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1.
Sensors (Basel) ; 24(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38544245

RESUMO

This paper presents a 5G new radio (NR) FR2 beamforming system with an integrated transceiver module. A real-time operating module providing enhanced flexibility and capability has been proposed. The integrated RF beamforming system with an integrated transceiver module can be operated in 8Tx-8Rx mode configuration simultaneously. A series-fed structure 8 × 7 microstrip antenna array for compact size and improved directivity is employed in the RF beamforming module. The RF beamforming module incorporates a custom 28 GHz, eight-channel fully differential beamforming IC (BFIC). An eight-channel BFIC in a phased-array beamforming system offers advantages in terms of increased antenna density and improved beam steering precision. The RF beamforming module is integrated with an RF transceiver module that enables the simultaneous up-conversion and down-conversion of the baseband signal. The RF transmitter module consists of a transmitter, a receiver, a signal generator, a power supply, and a control unit. The RF beamforming system can scan horizontally from -50° to +50° with a step of 10°. To achieve an optimized beam pattern, a calibration was conducted. The transmit and receive conversion gain of around 20 dB is achieved with the transceiver module. To verify the communication performance of the manufactured integrated RF beamforming system, a real-time wireless video transmission/reception test was performed at a frequency of 28 GHz, and the video file was transmitted smoothly in real time without interruption within a range of ±50°.

2.
Sensors (Basel) ; 24(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38474998

RESUMO

A fully integrated 24-GHz radar transceiver with one transmitter (TX) and two receivers (RXs) for compact frequency modulated continuous wave (FMCW) radar applications is here presented. The FMCW synthesizer was realized using a fractional-N phase-locked loop (PLL) and programmable chirp generator, which are completely integrated in the proposed transceiver. The measured output phase noise of the synthesizer is -80 dBc/Hz at 100 kHz offset. The TX consists of a three-bit bridged t-type attenuator for gain control, a two-stage drive amplifier (DA) and a one-stage power amplifier (PA). The TX chain provides an output power of 13 dBm while achieving <0.5 dB output power variation within the range of 24 to 24.25 GHz. The RX with a direct conversion I-Q structure is composed of a two-stage low noise amplifier (LNA), I-Q generator, mixer, transimpedance amplifier (TIA), a two-stage biquad band pass filter (BPF), and a differential-to-single (DTS) amplifier. The TIA and the BPF employ a DC offset cancellation (DCOC) circuit to suppress the strong reflection signal and TX-RX leakage. The RX chain exhibits an overall gain of 100 dB. The proposed radar transceiver is fabricated using a 65 nm CMOS technology. The transceiver consumes 220 mW from a 1 V supply voltage and has 4.84 mm2 die size including all pads. The prototype FMCW radar is realized with the proposed transceiver and Yagi antenna to verify the radar functionality, such as the distance and angle of targets.

3.
Sensors (Basel) ; 23(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36772379

RESUMO

With the advent of the Internet of Things (IoT) era, a wide array of wireless sensors supporting the IoT have proliferated. As key elements for enabling the IoT, wireless sensor nodes require minimal energy consumption and low device complexity. In particular, energy-efficient resource scheduling is critical in maintaining a network of wireless sensor nodes, since the energy-intensive processing of wireless sensor nodes and their interactions is too complicated to control. In this study, we present a practical deep Q-network (DQN)-based packet scheduling algorithm that coordinates the transmissions of multiple IoT devices. The scheduling algorithm dynamically adjusts the connection interval (CI) and the number of packets transmitted by each node within the interval. Through various experiments, we verify how effectively the proposed scheduler improves energy efficiency and handles the time-varying nature of the network environment. Moreover, we attempt to gain insight into the optimized packet scheduler by analyzing the policy of the DQN scheduler. The experimental results show that the proposed scheduling algorithm can further prolong a network's lifetime in a dynamic network environment in comparison with that in other alternative schemes while ensuring the quality of service (QoS).

4.
Sensors (Basel) ; 23(15)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37571609

RESUMO

This paper presents a wideband 4-bit true time delay IC using a 0.25 µm GaN HEMT (High-Electron-Mobility Transistor) process for the beam-squint-free phased array antennas. The true time delay IC is implemented with a switched path circuit topology using DPDT (Double Pole Double Throw) with no shunt transistor in the inter-stages to improve the bandwidth and SPDT (Single Pole Single Throw) switches at the input and the output ports. The delay lines are implemented with CLC π-networks with the lumped element to ensure a compact chip size. A negative voltage generator and an SPI controller are implemented in the PCB (Printed Circuit Board) due to the lack of digital control logic in GaN technology. A maximum time delay of ~182 ps with a time delay resolution of 10.5 ps is achieved at DC-6 GHz. The RMS (Root Mean Square) time delay and amplitude error are <5 ps and <0.6 dB, respectively. The measured insertion loss is <6.8 dB and the input and output return losses are >10 dB at DC-6 GHz. The current consumption is nearly zero with a 3.3 V supply. The chip size including pads is 2.45 × 1.75 mm2. To the authors' knowledge, this is the first demonstration of a true time delay IC using GaN HEMT technology.

5.
Sensors (Basel) ; 23(13)2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37447973

RESUMO

A 28 GHz fully differential eight-channel beamforming IC (BFIC) with multimode operations is implemented in 65 nm CMOS technology for use in phased array transceivers. The BFIC has an adjustable gain and phase control on each channel to achieve fine beam steering and beam pattern. The BFIC has eight differential beamforming channels each consisting of the two-stage bi-directional amplifier with a precise gain control circuit, a six-bit phase shifter, a three-bit digital step attenuator, and a tuning bit for amplitude and phase variation compensation. The Tx and Rx mode overall gains of the differential eight-channel BFIC are around 11 dB and 9 dB, respectively, at 27.0-29.5 GHz. The return losses of the Tx mode and Rx mode are >10 dB at 27.0-29.5 GHz. The maximum phase of 354° with a phase resolution of 5.6° and the maximum attenuation of 31 dB, including the gain control bits with an attenuation resolution of 1 dB, is achieved at 27.0-29.5 GHz. The root mean square (RMS) phase and amplitude errors are <3.2° and <0.6 dB at 27.0-29.5 GHz, respectively. The chip size is 3.0 × 3.5 mm2, including pads, and Tx mode current consumption is 580 mA at 2.5 V supply voltage.


Assuntos
Amplificadores Eletrônicos , Tecnologia sem Fio , Desenho de Equipamento , Tecnologia , Carmustina
6.
Korean J Parasitol ; 60(1): 25-34, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35247951

RESUMO

Alveolar echinococcosis (AE) caused by infection with E. multilocularis metacestode, represents one of the most fatal helminthic diseases. AE is principally manifested with infiltrative, proliferating hepatic mass, resembling primary hepatocellular carcinoma. Sometimes metastatic lesions are found in nearby or remote tissue. AE diagnosis largely depends on imaging studies, but atypical findings of imaging features frequently require differential diagnosis from other hepatic lesions. Serological tests may provide further evidence, while obtaining reliable AE materials is not easy. In this study, alternative antigens, specific to AE were identified by analyzing E. granulosus protoscolex proteins. An immunoblot analysis of E. granulosus protoscolex showed that a group of low-molecular-weight proteins in the range from 14 kDa to 16 kDa exhibited a sensitive and specific immune response to AE patient sera. Partial purification and proteomic analysis indicated that this protein group contained myosin, tubulin polymerization promoting protein, fatty-acid binding protein, uncharacterized DM9, heat shock protein 90 cochaperone tebp P-23, and antigen S. When the serological applicability of recombinant forms of these proteins was assessed using enzyme-linked immunosorbent assay, DM9 protein (rEgDM9) showed 90.1% sensitivity (73/81 sera tested) and 94.5% specificity (172/181 sera tested), respectively. rEgDM9 showed weak cross-reactions with patient sera from the transitional and chronic stages of cystic echinococcosis (3 to 5 stages). rEgDM9 would serve as a useful alternative antigen for serodiagnosis of both early- and advanced-stage AE cases.


Assuntos
Carcinoma Hepatocelular , Equinococose , Echinococcus granulosus , Neoplasias Hepáticas , Animais , Anticorpos Anti-Helmínticos , Antígenos de Helmintos , Equinococose/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Proteômica , Sensibilidade e Especificidade , Testes Sorológicos
7.
Sensors (Basel) ; 21(7)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917332

RESUMO

An 18.8-33.9 GHz, 2.26 mW current-reuse (CR) injection-locked frequency divider (ILFD) for radar sensor applications is presented in this paper. A fourth-order resonator is designed using a transformer with a distributed inductor for wideband operating of the ILFD. The CR core is employed to reduce the power consumption compared to conventional cross-coupled pair ILFDs. The targeted input center frequency is 24 GHz for radar application. The self-oscillated frequency of the proposed CR-ILFD is 14.08 GHz. The input frequency locking range is from 18.8 to 33.8 GHz (57%) at an injection power of 0 dBm without a capacitor bank or varactors. The proposed CR-ILFD consumes 2.26 mW of power from a 1 V supply voltage. The entire die size is 0.75 mm × 0.45 mm. This CR-ILFD is implemented in a 65 nm complementary metal-oxide semiconductor (CMOS) technology.

8.
Sensors (Basel) ; 19(1)2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30621117

RESUMO

In recent years, wireless multimedia sensor networks (WMSNs) have emerged as a prominent technique for delivering multimedia information such as still images and videos. Being under the great spotlight of research communities, however, multimedia delivery over resourceconstraint WMSNs poses great challenges, especially in terms of energy efficiency and quality-ofservice (QoS) guarantees. In this paper, recent developments in techniques for designing highly energy-efficient and QoS-capable WMSNs are surveyed. We first study the unique characteristicsand the relevantly imposed requirements of WMSNs. For each requirement we also summarize their existing solutions. Then we review recent research efforts on energy-efficient and QoS-awarecommunication protocols, including MAC protocols, with a focus on their prioritization and service differentiation mechanisms and disjoint multipath routing protocols.

9.
Proteomics ; 18(7): e1700341, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29409117

RESUMO

The obligatory intracellular protozoan parasite Entamoeba histolytica causes amebic dysentery and liver abscess. E. histolytica adheres to the host tissues in a contact-dependent manner. E. histolytica excretory-secretory products (ESP) might play critical roles during invasion. We comparatively analyzed the secretome profile of E. histolytica pathogenic HM-1:IMSS and non-pathogenic Rahman strains. The two ESP revealed similar but distinct spotting patterns. In both ESP, alcohol dehydrogenase, enolase 1, and transketolase, which control classical carbohydrate metabolism and other moonlighting effects, constituted the most abundant fractions. We recognized differently secreted molecules. Secretion of cytoskeletal organization proteins (actin, actin binding protein, and EHI_068510), protein remodeling amino peptidase, and multifunctional elongation factor 1-α were increased in Rahman. Conversely, carbohydrate metabolizing enolase 1, alcohol dehydrogenase, transketolase, calponin, phosphoglucose mutase, malic enzyme and EHI_156420, xenobiotic scavenging superoxide dismutase and EHI_140740, and pyruvate:ferredoxin oxidoreductase and coronin (carbohydrate metabolism/detoxification) showed reduced secretion. Transcription levels of some genes involved in these processes also decreased. Changes of secretory behavior, especially decreased secretion of multifunctional carbohydrate metabolizing enzymes and detoxifying proteins that importantly participated in amoeba pathogenesis might reflect avirulent nature of Rahman strain in the host.


Assuntos
Entamoeba histolytica/metabolismo , Entamoeba histolytica/patogenicidade , Proteínas de Protozoários/genética , Entamoeba histolytica/genética , Regulação da Expressão Gênica , Proteômica , Análise de Sequência de Proteína , Virulência
10.
J Korean Med Sci ; 33(44): e273, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30369856

RESUMO

BACKGROUND: Sparganosis is a larval cestodiasis caused by the plerocercoid of Spirometra spp. Since the first description of human sparganosis in 1924, several hundred cases have been reported in Korea. However, systematic approaches for literature surveys of Korean sparganosis have seldom appeared. METHODS: We searched publicly available databases such as PubMed, Research Information Sharing Service, and Korea Medical Citation Index with relevant Medical Subject Headings. RESULTS: At least 438 Korean sparganosis cases have been described from 1924 to 2015. Preoperative diagnosis has been significantly increased since the 1980s due to popularization of serological and imaging diagnostics. Cases were largely detected from fifth decades in general, but cerebral sparganosis was detected in relatively young age groups (third and fourth decades). Sparganosis was prevalent in men (75.9%). Consumption of frog/snake and drinking unfiltered water were found in 63.4% and 16.9% of patients, respectively. Most frequently affected sites were subcutaneous tissues (49.9%), followed by the central nervous system (36.2%). Involvements of visceral organs (7.6%), ocular regions (3.6%), and muscles (2.7%) were noticed. In women, breast sparganosis constituted a large proportion (34.2%). Sparganosis associated with immunocompromised patients has recently been reported. CONCLUSION: Sparganosis has been continuously reported in Korea during the past 90 years, although its incidence has decreased during the last 20 years. The disease is mostly characterized by subcutaneous nodule, but infection of the worm in vital organs often results in serious illness. Continuous awareness is warranted to monitor sparganosis occurrence and associated clinical consequences.


Assuntos
Esparganose/diagnóstico , Esparganose/epidemiologia , Spirometra , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prevalência , República da Coreia/epidemiologia , Água/parasitologia , Adulto Jovem
11.
Sensors (Basel) ; 18(4)2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29614777

RESUMO

Recently, studies have been actively carried out to implement motion detecting sensors by applying radar techniques. Doppler radar or frequency-modulated continuous wave (FMCW) radar are mainly used, but each type has drawbacks. In Doppler radar, no signal is detected when the movement is stopped. Also, FMCW radar cannot function when the detection object is near the sensor. Therefore, by implementing a single continuous wave (CW) radar for operating in dual-mode, the disadvantages in each mode can be compensated for. In this paper, a dual mode local oscillator (LO) is proposed that makes a CW radar operate as a Doppler or FMCW radar. To make the dual-mode LO, a method that controls the division ratio of the phase locked loop (PLL) is used. To support both radar mode easily, the proposed LO is implemented by adding a frequency sweep generator (FSG) block to a fractional-N PLL. The operation mode of the LO is determined by according to whether this block is operating or not. Since most radar sensors are used in conjunction with microcontroller units (MCUs), the proposed architecture is capable of dual-mode operation by changing only the input control code. In addition, all components such as VCO, LDO, and loop filter are integrated into the chip, so complexity and interface issues can be solved when implementing radar sensors. Thus, the proposed dual-mode LO is suitable as a radar sensor.

12.
J Proteome Res ; 16(2): 806-823, 2017 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-27959569

RESUMO

Alveolar echinococcosis (AE) caused by Echinococcus multilocularis metacestode is frequently associated with deleterious zoonotic helminthiasis. The growth patterns and morphological features of AE, such as invasion of the liver parenchyme and multiplication into multivesiculated masses, are similar to those of malignant tumors. AE has been increasingly detected in several regions of Europe, North America, Central Asia, and northwestern China. An isoform of E. multilocularis antigen B3 (EmAgB3) shows a specific immunoreactivity against patient sera of active-stage AE, suggesting that EmAgB3 might play important roles during adaptation of the parasite to hosts. However, expression patterns and biochemical properties of EmAgB3 remained elusive. The protein profile and nature of component proteins of E. multilocularis hydatid fluid (EmHF) have never been addressed. In this study, we conducted proteome analysis of EmHF of AE cysts harvested from immunocompetent mice. We observed the molecular and biochemical properties of EmAgB3, including differential transcription patterns of paralogous genes, macromolecular protein status by self-assembly, distinct oligomeric states according to individual anatomical compartments of the worm, and hydrophobic ligand-binding protein activity. We also demonstrated tissue expression patterns of EmAgB3 transcript and protein. EmAgB3 might participate in immune response and recruitment of essential host lipids at the host-parasite interface. Our results might contribute to an in depth understanding of the biophysical and biological features of EmAgB3, thus providing insights into the design of novel targets to control AE.


Assuntos
Equinococose Hepática/imunologia , Echinococcus multilocularis/imunologia , Proteínas de Helminto/imunologia , Interações Hospedeiro-Parasita , Lipoproteínas/imunologia , Proteoma/imunologia , Adaptação Fisiológica/genética , Adaptação Fisiológica/imunologia , Animais , Clonagem Molecular , Modelos Animais de Doenças , Equinococose , Equinococose Hepática/genética , Equinococose Hepática/parasitologia , Equinococose Hepática/patologia , Echinococcus multilocularis/crescimento & desenvolvimento , Echinococcus multilocularis/patogenicidade , Escherichia coli/genética , Escherichia coli/metabolismo , Feminino , Expressão Gênica , Regulação da Expressão Gênica , Proteínas de Helminto/genética , Homeostase/genética , Homeostase/imunologia , Humanos , Lipoproteínas/genética , Camundongos , Ácido Oleico/metabolismo , Proteoma/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
13.
J Clin Microbiol ; 54(10): 2553-62, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27487955

RESUMO

Larval Taeniidae, such as metacestodes of Taenia solium, Echinococcus granulosus, and Echinococcus multilocularis, produce chronic and fatal helminthic diseases. Proper identification of these zoonotic cestodiases is often challenging and is hampered in some clinical settings. Endophilin B1 plays critical roles in the maintenance of membrane contours and endocytosis. We isolated proteins homologous to endophilin B1 from T. solium, Taenia saginata, and Taenia asiatica The three Taeniidae endophilin B1 proteins shared 92.9 to 96.6% sequence identity. They harbored a Bin1/amphiphysin/Rvs (BAR) domain and residues for a dimeric interface but lacked a SRC homology 3 (SH3) domain. Endophilin B1 showed a unique immunological profile and was abundantly expressed in the tegumental syncytium of Taeniidae metacestodes and adults. Bacterially expressed recombinant T. solium endophilin B1 (rTsMEndoB1) demonstrated a sensitivity of 79.7% (345/433 cases) for serodiagnosis of larval Taeniidae infections. The protein showed strong immune recognition patterns against sera from patients with chronic neurocysticercosis, cystic echinococcosis, or advanced-stage alveolar echinococcosis. Adult Taeniidae infections exhibited moderate degrees of positive antibody responses (65.7% [23/35 samples]). rTsMEndoB1 showed some cross-reactivity with sera from patients infected with Diphyllobothriidae (23.6% [25/106 samples]) but not with sera from patients with other parasitic diseases or normal controls. The specificity was 91.7% (256/301 samples). The positive and negative predictive values were 93.6% and 73.4%, respectively. Our results demonstrate that Taeniidae endophilin B1 may be involved in the control of membrane dynamics, thus contributing to shaping and maintaining the tegumental curvature. rTsMEndoB1 may be useful for large-scale screening, as well as for individual diagnosis and follow-up surveillance of Taeniidae infections.


Assuntos
Aciltransferases/biossíntese , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/biossíntese , Perfilação da Expressão Gênica , Imunoensaio/métodos , Taenia/imunologia , Teníase/diagnóstico , Aciltransferases/genética , Aciltransferases/imunologia , Animais , Antígenos de Helmintos/genética , Antígenos de Helmintos/imunologia , Humanos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Análise Espaço-Temporal
14.
Bioorg Med Chem Lett ; 26(13): 3148-3152, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27173797

RESUMO

We have previously reported amidopiperidine derivatives as a novel peptide deformylase (PDF) inhibitor and evaluated its antibacterial activity against Gram-positive bacteria, but poor pharmacokinetic profiles have resulted in low efficacy in in vivo mouse models. In order to overcome these weaknesses, we newly synthesized aminopiperidine derivatives with remarkable antimicrobial properties and oral bioavailability, and also identified their in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and penicillin-resistant Streptococcus pneumoniae (PRSP).


Assuntos
Antibacterianos/farmacologia , Inibidores Enzimáticos/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Piperidinas/farmacologia , Administração Oral , Amidoidrolases/antagonistas & inibidores , Amidoidrolases/metabolismo , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Bactérias Gram-Positivas/enzimologia , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piperidinas/administração & dosagem , Piperidinas/química , Relação Estrutura-Atividade
15.
J Clin Microbiol ; 53(10): 3310-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26269620

RESUMO

Alveolar echinococcosis (AE), caused by the Echinococcus multilocularis metacestode, represents one of the most frequently fatal zoonoses. Early diagnosis significantly reduces morbidity and mortality associated with AE. Diagnosis of AE largely depends on a combination of imaging and serological tests due to its minimal clinical manifestations. Several antigens derived from the whole worm and protoscolex have been targeted for AE serodiagnosis, while the antigenic properties of E. multilocularis hydatid fluid (EmHF) are unclear. We observed two AE-specific 6- and 8-kDa antigen proteoforms through an immunoproteome array of the EmHF. We identified these proteins as representing an E. multilocularis antigen B3 (EmAgB3) isoform, and the proteins were shown to be encoded by the same gene. We cloned the gene and expressed the recombinant EmAgB3 protein (rEmAgB3) in Escherichia coli. rEmAgB3 exhibited sensitivity of 90.9% (80/88 cases) and specificity of 98.5% (597/606 samples) by immunoblotting. The positive and negative predictive values were 89.9% and 98.6%, respectively. The protein did not show antibody responses to 33 AE sera collected during posttreatment follow-up monitoring. Mouse sera experimentally infected with AE protoscoleces began to demonstrate specific antibody responses to native and recombinant EmAgB3 6 months after infection. At that stage, fully mature metacestode vesicles that harbored the brood capsule, primary cell, and protoscolex were observed within an AE mass(es). The response declined along with worm degeneration. Our results demonstrate that the immune responses to this EmAgB3 isoform were highly correlated with worm viability accompanied with AE progression. rEmAgB3 is a promising biomarker for serological assessment of AE patients.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Equinococose Hepática/diagnóstico , Echinococcus multilocularis/imunologia , Adolescente , Adulto , Idoso , Animais , Criança , Equinococose , Equinococose Hepática/imunologia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
16.
Antioxidants (Basel) ; 12(3)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36978808

RESUMO

Pathogenic helminths have evolved mechanisms to preserve reproductive function while surviving long-term in the host via robust protective responses. A protective role of antioxidant enzymes in preventing DNA degradation has long been proposed, but little evidence has been provided. Here, we show that omega-class glutathione transferases (GSTOs) are critical for maintaining viability by protecting the reproductive cell DNA of the carcinogenic liver fluke, Clonorchis sinensis. Clonorchis sinensis GSTO (CsGSTO) activities modified by changes in the GSH/GSSG and NADPH/NADP+ molar ratios suppressed the overproduction of reactive oxygen species. CsGSTO1 and CsGSTO2 catalyzed deglutathionylation under physiologic and low-stress conditions (GSH/GSSG ratio of 6:1 or higher) but promoted glutathionylation under high-stress conditions (GSH/GSSG ratio of 3:1 or lower). Gliotoxin-induced functional disruption of CsGSTOs in living C. sinensis reduced the GSH/GSSG molar ratio and increased the production of protein glutathionylation (PSSG) under physiologic and low-stress conditions, indicating that suppression of GSTO function did not affect deglutathionylation. However, the perturbation of CsGSTOs decreased the GSH/GSSG ratio but also reduced PSSG production under high oxidative stress, demonstrating that glutathionylation was impeded. In response to oxidative stimuli, C. sinensis decreased GSTO-specific dehydroascorbate reductase and thiol transferase activities and the GSH/GSSG ratio, while it increased the NADPH/NADP+ ratio and PSSG. CsGSTOs utilized GSH to regulate GSH/GSSG and NADPH/NADP+ recycling and triggered a redox signal leading to nuclear translocation. Nuclear-imported CsGSTOs were modified by glutathionylation to prevent DNA damage. Antibodies specific to CsGSTOs dose-dependently inhibited this process. Disruption of CsGSTOs or the depletion of GSH caused glutathionylation defects, leading to DNA degradation. Our results demonstrate that CsGSTOs and the GSH system play a previously unappreciated role in protecting DNA from oxidative stress.

17.
PLoS Negl Trop Dis ; 16(3): e0010240, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35294433

RESUMO

Cerebral paragonimiasis (CP), caused by aberrant migration of Paragonimus worms, frequently invokes serious illness. The causal relationship between the lesion characteristics and patients' symptoms has poorly been understood. CP serodiagnosis has not been properly evaluated to date. A total of 111 CP cases were diagnosed in our laboratory between 1982 and 2003. This study retrospectively assessed the clinical and imaging characteristics of the 105 patients along with the evaluation of diagnostic potentials of recombinant P. westermani yolk ferritin (rPwYF) by enzyme-linked immunosorbent assay (ELISA) employing patients' sera and cerebrospinal fluids (CSFs). We analyzed 60 male and 45 female patients; 50 early-stage patients with non-calcified enhancing nodule(s) (median age, 38 years; interquartile range [IQR], 24.75-52; median symptom duration, 0.75 years; IQR, 0.2-2) and 54 chronic cases having calcified lesion(s) (median age, 33 years; IQR, 25-41; median symptom duration, 10 years; IQR, 5-20). One patient showed a normal neuroimage. The patients were largely diagnosed in their 30s. The parietal lobe was most commonly affected, followed by occipital, frontal, and temporal lobes. Twenty-six patients had lesions encompassing ≥ two lobes. The patients complained mainly of seizures, headaches, hemiparesis, and focal neurologic deficits (P < 0.001). Seizures and visual defects were predominant in patients with calcified lesion(s) (P < 0.001). The diagnostic sensitivity and specificity of rPwYF against serum/CSF were 100%/97% and 97.2%/92.5%, respectively. The specific IgG antibody levels against rPwYF in sera and CSFs showed a positive correlation (r = 0.59). The clinical manifestations of the early-stage patients might be associated with cortical lesions or meningeal irritation, while those in the chronic stage were caused by conglomerated space-occupying lesions. rPwYF would be useful for the serodiagnosis of both early and chronic CP cases.


Assuntos
Paragonimíase , Paragonimus , Animais , Anticorpos Anti-Helmínticos , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Ferritinas , Humanos , Masculino , Paragonimíase/diagnóstico , Estudos Retrospectivos , Convulsões , Testes Sorológicos
18.
J Transl Med ; 9: 181, 2011 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-22017805

RESUMO

Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs) of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here.


Assuntos
Tecido Adiposo/citologia , Doenças Autoimunes/terapia , Técnicas de Cultura de Células/métodos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Adulto , Idoso , Animais , Proliferação de Células , Ensaios de Uso Compassivo , Humanos , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Transplante Autólogo , Adulto Jovem
19.
Antioxidants (Basel) ; 10(7)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202740

RESUMO

The small liver fluke Clonorchis sinensis causes hepatobiliary ductal infections in humans. Clonorchiasis is characterized histopathologically by ductal dysplasia, hyperplasia and metaplasia, which closely resembles cholangiocarcinoma (CCA). The disruption of programmed cell death is critical for malignant transformation, while molecular events underlying these phenomena have poorly been understood in clonorchiasis-related CCA tumorigenesis. We incorporated recombinant C. sinensis omega-class glutathione transferase (rCsGSTo) 1 or 2 into human intrahepatic biliary epithelial cells (HIBECs) and analyzed pathophysiological alterations of HIBECs upon the application of oxidative stress. rCsGSTos partially but significantly rescued HIBECs from cell death by inhibiting oxidative stress-induced apoptosis (p < 0.01). rCsGSTos modulated transcriptional levels of numerous genes. We analyzed 13 genes involved in programmed cell death (the upregulation of five antiapoptotic and two apoptotic genes, and the downregulation of one antiapoptotic and five apoptotic genes) and 11 genes associated with cell differentiation (the increase in seven and decrease in four genes) that showed significant modifications (p < 0.05). The induction profiles of the mRNA and proteins of these differentially regulated genes correlated well with each other, and mostly favored apoptotic suppression and/or cell differentiation. We detected increased active, phosphorylated forms of Src, PI3K/Akt, NF-κB p65, MKK3/6 and p38 MAPK, but not JNK and ERK1/2. CsGSTos were localized in the C. sinensis-infected rat cholangiocytes, where cytokeratin 19 was distributed. Our results demonstrated that CsGSTos excreted to the biliary lumen are internalized and accumulated in the host cholangiocytes. When cholangiocytes underwent oxidative stressful condition, CsGSTos appeared to be critically involved in both antiapoptotic process and the differentiation of host cholangiocytes through the regulation of target genes following the activation of responsible signal molecules.

20.
J Infect ; 82(1): 150-158, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33017628

RESUMO

OBJECTIVES: Paragonimiasis is a global foodborne zoonosis. Overlapping clinical and imaging features with other lung pathologies hamper correct diagnosis and require differential diagnosis. METHODS: During 1982-2003, 49,012 samples were referred for immunodiagnosis of helminthiases. We detected paragonimiasis cases by enzyme-linked immunosorbent assay (ELISA). We assessed clinical, radiographical and laboratory characteristics, and diagnostic dilemmas associated with delayed diagnosis. RESULTS: We analyzed 685 pleuropulmonary paragonimiasis cases. ELISA-positive was 665. Eggs were detected in 50. Symptom duration correlated well with the appearance of chest radiographs; 359 pleural, 33 pleuroparenchymal, and 264 parenchymal lesions (P < 0.001). Twenty-nine had normal chest images. Eosinophilia, seen in 304, was common in pleural and pleuroparenchymal patients (P < 0.05). Chest pain and dyspnea were characteristic for pleurisy patients. Sputum (odds ratios [OR]: 6.79; 95% CI: 4.41-10.47), blood-tinged sputum (OR: 5.62; 95% CI: 3.75-8.42), and foul-odor (OR: 2.70; 95% CI: 1.42-5.16) were significant in parenchymal patients. Delayed diagnosis (119) for ≥ 25 weeks was attributed mainly to misdiagnosis as tuberculosis, malignancy, or chronic obstructive pulmonary disease (COPD) (OR: 111.75; 95% CI: 43.25-288.74). CONCLUSIONS: Variable symptoms and radiographs of pleuropulmonary paragonimiasis depended on the stage of infection. Suspicion of tuberculosis, malignancy, or COPD was major cause of delayed diagnosis.


Assuntos
Eosinofilia , Paragonimíase , Tuberculose , Humanos , Paragonimíase/diagnóstico por imagem , Paragonimíase/epidemiologia , Pleura , Escarro
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