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Fabry disease (FD) is an X-linked hereditary disorder that results in the malfunction of α-galactosidase A (αGLA), leading to the accumulation of globotriaosylceramide (GB3) in cells and causing organ damage. This condition induces several pathological intracellular signaling pathways, with the dysfunction in autophagy being a crucial component. Phospholipid–polyethylene glycol-capped Ceria–Zirconia antioxidant nanoparticles (PEG–CZNPs) have been reported to enhance autophagy flux. This study aims to assess the mechanisms of action of PEG–CZNPs in autophagy regulation and examine their effects on chronic kidney injury in cellular and animal models of FD. A stable cellular model of FD was successfully created through the shRNA transfection of αGLA. PEG–CZNPs were found to enhance autophagy flux by translocating Transcription factor EB (TFEB) to the nucleus. To demonstrate TFEB's importance in autophagy flux by PEG–CZNPs, HK-2 cells were transfected with siTFEB. Autophagy flux significantly decreased after the knockdown of TFEB, despite PEG–CZNPs treatment. We next assessed the upper signaling pathway of TFEB by PEG–CZNPs. TFEB dephosphorylation was significantly influenced by the Akt/GSK3ß signaling pathway in response to PEG–CZNPs. PEG–CZNPs successfully reduced intracellular GB3 accumulation and decreased fibrous markers such as α-smooth muscle actin (αSMA), collagen type IV (ColIV), and matrix metallopeptidase 9 (MMP9) expression in the cellular model of FD. To evaluate the impact of PEG–CZNPs on kidney injury in a mouse model of FD, saline or PEG–CZNPs (10 mg/kg/day) were administered intraperitoneally twice per week for 24 or 48 weeks, starting at the age of 4 weeks. PEG–CZNPs significantly reduced both GB3 accumulation and αSMA expression in the kidneys. In conclusion, these results suggest that PEG–CZNPs promote autophagy flux through the Akt/GSK3β-TFEB signaling pathway and demonstrate a beneficial effect on kidney fibrosis and intracellular GB3 reduction in cellular and animal models of FD. These results provide valuable insights into potential therapeutics for FD. [ABSTRACT FROM AUTHOR]

Mycobacterium peregrinum (Mpgm) is a rapidly growing mycobacteria that is classified as a nontuberculous mycobacterium (NTM) and is commonly found in environmental sources such as soil, water, and animals. Mpgm is considered an opportunistic pathogen that causes infection in immunocompromised individuals or those with underlying medical conditions. Although there have been clinical reports on Mpgm, reports of the immune response and metabolic reprogramming have not been published. Thus, we studied standard Mpgm-ATCC and two clinical strains (Mpgm-S and Mpgm-R) using macrophages and mouse bone marrow-derived cells. Mpgm has two types of colony morphologies: smooth and rough. We grew all strains on the 7H10 agar medium to visually validate the morphology. Cytokine levels were measured via ELISA and real-time PCR. The changes in mitochondrial function and glycolysis in Mpgm-infected macrophages were measured using an extracellular flux analyzer. Mpgm-S-infected macrophages showed elevated levels of inflammatory cytokines, including interleukin (IL)-6, IL-12p40, and tumor necrosis factor (TNF)-α, compared to Mpgm-ATCC- and Mpgm-R-infected macrophages. Additionally, our findings revealed metabolic changes in Mpgm-ATCC and two clinical strains (Mpgm-S and Mpgm-R) during infection; significant changes were observed in the mitochondrial respiration, extracellular acidification, and the oxygen consumption of BMDMs upon Mpgm-S infection. In summary, within the strains examined, Mpgm-S displayed greater virulence, triggered a heightened immune response, and induced more profound shifts in bioenergetic metabolism than Mpgm-ATCC and Mpgm-R. This study is the first to document distinct immune responses and metabolic reorganization following Mpgm infection. These findings lay a crucial foundation for further investigations into the pathogenesis of Mpgm. [ABSTRACT FROM AUTHOR]

Endometrial receptivity is a complex process that prepares the uterine endometrium for embryo implantation; insufficient endometrial receptivity is one of the causes of implantation failure. Here, we analyzed the microRNA expression profiles of exosomes derived from both receptive (RL95-2) and non-receptive (AN3-CA) endometrial epithelial cell (EEC) lines to identify exosomal miRNAs closely linked to endometrial receptivity. Among the 466 differentially expressed miRNAs, miR-205-5p was the most highly expressed in exosomes secreted from receptive RL95-2 cells. miR-205-5p, enriched at the adhesive junction, was closely related to endometrial receptivity. ZEB1, a transcriptional repressor of E-cadherin associated with endometrial receptivity, was identified as a direct target of miR-205-5p. miR-205-5p expression was significantly lower in the endometrial tissues of infertile women than in that of non-infertile women. In vivo, miR-205-5p expression was upregulated in the post-ovulatory phase, and its inhibitor reduced embryo implantation. Furthermore, administration of genetically modified exosomes overexpressing miR-205-5p mimics upregulated E-cadherin expression by targeting ZEB1 and improved spheroid attachment of non-receptive AN3-CA cells. These results suggest that the miR-205-5p/ZEB1/E-cadherin axis plays an important role in regulating endometrial receptivity. Thus, the use of exosomes harboring miR-205-5p mimics can be considered a potential therapeutic approach for improving embryo implantation. [ABSTRACT FROM AUTHOR]

Endometrial receptivity is essential for successful embryo implantation and pregnancy initiation and is regulated via various signaling pathways. Adiponectin, an important adipokine, may be a potential regulator of reproductive system functions. The aim of the present study was to elucidate the regulatory role of adiponectin receptor 1 (ADIPOR1) in endometrial receptivity. The endometrial receptivity between RL95-2 and AN3CA cell lines was confirmed using an in vitro JAr spheroid attachment model. 293T cells were transfected with control or short hairpin (sh)ADIPOR1 vectors and RL95-2 cells were transduced with lentiviral particles targeting ADIPOR1. Reverse transcription-quantitative PCR and immunoblot assays were also performed. ADIPOR1 was consistently upregulated in the endometrium during the mid-secretory phase compared with that in the proliferative phase and in receptive RL95-2 cells compared with that in non-receptive AN3CA cells. Stable cell lines with diminished ADIPOR1 expression caused by shRNA showed reduced E-cadherin expression and attenuated in vitro endometrial receptivity. ADIPOR1 regulated AMP-activated protein kinase (AMPK) activity in endometrial epithelial cells. Regulation of AMPK activity via dorsomorphin and 5-aminoimidazole-4-carboxamide ribonucleotide affected E-cadherin expression and in vitro endometrial receptivity. The ADIPOR1/AMPK/E-cadherin axis is vital to endometrial receptivity. These findings can help improve fertility treatments and outcomes. [ABSTRACT FROM AUTHOR]

Endometrial receptivity is essential for successful pregnancy, and its impairment is a major cause of embryo-implantation failure. MicroRNAs (miRNAs) that regulate epigenetic modifications have been associated with endometrial receptivity. However, the molecular mechanisms whereby miRNAs regulate endometrial receptivity remain unclear. Therefore, we investigated whether miR-182 and its potential targets influence trophoblast cell attachment. miR-182 was expressed at lower levels in the secretory phase than in the proliferative phase of endometrium tissues from fertile donors. However, miR-182 expression was upregulated during the secretory phase in infertile women. Transfecting a synthetic miR-182-5p mimic decreased spheroid attachment of human JAr choriocarcinoma cells and E-cadherin expression (which is important for endometrial receptivity). miR-182-5p also downregulated N-Myc downstream regulated 1 (NDRG1), which was studied further. NDRG1 was upregulated in the secretory phase of the endometrium tissues and induced E-cadherin expression through the nuclear factor-κΒ (NF-κΒ)/zinc finger E-box binding homeobox 1 (ZEB1) signaling pathway. NDRG1-overexpressing or -depleted cells showed altered attachment rates of JAr spheroids. Collectively, our findings indicate that miR-182-5p-mediated NDRG1 downregulation impaired embryo implantation by upregulating the NF-κΒ/ZEB1/E-cadherin pathway. Hence, miR-182-5p is a potential biomarker for negative selection in endometrial receptivity and a therapeutic target for successful embryo implantation. [ABSTRACT FROM AUTHOR]

The physicochemical characteristics and flavor-related compounds of thigh meat derived from diverse Korean native chickens (KNC), namely Hanhyup No. 3 (HH3), Woorimatdag No 1 (WRMD 1), and Woorimatdag No 2 (WRMD 2), under fresh and frozen-thawed conditions were studied and compared with those of commercial broilers (CB). Regardless of the breed, KNC showed a higher (p < 0.05) percentage of linoleic and arachidonic acid. The highest proportion of docosahexaenoic acid was observed in WRMD 2. Despite having a higher collagen content, thigh meat derived from KNC maintained a similar texture profile in comparison to that of CB. The concentrations of most free amino acids (FAA), except for taurine, tryptophan, and carnosine, were higher in frozen-thawed meat than in fresh meat. Regarding volatile organic compounds (VOC), following freezing, the concentration of favorable VOCs increased in CB, but decreased in WRMD 1, suggesting a loss of pleasant flavor in frozen-thawed meat. This study indicated that changes in VOCs, including hydrocarbons (d-limonene, heptadecane, hexadecane, naphthalene, pentadecane, 3-methyl-, tridecane), esters (arsenous acid, tris(trimethylsilyl) ester, decanoic acid, ethyl ester, hexadecanoic acid, ethyl ester), alcohol (1-hexanol, 2-ethyl-), ketones (5,9-undecadien-2-one, 6,10-dimethyl-), and aldehydes (pentadecanal-, tetradecanal, tridecanal), may be a promising marker for distinguishing between fresh and frozen-thawed chicken thigh meat. These findings are of critical importance as preliminary data for developing high-quality chicken meat products. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is a complex inflammatory bowel disorder disease that can induce rectal and colonic dysfunction. Although the prevalence of IBD in Western countries is almost 0.5% of the general population, genetic causes are still not fully understood. In a recent discovery, itaconate was found to function as an immune-modulating metabolite in mammalian immune cells, wherein it is synthesized as an antimicrobial compound from the citric acid cycle intermediate cis-aconitic acid. However, the association between the Acod1 (Aconitate decarboxylase 1)-itaconate axis and ulcerative colitis has rarely been studied. To elucidate this, we established a DSS-induced colitis model with Acod1-deficient mice and then measured the mouse body weights, colon lengths, histological changes, and cytokines/chemokines in the colon. We first confirmed the upregulation of Acod1 RNA and protein expression levels in DSS-induced colitis. Then, we found that colitis symptoms, including weight loss, the disease activity index, and colon shortening, were worsened by the depletion of Acod1. In addition, the extent of intestinal epithelial barrier breakdown, the extent of immune cell infiltration, and the expression of proinflammatory cytokines and chemokines in Acod1-deficient mice were higher than those in wild-type mice. Finally, we confirmed that 4-octyl itaconate (4-OI) alleviated DSS-induced colitis in Acod1-deficient mice and decreased the expression of inflammatory cytokines and chemokines. To our knowledge, this study is the first to elucidate the role of the Acod1-itaconate axis in colitis. Our data clearly showed that Acod1 deletion resulted in severe DSS-induced colitis and substantial increases in inflammatory cytokine and chemokine levels. Our results suggest that Acod1 may normally play an important regulatory role in the pathogenesis of colitis, demonstrating the potential for novel therapies using 4-OI. [ABSTRACT FROM AUTHOR]

Problem: Intravenous immunoglobulin G (IVIG) is an emerging regimen for women with reproductive failures (RF) during‐ or pre‐pregnancy who have aberrant cellular immune reactions. Studies investigating teratogenicity of IVIG have been limited. Herein, we evaluated the fetal teratogenicity of IVIG and IVIG‐related obstetric complications. Method of study: Women who used IVIG during pregnancy due to RF with cellular immune aberrances were enrolled from four medical centers in Korea. The pregnancy outcomes were collected. Results: A total of 370 RF women who used IVIG during their pregnancy were enrolled. Most of the patients started the IVIG therapy before 12 weeks of gestation and 229 women continued IVIG treatment beyond 12 weeks of gestation. The mean age of the subjects was 34.8 years and the mean total dosage of IVIG was 125.3 g. A total of 307 women had livebirths and six of them were twins. Of 301 singleton livebirths, obstetric complications were developed as follows: preterm births (12.0%), gestational diabetes (7.0%), preeclampsia (4.0%), placental abruption (1.3%), placenta previa (4.3%), and placenta accrete (1.7%). Total six cases (1.99%) had major fetal anomalies in livebirths. The incidence of birth defects is similar to those of the general population in Korea and the previous report in infertile women. No IVIG ‐related viral contamination was noted. Conclusion: IVIG use during pregnancy did not increase obstetric complications and fetal teratogenicity. This study can be an evidence of maternal and fetal safety of IVIG administration during pregnancy. [ABSTRACT FROM AUTHOR]

Pathological maternal inflammation and abnormal placentation contribute to several pregnancy-related disorders, including preterm birth, intrauterine growth restriction, and preeclampsia. TANK-binding kinase 1 (TBK1), a serine/threonine kinase, has been implicated in the regulation of various physiological processes, including innate immune response, autophagy, and cell growth. However, the relevance of TBK1 in the placental pro-inflammatory environment has not been investigated. In this study, we assessed the effect of TBK1 inhibition on lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation and its underlying mechanisms in human trophoblast cell lines and mouse placenta. TBK1 phosphorylation was upregulated in the trophoblasts and placenta in response to LPS. Pharmacological and genetic inhibition of TBK1 in trophoblasts ameliorated LPS-induced NLRP3 inflammasome activation, placental inflammation, and subsequent interleukin (IL)-1 production. Moreover, maternal administration of amlexanox, a TBK1 inhibitor, reversed LPS-induced adverse pregnancy outcomes. Notably, TBK1 inhibition prevented LPS-induced NLRP3 inflammasome activation by targeting the mammalian target of rapamycin complex 1 (mTORC1). Thus, this study provides evidence for the biological significance of TBK1 in placental inflammation, suggesting that amlexanox may be a potential therapeutic candidate for treating inflammation-associated pregnancy-related complications. [ABSTRACT FROM AUTHOR]

Problem: Chorioamnionitis is caused by a bacterial infection that ascends from the vagina and can cause adverse pregnancy outcomes (APOs). Fusobacterium nucleatum (F. nucleatum) is a periodontal pathogen associated with the occurrence of APOs. In this study, we evaluated whether receptor‐interacting protein kinase 2 (Ripk2), an adaptor protein of the cytosolic receptors nucleotide‐binding oligomerization domain (NOD)1 and NOD2, in macrophages and human decidual stromal cells (hDSCs) contributes to immune responses against F. nucleatum. Method of Study: Bone marrow‐derived macrophages (BMDMs) isolated from wild‐type (WT) and Ripk2‐deficient mice and hDSCs were cultured with F. nucleatum (MOI 1, 10, 100). BMDMs and hDSCs were assessed using enzyme‐linked immunosorbent assay, Western blot analysis, real‐time PCR, and nitrite assay. Results: Fusobacterium nucleatum‐induced production of IL‐6, but not of TNF‐α and IL‐10, was lower in Ripk2‐deficient BMDMs than in WT cells. Western blotting revealed a decrease in F. nucleatum‐induced p65 phosphorylation in Ripk2‐deficient macrophages, whereas mitogen‐activated protein kinases activation was comparable between WT and Ripk2‐deficient cells. The production of nitric oxide (NO) in response to F. nucleatum and the gene and protein expression of inducible NO synthase was impaired in Ripk2‐deficient BMDMs. In hDSCs, F. nucleatum upregulated the gene and protein expression of NOD1, NOD2, and Ripk2 in a time‐dependent manner. F. nucleatum also increased the production of IL‐6, CXCL8, and CCL2, whereas this production was decreased by the Ripk2 inhibitors SB203580 and PP2. Conclusions: In conclusion, Ripk2 signaling appears to contribute to the F. nucleatum‐induced immune response and can be a preventive and therapeutic target against APOs. [ABSTRACT FROM AUTHOR]

Reproductive failure (RF) is the inability to conceive or to carry a pregnancy to term, and its prevalence is not negligible. Pregnancy is a prothrombotic condition, which can be abnormally exaggerated in women with thrombophilia. Antiphospholipid syndrome is a cause of RF and effectively managed with heparin and aspirin. However, there are yet insufficient data in patients with RF and inherited thrombophilia. This review focuses on the significance of inherited thrombophilia and RF and the role of anticoagulants in pregnancy outcomes. A few randomized case‐control studies have investigated the effect of anticoagulation in RF with thrombophilia, and the results are yet debatable. Some inherited thrombophilia including mutations of factor V Leiden, prothrombin, and methylenetetrahydrofolate reductase and protein S deficiency are associated with RF and/or late pregnancy complications. There are several implications which influence the diagnosis and treatment. First, there is a lack of studies revealing appropriate thrombophilia markers and its cutoff values for RF specifically. Second, some thrombophilia markers change with sex and age. Lastly, the study designs of previous studies are heterogeneous in selecting the thrombophilia markers and drugs. Further studies to find adequate thrombophilia markers of RF are warranted and eventually elucidate the subgroups beneficial to anticoagulation treatment. [ABSTRACT FROM AUTHOR]

Problem: Maternal obesity induces elevated saturated fatty acid palmitate levels in the blood and causes pregnancy complications such as gestational diabetes, preeclampsia, fetal growth abnormalities, and stillbirth. Sestrin2, a highly conserved stress‐inducible protein, is involved in the cellular responses of various stress conditions and homeostatic regulation. However, the effects of Sestrin2 on trophoblast cells have not yet been investigated. Here, we investigated the role of Sestrin2 in palmitate‐induced lipotoxicity and its underlying mechanisms in human first‐trimester trophoblast cells (Sw.71). Method of study: Mouse placental tissues were obtained from low‐fat diet‐fed mice (n = 14) and high‐fat diet‐fed mice (n = 14) at gestation day 17.5. Sw.71 cells were treated with palmitate or bovine serum albumin as vehicle controls. The role of Sestrin2 in palmitate‐induced lipotoxicity was examined by immunocytochemistry, immunoblot analysis, quantitative real‐time PCR, and invasion assay. Results: Expression of placental Sestrin2 was elevated in high‐fat diet‐fed dams compared to that of low‐fat diet‐fed dams. Prolonged treatment of Sw.71 cells with palmitate‐induced endoplasmic reticulum (ER) stress‐dependent expressions of Sestrin2 protein and mRNA, and the treatment also triggered apoptosis. Knockdown of Sestrin2 increased palmitate‐mediated ER stress, inflammatory signaling, and apoptosis. Furthermore, Sestrin2 suppressed impaired trophoblast invasion caused by palmitate and attenuated palmitate‐induced ER stress and inflammation via AMPK/mTORC1 pathways. Conclusion: Our study provides the relationship between Sestrin2, AMPK/mTORC1 pathway, and trophoblast function, suggesting that Sestrin2 may be a novel potential therapeutic target for the prevention of pregnancy complications. [ABSTRACT FROM AUTHOR]

Endometriosis is a chronic gynecological disorder, characterized by the presence of ectopic endometrial tissue outside the uterine cavity. Among several hypotheses, Sampson's theory of retrograde menstruation is still applicable. Recent studies have reported the importance of inflammation among endometrial tissue, the peritoneum, and immune cells. However, less is known regarding the role of bacterial infection in the pathophysiology of endometriosis. We hypothesized that Ureaplasma urealyticum infection might contribute to the development of endometriosis by inducing the production of inflammatory mediators by peritoneal mesothelial cells (PMCs), possibly through TLR2. Hence, our objective was to reveal whether PMC infection by U. urealyticum is associated with endometriosis. Moreover, we aimed to demonstrate the molecular mechanism involved in this relationship. We developed a new infection-induced mouse model of endometriosis with wild type and Tlr2-deficient mice. Based on the in vivo mouse model, U. urealyticum -infected mice showed significantly increased numbers and sizes of ectopic endometriotic lesions. U. urealyticum upregulated not only the production of IL-6, CXCL1, and CCL2, but also the expression of ICAM-1, VCAM-1, and MMP2 in murine PMCs. Similarly, endometrial stromal cells dose-dependently produced IL-6, CXCL1, and CCL2 in response to U. urealyticum infection. The series of inflammatory responses in PMCs was mediated mainly through TLR2. The phosphorylation of ERK and JNK was observed when U. urealyticum was added to PMCs and knock out of Tlr2 inhibited these MAPKs phosphorylation. Based on our co-culture study, U. urealyticum -infected PMCs exhibited significantly increased attachment to ESCs compared with uninfected PMCs. Collectively, U. urealyticum infection promotes the development of endometriosis by increasing inflammatory mediators, adhesion molecules, and MMP-2 expression in PMCs through TLR2 signaling. Through our results, we present a theory that infection-induced pelvic inflammation contributes to the initiation and progression of endometriosis. Appropriate treatment of reproductive tract infection may decrease the prevalence of endometriosis. [ABSTRACT FROM AUTHOR]

Aberrant apoptosis at the trophoblast–maternal interface and abnormal expression of Fas and Fas ligand (FasL) have been reported in complicated pregnancies with recurrent pregnancy losses (RPL) and preeclampsia. We assessed the prevalence of Fas and FasL genetic polymorphisms in Korean women with RPL and in fertile controls. In total, 306 women with RPL and 298 fertile controls were enrolled. Genotype distributions of Fas and FasL in RPL patients versus fertile controls were examined under the Hardy–Weinberg equilibrium. Fas −670 A/G genotype (AA versus AG versus GG, p = 0.340) and allele frequencies (A versus G, p = 0.412) were not different between the RPL and control groups. There was no difference in each Fas −1377 G/A and FasL −844 C/T genotype, and their allele frequencies. In addition, the unions of two zygosities of each genotype and their combined genotypes did not differ between two groups. No difference in the prevalence of Fas and FasL single-nucleotide polymorphisms (SNPs) was observed between women with RPL and fertile controls among Korean women. To determine the possibility of genetic polymorphisms in Fas and its ligand as risk factors for RPL, further studies in various races and a large study population are needed. [ABSTRACT FROM AUTHOR]

Since the first study was published reporting the candidate association between the prolactin receptor gene intron C/T polymorphism (rs37389) and recurrent miscarriage, no replication study has been performed. In this study, we investigated the role of the prolactin receptor gene C/T polymorphism in 311 Korean women with recurrent pregnancy loss and 314 controls. Genotyping for prolactin receptor gene intron C/T polymorphism was performed using a TaqMan assay. The significance of difference in the genotype distribution was assessed using a chi-square test, and continuous variables were compared using a Student’st-test. The genotype distribution of the prolactin receptor gene C/T polymorphism in the recurrent pregnancy loss group did not differ from that in the control group (CC/CT/TT rates were 49.8%/41.5%/8.7% and 52.5%/37.6%/9.9% for the recurrent pregnancy loss patient and control groups, respectively,p = .587). When the analysis was restricted to patients with three or more consecutive spontaneous miscarriages or patients without prior live birth, there were also no differences in the genotype distribution between these subgroups and controls. In conclusion, the findings of the current study suggest that the prolactin receptor gene intron C/T polymorphism is not a major determinant of the development of recurrent pregnancy loss.Impact statementWhat is already known: Many studies have investigated whether there is a genetic component for the risk of recurrent pregnancy loss. Recently, one study investigated whether genetic polymorphisms involved in the regulation of the hypothalamic-pituitary-ovarian axis would be associated with recurrent miscarriage. Among 35 polymorphisms in 20 candidate genes, genotype distribution with regard to the prolactin receptor gene intron C/T polymorphism (rs37389) differed between the recurrent miscarriage and the control groups. Since this study reporting the candidate association between the prolactin receptor gene and recurrent miscarriage, no replication study has been performed.What the results of this study add: The genotype distribution of the prolactin receptor gene C/T polymorphism in the recurrent miscarriage group did not differ from that in the control group.What the implications are of these findings: Our study may be useful in that it is the first replication study since the initial report of the association of prolactin receptor gene polymorphism with recurrent miscarriage. Although no association was found, the potential role of prolactin in pregnancy loss needs to be further investigated because prolactin and its receptor have been postulated to play an important role in the maintenance of normal pregnancy. [ABSTRACT FROM PUBLISHER]

BACKGROUND The endolichenic fungus Xylaria grammica KCTC 13121BP showed strong nematicidal activity against Meloidogyne incognita. This study aimed to identify the nematicidal metabolites and to evaluate the efficacy of the strain as a biocontrol agent under pot and field conditions. RESULTS Bioassay-guided fractionation and instrumental analyses led to grammicin being identified as the nematicidal metabolite. Because patulin is a mycotoxic isomer of grammicin and is known to have strong antibacterial and cytotoxic activities, several biological activities of the two compounds were compared. Grammicin showed strong second-stage juvenile killing and egg-hatching inhibitory effects, with a 50% effective concentration at 72 h (EC50/72 h) of 15.9 µg/mL and a 50% effective concentration at 14 days (EC50/14 days) of 5.87 µg/mL, respectively, whereas patulin was virtually inactive in both respects. Patulin was strongly active toward various phytopathogenic bacteria in vitro, whereas grammicin was weakly so. Patulin at the concentration range of 0.1-10 µg/mL also showed dose-dependent cytotoxicity toward the human first-trimester trophoblast cell line SW.71, whereas grammicin was not toxic toward this cell line. In pot and field experiments, a wettable powder-type formulation and fermentation broth filtrate of X. grammica KCTC 13121BP effectively suppressed the development of root-knot nematode disease on tomato and melon plants. CONCLUSION The results suggest that X. grammica and grammicin may have potential applications for control of root-knot nematode disease of various crops. © 2017 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Decidual stromal cells ( DSCs) are known to regulate trophoblast invasion via unveiled mechanism yet. And nucleotide-binding oligomerization domain-containing protein 1 ( NOD1) may influence on this DSC-trophoblast interaction. We investigated the mechanism underlying the DSC-mediated regulation of trophoblast invasion and the effect of NOD1 on their cross talk. Using human primary DSCs, BeWo cell invasion was measured. Cytokine secretion and MAP kinase signaling were examined in DSCs following treatment with NOD1 agonist, Tri- DAP. DSCs secreted IL-8 and increased trophoblast invasion. Tri- DAP further increased IL-8 secretion from DSCs via JNK pathway and facilitated both MMP-2 production and trophoblast invasion compared with control. Upon cotreatment of IL-8 and anti- IL-8 antibody to BeWo cells, the number of invading trophoblasts and MMP-2 production decreased significantly. These results suggest that IL-8 from DSCs may play a role to increase the invasiveness of trophoblast cells into the decidua via NOD1/ JNK pathway. [ABSTRACT FROM AUTHOR]