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1.
J Nat Med ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564154

RESUMO

Oxomollugin is a degraded product of mollugin and was found to be an active compound that inhibits LPS-induced NF-κB activation. In this study, we investigated the inhibitory activity of oxomollugin, focusing on TLR4 signaling pathway, resulting in NF-κB activation. Oxomollugin inhibited the LPS-induced association of essential factors for initial activation of TLR4 signaling, MyD88, IRAK4 and TRAF6. Furthermore, oxomollugin showed suppressive effects on LPS-induced modification of IRAK1, IRAK2 and TRAF6, LPS-induced association of TRAF6-TAK1/TAB2, and followed by IKKα/ß phosphorylation, which critical in signal transduction leading to LPS-induced NF-κB activation. The consistent results suggested that oxomollugin inhibits LPS-induced NF-κB activation via the suppression against signal transduction in TLR4 signaling pathway.The activities of oxomollugin reported in this study provides a deeper understanding on biological activity of mollugin derivatives as anti-inflammatory compounds.

2.
Anticancer Res ; 44(2): 561-565, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307547

RESUMO

BACKGROUND/AIM: Cytoglobin (Cygb), a protein involved in cellular oxygen metabolism and protection, has garnered attention owing to its potential role in the initiation and progression of cancer, particularly colon cancer (CC). This study investigated the expression and significance of Cygb in CC. PATIENTS AND METHODS: This study included 145 patients who underwent R0 surgery for CC (clinical stage II/III) at our institution between January 2007 and December 2014. Immunohistochemical analysis was performed to evaluate the Cygb expression patterns in CC tissues. Additionally, the correlation between Cygb expression levels and the clinicopathological characteristics of patients with CC was investigated. RESULTS: Colon cancer tissues were categorized into high-expression (95 cases) and low-expression (50 cases) groups. Cygb was highly expressed in well-differentiated cases, whereas its expression decreased in poorly differentiated cases. No significant differences in other clinicopathological factors were observed between the two groups. Cygb expression had no significant effect on recurrence-free survival or overall survival. CONCLUSION: This study contributes to the growing understanding of Cygb expression and its significance in CC. The expression of Cygb in CC was found to be unrelated to the recurrence rate and prognosis, but showed a correlation with differentiation status.


Assuntos
Neoplasias do Colo , Globinas , Humanos , Citoglobina , Globinas/metabolismo
3.
Ann Surg Oncol ; 31(4): 2309-2318, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37919449

RESUMO

BACKGROUND: Cancer-associated fibroblasts exhibit diversity and have several subtypes. The underlying relationship between the diversity of cancer-associated fibroblasts and their effect on gastric cancer progression remains unclear. In this study, mesenchymal stem cells were differentiated into cancer-associated fibroblasts with gastric cancer cell lines; clinical specimens were used to further investigate the impact of cancer-associated fibroblast diversity on cancer progression. METHODS: Nine gastric cancer cell lines (NUGC3, NUGC4, MKN7, MKN45, MKN74, FU97, OCUM1, NCI-N87, and KATOIII) were used to induce mesenchymal stem cell differentiation into cancer-associated fibroblasts. The cancer-associated fibroblasts were classified based on ACTA2 and PDPN expression. Cell function analysis was used to examine the impact of cancer-associated fibroblast subtypes on cancer cell phenotype. Tissue samples from 97gastric patients who underwent gastrectomy were used to examine the clinical significance of each subtype classified according to cancer-associated fibroblast expression. RESULTS: Co-culture of mesenchymal stem cells with nine gastric cancer cell lines revealed different subtypes of ACTA2 and PDPN expression in differentiated cancer-associated fibroblasts. Cancer-associated fibroblast subtypes with high ACTA2 plus PDPN expression levels significantly increased gastric cancer cell migration, invasion, and proliferation. The cancer-associated fibroblast subtype with ACTA2 plus PDPN expression was an independent prognostic factor along with lymph node metastasis for patients who had gastric cancer and were undergoing surgery. CONCLUSIONS: Cancer-associated fibroblasts are educated by gastric cancer cells during the development of cancer-associated fibroblast diversity. Differentiated cancer-associated fibroblasts with distinct expression patterns could affect gastric cancer progression and enable prognostic stratification for gastric cancer.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/metabolismo , Prognóstico , Fibroblastos Associados a Câncer/patologia , Técnicas de Cocultura , Fibroblastos/metabolismo , Fibroblastos/patologia
6.
Sci Rep ; 12(1): 20137, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36470937

RESUMO

Plasma flows in divergent magnetic fields resembling a magnetic nozzle can be found over wide scales ranging from astrophysical objects to terrestrial plasma devices. Plasma detachment from a magnetic nozzle is a frequent occurrence in natural plasmas, e.g., plasma ejection from the Sun and release from the Sun's magnetic field, forming the solar wind. Plasma detachment has also been a challenging problem relating to space propulsion devices utilizing a magnetic nozzle, especially the detachment of the magnetized electrons having a gyro-radius smaller than the system's scale is required to maintain zero net current exhausted from the system. Here we experimentally demonstrate that a cross-field transport of the electrons toward the main nozzle axis, which contributes to neutralizing the ions detached from the nozzle, is induced by the spontaneously excited magnetosonic wave having the frequency considerably higher than the ion cyclotron frequency and close to the lower hybrid frequency, driving an E × B drift that only effects the electrons. Wave-induced transport and loss have been one of many important issues in plasma physics over the past several decades. Conversely, the presently observed electron inward transport has a beneficial effect on the detachment by reducing the divergence of the expanding plasma beam; this finding will open a new perspective for the role of waves and instabilities in plasmas.

7.
Sci Rep ; 12(1): 18618, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357485

RESUMO

Innovations for terrestrial transportation technologies, e.g., cars, aircraft, and so on, have driven historical industries so far, and a similar breakthrough is now occurring in space owing to the successful development of electric propulsion devices such as gridded ion and Hall effect thrusters, where solar power is converted into the momentum of the propellant via acceleration of the ionized gases, resulting in a high specific impulse. A magnetic nozzle (MN) radiofrequency (rf) plasma thruster consisting of a low-pressure rf plasma source and a MN is an attractive candidate for a high-power electric propulsion device for spacecraft, as it will provide a long lifetime operation at a high-power level due to the absence of an electrode exposed to the plasma and a high thrust density. The high-density plasma produced in the source is transported along the magnetic field lines toward the open-source exit and the plasma is then spontaneously accelerated in the MN. By ejecting the plasma flow from the system, the reaction forces are exerted to the thruster structure including the source and the MN, and the spacecraft is resultantly propelled. The thruster will open the next door for space technologies, while the performance of the MN rf plasma thruster has been lower than those of the mature electric propulsion devices due to the energy loss to the physical walls. Here the thruster efficiency of about 30%, being the highest to date in this type of thruster, is successfully obtained in the MN rf plasma thruster by locating a cusp magnetic field inside the source, which acts as a virtual magnetic wall isolating the plasma from the source wall. The increase in the thrust by the cusp can be explained by considering the reductions of the loss area and the plasma volume in a thrust analysis combining a global source model and a one-dimensional MN model.

8.
Gan To Kagaku Ryoho ; 49(10): 1136-1138, 2022 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-36281611

RESUMO

We divided the patients with biliary tract cancer who underwent pancreaticoduodenectomy(PD)at our hospital into the 5-year recurrence-free and recurrence groups and investigated the prognostic factors. Additionally, we investigated the efficacy of adjuvant chemotherapy in patients with and without lymph node (LN) metastasis. There was no significant difference between the two groups for patient characteristics and perioperative factors. However, patients with LN metastasis tended to have a higher recurrence rate. For patients without LN metastasis, the median overall survival(OS)was not significantly different between the patients who received and did not receive adjuvant chemotherapy. For patients with LN metastasis, although it was not significantly different(p=0.234), the OS of patients who received adjuvant therapy was more than 3 times than that of patients who did not(58.6 months and 18.4 months, respectively). For patients with biliary tract cancer who underwent PD, positive LN metastasis may be a poor prognostic factor, and adjuvant therapy may possibly improve prognosis.


Assuntos
Neoplasias do Sistema Biliar , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/efeitos adversos , Prognóstico , Pancreatectomia , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/cirurgia , Metástase Linfática
9.
BMC Emerg Med ; 22(1): 30, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35227214

RESUMO

BACKGROUND: It is difficult to predict the return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR). Cerebral tissue oxygen saturation during CPR, as measured by near-infrared spectroscopy (NIRS), is anticipated to predict ROSC. General markers of cerebral tissue oxygen saturation, such as the tissue oxygenation index (TOI), mainly reflect venous oxygenation, whereas pulse-wave cerebral tissue oxygen saturation (SnO2), which represents hemoglobin oxygenation in the pulse wave within the cerebral tissue, is an index of arterial and venous oxygenation. Thus, SnO2 may reflect arterial oxygenation to a greater degree than does TOI. Therefore, we conducted this study to verify our hypothesis that SnO2 measured during CPR can predict ROSC. METHODS: Cardiac arrest patients who presented at the Emergency Department of Yamagata University Hospital in Japan were included in this retrospective, observational study. SnO2 and TOI were simultaneously measured at the patient's forehead using an NIRS tissue oxygenation monitor (NIRO 200-NX; Hamamatsu Photonics, Japan). We recorded the initial, mean, and maximum values during CPR. We plotted receiver operating characteristic curves and calculated the area under the curve (AUC) to predict ROSC. RESULTS: Forty-two patients were included. SnO2 was significantly greater in the ROSC group than in the non-ROSC group in terms of the initial (37.5% vs 24.2%, p = 0.015), mean (44.6% vs 10.8%, p < 0.001), and maximum (79.7% vs 58.4%, p < 0.001) values. Although the initial TOI was not significantly different between the two groups, the mean (45.1% vs 36.8%, p = 0.018) and maximum (71.0% vs 46.3%, p = 0.001) TOIs were greater in the ROSC group than in the non-ROSC group. The AUC was 0.822 for the mean SnO2 (95% confidence interval [CI]: 0.672-0.973; cut-off: 41.8%), 0.821 for the maximum SnO2 (95% CI: 0.682-0.960; cut-off: 70.8%), and 0.809 for the maximum TOI (95% CI: 0.667-0.951; cut-off: 49.3%). CONCLUSION: SnO2 values measured during CPR, including immediately after arrival at the emergency department, were higher in the ROSC group than in the non-ROSC group.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Humanos , Saturação de Oxigênio , Estudos Retrospectivos , Retorno da Circulação Espontânea
10.
J Plant Res ; 135(1): 69-79, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34973093

RESUMO

Assessing long-term changes in the biomass of old-growth forests with consideration of climate effects is essential for understanding forest ecosystem functions under a changing climate. Long-term biomass changes are the result of accumulated short-term changes, which can be affected by endogenous processes such as gap filling in small-scale canopy openings. Here, we used 26 years (1993-2019) of repeated tree census data in an old-growth, cool-temperate, mixed deciduous forest that contains three topographic units (riparian, denuded slope, and terrace) in northern Japan to document decadal changes in aboveground biomass (AGB) and their processes in relation to endogenous processes and climatic factors. AGB increased steadily over the 26 years in all topographic units, but different tree species contributed to the increase among the topographic units. AGB gain within each topographic unit exceeded AGB loss via tree mortality in most of the measurement periods despite substantial temporal variation in AGB loss. At the local scale, variations in AGB gain were partially explained by compensating growth of trees around canopy gaps. Climate affected the local-scale AGB gain: the gain was larger in the measurement periods with higher mean air temperature during the current summer but smaller in those with higher mean air temperature during the previous autumn, synchronously in all topographic units. The influences of decadal summer and autumn warming on AGB growth appeared to be counteracting, suggesting that the observed steady AGB increase in KRRF is not fully explained by the warming. Future studies should consider global and regional environmental factors such as elevated CO2 concentrations and nitrogen deposition, and include cool-temperate forests with a broader temperature range to improve our understanding on biomass accumulation in this type of forests under climate change.


Assuntos
Ecossistema , Florestas , Biomassa , Japão , Árvores
11.
Oncol Rep ; 47(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35029281

RESUMO

Diffuse­type gastric cancer, also known as scirrhous gastric cancer, is characterized by a larger number of stromal cells, referred to as cancer­associated fibroblasts (CAFs), than the number of cancer cells in the tissue. The present study focused on CAFs in gastric cancer and examined their potential as a blood biomarker. A total of 46 and 84 patients with gastric cancer were respectively included in a development and an independent validation cohort to assess the clinicopathological characteristics of plasma podoplanin (PDPN) levels. The prognostic impact of plasma PDPN was also investigated in the validation cohort. The cut­off value of the plasma­PDPN concentration was set to the median plasma PDPN concentration in the development cohort that was then divided into the high­PDPN and low­PDPN groups. The high­PDPN group tended to have more diffuse­type disease (P=0.079), which was further confirmed through logistic regression analysis (P=0.008). Kaplan­Meier survival estimates indicated that the recurrence­free survival rate was significantly lower in the high­PDPN group (P=0.029). In conclusion, plasma soluble PDPN was demonstrated to be a marker for diffuse gastric cancer and may reflect the prognosis of this disease.


Assuntos
Biomarcadores Tumorais/análise , Fibroblastos Associados a Câncer/patologia , Glicoproteínas de Membrana/metabolismo , Neoplasias Gástricas/patologia , Humanos , Prognóstico
12.
Bioconjug Chem ; 33(1): 142-151, 2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-34878263

RESUMO

Trivalent PROTACs having a functionalization site with controlled orientation were designed, synthesized, and evaluated. Based on the X-ray structure of BRD protein degrader MZ1 (1) in complex with human VHL and BRD4BD2, we expected that the 1,2-disubstituted ethyl group near the JQ-1 moiety in MZ1 (1) could be replaced by a planar benzene tether as a platform for further functionalization. To test this hypothesis, we first designed six divalent MZ1 derivatives, 2a-c and 3a-c, by combining three variations of substitution patterns on the benzene ring (1,2-, 1,3-, and 1,4-substitution) and two variations in the number of ethylene glycol units (2 or 1). We then tested the synthesized compounds for the BRD4 degradation activity of each. As expected, we found that 1,2D-EG2-MZ1 (2a), an MZ1 derivative with 1,2-disubstituted benzene possessing two ethylene glycol units, had an activity profile similar to that of MZ1 (1). Based on the structure of 2a, we then synthesized and evaluated four isomeric trivalent MZ1 derivatives, 15a-15d, having a tert-butyl ester unit on the benzene ring as a handle for further functionalization. Among the four isomers, 1,2,5T-EG2-MZ1 (15c) retained a level of BRD4 depletion activity similar to that of 2a without inducing a measurable Hook effect, and its BRD4 depletion kinetics was the same as that of MZ1 (1). Other isomers were also shown to retain BRD4 depletion activity. Thus, the trivalent PROTACs we synthesized here may serve as efficient platforms for further applications.


Assuntos
Proteínas Nucleares
13.
Antiviral Res ; 194: 105165, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34419484

RESUMO

The development of novel antivirals to treat hepatitis B virus (HBV) infection is still needed because currently available drugs do not completely eradicate chronic HBV in some patients. Recently, troglitazone and ciglitazone, classified among the compounds including the thiazolidinedione (TZD) moiety, were found to inhibit HBV infection, but these compounds are not clinically available. In this study, we synthesized 11 TZD derivatives, compounds 1-11, and examined the effect of each compound on HBV infection in HepG2 cells expressing NTCP (HepG2/NTCP cells). Among the derivatives, (Z)-5-((4'-(naphthalen-1-yl)-[1,1'-biphenyl]-4-yl)methylene)thiazolidine-2,4-dione (compound 6) showed the highest antiviral activity, with an IC50 value of 0.3 µM and a selectivity index (SI) of 85, but compound 6 did not affect HCV infection. Treatment with compound 6 inhibited HBV infection in primary human hepatocytes (PHHs) but did not inhibit viral replication in HepG2.2.15 cells or HBV DNA-transfected Huh7 cells. Moreover, treatment with compound 6 significantly impaired hepatitis delta virus (HDV) infection and inhibited a step in HBV particle internalization but did not inhibit attachment of the preS1 lipopeptide or viral particles to the cell surface. These findings suggest that compound 6 interferes with HBV infection via inhibition of the internalization process.


Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Antivirais/síntese química , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/virologia , Humanos , Concentração Inibidora 50 , Tiazolidinedionas/síntese química
14.
Sci Rep ; 11(1): 2768, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531602

RESUMO

Development of a magnetic nozzle radiofrequency (rf) plasma thruster has been one of challenging topics in space electric propulsion technologies. The thruster typically consists of an rf plasma source and a magnetic nozzle, where the plasma produced inside the source is transported along the magnetic field and expands in the magnetic nozzle. An imparted thrust is significantly affected by the rf power coupling for the plasma production, the plasma transport, the plasma loss to the wall, and the plasma acceleration process in the magnetic nozzle. The rf power transfer efficiency and the imparted thrust are assessed for two types of rf antennas exciting azimuthal mode number of [Formula: see text] and [Formula: see text], where propellant argon gas is introduced from the upstream of the thruster source tube. The rf power transfer efficiency and the density measured at the radial center for the [Formula: see text] mode antenna are higher than those for the [Formula: see text] mode antenna, while a larger thrust is obtained for the [Formula: see text] mode antenna. Two-dimensional plume characterization suggests that the lowered performance for the [Formula: see text] mode case is due to the plasma production at the radial center, where contribution on a thrust exerted to the magnetic nozzle is weak due to the absence of the radial magnetic field. Subsequently, the configuration is modified so as to introduce the propellant gas near the thruster exit for the [Formula: see text] mode configuration and the thruster efficiency approaching twenty percent is successfully obtained, being highest to date in the kW-class magnetic nozzle rf plasma thrusters.

15.
Sensors (Basel) ; 21(3)2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33498939

RESUMO

The paper discusses a way to configure a stepped-frequency continuous wave (SFCW) radar using a low-cost software-defined radio (SDR). The most of high-end SDRs offer multiple transmitter (TX) and receiver (RX) channels, one of which can be used as the reference channel for compensating the initial phases of TX and RX local oscillator (LO) signals. It is same as how commercial vector network analyzers (VNAs) compensate for the LO initial phase. These SDRs can thus acquire phase-coherent in-phase and quadrature (I/Q) data without additional components and an SFCW radar can be easily configured. On the other hand, low-cost SDRs typically have only one transmitter and receiver. Therefore, the LO initial phase has to be compensated and the phases of the received I/Q signals have to be retrieved, preferably without employing an additional receiver and components to retain the system low-cost and simple. The present paper illustrates that the difference between the phases of TX and RX LO signals varies when the LO frequency is changed because of the timing of the commencement of the mixing. The paper then proposes a technique to compensate for the LO initial phases using the internal RF loopback of the transceiver chip and to reconstruct a pulse, which requires two streaming: one for the device under test (DUT) channel and the other for the internal RF loopback channel. The effect of the LO initial phase and the proposed method for the compensation are demonstrated by experiments at a single frequency and sweeping frequency, respectively. The results show that the proposed method can compensate for the LO initial phases and ultra-wideband (UWB) pulses can be reconstructed correctly from the data sampled by a low-cost SDR.

16.
Phys Rev Lett ; 125(16): 165001, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33124839

RESUMO

The polytropic index of free electrons expanding in a magnetic nozzle of varying strength is experimentally investigated under a nearly zero electric field, allowing all the electrons to escape to the axial boundary and never return to the source. The measurements clearly demonstrate a continuous change in the polytropic index from adiabatic 5/3 for a strong magnetic field to isothermal unity for a weak magnetic field, showing that the polytropic index depends on the magnetic field strength. It is shown that the cross-field diffusion and the resultant plasma loss out of the magnetic nozzle effectively reduce the polytropic index. The azimuthal current induced in the plasma is diamagnetic, does work on the magnetic nozzle, and contributes to the reduction of the electron internal energy during the expansion.

17.
Rinsho Shinkeigaku ; 60(6): 420-424, 2020 Jun 06.
Artigo em Japonês | MEDLINE | ID: mdl-32435043

RESUMO

A 64-year-old woman visited our hospital with early-onset dementia and progressive gait disturbance. She had demonstrated a mild communication disorder at the age of ~40 years; however, her psychiatric symptoms at that time were mild and were not accompanied by social problems. At the age of 59, she presented with memory loss, visual hallucinations, and delusions. Over the following five years she developed gait difficulties that gradually deteriorated and suffered frequent falls. On admission, neurological examinations revealed severe pyramidal and extrapyramidal signs of akinetic mutism. MRI of the brain showed cerebral atrophy, enlarged lateral ventricles, thinning of the corpus callosum, and leukoencephalopathy in the frontal-parietal lobes. Additionally, CT revealed a small spotty calcification in the frontal subcortical white matter. Genetic analysis revealed a single-base substitution (c.2330G>A/p.R777Q) in exon 18 of the colony stimulating factor 1 receptor (CSF1R) gene, encoding the CSF1R protein. She was diagnosed with hereditary diffuse leukoencephalopathy with spheroids (HDLS). HDLS is included in the differential diagnosis of early-onset dementia and should be considered in patients with mild personality change and abnormal behavior in the early course of the illness.


Assuntos
Doenças dos Gânglios da Base/etiologia , Delusões/etiologia , Alucinações/etiologia , Leucoencefalopatias/complicações , Transtornos da Memória/etiologia , Neuroglia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Calcinose , Diagnóstico Diferencial , Feminino , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Leucoencefalopatias/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mutação , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Fatores de Tempo , Tomografia Computadorizada por Raios X
18.
Sci Rep ; 10(1): 1061, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974470

RESUMO

Most of the artificial low-pressure plasmas contact with physical walls in laboratories; the plasma loss at the wall significantly affects the plasma device performance, e.g., an electric propulsion device. Near the surface of the wall, ions are spontaneously accelerated by a sheath and deliver their momentum and energy to the wall, while most of the electrons are reflected there. The momentum flux of the ions is a vector field, i.e., having both the radial and axial components even if the azimuthal components are neglected in a cylindrical system. Here the spatially- and vector-resolved measurement of the momentum flux near the cylindrical source wall of a magnetic nozzle radiofrequency (rf) plasma thruster configuration is successfully demonstrated by using a momentum vector measurement instrument. The results experimentally identify the spatial profile of a non-negligible axial momentum flux to the wall, while the radially accelerated ions seem to be responsible for the energy loss to the wall. The spatial profiles of the radial and axial momentum fluxes and the energy lost to the wall are significantly affected by the magnetic field strength. The results contribute to understand how and where the momentum and energy in the artificial plasma devices are lost, in addition to the presently tested thruster.

19.
Malar J ; 18(1): 237, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307493

RESUMO

BACKGROUND: Basic blue 3 is a promising anti-malarial lead compound based on the π-delocalized lipophilic cation hypothesis. Its derivatives with nitrogen atoms bonded to carbon atoms at the 3- and 7-positions on the phenoxazine ring were previously shown to exert potent antiprotozoal activity against Plasmodium falciparum, Trypanosoma cruzi, Trypanosoma brucei rhodesiense, and Leishmania donovani parasites in vitro. However, compounds with nitrogen modification at the 10-position on the phenoxazine ring were not evaluated. METHODS: Six acylphenoxazine derivatives (ITT-001 to 006) with nitrogen modification at the 10-position on the phenoxazine ring, which were synthesized from basic blue 3, were characterized and evaluated for anti-malarial activity in vitro with an automated haematology analyzer (XN-30) and light microscopy. Intensity of self-fluorescence was measured using a fluorometer. Localization of basic blue 3 was observed by fluorescence microscopy. Cytotoxicity was evaluated using human cell lines, HEK293T and HepG2 cells. Finally, anti-malarial activity was evaluated in a rodent malaria model. RESULTS: All the six derivatives showed anti-malarial efficacy even against chloroquine-, pyrimethamine-, and artemisinin-resistant field isolates similar to the sensitive strains and isolates in vitro. The efficacy of basic blue 3 was the strongest, followed by that of ITT-001 to 004 and 006, while that of ITT-005 was the weakest. Basic blue 3 showed strong self-fluorescence, whereas ITT derivatives had five- to tenfold lower intensity than that of basic blue 3, which was shown by fluorescence microscopy to be selectively accumulated in the plasmodial cytoplasm. In contrast, ITT-003, 004, and 006 exhibited the lowest cytotoxicity in HEK293T and HepG2 cells in vitro and the highest selectivity between anti-malarial activity and cytotoxicity. The in vivo anti-malarial assay indicated that oral administration of ITT-004 was the most effective against the rodent malaria parasite, Plasmodium berghei NK65 strain. CONCLUSIONS: The six ITT derivatives were effective against chloroquine- and pyrimethamine-resistant strains and artemisinin-resistant field isolates as well as the sensitive ones. Among them, ITT-004, which had high anti-malarial activity and low cytotoxicity in vitro and in vivo, is a promising anti-malarial lead compound.


Assuntos
Antimaláricos/farmacologia , Oxazinas/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/toxicidade , Células HEK293 , Células Hep G2 , Humanos , Oxazinas/toxicidade , Testes de Toxicidade
20.
Anticancer Res ; 39(2): 1013-1018, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30711989

RESUMO

BACKGROUND/AIM: Although perioperative management and operative techniques for pancreatic surgery have improved, postoperative pancreatic fistula (POPF) remains the major cause of morbidity and mortality following distal pancreatectomy (DP). The purpose of this study was to evaluate the superiority of the reinforced stapler compared to the bare triple row stapler. PATIENTS AND METHODS: A total of 93 patients who underwent DP at the First Department of Surgery at Yamanashi University were examined. The patients were divided into two groups according to the closure method for the pancreatic stump; the bare triple-row stapler (BTRS) group and the reinforced triple-row stapler (RTRS) group. The postoperative outcomes were then compared in terms of several clinicopathological factors between the two groups. RESULTS: Seven patients were diagnosed with Grade B/C POPF in this series. The incidence of POPF in the RTRS group was lower than that in the BTRS group (3.6% vs. 13.5%), although there was no significant difference (p=0.077). Further detailed analysis demonstrated that RTRS significantly reduced POPF compared to BTRS in obese patients with a BMI >25.0 kg/m2 (p=0.038). CONCLUSION: Reinforced triple-row staplers may reduce the incidence of severe POPF, especially in obese patients with a BMI >25 kg/m2.


Assuntos
Pancreatectomia/efeitos adversos , Pancreatectomia/instrumentação , Fístula Pancreática/prevenção & controle , Grampeamento Cirúrgico/efeitos adversos , Grampeamento Cirúrgico/instrumentação , Idoso , Índice de Massa Corporal , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/cirurgia , Pancreatectomia/métodos , Fístula Pancreática/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Fatores de Risco , Grampeadores Cirúrgicos
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