groups.Spearman’s correlation was done followed by discriminant function analysis.RESULTS Reduction in the expression E-cadherin and altered localization were noted from OED to OSCC.Overexpression of ZEB1 along with cytoplasmic accumulation was noted in OED,with marked expression in OSCC.ZEB1 epithelium intensity and ZEB1 connective tissue percentage contributed to the discriminant function with an accuracy of 85%for the classification of OED from OSCC.CONCLUSION Loss of E-cadherin and up-regulation of ZEB1 from OED to OSCC,predisposes to induction of epithelial-mesenchymal transition.Discriminant formulas are developed to classify cases of OED and OSCC with 85%accuracy.
基金supported by the National Natural Science Foundation of China(U23A20445)the Science and Technology Program of Guangzhou(202206080009)。
文摘Radiochemotherapy-induced oral mucositis(OM)is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy.Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment.To date,differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties,which has increased the uncertainty of treatment effects.On the basis of current research evidence,this expert consensus outlines risk factors,clinical manifestations,clinical grading,ancillary examinations,diagnostic basis,prevention and treatment strategies and efficacy indicators for OM.In addition to strategies such as basic oral care,antiinflammatory and analgesic agents,anti-infective agents,pro-healing agents,and photobiotherapy recommended in previous guidelines,we also emphasize the role of traditional Chinese medicine in OM prevention and treatment.This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention,diagnosis,and treatment,standardizing clinical practice,reducing OM occurrence,promoting healing,and improving the quality of life of patients.
文摘Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(PTMs),such as phosphorylation,acetylation,methylation,and glycosylation,regulate osteogenic differentiation(OD).These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix.While the molecular mechanisms behind OD are increasingly understood,many questions remain,particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation.Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases.This review summarizes the role of PTMs in the OD of oral-derived stem cells,discusses their clinical applications,and suggests future research directions.
基金supported by the following funding:National Natural Science Foundations of China(82002888,82272899 and 82370974)Sichuan Science and Technology Program(2022YFS0207 and 2023YFS0127)+1 种基金Scientific Research Foundation,WestChinaHospital of Stomatology SichuanUniversity(RCDWJS2021-8)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-004).
文摘This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression pattern in OSCC,and the expression levels of PERs in OSCC patients are correlated with a favorable prognosis.PERs impact the occurrence and development of OSCC through multiple pathways.In the regulation of cell proliferation,they can function not only through cell cycle regultion but also via metabolic pathways.For example,PER1 can interact with receptors for activated C kinase 1(RACK1)and phosphatidylinositol 3-kinase(PI3K)through its PAS domain to inhibit glycolysis and thereby reduce cell proliferation.Regarding the regulation of cell death,PERs mediate various types of cell death in OSCC cells,such as p53-dependent apoptosis,protein kinase B(AKT)/mammalian target of rapamycin(mTOR)dependent autophagy,or hypoxia-inducible factor l-alpha(HIF-1a)mediated ferroptosis.In regulating epithelia-mesenchymal transition(EMT),PERs can lead to the downregulation of EMT related genes,such as zinc finger E-box binding homeobox 1/2(ZEBI/2),twist family BHLH transcription factor 1/2(TWIST1/2),and Vimentin,thereby influencing the migration and invasion capabilities of OSCC cells.In tumor angiogenesis,PERs exert regulatory effects on related factors,such as methionyl aminopeptidase 2(MetAP2)and vascular endothelial growth factor(VEGF).In the tumor immune microenvironment,PERs can inhibit the inhibitor of kappa B kinase(IKK)/nuclear factor kappa B(NF-kB)pathway and programmed cell death ligand 1(PD-L1)expression,thereby enhancing the cytotoxic effect of CD8+T cells on OSCC cells.In-depth studies focusing on elucidating the precise regulatory mechanisms of PERs can facilitate the development of therapeutic strategies targeting PERs,including restoration of PERs expression/activity,targeting PERs-regulated pathways,combination therapies,and chronotherapy.These furnish a theoretical foundation for formulating individualized treatment plans to achieve precise treatment for patients with OSCC.
基金supported by the National Natural Science Foundation of China grant(81974150).
文摘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.
基金supported by grants from the Seoul National University Bundang Hospital(SNUBH)Research Fund(Grant no.02-2020-0008)the Creative-Pioneering Researchers Program of Seoul National University(Grant no.860-20240109).
文摘Background:Oral cancer remains a significant global health challenge,as it has high morbidity and mortality rates.Current treatments show limited efficacy and have severe side effects,prompting searches for new therapeutic agents.SH003,a traditional herbal formulation comprising Astragalus membranaceus,Angelica gigas,and Trichosanthes kirilowii,has demonstrated potential anticancer properties in previous studies.However,its specific efficacy against oral cancer and the role of its key components,particularly Cucurbitacin D,remain underexplored.Methods:The cytotoxic effects of SH003 and its major components—i.e.,Cucurbitacin D,Decursin,Formononetin,and Nodakenin—were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide(MTT),Trypan Blue exclusion,and Lactate Dehydrogenase(LDH)release assays.Cell migration was analyzed via wound healing assays,and apoptosis induction was assessed using cell cycle analysis and caspase activation assays.Epithelial-tomesenchymal transition(EMT)marker expression(E-cadherin and N-cadherin)was measured using Western blotting and Quantitative reverse transcription PCR(qRT-PCR).Results:SH003 significantly reduced cell viability in a dosedependent manner,with YD-8 and YD-9 cells showing greater sensitivity than YD-38 cells.Of the individual compounds,Cucurbitacin D was identified as a key active agent,as it exhibited potent inhibition of cell migration and significant modulation of EMT markers,including the upregulation of E-cadherin and downregulation of N-cadherin.These effects were most pronounced in YD-9 cells.Conclusions:Taken together,these findings suggest that Cucurbitacin D plays a crucial role mediating the anticancer activity of SH003,particularly via the reversal of EMT and the reduction of migratory and invasive potential of oral cancer cells.This study provides valuable insight into the mechanistic basis of SH003,highlighting its potential as a therapeutic agent against oral cancer.Further research,including in vivo studies and clinical trials,is needed to elucidate its precise mechanisms and potential applications against other cancer types.
基金National Natural Science Foundation of China,Grant/Award Number:82173399Young Elite Scientists Sponsorship Program by CAST,Grant/Award Number:2022QNRC001+2 种基金Beijing Natural Science Foundation,Grant/Award Number:7252096Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund Project,Grant/Award Number:L222145CAMS&Comparative Medicine Center,PUMC (IACUC approval number:QC24002)
文摘Oral squamous cell carcinoma(OSCC)constitutes 90%of oral tumors.Advanced cases severely impair patients'life quality of life due to anatomical location and limited therapies.Conventional treatments often induce drug resistance or recurrence.Patientderived xenograft(PDX)models are widely used to simulate tumor progression and drug responses,serving as translational tools for precision medicine.This study aimed to establish drug-resistant OSCC PDX models.Human OSCC tissues were transplanted into immunodeficient mice and passaged(P1–P2).At P2(tumor volume:40–80 mm^(3)),mice received cisplatin(1 mg/kg,three times/week)with cetuximab(1 mg/kg,weekly),GSK690693(10 mg/kg,five times/week),or rapamycin(4 mg/kg,five times/week).PDX tissues from groups with less-therapeutic response(manifested as larger tumor volumes)were serially passaged to assess treatment efficacy.Tumor tissues with diminished drug sensitivity underwent histopathological analysis and identified stability of their tumor characteristics using hematoxylin–eosin(HE)and immunohistochemical staining after one additional passage and retreatment.Results demonstrated that successive passaging accelerates tumor growth.First-generation treatments showed universal sensitivity.At P2,cisplatin–cetuximab and rapamycin groups remained sensitive,whereas GSK690693 efficacy declined.Continued passaging of GSK690693-treated tumors confirmed resistance,as evidenced by exhibiting enhanced malignant characteristics at histological level.The GSK690693-resistant model was established first,whereas resistant models of other treatment groups were established according to similar protocols.These findings suggest that sequential passaging and drug exposure in PDX models recapitulated clinical tumor evolution,enabling the development of drug-resistant OSCC models.This study can offer methodological insights for precision therapy of OSCC.
基金the National Key Laboratory of Oral Disease Prevention and Treatment of Open Subject Project(SKLOD2024OF04)Luzhou City Science and Technology Plan Project(2023RCX171)Sichuan Province Medical Research Project Program(S23043)。
文摘Decorin(DCN)is primarily found in the connective tissues of various parts of the body,including the lungs,kidneys,bone tissue,aorta,and tendons.It is an important component of the extracellular matrix(ECM)and belongs to the class I small leucine-rich proteoglycans family.DCN is increasingly attracting attention due to its significant role in tumors,fibrotic diseases,and the regulation of vascular formation.Moreover,its anti-tumor properties have positioned it as a promising biomarker in the fight against cancer.Numerous studies have confirmed that DCN can exert inhibitory effects in various solid tumors,particularly in oral squamous cell carcinoma(OSCC),by activating its downstream pathways through binding with the epidermal growth factor receptor(EGFR)and mesenchymal-epithelial transition(MET)receptor,or by stabilizing and enhancing the expression of the tumor suppressor gene p53 to mediate apoptosis in cancer cells that have undergone mutation.The occurrence of OSCC is a continuous and dynamic process,encompassing the transition from normal mucosa to oral potentially malignant disorders(OPMDs),and further progressing from OPMDs to the malignant transformation into OSCC.We have found that DCN may exhibit a bidirectional effect in the progression of oral mucosal carcinogenesis,showing a trend of initial elevation followed by a decline,which decreases with the differentiation of OSCC.In OPMDs,DCN exhibits high expression and may be associated with malignant transformation,possibly linked to the increased expression of P53 in OPMDs.In OSCC,the expression of DCN is reduced,which can impact OSCC angiogenesis,and inhibit tumor cell proliferation,migration,and invasion capabilities,serving as a potential marker for predicting adverse prognosis in OSCC patients.This article reviews the current research status of DCN,covering its molecular structure,properties,and involvement in the onset and progression of oral mucosal carcinogenesis.It elucidates DCN’s role in this process and aims to offer insights for future investigations into its mechanism of action in oral mucosal carcinogenesis and its potential application in the early diagnosis and treatment of OSCC.
基金supported by Hebei Natural Science Foundation(H2024206476)Medical Science Research Project of Hebei(20240101).
文摘Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC.
文摘BACKGROUND Odontogenic infection is one of the common infectious diseases in oral and maxillofacial head and neck regions.Clinically,if early odontogenic infections such as acute periapical periodontitis,alveolar abscess,and pericoronitis of wisdom teeth are not treated timely,effectively and correctly,the infected tissue may spread up to the skull and brain,down to the thoracic cavity,abdominal cavity and other areas through the natural potential fascial space in the oral and maxillofacial head and neck.Severe multi-space infections are formed and can eventually lead to life-threatening complications(LTCs),such as intracranial infection,pleural effusion,empyema,sepsis and even death.CASE SUMMARY We report a rare case of death in a 41-year-old man with severe odontogenic multi-space infections in the oral and maxillofacial head and neck regions.One week before admission,due to pain in the right lower posterior teeth,the patient placed a cigarette butt dipped in the pesticide"Miehailin"into the"dental cavity"to relieve the pain.Within a week,the infection gradually spread bilaterally to the floor of the mouth,submandibular space,neck,chest,waist,back,temporal and other areas.The patient had difficulty breathing,swallowing and eating,and was transferred to our hospital as an emergency admission.Following admission,oral and maxillofacial surgeons immediately organized consultations with doctors in otolaryngology,thoracic surgery,general surgery,hematology,anesthesia and the intensive care unit to assist with treatment.The patient was treated with the highest level of antibiotics(vancomycin)and extensive abscess incision and drainage in the oral,maxillofacial,head and neck,chest and back regions.Unfortunately,the patient died of septic shock and multiple organ failure on the third day after admission.CONCLUSION Odontogenic infection can cause serious multi-space infections in the oral and maxillofacial head and neck regions,which can result in multiple LTCs.The management and treatment of LTCs such as multi-space infections should be multidisciplinary led by oral and maxillofacial surgeons.
基金supported by grants from the National Natural Science Foundation of China(Grant No.81460105)the National Natural Science Foundation of China(Grant No.81360407)+1 种基金the National Natural Science Foundation of Hainan Province(Grant No.2058321)Foundation of Health Department of Hainan Province(Grant No.14A210189)
文摘Objective: To develop a BALB/c mouse model of oral submucous fibrosis(OSF)induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes.Methods: BALB/c mice were randomly assigned to either the control(distilled water) or experimental group(arecoline)(n = 40). Eight mice from each group were sacrificed every 4 weeks since 8 weeks post treatment. Changes in histopathologic features, levels of collagen type Ⅰ and collagen type Ⅲ, and angiogenesis were measured.Results: In the 8th week, epithelium atrophy, collagen cumulation and micrangium pathologic changes in the lamina propria were observed in the oral mucosa. In the 20th week, hyaline degeneration of the connective tissues was observed on the tongue and palate mucosa. The angiogenesis and collagen type Ⅰ changed significantly as the diseases advanced(P < 0.05); however, collagen type Ⅲ was not statistically different.Conclusions: An OSF model involving mice can be rapidly induced by drinking a highdose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type Ⅰ.
基金Supported by Hamburger Stiftung zur Forderung der KrebsbekampfungNo.188 to Grobe A and Riethdorf SERC Advanced Investigator Grant "DISSECT"(Pantel K),No.269081.
文摘Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.
文摘Objective:To investigate the effect of Phyllanthus emblica(P.emblica) Linn,ethanolic extract on the adhesion of Candida albicans(C.albicans) to human buccal epithelial cells(BECs) and denture acrylic surfaces.Methods:Human BECs and transparent acrylic strips were pretreated with ethanolic extract solution of P.emblica fruits at concentration ranged from 18.7 to 300 mg/mL.After washing BECs and the strips were inoculated with three strains of C.albicans (ATCC 10281 and two clinical isolates)(10~7 cells/mL).Normal saline solution(NSS) and 0.2% chlorhexidine gluconate were used as negative and positive controls,respectively.BECs were harvested on 12μm-polycarbonate filters(Millipore,USA).The membrane filters and the strips were stained with Gram stain.Adherent yeast cells on 100 randomly selected epithelial cells and 20 randomly selected fields on each strip were counted under microscope.The statistical significance was calculated by Kruskal-Wallis and Tukey tests at a significant level of P【0.05. Results:Significant lower numbers of all strains of yeasts adhering to BECs and acrylic strips were observed after exposure to 75-300 mg/mL of plant extract compared with NSS.Conclusions: The present study demonstrates that P.emblica ethanolic extract interferes with the adhesion of C. albicans to BECs and denture acrylic surfaces in vitro.
基金supported by the National Natural Science Foundation of China(No.82071124,and 82002884)Sichuan Science and Technology Program(No.2019YFS0361,No.2021YFS0194 and No.2021YFH0143)Science and Technology Program of Chengdu City(No.2019YF0501151SN).
文摘As an important component of the tumor microenvironment,cancer-associated fibroblasts(CAFs)secrete energy metabolites to supply energy for tumor progression.Abnormal regulation of long noncoding RNAs(lncRNAs)is thought to contribute to glucose metabolism,but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined.In the present study,by using RNA sequencing and bioinformatics analysis,we analyzed the lncRNA/mRNA profiles of normal fibroblasts(NFs)derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma(OSCC).LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs.Using small interfering RNA(siRNA)strategies,we determined that lncRNA H19 knockdown affected proliferation,migration,and glycolysis in oral CAFs.We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway,6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)and miR-675-5p.Furthermore,the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs,as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor.Our study presents a new way to understand glucose metabolism in oral CAFs,theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.
文摘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.
基金supported by scholarship from Futoku Foundation and Hokkaido Gas Co.Ltd
文摘Objective: To investigate the effect of the roselle calyx extract(RCE)(Hibiscus sabdariffa L.) on the in vitro viability and biofilm formation ability of oral pathogenic bacteria. Methods:RCE was prepared by soaking roselle calyx powder with ethyl alcohol for 24 h at room temperature. After centrifugation, the extract was lyophilized. Then, the extract was dissolved in phosphate-buffered saline, the p H was adjusted, and the extract was aseptically filtered. We used Streptococcus mutans, Streptococcus sanguinis, Lactobacillus casei, Actinomyces naeslundii, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis and Prevotella intermedia in this study. The antibacterial activity of the RCE was determined by treating the cells of these bacteria with the extract for 10 or 20 min at room temperature. The minimum inhibitory concentration(MIC) and minimum bactericidal concentration was determined using the micro dilution method, and the effect of the RCE on the ability to form biofilm was determined using a polystyrene micro plate assay. In addition, we used the WST-1 assay to determine the cytotoxicity of the RCE on HGF, Ca9-22 and KB cells. Results: The RCE had antibacterial activity against oral bacteria used in this study. In particular, most significant antibacterial activity was observed against Fusobacterium nucleatum, Prevotella intermedia and Porphyromonas gingivalis. The MIC and minimum bactericidal concentration were 7.2 mg/m L–28.8 mg/m L and 14.4 to >57.6 mg/m L. The RCE had an inhibitory effect on biofilm formation at the MIC and sub-MIC levels. In addition, the RCE had low cytotoxic effects on HGF, Ca9-22 and KB cells. Conclusions: Thus, our results indicate that the RCE may be used for preventing oral diseases.
