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In Jeju Island, South Korea, a patient who consumed raw pig products had subdural empyema, which led to meningitis, sepsis, and status epilepticus. We identified Streptococcus suis from blood and the subdural empyema. This case illustrates the importance of considering dietary habits in similar clinical assessments to prevent misdiagnosis.
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Empiema Subdural , Sepsis , Infecciones Estreptocócicas , Streptococcus suis , Humanos , Animales , Porcinos , Empiema Subdural/diagnóstico , Streptococcus suis/genética , República de Corea , Conducta Alimentaria , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/tratamiento farmacológicoRESUMEN
BACKGROUND: Group B Streptococcus (GBS) causes invasive infections in newborns and elderly individuals, but is a noninvasive commensal bacterium in most immunocompetent people. Recently, the incidence of invasive GBS infections has increased worldwide, and there is growing interest in the molecular genetic characteristics of invasive GBS strains. Vaccines against GBS are expected in the near future. Here, we aimed to analyze the molecular epidemiology of GBS according to the invasiveness in South Korea. METHODS: We analyzed GBS isolates collected and stored in two hospitals in South Korea between January 2015 and December 2020. The invasiveness of these isolates was determined via a retrospective review of clinical episodes. Totally, 120 GBS isolates from 55 children and 65 adults were analyzed. Serotype and sequence type (ST) were determined using multiplex polymerase chain reaction (PCR) and multilocus sequence typing, respectively. Fourteen virulence factor-encoding genes of GBS were analyzed using multiplex PCR. RESULTS: Forty one (34.2%) were invasive infection-related GBS isolates (iGBS). The most frequently detected serotype was III (39/120, 32.5%), and it accounted for a high proportion of iGBS (21/41, 51.2%). The most frequent ST was ST19 (18/120, 15.0%), followed by ST2 (17/120, 14.2%). Serotype III/ST17 was predominant in iGBS (12/41, 29.3%), and all 17 ST2 strains were noninvasive. The distribution of most of the investigated virulence factors was not significantly related to invasiveness; noteworthily, most of the serotype III/ST17 iGBS carried pilus island (PI) 2b (10/12, 83.3%), and the prevalence of fbsB was significantly low compared with noninvasive GBS isolates (P = 0.004). Characteristically, the combination of bca(+)-cspA(+)-pavA(+)-fbsB(-)-rib(+)-bac(-) was predominant in iGBS (24.4%, 10/41). CONCLUSIONS: Serotype III/ST17 GBS carrying PI-2b was frequently detected in iGBS. There was no significant association between invasiveness and the pattern of virulence factors; however, a specific combination of virulence factors was predominant in iGBS.
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Epidemiología Molecular , Tipificación de Secuencias Multilocus , Serogrupo , Infecciones Estreptocócicas , Streptococcus agalactiae , Factores de Virulencia , Humanos , República de Corea/epidemiología , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , Factores de Virulencia/genética , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidad , Streptococcus agalactiae/clasificación , Streptococcus agalactiae/aislamiento & purificación , Adulto , Estudios Retrospectivos , Niño , Femenino , Masculino , Preescolar , Persona de Mediana Edad , Anciano , Reacción en Cadena de la Polimerasa Multiplex , Lactante , Adulto Joven , Adolescente , Recién NacidoRESUMEN
Whipple's disease caused by Tropheryma whipplei is difficult to diagnose because of a broad spectrum of manifestations and non-specific clinical signs. In the current global era, the incidence of duodenal infection/inflammation caused by T. whipplei in Korea may has been underestimated. Here we estimated the prevalence of T. whipplei in duodenal biopsy tissues of Koreans using real-time PCRs (RT-PCRs). A total of 252 duodenal biopsy tissues were collected from Korean patients who underwent esophagogastroduodenoscopy and duodenal biopsy. DNA extracted from the duodenal biopsy tissues was analyzed using three RT-PCRs targeting T. whipplei-specific regions of the 16S-23S rRNA intergenic spacer, hsp65, and Dig15 in parallel. In the samples positive in RT-PCRs, direct sequencing was performed for each RT-PCR target. The prevalence of T. whipplei was estimated based on the RT-PCR and sequencing results. Among the analyzed samples, T. whipplei was not detected. The prevalence of T. whipplei in duodenal biopsy tissues of Koreans was estimated to be less than 0.4%. This is the first study to attempt to detect T. whipplei in duodenal biopsy tissues of Koreans and estimate its prevalence. Our findings infer that while T. whipplei carriers exist in Korea, the incidence of duodenal infection/inflammation caused by T. whipplei is extremely rare.
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Inflamación , Tropheryma , Humanos , Tropheryma/genética , Prevalencia , Biopsia , República de Corea/epidemiologíaRESUMEN
The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein-protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs, deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, the mixture of three herbs had a combinational effect. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFA-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.
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BACKGROUND: We aimed to assess the trends in urinary tract infections (UTIs) and prognosis of patients with prostate cancer after radical prostatectomy (RP) and radiation therapy (RT) as definitive treatment options. METHODS: The data of patients diagnosed with prostate cancer between 2007 and 2016 were collected from the National Health Insurance Service database. The incidence of UTIs was evaluated in patients treated with RT, open/laparoscopic RP, and robot-assisted RP. The proportional hazard assumption test was performed using the scaled Schoenfeld residuals based on a multivariable Cox proportional hazard model. Kaplan-Meier analysis were performed to assess survival. RESULTS: A total of 28,887 patients were treated with definitive treatment. In the acute phase (< 3 months), UTIs were more frequent in RP than in RT; in the chronic phase (> 12 months), UTIs were more frequent in RT than in RP. In the early follow-up period, the risk of UTIs was higher in the open/laparoscopic RP group (aHR, 1.63; 95% CI, 1.44-1.83; p < 0.001) and the robot-assisted RP group (aHR, 1.26; 95% CI, 1.11-1.43; p < 0.001), compared to the RT group. The robot-assisted RP group had a lower risk of UTIs than the open/laparoscopic RP group in the early (aHR, 0.77; 95% CI, 0.77-0.78; p < 0.001) and late (aHR, 0.90; 95% CI, 0.89-0.91; p < 0.001) follow-up periods. In patients with UTI, Charlson Comorbidity Index score, primary treatment, age at UTI diagnosis, type of UTI, hospitalization, and sepsis from UTI were risk factors for overall survival. CONCLUSIONS: In patients treated with RP or RT, the incidence of UTIs was higher than that in the general population. RP posed a higher risk of UTIs than RT did in early follow-up period. Robot-assisted RP had a lower risk of UTIs than open/laparoscopic RP group in total period. UTI characteristics might be related to poor prognosis.
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Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Infecciones Urinarias , Masculino , Humanos , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Prostatectomía/efectos adversos , Pronóstico , Procedimientos Quirúrgicos Robotizados/efectos adversos , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiología , Infecciones Urinarias/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVES: We compared the performance of a new interferon gamma release assay (IGRA) format assay, the ichroma™ COVID-19 IGRA (IGRA-SARS), with that of the widely used QuantiFERON SARS-CoV-2 ELISA kit (QFN-SARS) in vaccinated healthcare workers (HCWs). Additionally, we analyzed the long-term changes in IGRA results after the final vaccine dose. METHODS: A total of 383 specimens from 281 HCWs were enrolled in this study, and the results of SARS-IGRA and QFN-SARS assays were compared. In addition, we performed the receive operator curve analysis to estimate the optimal cut-off value for IGRA-SARS. RESULTS: For all specimens, IGRA-SARS and QFN-SARS showed 75.7% and 64.2% of the positive results, respectively. The absolute agreement between IGRA-SARS and QFN-SARS was 80.0%, and the Fleiss' κ value was 0.525, indicating moderate agreement. ROC curve analysis of the IGRA-SARS results showed a cut-off value of >0.254 IU/mL, which was consistent with the manufacturer's specifications. The positive rates of both IGRA assays decreased significantly after a postvaccination period of 6 months. CONCLUSIONS: IGRA-SARS showed acceptable performance in the detection of vaccine-induced immunity against COVID-19; however, harmonization of IGRA assays has not yet been achieved. Additionally, the significant decline of positive rates of IGRA after the last vaccination would support the necessity of booster vaccination after a postvaccination period of 6 months.
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COVID-19 , Vacunas , Humanos , COVID-19/diagnóstico , Personal de Salud , Ensayos de Liberación de Interferón gamma , SARS-CoV-2 , Vacunas contra la COVID-19RESUMEN
BACKGROUND: The prevalence of Tropheryma whipplei varies depending on age, region, and underlying disease. We estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea using real-time PCR (RT-PCR) and compared three RT-PCR targets, rpoB, hsp65, and Dig15. METHODS: A total of 1404 nucleic acid samples extracted from the stools of Korean patients with diarrhea were tested using an initial RT-PCR targeting T. whipplei-specific regions of 16S-23S rRNA intergenic spacer. Subsequently, the samples positive for the initial RT-PCR were tested using the follow-up RT-PCRs targeting rpoB, hsp65, and Dig15 and analyzed by sequencing to confirm the presence of T. whipplei. We estimated the prevalence of T. whipplei and compared them according to gender and age. We also compared the performance of three targets in the follow-up RT-PCRs. RESULTS: T. whipplei was detected in 1.4% of all samples (20 of 1404), and there were no differences according to gender and age. In pediatric samples (≤ 19 years), T. whipplei was detected higher in children aged 6-19 than in those aged 1-5 (2.7% vs. 0.7%, P = 0.01). Sensitivities of the rpoB, hsp65, and Dig15 RT-PCR were 50.0%, 85.0%, and 95.0%, respectively; specificities were 100.0%, 100.0%, and 84.6%, respectively. CONCLUSIONS: This is the first study that estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea. This study demonstrated the presence of T. whipplei in stools of Koreans, even though the bacterium was detected low. The RT-PCRs targeting hsp65 and Dig15 showed reliable performance, and a multiplex PCR including these targets is expected to be useful for T. whipplei detection.
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Tropheryma , Humanos , Niño , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
PURPOSE: This study aimed to evaluate the trend of adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC) in patients who underwent radical nephroureterectomy with bladder cuff excision (NUx) for upper tract urothelial carcinoma (UTUC) to compare the perioperative outcomes and overall survival (OS) between AC and NAC using nationwide population-based data. MATERIALS AND METHODS: We collected data on patients diagnosed with UTUC and treated with NUx between 2004 and 2016 using the National Health Insurance Service database, and evaluated the overall treatment trends. The AC and NAC groups were propensity score-matched. Cox proportional hazard and Kaplan-Meier analyses were used to assess survival. RESULTS: Of the 8,705 enrolled patients, 6,627 underwent NUx only, 94 underwent NAC, and 1,984 underwent AC. The rate of NUx without perioperative chemotherapy increased from 70.8 to 78.2% (R2 = 0.632; p < 0.001). The rates of dialysis (p = 0.398), TUR-BT (p = 1.000), and radiotherapy (p = 0.497) after NUx were similar. In the Kaplan-Meier curve, the NAC and AC groups showed no significant difference (p = 0.480). In multivariate analysis, treatment with AC or NAC was not associated with OS (hazard ratio 0.83, 95% confidence interval 0.49-1.40, p = 0.477). CONCLUSION: The use of NUx without perioperative chemotherapy has tended to increase in South Korea. Dialysis, TUR-BT, and radiotherapy rates after NUx were similar between the NAC and AC groups. There was no significant difference in OS between the NAC and AC groups. Proper perioperative chemotherapy according to patient and tumor conditions should be determined by obtaining more evidence of UTUC.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Terapia Neoadyuvante , Neoplasias de la Vejiga Urinaria/cirugía , Estudios de Cohortes , Quimioterapia Adyuvante , Estudios RetrospectivosRESUMEN
BACKGROUND: Inconclusive results in SARS-CoV-2 molecular assays cause confusion among clinicians and delay appropriate infection prevention and control. In this study, we aimed to characterize the respiratory specimens associated with inconclusive SARS-CoV-2 molecular assay results. METHODS: We re-evaluated inconclusive specimens by 3 additional RT-PCR assays and attempted to detect subgenomic RNA (sgRNA) in these specimens. RESULTS: Among follow-up tests from confirmed SARS-CoV-2 cases, 36.3% of the inconclusive results were classified as presumptive positive results (45/124). However, none of the specimens from 36 screening cases was classified as a presumptive positive result. Among 160 inconclusive specimens, sgRNAs were detected in 78 samples (48.8%): 58 were confirmed cases (58/124, 46.8%) and 20 were screening cases (20/36, 55.6%). CONCLUSIONS: The results of our study suggest the recommendation of considering inconclusive results as positive results for confirmed SARS-CoV-2 cases. In screening cases, viral remnants could be partially amplified in PCR assays, and these inconclusive results could be related to previous infections. In addition, sgRNAs were detected in about half of the inconclusive specimens; however, the clinical significance of sgRNA is not yet clear.
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COVID-19 , SARS-CoV-2 , Prueba de COVID-19 , Humanos , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Human metapneumovirus (hMPV) commonly causes upper and lower respiratory tract infections. Here, we performed long-term retrospective surveillance of hMPV infection among patients hospitalized in South Korea between 2007 and 2016 and investigated seasonal dynamics and clinical characteristics associated with each virus subtype/genotype. METHODS: Patient specimens were tested for hMPV and other respiratory viruses by commercial molecular assays. Medical records of hMPV-positive patients were reviewed, and hMPV subtype/genotype analysis was performed. We also collected meteorological data and analyzed relationships with hMPV activity. RESULTS: Of 23 694 specimens, 1275 (5.4%) were positive; among them, 94.0% were classified into 5 subtypes (A1, A2a, A2b, B1, and B2). Some clinical manifestations differed according to hMPV genotype; however, there was no correlation between hMPV subtype and clinical outcome. Viral activity peaked at 13-20 weeks (April and May) and was associated with climate-specific factors, including temperature, relative humidity, diurnal temperature variation, wind speed, and sunshine duration. CONCLUSIONS: This large-scale, 10-year study provides valuable information about the clinical characteristics associated with hMPV subtypes and climate factors contributing to virus transmission.
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Metapneumovirus , Infecciones por Paramyxoviridae , Infecciones del Sistema Respiratorio , Genotipo , Humanos , Lactante , Metapneumovirus/genética , Infecciones por Paramyxoviridae/epidemiología , República de Corea/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Estudios RetrospectivosRESUMEN
Delivering biomolecules, such as antibodies, proteins, and peptides, to the cytosol is an important and challenging aspect of drug development and chemical biology. Polyarginine-a well-known cell-penetrating peptide (CPP)-is capable of exploiting its positive charge and guanidium groups to carry a fused cargo into the cytosol. However, the precise mechanism by which this occurs remains ambiguous. In the present study, we established a new method of quantitatively assessing cell penetration. The method involves inducing cell death by using a polyarginine (R8) to deliver a peptide-ie, mitochondrial targeting domain (MTD)-to the cytosol. We found that 4,4'-diisothiocyanatostilbene-2,2'-di-sulfonate (DIDS)-an anion channel blocker-inhibited the ability of octa-arginine (R8)-fused MTD to penetrate cells. Other anion channel blockers did not inhibit the penetration of peptides fused with R8. Comparison of DIDS with other structurally similar chemicals revealed that the isothiocyanate group of DIDS may be primarily responsible for the inhibitory effect than its stilbene di-sulfonate backbone. These results imply that the inhibitory effect of DIDS may not be derived from the interaction between stilbene di-sulfonate and the anion channels, but from the interaction between the isothiocyanate groups and the cell membrane. Our new MTD method enables the quantitative assessment of cell penetration. Moreover, further studies on the inhibition of CPPs by DIDS may help clarify the mechanism by which penetration occurs and facilitate the design of new penetrative biomolecules.
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Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/efectos adversos , Péptidos de Penetración Celular/farmacología , Oligopéptidos/química , Proteínas Proto-Oncogénicas c-bcl-2/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Péptidos de Penetración Celular/química , Interacciones Farmacológicas , Células HeLa , Humanos , Ratones , Dominios ProteicosRESUMEN
Despite multitudes of reports on cancer remedies available, we are far from being able to declare that we have arrived at that defining anti-cancer therapy. In recent decades, researchers have been looking into the possibility of enhancing cell death-related signaling pathways in cancer cells using pro-apoptotic proteins. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Mu-2/AP1M2 domain containing, death-inducing (MUDENG, MuD) have been established for their ability to bring about cell death specifically in cancer cells. Targeted cell death is a very attractive term when it comes to cancer, since most therapies also affect normal cells. In this direction TRAIL has made noteworthy progress. This review briefly sums up what has been done using TRAIL in cancer therapeutics. The importance of MuD and what has been achieved thus far through MuD and the need to widen and concentrate on applicational aspects of MuD has been highlighted. This has been suggested as the future perspective of MuD towards prospective progress in cancer research.
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Complejo 1 de Proteína Adaptadora/genética , Subunidades mu de Complejo de Proteína Adaptadora/genética , Proteínas Reguladoras de la Apoptosis/genética , Neoplasias/tratamiento farmacológico , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Complejo 1 de Proteína Adaptadora/antagonistas & inhibidores , Subunidades mu de Complejo de Proteína Adaptadora/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias/genética , Neoplasias/patología , Transducción de Señal/efectos de los fármacos , Ligando Inductor de Apoptosis Relacionado con TNF/antagonistas & inhibidoresRESUMEN
Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has significant potential for application in the treatment of urothelial carcinoma (URCa) of the bladder. Previous studies have shown that regulation of the AMP-activated serine/threonine protein kinase (AMPK)-mTOR signaling pathway enhances apoptosis by inducing autophagy or mitophagy in bladder cancer. Alteration of liver kinase B1 (LKB1)-AMPK signaling leads to mitochondrial dysfunction and the accumulation of autophagy-related proteins as a result of mitophagy, resulting in enhanced cell sensitivity to drug treatments. Therefore, we hypothesized that LKB1 deficiency in URCa cells could lead to increased sensitivity to rapamycin by inducing mitochondrial defect-mediated mitophagy. To test this, we established stable LKBI-knockdown URCa cells and analyzed the effects of rapamycin on their growth. Rapamycin enhanced growth inhibition and apoptosis in stable LKB1-knockdown URCa cells and in a xenograft mouse model. In spite of the stable downregulation of LKB1 expression, rapamycin induced AMPK activation in URCa cells, causing loss of the mitochondrial membrane potential, ATP depletion, and ROS accumulation, indicating an alteration of mitochondrial biogenesis. Our findings suggest that the absence of LKB1 can be targeted to induce dysregulated mitochondrial biogenesis by rapamycin treatment in the design of novel therapeutic strategies for bladder cancer.
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Antineoplásicos/farmacología , Carcinoma de Células Transicionales/patología , Mitofagia/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Sirolimus/farmacología , Neoplasias de la Vejiga Urinaria/patología , Quinasas de la Proteína-Quinasa Activada por el AMP , Animales , Carcinoma de Células Transicionales/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Ratones , Ratones Desnudos , Mitofagia/fisiología , Transducción de Señal/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The adaptor-related protein complex 5 subunit mu 1 (AP5M1) is an evolutionally conserved protein with ubiquitous expression in human tissues. However, the major function of AP5M1 in living organisms is unclear owing to few published studies. Here, we demonstrate that AP5M1 is a potent apoptosis-inducing molecule in cervical cancer cells. We also found that AP5M1 upregulated the level of BAX protein, a key pro-apoptotic B cell lymphoma (BCL)-2 family member regulating mitochondrial apoptotic cell death pathway. Moreover, AP5M1 completely lost its apoptotic activity in BAX-knockout or -knockdown cells, indicative of its functional dependence on BAX. Comparative analysis of cervical tissues from patients with cervical carcinoma and non-cancer control revealed a prominent downregulation in AP5M1 expression with a concomitant downregulation in BAX expression; AP5M1 and BAX mRNA expression levels in cervical tissues exhibited a strong positive correlation (râ¯=â¯0.97). Thus, we identified AP5M1 as a previously unrecognized apoptotic protein that governs BAX expression and revealed the association between AP5M1 and malignancy.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Apoptosis , Neoplasias del Cuello Uterino/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Proliferación Celular , Femenino , Células HeLa , Humanos , Células Tumorales Cultivadas , Neoplasias del Cuello Uterino/patologíaRESUMEN
Noxa is a weak apoptosis activator consisting of a BH3 domain and a mitochondrial-targeting domain (MTD). BH3 binds Mcl-1 and Bcl2A1 and inactivates their anti-apoptotic activities, while MTD delivers BH3 to mitochondria. Previously we revealed that MTD may also function as an inducer of necrosis via conjugation with octa-arginine, which induces cytosolic Ca2+ influx from mitochondria. However, the mechanism(s) underlying this process has not been elucidated yet. Here, we show that calcium influx induced by an MTD peptide fused with octa-arginine residue (R8:MTD) originates not only from mitochondria but also from the extracellular space. However, calcium spikes were not sufficient for necrosis. R8:MTD induced mitochondrial permeability transition pore opening, fragmentation, and swelling. These mitochondrial events induced by MTD appeared to be necessary for necrosis induction, since DIDS, a VDAC inhibitor, inhibited the mitochondrial swelling and cell death induced by MTD. We show that R8:MTD disrupted endoplasmic reticulum (ER) structures but not peroxisomes or Golgi, indicating that R8:MTD causes necrosis by inducing ER events as well.
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Retículo Endoplásmico/metabolismo , Mitocondrias/metabolismo , Péptidos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/química , Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/farmacología , Calcio/metabolismo , Muerte Celular/efectos de los fármacos , Citosol/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Espacio Extracelular/metabolismo , Células HeLa , Humanos , Mitocondrias/efectos de los fármacos , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial , Dilatación Mitocondrial/efectos de los fármacos , Péptidos/química , Dominios Proteicos , Canales Aniónicos Dependientes del Voltaje/antagonistas & inhibidores , Canales Aniónicos Dependientes del Voltaje/metabolismoRESUMEN
The laboratory diagnosis of latent tuberculosis infection (LTBI) is mainly performed with interferon gamma release assays (IGRAs). We compared the performance of a new enzyme-linked immunosorbent assay (ELISA)-based IGRA, the Standard E TB-Feron ELISA (TBF; SD Biosensor, Gyeonggi-do, Republic of Korea), with that of a widely used assay, the QuantiFERON-TB Gold In-Tube assay (QFT-GIT; Qiagen, Hilden, Germany), in a population of 425 health care workers (HCWs). All HCWs were screened by both assays per the manufacturers' protocols and in a cross-manner, where tube sets from one assay were used with the alternative ELISA. The results were compared both qualitatively and quantitatively. TBF and QFT-GIT identified 11.3% (48/425) and 12.9% (55/425) of the positive samples, respectively. TBF demonstrated 81.6% positive and 97.4% negative percent agreement with QFT-GIT, with a Cohen's kappa value of 0.78 (strong agreement). Discordant results were detected in 20 subjects (4.3%): 13 samples (65.0%) were TBF negative and QFT-GIT positive, 6 samples (30.0%) were TBF positive and QFT-GIT negative, and 1 sample provided TBF and QFT-GIT indeterminate/negative results. We observed a statistically significant degree of correlation between the interferon gamma reactivity between the two assays (Spearman's rho [rs ] value = 0.551, P < 0.01) and between standard assays and cross-manner tests (rs value range, 0.449 to 0.816; P < 0.01 for all combinations). Cross-manner tests also revealed that the ELISA kit of TBF provided higher values for the tube containing the tuberculosis (TB) antigen and the negative-control tube than the ELISA of QFT-GIT under the same conditions (P < 0.01), although these differences disappeared when the value for the negative-control tube was subtracted from that for the TB antigen tube. TBF showed a comparable and acceptable clinical performance in detecting LTBI compared to QFT-GIT. TBF represents a useful alternative tool as an ELISA-based IGRA, especially for large-scale screening for LTBI in HCWs.
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Pruebas Diagnósticas de Rutina/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Personal de Salud , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis Latente/diagnóstico , Exposición Profesional , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Adulto JovenRESUMEN
ABSTRACTBACKGROUND: Although immunoassays play a major role in the detection of hepatitis viruses, there is a need for a point-of-care (POC) test. We evaluated the EuDx-HE (A,B,C) kit (EUDIPIA, Cheongju, Korea), which detects anti-hepatitis A virus (HAV) immunoglobulin M (IgM), hepatitis B virus surface antigen (HBsAg), and anti-hepatitis C virus (HCV) immunoglobulin G (IgG) simultaneously using an immunochromatographic method within 15 minutes. METHODS: A total of 1581 serum samples including 57, 477, and 451 samples positive for anti-HAV IgM, HBsAg, and anti-HBV IgG, respectively, were analyzed. We investigated the diagnostic accuracy of the EuDx-HE (A,B,C) kit by comparison with SD BIOLINE POC kits (Abbott, Chicago, IL) using Architect immunoassays as a reference method. RESULTS: For anti-HAV IgM and HBsAg detection, the EuDx-HE (A,B,C) kit showed a higher sensitivity and a slightly lower specificity than the SD BIOLINE kit. For anti-HCV IgG detection, the EuDx-HE (A,B,C) kit had a higher sensitivity and a higher specificity than the SD BIOLINE kit. The agreement for positivity between the POC tests was >89.47%, with κ values of 0.844, 0.941, and 0.943 for HAV, HBV, and HCV, respectively. CONCLUSION: The EuDx-HE (A,B,C) kit showed an acceptable clinical performance for detecting anti-HAV IgM, HBsAg, and anti-HCV.
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Anticuerpos Antivirales/sangre , Antígenos Virales/sangre , Hepatitis A/diagnóstico , Hepatitis B/diagnóstico , Hepatitis C/diagnóstico , Inmunoensayo/normas , Sistemas de Atención de Punto/normas , Antígenos Virales/inmunología , Hepacivirus/aislamiento & purificación , Virus de la Hepatitis A/aislamiento & purificación , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Inmunoensayo/métodos , Pruebas en el Punto de Atención/normas , Sensibilidad y EspecificidadRESUMEN
The aggregation and accumulation of amyloid beta (Aß) peptide is believed to be the primary cause of Alzheimer's disease (AD) pathogenesis. Vitamin D-binding protein (DBP) can attenuate Aß aggregation and accumulation. A biocompatible polymer poly (D,L-lactic acid-co-glycolic acid) (PLGA) can be loaded with therapeutic agents and control the rate of their release. In the present study, a PLGA-based drug delivery system was used to examine the therapeutic effects of DBP-PLGA nanoparticles in Aß-overexpressing (5XFAD) mice. DBP was loaded into PLGA nanoparticles and the characteristics of the DBP-PLGA nanoparticles were analyzed. Using a thioflavin-T assay, we observed that DBP-PLGA nanoparticles significantly inhibited Aß aggregation in vitro. In addition, we found that intravenous injection of DBP-PLGA nanoparticles significantly attenuated the Aß accumulation, neuroinflammation, neuronal loss and cognitive dysfunction in the 5XFAD mice. Collectively, our results suggest that DBP-PLGA nanoparticles could be a promising therapeutic candidate for the treatment of AD.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Portadores de Fármacos/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Proteína de Unión a Vitamina D/administración & dosificación , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Animales , Masculino , Ratones , Ratones Transgénicos , Nanopartículas/química , Agregación Patológica de Proteínas/tratamiento farmacológico , Agregación Patológica de Proteínas/metabolismo , Agregación Patológica de Proteínas/patología , Proteína de Unión a Vitamina D/uso terapéuticoRESUMEN
The mitochondrial targeting domain (MTD) of Noxa has necrosis-inducing activity when conjugated with cell-penetrating peptide (CPP). In this study, we report another MTD-like motif, B1MLM, found in BNIP1, a pro-apoptotic BH3-only protein found in the endoplasmic reticulum membrane. The B1MLM peptide, conjugated with CPP, induced necrosis in a way similar to that of R8:MTD. R8:B1MLM caused an intracellular calcium spike, mitochondrial reactive oxygen species generation, and mitochondrial fragmentation. The cytosolic calcium spike was likely due to the opening of the mitochondrial permeability transition pore.
Asunto(s)
Señalización del Calcio , Proteínas Proto-Oncogénicas c-bcl-2/química , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/metabolismo , Células HeLa , Humanos , Mitocondrias/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial , Necrosis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Multiple trials have attempted to demonstrate the effective induction of cell death in TRAIL-resistant cancer cells, including using a combined treatment of recombinant TRAIL and various proteasome inhibitors. These studies have yielded limited success, as the mechanism of cell death is currently unidentified. Understanding this mechanism's driving forces may facilitate the induction of cell death in TRAIL-resistant cancer cells. METHODS: Three kinds of recombinant soluble TRAIL proteins were treated into TRAIL-resistant cells and TRAIL-susceptible cells, with or without bortezomib, to compare their respective abilities to induce cell death. Recombinant TRAIL was treated with bortezomib to investigate whether this combination treatment could induce tumor regression in a mouse syngeneic tumor model. To understand the mechanism of combined treatment-induced cell death, cells were analyzed by flow cytometry and the effects of various cell death inhibitors on cell death rates were examined. RESULTS: ILz:rhTRAIL, a recombinant human TRAIL containing isoleucine zipper hexamerization domain, showed the highest cell death inducing ability both in single treatment and in combination treatment with bortezomib. In both TRAIL-resistant and TRAIL-susceptible cells treated with the combination treatment, an increase in cell death rates was dependent upon both the dose of TRAIL and its intrinsic properties. When a syngeneic mouse tumor model was treated with the combination of ILz:rhTRAIL and bortezomib, significant tumor regression was seen as a result of the effective induction of cancer cell death. The combination treatment-induced cell death was both inhibited by TRAIL blocking antibody and caspase-dependent. However, it was not inhibited by various ER stress inhibitors and autophagy inhibitors. CONCLUSIONS: The combination treatment with ILz:rhTRAIL and bortezomib was able to induce cell death in both TRAIL-susceptible and TRAIL-resistant cancer cells through the intracellular TRAIL signaling pathway. The efficiency of cell death was dependent on the properties of TRAIL under the environment provided by bortezomib. The combination treatment-induced cell death was not regulated by bortezomib-induced ER stress response or by autophagy.