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Vasomotion is the oscillation of vascular tone which gives rise to flow motion of blood into an organ. As is well known, spontaneous contractile organs such as heart, GI, and genitourinary tract produce rhythmic contraction. It imposes or removes pressure on their vessels alternatively for exchange of many substances. It was first described over 150 years ago, however the physiological mechanism and pathophysiological implications are not well understood. This study aimed to elucidate underlying mechanisms and physiological function of vasomotion in human arteries. Conventional contractile force measurement, immunohistochemistry, and Western blot analysis were employed to study human left gastric artery (HLGA) and uterine arteries (HUA). RESULTS: Circular muscle of HLGA and/or HUA produced sustained tonic contraction by high K+ (50 mM) which was blocked by 2 µM nifedipine. Stepwise stretch and high K+ produced nerve-independent spontaneous contraction (vasomotion) (around 45% of tested tissues). Vasomotion was also produced by application of BayK 8644, 5-HT, prostagrandins, oxytocin. It was blocked by nifedipine (2 µM) and blockers of intracellular Ca2+ stores. Inhibitors of Ca2+ -activated Cl- channels (DIDS and/or niflumic acid) and ATP-sensitive K+ (KATP ) channels inhibited vasomotion reversibly. Metabolic inhibition by sodium cyanide (NaCN) and several neuropeptides also regulated vasomotion in KATP channel-sensitive and -insensitive manner. Finally, we identified TMEM16A Ca2+ -activated Cl- channels and subunits of KATP channels (Kir 6.1/6.2 and sulfonylurea receptor 2B [SUR2B]), and c-Kit positivity by Western blot analysis. We conclude that vasomotion is sensitive to TMEM16A Ca2+ -activated Cl- channels and metabolic changes in human gastric and uterine arteries. Vasomotion might play an important role in the regulation of microcirculation dynamics even in pacemaker-related autonomic contractile organs in humans.
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Artérias , Canais Iônicos , Contração Isométrica , Humanos , Canais Iônicos/fisiologia , Nifedipino/farmacologia , Artéria Uterina , Artérias/fisiologiaRESUMO
We have developed a membrane filter-assisted cell-based biosensing platform by using a polyester membrane as a three-dimensional (3D) cell culture scaffold in which cells can be grown by physical attachment. The membrane was simply treated with ethanol to increase surficial hydrophobicity, inducing the stable settlement of cells via gravity. The 3D membrane scaffold was able to provide a relatively longer cell incubation time (up to 16 days) as compared to a common two-dimensional (2D) cell culture environment. For a practical application, we fabricated a cylindrical cartridge to support the scaffold membranes stacked inside the cartridge, enabling not only the maintenance of a certain volume of culture media but also the simple exchange of media in a flow-through manner. The cartridge-type cell-based analytical system was exemplified for pathogen detection by measuring the quantities of toll-like receptor 1 (TLR1) induced by applying a lysate of P. aeruginosa and live E. coli, respectively, providing a fast, convenient colorimetric TLR1 immunoassay. The color images of membranes were digitized to obtain the response signals. We expect the method to further be applied as an alternative tool to animal testing in various research areas such as cosmetic toxicity and drug efficiency.
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Técnicas Biossensoriais , Escherichia coli , Animais , Técnicas de Cultura de Células , ImunoensaioRESUMO
BACKGROUND: IL-32 is a novel cytokine involved in many inflammatory diseases. However, the role of IL-32γ, an isotype of IL-32, in atopic dermatitis (AD) has not been reported. OBJECTIVE: We investigated the effects of IL-32γ on development of AD and its action mechanisms. METHODS: We used phthalic anhydride (PA) and an MC903-induced AD model using wild-type and IL-32γ transgenic mice. We conducted the therapy experiments by using recombinant IL-32γ protein in a reconstructed human skin model and PA-induced model. We conducted a receiver operating characteristic analysis of IL-32γ with new AD biomarkers, IL-31 and IL-33, in serum from patients with AD. RESULTS: Dermatitis severity and epidermal thickness were significantly reduced in PA- and MC903-induced IL-32γ transgenic mice compared with in wild-type mice. The concentration of AD-related cytokines was reduced in PA- and MC903-induced IL-32γ transgenic mice compared with in wild-type mice. Subsequent analysis showed that IL-32γ inhibits miR-205 expression in PA- and MC903-induced skin tissue samples and TNF-α/IFN-γ-treated HaCaT cells. IL-32γ reduced NF-κB activity in skin tissue samples from PA- and MC903-induced mice and TNF-α/IFN-γ-treated HaCaT cells. NF-κB inhibitor treatment with IL-32γ expression further suppressed expression of inflammatory mediators as well as miR-205 in TNF-α/IFN-γ-treated HaCaT cells. Furthermore, recombinant IL-32γ protein alleviated AD-like inflammation in in vivo and reconstructed human skin models. Spearman correlation analysis showed that serum levels of IL-32γ and miR-205 were significantly concordant in patients with AD. CONCLUSION: Our results indicate that IL-32γ reduces AD through the inhibition of miR-205 expression via inactivation of NF-κB.
Assuntos
Dermatite Atópica/imunologia , Regulação da Expressão Gênica/imunologia , Interleucinas/imunologia , MicroRNAs/imunologia , NF-kappa B/imunologia , Animais , Linhagem Celular , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucinas/genética , Camundongos , Camundongos Transgênicos , MicroRNAs/genética , NF-kappa B/genética , Anidridos Ftálicos/toxicidadeRESUMO
A Gram-stain-positive, aerobic, endospore-forming, moderately halophilic rod, designated strain R1(T), was isolated from rice husks and subjected to a taxonomic study using a polyphasic approach. Strain R1(T) produced spherical or ellipsoidal endospores at a subterminal position in swollen sporangia, and was catalase- and oxidase-positive. The isolate grew optimally at 37 °C and pH 6.0-7.0, and could grow in the presence of up to 9% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain R1(T) belongs to the genus Bacillus. The closest relatives of strain R1(T) were Bacillus subtilis subsp. subtilis NCIB 3610(T), Bacillus aquimaris TF-12(T), and Bacillus marisflavi TF-11(T), with 16S rRNA gene sequence similarities of 96.0%, 98.4%, and 98.7%, respectively. DNA-DNA relatedness values between the isolate and the reference strains were ≤42±3%. The predominant menaquinones were MK-5 (50%) and MK-7 (50%). The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, and phosphatidylethanolamine. The major cellular fatty acids were iso-C(15â:â0) (48.6%) and anteiso-C(15â:â0) (20.6%), and the cell-wall diamino acid was meso-diaminopimelic acid. On the basis of 16S rRNA gene sequence analyses and chemotaxonomic and phenotypic characteristics, it is concluded that strain R1(T) represents a novel species of the genus Bacillus, for which we propose the name Bacillus oryzaecorticis sp. nov. The type strain is R1(T) (â=âKACC 17217(T)â=âKCCM 90231(T)â=âJCM 19602(T)).
Assuntos
Bacillus/classificação , Oryza/microbiologia , Filogenia , Bacillus/genética , Bacillus/isolamento & purificação , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Pigmentação , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Vitamina K 2/químicaRESUMO
Climate change has increased variable weather patterns that affect plants. To address these issues, we developed a microbial biocontrol agent against drought stress in kimchi cabbage (Brassica rapa L. subsp. pekinensis). We selected three bacterial strains (Leifsonia sp. CS9, Bacillus toyonensis TSJ7, and Lysinibacillus capsici TT41) because they showed a survival rate of up to 50% and good growth rate when treated with 30% PEG 6000. The three strains were treated with kimchi cabbage to confirm their enhanced drought stress resistance under non-watering conditions. Among the three strains, the TT41 treated group showed a significant increase in various plant parameters compared with the negative control on the 7th day. We performed extensive profiling of primary and secondary metabolites from kimchi cabbage and the TT41 strain. Multivariate and pathway analyses revealed that only the TT41 group clustered with the well-watered group and showed almost the same metabolome on the 7th day. When treated with TT41, lactic acid was identified as an indicator metabolite that significantly improved drought stress tolerance. Furthermore, lactic acid treatment effectively induced drought stress tolerance in kimchi cabbage, similar to that achieved with the TT41 strain.
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Although soybean (Glycine max) leaves generate building blocks to produce seeds, a comprehensive understanding of the metabolic changes in soybean leaves during the entire growth stages is limited. Here, we investigated the metabolite changes in soybean leaves from five cultivars among four vegetative (V) and eight reproductive (R) stages using metabolite profiling coupled with chemometrics. Principal component analysis (PCA) of all samples showed a clear separation by growth stage. The total amount of monosaccharides and organic acids for energy production were highly detected in the V stage samples, accumulating in concentrations 2.5 and 1.7 times higher than in the R stage samples, respectively. The results of partial least-squares-discriminant analysis (PLS-DA) revealed a clear separation from R1 to R5 by the first PLS, suggesting significant alterations in the metabolic networks up to R5. After flowering, the stage of seed formation, R5, was associated with lower levels of most amino acids and an accumulation of phytosterols. The negative correlation observed between amino acids and phytosterol levels suggests a sophisticated coordination between carbon and nitrogen metabolism in plant, ensuring and supporting optimal growth (r = -0.50085, P = 0.0001). In addition, R-stage samples had decreased monosaccharide levels, indicating redistribution to seeds and senescence-related metabolite changes. Thus, metabolite profiling coupled with chemometrics could be a useful tool for investigating alterations in metabolic networks during various plant growth and development stages. Furthermore, we observed variations in flavonoid contents among the different cultivars. The results could be a basis of further studies on the source-sink interactions in the plant system.
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Bioelectronic devices that offer real-time measurements, biological signal processing, and continuous monitoring while maintaining stable performance are in high demand. The materials used in organic electrochemical transistors (OECTs) demonstrate high transconductance (GM) and excellent biocompatibility, making them suitable for bioelectronics in a biological environment. However, ion migration in OECTs induces a delayed response time and low cut-off frequency, and the adverse biological environment causes OECT durability problems. Herein, we present OECTs with a faster response time and improved durability, made possible by using a nanofiber mat channel of a conventional OECT structure. Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)/polyacrylamide (PAAm) nanofiber mat channel OECTs are fabricated and subjected to various durability tests for the first time based on continuous measurements and mechanical stability assessments. The results indicate that the nanofiber mat channel OECTs have a faster response time and longer life spans compared to those of film channel OECTs. The improvements can be attributed to the increased surface area and fibrous structure of the nanofiber mat channel. Furthermore, the hydrogel helps to maintain the structure of the nanofiber, facilitates material exchange, and eliminates the need for a crosslinker.
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Biomonitoring of workers is an approach of evaluating workers' exposure to chemicals and particulate matter by measuring biomarkers of parent chemicals, their metabolites, and reaction products in workers' biospecimens. Prerequisites for biological monitoring in the workplace include permission to enter the workplace, approval of the study plan from the IRB (Institutional Review Board), and obtaining consent from workers. Because of the complex legal process involved in biomonitoring, few studies have been conducted so far on biomonitoring of workers' exposures to nanoparticles and other hazards from emerging materials and advanced nanotechnologies. We have developed a cell-based biomonitoring device that can evaluate acute cytotoxicity and various other effect biomakers, such as inflammation, at realistic workplace exposure. This device is based on air-liquid interphase (ALI) and can be used to evaluate cell toxicity and early effect biomarkers along adverse outcome pathways. Following exposure of A549 lung epithelial cells in ALI to workplace air for 1-2 h, the cells were processed to assess the induction of inflammatory and cell damage biomarkers. Initially, we estimated the deposition rate of nanoparticles in the transwell by exposing the cell-free ALI device to silver nanoparticle aerosols (AgNP 20-30 nm) for 2 h in the laboratory. Then A549 lung epithelial cells cultured on the transwell in the ALI device were exposed to AgNP nanoaerosols for 2 h and evaluated for cytotoxicity and induction of mRNAs of pro-inflammatory cytokines IL-1b, IL-6, and TNF-α. Then the cells in the ALI device were exposed to 3-D printer emissions at the workplace and evaluated for the same matched endpoints. The mRNA levels for IL-1b, IL-6, and TNF-α increased significantly at the end of 2-h exposure of A549 cells to the positive control AgNP aerosols. These mRNAs, as well as LDH and microprotein concentrations, increased even more after 24-h post-exposure incubation (p < 0.05). Cytotoxicity evaluation of 3-D printer emissions at 810 and 957 µg/m3, which was more than 80 times higher than the airborne total suspended particulate concentrations in the workplace air (9-12.5 µg/m3), suggested no significant acute cytotoxicity at the end of 2-h exposure to 3-D-printing emission, as well as at 24-h post-exposure incubation. Hyperspectral microscopic observation showed that 3-D printers emitted particles to be attached to A549 cells after 2-h exposure, and many particles were internalized by A549 cells after 24 h of post-exposure incubation. The mRNA expression of pro-inflammatory cytokine IL-1b and IL-6 increased significantly after 2-h exposure to 3-D printer emissions and after 24-h incubation (only IL-6). In contrast, the expression of TNF-α mRNA decreased significantly after 2 h of exposure to 3-D printers and decreased even more after 24-h post-exposure incubation. These results support the use of cell-based ALI devices for direct assessment of airborne hazards in the workplace, for probing toxicological properties of airborne contaminants using adverse molecular pathways, and for guiding study design for workplace biomonitoring. ALI devices can bridge conventional exposure assessment with cellular toxicity testing platforms for hazard and risk assessment.
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Organic neuromorphic computing/sensing platforms are a promising concept for local monitoring and processing of biological signals in real time. Neuromorphic devices and sensors with low conductance for low power consumption and high conductance for low-impedance sensing are desired. However, it has been a struggle to find materials and fabrication methods that satisfy both of these properties simultaneously in a single substrate. Here, nanofiber channels with a self-formed ion-blocking layer are fabricated to create organic electrochemical transistors (OECTs) that can be tailored to achieve low-power neuromorphic computing and fast-response sensing by transferring different amounts of electrospun nanofibers to each device. With their nanofiber architecture, the OECTs exhibit a low switching energy of 113 fJ and operate within a wide bandwidth (cut-off frequency of 13.5 kHz), opening a new paradigm for energy-efficient neuromorphic computing/sensing platforms in a biological environment without the leakage of personal information.
Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/métodos , Nanofibras/química , Polímeros/química , Sinapses/fisiologia , Transistores Eletrônicos/normas , Redes Neurais de ComputaçãoRESUMO
Biodegradable electronics are disposable green devices whose constituents decompose into harmless byproducts, leaving no residual waste and minimally invasive medical implants requiring no removal surgery. Stretchable and flexible form factors are essential in biointegrated electronic applications for conformal integration with soft and expandable skins, tissues, and organs. Here a fully biodegradable MgZnCa metallic glass (MG) film is proposed for intrinsically stretchable electrodes with a high yield limit exploiting the advantages of amorphous phases with no crystalline defects. The irregular dissolution behavior of this amorphous alloy regarding electrical conductivity and morphology is investigated in aqueous solutions with different ion species. The MgZnCa MG nanofilm shows high elastic strain (≈2.6% in the nano-tensile test) and offers enhanced stretchability (≈115% when combined with serpentine geometry). The fatigue resistance in repeatable stretching also improves owing to the wide range of the elastic strain limit. Electronic components including the capacitor, inductor, diode, and transistor using the MgZnCa MG electrode support its integrability to transient electronic devices. The biodegradable triboelectric nanogenerator of MgZnCa MG operates stably over 50 000 cycles and its fatigue resistant applications in mechanical energy harvesting are verified. In vitro cell toxicity and in vivo inflammation tests demonstrate the biocompatibility in biointegrated use.
RESUMO
This study monitored particulates, and volatile organic compounds (VOCs) emitted from 3-D printers using acrylonitrile-butadiene-styrene copolymer (ABS) filaments at a workplace to assess exposure before and after introducing exposure mitigation measures. Air samples were collected in the printing room and adjacent corridor, and real-time measurements of ultrafine and fine particle were also conducted. Extensive physicochemical characterizations of 3-D printer emissions were performed, including real-time (size distribution, number concentration) nanoparticle characterization, size-fractionated mass distribution and concentration, as well as chemical composition for metals by ICP-MS and VOCs by GC-FID, real-time VOC monitors, and proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF-MS). Air sampling showed low levels of total suspended particulates (TSP, 9-12.5/m3), minimal levels (1.93-4 ppm) of total volatile organic chemicals (TVOC), and formaldehyde (2.5-21.7 ppb). Various harmful gases, such as formaldehyde, acrolein, acetone, hexane, styrene, toluene, and trimethylamine, were detected at concentrations in the 1-100 ppb by PTR-TOF-MS when air sample was collected into the Tedlar bag from the front of the 3-D printer. Ultrafine particles having an average particle size (30 nm count median diameter and 71 nm mass median diameter) increased during the 3-D printing operation. They decreased to the background level after the 3-D printing operation, while fine particles continually increased after the termination of 3-D printing to the next day morning. The exposure to 3-D printer emissions was greatly reduced after isolating 3-D printers in the enclosed space. Particle number concentration measured by real-time particle counters (DMAS and OPC) were greatly reduced after isolating 3-D printers to the isolated place.
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Electronic skins (e-skins)-electronic sensors mechanically compliant to human skin-have long been developed as an ideal electronic platform for noninvasive human health monitoring. For reliable physical health monitoring, the interface between the e-skin and human skin must be conformal and intact consistently. However, conventional e-skins cannot perfectly permeate sweat in normal day-to-day activities, resulting in degradation of the intimate interface over time and impeding stable physical sensing. Here, we present a sweat pore-inspired perforated e-skin that can effectively suppress sweat accumulation and allow inorganic sensors to obtain physical health information without malfunctioning. The auxetic dumbbell through-hole patterns in perforated e-skins lead to synergistic effects on physical properties including mechanical reliability, conformability, areal mass density, and adhesion to the skin. The perforated e-skin allows one to laminate onto the skin with consistent homeostasis, enabling multiple inorganic sensors on the skin to reliably monitor the wearer's health over a period of weeks.
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In regulation of the developmental process, the balance between cellular proliferation and cell death is critical. Placental development tightly controls this mechanism, and increased apoptosis of placental trophoblasts can cause a variety of gynecological diseases. Members of the immortalization-upregulated protein (IMUP) family are nuclear proteins implicated in SV40-mediated immortalization and cellular proliferation; however, the mechanisms by which their expression is regulated in placental development are still unknown. We compared IMUP-2 expression in normal and pre-eclamptic placental tissues and evaluated the function of IMUP-2 in HTR-8/SVneo trophoblast cells under hypoxic conditions. IMUP-2 was expressed in syncytiotrophoblasts and syncytial knots of the placental villi. IMUP-2 expression was significantly higher in preterm pre-eclampsia patients than in patients who went to term (P < 0.001); however, we observed no differences in IMUP-2 expression between normal term patients with and without pre-eclampsia. Hypoxic conditions increased apoptosis of HTR8/SVneo trophoblast cells and induced IMUP-2 expression. Also, apoptosis of HTR-8/SVneo trophoblast cells was increased after IMUP-2 gene transfection. These results suggest that IMUP-2 expression is specifically elevated in preterm pre-eclampsia and under hypoxic conditions, and that IMUP-2 induces apoptosis of the trophoblast. Therefore, IMUP-2 might have functional involvement in placental development and gynecological diseases such as pre-eclampsia.
Assuntos
Apoptose/fisiologia , Hipóxia/metabolismo , Proteínas Nucleares/fisiologia , Pré-Eclâmpsia/metabolismo , Fatores de Transcrição/fisiologia , Trofoblastos/metabolismo , Sequência de Bases , Western Blotting , Estudos de Casos e Controles , Linhagem Celular Transformada , Primers do DNA , Feminino , Humanos , Hipóxia/patologia , Hibridização In Situ , Pré-Eclâmpsia/patologia , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trofoblastos/patologiaRESUMO
Alcohol overconsumption and abuse leads to alcoholic liver disease (ALD), which is a major chronic liver disease worldwide. Field water-dropwort (Oenanthe javanica (Blume) DC.) is a small perennial herb and has been cultivated in Asia for thousands of years and traditionally used to treat various diseases including hepatitis, jaundice, hypertension and polydipsia, as well as its therapeutic benefits have been recognized for centuries in Asia. Although several studies have reported that water-dropwort extracts have pharmacological effects on various diseases, the pharmacological ability of fermented field water-dropwort in ALD is not reported yet. Thus, we investigated the effect of fermented field water-dropwort extracts (FDE) on chronic plus binge ethanol-induced liver injury. C57BL/6 male mice (9 weeks old) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 10 days with parallel saline or FDE orally administered each day. Ethanol-induced hepatic triglyceride (TG) levels and the mRNA levels of TG synthesis-related genes such as sterol regulatory element binding protein 1 (SREBP1), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were decreased in the liver of mice with FDE administration. Moreover, FDE administered mice showed decreasing ethanol-induced oxidative stress such as increasing oxidised glutathione and lipid peroxidation in the liver. In primary hepatic cells, FDE treated cells exhibited decreased ethanol-induced lipid accumulation and the mRNA levels of TG synthesis-related genes, SREBP-1, ACC and FAS. In conclusions, FDE has the potential to be explored as a candidate treatment agent for ALD by inhibiting TG synthesis and blocking of oxidative stress.
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As the technology of flexible electronics has remarkably advanced, the long-term reliability of flexible devices has attracted much attention, as it is an important factor for such devices in reaching real commercial viability. To guarantee the bending fatigue lifetime, the exact evaluation of bending strain and the change in electrical resistance is required. In this study, we investigated the bending strains of Cu thin films on flexible polyimide substrates with different thicknesses using monolayer and bilayer bending models and monitored the electrical resistance of the metal electrode during a bending fatigue test. For a thin metal electrode, the bending strain and fatigue lifetime were similar regardless of substrate thickness, but for a thick metal film, the fatigue lifetime was changed by different bending strains in the metal electrode according to substrate thickness. To obtain the exact bending strain distribution, we conducted a finite-element simulation and compared the bending strains of thin and thick metal structures. For thick metal electrodes, the real bending strain obtained from a bilayer model or simulation showed values much different from those from a simple monolayer model. This study can provide useful guidelines for developing highly reliable flexible electronics.
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Chronic diarrhea is one of the most frequent gastro-intestinal manifestations in acquired immunodeficiency syndrome (AIDS). Protozoa and nontuberculous mycobacteria (NTM) are opportunistic pathogens that can easily infect these patients. Among the NTM, Mycobacterium avium complex (MAC) is the most frequently observed pathogen in HIV-infected patients. However, NTMs other than MAC have not been reported as a gastrointestinal pathogen as yet. We present a case of chronic diarrhea in an AIDS patient in whom Mycobacterium ulcerans and cryptosporidium co-infection is evidenced from colonic tissue.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Úlcera de Buruli/diagnóstico , Diarreia/microbiologia , Mycobacterium ulcerans/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Adulto , Úlcera de Buruli/complicações , Doença Crônica , Criptosporidiose/complicações , DNA Bacteriano/análise , Diarreia/parasitologia , Humanos , Masculino , Mycobacterium ulcerans/genéticaRESUMO
Leiomyosarcoma is a rare tumor of the liver. It usually arises from many other organs including uterus, gastrointestinal tract, retroperitoneum, and soft tissues. Primary hepatic leiomyosarcoma progresses very slowly and is not associated with chronic liver disease. When the tumor is detected early enough to be treated by operation, the prognosis is favorable. While several cases of primary hepatic leiomyosarcoma have been reported in Korea, there was no case associated with acute bleeding. We report a 80-year old male patient with huge primary hepatic leiomyosarcoma, who presented with acute bleeding and IVC obstruction. The patient was treated by embolization and IVC stenting.
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Hemorragia/diagnóstico , Leiomiossarcoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Doença Aguda , Idoso de 80 Anos ou mais , Oclusão com Balão , Biomarcadores Tumorais , Humanos , Leiomiossarcoma/irrigação sanguínea , Leiomiossarcoma/patologia , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/patologia , Masculino , Stents , Tomografia Computadorizada por Raios XRESUMO
The aim of the present study was to examine the antioxidative activity of (+)-lariciresinol (LRSL), an optically active lignan isolated from Rubia philippinensis in several in vitro assays. LRSL was also subjected to evaluate its inhibitory effect against the generation of reactive oxygen species (ROS) in murine macrophage (RAW 264.7) cells. The results showed that LRSL possessed very strong radical scavenging activity and reducing power, as well as inhibited ROS generation in a dose-dependent manner without showing any cytotoxicity. The transcriptional and translational levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were markedly higher in the sample treated group. LRSL treatment also increased the transcriptional and translational activities of NF-E2-related factor-2 (Nrf-2) with a corresponding increase in the transcriptional and translational activities of the heme oxygenase-1 (HO-1). LRSL activated p38 and treatments with SB239063 (a p38 inhibitor) suppressed the LRSL-induced activation of Nrf2, resulting in a decrease in HO-1 expression. Collectively, the data demonstrated that LRSL has potent antioxidative activity, decreasing ROS generation in RAW 264.7 cells and increasing the transcriptional and translational levels of antioxidant enzymes by activating Nrf2-mediated HO-1 induction via p38 signaling.
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Antioxidantes/farmacologia , Furanos/isolamento & purificação , Furanos/farmacologia , Heme Oxigenase-1/metabolismo , Lignanas/isolamento & purificação , Lignanas/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Rubia/química , Regulação para Cima/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Amidinas , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Furanos/química , Lignanas/química , Desintoxicação Metabólica Fase II , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismoRESUMO
In this study, the authors investigated the anti-melanogenic effects of 3,8-dihydroxyquinoline (jineol) isolated from Scolopendra subspinipes mutilans, the mechanisms responsible for its inhibition of melanogenesis in melan-a cells, and its antioxidant efficacy. Mushroom tyrosinase activities and melanin contents were determined in melan-a cells, and the protein and mRNA levels of MITF, tyrosinase, TYRP-1, and TYRP-2 were assessed. Jineol exhibited significant, concentration-dependent antioxidant effects as determined by DPPH, ABTS, CUPRAC, and FRAP assays. Jineol significantly inhibited mushroom tyrosinase activity by functioning as an uncompetitive inhibitor, and markedly inhibited melanin production and intracellular tyrosinase activity in melan-a cells. In addition, jineol abolished the expressions of tyrosinase, TYRP-1, TYRP-2, and MITF, thereby blocking melanin production and interfering with the phosphorylations of ERK1/2 and p38. Furthermore, specific inhibitors of ERK1/2 and p38 prevented melanogenesis inhibition by jineol, and the proteasome inhibitor (MG-132) prevented jineol-induced reductions in cellular tyrosinase levels. Taken together, jineol was found to stimulate MAP-kinase (ERK1/2 and p38) phosphorylation and the proteolytic degradation pathway, which led to the degradations of MITF and tyrosinase, and to suppress the productions of melanin.
Assuntos
Melaninas/genética , Fator de Transcrição Associado à Microftalmia/genética , Monofenol Mono-Oxigenase/genética , Animais , Artrópodes/genética , Artrópodes/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Melaninas/biossíntese , Melanócitos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/genética , Monofenol Mono-Oxigenase/química , Fosforilação/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
This study was undertaken to characterize a lactic acid bacterium 4I1, isolated from the freshwater fish, Zacco koreanus. Morphological, biochemical, and molecular characterization of 4I1 revealed it to be Pediococcus pentosaceus 4I1. The cell free supernatant (CFS) of P. pentosaceus 4I1 exhibited significant (p < 0.05) antibacterial effects (inhibition zone diameters: 16.5-20.4 mm) against tested foodborne pathogenic bacteria with MIC and MBC values of 250-500 and 500-1,000 µg/mL, respectively. Further, antibacterial action of CFS of P. pentosaceus 4I1 against two selected bacteria Staphylococcus aureus KCTC-1621 and Escherichia coli O157:H7 was determined in subsequent assays. The CFS of P. pentosaceus 4I1 revealed its antibacterial action against S. aureus KCTC-1621 and E. coli O157:H7 on membrane integrity as confirmed by a reduction in cell viability, increased potassium ion release (900 and 800 mmol/L), reduced absorption at 260-nm (3.99 and 3.77 OD), and increased relative electrical conductivity (9.9 and 9.7%), respectively. Gas chromatography-mass spectrometry (GC-MS) analysis of the CFS of P. pentosaceus 4I1 resulted in the identification of seven major compounds, which included amino acids, fatty acids and organic acids. Scanning electron microscopic-based morphological analysis further confirmed the antibacterial effect of CFS of P. pentosaceus 4I1 against S. aureus KCTC-1621 and E. coli O157:H7. In addition, the CFS of P. Pentosaceus 4I1 displayed potent inhibitory effects on biofilms formation by S. aureus KCTC-1621 and E. coli O157:H7. The study indicates the CFS of P. pentosaceus 4I1 offers an alternative means of controlling foodborne pathogens.