Metabolomics reveals that chronic restraint stress alleviates carbon tetrachloride-induced hepatic fibrosis through the INSR/PI3K/AKT/AMPK pathway.

Hepatic fibrosis (HF) could be developed into liver cirrhosis or even hepatocellular carcinoma. Stress has an important role in the occurrence and development of various considerable diseases. However, the effect of a certain degree stress on HF is still controversial. In our study, stress was simulated with regular chronic restraint stress (CRS) and HF model was induced with CCl4 in mice. We found that CRS was able to attenuate CCl4-induced liver injury and fibrosis in mice. Surprisingly, behavioral analysis showed that the mice in the HF group exhibited depression-like behavior. Further, the metabolomic analysis revealed that 119 metabolites and 20 metabolic pathways were altered in mice liver, especially the betaine metabolism pathway. Combined with the results of Ingenuity Pathway Analysis (IPA), the key proteins INSR, PI3K, AKT, and p-AMPK were identified and verified, and the results showed that CRS could upregulate the protein levels and mRNA expression of INSR, PI3K, AKT, and p-AMPK in liver tissues of HF mice. It suggested that CRS alleviated CCl4-induced liver fibrosis in mice through upregulation of the INSR/PI3K/AKT/AMPK pathway. Proper stress might be a potential therapeutic strategy for the treatment of chronic liver disease, which provided new insights into the treatment of HF. KEY MESSAGES: Chronic restraint stress mitigated CCl4-induced liver injury and hepatic fibrosis. CCl4-induced liver fibrosis could cause depression-like behavior. Chronic restraint stress altered metabolomic profiles in hepatic fibrosis mice, especially the betaine metabolism pathway. Chronic restraint stress increased betaine levels in liver tissue. Chronic restraint stress regulated the INSR/PI3K/AKT/AMPK signaling pathway in hepatic fibrosis mice.

Role and new insights of microfibrillar-associated protein 4 in fibrotic diseases.

Fibrosis is one of the most worrisome complications of chronic inflammatory diseases, leading to tissue damage, organ failure, and ultimately, death. The most notable pathological characteristic of fibrosis is the excessive accumulation of extracellular matrix (ECM) components such as collagen and fibronectin adjacent to foci of inflammation or damage. The human microfibrillar-associated protein 4 (MFAP4), an important member of the superfamily of fibrinogen-related proteins, is considered to have an extremely important role in ECM transformation of fibrogenesis. This review summarizes the structure, characteristics, and physiological functions of MFAP4 and the importance of MFAP4 in various fibrotic diseases. Meanwhile, we elaborated the underlying actions and mechanisms of MFAP4 in the development of fibrosis, suggesting that a better understand of MFAP4 broadens novel perspective for early screening, diagnosis, prognostic risk assessment, and treatment of fibrotic diseases.

Insight into the mechanism of Xiao-Chai-Hu-Tang alleviates irinotecan-induced diarrhea based on regulating the gut microbiota and inhibiting Gut ß-GUS.

BACKGROUND: Irinotecan (CPT-11, Camptosar@) is a first-line drug for metastatic colorectal cancer. CPT-11-induced diarrhea, which is closely related to the concentrations of ß-glucuronidase (ß-GUS) and SN-38 in the gut, largely limits its clinical application. PURPOSE: Herein, Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese formula, was applied to mitigate CPT-11-induced toxicity. This study initially explored the mechanism by which XCHT alleviated diarrhea, especially for ß-GUS from the gut microbiota. METHODS: First, we examined the levels of the proinflammatory cytokines and the anti-inflammatory cytokines in the intestine. Furthermore, we researched the community abundances of the gut microbiota in the CPT-11 and XCHT-treated mice based on 16S rRNA high-throughput sequencing technology. Meanwhile, the level of SN-38 and the concentrations of ß-GUS in intestine were examined. We also resolved the 3D structure of ß-GUS from gut microbiota by X-ray crystallography technology. Moreover, we used virtual screening, SPR analysis, and enzyme activity assays to confirm whether the main active ingredients from XCHT could selectively inhibit ß-GUS. RESULTS: In XCHT-treated mice, the levels of the proinflammatory cytokines decreased, the anti-inflammatory cytokines increased, and the community abundances of beneficial Firmicutes and Bacteroidota improved in the gut microbiota. We also found that the concentrations of ß-GUS and the level of SN-38, the major ingredient that induces diarrhea in the gut, significantly decreased after coadministration of XCHT with CPT-11 in the intestine. Additionally, we revealed the structural differences of ß-GUS from different gut microbiota. Finally, we found that EcGUS had good affinity with baicalein and meanwhile could be selectively inhibited by baicalein from XCHT. CONCLUSIONS: Overall, XCHT could relieve the delayed diarrhea induced by CPT-11 through improving the abundance of beneficial gut microbiota and reduced inflammation. Furthermore, based on the three-dimensional structure, baicalein, especially, could be used as a candidate EcGUS inhibitor to alleviate CPT-11-induced diarrhea.

The Effects of Early-Life Stress on Liver Transcriptomics and the Protective Role of EPA in a Mouse Model of Early-Life-Stress-Induced Adolescent Depression.

Early-life stress (ELS) was found to increase the risk of adolescent depression, and clinical evidence indicated that eicosapentaenoic acid (EPA) was decreased in patients with adolescent depression, but the underlying mechanisms are unclear. Here, we utilized an ELS model of maternal separation with early weaning to explore the protective role of EPA in adolescent depression. We found that that ELS induced depression-like behavior rather than anxiety-like behavior in adolescent mice. RNA-sequencing results showed that ELS changed the transcription pattern in the liver, including 863 upregulated genes and 971 downregulated genes, especially those related to the biosynthesis of unsaturated fatty acids metabolism in the liver. Moreover, ELS decreased the expression of the rate-limiting enzymes, fatty acid desaturases 1/2 (FADS1/2), involved in the biosynthesis of EPA in the liver. Additionally, ELS reduced the levels of EPA in the liver, serum, and hippocampus, and EPA administration improved depression-like behavior-induced by ELS. Our results provide transcriptomic evidence that ELS increases the risk of adolescent depression by reducing the synthesis of unsaturated fatty acids in the liver, especially EPA, and suggest that supplementation with EPA should be investigated as a potential treatment for adolescent depression.

Unravelling the Link between Psychological Distress and Liver Disease: Insights from an Anxiety-like Rat Model and Metabolomics Analysis.

Psychological distress is associated with an increase in liver disease mortality. This association highlights the close relationship between psychological and physical health. The underlying mechanism of this association needs to be elucidated. In this study, a rat model of anxiety was developed via compound stress. Changes in the HPA axis and inflammatory factors in the brains of the rats were evaluated for behavioral tests and liver function, respectively. The liver metabolic profiles of the rats were characterized through liquid chromatography-mass spectrometry (LC-MS). Differential metabolites were screened based on the conditions of p < 0.05 and VIP > 1. A pathway enrichment analysis was performed on the metabolomics data using the Ingenuity Pathway Analysis (IPA). Immunofluorescence (IF), immunohistochemistry (IHC), and Western blotting assays were performed to examine the expression of the screened target epidermal growth factor receptor (EGFR) and to elucidate the pathway associated with the mechanism. The results showed the impairment of liver function among the rats in an anxiety-like state. Additionally, 61 differential metabolites in the control and anxiety groups were screened using metabolomics (p < 0.05, VIP > 1). The results of the IPA analysis showed that the key target was EGFR. We also found that an anxiety-like state in rats may cause liver injury through the EFGR/PI3K/AKT/NF-κB pathway, which can lead to the production of inflammatory factors in the liver. Our results revealed a mechanism by which anxiety-like behavior leads to liver damage in rats. The findings of this study provided new insights into the deleterious effects of psychological problems on physical health.

A rare case of pemphigus vulgaris disguised as a malignant gingival ulcer.

BACKGROUND: Pemphigus vulgaris (PV) is a kind of rare and severe autoimmune bullous disease. In this case, the specificity of oral PV lies in the clinical manifestations of a single palatal ulcer, and no blisters were found in the oral mucosa. This case provides a powerful reference for dentists diagnosing and treating oral PV with atypical clinical presentations. CASE PRESENTATION: A 54 years old female patient presented with a non-healing palatal gingival ulcer for over three months. By histopathological H&E staining and the direct immunofluorescence (DIF) test, the final diagnosis was oral PV. After topical glucocorticoid therapy, the affected area was cured. CONCLUSIONS: In patients with prolonged erosion of the skin or oral mucosa, even if complete blisters are not visible, the physician should consider autoimmune bullous diseases and pay attention to avoid diagnostic defects.

Multi-disciplinary treatment of severe palatal radicular groove of maxillary lateral incisor: A case report and literature review. / 上颌侧切牙重度畸形舌侧沟多学科联合治疗1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Palatal radicular groove is a developmental malformation of maxillary incisors, lateral incisors in particular, which often causes periodontal destruction. This paper reports a case of combined periodontal-endodontic lesions induced by palatal radicular groove, which was initially misdiagnosed as a simple periapical cyst. After root canal therapy and periapical cyst curettage, the course of disease was prolonged, resulting in the absence of buccal and maxillary bone plates in the affected tooth area. After the etiology was determined, the affected tooth was extracted and guide bone tissue regeneration was performed at the same time, followed by implantation and restoration at the later stage, leading to clinical cure. The palatal radicular groove is highly occult, and the clinical symptoms are not typical. If the abscess of the maxillary lateral incisor occurs repeatedly, and the abscess of the maxillary lateral incisor has not been cured after periodontal and root canal treatment, cone-beam computed tomographic and periodontal flap surgery should be considered.

White Sponge Nevus Caused by Keratin 4 Gene Mutation: A Case Report.

White sponge nevus (WSN) is a rare autosomal dominant disease with a family history, often caused by mutations of the keratin 4 (K4) and keratin 13 (K13) genes in patients. It is characterized by frequently occurred white corrugated folds in the bilateral buccal mucosa with soft texture. On histopathological examination, hyperkeratosis of epithelial cells, edema, and vacuolar changes in the spinous cells are observed in the lesions, despite a normal layer of basal cells. WSN should be differentiated from other oral white spot diseases, mainly oral lichen planus, oral candidiasis, oral white edema, and Heck's disease, to reduce misdiagnosis and unnecessary treatment. At present, there is no specific treatment method. The purpose of this study was to report the clinical data of four WSN patients of the same family with the K4 gene mutation. The occurrence of WSN in a pair of monozygotic twins with very similar clinical presentations was identified for the first time. The gene sequencing results showed that there was a heterozygous deletion (C. 438_440delCAA) in exon 1 of the K4 gene, resulting in an aspartic acid loss in both the proband and his father. Finally, the etiology, pathogenesis, pathological manifestations, clinical manifestations, diagnosis, differential diagnosis, and related treatment methods are discussed to provide a reference for clinical treatment of the disease.

Hermansky-Pudlak syndrome type 2: A rare cause of severe periodontitis in adolescents-A case study.

Background and aims: Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA) and platelet storage pool deficiency. The HPS-2 subtype is distinguished by neutropenia, and little is known about its periodontal phenotype in adolescents. AP3B1 is the causative gene for HPS-2. A 13-year-old Chinese girl presented to our department suffering from gingival bleeding and tooth mobility. Her dental history was otherwise unremarkable. Suspecting some systemic diseases as the underlying cause, the patient was referred for medical consultation, a series of blood tests, and genetic tests. In this case study, periodontal status and mutation screening of one HPS-2 case are presented. Methods: Blood analysis including a complete blood count (CBC) and glycated hemoglobin levels were measured. Platelet transmission electron microscopy (PTEM) was performed to observe the dense granules in platelets. Whole-exome sequencing (WES) and Sanger sequencing were performed to confirm the pathogenic variants. Results: A medical diagnosis of HPS-2 was assigned to the patient. Following the medical diagnosis, a periodontal diagnosis of "periodontitis as a manifestation of systemic disease" was assigned to the patient. We identified novel compound heterozygous variants in AP3B1 (NM_003664.4: exon7: c.763C>T: p.Q255*) and (NM_003664.4: exon1: c.53_56dup: p.E19Dfs*21) in this Chinese pedigree with HPS-2. Conclusion: This case study indicates the importance of periodontitis as a possible indicator of underlying systemic disease. Systemic disease screening is needed when a young patient presents with unusual, severe periodontitis, as the oral condition may be the first of a systemic abnormality. Our work also expands the spectrum of AP3B1 mutations and further provides additional genetic testing information for other HPS-2 patients.

Simultaneous determination of oxalate and citrate in urine and serum of calcium oxalate kidney stone rats by IP-RP LC-MS/MS.

Oxalate and citrate in 24 h urine and serum are considered to be associated with the incidence and recurrence risk of calcium oxalate kidney stones. The quantification of oxalate and citrate contributes to understand the pathological metabolism of kidney stones and guide the early diagnosis and recurrence monitoring. Although simultaneous quantification of oxalate and citrate in urine using liquid chromatography tandem mass spectrometry (LC-MS/MS) have been reported, the optimization of chromatographic column, mobile phase and mass spectrometry (MS) parameters has not been performed. In addition, these is a lack of suitable method for simultaneous detection of oxalate and citrate both in serum and urine. Therefore, we developed a method for the simultaneous determination of oxalate and citrate in urine and serum based on ion-pairing reversed-phase (IP-RP) LC-MS/MS. Herein, five ion-pair reagents, namely, triethanolamine, dimethylbutyl amine, diisopropenyl amine, N,N-dimethylcyclohexylamine and tripropylamine, and three ion-pairing reagent (IPR) buffers, namely, acetic acid, hexafluoro-2-isopropanol, and hexafluoro-2-methyl-2-propanol, were compared in regard to their chromatographic peak abundance and separation of oxalate and citrate. Moreover, MS parameters and the multiple reaction monitoring (MRM) conditions were also evaluated and optimized to obtain the maximum peak abundance. After that, the method was validated in the linear range of 0.25-1000 µM, and the correlation coefficient was ≥ 0.99. The precision and accuracy were < 14.70% and < 19.73%, respectively. The extraction recovery was 80.53-108.79%, and the matrix effect was < 8.79%. The quality control samples were stable at room temperature for 4 h, 4 °C for 24 h, and for 3 freeze-thaw cycles. Finally, this method was applied to the determination of oxalate and citrate in the serum and urine of rats with calcium oxalate kidney stones. The establishment of a stable and effective oxalate and citrate detection method is conducive to the diagnosis and monitoring of kidney stones.

Low LINC02147 expression promotes the malignant progression of oral submucous fibrosis.

BACKGROUND: Key lncRNAs associated with the malignant progression of oral submucous fibrosis (OSF) to oral squamous cell carcinoma (OSCC) were identified. METHODS: Key lncRNAs with sequential changes from normal oral mucosa (NOM) to OSF to OSCC were identified based on the GEO database. Kaplan-Meier analysis was used to screen lncRNAs related to OSCC prognosis. Cox regression analysis was used to validate the independent prognostic value. qPCR was used to confirm the expression of the candidate lncRNAs. Gene set enrichment analysis (GSEA), nucleocytoplasmic separation assay, fluorescence in situ hybridization, RNA knockdown, western blot, and cell viability assay were performed to investigate the biological functions of the candidate lncRNA. A nomogram was constructed to quantitatively predict OSCC prognosis based on TCGA. RESULTS: Bioinformatics methods indicated that LINC02147 was sequentially downregulated from NOM to OSF to OSCC, as confirmed by clinical tissues and cells. Meanwhile, low LINC02147 expression, as an independent prognostic factor, predicted a poor prognosis for OSCC. GSEA and in vitro studies suggested that low LINC02147 expression promoted OSF malignant progression by promoting cell proliferation and differentiation. A LINC02147 signature-based nomogram successfully quantified each indicator's contribution to the overall survival of OSCC. CONCLUSIONS: Low LINC02147 expression promoted OSF malignant progression and predicted poor OSCC prognosis.

Er,Cr:YSGG Laser Therapy for Drug-Induced Gingival Overgrowth: A Report of Two Case Series.

Background: Drug-induced gingival overgrowth is common but neglected in patients with systemic disease medications until it seriously affects the quality of life. Methods: Initial periodontal treatment, combined with water laser surgery, was performed sequentially in two cases. Results: The therapeutic effect was good, and there was no recurrence along with good oral hygiene. Conclusion: Water laser equipment surgery, as well as initial periodontal treatment, required that surgeons are trained specifically. A tool was devised for various oral diseases, and it was safer, more efficient and more comfortable than others.

FCGBP Is a Promising Prognostic Biomarker and Correlates with Immunotherapy Efficacy in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck. In OSCC patients, the prognosis was dramatically different. In this research, we aimed to study the expressions and prognostic values of IgG Fc binding protein (FCGBP) in OSCC patients. The expression of FCGBP was analyzed using TCGA datasets and GEO datasets. FCGBP was evaluated for its predictive significance in OSCC patients by the use of a Kaplan-Meier and Cox regression model. Enrichment analysis for the GO and KEGG databases were conducted. CIBERSORT used TCGA datasets to show immune cell infiltration. In addition, researchers looked into the relationships between FCGBP and immune cells. The levels of FCGBP in OSCC cells was examined through the use of RT-PCR. FCGBP overexpression was tested for its effects on OSCC cell proliferation and invasion using CCK-8 and Transwell assays. We observed that FCGBP expressions were distinctly downregulated in OSCC specimens compared with nontumor tissues in both TCGA and GEO datasets, which was further confirmed by RT-PCR. OSCC patients with advanced clinical stages and poor prognoses had lower levels of FCGBP expression. Many immune-related biological activities and signaling pathways were found to be considerably abundant in KEGG tests and GO analysis results. The correlation analysis indicated that FCGBP was associated with a number of immune cells in a positive way. We found that FCGBP expressions were strongly and distinctly linked to the expressions of known immunological checkpoints, and FCGBP expression had significant positive connections with tumor mutational burden. FCGBP upregulation distinctly slowed the growth and invasion of OSCC cells in functional experiments. FCGBP has the potential to be a therapeutic target for OSCC and a biomarker for OSCC patients' prognosis.

Oral submucous fibrosis induced by graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Graft-versus-host disease (GVHD) is one of the most common and serious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). About 45%∼83% of patients develop GVHD in the oral cavity. There has no medical records of oral submucous fibrosis (OSF) induced by GVHD after allo-HSCT, which should be brought to the attention of dentists.

A novel FAM83H variant causes familial amelogenesis imperfecta with incomplete penetrance.

BACKGROUND: Amelogenesis imperfecta (AI) is known to be a monogenic genetic disease caused by a variety of genes demonstrating a wide spectrum of penetrance. FAM83H is reported to be involved in AI: however, whether FAM83H causes AI with incomplete penetrance is unclear. METHODS: Whole-exome sequencing was performed on two patients with AI, and putative disease-related variants were validated by Sanger sequencing. Bioinformatic and in vitro functional analyses were performed to functionally characterize the identified disease-causing variants. RESULTS: We identified a novel heterozygous nonsense variant of FAM83H (NM_198488: c.1975G > T, p.Glu659Ter); in vitro functional analysis showed that this mutant produced mislocalized proteins and was deleterious. Surprisingly, the clinical manifestations of each of the six individuals carrying this variant were different, with one carrier appearing to be completely asymptomatic for AI. CONCLUSION: Our findings expand the variant spectrum for FAM83H and the phenotypic spectrum for FAM83H-associated AI and suggest that FAM83H-mediated AI exhibits incomplete penetrance.

Comparative molecular analysis of oral submucous fibrosis and other organ fibrosis based on weighted gene co-expression network analysis. / åŸºäºŽåŠ æƒåŸºå› å ±è¡¨è¾¾ç½‘ç»œåˆ†æžçš„å£è ”é»è†œä¸‹çº¤ç»´åŒ–ä¸Žå ¶ä»–å™¨å®˜çº¤ç»´åŒ–çš„æ¯”è¾ƒåˆ†å­åˆ†æžï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: There is currently a lack of economic and suitable animal models that can accurately recapitulate the oral submucous fibrosis (OSF) disease state for indepth study. This is one of the primary reasons for the limited therapeutic methods available for OSF. Based on the underlying logic of pan-cancer analysis, this study systematically compares OSF and the other four types of organ fibrosis from the aspects of molecules, signaling pathways, biological processes, etc. A comprehensive analysis of the similarities and differences between OSF and other organ fibrosis is helpful for researchers to discover some general rules of fibrosis disease and may provide new ideas for studying OSF. METHODS: Microarray data of the GSE64216, GSE76882, GSE171294, GSE92592, and GSE90051 datasets were downloaded from GEO. Differentially expressed mRNAs (DEmRNAs) of each type of fibrosis were identified by Limma package. Weighted gene co-expression network analysis (WGCNA) was used to identify each type of fibrosis-related module. The similarities and differences of each fibrosis-related-module genes were analyzed by function and pathway enrichment analysis. RESULTS: A total of 6 057, 10 910, 27 990, 10 480, and 4 801 DEmRNAs were identified in OSF, kidney intestinal fibrosis (KIF), liver fibrosis (LF), idiopathic pulmonary fibrosis (IPF), and skin fibrosis (SF), respectively. By using WGCNA, each type of fibrosis-related module was identified. The co-expression networks for each type of fibrosis were constructed respectively. Except that KIF and LF have 5 common hub genes, other fibrotic diseases have no common hub genes with each other. The common pathways of OSF, KIF, LF, IPF, and SF mainly focus on immune-related pathways. CONCLUSIONS: OSF and the other 4 types of fibrotic diseases are tissue- and organ-specific at the molecular level, but they share many common signaling pathways and biological processes, mainly in inflammation and immunity.

Pathological investigations and correlation research of microfibrillar-associated protein 4 and tropoelastin in oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF), distinguished by abnormal collagen deposition, is a potentially malignant disorder with 4.2% (95% CI 2.7-5.6%) of malignant transformation and rising global prevalence. However, the precise pathogenesis and effective treatment remain elusive and controversial despite the abundance of literature on this topic. Therefore, it is crucial to explore the clinicopathological characteristics and potential markers for the diagnosis and prognosis of OSF. The objective of this study was to evaluate the influence and correlation of Microfibrillar-associated protein 4 (MFAP4) and tropoelastin (TE) in the development of OSF patients. MATERIAL AND METHODS: Clinicopathological factors, hematoxylin-eosin (HE) and Masson trichome staining, immunohistochemical characteristics and the correlation between MFAP4 and TE were recorded and compared among different stages of OSF progression among cases (n = 60) and controls (n = 10). Student's t test, ANOVA analysis, and the chi-square test were performed to compare the categorical variables for clinicopathological characteristics and the expression level of MFAP4 and TE between the fibrotic and normal tissues. Correlation analysis of MFAP4 and TE was performed using Pearson's correlation test and linear regression. RESULTS: MFAP4 and TE proteins are upregulated and increased gradually in patients with varying stages of OSF, relative to the control group. Furthermore, statistical analyses revealed that the expression level of MFAP4 was positively associated with TE, with a Pearson correlation coefficient of 0.3781 (p = 0.0048). Clinically, we found that OSF affected more males than females, with a ratio of 29:1. The age range was 16-60 years, and the mean age was 36.25 ± 10.25 years. In patients younger than 40 years, the positive expression rate of MFAP4 and TE was higher than in those over 40 years. All OSF cases had chewed areca nut, with 51.67% smoking tobacco. CONCLUSIONS: Our study elucidates that the accumulation of MFAP4 and TE proteins may play a vital role in the occurrence and development of OSF and may be promising candidate moleculars for prevention, diagnosis, and treatment strategies for OSF in the future.

Adipose-derived mesenchymal stem cell exosomes inhibit transforming growth factor-ß1-induced collagen synthesis in oral mucosal fibroblasts.

Oral submucosal fibrosis (OSF) is a potentially malignant oral disorder that requires the further development of advanced treatment strategies. TGF-ß1 has been reported to be the main trigger for the increased collagen production and reduced activity of matrix degradation pathways in OSF. Exosomes are key mediators of paracrine signaling that have been proposed for direct use as therapeutic agents for tissue repair and regeneration. The present study aimed to investigate the effects of human adipose-derived mesenchymal stem cell (ADSC) exosomes (ADSC-Exos) on TGF-ß1-treated oral fibroblasts in vitro and to unravel the potential underlying mechanism of action. Oral mucosal fibroblasts were obtained from the buccal tissues of patients without OSF during extraction of the third molar. ADSCs were obtained from three healthy female individuals during liposuction procedures. ADSC-Exos were isolated by ultracentrifugation and identified by electron microscopy, nanoparticle tracking and western blotting. Immunofluorescence and immunocytochemistry staining were performed to measure the expression levels of vimentin and α-smooth muscle actin in the fibroblasts. Reverse transcription-quantitative PCR and western blotting were used to determine the expression levels of mRNAs and proteins associated with collagen production. The p38 MAPK activator anisomycin was used to identify the underlying mechanisms of the effects of ADSC-Exos on TGF-ß1-induced collagen synthesis in oral mucosal fibroblasts. The results of the present study revealed that ADSC-Exos exhibited a cup- or sphere-shaped morphology, with a mean diameter of 58.01±16.17 nm. ADSC-Exos were also found to be positive for CD63 and tumor susceptibility 101 expression. ADSC-Exos treatment reversed the TGF-ß1-induced upregulation of collagen I and III protein expression. In addition, in the presence of TGF-ß1, the expression levels of collagen type I α 1 chain and collagen type III α 1 chain mRNA were downregulated, whilst the expression levels of matrix metalloproteinase (MMP)1 and MMP3 were upregulated following ADSC-Exos treatment. The TGF-ß1-induced upregulation in the phosphorylation of p38 in addition to the increased protein expression of collagens I and III were also reversed in fibroblasts following ADSC-Exos treatment. However, anisomycin treatment alleviated these ADSC-Exos-induced changes. In conclusion, findings from the present study suggest that ADSC-Exos may represent a promising strategy for OSF treatment by targeting the p38 MAPK signaling pathway.