Pedunculoside promotes oral ulcer healing in mice by upregulating STAT3 and Smad3

Background:Pedunculoside(PE)is a pentacyclic triterpenoid saponin found in the dried barks of the Ilex rotunda Thunb.In traditional Chinese medicine,the juice extracted from various Ilex species is commonly used for treating inflammatory diseases.Objective:This study aims to investigate the potential of PE in promoting the healing of oral ulcers in mice and to explore its possible mechanism.Materials and Methods:A mouse model of oral ulcer was established to evaluate the healing promotion effects of PE,and an in-vitro inflammatory cell model was established by using primary fibroblasts isolated from mouse oral mucosal tissue.Gene transcription and protein expression related to cell proliferation,migration,and collagen synthesis were measured.Results:PE showed the highest cure rate of 85.7%for oral ulcers in mice within 7-days treatment.It significantly promoted cell proliferation and collagen secretion in fibroblast in-vitro model.PE also upregulated the gene transcription of Smad3,Col1a1 and Col3a1.Furthermore,PE antagonized the inhibitory effect of WP1066 on STAT3activation,but did not affect cell migration.Conclusion:This study demonstrates that PE has potential therapeutic effects in promoting oral ulcer healing in mice.The improvement was achieved by the increasing collagen synthesis through the upregulation of STAT3 and Smad3 in mucosa fibroblasts.These results provide a preliminary pharmacological work for developing PE as a potential treatment agent for oral ulcers.

Multidrug dissolvable microneedle patch for the treatment of recurrent oral ulcer

Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work reports a hyaluronic acid-based dissolvablemicroneedle patch(ROUMNpatch,short for recurrent oral ulcer microneedle)loaded with dexamethasone acetate,vitamin C and tetracaine hydrochloride for the treatment of recurrent oral ulcers.The ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin C.In vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide(LPS)-induced interleukin-6(IL-6)expression than dexamethasone alone.Cell proliferation and migrationwere also significantly promoted byROUMNcompared to vitamin C alone.The healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in rats.ROUMN as a treatment accelerated the healing process of oral ulcers,shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost,a commonly used over-the-counter(OTC)drug for oral ulcers.The rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers.

Effect and mechanism of persimmon leaf flavonoid treatment of experimental oral ulcer

OBJECTIVE To explore the therapeutic effect and its mechanism of persimmon leaf flavonoids(PLF) on rats with oral ulcer. METHODS The oral ulcer model was induced by acetic acid,was used for intervention of Guilin watermelon frost and different dose(20,40 and 80 mg·kg^(-1)) of PLF.Ulcer area was calculated on the fourth and the seventh day after injury; the changes of superoxide dismutase(SOD) and malondialdehyde(MDA) in serum and ulcer tissues were observed; the level of tumor necrosis factor alpha(TNF-alpha) in ulcer tissue was measured. To observe the pathological morphological changes of H-E staining. RESULTS Guilin watermelon frost and PLF(40 and 80 mg·kg^(-1))can reduce the ulcer area(P<0.05); PLF(20,40 and 80 mg·kg^(-1)) can increase the activity of SOD and decrease the content of MDA in serum and ulcer tissue(P<0.05); Guilin watermelon frost and PLF could significantly decrease the levels of TNF-alpha in ulcer tissue(P<0.05),and improve the inflammatory infiltration of ulcer tissue. CONCLUSION PLF has certain therapeutic effects on oral ulcer induced by acetic acid,and the mechanism may be related to improve oxidative damage and reduce inflammatory reaction.

Experimental Study of Emilia Sonchifolia Combined with Coptidis Rhizoma for the Prevention and Treatment of Oral Ulcer

Objective: This paper aims to investigate the therapeutic effect of the combination of Emilia Sonchifolia and Coptidis Rhizoma on oral ulcer rats. Methods: 36 SD rats of half male and half female were kept for 7 days, and 6 rats among them were selected as normal group by random sampling method, and the rest rats were randomly divided into model group, positive control group, Emilia Sonchifolia group, Coptidis Rhizoma group and combined group after the establishment of oral ulcer model. The normal group and model group were given blank film, the positive control group was given Guilin Watermelon Frost, and the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were given the corresponding oral film, which was administered to the ulcer for 7 days continuously, 2 times per day. The healing of oral ulcer was assessed at the end of the last day of administration, and the ulcer area was calculated on the 1st, 3rd, 5th and 7th days after successful modeling, and the serum levels of IL-2 and TNF-α in rats were detected by Emilia Sonchifolia. Results: The grading of ulcer healing in the positive control group and the combined group was better than the other groups, and the difference was statistically significant when compared with the model group (p Coptidis Rhizoma group, Emilia Sonchifolia group, combined group and positive control group was smaller than that in the model group, and the difference was statistically significant (p Emilia Sonchifolia group, Coptidis Rhizoma group and combined group were all effective in reducing the area of oral ulcer, among which the combined group was more effective. The level of pro-inflammatory factor TNF-α was reduced and the level of anti-inflammatory factor IL-2 was increased in the Emilia Sonchifolia group, Coptidis Rhizoma group and combined group, and the difference was statistically significant (p Conclusion: The combination of Coptidis Rhizoma and Emilia Sonchifolia is effective in the treatment of oral ulcer in rats, and the effect of the combination is better than that of the drug alone.

Treatment of oral ulcer based on TCM syndrome differentiation

Oral ulcer is a kind of ulcerative injury that occurs in the oral mucosa and is very common in clinic.In severe case,it can affect the quality of life of the patients.Western medicine treatment of oral ulcer is often prone to relapse,while the effect of traditional Chinese medicine treatment is remarkable.

Test Case Analysis Application of Jiawei-yinhuo Soup the Treatment of Recurrent Oral Ulceration

Recurrent oral ulceration,which is small but not easy to cure,seriously affects the quality of life of the patients.This paper analyzes professor Wang Xiaoyan's application of Yinhuotanghuacai to treat oral ulcer with floating of yang in deficiency condition,which can significantly improve the clinical symptoms of patients and improve the quality of life of patients.

Metabolomics characterization of Qingwei San on oral ulcer in db/db mice with stomach heat pattern

Objective:To characterize the effects of Qingwei San(QWS)on diabetic oral ulcer(OU)mice with stomach heat pattern through metabolomic analysis.Methods:A stomach heat pattern mouse model was established by treating C57BLKS/J Leprdb/db(db/db)mice with dried Zingiber officinale Rosc.rhizome(Z.officinale,Gan Jiang)decoction by gavage.All model mice had blood glucose levels of≥11.1 m M.Subsequently,OU was induced by Na OH cauterization.After 1 week of administration of QWS,non-targeted metabolomic analysis of serum was conducted using ultra high performance liquid chromatography coupled with mass spectrometry(UHPLC-MS/MS).Results:The non-targeted metabolomics results indicated that tryptophan metabolism,2-oxocarboxylic acid metabolism,serotonergic synapses,amino sugar and nucleotide sugar metabolism,and amino acid biosynthesis were involved in the therapeutic effects of QWS,with tryptophan metabolism playing a predominant role.Conclusion:QWS treatment can significantly improve the pathological status of diabetic OU mice with stomach heat pattern.QWS may regulate the release of inflammatory factors through the tryptophan metabolism pathway.

New therapy for oral ulcer:Evodia rutaecarpa patch combined with acupoint application

Background:Oral ulcer is the most common and easily recurrent disease in stomatology,which influence the patients’communication,normal dietary,and sleep.Evodia rutaecarpa(ER)is a traditional Chinese herbal medicine recorded in ancient Chinese medical books,which has a medicinal history of more than 2,000 years.Clinically,the application of ER at plantar Yongquan point(KI1)is effective in the treatment of oral ulcer.The purpose of this study was to combine the modern transdermal drug delivery system with traditional Chinese medicine to develop the transdermal absorption patch of ER and apply it to the treatment of oral ulcer at Yongquan point of plantar.Methods:Firstly,the medicinal materials of ER were extracted and the extracted materials were prepared into dispersed ER patch.The formulation and preparation process were screened by orthogonal design method and single factor investigation method.The adhesive and transdermal properties of the patch were used as the evaluation index of the preparation.Secondly,Wistar rats were used as experimental animals to establish a rat model of mouth ulcers.Wistar rats were randomly divided into normal group,model group(A),model group(B),low dose group,medium dose group and high dose group.the efficacy of ER on rat’s oral ulcer model was evaluated through three aspect such as apparent index,pathological index and biochemical index.Results:The patch had suitable adhesion and good skin penetration,which was an effective treatment for oral ulcer.In vivo pharmacodynamic studies,compared with the normal group,the body mass and food intake of rats in each group after modeling decreased,the amount of drinking water increased,the tissue structure of oral mucosa was damaged,and the levels of inflammatory factors(TNF-α,IL-6)and malondialdehyde increased,the levels of anti-inflammatory factors(IL-10),cell growth factor(epidermal growth factor,TGF-β_(1))and superoxide dismutase decreased.Compared with the model group,the body weight and food intake of each dosing group increased,water consumption decreased,the oral mucosal tissue structure was more complete,the levels of TNF-α,IL-6 and malondialdehyde decreased,the levels of IL-10,epidermal growth factor,TGF-β1 and superoxide dismutase increased,and the changes of various indexes were dose-related.Conclusion:ER patch can inhibit inflammatory reaction,enhance the antioxidant defense ability of the body,and promote the repair of damaged oral mucosa,so as to play an effective role in the treatment of oral ulcer.

Treatment of Oral Ulcer based on TCM Syndrome Differentiation

Oral ulcer is a kind of ulcerative injury that occurs in the oral mucosa and is very common in clinic.In severe case,it can affect the quality of life of the patients.Western medicine treatment of oral ulcer is often prone to relapse,while the effect of traditional Chinese medicine treatment is remarkable.

Oral ulcerations as the first manifestations of acute leukemia: A case report

Acute myeloblastic leukemia (AML) is a highly fatal malignant bone marrow disease. Physicians, dentists and all other healthcare professionals should be aware of sinister oral signs and symptoms in order to early diagnosis and referral of patients. Here we report a case of AML who presented with oral ulcers. Ulcers developed after a parrot bite, which initially misled the physicians. Unfortunately our patient did not survive, but early diagnosis and prompt investigation and treatment can be life-saving in many other similar cases.

Multivariate analysis of oral mucosal ulcers during orthodontic treatment

BACKGROUND Orthodontic treatment can easily cause local soft tissue reactions in the oral cavity of patients under mechanical stress,leading to oral mucosal ulcers and affecting their quality of life.At present,only limited literature has explored the factors leading to oral ulcers in orthodontic treatment,and these research results are still controversial.AIM To investigate the current status and related factors of oral mucosal ulcers during orthodontic treatment,aiming to provide a valuable reference for preventing this disease in clinical practice.METHODS A total of 587 patients who underwent orthodontic treatment at the Peking University School of Stomatology and Hospital of Stomatology between 2020 and 2022 were selected and allocated to an observation or control group according to the incidence of oral mucosal ulcers during orthodontic therapy.A questionnaire survey was constructed to collect patient data,including basic information,lifestyle and eating habits,treatment details,mental factors,and trace element levels,and a comparative analysis of this data was performed between the two groups.RESULTS A logistic regression model with oral ulcers as the dependent variable was established.The regression results showed that age(≥60 years:odds ratio[OR]:6.820;95%confidence interval[CI]:2.226–20.893),smoking history(smoking:OR:4.434;95%CI:2.527–7.782),toothbrush hardness(hard:OR:2.804;95%CI:1.746–4.505),dietary temperature(hot diet:OR:1.399;95%CI:1.220–1.722),treatment course(>1 year:OR:3.830;95%CI:2.203–6.659),and tooth brushing frequency(>1 time per day:OR:0.228;95%CI:0.138–0.377)were independent factors for oral mucosal ulcers(P<0.05).Furthermore,Zn level(OR:0.945;95%CI:0.927–0.964)was a protective factor against oral ulcers,while the SAS(OR:1.284;95%CI:1.197–1.378)and SDS(OR:1.322;95%CI:1.231–1.419)scores were risk factors.CONCLUSION Age≥60 years,smoking history,hard toothbrush,hot diet,treatment course for>1 year,tooth brushing frequency of≤1 time per day,and mental anxiety are independent risk factors for oral mucosal ulcers.Therefore,these factors should receive clinical attention and be incorporated into the development and optimization of preventive strategies for reducing oral ulcer incidence.

A cuttlefish ink nanoparticle-reinforced biopolymer hydrogel with robust adhesive and immunomodulatory features for treating oral ulcers in diabetes

Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines.However,many patients experience minimal benefits from certain medical treatments because of poor compliance,short retention times in the oral cavity,and inadequate drug efficacy.Herein,we present a novel hydrogel patch(SCE2)composed of a biopolymer matrix(featuring ultraviolet-triggered adhesion properties)loaded with cuttlefish ink nanoparticles(possessing pro-healing functions).Applying a straightforward local method initiates the formation of a hydrogel barrier that adheres to mucosal injuries under the influence of ultraviolet light.SCE2 then demonstrates exceptional capabilities for near-infrared photothermal sterilization and neutralization of reactive oxygen species.These properties contribute to the elimination of bacteria and the management of the oxidation process,thus accelerating the healing phase’s progression from inflammation to proliferation.In studies involving diabetic rats with oral ulcers,the SCE2 adhesive patch significantly quickens recovery by altering the inflamed state of the injured area,facilitating rapid re-epithelialization,and fostering angiogenesis.In conclusion,this light-sensitive hydrogel patch offers a promising path to expedited wound healing,potentially transforming treatment strategies for clinical oral ulcers.

Formulation of a new phenytoin-containing mucoadhesive and evaluation of its healing effects on oral biopsy ulcers

Background and Objective: Several studies have shown the wound healing effect of topical phenytoin, which is applied by its effect on connective tissue intracellular matrix. However, there are still some controversies about its effect on various kinds of wounds, especially in the experimental models. This study is aimed at evaluating the effect of mucoadhesive paste compared to phenytoin mucoadhesive paste on wound healing after oral biopsy. Material and Methods: In this double blind randomized clinical trial, 20 patients who were eligible for oral biopsy were allocated into the case and control groups. After the biopsy, patients having ulcers ranging between one and two centimeters were treated by simple or 1% phenytoin mucoadhesive paste. All patients were instructed to apply their paste at least three times a day for five days after the biopsy. Patients in both groups were evaluated every other day for size of the ulcer, degree of pain and diameter of the inflammatory halo. Statistical analysis was done using SPSS software and Mann-Whitney test. Results: After the second and third appointments, it was observed that the rate of wound healing and decrease in the size of the ulcers were significantly quicker in the treatment group (p = 0.001 and p = 0.003 respectively) and the patients in the phenytoin group reported less pain. Diameter of the inflammatory halo was not significantly different between two groups. Conclusion: Applying 1% phenytoin mucoadhesive paste on biopsy ulcers resulted in accelerated wound healing and decrease in pain, but had no effect on the diameter of the inflammatory halo.

Novel oral-targeted therapies for mucosal healing in ulcerative colitis

Ulcerative colitis(UC), a chronic, relapsing, remitting disease of the colon and rectum, is characterized by inflammatory ulceration of the mucosa. Current UC therapy relies on controlling acute episodes and preventing relapse. To predict modifications in the natural course of UC, mucosal healing(MH) has emerged as a major treatment goal. Endoscopic evaluation is considered the gold standard for assessing MH, which can be achieved by conventional drugs and biologics in many, but not all, patients. Consequently, interest is focusing on the development of new substances for UC therapy, and new oral agents are in the pipeline. This review will focus on the ability of newly developed oral drugs to induce and maintain MH in UC patients.

铜代谢与口腔疾病的诊断及治疗

背景:铜是人体的必需微量元素,在机体各项生理活动中起着重要作用,其代谢异常与多种疾病密切相关。铜代谢主要涉及铜离子的吸收、转运、储存和排泄等过程,这些过程共同调节铜稳态。近年来,多项研究证实铜稳态失调会严重影响人体的代谢活动,引起各个系统的疾病,而其中铜在口腔疾病中的作用也一直备受关注。目的:探讨铜在口腔疾病发生发展和治疗中的作用,并对这一领域的研究进展进行综合概述。方法:由第一作者应用计算机在PubMed、Web of Science、中国知网检索铜在口腔疾病中的相关研究,以“Cu,Copper,Copper metabolism,Oraldiseases,Oral squamous cell carcinoma,Periodontitis,Oral submucous fibrosis,Oral lichen planus,Recurrent oral ulceration,Pulpitis”等为英文检索词,以“铜,铜代谢,口腔疾病,口腔鳞状细胞癌,牙周炎,口腔黏膜纤维下变性,口腔扁平苔藓,口腔溃疡,牙髓炎”等为中文检索词,经过筛选后纳入78篇文献进行综述分析。结果与结论:(1)口腔鳞状细胞癌患者血清及唾液内的铜浓度升高,升高的铜通过氧化应激和促进血管生成,促进癌症进展。而通过靶向过度升高或降低肿瘤细胞内铜浓度均可抑制肿瘤细胞生长,铜与抗癌药物联合应用,能显著提高药物疗效。(2)牙周炎患者血清中铜浓度升高,铜过量可促进氧化应激,加重牙周炎。而铜与药物制剂联合作用,可促进牙周骨再生和牙周组织愈合。(3)体内铜水平与口腔黏膜纤维化程度呈正相关关系,升高的铜进入口腔黏膜内,上调赖氨酰氧化酶的活性,从而增加胶原蛋白的产生,促进口腔黏膜纤维化。(4)口腔扁平苔藓患者体内铜含量升高,升高的铜可能通过调控免疫细胞功能促进扁平苔藓的进展。(5)复发性口腔溃疡患者血清铜水平显著增高,铜利用发生障碍,可导致含铜酶活性降低,从而影响溃疡的愈合。由此可见:铜与多种口腔疾病密切相关,针对铜的相关治疗可显著提高药物疗效,但还需进一步研究其作用机制,为口腔疾病提供更完善的治疗策略奠定基础。

葛惠男运用清口方治疗顽固性口腔溃疡经验

顽固性口腔溃疡是一种发生于口腔黏膜上的溃疡性疾病,具有病程反复、发作频率高的特点。葛惠男认为,本病病机以火为主,可夹湿、夹虚、夹瘀,以清热益阴、利湿通络为治疗原则,自创清口方随证加减治疗该病,疗效颇丰。本文总结葛惠男运用清口方治疗顽固性口腔溃疡经验,附验案1则。

泻心导赤散加味联合西药治疗心脾积热型复发性口腔溃疡临床研究

目的:观察泻心导赤散加味联合西药治疗心脾积热型复发性口腔溃疡(ROU)的临床疗效。方法:采用随机数字表法将2020年6月—2023年4月玉环海成口腔门诊部收治的82例心脾积热型ROU患者分为观察组与对照组各41例。对照组给予常规西药治疗,观察组在对照组基础上加用泻心导赤散加味治疗。2组均连续治疗2周。比较2组治疗前后中医证候评分、视觉模拟评分法(VAS)评分、溃疡直径、免疫功能指标以及血清肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6水平,评估2组临床疗效、疾病复发情况。结果:治疗后,观察组总有效率高于对照组(P<0.05)。治疗后,2组中医证候评分、VAS评分、溃疡直径及CD8^(+)、TNF-α和IL-6水平均较治疗前降低,CD3^(+)、CD4^(+)水平升高(P<0.05),且观察组中医证候评分、VAS评分、溃疡直径及CD8^(+)、TNF-α和IL-6水平低于对照组,CD3^(+)、CD4^(+)水平高于对照组(P<0.05)。观察组疾病复发率4.76%(1/21),低于对照组42.86%(6/14)(P<0.05)。结论:泻心导赤散加味联合西药治疗心脾积热型ROU疗效确切,能够减轻患者疼痛,提高免疫功能,降低炎症反应及疾病复发率。

Effect of lead on IL-8 production and cell proliferation in human oral keratinocytes

Objective:To investigate the effect of lead on the production of IL-8 and cell proliferation in normal human oral keratinocytes（NHKs）.Methods:NHKs were prepared as outgrowths from normal human buccal mucosa.The cells were treated with three concentrations of lead glutamate(4.5×10-5M,4.5×10-6M and 4.5×10-7M).NHKs grown in glutamic acid were used as control.The amounts of IL-8 secreted in the culture supernatants were evaluated at 12 and 24 h using enzyme-linked immunospecific assay（ELISA）.Cell proliferation was determined by the MTT colorimetric assay.Three cultures were used for each experiment,and three independent experiments were performed.Analysis of variance and Duncan’s multiple range tests were used for statistical analysis.Results:An elevation of IL-8 in culture supernatants of NHKs treated with lead at all concentrations at 12 and 24 h after exposure in a dose-dependent manner was revealed.A significant increase in cell numbers was observed only at 24 h exposed to 4.5×10- 5M lead glutamate.Conclusions:The capacity of NHKs,to secrete IL-8,enhanced by lead glutamate,is demonstrated here.Induction of cell proliferation is revealed only after exposure to high lead concentration.The elevation of secreted IL-8 is a probable initial sign for the acute inflammatory response and may be involved in the pathogenesis of lead stomatitis.

基于“阴火理论”探析干燥综合征口腔溃疡辨治思路

口腔溃疡是干燥综合征患者常见的口腔黏膜病变,易反复发作,令人痛苦不堪。干燥综合征患者口腔溃疡多是由于脾胃虚弱、阴津不足、火热上炎、瘀毒蕴结而导致与阴火的发病机制以及临床表现有相通之处,可从阴火理论治口腔溃疡,故而提出“调补脾胃、兼顾先天”“滋阴润燥、养血生津”“降泻阴火、升提清阳”“行气活、化瘀解毒”的治疗方法,以便临床应用,促进疾病向愈。

康志媛从心肾不交论治女性复发性口糜经验

心阳下降,肾阴上泽,心肾相济,维持着人体阴阳的平衡,心肾不交,虚火上炎则致口糜。河南省名中医康志媛教授认为该病病位在口腔,病机为心肾不交,虚阳浮越,由于女性生理病理特点与心肾密切相关,在治疗女性反复口腔溃疡时善用归肾丸加肉桂引火归元,使浮阳潜藏,口糜自愈。该文对康志媛教授用药经验予以总结,以便名医经验更好地传承。