Mechanism Behind the Loss of Fast Charging Capability in Nickel-Rich Cathode Materials.

Fast charging technology for electric vehicles (EVs), offering rapid charging times similar to conventional vehicle refueling, holds promise but faces obstacles owing to kinetic issues within lithium-ion batteries (LIBs). Specifically, the significance of cathode materials in fast charging has grown because Ni-rich cathodes are employed to enhance the energy density of LIBs. Herein, the mechanism behind the loss of fast charging capability of Ni-rich cathodes during extended cycling is investigated through a comparative analysis of Ni-rich cathodes with different microstructures. The results revealed that microcracks and the resultant cathode deterioration significantly compromised the fast charging capability over extended cycling. When thick rocksalt impurity phases form throughout the particles owing to electrolyte infiltration via microcracks, the limited kinetics of Li+ ions create electrochemically unreactive areas under high-current conditions, resulting in the loss of fast charging capability. Hence, preventing microcrack formation by tailoring microstructures is essential to ensure stability in fast charging capability. Understanding the relationship between microcracks and the loss of fast charging capability is essential for developing Ni-rich cathodes that facilitate stable fast charging upon extended cycling, thereby promoting widespread EV adoption.

Intergranular Shielding for Ultrafine-Grained Mo-Doped Ni-Rich Li[Ni0.96 Co0.04 ]O2 Cathode for Li-Ion Batteries with High Energy Density and Long Life.

Deploying Ni-enriched (Ni≥95 %) layered cathodes for high energy-density lithium-ion batteries (LIBs) requires resolving a series of technical challenges. Among them, the structural weaknesses of the cathode, vigorous reactivity of the labile Ni4+ ion species, gas evolution and associated cell swelling, and thermal instability issues are critical obstacles that must be solved. Herein, we propose an intuitive strategy that can effectively ameliorate the degradation of an extremely high-Ni-layered cathode, the construction of ultrafine-scale microstructure and subsequent intergranular shielding of grains. The formation of ultrafine grains in the Ni-enriched Li[Ni0.96 Co0.04 ]O2 (NC96) cathode, achieved by impeding particle coarsening during cathode calcination, noticeably improved the mechanical durability and electrochemical performance of the cathode. However, the buildup of the strain-resistant microstructure in Mo-doped NC96 concurrently increased the cathode-electrolyte contact area at the secondary particle surface, which adversely accelerated parasitic reactions with the electrolyte. The intergranular protection of the refined microstructure resolved the remaining chemical instability of the Mo-doped NC96 cathode by forming an F-induced coating layer, effectively alleviating structural degradation and gas generation, thereby extending the battery's lifespan. The proposed strategies synergistically improved the structural and chemical durability of the NC96 cathode, satisfying the energy density, life cycle performance, and safety requirements for next-generation LIBs.

Microstructural Degradation of Ni-Rich Li[Nix Coy Mn1 -x-y ]O2 Cathodes During Accelerated Calendar Aging.

Because electric vehicles (EVs) are used intermittently with long resting periods in the fully charged state before driving, calendar aging behavior is an important criterion for the application of Li-ion batteries used in EVs. In this work, Ni-rich Li[Nix Coy Mn1 -x-y ]O2 (x = 0.8 and 0.9) cathode materials with high energy densities, but low cycling stabilities are investigated to characterize their microstructural degradation during accelerated calendar aging. Although the particles seem to maintain their crystal structures and morphologies, the microcracks which develop during calendar aging remain even in the fully discharged state. An NiO-like phase rock-salt structure of tens of nanometers in thickness accumulates on the surfaces of the primary particles through parasitic reactions with the electrolyte. In addition, the passive layer of this rock-salt structure near the microcracks is gradually exfoliated from the primary particles, exposing fresh surfaces containing Ni4+ to the electrolyte. Interestingly, the interior primary particles near the microcracks have deteriorated more severely than the outer particles. The microstructural degradation is worsened with increasing Ni contents in the cathode materials, directly affecting electrochemical performances such as the reversible capacities and voltage profiles.

The growth of K562 human leukemia cells was inhibited by therapeutic neural stem cells in cellular and xenograft mouse models.

To confirm the anti-tumor effect of engineered neural stem cells (NSCs) expressing cytosine deaminase (CD) and interferon-ß (IFN-ß) with prodrug 5-fluorocytosine (FC), K562 chronic myeloid leukemia (CML) cells were co-cultured with the neural stem cell lines HB1.F3.CD and HB1.F3.CD.IFN-ß in 5-FC containing media. A significant decrease in the viability of K562 cells was observed by the treatment of the NSC lines, HB1.F3.CD and HB1.F3.CD.IFN-ß, compared with the control. A modified trans-well assay showed that engineered human NSCs significantly migrated toward K562 CML cells more than human normal lung cells. In addition, the important chemoattractant factors involved in the specific migration ability of stem cells were found to be expressed in K562 CML cells. In a xenograft mouse model, NSC treatments via subcutaneous and intravenous injections resulted in significant inhibitions of tumor mass growth and extended survival dates of the mice. Taken together, these results suggest that gene therapy using genetically engineered stem cells expressing CD and IFN-ß may be effective for treating CML in these mouse models.

An antimicrobial protein, lactoferrin exists in the sweat: proteomic analysis of sweat.

The main function of the eccrine gland has been considered to be thermoregulation. Recently, it has been reported that antimicrobial peptides including cathelicidin and dermcidin exist in the sweat. Lactoferrin is found in body fluids such as milk tears and saliva. It is known as a component of host defense against infection and inflammation. In this study, we explored whether lactoferrin is produced by eccrine glands, thereby establishing its potential role in the skin defense. By immunohistochemistry, lactoferrin was detected in eccrine glands of normal human skin. In Western blot analysis, lactoferrin was found in sweat and skin surface substances obtained from healthy volunteers. By proteomic analysis, lactoferrin and other antimicrobial peptides were detected in sweat. In addition, we measured the concentration of lactoferrin in sweat by enzyme-linked immunosorbent assay. These findings suggest that lactoferrin may contribute to skin defense against infection through its secretion in sweat.

Electrolyte-Mediated Stabilization of High-Capacity Micro-Sized Antimony Anodes for Potassium-Ion Batteries.

Alloying anodes exhibit very high capacity when used in potassium-ion batteries, but their severe capacity fading hinders their practical applications. The failure mechanism has traditionally been attributed to the large volumetric change and/or their fragile solid electrolyte interphase. Herein, it is reported that an antimony (Sb) alloying anode, even in bulk form, can be stabilized readily by electrolyte engineering. The Sb anode delivers an extremely high capacity of 628 and 305 mAh g-1 at current densities of 100 and 3000 mA g-1 , respectively, and remains stable for more than 200 cycles. Interestingly, there is no need to do nanostructural engineering and/or carbon modification to achieve this excellent performance. It is shown that the change in K+ solvation structure, which is tuned by electrolyte composition (i.e., anion, solvent, and concentration), is the main reason for achieving this excellent performance. Moreover, an interfacial model based on the K+ -solvent-anion complex behavior is presented. The electronegativity of the K+ -solvent-anion complex, which can be tuned by changing the solvent type and anion species, is used to predict and control electrode stability. The results shed new light on the failure mechanism of alloying anodes, and provide a new guideline for electrolyte design that stabilizes metal-ion batteries using alloying anodes.

Interfacial Model Deciphering High-Voltage Electrolytes for High Energy Density, High Safety, and Fast-Charging Lithium-Ion Batteries.

High-voltage lithium-ion batteries (LIBs) enabled by high-voltage electrolytes can effectively boost energy density and power density, which are critical requirements to achieve long travel distances, fast-charging, and reliable safety performance for electric vehicles. However, operating these batteries beyond the typical conditions of LIBs (4.3 V vs Li/Li+ ) leads to severe electrolyte decomposition, while interfacial side reactions remain elusive. These critical issues have become a bottleneck for developing electrolytes for applications in extreme conditions. Herein, an additive-free electrolyte is presented that affords high stability at high voltage (4.5 V vs Li/Li+ ), lithium-dendrite-free features upon fast-charging operations (e.g., 162 mAh g-1 at 3 C), and superior long-term battery performance at low temperature. More importantly, a new solvation structure-related interfacial model is presented, incorporating molecular-scale interactions between the lithium-ion, anion, and solvents at the electrolyte-electrode interfaces to help interpret battery performance. This report is a pioneering study that explores the dynamic mutual-interaction interfacial behaviors on the lithium layered oxide cathode and graphite anode simultaneously in the battery. This interfacial model enables new insights into electrode performances that differ from the known solid electrolyte interphase approach to be revealed, and sets new guidelines for the design of versatile electrolytes for metal-ion batteries.

Electrolyte Chemistry in 3D Metal Oxide Nanorod Arrays Deciphers Lithium Dendrite-Free Plating/Stripping Behaviors for High-Performance Lithium Batteries.

Lithium dendrite-free deposition is crucial to stabilizing lithium batteries, where the three-dimensional (3D) metal oxide nanoarrays demonstrate an impressive capability to suppress dendrite due to the spatial effect. Herein, we introduce a new insight into the ameliorated lithium plating process on 3D nanoarrays. As a paradigm, novel 3D Cu2O and Cu nanorod arrays were in situ designed on copper foil. We find that the dendrite and electrolyte decomposition can be mitigated effectively by Cu2O nanoarrays, while the battery failed fast when the Cu nanoarrays were used. We show that Li2O (i.e., formed in the lithiation of Cu2O) is critical to stabilizing the electrolyte; otherwise, the electrolyte would be decomposed seriously. Our viewpoint is further proved when we revisit the metal (oxide) nanoarrays reported before. Thus, we discovered the importance of electrolyte stability as a precondition for nanoarrays to suppress dendrite and/or achieve a reversible lithium plating/stripping for high-performance lithium batteries.

Crystallization and preliminary X-ray crystallographic analysis of L-rhamnose isomerase with a novel high thermostability from Bacillus halodurans.

L-Rhamnose isomerases catalyze isomerization between L-rhamnose (6-deoxy-L-mannose) and L-rhamnulose (6-deoxy-L-fructose), which is the first step in rhamnose catabolism. L-Rhamnose isomerase from Bacillus halodurans ATCC BAA-125 (BHRI) exhibits interesting characteristics such as high thermostability and selective substrate specificity. BHRI fused with an HHHHHH sequence was purified and crystallized in order to elucidate the molecular basis of its unique enzymatic properties. The crystals were grown by the hanging-drop vapour-diffusion method and belonged to the monoclinic space group P2(1), with unit-cell parameters a = 83.2, b = 164.9, c = 92.0 A, beta = 116.0 degrees . Diffraction data were collected to 2.5 A resolution. According to a Matthews coefficient calculation, there are four monomers in the asymmetric unit with a V(M) of 3.0 A(3) Da(-1) and a solvent content of 59.3%. The initial structure of BHRI has been determined by the molecular-replacement method.

Anti-proliferative Effect of Engineered Neural Stem Cells Expressing Cytosine Deaminase and Interferon-ß against Lymph Node-Derived Metastatic Colorectal Adenocarcinoma in Cellular and Xenograft Mouse Models.

PURPOSE: Genetically engineered stem cells may be advantageous for gene therapy against various human cancers due to their inherent tumor-tropic properties. In this study, genetically engineered human neural stem cells (HB1.F3) expressing Escherichia coli cytosine deaminase (CD) (HB1.F3.CD) and human interferon-ß (IFN-ß) (HB1.F3.CD.IFN-ß) were employed against lymph node-derived metastatic colorectal adenocarcinoma. MATERIALS AND METHODS: CD can convert a prodrug, 5-fluorocytosine (5-FC), to active 5-fluorouracil, which inhibits tumor growth through the inhibition of DNA synthesis,while IFN-ß also strongly inhibits tumor growth by inducing the apoptotic process. In reverse transcription polymerase chain reaction analysis, we confirmed that HB1.F3.CD cells expressed the CD gene and HB1.F3.CD.IFN-ß cells expressed both CD and IFN-ß genes. RESULTS: In results of a modified trans-well migration assay, HB1.F3.CD and HB1.F3.CD.IFN-ß cells selectively migrated toward SW-620, human lymph node-derived metastatic colorectal adenocarcinoma cells. The viability of SW-620 cells was significantly reduced when co-cultured with HB1.F3.CD or HB1.F3.CD.IFN-ß cells in the presence of 5-FC. In addition, it was found that the tumor-tropic properties of these engineered human neural stem cells (hNSCs) were attributed to chemoattractant molecules including stromal cell-derived factor 1, c-Kit, urokinase receptor, urokinase-type plasminogen activator, and C-C chemokine receptor type 2 secreted by SW-620 cells. In a xenograft mouse model, treatment with hNSC resulted in significantly inhibited growth of the tumor mass without virulent effects on the animals. CONCLUSION: The current results indicate that engineered hNSCs and a prodrug treatment inhibited the growth of SW-620 cells. Therefore, hNSC therapy may be a clinically effective tool for the treatment of lymph node metastatic colorectal cancer.

Potential Anti-proliferative and Immunomodulatory Effects of Marine Microalgal Exopolysaccharide on Various Human Cancer Cells and Lymphocytes In Vitro.

Marine microalgal exopolysaccharides (EPSs) have drawn great attention due to their biotechnological potentials such as anti-viral, anti-oxidant, anti-lipidemic, anti-proliferative, and immunomodulatory activities, etc. In the present study, the EPS derived from microalgae Thraustochytriidae sp.-derived mutant GA was investigated for its anti-proliferation and immunomodulation. Anti-cancer efficacy of the microalgal EPS was examined for the alterations in cell proliferation and cell cycle-related gene expression that occur in three types of human cancer cell lines, BG-1 ovarian, MCF-7 breast, and SW-620 colon cancer cell lines, by its treatment. Alterations in immunoreactivity by the microalgal EPS were examined by measuring its influence on the growth of T and B lymphocytes and cytokine production of T cells. In cell viability assay, the microalgal EPS inhibited cancer cell growth at the lowest concentration of 10-11 dilution and in a dose-responsive manner within the range of dilution of 10-11~10-3. In addition, the protein expression of cell cycle progression genes such as cyclin D1 and E in these cancer cell lines was significantly reduced by the microalgal EPS in a dose- and a time-dependant manner. In cell proliferation assay using T and B cells, the microalgal EPS induced B cell proliferation even at the lowest dilution of 10-11, but not T cells. In cytokine assay, the microalgal EPS decreased the formation of IL-6 and INF-γ at 10-3 dilution compared to the control and had no significant effects on TNF-α. Collectively, these findings suggest that the EPS derived from microalgae Thraustochytriidae sp. GA has an anti-proliferative activity against cancer cells and an immunomodulatory effect by having an influence on B cell proliferation and cytokine secretion of T cells.

Bone morphogenetic protein-2 (BMP-2) transactivates Dlx3 through Smad1 and Smad4: alternative mode for Dlx3 induction in mouse keratinocytes.

Expression of the Dlx3 homeodomain gene is induced in terminally differentiated epidermal cells. Dlx3 regulates gene expression in skin and plays important roles in patterning of the embryonic ectoderm through differential sensitivity to bone morphogenetic protein (BMP) signaling. We analyzed the expression of BMP family members in murine keratinocytes; BMP-2 is expressed in proliferative basal and differentiated suprabasal keratinocytes. BMP-2 induced transcription of Dlx3 within 12 h of treatment of keratinocytes cultured in vitro. We proceeded to delineate the BMP-2-responsive region to an area between -1917 and -1747 in the Dlx3 promoter. Gel shift assays with recombinant Smad1 and Smad4 demonstrated that this DNA fragment (-1917 to -1747) was competent in the formation of protein-DNA complexes. By deletion and mutational analyses we localized a Smad1/Smad4-binding site containing a GCAT motif, which showed similarity to other TGF-beta family responsive elements. Supershift assays with keratinocyte nuclear extracts and antibodies against members of the Smad family showed that this motif was able to form a complex with Smad1. Mutation of the Smad1/Smad4-binding site inhibited transcriptional activation of the Dlx3 gene by BMP-2. In the hair follicle, where Dlx3 is expressed in the hair matrix cells, BMP-2 also activates Dlx3 transcription. These results provide a possible mechanism of action for the BMP signaling pathway on the regulation of Dlx3.

Advanced new strategies for metastatic cancer treatment by therapeutic stem cells and oncolytic virotherapy.

The field of therapeutic stem cell and oncolytic virotherapy for cancer treatment has rapidly expanded over the past decade. Oncolytic viruses constitute a promising new class of anticancer agent because of their ability to selectively infect and destroy tumor cells. Engineering of viruses to express anticancer genes and specific cancer targeting molecules has led to the use of these systems as a novel platform of metastatic cancer therapy. In addition, stem cells have a cancer specific migratory capacity, which is available for metastatic cancer targeting. Prodrug activating enzyme or anticancer cytokine expressing stem cells successfully inhibited the proliferation of cancer cells. Preclinical models have clearly demonstrated anticancer activity of these two platforms against a number of different cancer types and metastatic cancer. Several systems using therapeutic stem cells or oncolytic virus have entered clinical trials, and promising results have led to late stage clinical development. Consequently, metastatic cancer therapies using stem cells and oncolytic viruses are extremely promising. The following review will focus on the metastatic cancer targeting mechanism of therapeutic stem cells and oncolytic viruses, and potential challenges ahead for advancing the field.

Application of SV40 T-transformed human corneal epithelial cells to evaluate potential irritant chemicals for in vitro alternative eye toxicity.

Assessment of eye irritation potential is important to human safety, and it is necessary for various cosmetics and chemicals that may contact the human eye. Until recently, the Draize test was considered the standard method for estimating eye irritation, despite its disadvantages such as the need to sacrifice many rabbits for subjective scoring. Thus, we investigated the cytotoxicity and inflammatory response to standard eye irritants using SV40 T-transformed human corneal epithelial (SHCE) cells as a step toward development of an animal-free alternative eye irritation test. MTT and NRU assays of cell viability were performed to investigate the optimal experimental conditions for SHCE cell viability when cells were exposed to sodium dodecyl sulfate (SDS) as a standard eye irritant at 6.25×10(-3) to 1×10(-1)%. Additionally, cell viability of SHCE cells was examined in response to six potential eye irritants, benzalkonium chloride, dimethyl sulfoxide, isopropanol, SDS, Triton X-100 and Tween 20 at 5×10(-3) to 1×10(-1)%. Finally, we estimated the secretion level of cytokines in response to stimulation by eye irritants in SHCE cells. SHCE cells showed a good response to potential eye irritants when the cells were exposed to potential irritants for 10min at room temperature (RT), and cytokine production increased in a concentration-dependent manner, indicating that cytotoxicity and cytokine secretion from SHCE cells may be well correlated with the concentrations of irritants. Taken together, these results suggest that SHCE cells could be an excellent alternative in vitro model to replace in vivo animal models for eye irritation tests.

Effects of microalgal polyunsaturated fatty acid oil on body weight and lipid accumulation in the liver of C57BL/6 mice fed a high fat diet.

Dietary polyunsaturated fatty acids (PUFAs), which are abundant in marine fish oils, have recently received global attention for their prominent anti-obesogenic effects. Among PUFAs, eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), which are n-3 long-chain PUFAs widely referred to as omega-3 oils, were reported to prevent the development of obesity in rodents and humans. In the present study, we evaluated the anti-obesity effects of microalgal oil on high-fat induced obese C57BL/6 mice, compared with commercial omega-3 fish oil and vegetable corn oil. Microalgal oil is an inherent mixture of several PUFAs, including EPA, DHA and other fatty acids produced from a marine microalgal strain of Thraustochytriidae sp. derived mutant. It was found to contain more PUFAs (>80%) and more omega-3 oils than commercial omega-3 fish oil (PUFAs >31%) and corn oil (PUFAs 59%). All three types of oils induced weight loss in high-fat-induced obese mice, with the loss induced by microalgal oil being most significant at 9 weeks (10% reduction). However, the oils tested did not improve blood lipid levels, although microalgal oil showed an apparent inhibitory effect on lipid accumulation in the liver. These findings may be attributed to the higher PUFA content, including omega-3 oils of microalgal oil than other oils. Collectively, these findings suggest that microalgal oil, derived from Thraustochytriidae sp. derived mutant, is a prominent candidate for replacement of omega-3 fish oils based on its apparent anti-obesity effect in vivo.

Functional interaction between hMYH and hTRADD in the TNF-α-mediated survival and death pathways of HeLa cells.

UNLABELLED: The tumor necrosis factor (TNF) signaling pathway is a classical immune system pathway that plays a key role in regulating cell survival and apoptosis. The TNF receptor-associated death domain (TRADD) protein is recruited to the death domain of TNF receptor 1 (TNFR1), where it interacts with TNF receptor-associated factor 2 (TRAF2) and receptor-interacting protein (RIP) for the induction of apoptosis, necrosis, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and mitogen-activated protein (MAP) kinase activation. In this study, we found that the human MutY homolog (hMYH) interacted with human TRADD (hTRADD) via the C-terminal domain of hMYH. Moreover, under conditions promoting TNF-α-induced cell death or survival in HeLa cells, this interaction was weakened or enhanced, respectively. The interaction between hMYH and hTRADD was important for signaling pathways mediated by TNF-α. Our results also suggested that the hTRADD-hMYH association was involved in the nuclear translocation of NFκB and formation of the TNFR1-TRADD complex. Thus, this study identified a novel mechanism through which the hMYH-hTRADD interaction may affect the TNF-α signaling pathway. IMPLICATIONS: In HeLa cells, the hTRADD-hMYH interaction functioned in both cell survival and apoptosis pathways following TNF-α stimulation.

DNA methylation analysis of CD4+ T cells in patients with psoriasis.

Psoriasis is a chronic inflammatory skin disease that is characterized by aberrant cross-talk between keratinocytes and immune cells such as CD4+ T cells, resulting in keratinocyte hyperproliferation in the epidermis. DNA methylation, one of several epigenetic mechanisms, plays an important role in gene expression without changing the DNA sequence. Several studies have suggested the involvement of epigenetic regulation in skin lesions from patients with psoriasis. In this study, we investigated the genome-wide DNA methylation status of CD4+ T cells in patients with psoriasis compared with healthy subjects using methylated DNA immunoprecipitation sequencing (MeDIP-Seq). The results of MeDIP-Seq showed that the global methylation values of CD4+ T cells are higher in patients with psoriasis than in healthy controls, particularly in the promoter regions. Among the most hypermethylated genes in the promoter regions, we selected the genes whose expression is significantly reduced in the CD4+ T cells of psoriasis patients. Studies using the methylation inhibitor 5-azacytidine in vitro methylation assays have shown that the differential expression levels were associated with the methylation status of each gene. Bisulfite sequencing of the transcription start region of phosphatidic acid phosphatase type 2 domain containing 3 (PPAPDC3), one of the selected genes, showed hypermethylation in the CD4+ T cells of psoriasis patients. These results suggested that the methylation status, which is identified by MeDIP-Seq of the genes, was correlated with the mRNA expression level of the genes. Collectively, the DNA methylation status in CD4+ T cells might be associated with the pathogenesis of psoriasis.

Nuclear localization of Obox4 is dependent on its homeobox domain.

OBJECTIVE: Oocyte-specific homeobox 4 (Obox4) is preferentially expressed in oocytes and plays an important role in the completion of meiosis of oocytes. However, the Obox4 expression pattern has not been reported yet. In this study, we investigated the subcellular localization of Obox4 using a green fluorescent protein (GFP) fusion expression system. METHODS: Three regions of Obox4 were divided and fused to the GFP expression vector. The partly deleted homeodomain (HD) regions of Obox4 were also fused to the GFP expression vector. The recombinant vectors were transfected into HEK-293T cells plated onto coated glass coverslips. The transfected cells were stained with 4',6-diamidino-2-phenylindol and photographed using a fluorescence microscope. RESULTS: Mutants containing the HD region as well as full-length Obox4 were clearly localized to the nucleus. In contrast, the other mutants of either the N-terminal or C-terminal region without HD had impaired nuclear localization. We also found that the N-terminal and C-terminal of the Obox HD contributed to nuclear localization and the entire HD was necessary for nuclear localization of Obox4. CONCLUSION: Based on the results of the present study, we demonstrated that the intact HD region of Obox4 is responsible for the nuclear localization of Obox4 protein in cells.

Novel isonahocol E(3) exhibits anti-inflammatory and anti-angiogenic effects in endothelin-1-stimulated human keratinocytes.

Endothelin-1 (ET-1) is reported to be a potent mitogenic and pro-angiogenic factor that plays a vital role in both physiological and pathological processes. ET-1 is implicated in dermal cell proliferation and skin disorders, such as psoriasis and atopic dermatitis. ET-1, endothelin ET(A) receptor, and endothelin ET(B) receptor could be potential targets for developing specific therapeutics to treat such disorders. Here, we provide the first report that an isonahocol [2,-5-hihydroxy-3-(13-hydroxy-3,-7,-11,-15-tetramethyl-12-oxo-hexadeca-2,-6,-14-trienyl)-phenyl]-acetic acid methyl ester (isonahocol E(3)) from the brown algae Sargassum siliquastrum has functional antagonistic activities against ET-1 induced inflammatory and proangiogenic effects. Isonahocol E(3) significantly inhibited ET-1-induced cell proliferation, as well as inflammatory mediators, such as interleukin-6 (IL-6) and interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α), and pro-angiogenic factors including metalloproteinases in immortalized human keratinocytes. We also found that isonahocol E(3) reduced expression level of endothelin ET(A) receptor, and endothelin ET(B) receptor as well as suppressed ET-1 induced extracellular signal-regulated kinase (ERK) phosporylation. Taken together, our results suggest that isonahocol E(3) can exert anti-inflammatory and anti-angiogenic activities at least by regulating the expression of ET-1 receptors and ERK signaling pathway.

Lin28 regulates the expression of neuropeptide Y receptors and oocyte-specific homeobox genes in mouse embryonic stem cells.

OBJECTIVE: Lin28 has been known to control the proliferation and pluripotency of embryonic stem cells. The purpose of this study was to determine the downstream effectors of Lin28 in mouse embryonic stem cells (mESCs) by RNA interference and microarray analysis. METHODS: The control siRNA and Lin28 siRNA (Dharmacon) were transfected into mESCs. Total RNA was prepared from each type of transfected mESC and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis to confirm the downregulation of Lin28. The RNAs were labeled and hybridized with an Affymetrix Gene-Chip Mouse Genome 430 2.0 array. The data analysis was accomplished by GenPlex 3.0 software. The expression levels of selected genes were confirmed by quantitative real-time RT-PCR. RESULTS: According to the statistical analysis of the cDNA microarray, a total of 500 genes were altered in Lin28-downregulated mESCs (up-regulated, 384; down-regulated, 116). After differentially expressed gene filtering, 31 genes were selected as candidate genes regulated by Lin28 downregulation. Among them, neuropeptide Y5 receptor and oocyte-specific homeobox 5 genes were significantly upregulated in Lin28-downregulated mESCs. We also showed that the families of neuropeptide Y receptor (Npyr) and oocyte-specific homeobox (Obox) genes were upregulated by downregulation of Lin28. CONCLUSION: Based on the results of this study, we suggest that Lin28 controls the characteristics of mESCs through the regulation of effectors such as the Npyr and Obox families.