Advances in the Study of Non-Coding RNA in the Signaling Pathway of Pulmonary Fibrosis.

Pulmonary fibrosis is a group of chronic, progressive, and irreversible interstitial lung diseases, which are common to most end-stage lung diseases and are one of the most difficult diseases of the respiratory system. In recent years, due to the frequent occurrence of air pollution and smog, the incidence of pulmonary fibrosis in China has increased year by year, the morbidity and mortality rates of pulmonary fibrosis have gradually increased and the age of the disease tends to be younger. However, the pathogenesis of pulmonary fibrosis is not yet fully understood and is needed to further explore new drug targets. Studies have shown that non-coding RNAs play an important role in regulating the process of pulmonary fibrosis, non-coding RNAs and their specifically expressed can promote or inhibit the process. Here, we review the role of some in the regulation of pulmonary fibrosis signaling pathways and provide new ideas for the clinical diagnosis and treatment of pulmonary fibrosis.

Label-Free Detection of DNA Supramolecular Structure Formation by Surface-Enhanced Raman Spectroscopy.

The precise self-assembly of DNA molecules can be used to create nanoprecision supramolecular materials. However, the lack of methods to characterize such supramolecular materials limits their development. Surface-enhanced Raman spectroscopy (SERS) is widely used to detect the secondary structure of simple DNA molecules, but its application in the revealing of complex DNA supramolecular information remains challenging. Herein, we proposed a modified SERS-based platform able to provide structural information on DNA supramolecular materials. The silver nanoparticle-enhanced substrate uses acetonitrile as an internal standard and modifier, and calcium ions are used as an aggregating agent to induce the formation of stable "hotspots" of silver nanoparticles, where the base planes in DNA supramolecules are perpendicular to the surface of the substrate, obtaining enhanced Raman signals of base ring in both single-stranded DNA and DNA supramolecules for the first time. The structure of DNA supramolecules was efficiently characterized using this technique, showing the great application potential of this technique in the structural analysis of nucleic acids and their ligands.

Endoscopic therapy combined with photodynamic therapy for intratracheal inflammatory myofibroblastic tumor.

Inflammatory myofibroblastic tumor (IMT) is a rare intermediate tumor that exhibits both benign and malignant behaviors. Whether IMT is an inflammatory or a neoplastic disease remains controversial, and there is currently no standard treatment for this disease. The treatment strategies include surgical tumor removal and drug therapy; however, several patients experience tumor recurrence post-treatment. Herein, we report the endoscopic manifestations and treatment process in a case of IMT. We performed photodynamic therapy (PDT) after endoscopic tumor resection, and no recurrence was found in the patient's re-examination a year later. This indicates that PDT can improve IMT prognosis and reduce its local recurrence, signifying the therapy's potential application value for IMT.

Effectiveness of corticosteroids to treat severe COVID-19: A systematic review and meta-analysis of prospective studies.

OBJECTIVES: To assess the effects of corticosteroid therapy for patients with severe coronavirus disease 2019 (COVID-19). METHODS: We comprehensively searched articles published in the Cochrane Library, PubMed, Embase, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases from January 1, 2019, to March 20, 2021. RESULTS: A total of 6771 patients from eight prospective studies were included in our meta-analysis. The results showed that corticosteroid therapy was associated with lower mortality in severe COVID-19 (OR = 0.70, 95% CI = 0.54-0.92, P = 0.009; I2 = 54.5%). Since the proportion of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial included in the meta-analysis was as high as 71.88%, we removed it and recalculated the pooled OR. The results of the remaining seven studies still suggested such a survival benefit (OR = 0.65, 95% CI = 0.44-0.96, P = 0.030; I2 = 59.8%). Furthermore, subgroup analysis suggested that the pooled OR of three studies using corticosteroids in the early stages of treatment was much lower (OR = 0.37, 95% CI = 0.25-0.57, P < 0.001; I2 = 47.8%). However, after excluding the RECOVERY trial, the pooled OR of the remaining four studies with unspecific administration timing of corticosteroid therapy no longer supported this result (OR = 0.90, 95% CI = 0.69-1.17, P = 0.415; I2 = 0.0%). CONCLUSIONS: In this meta-analysis, evidence based on seven randomized controlled trials and one prospective cohort study indicates that corticosteroid therapy was associated with a reduction in the mortality of severe COVID-19, especially when administered at an earlier time.

Relationship between blood eosinophil levels and COVID-19 mortality.

OBJECTIVES: A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is causing the worldwide coronavirus disease 2019 (COVID-19) outbreak with high mortality. A unique finding among COVID-19 patients was a decline of eosinophil levels (eosinopenia). However, results from previous studies on the relationship between eosinopenia and disease severity were inconsistent. The objective of this study is to determine the relationship between eosinopenia and COVID-19 mortality as well as the clinical conditions that could potentially lead to mortality. METHODS: One hundred ninety patients diagnosed as moderate, severe, or critical COVID-19 at hospital admission were enrolled. Data collected from patients' medical records on the second day after hospital admission included medical histories, clinical symptoms, chest images of computed tomography (CT), laboratory examinations, and outcomes. RESULTS: Eosinophil levels were significantly lower in patients with critical disease, when compared to those with moderate and severe diseases. After controlled for confounding factors, ie, age, gender, hypertension, coronary heart disease, diabetes, and chronic lung disease, a progressive decline of eosinophil levels was independently associated with mortality. Moreover, eosinophil levels significantly and positively correlated with platelet and D-dimer levels but significantly and inversely correlated with serum levels of urea, creatinine, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase. CONCLUSIONS: Eosinopenia, if progressively worsening, indicates that COVID-19 patients may progress to critical disease and have a significantly higher chance of mortality. Additionally, eosinopenia correlates with biomarkers of coagulation disorder and those of tissue damage in kidney, liver, and other tissues.

HOXA10 promotion of HDAC1 underpins the development of lung adenocarcinoma through the DNMT1-KLF4 axis.

BACKGROUND: Previous research has highlighted the ability of Homeobox A10 (HOXA10) to the promote proliferation, migration, and epithelial-mesenchymal transformation of various cancers, including lung adenocarcinoma (LAD), which is characterized by an aggressive disease course that exhibits rapid proliferation and migration, with studies suggesting histone deacetylase 1 (HDAC1) to be a downstream mediator of HOXA10. The current study aimed to investigate the mechanism by which HOXA10-mediated HDAC1 influences the development of LAD. METHODS: The expression patterns of HOXA10, HDAC1, DNA methyltransferase 1 (DNMT1), and Kruppel-like factor 4 (KLF4) were determined. Additionally, the effect of HOXA10, HDAC1, or DNMT1 on invasive phenotypes of LAD was analyzed using depletion experiments. The interactions among HOXA10, HDAC1, DNMT1, and KLF4 were evaluated via chromatin immunoprecipitation, dual luciferase assay or co-immunoprecipitation. Furthermore, the tumorigenic ability of the LAD cells following HOXA10 silencing and/or HDAC1 overexpression in vivo was also investigated. RESULTS: In the LAD tissues and cells, HOXA10, HDAC1, and DNMT1 all exhibited high levels of expression, while KLF4 was poorly expressed. HOXA10 silencing inhibited the expression of HDAC1, reduced LAD cell proliferation, migration, and invasion, and promoted the apoptosis. HDAC1 promoted DNMT1 expression through deacetylation, and DNMT1 inhibited the KLF4 expression through DNA methyltransferase. The in vitro findings were further attested through the use of in vivo assays. CONCLUSION: Taken together, the key observations of the current study highlight the role of HOXA10 and HDAC1 in promoting the proliferation and migration of LAD cells. HOXA10-induced upregulation of HDAC1 interacts with DNMT1-KLF4 axis, while the inhibition of HOXA10 or HDAC1 represents a promising anti-tumor therapy target for LAD.

Decrypting the crosstalk of noncoding RNAs in the progression of IPF.

Idiopathic pulmonary fibrosis (IPF) is an agnogenic, rare, and lethal disease, with high mortality and poor prognosis and a median survival time as short as 3 to 5 years after diagnosis. No effective therapeutic drugs are still not available not only in clinical practice, but also in preclinical phases. To better and deeper understand pulmonary fibrosis will provide more effective strategies for therapy. Mounting evidence suggests that noncoding RNAs (ncRNAs) and their interactions may contribute to lung fibrosis; however, the mechanisms underlying their roles are largely unknown. In this review, we systematically summarized the recent advances regarding the crucial roles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) and crosstalk among them in the development of IPF. The perspective for related genes was well highlighted. In summary, ncRNA and their interactions play a key regulatory part in the progression of IPF and are bound to provide us with new diagnostic and therapeutic targets.

Tumor-Promoting Activity of Long Noncoding RNA LINC00466 in Lung Adenocarcinoma via miR-144-Regulated HOXA10 Axis.

Previous investigations have implicated long noncoding RNAs in lung adenocarcinoma, which is an aggressive disease with poor prognosis and high mortality. Through the alteration of lung adenocarcinoma-related long noncoding RNA and miRNA based on microarray analysis, our aim was to understand the role of LINC00466 and miR-144 in lung adenocarcinoma progression. The relationship among LINC00466, miR-144, and HOXA10 was also verified. Moreover, to examine whether the LINC00466/miR-144/HOXA10 axis contributed to the cellular processes in lung adenocarcinoma, A549 and XWLC-05 cells were transduced with siRNA LINC00466, siRNA HOXA10, or miR-144 mimic plasmids. Highly expressed LINC00466 and HOXA10 and lowly expressed miR-144 were eventually revealed in lung adenocarcinoma tissues. HOXA10 was down-regulated in response to the overexpression of miR-144, whereas inhibition of LINC00466 decreased its binding to miR-144, thereby up-regulating miR-144, which, in turn, halted the lung adenocarcinoma progression. LINC00466 silencing or miR-144 up-regulation exerted an inhibitory role in the tumorigenicity, invasion, migration, and proliferation, and it also promoted apoptosis of lung adenocarcinoma cells. Furthermore, tumor formation was inhibited by knockdown of LINC00466 or overexpression of miR-144. Taken together, LINC00466 could restrain the miR-144 expression to up-regulate HOXA10 and, therefore, promote lung adenocarcinoma.

Interleukin­33 promotes obstructive renal injury via macrophages.

Chronic kidney disease is the outcome of most kidney diseases, and renal fibrosis is a pathological process involved in the progression of these disorders. The role of interleukin (IL)­33 was previously investigated in fibrotic disorders affecting various organs, including liver, lungs and heart; however, its role in renal fibrosis remains unclear. Previous studies have demonstrated that macrophages are involved in obstructive renal injury. In the present study, the roles of IL­33 and macrophages on renal fibrosis were investigated using a mouse model of unilateral ureteral obstruction (UUO). Compared with non­obstructed kidneys, the expression levels of IL­33 and its receptor, interleukin 1 receptor like 1, increased after UUO. Furthermore, the infiltration of macrophages and the degree of renal fibrosis increased after treatment with IL­33. Additionally, the expression level of arginase­1, a marker of M2 macrophages, increased in renal tissue. After depletion of macrophages, the administration of exogenous IL­33 was not sufficient to reverse the reduction in fibrosis caused by elimination of these cells. Collectively, the present results suggested that IL­33 promoted renal fibrosis in UUO­induced renal injury by regulating macrophage polarization.

Efficacy and Safety of Antigen-specific Immunotherapy in the Treatment of Patients with Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). METHODS: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. RESULTS: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). CONCLUSION: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

IDH1 mutation promotes lung cancer cell proliferation through methylation of Fibulin-5.

Mutation in isocitrate dehydrogenase (IDH) leads to an aberrant function of the enzyme, leading to the production of hydroxyglutarate, as well as changes in cellular metabolism, DNA methylation and histone modification. Previous studies uncovered mutations in IDH1 in several malignancies, with the most frequent mutation being IDH1 R132H. It has been demonstrated that IDH1 expression is induced in non-small-cell lung cancer (NSCLC). However, the contribution of IDH1 mutation in the malignant transformation and development of NSCLC is unclear. In our study, we show that IDH1 R132H enhanced the migration and proliferation of NSCLC cells. Moreover, IDH1 R132H was a crucial modulator of 2-hydroxyglutarate, whose production from cells with IDH1 mutation promoted the binding of DNA-methyltransferase 1 (DNMT1) to the Fibulin-5 promoter, leading to its methylation. As a result, Fibulin-5 silencing in cells with IDH1 mutation enhanced the migration and proliferation of NSCLC cells. We show that the IDH1 mutation was present in tissues sampled from patients with NSCLC, which was reversely linked to Fibulin-5 expression. In this study, we suggest an innovative model for IDH1 R132H/Fibulin-5 pathway, which could throw light upon the activity of IDH1 R132H in NSCLC.

A novel circular RNA hsa_circ_0020123 exerts oncogenic properties through suppression of miR-144 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide, while circulatory. Circular RNAs (circRNAs) are found to play important roles in cancer initiation and development. Herein, a novel functional circRNA hsa_circ_0020123 had been identified in NSCLC progression in this study, and elevated hsa_circ_0020123 expression could be observed in cancer tissues compared with that in matched normal lung tissues. Moreover, up-regulation of hsa_circ_0020123 was recognized to be closely associated with a poor differentiation degree, lymph node metastasis, a high TNM stage and dismal prognosis for NSCLC patients. Typically, knockdown of hsa_circ_0020123 could inhibit the NSCLC growth and metastasis both in vitro and in vivo, which could be reversed by the hsa_circ_0020123 overexpression. Importantly, miR-144 was identified as the hsa_circ_0020123-associated miRNA through performing RNA in vivo precipitation (RIP) in NSCLC cells using a biotin-labeled hsa_circ_0020123 probe. Besides, our results suggested that, miR-144 suppression had determined the oncogenic properties mediated by hsa_circ_0020123. In addition, hsa_circ_0020123 could upregulate ZEB1 and EZH2 through competitively binding with miR-144. Finally, the administration of hsa_circ_0020123 siRNA could suppress the growth and metastasis in NSCLC-bearing mice in vivo. In conclusion, the hsa_circ_0020123-miR-144-ZEB1/EZH2 axis is critical for NSCLC progression, which indicates that hsa_circ_0020123 is a potential target for NSCLC treatment.

Maternal exposure to farming environment protects offspring against allergic diseases by modulating the neonatal TLR-Tregs-Th axis.

BACKGROUND: As the development of urbanization in China, the morbidity of allergic disease rise up prominently even in children, which may be partially associated with the excessively clean environment. It has been reported that common microorganism in rural environment shows protective effects on allergic disease by modulating TLRs-Tregs/Th cell axis. But the mechanism of this protection still needs to be elucidated in detail. We investigated the effects of maternal exposure to farming environment on the neonatal innate immune system, especially on the TLR-Treg-Th (Th1, Th2, Th9, and Th17) axis, in the Jilin province of China. METHODS: Eighty-four non-farming and 42 farming pregnant women were recruited. Endotoxins and glucans in dust from the living rooms of the pregnant mothers were measured. Cord blood mononuclear cells were challenged with phytohemagglutinin, lipopolysaccharide, or peptidoglycan. Proliferative response of lymphocyte was measured by 3H-TdR incorporation methods, CD4 + CD25 + FOXP3 + T cells percentage was assessed with flow cytometry, Tregs specific genes (FOXP3, LAG3, GITR, CTLA-4 and TGF-ß) and TLR2, TLR4 genes expression were detected by RT-PCR, specific cytokines of Th1, Th2, Th9, Th17 and Tregs were measured with flow cytometer, suppressive capacity of Tregs was tested by culturing with effector cells in vitro, and TLR2/4 gene polymorphism was detected. RESULTS: Higher endotoxin content was observed in the living rooms of the farming mothers. Compared with that in the non-farming group, in farming neonatal CBMCs, lymphocyte proliferation declined; the IFN-γ/IL-13 ratio increased; and the quantity of Tregs and gene expression of FOXP3, GITR, CTLA4 and TLR2 increased significantly (P < 0.05). Isolated Tregs suppressed the proliferation of effector T cells and IL-13 production more strongly in vitro (P = 0.04, 0.03, respectively), and the TLR2 polymorphism affected FOXP3 expression and IFN-γ and IL-13 production. CONCLUSIONS: Maternal exposure to farming affected the quantity and function of neonatal Tregs upon stimulation with PPG and LPS, which partly contributed to reducing the risk for allergic diseases in the offspring. The results of our study will lay the theoretical foundation for allergic disease prevention in early life.

LncRNA H19-elevated LIN28B promotes lung cancer progression through sequestering miR-196b.

LncRNA H19 is involved in the development of multiple cancers. Here, we firstly provide new evidence that H19 can induce LIN28B, a conserved RNA binding protein, to accelerate lung cancer growth through sponging miR-196b. Abundance in LIN28B was observed in clinical lung cancer samples. A positive link was observed between H19 and LIN28B in clinical lung cancer samples. In lung cancer cells, H19 was capable of increasing LIN28B expression. Mechanistically, miR-196b directly targeted LIN28B to inhibit LIN28B expression. H19 was capable of promoting LIN28B expression through sequestering miR-196b. Functionally, H19-increased LIN28B conferred the cell proliferation of lung cancer. Our finding indicates that H19 depresses miR-196b to elevate LIN28B, resulting in accelerating cell proliferation in lung cancer.

Effect of SLC34A2 gene mutation on extracellular phosphorus transport in PAM alveolar epithelial cells.

A mutation in the IIb sodium phosphate transporter SLC34A2 gene has recently been described in pulmonary alveolar microlithiasis (PAM) patients. Experiments in this study were aimed at confirming the role of the gene product in PAM by comparing phosphorylated products in extracellular fluid of alveolar epithelial cells overexpressing the SLC34A2 gene or its mutated version. Eukaryotic expression vectors were constructed and transfected into A549 human alveolar epithelial cells. There were three groups of cells including those transfected with empty vector plasmid pcDNA3.1(+) (plasmid control group), those transfected with normal SLC34A2 gene expressed from pcDNA3.1 (normal control group), and those transfected with a version of the PAM SLC34A2 gene linked to the pcDNA3.1(+) (PAM group). Transfection efficiencies were detected by reverse transcription-polymerase chain reaction (RT-PCR). At 48 h after transfection, the concentration of inorganic phosphorus in the culture medium was detected using an automatic biochemical analyzer. Our results showed the concentration of inorganic phosphorus in the supernatant of the normal control group was significantly lower than that in the plasmid control and PAM groups (P<0.01), and the concentration in the PAM group was significantly lower than that in the plasmid control group (P<0.01). Based on our findings it is possible that the SLC34A2 gene mutation is the cause of the pathogenic changes observed in PAM patients, given that the function of the phosphate transporter seems to be affected and it is conceivable that it would lead to extracellular fluid alterations in vivo.

Antioxidative Effects of Natural Products on Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes and results in high mortality. It is therefore imperative to develop novel therapeutics for the prevention or inhibition of the progression of DCM. Oxidative stress is a key mechanism by which diabetes induces DCM. Hence, targeting of oxidative stress-related processes in DCM could be a promising therapeutic strategy. To date, a number of studies have shown beneficial effects of several natural products on the attenuation of DCM via an antioxidative mechanism of action. The aim of the present review is to provide a comprehensive and concise overview of the previously reported antioxidant natural products in the inhibition of DCM progression. Clinical trials of the antioxidative natural products in the management of DCM are included. In addition, discussion and perspectives are further provided in the present review.

Sulforaphane prevents bleomycin­induced pulmonary fibrosis in mice by inhibiting oxidative stress via nuclear factor erythroid 2­related factor­2 activation.

Lung fibrosis is associated with inflammation, apoptosis and oxidative damage. The transcription factor nuclear factor erythroid 2­related factor­2 (Nrf2) prevents damage to cells from oxidative stress by regulating the expression of antioxidant proteins. Sulforaphane (SFN), an Nrf2 activator, additionally regulates excessive oxidative stress by promoting the expression of endogenous antioxidants. The present study investigated if SFN protects against lung injury induced by bleomycin (BLM). The secondary aim of the present study was to assess if this protection mechanism involves upregulation of Nrf2 and its downstream antioxidants. Pulmonary fibrosis was induced in C57/BL6 mice by intratracheal instillation of BLM. BLM and age­matched control mice were treated with or without a daily dose of 0.5 mg/kg SFN until sacrifice. On days 7 and 28, mice were assessed for induction of apoptosis, inflammation, fibrosis, oxidative damage and Nrf2 expression in the lungs. The lungs were investigated with histological techniques including haematoxylin and eosin staining, Masson's trichrome staining and terminal deoxynucleotidyl transferase UTP nick end labeling. Inflammatory, fibrotic and apoptotic processes were confirmed by western blot analysis for interleukin­1ß, tumor necrosis factor­α, transforming growth factor­ß and caspase­3 protein expressions. Furthermore, protein levels of 3­nitro­tyrosine, 4­hydroxynonenal, superoxide dismutase 1 and catalase were investigated by western blot analysis. It was demonstrated that pulmonary fibrosis induced by BLM significantly increased apoptosis, inflammation, fibrosis and oxidative stress in the lungs at days 7 and 28. Notably, SFN treatment significantly attenuated the infiltration of the inflammatory cells, collagen accumulation, epithelial cell apoptosis and oxidative stress in the lungs. In addition, SFN treatment increased expression of the Nrf2 gene and its downstream targets. In conclusion, these results suggested that SFN treatment of pulmonary fibrosis mouse models may attenuate alveolitis, fibrosis, apoptosis and lung oxidative stress by increasing the expression of antioxidant enzymes, including NAPDH quinone oxidoreductase, heme oxygenase­1, superoxide dismutase and catalase, via upregulation of Nrf2 gene expression. Thus, the results from the present study may facilitate the development of therapies for BLM­toxicity and pulmonary fibrosis.

Maternal allergic disease history affects childhood allergy development through impairment of neonatal regulatory T-cells.

BACKGROUND: Maternal allergic disease history and impaired regulatory T-cells (Tregs) are critical risk factors for allergy development in children. However, the mechanisms that underlie these risk factors remain poorly defined. Therefore, the aim of this study was to assess whether maternal allergies affect the Tregs of offspring and lead to allergy development in childhood. METHODS: A total of 332 mothers of healthy newborns (234 from no allergic mothers, 98 from allergic mothers) were recruited to this study. Detailed questionnaires were administered yearly to determine the allergy status of the mothers and the newborns from birth to 3 years of age. Cord blood samples obtained at the time of birth were analysed for Treg counts, as well Treg activity, based on their response to Toll-like receptor (TLR) stimuli such as lipid A (LPA) and peptidoglycans (PPG). Surface markers, associated genes, suppressive capacity, and cytokine levels of Tregs were also measured. Possible correlations between Treg activity and maternal or neonate allergies were assessed. In addition, environmental microbial content and other known risk factors for allergies were measured. RESULTS: Cord blood mononuclear cells (CBMCs) from offspring with allergic mothers showed fewer CD4(+)CD25(+)FOXP3(+) T cells, lower expression levels of associated genes, and reduced cytokine production of interleukin (IL)-10 and interferon-γ (P < 0.05), especially via the PPG-TLR2 pathway. Suppression of effector T cells by Tregs from children of mothers with allergies was impaired, especially IL-13 production by Type 2 T helper (Th2) cells (P = 0.026). Children who developed allergies in the first 3 years of life had lower numbers of CD4(+)CD25(+)FOXP3(+) T cells and reduced FOXP3 expression and IL-10 production as newborns (P < 0.05). Maternal allergic background was identified as a risk factor for allergy development in the children (Odds ratio (OR) = 2.46, 95 % CI = 1.05-5.79); while declining Treg numbers, IL-10 production, and FOXP3 expression in neonates (PPG and LPA stimulated) were identified as independent risk factors for allergic diseases in offspring at 3 years of age after adjusting for maternal allergic history and environmental factors (P < 0.05). CONCLUSION: Maternal allergy correlated with impaired Tregs in neonates, and this could enhance the susceptibility of offspring to allergic diseases in early childhood due to an imbalance of Th1 and Th2 cells.