Morphological Studies on Seeds of Scrophulariaceae s.l. and Their Systematic Significance

This study employed scanning electron microscopy and light microscopy to observe seed surface micromorphology and seed coat anatomy in the Scrophulariaceae s.l. to investigate seed characters of taxonomic importance. Seeds of 41 taxa corresponding to 13 genera of the family were carefully investigated. Seeds were minute and less than or slightly larger than 1 millimeter in length except for Melampyrum and Pedicularis species. The seed shape ranged from elliptical to broad elliptical and ovoid. In the studied species the surface sculpture was predominantly reticulate-striate, regular reticulate, sometimes colliculate, and rugose, or - rarely - ribbed, as in Lindernia procumbens and Paulownia coreana. Seed coats comprised the epidermis and the endothelium. Nevertheless, in all Melampyrum and some Veronica species the seed coat was very poorly represented and only formed by a papery layer of epidermis. According to correspondence analysis (CA) and unweighted pair group method with arithmetic mean (UPGMA) based cluster analysis the close affinities among the species of Scrophularia were well supported by their proximity to one another. Similarly, the proximity of Melampyrum species and Pedicularis species cannot be denied. In contrast, Veronica species were divided into two groups in CA plots and even three in the UPGMA tree. Regardless of the limited range taxa considered we found that similarities and differences in seed morphology between different genera could help us to understand the systematic relationships involved

Deleterious effects in reproduction and developmental immunity elicited by pulmonary iron oxide nanoparticles

With the extensive application of iron oxide nanoparticles (FeNPs), attention about their potential risks to human health is also rapidly raising, particularly in sensitive subgroups such as pregnant women and babies. In this study, we a single instilled intratracheally FeNPs (1, 2, and 4 mg/kg) to the male and female parent mice, mated, then assessed reproductive toxicity according to the modified OECD TG 421. During the pre-mating period (14 days), two female parent mice died at 4 mg/kg dose, and the body weight gain dose-dependently decreased in male and female parent mice exposed to FeNPs. Additionally, iron accumulation and the enhanced expression of MHC class II molecules were observed in the ovary and the testis of parent mice exposed to the highest dose of FeNPs, and the total sex ratio (male/female) of the offspring mice increased in the groups exposed to FeNPs. Following, we a single instilled intratracheally to their offspring mice with the same doses and evaluated the immunotoxic response on day 28. The increased mortality and significant hematological- and biochemical- changes were observed in offspring mice exposed at 4 mg/kg dose, especially in female mice. More interestingly, balance of the immune response was shifted to a different direction in male and female offspring mice. Taken together, we conclude that the NOAEL for reproductive and developmental toxicity of FeNPs may be lower than 2 mg/kg, and that female mice may show more sensitive response to FeNPs exposure than male mice. Furthermore, we suggest that further studies are necessary to identify causes of both the alteration in sex ratio of offspring mice and different immune response in male and female offspring mice.

NF-κB activation mechanism of 4-hydroxyhexenal via NIK/IKK and p38 MAPK pathway

Abstract4-Hydroxyhexenal (HHE) is known to affect redox balance during aging, included are vascular dysfunctions. To better understand vascular abnormality through the molecular alterations resulting from HHE accumulation in aging processes, we set out to determine whether up-regulation of mitogen-activated protein kinase (MAPK) by HHE is mediated through nuclear factor kappa B (NF-κB) activation in endothelial cells. HHE induced NF-κB activation by inhibitor of κB (IκB) phosphorylation via the IκB kinase (IKK)/NF-κB inducing kinase (NIK) pathway. HHE increased the activity of p38 MAPK and extracellular signal regulated kinase (ERK), but not c-jun NH2-terminal kinase, indicating that p38 MAPK and ERK are closely involved in HHE-induced NF-κB transactivation. Pretreatment with ERK inhibitor PD98059, and p38 MAPK inhibitor SB203580, attenuated the induction of p65 translocation, IκB phosphorylation, and NF-κB luciferase activity. These findings strongly suggest that HHE induces NF-κB activation through IKK/NIK pathway and/or p38 MAPK and ERK activation associated with oxidative stress in endothelial cells

Metastatic hepatocellular carcinoma presenting as facial nerve palsy and facial pain

Facial nerve palsy due to temporal bone metastasis of hepatocellular carcinoma (HCC) has rarely been reported. We experienced a rare case of temporal bone metastasis of HCC that initially presented as facial nerve palsy and was diagnosed by surgical biopsy. This patient also discovered for the first time that he had chronic hepatitis B and C infections due to this facial nerve palsy. Radiation therapy greatly relieved the facial pain and facial nerve palsy. This report suggests that hepatologists should consider metastatic HCC as a rare but possible cause of new-onset cranial neuropathy in patients with chronic viral hepatitis

Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells

Background : The requirement of the Mek1 inhibitor (iMek1) during naïve pluripotency maintenance results from the activation of the Mek1-Erk1/2 (Mek/Erk) signaling pathway upon leukemia inhibitory factor (LIF) stimulation. Methods : Through a meta-analysis of previous genome-wide screening for negative regulators of naïve pluripotency, Ptpn11 (encoding the Shp2 protein, which serves both as a tyrosine phosphatase and putative adapter), was predicted as one of the key factors for the negative modulation of naïve pluripotency through LIF-dependent Jak/Stat3 signaling. Using an isogenic pair of naïve and primed mouse embryonic stem cells (mESCs), we demonstrated the differential role of Shp2 in naïve and primed pluripotency. Results : Loss of Shp2 increased naïve pluripotency by promoting Jak/Stat3 signaling and disturbed in vivo differentiation potential. In sharp contrast, Shp2 depletion significantly impeded the self-renewal of ESCs under primed culture conditions, which was concurrent with a reduction in Mek/Erk signaling. Similarly, upon treatment with an allosteric Shp2 inhibitor (iShp2), the cells sustained Stat3 phosphorylation and decoupled Mek/Erk signaling, thus iShp2 can replace the use of iMek1 for maintenance of naïve ESCs. Conclusions : Taken together, our findings highlight the differential roles of Shp2 in naïve and primed pluripotency and propose the usage of iShp2 instead of iMek1 for the efficient maintenance and establishment of naïve pluripotency.This work was supported by a grant from the National Research Foundation of Korea (NRF-2020R1A2C2005914). This work was also supported by the Creative-Pioneering Researchers Program through Seoul National University (SNU)

Ginsenoside F1 Promotes Cytotoxic Activity of NK Cells via Insulin-Like Growth Factor-1-Dependent Mechanism

Ginsenosides are the principal active components of ginseng and are considered attractive candidates for combination cancer therapy because they can kill tumors and have favorable safety profiles. However, the overall benefit of ginsenosides remains unclear, particularly in cancer immunosurveillance, considering the controversial results showing repression or promotion of immune responses. Here we identify a potentiating role of ginsenoside F1 (G-F1) in cancer surveillance by natural killer (NK) cells. Among 15 different ginsenosides, G-F1 most potently enhanced NK cell cytotoxicity in response to diverse activating receptors and cancer cells. G-F1 also improved cancer surveillance in mouse models of lymphoma clearance and metastatic melanoma that rely on NK cell activity. G-F1-treated NK cells exhibited elevated cytotoxic potential such as upregulation of cytotoxic mediators and of activation signals upon stimulation. NK cell potentiation by G-F1 was antagonized by insulin-like growth factor (IGF)-1 blockade and recapitulated by IGF-1 treatment, suggesting the involvement of IGF-1. Thus, our results suggest that G-F1 enhances NK cell function and may have chemotherapeutic potential in NK cell-based immunotherapy. We anticipate our results to be a starting point for further comprehensive studies of ginsenosides in the immune cells mediating cancer surveillance and the development of putative therapeutics

Decreased Exosomal Acetylcholinesterase Activity in the Plasma of Patients With Parkinson’s Disease

Exosomes, which are small extracellular vesicles produced from various cell types, contain a variety of molecular constituents, such as proteins, lipids, and RNA. Recently, exosomal biomarkers have been investigated to probe the understanding and diagnosis of neurodegenerative disorders. Previous reports have demonstrated increased exosomal α-synuclein (α-syn) in patients with Parkinson’s disease (PD) in comparison to healthy controls (HC). Interestingly, the cholinergic loss was revealed in the central and peripheral nervous systems in histopathology and molecular neuroimaging. Thereby, we simultaneously examined acetylcholinesterase (AChE) with α-syn as exosomal markers. Exosomes were isolated from the plasma of 34 FP-CIT PET proven patients with PD and 29 HC. Exosomal α-syn and AChE activity were quantified andthe relationship with clinical parameters was analyzed. Remarkably, exosomal AChE activity was significantly decreased in PD compared to HC (P = 0.002). Moreover, exosomal AChE activity in PD revealed a strong negative correlation with disease severity, including H&Y (P = 0.007) and UPDRS part III (P = 0.047) scores. By contrast, no significant difference in exosomal α-syn concentration was observed between groups. These results support the occurrence of cholinergic dysfunction in PD, and they could be implicated with disease progression, especially motor deficits. Exosomal AChE activity with advanced exosome isolation techniques may be a reliable biomarker for the early diagnosis and prognosis of PD

The genome sequence of Xanthomonas oryzae pathovar oryzae KACC10331, the bacterial blight pathogen of rice

The nucleotide sequence was determined for the genome of Xanthomonas oryzae pathovar oryzae (Xoo) KACC10331, a bacterium that causes bacterial blight in rice (Oryza sativa L.). The genome is comprised of a single, 4 941 439 bp, circular chromosome that is G + C rich (63.7%). The genome includes 4637 open reading frames (ORFs) of which 3340 (72.0%) could be assigned putative function. Orthologs for 80% of the predicted Xoo genes were found in the previously reported X.axonopodis pv. citri (Xac) and X.campestris pv. campestris (Xcc) genomes, but 245 genes apparently specific to Xoo were identified. Xoo genes likely to be associated with pathogenesis include eight with similarity to Xanthomonas avirulence (avr) genes, a set of hypersensitive reaction and pathogenicity (hrp) genes, genes for exopolysaccharide production, and genes encoding extracellular plant cell wall-degrading enzymes. The presence of these genes provides insights into the interactions of this pathogen with its gramineous host

Predicting Mechanical Complications After Adult Spinal Deformity Operation Using a Machine Learning Based on Modified Global Alignment and Proportion Scoring With Body Mass Index and Bone Mineral Density

Objective This study aimed to create an ideal machine learning model to predict mechanical complications in adult spinal deformity (ASD) surgery based on GAPB (modified global alignment and proportion scoring with body mass index and bone mineral density) factors. Methods Between January 2009 and December 2018, 238 consecutive patients with ASD, who received at least 4-level fusions and were followed-up for ≥2 years, were included in the study. The data were stratified into training (n=167, 70%) and test (n=71, 30%) sets and input to machine learning algorithms, including logistic regression, random forest gradient boosting system, and deep neural network. Results Body mass index, bone mineral density, the relative pelvic version score, the relative lumbar lordosis score, and the relative sagittal alignment score of the global alignment and proportion score were significantly different in the training and test sets (p<0.05) between the complication and no complication groups. In the training set, the area under receiver operating characteristics (AUROCs) for logistic regression, gradient boosting, random forest, and deep neural network were 0.871 (0.817–0.925), 0.942 (0.911–0.974), 1.000 (1.000–1.000), and 0.947 (0.915–0.980), respectively, and the accuracies were 0.784 (0.722–0.847), 0.868 (0.817–0.920), 1.000 (1.000–1.000), and 0.856 (0.803–0.909), respectively. In the test set, the AUROCs were 0.785 (0.678–0.893), 0.808 (0.702–0.914), 0.810 (0.710–0.910), and 0.730 (0.610–0.850), respectively, and the accuracies were 0.732 (0.629–0.835), 0.718 (0.614–0.823), 0.732 (0.629–0.835), and 0.620 (0.507–0.733), respectively. The random forest achieved the best predictive performance on the training and test dataset. Conclusion This study created a comprehensive model to predict mechanical complications after ASD surgery. The best prediction accuracy was 73.2% for predicting mechanical complications after ASD surgery. This information can be used to prevent mechanical complications during ASD surgery