Association of the MMP-3, MMP-9 and MMP-12 gene polymorphisms with COPD risk: a meta-analysis.

Introduction: Given the evidence that the matrix metalloproteinases (MMPs) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), a number of case-control studies have attempted to assess the relationship between genetic polymorphisms in MMP genes and COPD risk. However, reliable measures of these results are lacking. Material and methods: We assessed the published evidence for association of the MMP-3, MMP-9 and MMP-12 polymorphisms with COPD risk using meta-analytic techniques. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each study using fixed or random effect models. Results: A total of 23 case-control studies were included in the meta-analysis. No significant association was observed between the MMP-9 rs3918242 polymorphism and COPD risk in the overall populations under the dominant (T/T + C/T vs. C/C: OR = 1.30, 95% CI: 1.00-1.69, p = 0.054) and allele contrast (T allele vs. C allele: OR = 1.22, 95% CI: 0.97-1.53, p = 0.088) models. However, in sub-group analysis the polymorphism rs3918242 was significant in Asians under the dominant model (T/T + C/T vs. C/C: OR = 1.66, 95% CI: 1.02-2.72, p = 0.043). The results for MMP-12 rs2276109 showed an association with COPD only in mixed populations (G/G + A/G vs. A/A: OR = 1.57, 95% CI: 1.10-2.24, p = 0.013; G allele vs. A allele: OR = 1.52, 95% CI: 1.09-2.14, p = 0.015). We did not find any significant association of the MMP-12 rs652438 and MMP-3 rs35068180 polymorphisms with COPD. Conclusions: The findings of this meta-analysis suggest that there is a risk of COPD associated with the MMP-9 rs3918242 and MMP-12 rs2276109 polymorphisms in certain ethnic groups.

Description of a new species of Forcipomyia (Lasiohelea) (Diptera: Ceratopogonidae) and a key to species of the F. (L.) taiwana species group in China.

Forcipomyia (Lasiohelea) (Meigen, Diptera: Ceratopogonidae) penguin sp. nov. is described and illustrated based on male specimens from China. It is characterized by the approximately rectangular aedeagus, which is longitudinally split in the middle, with the apices slightly bending to the outside, making it into the shape of a hook; bilobed aedeagus is very closely connected. The description is provided using scanning electron microscopes, light microscopes, and camera lucida drawing. The specimens were collected from woods near a pond in Liping County, Guizhou Province. We provide both keys to male and female of Forcipomyia (Lasiohelea) taiwana species group in China.

Bufalin induces apoptosis and autophagy via the Ca2+/CaMKKß/AMPK/Beclin1 signaling pathway in osteosarcoma cells.

Bufalin, a major cardiotonic compound of the traditional Chinese medicine Chanshu has been used for cancer treatment for several years. However, the molecular mechanisms of Bufalin-induced autophagy in osteosarcoma (OS) is not fully understood. In the present study, it was shown that Bufalin induced crosstalk between apoptosis and autophagy, which resulted in OS cell death. Mechanistically, Bufalin induced autophagy by increased the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I, and inducing apoptosis via the caspase-dependent pathway. Inhibition of autophagy promoted Bufalin-induced cell death. In contrast, suppression of apoptosis enhanced Bufalin-induced autophagy. In addition, it was found that Bufalin activated the Ca2+ /calmodulin-dependent protein kinase ß/AMPK/Beclin1 pathway, which resulted in induction of autophagy. These findings provide a mechanistic understanding of the means by which Bufalin mediates autophagy and apoptosis in OS cells.

Comprehensive analysis of protein phosphatase 1 regulatory inhibitor subunit 14B, a molecule related to tumorigenesis, poor prognosis, and immune cell infiltration in lung adenocarcinoma.

OBJECTIVE: To explore the relationship between Protein Phosphatase 1 Regulatory Inhibitor Subunit 14B (PPP1R14B) and the occurrence of lung adenocarcinoma (LUAD). METHOD: PPP1R14B expression was investigated using various databases, and its molecular functions and pathways were evaluated using Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Then, the correlation between tumor mutations and PPP1R14B expression was analyzed. Furthermore, the regulation network and expression pathway axes of PPP1R14B were constructed. The correlation analysis between PPP1R14B and immune cell infiltration was performed using deconvolution algorithm analysis and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining of the clinical samples were used for expression validation. RESULTS: PPP1R14B showed high expression in tumor tissue. PPP1R14B was associated with T and N stages and poor prognosis and was linked to the cell cycle, DNA repair, and low immune response. High PPP1R14B expression was associated with high tumor mutation rates. The upstream and downstream genes of PPP1R14B were identified, along with the construction of a protein-protein interaction network (PPI network) and the expression pathway axes of PPP1R14B. PPP1R14B expression was associated with poor immune cell infiltration and a negative correlation between PPP1R14B and mast cell and eosinophil infiltration. CONCLUSION: This study reveals high PPP1R14B expression in LUAD, its contribution to poor prognosis, molecular function, biological pathways, and impact on immune cell infiltration, and provides great insight into the role of PPP1R14B in LUAD tumorigenesis.

The Effects of Different Doses of Alfentanil and Dexmedetomidine on Prevention of Emergence Agitation in Pediatric Tonsillectomy and Adenoidectomy Surgery.

Background: Emergence agitation (EA) is a common problem often observed in children after sevoflurane anesthesia, which can be prevented by dexmedetomidine and alfentanil. This study aims to compare the effectiveness of dexmedetomidine alone and with different doses of alfentanil in preventing EA in children under sevoflurane anesthesia. Materials and Methods: In a double-blind trial, 80 children (ASA I or II, 3-7 years old) undergoing tonsillectomy alone and adenotonsillectomy with sevoflurane anesthesia were randomly assigned into four groups: the control group, dexmedetomidine (DEX) group, dexmedetomidine plus 10 µg/kg alfentanil group (DEX + Alf1), and dexmedetomidine plus 20 µg/kg alfentanil group (DEX + ALf2). The incidence of EA was assessed with the Aono's scale, and the severity of EA was evaluated with the Pediatric Anesthesia Emergence Delirium (PAED) scale. The time of tracheal extubation and time of wake were recorded. Postoperative pain and complications such as nausea and vomiting, cough, laryngospasm, and bradycardia were recorded. Results: The incidence of EA was 50% in the control group, 25% in the DEX group, and 5% in the DEX + Alf1 group, and it never happened in the DEX + Alf2 group. The Aono's scale, the PAED scale, and the FLACC scale in the control group and the DEX group were significantly more than those in the DEX + Alf1 group and the DEX + Alf2 group after the tracheal extubation (p < 0.05). The time of tracheal extubation of the control group and the DEX group were significantly shorter than those in the DEX + Alf1 group and the DEX + Alf2 group (p < 0.05). The awakening time of the DEX + Alf2 group is significantly longer than those in other groups (p < 0.05). The case of postoperative nausea and vomiting in the DEX + Alf1 group was fewer than those in the other groups (p < 0.05). And, the cases of cough and laryngospasm and bronchospasm in the DEX + Alf1 group and the DEX + Alf2 group were significantly less than those in the control group and the DEX group after the tracheal extubation (p < 0.05). Conclusion: The combined administration of alfentanil and dexmedetomidine can reduce EA in children undergoing tonsillectomy alone and adenotonsillectomy with sevoflurane anesthesia. Dexmedetomidine plus 10 µg/kg alfentanil seems to be more appropriate than other dose combinations as it reduced EA and postoperative nausea and vomiting but did not prolong the time to awake.

Mycobacterium vaccae Nebulization in the Treatment of COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with strong infectiousness and has no effective therapy. We aimed to explore the efficacy and safety of Mycobacterium vaccae nebulization in the treatment of Coronavirus Disease 2019 (COVID-19). Methods: In this randomized, double-blind, placebo-controlled clinical trial, we included 31 adult patients with moderate COVID-19 who were admitted to the Fourth People's Hospital of Nanning (Nanning, China) between January 22, 2020 and February 17, 2020. Patients were randomly divided into two groups: group A (standard care group) and group B (M. vaccae in combination with standard care group). The primary outcome was the time interval from admission to viral RNA negative conversion (oropharyngeal swabs were used in this study). Secondary outcomes included chest computed tomography (CT), mortality, length of hospital stay, complications during treatment, and so on. Patients were followed up to 4 weeks after discharge (reexamination of viral RNA, chest CT, etc.). Results: Nucleic acid test negative conversion time in group B was shorter than that in group A (2.9 days [2.7-8.7] vs. 6.8 days [3.3-13.8]; p = 0.045). No death and no conversion to severe or critical cases were observed in both groups. Two weeks after discharge, neither "relapse" nor "return to positive" cases were found. Four weeks after discharge, it was found that there was no case of " relapse " or "return to positive" in group B, and 1 patient in group A showed "return to positive", but there was no clinical manifestation and imaging progression. No adverse reactions related to M. vaccae were found during observation period. Conclusion:M. vaccae treatment might shorten the time interval from admission to viral RNA negative conversion, which might be beneficial to the prevention and treatment of COVID-19. Clinical Trial Registration: ChiCTR2000030016.

Mycobacterium vaccae nebulization protects Balb/c mice against bronchial asthma through neural mechanisms.

OBJECTIVES: Bronchial asthma can be effectively controlled but not be cured, its etiology and pathogenesis are still unclear, and there are no effective preventive measures. The key characteristic of asthma is chronic airway inflammation, and recent research has found that airway neurogenic inflammation plays an important role in asthma. We previously found that Mycobacterium vaccae nebulization protects against asthma. Therefore, this objective of this study is to explore the effect of M. vaccae nebulization on asthmatic neural mechanisms. METHODS: A total 18 of female Balb/c mice were randomized into normal, asthma control, and M. vaccae nebulization (Neb.group) groups, and mice in the Neb.group were nebulized with M. vaccae one month before the asthmatic model was established. Then, 1 month later, the mice were sensitized and challenged with ovalbumin. Twenty-four hours after the last challenge, mouse airway responsiveness; pulmonary brain-derived neurotropic factor (BDNF), neurofilament-medium length (NF-M, using NF09 antibody), and acetylcholine expression; and nerve growth factor (NGF) mRNA level were determined. RESULTS: We found that the BDNF, NF09, acetylcholine expression, and NGF mRNA level were decreased in the Neb.group compared with levels in the asthma control group. CONCLUSION: M. vaccae nebulization may protected in Balb/c mice against bronchial asthma through neural mechanisms.

The copper(II) complexes of new anthrahydrazone ligands: In vitro and in vivo antitumor activity and structure-activity relationship.

Two new copper(II) complexes, 9-PMAH-Cu (1) and 9-FPMAH-Cu (2), of anthrahydrazone were synthesized and structurally characterized, in which 9-FPMAH (9-(4'-trifluoromethyl)-pyrimidine anthrahydrazone) is the 4'-CF3 derivative of 9-PMAH (9-pyrimidine anthrahydrazone). Both complexes 1 and 2 showed similar intercalative binding modes towards DNA and might compete with the typical DNA intercalator, GelRed, in the same binding site. They could also act as topoisomerase (type I) suppressor to effectively inhibit its activity, in which complex 1 was more effective than 2. The in vitro antitumor screening indicated that complex 1 displayed much higher antiproliferative ability than 2 and cisplatin towards all the tested tumor cell lines. On the other hand, complex 1 also showed high cytotoxicity against human normal liver cell line HL-7702, suggesting it is a potential high cytotoxic antitumor candidate. While it was also suggested that the loss of activity of complex 2 might be due to the presence of 4'-CF3 on the pyrimidine ring. Studies on the cellular level showed that complex 1 could arrest the cell cycle of the most sensitive T-24 cells at G2/M phase and induced cell apoptosis. Complex 1 further showed a significant suppression on the tumor growth on the T-24 tumor xenograft mouse model, but not reduced the body weight. Especially, complex 1 could retain its coordination state in H2O even in the presence of HSA. The results suggests that complex 1 is of enough safety to be considered as a promising anticancer candidate by combining the bioactive Cu(II) and the anthrahydrazone pharmacophore.

Morphology of the immature stages of Dasyhelea silvatica Wang, Zhang & Yu with redescriptions of adults (Diptera, Ceratopogonidae).

The immatures of the biting midge Dasyhelea silvatica are described and illustrated for the first time and a complete description of the adult male and female are provided using scanning electron and compound microscopes. The specimens were collected from flooded soil near a pond in Guizhou Province, China, and reared in the laboratory.

The effect of an overall healthy lifestyle on early-onset stroke: a cross-sectional study.

BACKGROUND: The impact of an overall healthy lifestyle on early-onset stroke is still unclear. Our study thus aimed to investigate the association of overall healthy lifestyle on early-onset stroke in Chinese hospitalized stroke patients. METHODS: This retrospective study included 821 hospitalized stroke patients from the First People's Hospital of Changzhou. An overall healthy lifestyle was defined as the presence of more than 2 of the following items: healthy diet, no smoking, normal body mass index (BMI <24 kg/m2 ), engaging in moderate to high physical activity (≥3 times/week, and ≥30 minutes each time). Early-onset stroke was defined as a stroke first occurring at 50 years old or younger. RESULTS: Among all participants, there were 98 early-onset stroke patients and 723 late-onset stroke patients. Early-onset patients had a lower prevalence of overall healthy lifestyles than that of late-onset patients (P<0.001). Multivariate logistic regression revealed that an overall healthy lifestyle significantly reduced the risk of early-onset stroke. In reference to those without an overall healthy lifestyle, the multivariate-adjusted odds ratios (ORs) for early-onset stroke among participants with an overall healthy lifestyle was 0.27 [95% confidence interval (CI): 0.07-0.98]. CONCLUSIONS: In Chinese stroke patients, a healthy lifestyle was significantly associated with early-onset stroke. Individuals who were adhering to an overall healthy lifestyle had a lower risk of early-onset stroke compared to those who were not.

Inhalation of nebulized Mycobacterium vaccae can protect against allergic bronchial asthma in mice by regulating the TGF-ß/Smad signal transduction pathway.

BACKGROUND: Mycobacterium vaccae nebulization imparted protective effect against allergic asthma in a mouse model. The TGF-ß/Smad signal transduction pathway plays an important role in allergic bronchial asthma. However, the effect of M. vaccae nebulization on the TGF-ß/Smad signal transduction pathway in mouse models of allergic asthma remains unclear. This study investigated the preventive effect of M. vaccae nebulization during bronchial asthma in a mouse model and elucidate the implication of TGF-ß/Smad signal transduction pathway in the process. METHODS: In total, 24 female Balb/c mice were randomized to normal control (group A), asthma control (group B), and M. vaccae nebulization (group C) groups. Both groups B and C were sensitized using ovalbumin for establishment of the asthmatic model; group A received phosphate-buffered solution. Prior to the establishment of asthma, Group C was nebulized with M. vaccae. Airway responsiveness was measured in all the groups, using a noninvasive lung function machine before and 24 h after establishment of the asthmatic model. The animals were then harvested, and bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The total cell counts in BALF was estimated. Protein expression of TGF-ß1, TßR1, Smad1, and Smad7 was detected by immunohistochemistry. The population of CD3 + γδT, IL-13 + CD3 + T, TGF-ß + CD3 + T, IL-13 + CD3 + γδT, and TGF-ß+ CD3+ γδT cells were detected by flow cytometry. One-way analysis of variance for within-group comparisons, the least significant difference t-test or Student-Newman-Keuls test for intergroup comparisons, and the nonparametric rank sum test for analysis of airway inflammation scores were used in the study. RESULTS: The eosinophil count; protein expression of TGF-ß1, TßR1, and Smad1; and percentages of CD3 + γδT and IL-13 + CD3 + T cells were significantly lower in the M. vaccae nebulization group than in the asthma control group (P < 0.01). There were significant intergroup differences in the percentages of TGF-ß + CD3 + T and IL-13 + CD3 + γδT cells (P < 0.05). CONCLUSIONS: Mycobacterium vaccae nebulization could confer protection against allergic bronchial asthma by reducing airway responsiveness and alleviating airway inflammation in mice. The underlying mechanism might be attributed its effect on the deregulated expression of TGF-ß1, TßR1, Smad1, and Smad7 of the TGF-ß/Smad signal transduction pathway.

Effect of Podophyllotoxin Conjugated Stearic Acid Grafted Chitosan Oligosaccharide Micelle on Human Glioma Cells.

OBJECTIVE: To study the physiochemical characteristics of podophyllotoxin (PPT) conjugated stearic acid grafted chitosan oligosaccharide micelle (PPT-CSO-SA), and evaluate the ability of the potential antineoplastic effects against glioma cells. METHODS: PPT-CSO-SA was prepared by a dialysis method. The quality of PPT-CSO-SA including micellar size, zeta potential, drug encapsulation efficiency and drug release profiles was evaluated. Glioma cells were cultured and treated with PPT and PPT-CSO-SA. The ability of glioma cells to uptake PPT-CSO-SA was observed. The proliferation of glioma cells was determined by 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The apoptosis and morphology of U251 cells were observed by 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) dye staining. Cell cycle analysis was performed by flow cytometry. The migration ability of U251 cells was determined by wound healing test. RESULTS: PPT-CSO-SA had nano-level particle size and sustained release property. The encapsulation efficiency of drug reached a high level. The cellular uptake percentage of PPT in glioma cells was lower than that of PPT-CSO-SA (p<0.05). The inhibitory effect of PPT-CSO-SA on glioma cells proliferation was significantly stronger than that of PPT (p<0.05). The morphologic change of apoptosis cell such as shrinkage, karyorrhexis and karyopyknosis were observed. The percentage of U251 cells in G2/M phase increased significantly in the PPT-CSO-SA group compared with PPT group (p<0.05). Compared with the PPT group, the cell migration ability of the PPT-CSO-SA group was significantly inhibited after 12 and 24 hours (p<0.05). CONCLUSION: PPT-CSO-SA can effectively enhance the glioma cellular uptake of drugs, inhibit glioma cells proliferation and migration, induce G2/M phase arrest of them, and promote their apoptosis. It may be a promising anti-glioma nano-drug.

Regulation of Circulatory Muscle-specific MicroRNA during 8 km Run.

Acute prolonged endurance running has been shown to alter muscle-specific circulating microRNA (miRNA) levels. Here, eighteen participants completed an 8 km run. We assessed the levels of hsa-miR-1-3p, -133a-3p, -133b, and -206 and their correlation with conventional biomarkers following exercise. Compared to before exercise (Pre), 8 km run significantly increased the lactate level immediately after exercise (0 h). Myoglobin (Mb) level increased at 0 h while creatine kinase (CK) level increased 24 h after exercise (24 h). The levels of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin I (cTnI) were all elevated at 24 h and within the normal physiological range; The levels of hsa-miR-1-3p, -133a-3p, -133b significantly increased at 0 h but only hsa-miR-133a-3p still elevated at 24 h. Only hsa-miR-206 level decreased at 24 h; Additionally, the changes of hsa-miR-1-3p and hsa-miR-133a-3p were correlated with Mb at 24 h. These findings suggest that muscle-specific miRNA elevation in plasma is likely physiological and that these miRNA may be used as potential biomarkers for load monitoring in individuals.

One-Week Nebulization of Mycobacterium vaccae Can Protect Against Pulmonary Respiratory Syncytial Virus Infection in Balb/c Mice.

Background: Respiratory syncytial virus (RSV) infection is the most common cause of acute lower respiratory tract infection in children, leading to their death. Currently, no effective prevention and treatment methods for RSV infection are available. RSV and many other unknown viruses pose a serious threat to human health. Our previous study demonstrated that Mycobacterium vaccae nebulization can protect against allergic asthma. As RSV infection and asthma are closely related, we hypothesized that M. vaccae could protect against pulmonary RSV infection. Therefore, we evaluated the effect of M. vaccae on RSV infection in Balb/c mice. Methods: The mice were randomized into three groups: normal, RSV, and M. vaccae. One week before the RSV infection model was established, the mice in the M. vaccae group were nebulized with M. vaccae. On the fourth day after RSV infection, airway responsiveness, airway inflammation, pulmonary RSV infection, mRNA levels of pulmonary toll-like receptor (TLR) 7 and TLR8, and pulmonary NF09, acetylcholine, and epidermal growth factor regulator (EGFR) expression levels in all mice were measured. Results: The airway inflammation in the M. vaccae group was alleviated compared with that in the RSV group. In the M. vaccae group, the pulmonary mRNA level of RSV and the pulmonary expression levels of NF09, acetylcholine, and EGFR were decreased considerably, whereas the mRNA levels of TLR7 and TLR8 were increased significantly. Conclusions: One-week nebulization of M. vaccae can protect against RSV infection in Balb/c mice. The mechanism involves the regulation of neurotransmitters and expression of TLR7, TLR8, and EGFR.

Description of a New Species of Forcipomyia (Forcipomyia) (Diptera: Ceratopogonidae) and a Key to Species of the Subgenus From the Chinese Mainland.

Forcipomyia (Forcipomyia) makanensis Hou sp. n. (Diptera: Ceratopogonidae) is described and illustrated based on male and female specimens from China. It is characterized by the male aedeagus triangular, with large cone-shaped process at apex, basal arch high, basal arm slender and curved, parameres separate narrower distance at base, cone-shaped apically, and the female subgenital plate pliers-shaped, without lateral process, with two spermathecae, oval, nearly equal. The new species is compared with the similar congener F. (Forcipomyia) lochmocola Zou and Yu, 1991. We provide separate keys for identification of the males and females of the species of subgenus F. (Forcipomyia) Meigen in China.

First description of the immature stages of Dasyheleaalula and a redescription of adults from China (Diptera, Ceratopogonidae).

The fourth instar larva and pupa of Dasyheleaalula Yu, 2005 are described and illustrated using a Scanning Electron Microscope. The adult male and female of this species are redescribed. Immatures were collected from flooded soil near a pond in Xiaojiawan village, Guizhou province, China and reared in the laboratory. The studied material is deposited in the Insect Collection of Zunyi Medical University.

A species checklist of the subgenus Culicoides (Avaritia) in China, with a description of a new species (Diptera, Ceratopogonidae).

A checklist of the subgenus Culicoides (Avaritia Fox) (Diptera: Ceratopogonidae: Culicoides) in China, currently including 57 species, is provided. Their full citations, more detailed locations of the type locality, and distribution of each species by province, and/or state of each species are also provided. Culicoides (Avaritia) fenggangensis Liu & Hou, sp. n. is described and illustrated, based on both male and female specimens from China. The new species is compared with its similar congeners, C. (A.) comparis Liu & Yu, 2005 and C. (A.) dentiformis McDonald & Lu, 1972.

Effect of Intravenous Glucose Tolerance Test on Bone Turnover Markers in Adults with Normal Glucose Tolerance.

BACKGROUND It is well known that enteral nutrients result in acute suppression of bone turnover markers (BTMs), and incretin hormones are believed to play a significant role in this physiological skeletal response. However, there is limited research exploring the impact of parenteral nutrients on BTMs. Our aim was to assess the influence of intravenous glucose on BTMs in adults with normal glucose tolerance (NGT). MATERIAL AND METHODS We conducted 1-h intravenous glucose tolerance test (IVGTT) in 24 subjects with NGT. Blood samples were collected before and 5, 10, 15, 20, 30, 60 min after administration of glucose, then serum levels of bone formation marker procollagen type I N-terminal propeptide (P1NP) and resorption marker C-terminal cross-linking telopeptides of collagen type I (CTX) were measured. RESULTS During IVGTT, the fasting CTX level fell gradually and reached a nadir of 80.4% of the basal value at 60 min. Conversely, the fasting P1NP level decreased mildly and reached a nadir of 90.6% of the basal value at 15 min, then gradually increased and reached 96.6% at 60 min. The CTX-to-P1NP ratio increased slightly and reached a peak of 104.3% of the basal value at 10 min, then fell gradually and reached a nadir of 83% at 60 min. CONCLUSIONS Our study indicates that intravenous glucose results in an acute suppression of BTMs in the absence of incretin hormones. The mechanism responsible for this needs further investigation.

Obesity enhances Th2 inflammatory response via natural killer T cells in a murine model of allergic asthma.

BACKGROUND: Obesity increases the incidence of asthma, but mechanism between asthma and obesity isn't utterly understood. NKT cells are intermediary activist between the innate and adaptive immune. It may play an equally important role in both obesity and asthma. We studied an obese mouse model of allergic asthma to test whether NKT cells act as a linkage in the development of obesity with asthma. METHODS: Balb/c mice were divided into control group (A), asthma model group (B), the obesity group (C) and obesity with asthma group (D), asthma model made by OVA. Obesity was induced. AHR were measured; HE staining of lung was made; NKT cells were detected and IL-4 and IFN-γ concentration were determined. RESULTS: Lung histology showed airway inflammatory in obesity with asthma are significant than in asthma. IL-4 levels were increased compared with the control group. IFN-γ levels were decreased compared with the control group. More CD69+NKT cells of asthma group and obese asthma group correlated to the enhancement of airway inflammation and AHR. IFN-γ+NKT cells vary in different states not paralleling with CD69+NKT cells. CONCLUSION: The activity level of NKT cells in obesity with asthma mice enhances Th2 Inflammatory response by regulating IL-4 and IFN-γ secretion. The activation of NKT enhanced asthma TH2 inflammatory responce. NKT cells play an important role in the development of asthma in obesity.

Effect of BIX-01294 on H3K9me2 levels and the imprinted gene Snrpn in mouse embryonic fibroblast cells.

Histone H3 lysine 9 dimethylation (H3K9me2) hypermethylation is thought to be a major influential factor in cellular reprogramming, such as somatic cell nuclear transfer (SCNT) and induction of pluripotent stem cells (iPSCs). The diazepin-quinazolin-amine derivative (BIX-01294) specifically inhibits the activity of histone methyltransferase EHMT2 (euchromatic histone-lysine N-methyltransferase 2) and reduces H3K9me2 levels in cells. The imprinted gene small nuclear ribonucleoprotein N (Snrpn) is of particular interest because of its important biological functions. The objective of the present study was to investigate the effect of BIX-01294 on H3K9me2 levels and changes in Snrpn DNA methylation and histone H3K9me2 in mouse embryonic fibroblasts (MEFs). Results showed that 1.3 µM BIX-01294 markedly reduced global levels of H3K9me2 with almost no cellular toxicity. There was a significant decrease in H3K9me2 in promoter regions of the Snrpn gene after BIX-01294 treatment. A significant increase in methylation of the Snrpn differentially methylated region 1 (DMR1) and slightly decreased transcript levels of Snrpn were found in BIX-01294-treated MEFs. These results suggest that BIX-01294 may reduce global levels of H3K9me2 and affect epigenetic modifications of Snrpn in MEFs.