FoxO6-mediated ApoC3 upregulation promotes hepatic steatosis and hyperlipidemia in aged rats fed a high-fat diet.

FoxO6, an identified factor, induces hyperlipidemia and hepatic steatosis during aging by activating hepatic lipoprotein secretion and lipogenesis leading to increased ApoC3 concentrations in the bloodstream. However, the intricate mechanisms underlying hepatic steatosis induced by elevated FoxO6 under hyperglycemic conditions remain intricate and require further elucidation. In order to delineate the regulatory pathway involving ApoC3 controlled by FoxO6 and its resultant functional impacts, we employed a spectrum of models including liver cell cultures, aged rats subjected to HFD, transgenic mice overexpressing FoxO6 (FoxO6-Tg), and FoxO6 knockout mice (FoxO6-KO). Our findings indicate that FoxO6 triggered ApoC3-driven lipid accumulation in the livers of aged rats on an HFD and in FoxO6-Tg, consequently leading to hepatic steatosis and hyperglycemia. Conversely, the absence of FoxO6 attenuated the expression of genes involved in lipogenesis, resulting in diminished hepatic lipid accumulation and mitigated hyperlipidemia in murine models. Additionally, the upregulation of FoxO6 due to elevated glucose levels led to increased ApoC3 expression, consequently instigating cellular triglyceride mediated lipid accumulation. The transcriptional activation of FoxO6 induced by both the HFD and high glucose levels resulted in hepatic steatosis by upregulating ApoC3 and genes associated with gluconeogenesis in aged rats and liver cell cultures. Our conclusions indicate that the upregulation of ApoC3 by FoxO6 promotes the development of hyperlipidemia, hyperglycemia, and hepatic steatosis in vivo, and in vitro. Taken together, our findings underscore the significance of FoxO6 in driving hyperlipidemia and hepatic steatosis specifically under hyperglycemic states by enhancing the expression of ApoC3 in aged rats.

Multi-proteomic analyses of 5xFAD mice reveal new molecular signatures of early-stage Alzheimer's disease.

An early diagnosis of Alzheimer's disease is crucial as treatment efficacy is limited to the early stages. However, the current diagnostic methods are limited to mid or later stages of disease development owing to the limitations of clinical examinations and amyloid plaque imaging. Therefore, this study aimed to identify molecular signatures including blood plasma extracellular vesicle biomarker proteins associated with Alzheimer's disease to aid early-stage diagnosis. The hippocampus, cortex, and blood plasma extracellular vesicles of 3- and 6-month-old 5xFAD mice were analyzed using quantitative proteomics. Subsequent bioinformatics and biochemical analyses were performed to compare the molecular signatures between wild type and 5xFAD mice across different brain regions and age groups to elucidate disease pathology. There was a unique signature of significantly altered proteins in the hippocampal and cortical proteomes of 3- and 6-month-old mice. The plasma extracellular vesicle proteomes exhibited distinct informatic features compared with the other proteomes. Furthermore, the regulation of several canonical pathways (including phosphatidylinositol 3-kinase/protein kinase B signaling) differed between the hippocampus and cortex. Twelve potential biomarkers for the detection of early-stage Alzheimer's disease were identified and validated using plasma extracellular vesicles from stage-divided patients. Finally, integrin α-IIb, creatine kinase M-type, filamin C, glutamine γ-glutamyltransferase 2, and lysosomal α-mannosidase were selected as distinguishing biomarkers for healthy individuals and early-stage Alzheimer's disease patients using machine learning modeling with approximately 79% accuracy. Our study identified novel early-stage molecular signatures associated with the progression of Alzheimer's disease, thereby providing novel insights into its pathogenesis.

New autophagy-modulating lanostane-type triterpenoids from a hallucinogenic poisonous mushroom Gymnopilus orientispectabilis.

Gymnopilus orientispectabilis, also known as "big laughter mushroom," is a hallucinogenic poisonous mushroom that causes excessive laughter upon ingestion. From the fruiting bodies of G. orientispectabilis, eight lanostane-type triterpenoids (1-8), including seven novel compounds: gymnojunols A-G (2-8), were isolated. The chemical structures of these new compounds (2-8) were determined by analyzing their 1D and 2D NMR spectra and HR-EISMS, and their absolute configurations were unambiguously assigned by quantum chemical ECD calculations and a computational method coupled with a statistical procedure (DP4+). Upon evaluating autophagic activity, compounds 2, 6, and 7 increased LC3B-II levels in HeLa cells to a similar extent as bafilomycin, an autophagy inhibitor. In contrast, compound 8 decreased the levels of both LC3B-I and LC3B-II, and a similar effect was observed following treatment with rapamycin, an autophagy inducer. Our findings provide experimental evidence for new potential autophagy modulators in the hallucinogenic poisonous mushroom G. orientispectabilis.

Amelioration of Astrocyte-Mediated Neuroinflammation by EI-16004 Confers Neuroprotection in an MPTP-induced Parkinson's Disease Model.

Parkinson's disease (PD) is a neurodegenerative disorder that results in motor impairment due to dopaminergic neuronal loss. The pathology of PD is closely associated with neuroinflammation, which can be characterized by astrocyte activation. Thus, targeting the inflammatory response in astrocytes might provide a novel therapeutic approach. We conducted a luciferase assay on an in-house chemical library to identify compounds with anti-inflammatory effects capable of reducing MPP+-induced NF-κB activity in astrocytes. Among the compounds identified, EI-16004, a novel 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides, exhibited a significant anti-inflammatory effect by significantly reducing MPP+-induced astrocyte activation. Biochemical analysis and docking simulation indicated that EI-16004 inhibited the MPP+-induced phosphorylation of p65 by attenuating ERK phosphorylation, and EI-16004 reduced pro-inflammatory cytokine and chemokine levels in astrocytes. In vivo studies on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in male C57BL/6 mice showed that EI-16004 ameliorated motor impairment and protected against dopaminergic neuronal loss, and EI-16004 effectively mitigated the MPTP-induced astrocyte activation in striatum (STR) and substantia nigra (SN). These results indicate EI-16004 is a potential neuroprotective agent for the prevention and treatment of astrocyte-mediated neuroinflammatory conditions in PD.

Specc1l deficiency leads to abnormal oocyte meiosis and reduced blastocyst development in mouse.

In brief: Proper oocyte maturation is important in early embryo development. This study provides evidence that abnormal meiotic maturation can impact the developmental competency of preimplantation embryos. Abstract: This study aimed to investigate the potential role of the mouse SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1 like), a microtubule and actin cytoskeleton-associated protein during oocyte meiotic maturation and its potential effects on preimplantation development. This study shows that the transcriptional levels of Specc1l did not significantly change from the germinal vesicle (GV) stage to the metaphase II (MII) stage, but maternal transcripts rapidly and gradually degraded after fertilization. SPECC1L was detected in both the cytoplasm and GV, but not in the nucleolus-like body in the GV intact oocyte. At the MII stages, SPECC1L was widely distributed in the cytoplasm but did not co-localize with chromatin. Knockdown of Specc1l expression in oocytes resulted in abnormal spindle morphology and misaligned chromosomes, as well as a decrease in the rate of polar body extrusion and a reduced developmental competence of oocytes, leading to decreased blastocyst formation rate. In conclusion, this study provides evidence that SPECC1L plays a critical role in mouse oocyte meiotic maturation and early embryo development, specifically in proper bipolar spindle assembly and extrusion of the first polar body.

Cationic nanoplastic causes mitochondrial dysfunction in neural progenitor cells and impairs hippocampal neurogenesis.

Nanoplastics (NPs) exposure to humans can occur through various routes, including the food chain, drinking water, skin contact, and respiration. NPs are plastics with a diameter of less than 100 nm and have the potential to accumulate in tissues, leading to toxic effects. This study aimed to investigate the neurotoxicity of polystyrene NPs on neural progenitor cells (NPCs) and hippocampal neurogenesis in a rodent model. Toxicity screening of polystyrene NPs based on their charge revealed that cationic amine-modified polystyrene (PS-NH3+) exhibited cytotoxicity, while anionic carboxylate-modified polystyrene (PS-COO-) and neutral NPs (PS) did not. NPCs treated with PS-NH3+ showed a significant reduction in growth rate due to G1 cell cycle arrest. PS-NH3+ increased the expression of cell cycle arrest markers p21 and p27, while decreasing cyclin D expression in NPCs. Interestingly, PS-NH3+ accumulated in mitochondria, leading to mitochondrial dysfunction and energy depletion, which caused G1 cell cycle arrest. Prolonged exposure to PS-NH3+ in C17.2 NPCs increased the expression of p16 and senescence-associated secretory phenotype factors, indicating cellular senescence. In vivo studies using C57BL/6 mice demonstrated impaired hippocampal neurogenesis and memory retention after 10 days of PS-NH3+ administration. This study suggests that NPs could deplete neural stem cell pools in the brain by mitochondrial dysfunction, thereby adversely affecting hippocampal neurogenesis and neurocognitive functions.

N,N-Dimethyl-anthranilic Acid from Calvatia nipponica Mushroom Fruiting Bodies Induces Apoptotic Effects on MDA-MB-231 Human Breast Cancer Cells.

Breast cancer ranks among the most prevalent malignancies affecting women worldwide, and apoptosis-targeting drugs are attractive candidates for the treatment of cancer. In the current study, we investigated the in vitro cytotoxicity of the mushroom Calvatia nipponica in human breast cancer cells (MDA-MB-231), identified potential antitumor compounds through bioactivity-guided isolation, and elucidated the antitumor, pro-apoptotic molecular mechanisms of the identified bioactive compounds. C. nipponica is edible when young, and it has been used as a food source as well as a traditional medicine in wound dressings. However, only a limited number of studies have reported its chemical composition and biological activities. In the screening test, the methanol extract of C. nipponica fruiting bodies exhibited cytotoxicity against MDA-MB-231 cells. Bioactivity-guided fractionation of the methanol (MeOH) extract and chemical investigation of the active fractions resulted in the isolation of fourteen compounds (1-14), including six alkaloids (1-3, 5, 7, and 8), two phenolic compounds (4 and 6), one fatty acid (9), and five steroids (10-14). The structures of the isolated compounds were determined using NMR spectroscopic methods, liquid chromatography-mass spectrometry, and comparison of data with previously reported values. The isolated compounds (1-14) were tested for cytotoxicity against MDA-MB-231 cells, where compound 1, i.e., N,N-dimethyl-anthranilic acid, exhibited the most significant cytotoxicity against MDA-MB-231 cells, with an IC50 value of 90.28 ± 4.23 µM and apoptotic cell death of 56.01% ± 2.64% at 100 µM. Treatment with compound 1 resulted in an upregulation of protein levels, including cleaved caspase-8, cleaved poly (ADP-ribose) polymerase, Bcl-2-associated X protein (Bax), cleaved caspase-3, cleaved caspase-9, Bad, and Cytochrome c, but decreased the levels of B-cell lymphoma 2 (Bcl-2). Overall, these results indicate that N,N-dimethyl-anthranilic acid (1) may have anti-breast cancer activity and is probably involved in the induction of apoptosis mediated by extrinsic and intrinsic signaling pathways.

The Effectiveness of Virtual Reality Intervention for COVID-19-Related Psychological Distress: A Systematic Review.

OBJECTIVE: The prolonged coronavirus disease-2019 (COVID-19) pandemic is likely to cause psychological distress in people. This systematic review aimed to identify the effectiveness of virtual reality (VR)-based psychological intervention among individuals with psychological distress during the COVID-19 crisis. PubMed, Ovid MEDLINE, Cochrane Library, Web of Science, Embase, and PsycINFO databases were searched for articles published until July 2022. METHODS: The available citations were deduplicated and screened by two authors using the title and abstract information. Eligibility criteria were constructed according to the PICOT guidelines. Empirical studies of all designs and comparator groups were included if they appraised the impact of an immersive VR intervention on any standardized measure indicative of psychological distress (stress, anxiety, depression, and post-traumatic symptoms) or improvements in quality of life in participants, including COVID-19 patients, medical staff working with COVID-19 patients, and people who had experienced strict social distancing during the COVID-19 pandemic. RESULTS: The results were discussed using a narrative synthesis because of the heterogeneity between studies. Seven of the studies met the inclusion criteria. There were two randomized controlled trials and five uncontrolled studies on VR interventions. CONCLUSION: All studies reported significant improvement in a wide range of psychological distress during COVID-19, ranging from stress, anxiety, depression, and post-traumatic symptoms to quality of life, supporting the efficacy of VR-based psychological intervention. Our results suggest that VR intervention has potential to ameliorate COVID-19-related psychological distress with efficacy and safety.

Methoxyflavones from Black Ginger (Kaempferia parviflora Wall. ex Baker) and their Inhibitory Effect on Melanogenesis in B16F10 Mouse Melanoma Cells.

Kaempferia parviflora Wall. ex Baker (Zingiberaceae), commonly known as Thai ginseng or black ginger, is a tropical medicinal plant in many regions. It has been traditionally used to treat various ailments, including ulcers, dysentery, gout, allergies, abscesses, and osteoarthritis. As part of our ongoing phytochemical study aimed at discovering bioactive natural products, we investigated potential bioactive methoxyflavones from K. parviflora rhizomes. Phytochemical analysis aided by liquid chromatography-mass spectrometry (LC-MS) led to the isolation of six methoxyflavones (1-6) from the n-hexane fraction of the methanolic extract of K. parviflora rhizomes. The isolated compounds were structurally determined to be 3,7-dimethoxy-5-hydroxyflavone (1), 5-hydroxy-7-methoxyflavone (2), 7,4'-dimethylapigenin (3), 3,5,7-trimethoxyflavone (4), 3,7,4'-trimethylkaempferol (5), and 5-hydroxy-3,7,3',4'-tetramethoxyflavone (6), based on NMR data and LC-MS analysis. All of the isolated compounds were evaluated for their anti-melanogenic activities. In the activity assay, 7,4'-dimethylapigenin (3) and 3,5,7-trimethoxyflavone (4) significantly inhibited tyrosinase activity and melanin content in IBMX-stimulated B16F10 cells. In addition, structure-activity relationship analysis revealed that the methoxy group at C-5 in methoxyflavones is key to their anti-melanogenic activity. This study experimentally demonstrated that K. parviflora rhizomes are rich in methoxyflavones and can be a valuable natural resource for anti-melanogenic compounds.

Protective Effects of Withagenin A Diglucoside from Indian Ginseng (Withania somnifera) against Human Dermal Fibroblast Damaged by TNF-α Stimulation.

Human skin is constructed with many proteins such as collagen and elastin. Collagen and elastin play a key role in providing strength and elasticity to the human skin and body. However, damage to collagen causes various symptoms such as wrinkles and freckles, which suggests that they are important to maintain skin condition. Extrinsic or intrinsic skin aging produces an excess of skin destructive factors such as tumor necrosis factor (TNF)-α, which is a major mediator of the aging process. In aged skin, TNF-α provokes the generation of intracellular ROS (reactive oxygen species). It triggers the excessive secretion of MMP-1, which is a collagen-degrading enzyme that causes the collapse of skin collagen. Therefore, we aimed to search for a natural-product-derived candidate that inhibits the skin damage caused by TNF-α in human dermal fibroblasts. In this study, the protective effect of withagenin A diglucoside (WAD) identified from Withania somnifera against TNF-α-stimulated human dermal fibroblasts is investigated. W. somnifera (Solanaceae), well-known as 'ashwagandha', is an Ayurvedic medicinal plant useful for promoting health and longevity. Our experimental results reveal that WAD from W. somnifera suppresses the generation of intercellular ROS. Suppressing intracellular ROS generation inhibits MMP-1 secretion and the collapse of type 1 collagen. The effect of WAD is shown to depend on the inhibition of MAPK phosphorylation, Akt phosphorylation, c-Jun phosphorylation, COX-2 expression, and NF-κB phosphorylation. Further, WAD-depressed expression of the pro-inflammatory cytokines IL-6 and IL-8 triggers various inflammatory reactions in human skin. These findings suggest that WAD has protective effects against skin damage. Accordingly, our study provides experimental evidence that WAD can be a potential agent that can be applied in various industrial fields, such as cosmetics and pharmaceuticals related to skin aging.

Anti-Inflammatory and Neuroprotective Effects of Morin in an MPTP-Induced Parkinson's Disease Model.

Neurodegenerative diseases such as Parkinson's disease (PD) are known to be related to oxidative stress and neuroinflammation, and thus, modulating neuroinflammation offers a possible means of treating PD-associated pathologies. Morin (2',3,4',5,7-pentahydroxy flavone) is a flavonol with anti-oxidative and anti-inflammatory effects found in wines, herbs, and fruits. The present study was undertaken to determine whether a morin-containing diet has protective effects in an MPTP-induced mouse model of PD. Mice were fed a control or morin diet for 34 days, and then MPTP (30 mg/kg, i.p.) was administered daily for 5 days to induce a PD-like pathology. We found that dietary morin prevented MPTP-induced motor dysfunction and ameliorated dopaminergic neuronal damage in striatum (STR) and substantia nigra (SN) in our mouse model. Furthermore, MPTP-induced neuroinflammation was significantly reduced in mice fed morin. In vitro studies showed that morin effectively suppressed glial activations in primary microglia and astrocytes, and biochemical analysis and a docking simulation indicated that the anti-inflammatory effects of morin were mediated by blocking the extracellular signal-regulated kinase (ERK)-p65 pathway. These findings suggest that morin effectively inhibits glial activations and has potential use as a functional food ingredient with therapeutic potential for the treatment of PD and other neurodegenerative diseases associated with neuroinflammation.

Brain lipidomics: From functional landscape to clinical significance.

Lipids are crucial components of cellular function owing to their role in membrane formation, intercellular signaling, energy storage, and homeostasis maintenance. In the brain, lipid dysregulations have been associated with the etiology and progression of neurodegeneration and other neurological pathologies. Hence, brain lipids are emerging as important potential targets for the early diagnosis and prognosis of neurological diseases. This review aims to highlight the significance and usefulness of lipidomics in diagnosing and treating brain diseases. We explored lipid alterations associated with brain diseases, paying attention to organ-specific characteristics and the functions of brain lipids. As the recent advances in brain lipidomics would have been impossible without advances in analytical techniques, we provide up-to-date information on mass spectrometric approaches and integrative analysis with other omic approaches. Last, we present the potential applications of lipidomics combined with artificial intelligence techniques and interdisciplinary collaborative research for treating brain diseases with clinical heterogeneities.

Bioactive Secondary Metabolites Isolated from the Antarctic Lichen Himantormia lugubris.

Two new depsidones, himantormiones A and B (1 and 2) were isolated and identified from the Antarctic lichen, Himantormia lugubris (Parmeliaceae), with seven known compounds (3-9). The structures of two new compounds (1 and 2) were determined by means of spectroscopic analyses, including 1D and 2D NMR and HR-MS. The isolated compounds were tested for antimicrobial and cytotoxic activities, where himantormione B (2) exhibited inhibitory effect against Staphylococcus aureus with the IC50 value of 7.01±0.85 mM. Compound 2 also exhibited strong cytotoxic activity against HCT116 cells (colon cancer) with the EC50 value of 1.11±0.85 µM, where that of the positive control, 5-fluouracil, was 9.4±1.90 µM.

Comparison of Fatty Acid Contents and MMP-1 Inhibitory Effects of the Two Antarctic Fish, Notothenia rossii and Champsocephalus gunnari.

Total fatty-acid (FA) contents of different organs (stomach, liver, brain, and skin) of two Antarctic fish, marbled rockcod (Notothenia rossii) and mackerel icefish (Champsocephalus gunnari), were examined using gas chromatography-mass spectrometry (GC-MS). N. rossii possessed higher contents of total omega-3, where eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the most represented omega-3 FAs, were distributed throughout all parts of the fish. The highest level of EPA was observed in the skin and that of DHA was observed in the brain of N. rossii. C. gunnari showed organ peculiarity in that most of the omega-3 FAs were found in stomach and skin. Specifically, the highest levels of EPA and DHA were both observed in the stomach. Although N. rossii and C. gunnari both inhabit the Antarctic Southern Oceans, their characteristics in terms of the composition of fatty acids were shown to vary. The extracts were also evaluated for matrix metalloproteinase-1 (MMP-1)-inhibitory activities in UVB-induced human dermal fibroblasts, where extracts of the skin and liver of N. rossii showed the most significant inhibition upon MMP-1 production. These findings provide experimental evidence that the extracts of the Antarctic fish could be utilized as bioactive nutrients, particularly in the enhancement of skin health.

Screen-printed carbon electrode modified with de-bundled single-walled carbon nanotubes for voltammetric determination of norepinephrine in ex vivo rat tissue.

A voltammetric sensor for norepinephrine (NE) detection was developed by modifying a disposable screen-printed carbon electrode (SPCE) with de-bundled single-walled carbon nanotubes (D-SWCNTs). The de-bundling was carried out using a newly synthesized polymeric dispersant, a co-polymer of polystyrene sulfonate and methacrylate of lipoic acid. The D-SWCNTs/SPCE showed better sensitivity towards NE compared to the bare SPCE and that modified with bundled SWCNTs. The sensor was optimized for detecting NE by differential pulse voltammetry (DPV) in terms of the D-SWCNTs concentration, DPV parameters, and solution pH. Under the optimum conditions, the sensor exhibited a dynamic linear range of 100 nM-2.0 µM NE, and the detection limit was 62.0 nM (S/N = 3). Additionally, the effects of possible interferents were investigated. The relative standard deviation for five successive measurements of 2.0 µM NE was 7.6%, and approximately 75.8% of the sensor activity was retained after four weeks of storage. The practical potential of this sensor was demonstrated by quantifying NE in ex vivo rat tissue samples.

Bioactive Terphenyls Isolated from the Antarctic Lichen Stereocaulon alpinum.

Three p-terphenyls (2-4)-2-hydroxy-3,5-dimethoxy-p-terphenyl (2), 2-hydroxy-3,6-dimethoxy-p-terphenyl (3), and 2,3,5,6-tetramethoxy-p-terphenyl (4)-were isolated for the first time as natural products along with seven known compounds (1, 5-10) from the Antarctic lichen Stereocaulon alpinum. Structures of the new compounds were elucidated by comprehensive analyses of 1D and 2D NMR and HREIMS experiments. Compound 3 exhibited cytotoxicity against HCT116 cells with the IC50 value of 3.76 ± 0.03 µM and also inhibited NO production in LPS-induced RAW264.7 macrophages with the IC50 value of 22.82 ± 0.015 µM.

Correlation between Stress and Anxiety to Viral Epidemics (SAVE) and Burnout among Korean Dental Hygienists during the COVID-19 Pandemic: A Cross-Sectional Study.

This study aimed to investigate the correlations among Stress and Anxiety to Viral Epidemics (SAVE), job stress (JS), and burnout among Korean dental hygienists during the COVID-19 pandemic and to identify the moderating effect of JS. As a cross-sectional study, a self-reporting questionnaire was used to survey 204 clinical dental hygienists to measure the levels of SAVE, JS, and burnout, along with their demographic characteristics as the control variables. Pearson correlation analysis and hierarchical multiple regression analysis were performed to analyse the correlations among burnout, SAVE, and JS, including the moderating effect of JS. With education level and subjective health controlled, JS (ß = 1.05, p < 0.001), SAVE (ß = 0.69, p = 0.020) and the interaction between SAVE and JS (ß = −0.93, p = 0.050) were identified as significant influencing factors of burnout. The adjusted explanatory power of the model was found to be 52.4%. In summary, both SAVE and JS were significant influencing factors of burnout among dental hygienists, while a moderating effect of JS was also identified. Therefore, it is necessary to create a work environment that can relieve SAVE and JS to reduce burnout among dental hygienists.

Regulation of Tjp1 mRNA by CPEB2 for tight junction assembly in mouse blastocyst.

Cytoplasmic polyadenylation element-binding protein 2 (CPEB2) is an mRNA-binding protein that regulates the cytoplasmic polyadenylation of mRNA and is required for tight junction (TJ) assembly in the trophectoderm epithelium during porcine preimplantation development. However, the regulatory mechanism underlying TJ assembly by CPEB2 has not been examined. The aim of this study was to elucidate how Cpeb2 regulates the subcellular localisation and stabilisation of Tjp1 mRNA for TJ biogenesis during mouse preimplantation. CPEB2 was detected in nuclei during the early stages of development and was localised at apical cell membranes from the morula stage onwards. In the Cpeb2 knockdown (KD), we observed reduced blastocyst formation with impaired TJs, defective inner cell mass development in the blastocyst outgrowth assay, and loss of pregnancy after embryo transfer. More importantly, Tjp1 mRNA was localised apically in the outer cells of control morulae but not in the Cpeb2 KD embryos, indicating that CPEB2 mediated the translocalisation of Tjp1 mRNA from the nuclei. Finally, in the control embryos, the length of the Tjp1 mRNA poly (A) tail was varied, while only a single peak was detected in the Cpeb2 KD embryos. These findings suggest that the binding of CPEB2 to the cytoplasmic polyadenylation element in the 3'-UTR can confer stability on Tjp1 mRNA and translational regulation. In summary, we demonstrated for the first time that CPEB2 mediates Tjp1 mRNA stabilisation and subcellular localisation for TJ assembly during mouse blastocyst formation.

Stereocalpin B, a New Cyclic Depsipeptide from the Antarctic Lichen Ramalina terebrata.

Stereocalpin B, a new cyclic depsipeptide (1), and a new dibenzofuran derivative (3), were isolated from the Antarctic lichen, Ramalina terebrata (Ramalinaceae), along with a known cyclic depsipeptide (2). The structures of new compounds were characterized by comprehensive spectrometric analyses; high-resolution fast atom bombardment mass spectrometry (HR-FABMS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Stereocalpin B (1) existed in a rotameric equilibrium, which was confirmed using nuclear Overhauser effect spectroscopy (NOESY)/exchange spectroscopy (EXSY) spectrum. Absolute configurations of the amino acid units in 1 were assigned using the advanced Marfey's method and subsequent NOESY analysis of the 5-hydroxy-2,4-dimethyl-3-oxo-decanoic acid residue confirmed the complete stereochemistry of 1. Compounds 1-3 exhibited moderate antimicrobial activities against E. coli, with the IC50 values ranging from 18-30 µg/mL. Compound 2 exhibited cell growth inhibition against HCT116 cell lines, with the IC50 value of 20 ± 1.20 µM, and compounds 1 and 2 also showed potent anti-inflammatory activities against lipopolysaccharide (LPS)-induced RAW264.7 macrophages with the IC50 values ranging from 5-7 µM.

Two New Fatty Acid Derivatives, Omphalotols A and B and Anti-Helicobacter pylori Fatty Acid Derivatives from Poisonous Mushroom Omphalotus japonicus.

As part of ongoing systematic research into the discovery of bioactive secondary metabolites with novel structures from Korean wild mushrooms, we investigated secondary metabolites from a poisonous mushroom, Omphalotus japonicus (Kawam.) Kirchm. & O. K. Mill. belonging to the family Marasmiaceae, which causes nausea and vomiting after consumption. The methanolic extract of O. japonicus fruiting bodies was subjected to the fractionation by solvent partition, and the CH2Cl2 fraction was analyzed for the isolation of bioactive compounds, aided by an untargeted liquid chromatography mass spectrometry (LC-MS)-based analysis. Through chemical analysis, five fatty acid derivatives (1-5), including two new fatty acid derivatives, omphalotols A and B (1 and 2), were isolated from the CH2Cl2 fraction, and the chemical structures of the new compounds were determined using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and high resolution electrospray ionization mass spectrometry (HR-ESIMS), as well as fragmentation patterns in MS/MS data and chemical reactions followed by the application of Snatzke's method and competing enantioselective acylation (CEA). In the anti-Helicobacter pylori activity test, compound 1 showed moderate antibacterial activity against H. pylori strain 51 with 27.4% inhibition, comparable to that of quercetin as a positive control. Specifically, compound 3 exhibited the most significant antibacterial activity against H. pylori strain 51, with MIC50 and MIC90 values of 9 and 20 µM, respectively, which is stronger inhibitory activity than that of another positive control, metronidazole (MIC50 = 17 µM and MIC90 = 46 µM). These findings suggested the experimental evidence that the compound 3, an α,ß-unsaturated ketone derivative, could be used as a moiety in the development of novel antibiotics against H. pylori.