RESUMEN
OBJECTIVE: To explore the clinical epidemiological characteristics of oral lichen planus (OLP) and risk factors for erosive/ulcerative OLP. MATERIALS AND METHODS: Patients diagnosed with OLP from 11 different hospitals were included in the study. Descriptive statistical methods were used to explore the clinical epidemiological characteristics and logistic regression, sensitivity analysis, and subgroup analysis were utilized to explore the risk factors for erosive/ulcerative OLP. RESULTS: The average age of patients was 49.2 ± 13.3 years, and 61.4% of the patients were women. The ratios of patients with reticular, hyperemic/erythematous, and erosive/ulcerative lesions were 47.9%, 27.8%, and 24.2%, respectively. Analysis of risk factors for erosive/ulcerative OLP identified the following variables: age, course of disease of 12 months or more, II°-III° dental calculus, hypertension, diabetes, and heart disease, as well as regions of habitation. Subgroup analysis showed significant differences in risk factors for erosive/ulcerative OLP in patients with and without risk behaviors. CONCLUSION: The clinical epidemiological characteristics of patients with OLP in the Chinese population in this study are basically consistent with existing reports in developed countries. And we identified clinical characteristics associated with erosive/ulcerative OLP through clinical epidemiological analysis.
RESUMEN
Oropharyngeal candidiasis (OPC) is an opportunistic infection treated with anti-fungal agents. Herein, we evaluate the efficacy and safety of miconazole buccal tablets (MBT) and itraconazole capsules in the localized treatment of patients with OPC. In this multi-centered, double-blinded, phase III trial (CTR20130414), both males and non-pregnant females (≥18 years) with OPC were randomized (1:1) to MBT plus placebo (experimental group) or itraconazole capsules plus placebo (control group). The primary endpoint was clinical cure at the end-of-treatment period [visit 4 (V4)] while secondary endpoints were clinical remission rates, partial remission rates, mycological cure, clinical relapse, and adverse events (AEs). All endpoints were statistically analyzed in both the full analysis set (FAS) and per-protocol (PP) set. A total of 431 (experimental: 216; control: 215) subjects were included. At V4, in the FAS set, the clinical cure was achieved in 68% and 59% patients in experimental and control groups, respectively with a treatment difference of 9% [95% confidence interval (CI): -1,19; P < .001] demonstrating non-inferiority of MBT over itraconazole. At V4, mycological cure rates were 68.2% and 42.0% in the experimental group and control groups (P < .001), respectively in FAS. The relapse rates were 5.4% and 6.6%, respectively, in the experimental and control groups. A total of 210 patients experienced AEs during treatment with 47.7% in the experimental group and 49.8% in the control group with no deaths. This study demonstrated that once-daily treatment with MBT was non-inferior to itraconazole with higher mycological cure rates and was tolerable with mild AE in patients with OPC.
Miconazole is an antifungal drug against certain types of fungus or yeast infections. In this study, we showed that treatment with once-daily miconazole buccal tablets was as effective as systemic itraconazole capsules in Chinese patients infected by oropharyngeal candidiasis with minimum side effects.
Asunto(s)
Candidiasis Bucal , Miconazol , Femenino , Masculino , Adhesivos/uso terapéutico , Antifúngicos/efectos adversos , Candidiasis Bucal/tratamiento farmacológico , Candidiasis Bucal/veterinaria , Método Doble Ciego , Itraconazol/efectos adversos , Miconazol/efectos adversos , Recurrencia , Comprimidos/uso terapéuticoRESUMEN
Smoking and Candida albicans (C. albicans) infection are risk factors for many oral diseases. Several studies have reported a close relationship between smoking and the occurrence of C. albicans infection. However, the exact underlying mechanism of this relationship remains unclear. We established a rat infection model and a C. albicans-Leuk1 epithelial cell co-culture model with and without smoke exposure to investigate the mechanism by which smoking contributes to C. albicans infection. Oral mucosa samples from healthy individuals and patients with oral leucoplakia were also analysed according to their smoking status. Our results indicated that smoking induced oxidative stress and redox dysfunction in the oral mucosa. Smoking-induced Nrf2 negatively regulated the NLRP3 inflammasome, impaired the oral mucosal defence response and increased the oral mucosa susceptibility to C. albicans. The results suggest that the Nrf2 pathway could be involved in the pathogenesis of oral diseases by mediating an antioxidative response to cigarette smoke exposure and suppressing host immunity against C. albicans.
Asunto(s)
Candida albicans/patogenicidad , Candidiasis/microbiología , Fumar Cigarrillos/efectos adversos , Inflamasomas/metabolismo , Mucosa Bucal/microbiología , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Candida albicans/aislamiento & purificación , Candidiasis/metabolismo , Candidiasis/patología , Línea Celular , Modelos Animales de Enfermedad , Femenino , Humanos , Técnicas In Vitro , Masculino , Mucosa Bucal/metabolismo , Mucosa Bucal/patología , Factor 2 Relacionado con NF-E2/genética , Ratas , Ratas WistarRESUMEN
Myocardial ischaemia is usually accompanied by inflammatory response which plays a critical role in the myocardial healing and scar formation, while persistent inflammatory response contributes greatly to the myocardial remodeling and consequent heart failure. Metformin (Met), a widely used hypoglycemic drug, has increasingly been shown to exert remarkable cardioprotective effect on ischaemic myocardial injury such as acute myocardial infarction (AMI). However, the underlying mechanisms are still far from being fully understood. In this study, a mouse model of AMI was established through ligating the left anterior descending coronary artery (LAD), 100 mg/kg Met was given immediately after operation once daily for 3 days. It was demonstrated that Met effectively improved the cardiac haemodynamics (LVSP, LVEDP, +dp/dt, -dp/dt), diminished the infarct size, alleviated the disarrangement of myocardial cells and reduced the infiltration of inflammatory cells (macrophages, neutrophils and lymphocytes) in the heart of AMI mice. Mechanistically, Met decreased the expression of NLRP3 and enhanced the accumulation of LC3 puncta in F4/80-positive macrophages in the heart of AMI mice. Single cell suspension of cardiac macrophages was prepared from AMI mice and exhibited increased NLRP3 mRNA and protein expression. In contrast, Met decreased the expression of NLRP3 and p62, whereas increased the ratio of LC3II/LC3I. Additionally, both conditioned medium from H9c2 cardiomyocytes exposed to hydrogen peroxide (H9c2-H2O2-CM) and combination of mtDNA and ATP (mtDNA-ATP) increased the expression of NLRP3 and cleaved caspase-1 (p10) as well as intracellular ROS production in RAW264.7 macrophages, which were abrogated by Met treatment. Strikingly, chloroquine (CQ), 3-methyladenine (3-MA) and knockdown of autophagy-related gene (Atg5) abrogated the inhibitory effects of Met on H9c2-H2O2-CM and mtDNA-ATP-induced NLRP3 expression, release of IL-1ß and IL-18 as well as ROS production in RAW264.7 macrophages. Collectively, these findings suggest that Met protects against ischaemic myocardial injury through alleviating autophagy-ROS-NLRP3 axis-mediated inflammatory response in macrophages.
Asunto(s)
Autofagia , Inflamación/patología , Macrófagos/patología , Metformina/uso terapéutico , Isquemia Miocárdica/patología , Isquemia Miocárdica/prevención & control , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Autofagia/efectos de los fármacos , ADN Mitocondrial/metabolismo , Femenino , Hemodinámica/efectos de los fármacos , Peróxido de Hidrógeno/toxicidad , Macrófagos/efectos de los fármacos , Macrófagos/ultraestructura , Masculino , Metformina/farmacología , Ratones , Ratones Endogámicos C57BL , Isquemia Miocárdica/fisiopatología , Miocardio/patología , Células RAW 264.7 , RatasRESUMEN
BACKGROUND: Healthcare workers (HCWs) at the frontline are facing a substantial risk of infection during the coronavirus disease 2019 (COVID-19) outbreak. METHODS: We acquired information and data on general information on and infection and death status of HCWs in Wuhan during the COVID-19 outbreak and completed statistical analyses. RESULTS: We obtained the data on 2457 infected cases among HCWs in Wuhan, China. More than half of the infected individuals were nurses (52.06%), whereas 33.62% of infected cases were doctors and 14.33% of cases were medical staff. In particular, the case infection rate of nurses (2.22%) was remarkably higher than that of doctors (1.92%). Most infected cases among HCWs were female (72.28%). A majority of the infected HCWs (89.26%) came from general hospitals, followed by specialized hospitals (5.70%) and community hospitals (5.05%). The case infection rate of HCWs (2.10%) was dramatically higher than that of non-HCWs (0.43%). The case fatality rate of HCWs (0.69%) was significantly lower than that of non-HCWs (5.30%). CONCLUSIONS: The infection risk of HCWs is clearly higher than that of non-HCWs. HCWs play an essential role in fighting the pandemic. The analysis of the infection status of HCWs is essential to attract enough attention from the public, provide effective suggestions for government agencies, and improve protective measures for HCWs.
Asunto(s)
COVID-19/epidemiología , China/epidemiología , Estudios Transversales , Brotes de Enfermedades/estadística & datos numéricos , Femenino , Personal de Salud/estadística & datos numéricos , Humanos , Masculino , PandemiasRESUMEN
Extracellular vesicles are heterogeneous populations of naturally occurring secreted small vesicles. EVs function as signaling platforms to facilitate intracellular communication, which indicates the physiological or pathophysiological conditions of cells or tissues. Considering that EVs can be isolated from most body fluids and that molecular constituents could be reprogrammed according to the physiological status of the secreting cells, EVs are regarded as novel diagnostic and prognostic biomarkers for many diseases. The ability to protect encapsulated molecules from degradation in body fluids suggests the potential of EVs as biological medicines or drug delivery systems. This article focuses on the EV-associated biomarkers and therapeutic approaches in autoimmune diseases.
Asunto(s)
Enfermedades Autoinmunes , Líquidos Corporales , Vesículas Extracelulares , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/tratamiento farmacológico , Biomarcadores , Sistemas de Liberación de Medicamentos , HumanosRESUMEN
OBJECTIVE: The immunological mechanisms behind different mucosa against candidiasis are largely unknown. In this study, we investigate the natural protective mechanisms and local cytokine responses of C. albicans-infected oral and vaginal epithelial cells. METHOD: The cell lines (Leuk-1 and VK2/E6E7) were cultured with C. albicans (SC5314, Δals3, and Δssa1) in indicated ratio, respectively. The morphological changes and colony growth of C. albicans were observed to evaluate the fungicidal ability of epithelial cells, and the cellular morphological changes and LDH activity measurements were used to assess cell damage. Further, we assess the production of cytokines and chemokines in co-culture supernatants using enzyme-linked immunosorbent assay (ELISA). RESULT: Our results show that the oral and vaginal epithelial cells use different strategies to combat this pathogen. Infected oral epithelial cells are adept at the production of cytokines (GM-CSF, IL-1α, and IL-1ß) and chemokines (IL-8, MIP-3α, and RANTES), and yet, vaginal cells are more proficient at direct fungal killing. However, both epithelial cells play only a minor role in adaptive immunity to C. albicans. Further, C. albicans Als3p and Ssa1p genes also participate in local immune response since deletion of ALS3 or SSA1 causes reduction in cytokine and chemokine levels in both oral and vaginal cells. The dramatic decreases in both fungal % of cytotoxicity and the secretion of such cytokines as GM-CSF, MIP-3α, and RANTES in Δssa1-infected oral cells were consistent with a delayed germination process in that mutant. CONCLUSION: Human oral and vaginal epithelial cells performed different host response to C. albicans by fungal killing ability or secreting cytokines and chemokines.
Asunto(s)
Candida albicans/inmunología , Células Epiteliales/inmunología , Células Epiteliales/microbiología , Interacciones Huésped-Patógeno , Inmunidad Innata , Mucosa Bucal/inmunología , Vagina/inmunología , Línea Celular , Supervivencia Celular , Técnicas de Cocultivo , Citocinas/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Factores Inmunológicos/análisisRESUMEN
Cigarette smoking is an established risk factor for some oral diseases. As an essential fluid in the oral cavity, saliva is crucial to maintain oral health. Relative to active smoking, there are very few studies assessing the effect of passive smoking on salivary cytokines levels. In the present study, we established the rat models by the means of the intraoral cigarette smoking or whole body cigarette smoke exposure to simulate human active or passive smoking, respectively. The effects of active or passive smoking on salivary cytokines levels were assessed by using ProcartaPlex multiplex immunoassays. The results of the current study indicated that both active and passive smoking diminished the body weights of rats and increased the levels of some blood counts. Intriguingly, active smoking enhanced the salivary levels of IL-6 and IL-12 p70 and passive smoking elevated the salivary IL-6 level. Moreover, active smoking appeared to have a more prominent activation effect on the salivary IL-6 level. It was noted that active or passive smoking had no significant effect on the salivary IFN-γ level. Active or passive smoking could have potential effects on the salivary levels of some pro-inflammatory cytokines.
Asunto(s)
Citocinas/análisis , Saliva/química , Fumar/fisiopatología , Contaminación por Humo de Tabaco/análisis , Animales , Peso Corporal , Femenino , Interleucina-6/análisis , Masculino , Proyectos Piloto , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To investigate the effects of end time of night feeding on body height, body weight, nutritional status, and prevalence rate of dental caries in children at the age of 30 months. METHODS: A total of 416 children who were born from January 2014 to September 2015 and had completed a physical examination as required were enrolled. During the physical examination performed at the age of 30 months, the comprehensive child care record and a self-made questionnaire were used. The children who continued to receive night feeding after the age of 6 months were enrolled as study group (n=269), and those for whom night feeding was ended at the age of 6 months were enrolled as control group (n=147). The two groups were compared in terms of body height, body weight, incidence rate of overweight/obesity, and prevalence rate of dental caries at the age of 30 months. RESULTS: Compared with the control group, the study group had a significantly lower body height (92.4±3.0â cm vs 93.3±2.8â cm; P<0.05), a significantly higher incidence rate of overweight/obesity (23.8% vs 12.2%; P<0.05), and a significantly higher prevalence rate of dental caries (14.9% vs 7.5%; P<0.05) at the age of 30 months. CONCLUSIONS: Night feeding continued after the age of 6 months can affect the growth and development of infants/toddlers, cause overnutrition, and increase the prevalence rate of dental caries.
Asunto(s)
Conducta Alimentaria , Estatura , Índice de Masa Corporal , Peso Corporal , Preescolar , Caries Dental , Humanos , Lactante , Obesidad , Sobrepeso , PrevalenciaRESUMEN
BACKGROUND/AIMS: In order to further characterize the biological traits of Dp71, HBE over expressing two most abundantly expressed Dp71 spliced isoforms, Dp71d and Dp71f, were established and their biological traits were explored. METHODS: The proliferation, migration and invasion capabilities of HBE-Dp71d and HBE-Dp71f cells were evaluated by MTT, colony formation, transwell and scratch assay. Cell cycle and apoptosis induced by H2O2 were measured by flow cytometer. Co-IP was performed to prove the interaction between lamin B1, FAK and Dp71. Western blot was performed to detect lamin B1, FAK, ERK and Cyclin D expression in HBE-Dp71d and HBE-Dp71f cells. RESULTS: HBE-Dp71d and HBE-Dp71f cells proliferated faster than their mock and blank controls; shortened their G0/G1 phase; enhanced their invasion and migration capabilities; reduced their apoptosis induced by H2O2. Co-IP proved Dp71 directly interacting with focal adhesion kinase (FAK) and lamin B1 in HBE cells. Increased lamin B1, FAK mRNA and protein expression, over activation of integrin/focal adhesion kinase/extracellular signal-regulated kinase (ERK)/cyclin D pathway were observed in HBE-Dp71d and HBE-Dp71f cells. CONCLUSIONS: Via increasing FAK in the cytoplasmic FAK-Dp71 , lamin B1 of nucleus laminB1-Dp71 complex, HBE-Dp71d and HBE-Dp71f cells alter their proliferation, migration, invasion, cell cycle and apoptosis rate induced by H2O2.
Asunto(s)
Distrofina/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Ciclina D/metabolismo , Distrofina/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Quinasa 1 de Adhesión Focal/metabolismo , Fase G1/genética , Fase G1/fisiología , Células HeLa , Humanos , Peróxido de Hidrógeno/farmacología , Células PC12 , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratas , Fase de Descanso del Ciclo Celular/genética , Fase de Descanso del Ciclo Celular/fisiologíaRESUMEN
BACKGROUND: Oral lichen planus (OLP) is a T cell-mediated autoimmune disease. The aetiology and molecular mechanisms of OLP remain unclear. Human cytomegalovirus (HCMV) infection is a causal factor in the development of various diseases, but the clinical relevance of HCMV in OLP has not been thoroughly investigated. METHODS: In the present study, we firstly examined twenty-three HCMV-encoded microRNA (miRNA) expression profiles in plasma from training set that including 21 OLP patients and 18 healthy controls using RT-qPCR technology. Dysregulated miRNAs were subsequently confirmed in another larger cohort refereed as validation set consisting of 40 OLP patients and 33 healthy controls. HCMV DNA in peripheral blood leukocytes (PBLs) was also measured in an additional cohort of 13 OLP patients and 12 control subjects. Furthermore, bioinformatics analyses, luciferase reporter assay and western blotting were also performed to predict and verify the direct potential targets of HCMV-encoded miRNAs. RESULTS: The RT-qPCR results showed that the plasma levels of five HCMV-encoded miRNAs including hcmv-miR-UL112-3p, hcmv-miR-UL22a-5p, hcmv-miR-UL148d, hcmv-miR-UL36-5p and hcmv-miR-UL59 were significantly increased in OLP patients in both training and validation sets. HCMV DNA in PBLs was also significantly higher in OLP patients than in control subjects. Additionally, by using a combination of luciferase reporter assay and western blotting, we demonstrated that cytomegalovirus UL16-binding protein 1, a molecule that mediates the killing of virus-infected cells by natural killer cells, is a direct target of hcmv-miR-UL59. CONCLUSIONS: Our results demonstrate a distinct expression pattern of HCMV-encoded miRNAs in OLP patients, which may provide insight into the relationship between HCMV infection and OLP, and warrants additional study in the diagnosis and aetiology of OLP.
Asunto(s)
Perfilación de la Expresión Génica , Liquen Plano Oral/genética , Liquen Plano Oral/virología , MicroARNs/genética , Secuencia de Bases , Estudios de Casos y Controles , Citomegalovirus , Demografía , Exosomas/metabolismo , Femenino , Proteínas Ligadas a GPI/metabolismo , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Liquen Plano Oral/sangre , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Reproducibilidad de los Resultados , Regulación hacia Arriba/genéticaRESUMEN
Recent studies show that NK cells play important roles in murine biliary atresia (BA), and a temporary immunological gap exists in this disease. In this study, we found high-mobility group box-1 (HMGB1) and TLRs were overexpressed in human and rotavirus-induced murine BA. The overexpressed HMGB1 released from the nuclei of rotavirus-infected cholangiocytes, as well as macrophages, activated hepatic NK cells via HMGB1-TLRs-MAPK signaling pathways. Immature NK cells had low cytotoxicity on rotavirus-injured cholangiocytes due to low expression of TLRs, which caused persistent rotavirus infection in bile ducts. HMGB1 up-regulated the levels of TLRs of NK cells and promoted NK cell activation in an age-dependent fashion. As NK cells gained increasing activation as mice aged, they gained increasing cytotoxicity on rotavirus-infected cholangiocytes, which finally caused BA. Adult NK cells eliminated rotavirus-infected cholangiocytes shortly after infection, which prevented persistent rotavirus infection in bile ducts. Moreover, adoptive transfer of mature NK cells prior to rotavirus infection decreased the incidence of BA in newborn mice. Thus, the dysfunction of newborn NK cells may, in part, participate in the immunological gap in the development of rotavirus induced murine BA.
Asunto(s)
Atresia Biliar/inmunología , Proteína HMGB1/inmunología , Células Asesinas Naturales/inmunología , Activación de Linfocitos/inmunología , Infecciones por Rotavirus/inmunología , Animales , Atresia Biliar/metabolismo , Atresia Biliar/virología , Western Blotting , Diferenciación Celular/inmunología , Separación Celular , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Proteína HMGB1/metabolismo , Humanos , Inmunohistoquímica , Células Asesinas Naturales/citología , Ratones , Ratones Noqueados , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rotavirus/inmunología , Infecciones por Rotavirus/complicaciones , Receptor Toll-Like 2/inmunología , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/inmunologíaRESUMEN
Dp71 is one of the most ubiquitously expressed isoforms of dystrophin, the pathological genes of DMD. In order to find whether the alteration of Dp71 can affect the phenotypes of cell other than PC12, an A549 cell line with stably transfected Dp71 siRNA plasmids was set up and named A549-Dp71AS cell. It is demonstrated for the first time that the A549-Dp71AS cell line displayed decreased invasion capabilities, reduced migration ability, decreased proliferation rate, and lessened clonogenic formation. Cisplatin-induced apoptosis was also increased in A549-Dp71AS cell line via enhancing the Caspase 3, Caspase 8, and Caspase 9 activities. Knocking down Dp71 expression can significantly inhibit the A549 xenograft tumor growth in nude mice. The A549-Dp71AS cells and xenograft tumor tissues displayed reduced lamin B1, Bcl-2, and MMP2 protein expression, which accounts for the reduced malignancy of A549-Dp71AS cells in vivo and in vitro.
Asunto(s)
Distrofina/deficiencia , Distrofina/genética , Técnicas de Silenciamiento del Gen , Neoplasias/genética , Neoplasias/patología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Modelos Animales de Enfermedad , Expresión Génica , Xenoinjertos , Humanos , Lamina Tipo B/genética , Lamina Tipo B/metabolismo , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Clasificación del Tumor , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genética , Ensayo de Tumor de Célula MadreRESUMEN
BACKGROUND/AIMS: Nucleotide binding oligomerization domain 1 (NOD1) signal pathway and human ß defensins (hBDs) play crucial roles in innate immune. Cigarette smoke has been confirmed to dampen innate immune in some human tissues, such as oral mucosa. The aim of this study was to evaluate potential effects of smoking on NOD1 signaling and hBDs expression in oral mucosa. METHODS: Tissue specimens of normal oral mucosa were collected from donors undergoing routine surgical treatment. All 20 participants were classified equally as two groups: non-smokers and smokers. By using Western blotting and immunohistochemistry, we investigated differential expression of crucial molecules in NOD1 signal pathway, hBD-1, -2, and -3 in oral mucosa tissues between non-smokers and smokers. Immortalized human oral mucosal epithelial (Leuk-1) cells were treated with various concentrations of cigarette smoke extract (CSE) for 24h. Western blotting and immunofluorescence assays were performed to study CSE-induced alteration of protein expression. Leuk-1 cells were treated with 4% CSE, iE-DAP (NOD1 agonist), CSE + iE-DAP, BAY 11-7082 (NF-κB inhibitor), 4% CSE + BAY 11-7082, respectively. Real-time PCR and ELISA were performed to detect the mRNA levels and secretion of hBD-1, -2, and -3, respectively. RESULTS: The levels of NOD1, NF-κB, hBD-1 and hBD-3 significantly reduced in oral mucosa tissues of smokers compared with non-smokers. The levels of RIP2 (receptor-interacting protein 2), phospho-NF-κB (P-NF-κB) and hBD-2 remarkably enhanced in oral mucosal tissues of smokers. CSE treatment suppressed NOD1 and NF-κB expression and activated RIP2 and P-NF-κB expression in Leuk-1 cells. The mRNA and secretory levels of hBD-1 and -3 were down-regulated by CSE, while the mRNA and secretory level of hBD-2 were up-regulated by CSE. The iE-DAP or BAY 11-7082 treatment reversed the regulatory effects of CSE on levels of hBDs. CONCLUSION: The present study indicated that cigarette smoke could potentially modulate the expression of crucial molecules of NOD1 signal pathway and hBDs in human oral mucosal epithelium. NOD1 signal pathway could play an important role in the regulatory effects of CSE on hBDs levels in oral mucosal epithelial cells.
Asunto(s)
Mucosa Bucal/inmunología , Proteína Adaptadora de Señalización NOD1/inmunología , Transducción de Señal , Fumar/inmunología , beta-Defensinas/inmunología , Adulto , Línea Celular , Supervivencia Celular , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Mucosa Bucal/metabolismo , Mucosa Bucal/patología , FN-kappa B/análisis , FN-kappa B/genética , FN-kappa B/inmunología , Proteína Adaptadora de Señalización NOD1/análisis , Proteína Adaptadora de Señalización NOD1/genética , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/análisis , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/genética , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/inmunología , Fumar/genética , Fumar/patología , Adulto Joven , beta-Defensinas/análisis , beta-Defensinas/genéticaRESUMEN
Sepsis, a systemic inflammatory response to infection, is the major cause of death in intensive care units (ICUs). The mortality rate of sepsis remains high even though the treatment and understanding of sepsis both continue to improve. Sinomenine (SIN) is a natural alkaloid extracted from Chinese medicinal plant Sinomenium acutum, and its hydrochloride salt (Sinomenine hydrochloride, SIN-HCl) is widely used to treat rheumatoid arthritis (RA). However, its role in sepsis remains unclear. In the present study, we investigated the role of SIN-HCl in sepsis induced by cecal ligation and puncture (CLP) in BALB/c mice and the corresponding mechanism. SIN-HCl treatment improved the survival of BALB/c mice that were subjected to CLP and reduced multiple organ dysfunction and the release of systemic inflammatory mediators. Autophagy activities were examined using Western blotting. The results showed that CLP-induced autophagy was elevated, and SIN-HCl treatment further strengthened the autophagy activity. Autophagy blocker 3-methyladenine (3-MA) was used to investigate the mechanism of SIN-HCl in vitro. Autophagy activities were determined by examining the autophagosome formation, which was shown as microtubule-associated protein light chain 3 (LC3) puncta with green immunofluorescence. SIN-HCl reduced lipopolysaccharide (LPS)-induced inflammatory cytokine release and increased autophagy in peritoneal macrophages (PM). 3-MA significantly decreased autophagosome formation induced by LPS and SIN-HCl. The decrease of inflammatory cytokines caused by SIN-HCl was partially aggravated by 3-MA treatment. Taken together, our results indicated that SIN-HCl could improve survival, reduce organ damage, and attenuate the release of inflammatory cytokines induced by CLP, at least in part through regulating autophagy activities.
Asunto(s)
Autofagia/efectos de los fármacos , Morfinanos/farmacología , Sepsis/tratamiento farmacológico , Adenina/análogos & derivados , Adenina/farmacología , Animales , Ciego/cirugía , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Riñón/patología , Lipopolisacáridos/toxicidad , Hígado/patología , Pulmón/patología , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Asociadas a Microtúbulos/metabolismo , Morfinanos/química , Morfinanos/uso terapéutico , Sepsis/etiología , Sepsis/mortalidad , Tasa de SupervivenciaRESUMEN
Tooth loss often results in alveolar bone resorption because of lack of mechanical stimulation. Thus, the mechanism of mechanical loading on stem cell osteogenesis is crucial for alveolar bone regeneration. We have investigated the effect of mechanical loading on osteogenesis in human dental pulp stromal cells (hDPSCs) in a novel in vitro model. Briefly, 1 × 10(7) hDPSCs were seeded into 1 ml 3% agarose gel in a 48-well-plate. A loading tube was then placed in the middle of the gel to mimic tooth-chewing movement (1 Hz, 3 × 30 min per day, n = 3). A non-loading group was used as a control. At various time points, the distribution of live/dead cells within the gel was confirmed by fluorescence markers and confocal microscopy. The correlation and interaction between the factors (e.g. force, time, depth and distance) were statistically analysed. The samples were processed for histology and immunohistochemistry. After 1-3 weeks of culture in the in-house-designed in vitro bioreactor, fluorescence imaging confirmed that additional mechanical loading increased the viable cell numbers over time as compared with the control. Cells of various phenotypes formed different patterns away from the reaction tube. The cells in the middle part of the gel showed enhanced alkaline phosphatase staining at week 1 but reduced staining at weeks 2 and 3. Additional loading enhanced Sirius Red and type I collagen staining compared with the control. We have thus successfully developed a novel in-house-designed in vitro bioreactor mimicking the biting force to enhance hDPSC osteogenesis in an agarose scaffold and to promote bone formation and/or prevent bone resorption.
Asunto(s)
Pulpa Dental/metabolismo , Osteogénesis/fisiología , Reactores Biológicos , Células Cultivadas , Pulpa Dental/citología , Femenino , Humanos , Masculino , Células del Estroma/citología , Células del Estroma/metabolismo , Andamios del Tejido/química , Soporte de Peso/fisiologíaRESUMEN
OBJECTIVE: Regulatory T cells (Tregs) have emerged as important mediators in inflammatory and autoimmune diseases. We investigated the possible involvement of Tregs in oral lichen planus (OLP) and the influence of clinical therapy (hydroxychloroquine and prednisone) on the frequencies of Tregs in OLP patients. MATERIALS AND METHODS: One hundred fifty patients diagnosed with OLP were the study cohort. Levels of Tregs in blood and tissues were detected using flow cytometry and immunostaining, respectively. Cytokine production was assessed using a proteome profiler array and determined by enzyme-linked immunosorbent assay. mRNA expression of transcription factors was detected by real-time quantitative PCR. Hydroxychloroquine or prednisone was used to treat patients randomly. The frequency of Tregs was detected before treatment and 2 weeks after treatment. RESULTS: Compared with healthy volunteers, OLP patients had a higher proportion of Tregs in serum and tissues before treatment (P < 0.001). Serum concentrations of interleukin (IL)-8, transforming growth factor (TGF)-ß1, and IL-10 were significantly higher in patients than those in healthy controls. mRNA expression of Treg-related genes, including TGF-ß, IL-10, signal transducer and activator of transcription 6, and GATA binding protein 3, were upregulated significantly in OLP patients. The frequency of Tregs was downregulated after hydroxychloroquine treatment. CONCLUSIONS: These results suggest that Tregs may contribute to the immunopathogenesis of OLP and may provide a new therapeutic target for OLP treatment. CLINICAL RELEVANCE: T cell-mediated immune dysfunction may have a crucial role in OLP development. However, T helper 1 (Th1)/Th2 imbalance does not appear to be sufficient to understand the pathogenesis of OLP. This is the first study to show that Tregs are involved in the immunopathogenesis of OLP.
Asunto(s)
Hidroxicloroquina/farmacología , Liquen Plano Oral/patología , Linfocitos T Reguladores/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Adulto , Femenino , Humanos , MasculinoRESUMEN
PURPOSE: To study the clinical and pathological characteristics of oral lichen planus (OLP) in a large sample. MATERIALS AND METHODS: A comprehensive analysis was conducted on 105 patients with oral lichen planus (OLP), considering various factors including sex, age, disease site, lesion type, lesion area, morphological characteristics, self-reported symptoms, and history of systemic diseases. Histopathological examination was performed for each patient, and the pathology results were analysed according to sex and age group. RESULTS: 70.5% of the OLP patients were female, and OLP was most likely to occur in the cheek, followed by the tongue, lips, gums and palate. The patients with moderate pain according to the VAS score accounted for 60%. Thirty-nine percent of the OLP patients had a systemic disease, and the most common clinical type of OLP was nonerosive. Most of the pathological results showed liquefaction degeneration of basal cells and infiltration of lamina propria lymphocytes. There was no statistically significant difference in pathological manifestations between male and female patients, and there were statistically significant differences in pathological manifestations among different ages patients. CONCLUSION: This study analysed the sociodemographic data and clinical manifestations of 105 OLP patients to guide follow-up treatment planning and disease monitoring. Moreover, pathological manifestations should be analysed to avoid delayed treatment and to monitor for carcinogenesis. Furthermore, the correlation of pathological manifestations among OLP patients with different sexes and ages is conducive to further research on the specific differential manifestations and possible underlying mechanisms involved.
Asunto(s)
Liquen Plano Oral , Humanos , Liquen Plano Oral/patología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , China/epidemiología , Adulto Joven , Anciano de 80 o más Años , Adolescente , Factores de Edad , Factores Sexuales , Pueblos del Este de AsiaRESUMEN
Smoking is a well-established risk factor for several oral diseases, including oral cancer, oral leukoplakia and periodontitis, primarily related to reactive oxygen species (ROS). SS-31, a mitochondria-targeting tetrapeptide, has exhibited demonstrable efficacy in medical conditions by attenuating mitochondrial ROS production. However, its potential in the treatment of oral diseases remains underexplored. The aim of this study was to investigate the therapeutic potential of SS-31 in mitigating smoking-induced oral epithelial injury. Through in vitro experiments, our results indicate that SS-31 plays a protective role against cigarette smoke extract (CSE) by reducing oxidative stress, attenuating inflammatory response, and restoring mitochondrial function. Furthermore, we found that mitophagy, regulated by PINK1 (PTEN-induced putative kinase 1)/Parkin (Parkin RBR E3 ubiquitin-protein ligase), was critical for the protective role of SS-31. Our findings offer valuable insights into SS-31's therapeutic potential in mitigating CSE-induced oxidative stress, inflammatory response, and mitochondrial dysfunction in oral epithelial cells. This study provides novel intervention targets for smoking-related oral diseases.
Asunto(s)
Células Epiteliales , Mitocondrias , Mitofagia , Oligopéptidos , Estrés Oxidativo , Proteínas Quinasas , Humo , Ubiquitina-Proteína Ligasas , Estrés Oxidativo/efectos de los fármacos , Mitofagia/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Humanos , Proteínas Quinasas/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Oligopéptidos/farmacología , Ubiquitina-Proteína Ligasas/metabolismo , Humo/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Nicotiana/química , Nicotiana/efectos adversosRESUMEN
PURPOSE: Periodontitis-associated bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are closely linked to the risk of oral squamous cell carcinoma (OSCC). Emerging studies have indicated that another common periodontal pathogen, Prevotella intermedia (P. intermedia), is enriched in OSCC and could affect the occurrence and progression of OSCC. Our aim is to determine the effects of P. intermedia on the progression of OSCC and the role of antibiotics in reversing these effects. METHODS: In this study, a murine xenograft model of OSCC was established, and the mice were injected intratumorally with PBS (control group), P. intermedia (P.i group), or P. intermedia combined with an antibiotic cocktail administration (P.i + ABX group), respectively. The effects of P. intermedia and ABX administration on xenograft tumor growth, invasion, angiogenesis, and metastasis were investigated by tumor volume measurement and histopathological examination. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the changes in serum cytokine levels. Immunohistochemistry (IHC) was adopted to analyze the alterations in the levels of inflammatory cytokines and infiltrated immune cells in OSCC tissues of xenograft tumors. Transcriptome sequencing and analysis were conducted to determine differential expression genes among various groups. RESULTS: Compared with the control treatment, P. intermedia treatment significantly promoted tumor growth, invasion, angiogenesis, and metastasis, markedly affected the levels of inflammatory cytokines, and markedly altered M2 macrophages and regulatory T cells (Tregs) infiltration in the tumor microenvironment. However, ABX administration clearly abolished these effects of P. intermedia. Transcriptome and immunohistochemical analyses revealed that P. intermedia infection increased the expression of interferon-stimulated gene 15 (ISG15). Correlation analysis indicated that the expression level of ISG15 was positively correlated with the Ki67 expression level, microvessel density, serum concentrations and tissue expression levels of inflammatory cytokines, and quantities of infiltrated M2 macrophages and Tregs. However, it is negatively correlated with the quantities of infiltrated CD4+ and CD8+ T cells. CONCLUSION: In conclusion, intratumoral P. intermedia infection aggravated OSCC progression, which may be achieved through upregulation of ISG15. This study sheds new light on the possible pathogenic mechanism of intratumoral P. intermedia in OSCC progression, which could be a prospective target for OSCC prevention and treatment.