In this paper, we present a classification of $2$-designs with $\gcd(r,\lambda)=1$ admitting flag-transitive automorphism groups. If $G$ is a flag-transitive automorphism group of a non-trivial $2$-design $\mathcal{D}$ with $\gcd(r,\lambda)=1$, then either $(\mathcal{D},G)$ is one of the known examples described in this paper, or $\mathcal{D}$ has $q = p^{d}$ points with $p$ prime and $G$ is a subgroup of $A\Gamma L_{1}(q)$.
To investigate the curative effects of inhaling signal transducer and activator of transcription 1 (STAT1) antisense oligonucleotide (ASON) on alveolitis and pulmonary fibrosis and the best administration time.Twenty-five adult female Wistar rats were randomly divided into 5 equal groups: BLM group, undergoing intra-tracheal perfusion of BLM so as to establish animal models of alveolitis and pulmonary fibrosis and then inhaling aerosolized normal saline (NS); NS group undergoing intra-tracheal perfusion of NS and then inhaling aerosolized NS; ASON 0 d group, undergoing intra-tracheal perfusion of BLM and then inhaling aerosolized STAT1 ASON 3 ml immediately; ASON 7 d group, undergoing intra-tracheal perfusion of BLM and then inhaling STAT1 ASON 3 ml 7 days later; and ASON 14 d group undergoing intra-tracheal perfusion of BLM and then inhaling aerosolized STAT1 ASON 3 ml 14 days later. Aerosolized inhalation was repeated once every other day for 4 times. Twenty-eight days after intra-tracheal perfusion the rats were sacrificed with their lungs taken out to undergo pathological examination. NS was infused into the right lungs to get bronchoalveolar lavage fluid (BALF). ELISA was used to examine the concentrations of transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) in the BALF.The pathology result of the lung tissues showed that compared with the BLM and ASON 14 d groups, the alveolitis and pulmonary fibrosis of the ASON 0 d group were obviously milder. The scores of alveolitis and pulmonary fibrosis of the ASON 0 d group were (1.80 +/- 0.84) and (2.60 +/- 0.55) respectively, both significantly lower than those of the BLM group [(2.40 +/- 0.55) and (4.40 +/- 0.55) respectively] and those of the ASON 7 d group [(2.20 +/- 0.45) and (3.00 +/- 0.71) respectively] (all P < 0.05). The scores of pulmonary fibrosis of the ASON 7 d group was significantly lower than those of the BLM and ASON 14 d groups (both P < 0.05). The concentrations of TGF-beta and TNF-alpha in BALF of the ASON 0 d group were (48.11 +/- 3.46) pg/ml and (1.93 +/- 0.14) ng/ml respectively, both significantly lower than those of the BLM group [(57.67 +/- 2.46) pg/ml and (2.45 +/- 0.25) ng/ml respectively, both P < 0.05]. The concentration of TGF-beta in BALF of the ASON 0 d group was significantly lower than those of the ASON 7 d and ASON 14 d groups [(51.42 +/- 3.57) pg/ml and (55.8 3 +/- 1.79) pg/ml respectively, both P < 0.05]. The concentration of TGF-beta in BALF of the ASON7 d group was significantly lower than those of the BLM and ASON 14 d groups (both P < 0.05).STAT1 ASON administered in the early stage helps depress the pulmonary fibrosis procedure, and the earlier the drug is administrated the better effect would be obtained. Aerosolized STAT1 ASON can be used as a therapeutic method for pulmonary fibrosis.
To investigate the regulatory effect of B cell activating transcription factor (BATF) on acute airway inflammation and its association with retinoic acid orphan nuclear receptors gammat (RORyt) in asthmatic mice.24 female BALB/c mice were randomly and equally divided into three groups (n 8): normal saline (NS) treated, asthma (AS) control and dexamethasone (DEX) treated. AS mice were sensitized and challenged with OVA to establish murine asthma model. Histological changes in lung tissues of the mice were observed by HE staining. Numbers of white blood cell (WBC), polymorphonuclear leukocyte (PMN) and eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) of the mice were counted. The concentration of interleukin-17 (IL-17) in BALF was measured by ELISA. Quantitative real-time PCR (RT-PCR) was performed to assess the mRNA expressions of BATF, IL-17 and RORγt in the lung tissues.The HE staining showed a higher level of inflammatory cell infiltration around the bronchi of AS mice compared with those treated with NS, predominantly in the forms of EOS, PMN and lymphocytes. The AS and DEX treated mice had higher levels of EOS, PMN, WBC and mRNA expressions of BATF, IL-17 and RORγt in BALF than those treated with NS (P < 0.05). DEX reduced the levels of EOS, PMN, WBC and IL-17 in BALF significantly (P < 0.05). The mRNA expression of BATF in lung tissues of mice was positively correlated with the expression of IL-17, RORγt and the counts of WBC,EOS and PMN in BALF (P < 0.05).Asthmatic mice have increased expressions of BATF, IL-17 and RORγt in bronchial and lung tissues. BATF can, through regulating the secretion of Th17 cells, readjust the airway inflammatory. The regulatory function may take effect through synergy with RORγt .
To observe the effects of Salvia combined with Ligustrazine on the TNF-α and TGF-β1 in sera and bronchoalveolar lavage fluid (BALF) of rats with pulmonary fibrosis induced by bleomycin (BLM).Male SD rats (n=90) were randomly assigned into 6 groups: normal saline (NS) group, BLM group, dexamethasone (DXM) group and three Chinese traditional herbal groups (C1: small dose group, C2: medium dose group, C3: large dose group). Rats were challenged intratracheally with BLM to establish pulmonary fibrosis rat models, while the NS group with 0.9% NaCl solution. Rats were given intra-peritoneal injections of normal saline (both the NS group and the BLM group), dexamethasone (the DXM group), or Salvia combined with Ligustrazine (the C1, C2, C3 groups). At the same time, 5 rats from the 6 groups were sacrificed at day 7, 14 and 28 after administration respectively. HE and Masson staining were performed to observe the extent of alveolitis and fibrosis; the levels of TNF-α and TGF-β1 in both sera and BALF were detected by ELISA.Compared with NS group, a great deal of inflammatory cell infiltration into the alveolar was observed in BLM group at day 7, the alveolitis was lessened at day 14, while fibrosis was found; at day 28, the alveolitis became relieved and the fibrosis developed seriously. The extent of alveolitis and pulmonary fibrosis in DXM group was milder than that in BLM group at day 7, 14 and 28 (P<0.05). Compared with BLM group, the extent of pulmonary fibrosis in group C1 didn't remarkably change (P>0.05). The extent of alveolitis and pulmonary fibrosis in group C2 and C3 was significantly milder than that in BLM group at day 14, and the extent of pulmonary fibrosis in group C2 and C3 was remarkably reduced at day 28 (P<0.05). Compared with NS group, the levels of TNF-α and TGF-β1 in both sera and BALF of the other groups were obviously higher (P<0.05). Compared with BLM group, the levels in DXM, C2 and C3 groups were lower at day 7, 14, 28 (P<0.05). Compared with DXM group, the levels in C1, C2 and C3 groups were lower at day 7, 14, 28 (P<0.05), and the difference between C2 and C3 groups was statistically significant (P>0.05). The levels of of TNF-α and TGF-β1 were consistent in rat sera and BALF.Medium and large doses of Salvia combined with Ligustrazine could abate the alveolitis and ameliorate the extent of pulmonary fibrosis by decreasing the levels of TNF-α and TGF-β1 in both serum and BALF.
Transforming growth factor-β (TGF-β) is known to promote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF-β family expressed in a variety of human carcinoma cell lines. The role of bone morphogenetic protein 9 (BMP9), the most powerful osteogenic factor, in osteosarcoma (OS) progression has not been fully clarified. The expression of BMP9 and its receptors in OS cell lines was analyzed by RT-PCR. We found that BMP9 and its receptors were expressed in OS cell lines. We further investigated the influence of BMP9 on the biological behaviors of OS cells. BMP9 overexpression in the OS cell lines 143B and MG63 inhibited in vitro cell migration and invasion. We further investigated the expression of a panel of cancer-related genes and found that BMP9 overexpression increased the phosphorylation of Smad1/5/8 proteins, increased the expression of ID1, and reduced the expression and activity of matrix metalloproteinase 9 (MMP9) in OS cells. BMP9 silencing induced the opposite effects. We also found that BMP9 may not affect the chemokine (C-X-C motif) ligand 12 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis to regulate the invasiveness and metastatic capacity of OS cells. Interestingly, CXCR4 was expressed in both 143B and MG63 cells, while CXCL12 was only detected in MG63 cells. Taken together, we hypothesize that BMP9 inhibits the migration and invasiveness of OS cells through a Smad-dependent pathway by downregulating the expression and activity of MMP9.
Bub1 is a critical component of the spindle assembly checkpoint (SAC) and closely linked to cell proliferation and differentiation. We previously found that spontaneous abortion embryos contained a low level of Bub1 protein but normal mRNA level, while the knockdown of Bub1 leads to abnormal numerical chromosomes in embryonic cells. Here, we investigated the mechanism through which governs the post-transcriptional regulation of Bub1 protein expression level. We first conducted bioinformatics analysis and identified eight putative miRNAs that may target Bub1. Luciferase reporter assay confirmed that miR-450a-3p can directly regulate Bub1 by binding to the 3′-untranslated region of Bub1 mRNA. We found that the overexpression of miR-450a-3p in mouse embryonic fibroblast (MEF) cells down-regulated Bub1 protein level, repressed cell proliferation, increased apoptosis and restricted most cells in G1 phase of the cell cycle. Furthermore, when the fertilized eggs were microinjected with miR-450a-3p mimics, the cleavage of zygotes was effectively suppressed. Our results strongly suggest that an abnormally decreased Bub1 level regulated by miRNAs may be implicated in the pathogenesis of spontaneous miscarriage. Therefore, the blockade of miR-450a-3p may be explored as a novel therapeutic strategy for preventing spontaneous miscarriages.
To investigate the effect of signal transducer and activator of transcription 1 (STAT1) antisense oligonucleotides on lung fibroblast proliferation and hydroxyproline secretion.Ten adult female Wistar rats were randomly divided into two groups: one group was intratracheally instilled with bleomycin (BLM), while another group with 0.9% NaCl solution (NS). After 7 days, the rats were killed by right ventricle of heart exsanguinations under ketamine anaesthesia, and bronchoalveolar lavage (BAL) was performed to obtain alveolar macrophage (AM). AMs from the BLM group were divided into four groups, treated with STAT1 antisense oligonucleotides, STAT1 sense oligonucleotides, dexamethasone and medium alone (control), respectively. AMs and media were collected after culture for 36 h. The mRNA and protein expression of STAT1 and ICAM-1 in AMs were detected by RT-PCR and Cell-ELISA, respectively. The conditioned media were co-cultured with lung fibroblasts for 30 h, and then the cell proliferation and the concentration of hydroxyproline were examined.(1) The STAT1 mRNA expression by AMs in the STAT1 antisense oligonucleotides group (31.8 +/- 3.5) was lower than those of AMs in the STAT1 sense oligonucleotides group (64.2 +/- 4.3), the dexamethasone group (44.1 +/- 4.6) and the control group (65.5 +/- 4.6) (P < 0.05). Moreover, the STAT1 mRNA expression by AMs in the dexamethasone group was also lower than those of AMs in the STAT1 sense oligonucleotides group and the control group (P < 0.05), but the STAT1 mRNA expression by AMs in the STAT1 sense oligonucleotides group was not different from that of the control group (P > 0.05). The STAT1 mRNA expression by AMs in the NS group (14.9 +/- 3.1) was lower than those of AMs in the STAT1 antisense oligonucleotides group, the STAT1 sense oligonucleotides group, the dexamethasone group and the control group (P < 0.05). (2) The mRNA expression of ICAM-1 showed similar changes to the STAT1 mRNA expression by AMs. (3) The STAT1 protein expression by AMs in the STAT1 antisense oligonucleotides group (4.4 +/- 0.6) or in the NS group (3.7 +/- 0.4) was lower than those of AMs in the STAT1 sense oligonucleotides group (7.7 +/- 0.7), the dexamethasone group (5.9 +/- 0.4) and the control group (7.6 +/- 0.6) (P < 0.05); and the STAT1 protein expression by AMs in the dexamethasone group was also lower than those of AMs in the STAT1 sense oligonucleotides group and the control group (P < 0.05), but the STAT1 protein expression by AMs in the STAT1 sense oligonucleotides group was not different from that of the control group (P > 0.05). (4) The changes of ICAM-1 protein expression, lung fibroblast proliferation and hydroxyproline concentration were consistent with the changes of STAT1 protein expression by AMs.STAT1 antisense oligonucleotides could inhibit the mRNA and the protein expression of STAT1 and ICAM-1 in AMs. STAT1 antisense oligonucleotides also inhibited lung fibroblast proliferation and hydroxyproline secretion.
Objective To survey the actuality of body composition for adults in Huai'an and know the relationship between body fat percentage and body mass index (BMI).Methods A total of 1700 health adults were enrolled in this study.It was measured by bioelectrical impedance for weight,WHR,F%,BMI,visceral fat area,in comparison with the part index of adult in Shanghai,Taiyuan and Tokyo.The obesity diagnosis outpoint was determined for the research object.Results Along with the age,BMI and F% were significantly increased year by year trend,but not balanced.The adult index of BMI or F% in Huai'an was similar to the distribution of Shanghai,Taiyuan and Tokyo,however,there were significant differences between that BMI of 20-30 years old male and F% of 50-60 years old female.As the growth of the age,the visceral fat area distribution was increasing.Men achieve 50% visceral type obesity than women about ten years earlier.The again obese outpoint of male in Huai'an was 24.625 kg/m2,and female was 22.505 kg/m2.Regression equations showed that:F%(male)=WHR×233.241-BMI×0.673-year×0.297-156.3;F%(female)=WHR×43.388+BMI×0.928-year×0.083-25.43.Conclusions There is malconformation between BMI and F%.Along with chronic disease prevention,the outpoint of obese diagnosis should be properly adjusted.
To investigate the effect of aerosolized signal transducer and activator of transcription 1 (STAT1) antisense oligodeoxynucleotides (ASON) on the expression of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and typeI and typeIII collagen mRNA of the bleomycin-induced rat pulmonary fibrosis.45 adult female Wistar rats were randomly divided into 3 groups: normal saline (NS) group, bleomycin (BLM) group and ASON group. BLM group and ASON group were intratracheally instilled with bleomycin (BLM) while NS group was instilled with NS. NS group and BLM group were aerosolized with NS while ASON group was aerosolized with STAT1 ASON on day 0, 2, 4 and 6 after intratracheal administration. Then each group was divided into 3 subgroups and the rats were sacrificed on day 7, 14 and 28. The concentration of IFN-gamma, TNF-alpha, TGF-beta1 and PDGF-BB in BALF was detected. The lung tissues were removed and HE and Masson staining was performed to observe the extent of alveolitis and fibrosis. The mRNA levels of typeI and typeIII collagen in the lung tissues were measured.Compared with BLM group, the scores of alveolitis and fibrosis in ASON group were remarkably meliorated (P<0.05). Compared with NS group, the concentration of TNF-alpha, TGF-beta1 and PDGF-BB in BALF in BLM group was significantly increased, but it was lower in ASON group than in BLMA group (P<0.05). The concentration of IFN-gamma in BALF was lower in BLM group than in NS group (P<0.05), but it was higher in ASON group than in BLM group (P<0.05). The mRNA levels of typeI and typeIII collagen at various time points in ASON group were significantly lower than those in BLM group (P<0.05).The aerosolized STAT1 ASON has anti-fibrosis effect, which may result from the lessened production of typeI and typeIII collagen through reducing the concentration of cytokines in BALF such as TNF-alpha, PDGF-BB and TGF-beta1 and inhibiting the decline of IFN-gamma in BALF.
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