Saliva and tongue microbiota in burning mouth syndrome: An exploratory study of potential roles.

OBJECTIVES: Burning mouth syndrome (BMS) is a chronic orofacial pain disorder with unclear etiology, in which the tongue is most commonly affected. This study aims to provide implication of the possible relationship between oral microbiota and the pathogenesis of BMS. MATERIALS AND METHODS: Saliva and tongue swabs of 15 primary BMS patients and 10 healthy controls were collected and assessed by 16S rRNA gene amplicon sequencing. The microbiota compositions were compared and bioinformatic analysis was conducted. RESULTS: Differences in microbiota compositions between BMS patients and healthy controls were revealed in both saliva and tongue samples. In saliva, Streptococcus, Rothia, and Neisseria were the predominant genus at the taxonomic level in BMS patients. In tongue samples, Prevotella, Streptococcus, and Neisseria were the dominant genus at the taxonomic level in BMS patients. LEfSe analysis and linear discriminant analysis score showed that Actinobacteria were the predominant phylum in saliva, and Selenomonas were enriched in the dorsum of the tongue of BMS patients. CONCLUSIONS: This study for the first-time reported saliva and tongue microbiota profiles were distinguished from that of healthy controls, indicating a necessity for further research on the possible relationship between oral microbes and the pathogenesis of BMS.

Relationship between burning mouth disorder and gastroesophageal reflux disease: A scoping review.

OBJECTIVE: This study aims to provide a scoping review and attempts to uncover the possible association between burning mouth disorder and gastroesophageal reflux disease. METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library, Ovid, Scopus, and a search platform (EBSCOhost) were searched from their inception to August 22, 2023. RESULTS: After screening 2795 records, 18 articles were included in the final review, comprising cross-sectional studies (n = 9), case-control studies (n = 5), case reports (n = 2), case series (n = 1), and experimental study (n = 1). The prevalence of gastroesophageal reflux disease and its extraesophageal manifestations of laryngopharyngeal reflux in burning mouth patients was reported 3.39%-23.4% and 50%-93.8%, respectively, while oral burning was reported in 9%-45% of patients with gastroesophageal reflux disease. In case-control studies, gastroesophageal reflux disease was more prevalent in patients with burning mouth disorder compared with controls. Burning mouth would be resolved after antireflux therapy in laryngopharyngeal reflux patients in case series. PH value and saliva alternation might be the possible mechanisms. CONCLUSION: The possibility of the correlation between burning mouth disorder and gastroesophageal reflux disease still needs to be clearly demonstrated through better-conducted studies. The link between them is worth to be explored in future research.

Systolic heart failure induced by butylparaben in zebrafish is caused through oxidative stress and immunosuppression.

Due to Butylparaben (BuP) widespread application in cosmetics, food, pharmaceuticals, and its presence as an environmental residue, human and animal exposure to BuP is common, potentially posing hazards to both human and animal health. Congenital heart disease is already a serious problem. However, the effects of BuP on the developing heart and its underlying mechanisms remain unclear. Here, zebrafish embryos were exposed to environmentally and human-relevant concentrations of BuP (0.6 mg/L, 1.2 mg/L, and 1.8 mg/L, calculated but not measured) at 6 h post-fertilization (hpf) and were treated until 72 hpf. Exposure to BuP led to cardiac morphological defects and cardiac dysfunction in zebrafish embryos, manifesting symptoms similar to systolic heart failure. The etiology of BuP-induced systolic heart failure in zebrafish embryos is multifactorial, including cardiomyocyte apoptosis, endocardial and atrioventricular valve damage, insufficient myocardial energy, impaired Ca2+ homeostasis, depletion of cardiac-resident macrophages, cardiac immune non-responsiveness, and cardiac oxidative stress. However, excessive accumulation of reactive oxygen species (ROS) in the cardiac region and cardiac immunosuppression (depletion of cardiac-resident macrophages and cardiac immune non-responsiveness) may be the predominant factors. In conclusion, this study indicates that BuP is a potential hazardous substance that can cause adverse effects on the developing heart and provides evidence and insights into the pathological mechanisms by which BuP leads to cardiac dysfunction. It may help to prevent the BuP-based congenital heart disease heart failure in human through ameliorating strategies and BuP discharge policies, while raising awareness to prevent the misuse of preservatives.

Candida albicans overgrowth disrupts the gut microbiota in mice bearing oral cancer.

Candida albicans is one of the most common opportunistic fungi in cancer patients. This study explored the influence of C. albicans on gut microbiota in oral tumour-bearing mice by means of 16S rRNA sequencing and ITS sequencing. It was found that C. albicans infection induced the decrease of alpha diversity of bacteria and fungi in the gut microbiome. For the bacteria, C. albicans caused the reduction of Ralstonia, Alistipes, Clostridia UCG-014, Ruminococcus, and Lachnospiraceae NK4A136 group. For the fungi, C. albicans inhibited the growth of other fungi including Aspergillus, Cladosporium, and Bipolaris. The neutralisation of γδT cells partly alleviated the out-of-balance of Firmicutes/Bacteroidota (F/B) ratio in the gut caused by C. albicans infection. However, γδT cell neutralisation boosted the overgrowth of C. albicans. Additionally, IL-17A neutralisation aggravated the microbial dysbiosis of bacteria and fungi caused by C. albicans infection. Further analysis indicated that C. albicans overgrowth might influence the correlations between fungal and bacterial kingdoms. In conclusion, C. albicans infection disturbed the gut microbiota of both bacteria and fungi in oral tumour-bearing mice, which may be associated with the intestinal immune components including γδT cells and IL-17A.

Surveillance and Resistance of Community-Onset Extended-Spectrum ß-Lactamase-Producing Escherichia coli and Klebsiella pneumonia in Oral and Maxillofacial Surgery Site Infections.

Background: The prevalence of community-onset infections of extended spectrum ß-lactamase (ESBL)-producing strains has increased globally, yet surveillance and resistance in patients with oral and maxillofacial surgery site infections is less investigated. Patients and Methods: A retrospective cohort study was performed to investigate risk factors and resistance of ESBL-producing Escherichia coli (ESBL-EC) and ESBL-producing Klebsiella pneumonia (ESBL-KP) among community-onset patients with oral and maxillofacial surgery during January 2010 to December 2016. Demographic features, predisposing factors, clinical outcomes, and antibiotic agent costs were analyzed. Antimicrobial susceptibility testing of nine antimicrobial agents against ESBL-KP and ESBL-EC were measured. Results: Among 2,183 cultures from infection sites in patients with oral and maxillofacial surgery site (45 cases [2.06%]) were confirmed with community-onset ESBL-KP (24; 1.10%) or ESBL-EC (21; 0.96%) infection. Multivariable analysis showed the independent risk factors for ESBL-producing bacterial infection were prior history of hospitalization (adjusted odds ratio [aOR], 10.984; 95% confidence interval [CI], 5.965-59.879; p = 0.025) and malignant condition (aOR, 3.373; 95% CI 2.947-7.634; p = 0.024). Based on antimicrobial susceptibility testing, 57.8% ESBL-KP and ESBL-EC were found receiving inappropriate antimicrobial therapy, and antibiotic agent costs were higher than non-ESBL-producing bacterial infections ($493.8 ± $367.3 vs. $304.1 ± $334.7; p = 0.031). Conclusions: Infections caused by ESBL-KP and ESBL-EC among patients in sites with oral and maxillofacial surgery are associated with prior history of hospitalization and malignant conditions. Prompt detection and appropriate antibiotic administration for community-onset infections of ESBLs are necessary for such populations.

Candida albicans-myeloid cells-T lymphocytes axis in the tumor microenvironment of oral tumor-bearing mice.

Candida albicans (C. albicans) is associated with the development of oral cancer. Here, we report the altered tumor microenvironment in oral tumor-bearing mice caused by C. albicans infection. Single-cell RNA sequencing showed that C. albicans infection influenced the tumor microenvironment significantly. Specifically, C. albicans infection reduced the CD8+ T cells but increased the IL-17A+ CD4+ T cells and IL-17A+ γδ T cells in oral tumor. The neutralization of IL-17A or TCR γ/δ alleviated the tumor progression caused by C. albicans infection. Additionally, C. albicans infection promoted the infiltration of myeloid-derived suppressor cells (MDSCs) into tumor, especially polymorphonuclear (PMN)-MDSCs, which infiltration was reduced after the neutralization of CCL2. Thus, our findings reveal the myeloid cells-T lymphocytes axis in oral tumor microenvironment with C. albicans infection, which helps to understand the mechanisms for C. albicans promoting oral cancer from the perspective of immune microenvironment.

Pembrolizumab in combination with lenvatinib in participants with hepatocellular carcinoma (HCC) before liver transplant as neoadjuvant therapY-PLENTY pilot study.

BACKGROUND: The high recurrent rate after liver transplantation (LT) remains a clinical challenge, especially for those exceeding the Milan criteria (MC) and with high RETREAT scores. Therefore, the authors aim to investigate whether neoadjuvant systemic therapy allows safely administered and effectively reduces post-LT recurrence for those patients. METHODS: In this prospective, randomized, open-label, pilot study, patients with HCC exceeding the MC were randomly assigned to PLENTY or control group before LT. The primary endpoint of the study was the recurrence-free survival after LT. RESULTS: Twenty-two patients were enrolled and randomly assigned: 11 to the PLENYT group and 11 to the control group. The 30-month tumor-specific RFS was 37.5% in the PLENTY group and 12.5% in the control group. The 12-month tumor-specific RFS after LT was significantly improved in the PLENTY group (87.5%) compared to the control group (37.5%) (P=0·0022). The objective response rate in the PLENTY group was 30 and 60% when determined by RECIST 1.1 and mRECIST, respectively. Six patients (60%) had significant tumor necrosis, including three (30%) who had complete tumor necrosis at histopathology. No acute allograft rejection after LT occurred in the PLENTY and Control group. CONCLUSION: Neoadjuvant pembrolizumab plus lenvatinib before LT appears to be safe and feasible, associated with significantly better RFS for patients exceeding the MC. Despite the limitations of small sample size, this is the first RCT to evaluate neoadjuvant PD-1 blockade combined with tyrosine kinase inhibitors in LT recipients, the results of this study will inform future research.

Candida albicans Promotes Oral Cancer via IL-17A/IL-17RA-Macrophage Axis.

The association between Candida albicans (C. albicans) and oral cancer (OC) has been noticed for a long time, but the mechanisms for C. albicans promoting OC are rarely explored. In this study, we determined that C. albicans infection promoted OC incidence in a 4-nitroquinoline 1-oxide (4NQO)-induced mouse tongue carcinogenesis model as well as promoted OC progression in a tongue tumor-bearing mouse model (C3H/HeN-SCC VII). We then demonstrated that tumor-associated macrophage (TAMs) infiltration was elevated during C. albicans infection. Meanwhile, the attracted TAMs polarized into M2-like macrophages with high expression of programmed death ligand 1 (PD-L1) and galectin-9 (GAL-9). Further analysis suggested that the interleukin (IL)-17A/IL-17RA pathway activated in OC cells was a contributor to the excessive TAMs infiltration in C. albicans-infected mice. Thus, we constructed IL-17A neutralization and macrophage depletion experiments in C3H/HeN-SCC VII mice to explore the role of IL-17A/IL-17RA and TAMs in OC development caused by C. albicans infection. The results showed that both IL-17A neutralization and macrophage depletion tended to reduce the TAMs number and tumor size in mice with C. albicans infection. Collectively, our finding revealed that C. albicans promoted OC development via the IL-17A/IL-17RA-macrophage axis, opening perspectives for revealing C. albicans-tumor immune microenvironment links. IMPORTANCE The relationship between fungi and cancer is gradually receiving attention. Among them, some clinical evidence has shown that Candida may be a contributor to gastrointestinal cancers, especially oral cancer. However, the underlying mechanisms for Candida promoting oral cancer need to be explored. For this reason, this study demonstrated the role of C. albicans in oral cancer development. Moreover, this study revealed the underlying mechanisms for C. albicans promoting oral cancer from the perspective of the tumor immune microenvironment.

Effects of Pu-erh and Dian Hong tea polyphenols on the gut-liver axis in mice.

Tea polyphenols (TP) are the most biologically active components in tea, with antioxidant, antiobesity, and antitumor properties, as well as the ability to modulate the composition and function of intestinal microbiota. This experimental study evaluated the chemical constituents of polyphenols in Pu-erh (PTP) and Dian Hong tea (DHTP). It also investigated the co-regulatory effects of PTP and DHTP on intestinal flora and liver tissues in mice using 16 S rRNA gene and transcriptome sequencing. The results revealed that DHT had higher concentrations of EGC (epigallocatechin), C (catechin), EC (epicatechin), and EGCG (epigallocatechin gallate). In contrast, PT had higher concentrations of GA (gallic acid), ECG (epicatechin-3-gallate), TF (theaflavin), and TB (theabrownin). PTP and DHTP consumption significantly reduced the rates of weight gain in mice. Microbial community diversity was significantly higher in PTP and DHTP-treated mice than in the control group. Notably, beneficial microbes such as Lactobacillus increased significantly in PTP-treated mice, whereas Lachnospiraceae increased significantly in DHTP-treated mice. Both PTP and DHTP improved the activity of the antioxidant enzymes (SOD) and total antioxidant capacity (T-AOC) in the liver. The transcriptome analysis revealed that the beneficial effects of PTP and DHTP were due to changes in various metabolic pathways, the majority of which were related to antioxidant and lipid metabolism. This study discovered that PTP and DHTP had beneficial effects in mice via the gut-liver axis.

Preventive effect and mechanism of Tibetan tea extract on thrombosis in arachidonic acid-induced zebrafish determined via RNA-seq transcriptome profiles.

Thrombosis is a key pathological event in cardiovascular diseases and is also the most important targeting process for their clinical management. In this study, arachidonic acid (AA) was used to induce thrombus formation in zebrafish larvae. Blood flow, red blood cell (RBCs) aggregation and cellular oxidative stress were measured to evaluate the antithrombotic effect of Tibetan tea (TT). Meanwhile, the potential molecular mechanism was further explored by transcriptome sequencing (RNA-seq). The results indicated that TT could significantly restore heart RBCs intensity of thrombotic zebrafish, whilst decreasing RBCs accumulation in the caudal vein. The transcriptome analysis revealed that the preventive effect of TT on thrombosis could be mostly attributed to changes in lipid metabolism related signaling pathways, such as fatty acid metabolism, glycerollipid metabolism, ECM-receptor interaction and steroid biosynthesis signaling pathway. This study demonstrated that Tibetan tea could alleviate thrombosis by reducing oxidative stress levels and regulating lipid metabolism.

In-silico annotation of the chemical composition of Tibetan tea and its mechanism on antioxidant and lipid-lowering in mice.

BACKGROUND/OBJECTIVES: Tibetan tea is a kind of dark tea, due to the inherent complexity of natural products, the chemical composition and beneficial effects of Tibetan tea are not fully understood. The objective of this study was to unravel the composition of Tibetan tea using knowledge-guided multilayer network (KGMN) techniques and explore its potential antioxidant and hypolipidemic mechanisms in mice. MATERIALS/METHODS: The C57BL/6J mice were continuously gavaged with Tibetan tea extract (T group), green tea extract (G group) and ddH2O (H group) for 15 days. The activity of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in mice was detected. Transcriptome sequencing technology was used to investigate the molecular mechanisms underlying the antioxidant and lipid-lowering effects of Tibetan tea in mice. Furthermore, the expression levels of liver antioxidant and lipid metabolism related genes in various groups were detected by the real-time quantitative polymerase chain reaction (qPCR) method. RESULTS: The results showed that a total of 42 flavonoids are provisionally annotated in Tibetan tea using KGMN strategies. Tibetan tea significantly reduced body weight gain and increased T-AOC and SOD activities in mice compared with the H group. Based on the results of transcriptome and qPCR, it was confirmed that Tibetan tea could play a key role in antioxidant and lipid lowering by regulating oxidative stress and lipid metabolism related pathways such as insulin resistance, P53 signaling pathway, insulin signaling pathway, fatty acid elongation and fatty acid metabolism. CONCLUSIONS: This study was the first to use computational tools to deeply explore the composition of Tibetan tea and revealed its potential antioxidant and hypolipidemic mechanisms, and it provides new insights into the composition and bioactivity of Tibetan tea.

In silico characterization of bla NDM-harboring plasmids in Klebsiella pneumoniae.

Klebsiella pneumoniae is a primary culprit of antibiotic-resistant nosocomial infections worldwide, and infections caused by NDM-producing strains are a major threat due to limited therapeutic options. The majority of bla NDM cases occur on plasmids; therefore, we explored the relationships between plasmids and bla NDM genes in K. pneumoniae by analyzing the variants of bla NDM, replicon types, conjugative transfer regions of 171 bla NDM-harboring plasmids from 4,451 K. pneumoniae plasmids. Of the nine identified bla NDM variants, bla NDM-1 (73.68%) and bla NDM-5 (16.37%) were the most dominant. Over half of the bla NDM-harboring plasmids of K. pneumoniae were classified into IncF plasmids. IncX3 single-replicon plasmids (46-57 kb) carried genes encoding relaxases of the MOBP family, T4CP genes of the VirD4/TraG subfamily, and VirB-like T4SS gene clusters, which were mainly geographically distributed in China. We found 10 bla NDM-harboring IncN plasmids (38.38-63.05 kb) carrying the NW-type origin of transfer (oriT) regions, genes coding for relaxases of MOBF family, genes encoding T4CPs of the TrwB/TraD subfamily, and Trw-like T4SS gene clusters, which were also mainly geographically distributed in China. Moreover, we identified 21 IncC plasmids carrying bla NDM-1 (140.1-329.2 kb), containing the A/C-type oriTs, genes encoding relaxases of MOBH family, genes encoding T4CPs belonging to TrwB/TraD subfamily, and Tra_F-like T4SS gene clusters. The bla NDM-harboring IncC plasmids were widely geographically distributed all over the world, mainly in the United States, China and Viet Nam. These findings enhance our understanding of the diversity of bla NDM-harboring plasmids in K. pneumoniae.

Network Pharmacology and Bioinformatics Methods Reveal the Mechanism of Zao-Jiao-Ci in the Treatment of LSCC.

OBJECTIVE: Zao-Jiao-Ci (ZJC), a traditional Chinese medicine, is considered as a promising candidate to treat laryngeal squamous cell carcinoma (LSCC). However, the underlying molecular mechanism remains unclear. METHODS: Gene expression profiles of GSE36668 were available from the GEO database, and differentially expressed genes (DEGs) of LSCC were obtained by R package; subsequently, enrichment analysis on KEGG and GO of DEGs was performed. The active ingredients of ZJC were screened from the TCMSP database, and the matched candidate targets were obtained by PharmMapper. Furthermore, we constructed protein-protein interaction (PPI) networks of DEGs and candidate targets, respectively, and we screened the core network from the merged network through combining the two PPI networks using Cytoscape 3.7.2. The key targets derived from the core network were analyzed to find out the associated KEGG signal enrichment pathway. By the GEPIA online website, Kaplan-Meier analysis was used to complete the overall survival and disease-free survival of the selected genes in the core module. RESULTS: We identified 96 candidate targets of ZJC and 86 DEGs of LSCC, the latter including 50 upregulated genes and 36 downregulated genes. DEGs were obviously enriched in the following biological functions: extracellular structure organization, the extracellular matrix organization, and endodermal cell differentiation. The 60 key targets from the core network were enriched in the signal pathways including transcriptional misregulation cancer, cell cycle, and so on. We found that LSCC patients with high expression of HIST1H3J, HIST1H3F, and ITGA4 had worse overall survival, while higher expression of NTRK1, COPS5, HIST1H3A, and HIST1H3G had significantly worse disease-free survival. CONCLUSION: It suggested that the interaction between ZJC and LSCC was related to the signal pathways of transcriptional misregulation cancer and cell cycle, revealing that it may be the mechanism of ZJC in the treatment of LSCC.

Association between Growth Differentiation Factor-15 and Risk of Cardiovascular Diseases in Patients with Adult Growth Hormone Deficiency.

OBJECTIVE: Patients with adult growth hormone deficiency (AGHD) confer a heightened risk of cardiovascular disease and increased mortality because of metabolic disorders. Growth differentiation factor-15 (GDF-15) plays an important role in predicting metabolic abnormalities. We sought to investigate the correlation between GDF-15 and cardiovascular risk in AGHD patients. METHODS: The study enrolled 80 AGHD patients and 80 healthy subjects. We analyzed the association between GDF-15 and some major biochemical indicators. The potential association between GDF-15 and cardiovascular disease risk was analyzed. RESULTS: The AGHD group exhibited increased waist-hip ratio and high-sensitivity C-reactive protein (hs-CRP) and lipid levels compared with the healthy control group. Serum GDF-15 levels in AGHD group were elevated significantly compared with the control group (P < 0.001). GDF-15 levels were negatively associated with insulin-like growth factor-1 in AGHD group (P=0.006) and positively correlated with waist-to-hip ratio (P=0.018), triglycerides (P=0.007), and hs-CRP (P=0.046). In addition, GDF-15 was positively correlated with Framingham risk score significantly after adjustment for other factors (r = 0.497, P < 0.001). Moreover, GDF-15 was an independent risk factor for cardiovascular disease in AGHD patients after adjusting for traditional cardiovascular risk factors. CONCLUSION: Elevated GDF-15 levels were significantly associated with cardiovascular risk factors and can be considered as a predictive biomarker of cardiovascular risk in AGHD patients.

Correction to: The ZJU index is a powerful index for identifying NAFLD in the general Chinese population.

In paragraph Index calculation formulae.

Association between Visceral Fat and Bone Mineral Density in Both Male and Female Patients with Adult Growth Hormone Deficiency.

AIM: Adult growth hormone deficiency (AGHD) is associated with an increased risk of fractures. The interactions between various body composition and bone are known to be complex in nature. However, very few studies have examined this crosstalk in AGHD. In this study, we sought to investigate the relationship between various parameters of body composition and bone mineral density (BMD) as well as determine the role of visceral fat in determining the bone mass in patients with AGHD. METHODS: We conducted a cross-sectional study on 57 patients with AGHD. Anthropometry, biochemistry, and analysis of body composition and BMD were performed according to standard protocols. Male and female patients were classified into those with osteoporosis and those without osteoporosis (normal subjects and patients with osteopenia). Further, we analyzed the correlation between the BMD and measurements obtained for various body composition parameters in male and female AGHD patients. RESULTS: Our findings indicated that among female AGHD patients, those with osteoporosis had a significantly higher levels of fat mass (FM) and visceral adipose tissue mass (VATM) (both, P < 0.05) than those without osteoporosis. Further, Pearson correlation analysis showed that the values of age, body mass index (BMI), FM, and VATM correlated negatively with BMD in women with AGHD (all P < 0.05); however, this association was not noted in men. After adjusting for the other covariates, VATM was found to be independently correlated with the BMD in female patients with AGHD. CONCLUSIONS: A close correlation was noted between VATM and BMD in female patients with AGHD.

The ZJU index is a powerful index for identifying NAFLD in the general Chinese population.

AIMS: The ZJU index is a novel model for detecting non-alcoholic fatty liver disease (NAFLD) that it is calculated based on combination of the body mass index, fasting plasma glucose, triglycerides, and the serum alanine aminotransferase-to-aspartate transaminase ratio. We aimed to evaluate the diagnostic accuracy of the ZJU index in detecting NAFLD in the Chinese population. METHODS: This was a cross-sectional study. Anthropometric measurements, laboratory data, and ultrasonography features were collected through a standard protocol. The ZJU index, fatty liver index, hepatic steatosis index, lipid accumulation product, and visceral adiposity index were calculated. Then the predictive values of the five indices were compared according to the area under receiver-operating characteristic curve (AUROC) values. RESULTS: A total of 19,804 participants were recruited, of whom 7324 participants were diagnosed with NFALD and 12,480 subjects were regarded as controls. The AUROC value for NAFLD identification by the ZJU index was 0.925 (95% confidence interval [CI]: 0.919-0.931), which was significantly higher than the values for the other four models (P < 0.001). Furthermore, from age 31 years to >60 years, the AUROC for the ZJU increased from 87.1 to 95.4%, values which were also greater than those for the other four indices. Analysis by sex also showed that the performance of the ZJU index in males and females was better than that of the other four indices. CONCLUSIONS: The ZJU index is an accurate and easy to employ tool for identifying NAFLD in the general Chinese population.

Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3.

OBJECTIVE: To explore the expression of microRNA (miRNA) let-7c and its function in chronic obstructive pulmonary disease (COPD) and alveolar macrophage cells. METHODS: Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice. MiRNA let-7c was overexpressed in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3 (STAT3) as well as phosphorylation level of STAT3 after LPS stimulation. Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3. RESULTS: MiRNA let-7c expression was significantly lower in patients with COPD compared with control group, and the similar result was found in COPD mice and LPS stimulated alveolar macrophages. Overexpression of miRNA let-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha, interleukin-6 and interleukin-1ß. Luciferase assay showed STAT3 was a targeting of miRNA let-7c in alveolar macrophages. CONCLUSIONS: MiRNA let-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage, which may provide a new target for COPD treatment strategies.