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PDE4 inhibitors are involved in anti‐inflammatory and immunomodulatory responses. Recently, they have been getting attention as a new class of drugs treating inflammatory airway diseases. The T lymphocyte is a major cell type present in the inflammatory infiltrate in the airway wall in patients with chronic obstructive pulmonary disease (COPD), and a previous study found that treatment with a PDE4 inhibitor significantly suppressed T cell proliferation. However, the mechanism of action of PDE4 inhibitors has not been elucidated. The present study aimed to investigate major signal transduction pathways of T lymphocyte and identify the phase, during which PDE4 inhibitors affect T cell proliferation. Isolated splenic CD4+ T cells were grown under stimulation with an anti‐CD3/CD28 antibody, and/or treated with roflumilast‐n‐oxide (RNO). A western blot assay was performed using major antibodies including anti‐p‐38, anti‐p‐PI3K, anti‐p‐JNK, anti‐p‐ERK 1/2, anti‐NFAT1 (NFATc2), and anti‐NF‐kB antibodies. Additional experiments conducted on the pathway showed significant change following RNO treatment, thus providing further evidence for signal transduction pathway concerning PDE4 inhibitors. T cell proliferation was suppressed by RNO treatment. In the pathways involved in T cell proliferation, only expression of anti‐NFAT1 antibody was suppressed by RNO treatment. In additional experiments on the NFAT pathway, the very first phase (TCR signalling) remained unchanged on treatment with RNO, but RNO treatment increased IP3R expression and suppressed calcineurin activity. Calcineurin activity, reduced by RNO, increased on treatment with an IP3 receptor agonist. PED4 inhibitor, roflumilast is speculated to suppress T cell proliferation by interfering with IP3‐IP3R binding to inhibit calcium emission, blocking pathway activation from this phase onward, eventually decreasing the level of a growth factor for T cell proliferation, IL‐2. [ABSTRACT FROM AUTHOR]

The hydrophilicity of bone graft material generally used as a carrier can play an important role in regulating bone morphogenetic protein (BMP) expression at the bone graft site. The hydrophilicity, altering physicochemical properties, and enhancing biological capabilities, can be increased via surface modification through ultraviolet (UV) photofunctionalization and the effect on de novo osteogenesis could be further improved. Therefore, this study aimed to assess the effects of UV‐irradiated TiO2‐coated hydroxyapatite (HA) in combination with rhBMP‐2 on bone regeneration in rabbit calvarial defects. The hydrophilicity of HA and TiO2‐coated HA pellets was evaluated by measuring the contact angle of water droplets with UV irradiation. To compare de novo osteogenesis in rabbit calvarial defects, the rabbits were segregated into four different groups: negative control, HA, TiO2‐coated HA, and TiO2‐coated HA with UV; histomorphometric analysis and micro‐computed tomography (μCT) imaging were performed after 4 and 8 weeks. In vivo analysis revealed that de novo osteogenesis occurred on the critical size defects in all groups and was significantly increased in the TiO2‐coated HA with UV group than in other groups (p < 0.05). The present results indicate that UV photofunctionalization promotes de novo osteogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1953–1959, 2019. [ABSTRACT FROM AUTHOR]

Summary: NADPH oxidase (NOX) plays an important role in inflammatory response by producing reactive oxygen species (ROS). The inhibition of NOX has been shown to induce anti‐inflammatory effects in a few experimental models. The aim of this study was to investigate the effects of diphenyleneiodonium (DPI), a NOX inhibitor, on lipopolysaccharide (LPS)‐induced acute lung injury (ALI) in a rat model. Sprague‐Dawley rats were intraperitoneally administered by DPI (5 mg/kg) 30 minutes after intratracheal instillation of LPS (3 mg/kg). After 6 hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The NOX activity in lung tissue was significantly increased in LPS‐treated rats. It was significantly attenuated by DPI. DPI‐treated rats showed significant reduction in the intracellular ROS, the number of inflammatory cells, and cytokines (TNF‐α and IL‐6) in BALF compared with LPS‐treated rats. In lung tissue, DPI‐treated rats showed significantly decreased malondialdehyde content and increased activity of glutathione peroxidase and superoxide dismutase compared with LPS‐treated rats. Lung injury score, myeloperoxidase activity, and inducible nitric oxide synthase expression were significantly decreased in DPI‐treated rats compared with LPS‐treated animals. Western blotting analysis demonstrated that DPI significantly suppressed LPS‐induced activation of NF‐κB and ERK1/2 and SAPK/JNK in MAPK pathway. Our results suggest that DPI may have protective effects on LPS‐induced ALI thorough anti‐oxidative and anti‐inflammatory effects which may be due to inactivation of the NF‐κB, ERK1/2, and SAPK/JNK pathway. These results suggest the therapeutic potential of DPI as an anti‐inflammatory agent in ALI. [ABSTRACT FROM AUTHOR]

• Nonhost resistance (NHR) is a plant immune response to resist most pathogens. The molecular basis of NHR is poorly understood, but recognition of pathogen effectors by immune receptors, a response known as effector-triggered immunity, has been proposed as a component of NHR. • We performed transient expression of 54 Phytophthora infestans RXLR effectors in pepper (Capsicum annuum) accessions. We used optimized heterologous expression methods and analyzed the inheritance of effector-induced cell death in an F2 population derived from a cross between two pepper accessions. • Pepper showed a localized cell death response upon inoculation with P. infestans, suggesting that recognition of effectors may contribute to NHR in this system. Pepper accessions recognized as many as 36 effectors. Among the effectors, PexRD8 and Avrblb2 induced cell death in a broad range of pepper accessions. Segregation of effector-induced cell death in an F2 population derived from a cross between two pepper accessions fit 15 : 1, 9 : 7 or 3 : 1 ratios, depending on the effector. • Our genetic data suggest that a single or two independent/complementary dominant genes are involved in the recognition of RXLR effectors. Multiple loci recognizing a series of effectors may underpin NHR of pepper to P. infestans and confer resistance durability. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Increased thrombin generation has been implicated as a mechanism for several obstetric syndromes including preterm birth preceded by preterm labor (PTL) and preterm premature rupture of membranes (PPROM). In this study, we attempted to determine whether PTL or PPROM are associated with changes in the maternal plasma thrombin level during the early second trimester. Methods This is a case-control study in which maternal thrombin-antithrombin (TAT) III complex concentrations at 15-21 weeks were compared between normal controls ( n = 85) and women subsequently delivering preterm, due to either PTL with intact membranes ( n = 21) or PPROM ( n = 20). Statistical analysis was conducted using non-parametric statistics. Results PTL patients with intact membranes showed non-significant differences in median plasma TAT level (110.1 µg/L) compared with the control group (107.9 µg/L). Similarly, women destined to deliver preterm because of PPROM had non-significantly higher plasma TAT level (134.3 µg/L) than those in the control group (107.9 µg/L) ( p > 0.05). Logistic regression analysis demonstrated that after controlling for confounders including vaginal bleeding, TAT levels remained not significantly associated with subsequent spontaneous preterm birth ( p = 0.27). Conclusion Maternal plasma TAT level is unsuitable as an early second trimester predictor of preterm birth preceded by PTL or PPROM. © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Citation Kim SY, Park SY, Choi JW, Kim DJ, Lee SY, Lim JH, Han JY, Ryu HM, Kim MH. Association between MTHFR 1298A>C polymorphism and spontaneous abortion with fetal chromosomal aneuploidy. Am J Reprod Immunol 2011; 66: 252-258 Problem Polymorphisms in genes involved in folate metabolism are commonly associated with defects in folate-dependent homocysteine metabolism, which can result in DNA hypomethylation and chromosome nondisjunction. This prospective study aimed to investigate the associations between MTHFR 677C>T, MTHFR 1298A>C, MTR 2756A>G, MTRR 66A>G, and CBS 844ins68 polymorphisms and spontaneous abortion (SA) with fetal chromosomal aneuploidy. Method of study Subjects included 33 SA with normal fetal karyotype, 24 SA with fetal chromosomal aneuploidy and 155 normal controls. Polymorphisms were genotyped by PCR-RFLP and QF-PCR analysis. Results The frequencies of MTHFR 1298AC and combined 1298AC/CC genotypes were higher in SA with fetal chromosomal aneuploidy than in controls. The 1298C allele frequency was also significantly higher in SA with fetal chromosomal aneuploidy than in controls. Moreover, the 1298C allele frequency was higher in SA with fetal chromosomal aneuploidy than in SA with normal fetal karyotype. The combined 1298AC/CC genotype was significantly associated with the risk of SA with fetal chromosomal aneuploidy compared with that of the 1298AA genotype (adjusted OR = 2.93, 95% CI: 1.11-7.69). There was no association between SA with fetal chromosomal aneuploidy and other polymorphisms. Conclusions Our findings indicate that MTHFR 1298A>C polymorphism may be an independent risk factor for SA with fetal chromosomal aneuploidy. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the differences of soluble endoglin (sEng) and transforming growth factor-beta1 (TGF-beta1) according to preeclamptic complications and to investigate the correlation between these factors and the clinical symptoms of preeclampsia. Method: We estimated the levels of sEng and TGF-beta1 in plasma collected in the second trimester at the time of genetic amniocentesis from 60 women who subsequently developed preeclampsia and 124 contemporaneous normotensive women. Results: sEng levels were higher in cases than in controls, whereas TGF-beta1 levels were lower (P < 0.001). sEng levels, but not TGF-beta1 levels, were higher in cases with severe or preterm delivery than in cases with mild preeclampsia or term delivery (P < 0.001) and were increased in cases destined to deliver a small gestational age neonate (P < 0.001). Moreover, sEng levels, but not TGF-beta1 levels, showed a positive correlation with maximum diastolic and systolic blood pressure (r = 0.57, P < 0.001; and r = 0.33, P < 0.001, respectively) and proteinuria (r = 0.42, P < 0.001). Conclusion: Early midtrimester plasma levels of sEng are predictive of subsequence occurrence and severity of preeclampsia, in terms of severity of hypertension and proteinuria, prematurity, and association with small for gestational age neonates. [ABSTRACT FROM AUTHOR]

Objective This study aimed to analyze the differences of soluble endoglin (sEng) and transforming growth factor-beta1 (TGF-β1) according to preeclamptic complications and to investigate the correlation between these factors and the clinical symptoms of preeclampsia. Method We estimated the levels of sEng and TGF-β1 in plasma collected in the second trimester at the time of genetic amniocentesis from 60 women who subsequently developed preeclampsia and 124 contemporaneous normotensive women. Results sEng levels were higher in cases than in controls, whereas TGF-β1 levels were lower ( P < 0.001). sEng levels, but not TGF-β1 levels, were higher in cases with severe or preterm delivery than in cases with mild preeclampsia or term delivery ( P < 0.001) and were increased in cases destined to deliver a small gestational age neonate ( P < 0.001). Moreover, sEng levels, but not TGF-β1 levels, showed a positive correlation with maximum diastolic and systolic blood pressure ( r = 0.57, P < 0.001; and r = 0.33, P < 0.001, respectively) and proteinuria ( r = 0.42, P < 0.001). Conclusion Early midtrimester plasma levels of sEng are predictive of subsequence occurrence and severity of preeclampsia, in terms of severity of hypertension and proteinuria, prematurity, and association with small for gestational age neonates. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Problem: The aim of this study was to investigate whether c.869T>C (Leu10Pro) and c.915G>C (Arg25Pro) polymorphisms in exon1 of the transforming growth factor-beta1 (TGF-beta1) gene are associated with development of pre-eclampsia (PE) in Korean women., Method of Study: We analyzed blood samples from 164 patients with PE and 182 healthy pregnant women using the polymerase chain reaction and DNA sequencing., Results: The frequencies of the 869CC and combined TC/CC genotypes were higher in patients with PE than in healthy controls. In the PE with intrauterine growth restriction (IUGR), the frequencies of these genotypes were also higher than that in controls. Furthermore, the 869C allele frequency was significantly higher in both PE and IUGR-complicated PE than in controls. Multivariate analysis showed that the 869TC, CC, and combined TC/CC genotypes were associated with an increased risk of PE compared with the 869TT genotype. In addition, the 869TC, CC, and combined TC/CC genotypes were significantly associated with an increased risk of IUGR-complicated PE compared with the 869TT genotype. The TGF-beta1 c.915G>C polymorphism was not detected in our population., Conclusion: Our findings indicate that the TGF-beta1 c.869T>C polymorphism may be a genetic risk factor for PE and IUGR-complicated PE.