RESUMEN
The SARS-CoV-2 pandemic has created a global public crisis and heavily affected personal lives, healthcare systems, and global economies. Virus variants are continuously emerging, and, thus, the pandemic has been ongoing for over two years. Vaccines were rapidly developed based on the original SARS-CoV-2 (Wuhan-Hu-1) to build immunity against the coronavirus disease. However, they had a very low effect on the virus' variants due to their low cross-reactivity. In this study, a multivalent SARS-CoV-2 vaccine was developed using ferritin nanocages, which display the spike protein from the Wuhan-Hu-1, B.1.351, or B.1.429 SARS-CoV-2 on their surfaces. We show that the mixture of three SARS-CoV-2 spike-protein-displaying nanocages elicits CD4+ and CD8+ T cells and B-cell immunity successfully in vivo. Furthermore, they generate a more consistent antibody response against the B.1.351 and B.1.429 variants than a monovalent vaccine. This leads us to believe that the proposed ferritin-nanocage-based multivalent vaccine platform will provide strong protection against emerging SARS-CoV-2 variants of concern (VOCs).
Asunto(s)
COVID-19 , Vacunas Virales , Anticuerpos Neutralizantes/genética , Linfocitos T CD8-positivos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Ferritinas/genética , Humanos , Inmunidad , Mutación , SARS-CoV-2 , Vacunas CombinadasRESUMEN
Since it was first reported in Wuhan, China, in 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic outbreak resulting in a tremendous global threat due to its unprecedented rapid spread and an absence of a prophylactic vaccine or therapeutic drugs treating the virus. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a key player in the viral entry into cells through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor protein, and the RBD has therefore been crucial as a drug target. In this study, we used phage display to develop human monoclonal antibodies (mAbs) that neutralize SARS-CoV-2. A human synthetic Fab phage display library was panned against the RBD of the SARS-CoV-2 spike protein (SARS-2 RBD), yielding ten unique Fabs with moderate apparent affinities (EC50 = 19-663 nM) for the SARS-2 RBD. All of the Fabs showed no cross-reactivity to the MERS-CoV spike protein, while three Fabs cross-reacted with the SARS-CoV spike protein. Five Fabs showed neutralizing activities in in vitro assays based on the Fabs' activities antagonizing the interaction between the SARS-2 RBD and ACE2. Reformatting the five Fabs into immunoglobulin Gs (IgGs) greatly increased their apparent affinities (KD = 0.08-1.0 nM), presumably due to the effects of avidity, without compromising their non-aggregating properties and thermal stability. Furthermore, two of the mAbs (D12 and C2) significantly showed neutralizing activities on pseudo-typed and authentic SARS-CoV-2. Given their desirable properties and neutralizing activities, we anticipate that these human anti-SARS-CoV-2 mAbs would be suitable reagents to be further developed as antibody therapeutics to treat COVID-19, as well as for diagnostics and research tools.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , COVID-19/inmunología , Fragmentos Fab de Inmunoglobulinas/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Monoclonales/inmunología , Sitios de Unión , Humanos , Inmunoglobulina G/inmunología , Biblioteca de Péptidos , Dominios Proteicos , Glicoproteína de la Espiga del Coronavirus/químicaRESUMEN
Surface reconstruction, reorganizing the surface atoms or structure, is a promising strategy to manipulate materials' electrical, electrochemical, and surface catalytic properties. Herein, a rapid surface reconstruction of indium sulfide (In2S3) is demonstrated via a high-temperature flame treatment to improve its charge collection properties. The flame process selectively transforms the In2S3 surface into a diffusionless In2O3 layer with high crystallinity. Additionally, it controllably generates bulk sulfur vacancies within a few seconds, leading to surface-reconstructed In2S3 (sr-In2S3). When using those sr-In2S3 as photoanode for photoelectrochemical water splitting devices, these dual functions of surface In2O3/bulk In2S3 reduce the charge recombination in the surface and bulk region, thus improving photocurrent density and stability. With optimized surface reconstruction, the sr-In2S3 photoanode demonstrates a significant photocurrent density of 8.5 mA cm-2 at 1.23 V versus a reversible hydrogen electrode (RHE), marking a 2.5-fold increase compared to pristine In2S3 (3.5 mA cm-2). More importantly, the sr-In2S3 photoanode exhibits an impressive photocurrent density of 7.3 mA cm-2 at 0.6 V versus RHE for iodide oxidation reaction. A practical and scalable surface reconstruction is also showcased via flame treatment. This work provides new insights for surface reconstruction engineering in sulfide-based semiconductors, making a breakthrough in developing efficient solar-fuel energy devices.
RESUMEN
This study investigated how process parameters of laser cladding affect the microstructure and mechanical properties of WC-12Co composite coating for use as a protective layer of continuous caster rolls. WC-Co powders, WC-Ni powders, and Ni-Cr alloy powder with various wear resistance characteristics were evaluated in order to determine their applicability for use as cladding materials for continuous caster roll coating. The cladding process was conducted with various parameters, including laser powers, cladding speeds, and powder feeding rates, then the phases, microstructure, and micro-hardness of the cladding layer were analyzed in each specimen. Results indicate that, to increase the hardness of the cladding layer in WC-Co composite coating, the dilution of the cladding layer by dissolution of Fe from the substrate should be minimized, and the formation of the Fe-Co alloy phase should be prevented. The mechanical properties and wear resistance of each powder with the same process parameters were compared and analyzed. The microstructure and mechanical properties of the laser cladding layer depend not only on the process parameters, but also on the powder characteristics, such as WC particle size and the type of binder material. Additionally, depending on the degree of thermal decomposition of WC particles and evolution of W distribution within the cladding layer, the hardness of each powder can differ significantly, and the wear mechanism can change.
RESUMEN
A hydrometallurgy is one of the most important techniques for recycling waste LIBs, where identifying the exact composition of the metal-leached solution is critical in controlling the metal extraction efficiency and the stoichiometry of the regenerated product. In this study, we report a simple and selective optical detection of high-concentrated Co2+ using a graphitic carbon nitride (g-CN)-based fluorescent chemosensor. g-CN is prepared by molten salt synthesis using dicyandiamide (DCDA) and LiI/KI. The mass ratio of LiI/KI to DCDA modifies the resulting g-CN (CNI) in terms of in-plane molecular distances of base sites including cyano functional groups (âCN) and fluorescent emission wavelength via nucleophilic substitution. The fluorescent sensing performance of CNIs is evaluated through photoluminescence (PL) emission spectroscopy in a broad Co2+ concentration range (10-4-100 M). The correlation between the surface exposure of hidden nitrogen pots (base sites) and PL intensity change is achieved where the linear relationship between the PL quenching and the logarithm of Co2+ concentration in the analyte solution is well established with the regression of 0.9959. This study will provide the design principle of the chemosensor suitable for the fast and accurate optical detection of Co2+ present in a broad concentration range for hydrometallurgy for the recycling of waste LIBs.
Asunto(s)
Grafito , Litio , Cobalto/química , Metales , Iones , Suministros de Energía Eléctrica , Reciclaje/métodos , ColorantesRESUMEN
We have previously reported anti-obesity effects of Lysimachia foenum-graecum in high-fat diet (HFD)-induced obesity model. Here we isolated a triterpene saponin foenumoside B as an active component of L. foenum-graecum. Foenumoside B blocked the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner with an IC50 of 0.2 µg/ml in adipogenesis assay and suppressed the induction of PPARγ, the master regulator of adipogenesis. Foenumoside B induced the activation of AMP-activated protein kinase (AMPK), and modulated the expression of genes involved in lipid metabolism towards lipid breakdown in differentiated adipocytes. In mouse model, oral administration of foenumoside B (10mg/kg/day for 6 weeks) reduced HFD-induced body weight gain significantly without affecting food intake. Treatment of foenumoside B suppressed lipid accumulation in white adipose tissues and the liver, and lowered blood levels of glucose, triglycerides, ALT, and AST in HFD-induced obese mice. Consistent with the in vitro results, foenumoside B activated AMPK signaling, suppressed the expression of lipogenic genes, and enhanced the expression of lipolytic genes in vivo. Foenumoside B also blocked HFD-induced proinflammatory cytokine production in adipose tissue, suggesting its protective role against insulin resistance. Taken together, these findings demonstrate that foenumoside B represents the anti-obesity effects of L. foenum-graecum, and suggest therapeutic potential of foenumoside B in obesity and obesity-related metabolic diseases.
Asunto(s)
Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Fármacos Antiobesidad/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Obesidad/tratamiento farmacológico , Primulaceae/química , Saponinas/uso terapéutico , Células 3T3-L1 , Quinasas de la Proteína-Quinasa Activada por el AMP , Adipocitos/citología , Animales , Fármacos Antiobesidad/farmacología , Activación Enzimática , Expresión Génica/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/etiología , Proteínas Quinasas/biosíntesis , Saponinas/farmacologíaRESUMEN
BACKGROUND: To clarify the most beneficial treatment of the management modality based on our experience with adult moyamoya disease (MMD). METHODS: From 1998 to 2010, clinical results of 142 patients (ischemic, 98; hemorrhagic, 44) with adult MMD were investigated according to management modality. Revascularization surgery (direct, indirect, and combined bypass) was performed in 124 patients. We observed the clinical course of 18 patients who were treated conservatively. Clinical outcome, angiographic features, hemodynamic change, and incidence of recurrent stroke were investigated pre- and postoperatively. RESULTS: In patients with ischemic MMD, direct and combined bypasses were more effective treatments to prevent recurrent ischemic stroke than indirect bypass surgery (P < 0.05). In patients with hemorrhagic MMD, rebleeding was less likely to occur in patients who had undergone bypass surgery. However, no significant difference was observed in the rebleeding rate between patients with and without revascularization surgery (P > 0.05). An angiogram after bypass surgery comparing the extent of revascularization and reduction of moyamoya vessels in patients treated with direct, indirect, and combined bypass showed a significant difference (P < 0.05) in favor of direct and combined bypass. Postoperative angiographic changes and SPECT results demonstrated significant statistical correlation (P < 0.05). CONCLUSION: Revascularization surgery was effective in further ischemic stroke prevention to a statistically significant extent. Direct and combined bypasses were more effective to prevent recurrent ischemic stroke than indirect bypass. However, there is still no clear evidence that revascularization surgery significantly prevents rebleeding in adult MMD patients. More significant angiographic changes were observed in direct and combined bypasses compared with indirect bypass.
Asunto(s)
Revascularización Cerebral/métodos , Enfermedad de Moyamoya/cirugía , Complicaciones Posoperatorias/etiología , Accidente Cerebrovascular/etiología , Adulto , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Angiografía Cerebral , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/cirugía , Evaluación de la Discapacidad , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Moyamoya/diagnóstico por imagen , Examen Neurológico , Complicaciones Posoperatorias/diagnóstico por imagen , Recurrencia , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
BACKGROUND: Acupuncture is widely-used to treat patients with low back pain, despite insufficient evidence of the technique's efficacy for acute back pain. Motion style acupuncture treatment (MSAT) is a non-traditional acupuncture treatment requiring a patient to exercise while receiving acupuncture. In Korea, MSAT is used to reduce musculoskeletal pain and improve functional status. The study aims to evaluate the effect of MSAT on acute low back pain with severe disability. METHODS/DESIGN: This study is a multicenter, randomized, active-controlled trial with two parallel arms. Participants with acute low back pain and severe functional disability, defined as an Oswestry Disability Index (ODI) value > 60%, will be randomly allocated to the acupuncture group and the nonsteroidal anti-inflammatory drug (NSAID) injection group. The acupuncture group will receive MSAT and the NSAID injection group will receive an intramuscular injection of diclofenac. All procedures will be limited to one session and the symptoms before and after treatment will be measured by assessors blinded to treatment allocation. The primary outcome will be measured at 30 minutes after treatment using the numerical rating scale (NRS) of low back pain while the patient is moving. Secondary outcomes will be measured at 30 minutes after treatment using the NRS of leg pain, ODI, patient global impression of change, range of motion (ROM) of the lumbar spine, and degrees of straight leg raising (SLR). Post-treatment follow-up will be performed to measure primary and secondary outcomes with the exception of ROM and SLR at 2, 4, and 24 weeks after treatment. DISCUSSION: The results of this trial will be discussed. TRIAL REGISTRATION: ClinicalTrial.gov NCT01315561.
Asunto(s)
Terapia por Acupuntura , Dolor Agudo/terapia , Dolor de la Región Lumbar/terapia , Adulto , Protocolos Clínicos , Personas con Discapacidad/rehabilitación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Large particulate photocatalysts allow efficient recovery or installation into the substrate, while limiting possible light-catalyst interaction or mass/charge-transfer. In this study, we developed monodisperse organic single-crystal monoliths with controllable dimensions in the range of 10-100 µm. These were prepared on a 10-g scale by a solution-processed molecular cooperative assembly between melamine (M) and trithiocyanuric acid (TCA) and then transformed into the corresponding g-CN (MTCA-CN) by thermal polycondensation. Molecular precursors that are tightly bound in the crystal undergo polycondensation without losing their macroscopic properties depending on the dimensions of MTCA, thereby changing the microstructure, electronic structure, and photocatalytic activity. Such dimensional tunability enables the fulfillment of various catalytic requirements such as particle size, light absorption, charge separation, band edge potential, and mass transfer. As a proof-of-concept, it was shown that MTCA-CN is tailored to have a high rate of evolution of hydrogen (3.19 µmol/h) from glucose via photoreforming under AM1.5G by using MTCA-100 crystals, leading to the formation of g-CN with the more positive highest occupied molecular orbital (HOMO) level. This study highlights the possibility of developing photocatalysts for practical use and obtaining value-added products (VAPs) without losing the photocatalytic activity relevant for wastewater treatment.
Asunto(s)
Glucosa , Luz Solar , Grafito , Hidrógeno , Nitrilos , Compuestos de NitrógenoRESUMEN
To prevent global warming, ESS development is in progress along with the development of electric vehicles and renewable energy. However, the state-of-the-art technology, i.e., lithium-ion batteries, has reached its limitation, and thus the need for high-performance batteries with improved energy and power density is increasing. Lithium-sulfur batteries (LSBs) are attracting enormous attention because of their high theoretical energy density. However, there are technical barriers to its commercialization such as the formation of dendrites on the anode and the shuttle effect of the cathode. To resolve these issues, a boron nitride nanotube (BNNT)-based separator is developed. The BNNT is physically purified so that the purified BNNT (p-BNNT) has a homogeneous pore structure because of random stacking and partial charge on the surface due to the difference of electronegativity between B and N. Compared to the conventional polypropylene (PP) separator, the p-BNNT loaded PP separator prevents the dendrite formation on the Li metal anode, facilitates the ion transfer through the separator, and alleviates the shuttle effect at the cathode. With these effects, the p-BNNT loaded PP separators enable the LSB cells to achieve a specific capacity of 1429 mAh/g, and long-term stability over 200 cycles.
RESUMEN
The lithium-polysulfide (LiPS) dissolution from the cathode to the organic electrolyte is the main challenge for high-energy-density lithium-sulfur batteries (LSBs). Herein, we present a multi-functional porous carbon, melamine cyanurate (MCA)-glucose-derived carbon (MGC), with superior porosity, electrical conductivity, and polysulfide affinity as an efficient sulfur support to mitigate the shuttle effect. MGC is prepared via a reactive templating approach, wherein the organic MCA crystals are utilized as the pore-/micro-structure-directing agent and nitrogen source. The homogeneous coating of spherical MCA crystal particles with glucose followed by carbonization at 600 °C leads to the formation of hierarchical porous hollow carbon spheres with abundant pyridinic N-functional groups without losing their microstructural ordering. Moreover, MGC enables facile penetration and intensive anchoring of LiPS, especially under high loading sulfur conditions. Consequently, the MGC cathode exhibited a high areal capacity of 5.79 mAh cm-2 at 1 mA cm-2 and high loading sulfur of 6.0 mg cm-2 with a minor capacity decay rate of 0.18% per cycle for 100 cycles.
RESUMEN
Acetyl-CoA carboxylases (ACCs) have been highlighted as therapeutic targets for obesity and diabetes, as they play crucial roles in fatty acid metabolism. ACC activity is regulated through the short-term mechanism of inactivation by reversible phosphorylation. Here, we report the crystal structures of the biotin carboxylase (BC) domain of human ACC2 phosphorylated by AMP-activated protein kinase (AMPK). The phosphorylated Ser222 binds to the putative dimer interface of BC, disrupting polymerization and providing the molecular mechanism of inactivation by AMPK. We also determined the structure of the human BC domain in complex with soraphen A, a macrocyclic polyketide natural product. This structure shows that the compound binds to the binding site of phosphorylated Ser222, implying that its inhibition mechanism is the same as that of phosphorylation by AMPK.
Asunto(s)
Acetil-CoA Carboxilasa/química , Biotina/química , Proteínas Quinasas/metabolismo , Serina/química , Quinasas de la Proteína-Quinasa Activada por el AMP , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Biotina/metabolismo , Cristalografía por Rayos X , Humanos , Macrólidos/química , Fosforilación , Estructura Terciaria de Proteína , Serina/genética , Serina/metabolismoRESUMEN
Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.
Asunto(s)
Carbolinas/metabolismo , Dominio Catalítico , Imidazoles/metabolismo , Hidrolasas Diéster Fosfóricas/química , Hidrolasas Diéster Fosfóricas/metabolismo , Piperazinas/metabolismo , 3',5'-GMP Cíclico Fosfodiesterasas , Sitios de Unión , Carbolinas/química , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 , Humanos , Enlace de Hidrógeno , Imidazoles/química , Modelos Moleculares , Piperazinas/química , Conformación Proteica , Purinas , Citrato de Sildenafil , Sulfonas , Tadalafilo , Triazinas , Diclorhidrato de VardenafilRESUMEN
Rechargeable lithium-sulfur batteries (LSBs) are emerging as some of the most promising next-generation battery alternatives to state-of-the-art lithium-ion batteries (LIBs) due to their high gravimetric energy density, being inexpensive, and having an abundance of elemental sulfur (S8). However, one main, well-known drawback of LSBs is the so-called polysulfide shuttling, where the polysulfide dissolves into organic electrolytes from sulfur host materials. Numerous studies have shown the ability of porous carbon as a sulfur host material. Porous carbon can significantly impede polysulfide shuttling and mitigate the insulating passivation layers, such as Li2S, owing to its intrinsic high electrical conductivity. This work suggests a scalable and straightforward one-step synthesis method to prepare a unique interconnected microporous and mesoporous carbon framework via salt templating with a eutectic mixture of LiI and KI at 800 °C in an inert atmosphere. The synthesis step used environmentally friendly water as a washing solvent to remove salt from the carbon-salt mixture. When employed as a sulfur host material, the electrode exhibited an excellent capacity of 780 mAh g-1 at 500 mA g-1 and a sulfur loading mass of 2 mg cm-2 with a minor capacity loss of 0.36% per cycle for 100 cycles. This synthesis method of a unique porous carbon structure could provide a new avenue for the development of an electrode with a high retention capacity and high accommodated sulfur for electrochemical energy storage applications.
RESUMEN
The C-type lectin-like domain of CLEC14a (CLEC14a-C-type lectin-like domain [CTLD]) is a key domain that mediates endothelial cell-cell contacts in angiogenesis. However, the role of CLEC14a-CTLD in pathological angiogenesis has not yet been clearly elucidated. In this study, through complementarity-determining region grafting, consecutive deglycosylation, and functional isolation, we generated a novel anti-angiogenic human monoclonal antibody that specifically targets CLEC14a-CTLD and that shows improved stability and homogeneity relative to the parental antibody. We found that this antibody directly inhibits CLEC14a-CTLD-mediated endothelial cell-cell contact and simultaneously downregulates expression of CLEC14a on the surface of endothelial cells. Using various in vitro and in vivo functional assays, we demonstrated that this antibody effectively suppresses vascular endothelial growth factor (VEGF)-dependent angiogenesis and tumor angiogenesis of SNU182 human hepatocellular carcinoma, CFPAC-1 human pancreatic cancer, and U87 human glioma cells. Furthermore, we also found that this antibody significantly inhibits tumor angiogenesis of HCT116 and bevacizumab-adapted HCT116 human colorectal cancer cells. These findings suggest that antibody targeting of CLEC14a-CTLD has the potential to suppress VEGF-dependent angiogenesis and tumor angiogenesis and that CLEC14a-CTLD may be a novel anti-angiogenic target for VEGF-dependent angiogenesis and tumor angiogenesis.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Moléculas de Adhesión Celular/metabolismo , Inmunoglobulina G/farmacología , Lectinas Tipo C/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Fisiológica/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Anticuerpos Monoclonales/inmunología , Moléculas de Adhesión Celular/genética , Comunicación Celular/efectos de los fármacos , Comunicación Celular/inmunología , Línea Celular Tumoral , Femenino , Células HCT116 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inmunoglobulina G/inmunología , Lectinas Tipo C/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neovascularización Patológica/inmunología , Neovascularización Fisiológica/inmunología , Factor A de Crecimiento Endotelial Vascular/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Toxoplasmic encephalitis (TE) is an opportunistic infection found in immunocompromised patients and TE related cerebral mass lesion is often reported in acquired immunodeficiency acquired immunodeficiency syndrome (AIDS) patients. However, incidence of TE related AIDS in Korea is still rare and is unfamiliar to neurosurgeons. Differential diagnosis is needed to rule out other brain lesions. A 39-year-old man visited the emergency room with rapid progressive left hemiparesis. Magnetic resonance imaging showed a ring-enhanced mass lesion in his right frontal lobe. Human immunodeficiency virus and Toxoplasma gondii immunoglobulin G were tested positive by a serologic test. We report here a rare case of patient with TE related AIDS.
RESUMEN
Long-chain unsaturated fatty acids, such as linoleic acid, show antibacterial activity and are the key ingredients of antimicrobial food additives and some antibacterial herbs. However, the precise mechanism for this antimicrobial activity remains unclear. We found that linoleic acid inhibited bacterial enoyl-acyl carrier protein reductase (FabI), an essential component of bacterial fatty acid synthesis, which has served as a promising target for antibacterial drugs. Additional unsaturated fatty acids including palmitoleic acid, oleic acid, linolenic acid, and arachidonic acid also exhibited the inhibition of FabI. However, neither the saturated form (stearic acid) nor the methyl ester of linoleic acid inhibited FabI. These FabI-inhibitory activities of various fatty acids and their derivatives very well correlated with the inhibition of fatty acid biosynthesis using [(14)C] acetate incorporation assay, and importantly, also correlated with antibacterial activity. Furthermore, the supplementation with exogenous fatty acids reversed the antibacterial effect of linoleic acid, which showing that it target fatty acid synthesis. Our data demonstrate for the first time that the antibacterial action of unsaturated fatty acids is mediated by the inhibition of fatty acid synthesis.
Asunto(s)
Antibacterianos/metabolismo , Bacterias , Ácidos Grasos Insaturados/metabolismo , Ácidos Grasos/biosíntesis , Oxidorreductasas/metabolismo , Bacterias/química , Bacterias/metabolismo , Enoil-ACP Reductasa (NADH) , Ácidos Grasos/química , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/genéticaRESUMEN
PRL-3, a novel class protein of prenylated tyrosine phosphatase, is important in cancer metastasis. Due to its high levels of expression in metastatic tumors, PRL-3 may constitute a useful marker for metastasis and might be a new therapeutic target. Here, we present the solution structure of the phosphatase domain of a human PRL-3 (residues 1-162) in phosphate-free state. The nuclear magnetic resonance (NMR) structure of PRL-3 is similar to that of other known phosphatases with minor differences in the secondary structure. But the conformation and flexibility of the loops comprising the active site differ significantly. When phosphate ions or sodium orthovanadate, which is a known inhibitor, are added to the apo PRL-3, the NMR signals from the residues in the active site appeared and could be assigned, indicating that the conformation of the residues has been stabilized.
Asunto(s)
Proteínas Inmediatas-Precoces/química , Neoplasias/enzimología , Neoplasias/patología , Proteínas Tirosina Fosfatasas/química , Secuencia de Aminoácidos , Sitios de Unión , Inhibidores Enzimáticos/farmacología , Humanos , Iones , Ligandos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Datos de Secuencia Molecular , Metástasis de la Neoplasia , Proteínas de Neoplasias , Fosfatos/química , Conformación Proteica , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido , Tirosina/química , Vanadatos/química , Vanadatos/farmacologíaRESUMEN
Recently, the interest toward human longevity free from diseases is being converged as one system frame along with the development of mobile computing environment, diversification of remote medical system and aging society. Such converged system enables implementation of a bioinformatics system created as various supplementary information services by sensing and gathering health conditions and various bio-information of mobile users to set up medical information. The existing bio-information system performs static and identical process without changes after the bio-information process defined at the initial system configuration executes the system. However, such static process indicates ineffective execution in the application of mobile bio-information system performing mobile computing. Especially, an inconvenient duty of having to perform initialization of new definition and execution is accompanied during the process configuration of bio-information system and change of method. This study proposes a dynamic process design and execution method to overcome such ineffective process.
Asunto(s)
Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Telemedicina/instrumentación , Telemedicina/métodos , Humanos , Integración de Sistemas , Telecomunicaciones , Interfaz Usuario-ComputadorRESUMEN
OBJECTIVE: According to the development of endovascular technique and devices, larger aneurysms on the distal internal carotid artery (ICA) can be treated using a less invasive method. The authors report on clinical and angiographic outcomes of these aneurysms treated using an endovascular technique. MATERIALS AND METHODS: Data on 21 patients with large aneurysms at distal ICA treated by endovascular method between January 2005 and December 2012 were included in this retrospective analysis. RESULTS: Clinical outcome of patients showed strong correlation with the initial neurologic status (p < 0.05). Aneurysm morphology showed saccular, fusiform, and wide-neck in 12, six and three patients. Six patients underwent stent assisted coiling and the other 15 patients underwent simple coiling. Aneurysm occlusion was performed immediately after embolization with near-complete (Raymond class 1-2) in 20 patients (95.2%) and incomplete (Raymond class 3) in one patient (4.8%). Delayed thrombotic occlusion occurred in two patients and their clinical result was fatal. Another five patients died in the hospital, from massive brain edema and/or increased intracranial pressure due to initial subarachnoid hemorrhage. Overall mortality was 30% (seven out of 21). Fatal complication related to the endovascular procedure occurred in two patients with thrombosis at middle cerebral artery (one with stent, the other without it). CONCLUSION: Recent developed endovascular device and technique is safe enough and a less invasive method for distal large or giant aneurysms. Based on our analysis of the study, we suspect that coil embolization of large distal ICA aneurysms (with or without stenting) is effective and safe.