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OBJECTIVES: This study explored the impacts of peri-operative changes in the neutrophil-to-lymphocyte ratio (NLR) on the survival rate after radical nephroureterectomy. METHODS: This retrospective analysis included a multicentric cohort of patients diagnosed with upper tract urothelial carcinoma (UTUC) who had undergone radical nephroureterectomy from 2012 to 2021. We assessed the preoperative NLR, postoperative NLR, delta-NLR (difference between postoperative and preoperative NLRs), and NLR change (ratio of postoperative to preoperative NLR). Additionally, patients were categorized according to increases in their preoperative and/or postoperative NLRs. Associations of survival with peri-operative changes in the NLR were investigated using Cox multivariate regression models. RESULTS: A total of 488 patients were included in the study, with a median age of 73 years. Among the patients, 105 (21.5%) exhibited elevated preoperative and postoperative NLRs, 88 (18.0%) exhibited elevated preoperative NLR only, 53 (10.9%) exhibited elevated postoperative NLR only, and 242 (49.6%) exhibited normal NLRs. Multivariate analysis indicated significant negative correlations between both preoperative and postoperative increased NLRs and oncological outcomes, including nonurothelial tract recurrence-free survival and cancer-specific survival (hazard ratio [HR]: 1.65, P = 0.017; HR: 2.12, P = 0.014, respectively). CONCLUSION: This is the first study to evaluate the association between peri-operative changes in the NLR and the outcomes of patients with UTUC who underwent radical nephroureterectomy. Patients with elevated NLRs at both time points experienced considerably worse outcomes. Further research should explore whether increases in the NLR during long-term follow-up could indicate impending disease recurrence.
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The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3, also called cryopyrin) inflammasome is an intracellular innate immune complex, which consists of the pattern-recognition receptor NLRP3, the adaptor apoptosis-assciated speck-like protein containing a caspase recruitment domain, and procaspase-1. Aberrant activation of the NLRP3 inflammasome causes an autoinflammatory disease called cryopyrin-associated periodic syndrome (CAPS). CAPS is caused by gain-of-function mutations in the NLRP3-encoding gene CIAS1; however, the mechanism of CAPS pathogenesis has not been fully understood. Thus, unknown regulators of the NLRP3 inflammasome, which are associated with CAPS development, are being investigated. To identify novel components of the NLRP3 inflammasome, we performed a high-throughput screen using a human protein array, with NLRP3 as the bait. We identified a NLRP3-binding protein, which we called the cryopyrin-associated nano enhancer (CANE). We demonstrated that CANE increased IL-1ß secretion after NLRP3 inflammasome reconstitution in human embryonic kidney 293T cells and formed a "speck" in the cytosol, a hallmark of NLRP3 inflammasome activity. Reduced expression of endogenous CANE decreased IL-1ß secretion upon stimulation with the NLRP3 agonist nigericin. To investigate the role of CANE in vivo, we developed CANE-transgenic mice. The PBMCs and bone marrow-derived macrophages of CANE-transgenic mice exhibited increased IL-1ß secretion. Moreover, increased autoinflammatory neutrophil infiltration was observed in the s.c. tissue of CANE-transgenic versus wild-type mice; these phenotypes were consistent with those of CAPS model mice. These findings suggest that CANE, a component of the NLRP3 inflammasome, is a potential modulator of the inflammasome and a contributor to CAPS pathogenesis.
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Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Animales , Inflamasomas/metabolismo , Inflamasomas/inmunología , Ratones , Humanos , Células HEK293 , Síndromes Periódicos Asociados a Criopirina/inmunología , Síndromes Periódicos Asociados a Criopirina/genética , Ratones Endogámicos C57BL , Interleucina-1beta/metabolismo , Ratones NoqueadosRESUMEN
Aluminum electrolytic capacitors are essential components in all electronic devices, and it is known that their longevity depends on the performance of their electrolytes. We synthesized dicarboxylic acids having ether bonds showing the good solubility in ethylene glycol as a solvent and simultaneously developed a complete halogen removal method, which is strictly prohibited in capacitors. Moreover, the incorporation of bulky α-substituents and cyclic structures dramatically improved their heat resistance and can withstand high voltage, i.e., 764 V.
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OBJECTIVE: We aimed to assess the impact of the timing of urinary drainage on clinical outcomes in patients with obstructive pyelonephritis (OPN) associated with upper urinary tract (UUT) stones. METHODS: We retrospectively evaluated the multicenter dataset of 240 patients with OPN associated with UUT stones who underwent urinary drainage. We divided the patients into two groups depending on the timing of urinary drainage; emergency drainage, defined as within 12 h from admission, and delayed drainage, defined as between 12 and 48 h from admission. The outcomes were the length of hospital stay, time to leukocyte normalization, and time to body temperature normalization. One-to-two propensity score matching (PSM) was applied to minimize the effect of confounders between the two groups. Subsequently, predictive patient factors for emergency drainage were analyzed using the logistic regression model. RESULTS: Only the time from admission to normal body temperature was significantly shorter in the emergency drainage group when compared with the delayed drainage group (median: 2 vs. 3 days; p = 0.02), while there was no difference in time from drainage to body temperature normalization between the two groups. On multivariable analysis, high pretreatment C-reactive protein (CRP) was associated with implementing emergency drainage within 12 h. CONCLUSIONS: The timing of urinary drainage was only associated with the duration of high fever, but it did not affect the postdrainage course. Emergency urinary drainage is more likely to be performed in severe patients, such as high pretreatment CRP.
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Pielonefritis , Cálculos Urinarios , Sistema Urinario , Humanos , Drenaje , Puntaje de Propensión , Pielonefritis/complicaciones , Estudios Retrospectivos , Cálculos Urinarios/complicaciones , Estudios Multicéntricos como AsuntoRESUMEN
The apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)/caspase-1/interleukin(IL)-1ß axis, also known as the inflammasome pathway, is indispensable for IL-1ß activation in response to various pathogens or own damages. Previously, we developed an NLRP3-inflammasome using a cell-free system and identified ASC targeting drugs; thus, examination of ASC-related histopathology in various diseases could help to provide indications for these drugs. Here, we generated mice deficient only in ASC-protein (ASC-deficient (AD) mice) using CRISPR/Cas9 technology, studied which tissues were most affected, and obtained histopathological images of lipopolysaccharide (LPS)-induced endotoxemia. C57BL/6 wild-type (WT) and (AD) mice were injected intraperitoneally with a lethal dose (50 µg/g) of LPS. Statistical analysis of the survival of C57BL/6 mice and AD mice was performed using the Kaplan-Meier method and the log-rank test. The histopathological findings of multiple tissues from these mice were compared. Acute inflammation (e.g., catarrhal inflammation), along with congestion was observed in the colon of WT mice but not in that of AD mice. Adhesion of neutrophils to capillaries, along with interstitial infiltration, were observed in multiple tissues from WT mice. In AD mice, neutrophil infiltration was less severe but remained evident in the stomach, small intestine, heart, liver, kidney, spleen, and brain. Notably, there was no difference between WT and AD mice with respect to alveolar neutrophil infiltration and interstitial edema. These findings suggest that even though ASC contributes to systemic inflammation, it is dependent on the tissue involved. Intestinal congestion and edema might be good candidates for anti-ASC-targeted therapy.
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Endotoxemia , Inflamasomas , Animales , Ratones , Inflamasomas/metabolismo , Lipopolisacáridos , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas Adaptadoras de Señalización CARD/genética , Proteínas Adaptadoras de Señalización CARD/metabolismo , Endotoxemia/inducido químicamente , Ratones Endogámicos C57BL , Caspasa 1/metabolismo , Inflamación/metabolismo , Interleucina-1beta/metabolismo , EdemaRESUMEN
BACKGROUND: Blood coagulation factor XIII (FXIII) promotes cross-linking between fibrin molecules at the final stage of the blood coagulation cascade. However, its expression in cells or tissues and function, particularly factor XIII subunit B (FXIII-B), remains controversial. Hemorrhagic FXIII deficiency following anti-interleukin-6 (IL-6) receptor antibody treatment has been reported in patients with rheumatoid arthritis (RA). Patients receiving this biologics have reduced FXIII activity when compared to the activity in those treated with other biologics. The relationship between pro-inflammatory cytokines and FXIII expression remains unknown. METHODS: To investigate the expression pattern of FXIII in synovial tissues, immunohistochemistry, RT-qPCR, and western blotting were performed. FXIII-A expressed monocyte-derived macrophages were treated with recombinant IL-6 and anti-IL-6 receptor antibody. RNA sequencing of FXIII-B-overexpressing cells was performed to clarify the function of FXIII-B. RESULTS: The immunohistochemical analysis of synovial tissues revealed that factor XIII subunit A (FXIII-A) was expressed in M2 macrophages, and FXIII-B was expressed in fibroblast-like synoviocytes. IL-6 stimulation upregulated FXIII-A expression in IL-4-induced monocyte-derived macrophages, and the anti-IL-6 receptor antibody suppressed FXIII-A expression. FXIII-B was more abundantly secreted in the supernatant of fibroblast-like synoviocytes compared with that of other cells. RNA sequencing showed that FXIII-B elevated the expression of genes associated with anti-apoptotic molecules and chemokines. CONCLUSIONS: Our findings highlight that synovial tissue is one of the sources of FXIII production. We also have demonstrated IL-6-dependent FXIII-A expression and the novel potential functions of FXIII-B.
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Nivalenol (NIV) is a trichothecene mycotoxin that is more toxic than deoxynivalenol. It accumulates in grains due to infection with Fusarium species, which are the causative agents of scab or Fusarium head blight. An immunoassay, which is a rapid and easy analytical method, is necessary for monitoring NIV in grains. However, a specific antibody against NIV has not been prepared previously. To establish an immunoassay, we prepared NIV, introduced a linker, and generated antibodies against it. NIV was prepared from a culture of Fusarium kyushuense obtained from pressed barley through chromatographic procedures with synthetic adsorbents and silica gel. NIV was reacted with glutaric anhydride, and the reaction was stopped before mono-hemiglutaryl-NIV was changed to di-hemiglutaryl-NIV. 15-O-Hemiglutaryl-NIV was isolated via preparative HPLC and bound to keyhole limpet hemocyanin (KLH) using the active ester method. Two different monoclonal antibodies were prepared by immunizing mice with the NIV-KLH conjugate. The 50% inhibitory concentration values were 36 and 37 ng/mL. These antibodies also showed high reactivity in a direct competitive enzyme-linked immunosorbent assay and specifically reacted with NIV and 15-acetyl-NIV but not with deoxynivalenol and 4-acetyl-NIV.
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Fusarium , Micotoxinas , Tricotecenos , Ratones , Animales , Micotoxinas/análisis , Anticuerpos Monoclonales , Tricotecenos/análisis , Fusarium/metabolismoRESUMEN
INTRODUCTION: Dialysis-related amyloidosis (DRA) caused by ß2-microgloblin (B2M) fibrils is a serious complication for patients with kidney failure on long-term dialysis. Deposition of B2M amyloid fibrils is thought to be due not only to serum extracellular B2M but also to infiltrating inflammatory cells, which may have an important role in B2M amyloid deposition in osteoarticular tissues in patients with DRA. Here, we asked whether B2M amyloid fibrils activate the inflammasome and contribute to formation and deposition of amyloid fibrils in cells. METHODS: Amyloid formation was confirmed by a thioflavin T (ThT) spectroscopic assay and scanning electron microscopy (SEM). Activation of inflammasomes was assessed by detecting interleukin (IL)-1ß in culture supernatants from human embryonic kidney (HEK) 293T cells ectopically expressing inflammasome components. IL-1ß secretion was measured by enzyme-linked immunosorbent assay. Expression and co-localization were analyzed by immunohistochemistry and dual immunofluorescence microscopy. RESULTS: B2M amyloid fibrils interacted directly with NLRP3/Pyrin and to activate the NLRP3/Pyrin inflammasomes, resulting in IL-1ß secretion. When HEK293T cells were transfected with inflammasome components NLRP3 or Pyrin, along with ASC, pro-caspase-1, pro-IL-1ß, and B2M, ThT fluorescence intensity increased. This was accompanied by IL-1ß secretion, which increased in line with the amount of transfected B2M. In this case, morphological glowing of amyloid fibrils was observed by SEM. In the absence of ASC, there was no increase in ThT fluorescence intensity or IL-1ß secretion, or any morphological glowing of amyloid fibrils. NLRP3 or Pyrin and B2M were co-localized in a "speck" in HEK293T cells, and co-expressed in infiltrated monocytes/macrophages in the osteoarticular synovial tissues in a patient with DRA. CONCLUSION: Taken together, these data suggest that inflammasome assembly is required for the subsequent triggering of intracellular formation of B2M amyloid fibrils, which may contribute to osteoarticular deposition of B2M amyloid fibrils and inflammation in patients with DRA.
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Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Amiloide , Células HEK293 , Humanos , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , PirinaRESUMEN
The mechanisms of oceanic animal migration remain enigmatic. Adult Japanese eels start their long-distance oceanic migration from coastal areas to breed near the West Mariana Ridge. We tracked acoustically tagged eels released in the Kuroshio Current (KC) area near Japan (five silver-phase eels, three of which had impaired swim bladders) and a tropical/subtropical (TS) area near/in the spawning area (two yellow-phase and three silver-phase eels). We analyzed their active swimming and transport by water currents. The strong flow of the KC dominated the eels' movements in the north, and TS area; their swimming influenced their movements. In the KC area, greater distances were covered at night than during the day, because eels swam in shallower layers with strong currents at night. Three and one eel in the TS and KC area in the upper 400 m showed counterclockwise and clockwise movements around the time of solar culmination, respectively. The meta-analysis showed that eels released at middle latitudes (20°-34° N) generally swam southward through currents, whereas those released at low latitudes (12°-13° N) generally swam northward through currents. Our study suggests the influence of the surrounding current and a potential effect of solar cues on the movements of Japanese eels.
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Anguilla , Migración Animal , Animales , Océanos y Mares , Plata , NataciónRESUMEN
BACKGROUND/AIM: Therapeutic strategies for prostate cancer are currently undergoing a paradigm shift due to the advent of next-generation androgen receptor inhibitors. Among these inhibitors, apalutamide is regarded as a key drug because of its effectiveness. However, risk factors for and the timing of the onset of apalutamide-related cutaneous adverse events remain unclear. Therefore, the present study investigated key risk factors for and timing of the onset of apalutamide-related cutaneous adverse events. PATIENTS AND METHODS: Sixty-two Japanese patients with non-metastatic castration-resistant prostate cancer treated with 240 mg/day of apalutamide were enrolled in the present study. RESULTS: Twenty-four patients (38.7%) developed cutaneous adverse events. Multivariable logistic regression analysis of age, height, and body weight identified body weight as a significant predictive factor for the incidence of cutaneous adverse events (p=0.019). When the mean body weight of patients (63.80 kg) was set as the cut-off value, the Kaplan-Meier analysis revealed that the risk of cutaneous adverse events was significantly increased in those with a body weight <63.8 kg (p=0.003, the log-rank test). The analysis also showed that cutaneous adverse events developed within the first 6 months regardless of body weight. CONCLUSION: A lower body weight is a significant risk factor for apalutamide-related cutaneous adverse events and their onset is within 6 months of initiation of therapy.
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Neoplasias de la Próstata Resistentes a la Castración , Peso Corporal , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Factores de Riesgo , Tiohidantoínas/efectos adversosRESUMEN
Geographical traceability of marine bivalves is becoming increasingly important to assure their quality and to defend the interest of consumers and producers. This study verifies the neodymium isotopic ratio (143Nd/144Nd) in Ruditapes philippinarum shells as a tracer of the geographic origin, based on the geochemical aspect that 143Nd/144Nd of their habitats strongly depends on the geology of its catchment areas. The 143Nd/144Nd ratios of clam shells from the Japanese and Chinese coastal areas displayed a heterogeneous pattern from local to international scales, reflecting the geological age of the catchment area. The blind test suggested that a part of Manila clam was sold with mislabeling in the Japanese market, demonstrating the high potential of 143Nd/144Nd to unmask the fraud labeling in a food market. Our findings emphasize the potential of 143Nd/144Nd as a tracer for the geographical origin of marine bivalves, and also as a strong deterrent against mislabeling.
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Bivalvos , Neodimio , Animales , Geografía , Isótopos , Alimentos MarinosRESUMEN
The long battle between humans and various physical, chemical, and biological insults that cause cell injury (e.g., products of tissue damage, metabolites, and/or infections) have led to the evolution of various adaptive responses. These responses are triggered by recognition of damage-associated molecular patterns (DAMPs) and/or pathogen-associated molecular patterns (PAMPs), usually by cells of the innate immune system. DAMPs and PAMPs are recognized by pattern recognition receptors (PRRs) expressed by innate immune cells; this recognition triggers inflammation. Autoinflammatory diseases are strongly associated with dysregulation of PRR interactomes, which include inflammasomes, NF-κB-activating signalosomes, type I interferon-inducing signalosomes, and immuno-proteasome; disruptions of regulation of these interactomes leads to inflammasomopathies, relopathies, interferonopathies, and proteasome-associated autoinflammatory syndromes, respectively. In this review, we discuss the currently accepted molecular mechanisms underlying several autoinflammatory diseases.
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PURPOSE: To assess the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiation therapy (EBRT) combined with long-term androgen deprivation therapy (ADT) in very-high-risk (VHR) versus high-risk (HR) prostate cancer (PCa), as defined in the National Comprehensive Cancer Network (NCCN) criteria. METHODS: Data from 338 consecutive HR or VHR PCa patients who had undergone this tri-modal therapy between 2005 and 2018 were retrospectively analyzed. Biochemical recurrence (BCR)-free, progression-free, overall, and cancer-specific survival (BCRFS/PFS/OS/CSS) rates were analyzed using the Kaplan-Meier method and Wilcoxon test. Cox regression models were used to evaluate candidate prognostic factors for survival. Cindexes were used to assess model discrimination. RESULTS: Within a median follow-up of 84 months, 68 patients experienced BCR, 58 had disease progression including only 3 with local progression, 27 died of any cause, and 2 died from PCa. The 5year BCRFS, PFS, OS, and CSS rates were 82.2% (HR 86.5%; VHR 70.0%), 90.0% (HR 94.3%; VHR 77.6%), 95.7% (HR, 97.1%; VHR, 91.8%), and 99.6% (HR, 100%; VHR, 98.0%), respectively. In multivariable analyses that adjusted for standard clinicopathologic features, the risk subclassification was associated both PFS and OS (pâ¯= 0.0003 and 0.001, respectively). Adding the risk subclassification improved the accuracy of models in predicting BCRFS, PFS, and OS. CONCLUSION: While the outcome of this trimodal approach appears favorable, VHR PCa patients had significantly worse oncological outcomes than those with HR PCa. The NCCN risk subclassification should be integrated into prognostic tools to guide risk stratification, treatment, and follow-up for unfavorable PCa patients receiving this trimodal therapy.
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Braquiterapia , Neoplasias de la Próstata , Antagonistas de Andrógenos/uso terapéutico , Andrógenos , Braquiterapia/métodos , Humanos , Masculino , Antígeno Prostático Específico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Estudios RetrospectivosRESUMEN
Cancer immunotherapy using T cells redirected with chimeric antigen receptor (CAR) has shown a lot of promise. We have established a single-chain antibody (scFv) generation system in which scFv library-expressing CAR-T cells can be screened appropriately based on their antitumor functions. A variable region library containing the variable and J regions of the human immunoglobulin light or heavy chain was fused with the variable region of a heavy or light chain encoded by an existing tumor-specific antibody to generate a new scFv library. Then, scFv library-expressing CAR-T cells were generated and stimulated with target cells to concentrate the antigen-specific population. Using this system, target-specific recognition of CAR-T cells appeared to be finely tuned by selecting a new variable region. Importantly, we have demonstrated that the newly optimized scFv-expressing CAR-T cells had better proliferation capacity and durable phenotypes, enabling superior reactivity against advanced tumors in vivo in comparison with the original CAR-T cells. Therefore, the optimization of an scFv is needed to maximize the in vivo antitumor functions of CAR-T cells. This system may allow us to adjust an immunological synapse formed by an scFv expressed by CAR-T cells and a target antigen, representing an ideal form of CAR-T-cell immunotherapy.
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Cadenas Pesadas de Inmunoglobulina/metabolismo , Cadenas Ligeras de Inmunoglobulina/metabolismo , Región Variable de Inmunoglobulina/metabolismo , Inmunoterapia Adoptiva , Linfoma/terapia , Receptores Quiméricos de Antígenos/metabolismo , Anticuerpos de Cadena Única/metabolismo , Linfocitos T/trasplante , Animales , Femenino , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Ligeras de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Sinapsis Inmunológicas , Células Jurkat , Células K562 , Linfoma/genética , Linfoma/inmunología , Linfoma/metabolismo , Ratones Endogámicos NOD , Ratones SCID , Receptores Quiméricos de Antígenos/genética , Anticuerpos de Cadena Única/genética , Linfocitos T/inmunología , Linfocitos T/metabolismo , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
2,3-Dimethoxy-2,3-dimethyl-1,4-dioxane readily prepared from biacetyl serves as a stable precursor to 2,3-dimethylene-1,4-dioxane which undergoes a [4+2] cycloaddition reaction with dienophiles to give functionalized cyclohexene derivatives. The cycloaddition adducts obtained by the present procedure are transformed into potentially useful intermediates for biologically important materials.
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Neoplasias de la Próstata , Humanos , Japón , Masculino , Prostatectomía , Neoplasias de la Próstata/cirugíaRESUMEN
NLRP3, an intracellular pattern recognition receptor, recognizes numerous pathogens and/or its own damage-associated molecules, and forms complexes with the adaptor protein ASC. These complexes constitute the NLRP3 inflammasome, a platform for processing interleukin (IL)-1ß and/or IL-18. Several NLRP3 mutations result in constitutive activation of the NLRP3 inflammasome, causing cryopyrin-associated periodic syndrome (CAPS). To the best of our knowledge, small compounds that specifically inhibit inflammasome activation through the pyrin domain (PYD) have not yet been developed. This study describes an attempt to develop small compounds targeting the NLRP3 inflammasome. A core chemical library of 9,600 chemicals was screened against reconstituted NLRP3 inflammasome in a cell-free system with an amplified luminescence proximity homogeneous assay and a cell-based assay by human peripheral blood mononuclear cells (PBMCs). Inflammasome activation was evaluated by ASC-speck formation in human PBMCs, accompanied by IL-1ß secretion and processing, and by using IL-1ß-based dual operating luciferase (IDOL) mice. The activity of these compounds was evaluated clinically using PBMCs from a patient with Muckle-Wells syndrome (MWS), a type of CAPS, with an R260W mutation in NLRP3. Screening identified KN3014, a piperidine-containing compound targeting the interaction between NLRP3 and ASC through the PYD. KN3014 reduced ASC-speck formation in human PBMCs, luminescence from IDOL mice, and auto-secretion of IL-1ß by PBMCs from the patient with MWS. These findings suggest that KN3014 may be an attractive candidate for treatment of MWS, as well as other NLRP3 inflammasomopathies.
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Antiinflamatorios/farmacología , Síndromes Periódicos Asociados a Criopirina/tratamiento farmacológico , Inflamasomas/efectos de los fármacos , Interleucina-1beta/antagonistas & inhibidores , Leucocitos Mononucleares/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Piperidinas/farmacología , Animales , Antiinflamatorios/química , Estudios de Casos y Controles , Síndromes Periódicos Asociados a Criopirina/metabolismo , Síndromes Periódicos Asociados a Criopirina/patología , Ensayos Analíticos de Alto Rendimiento , Humanos , Inflamasomas/metabolismo , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Masculino , Ratones , Piperidinas/químicaRESUMEN
PURPOSE: The incidence of prostate cancer is increasing in Asian countries. Studies using prostatectomy specimens have reported a racial difference in tumor location within the prostate, with a greater incidence of transition zone cancer in Asian men compared with Caucasian men. However, there may be potential biases in studies based on surgical specimens. We describe the pathological features of subclinical prostate cancer, such as latent cancer and incidental cancer, to elucidate tumor location of contemporary Japanese patients. We also compare the prevalence of latent and incidental prostate cancer to determine whether the incidence of prostate cancer is higher in patients with bladder cancer. MATERIALS AND METHODS: Overall 182 men autopsied and 148 who underwent cystoprostatectomy for bladder cancer were included in the study. Each prostate gland was fixed and sliced in step sections. Histological evaluation was performed by a single genitourinary pathologist. The index tumor location was categorized into transition zone or peripheral zone. RESULTS: Prostate cancer was found in 39.0% of the autopsy specimens and 31.6% of the cystoprostatectomy specimens. The prevalence and pathological characteristics were not significantly different between latent and incidental cancer. The prevalence of transition zone cancer was 39.0% (46 of 118). In elderly men peripheral zone cancer was more frequently diagnosed than transition zone cancer (p=0.049). The pathological characteristics of transition and peripheral zone cancers were similar except for the pT stage. CONCLUSIONS: Transition zone cancer was prevalent in contemporary Japanese men. The incidence of prostate cancer in men with bladder cancer might not be higher than that in healthy men.
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Carcinoma de Células Transicionales/patología , Neoplasias de la Próstata/patología , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Autopsia , Carcinoma de Células Transicionales/epidemiología , Carcinoma de Células Transicionales/cirugía , Cistectomía , Humanos , Incidencia , Hallazgos Incidentales , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Prostatectomía , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/cirugía , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
Interleukin-1, an inflammatory cytokine, is considered to have diverse physiological functions and pathological significances and play an important role in health and disease. In this decade, interleukin-1 family members have been expanding and evidence is accumulating that highlights the importance of interleukin-1 in linking innate immunity with a broad spectrum of diseases beyond inflammatory diseases. In this review, we look back on the definition of "inflammation" in traditional general pathology and discuss new insights into interleukin-1 in view of its history and the molecular bases of diseases, as well as current progress in therapeutics.
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New glycosyl donors have been developed that contained several para-substituted O-aryl protecting groups and their stereoselectivity for the glycosylation reaction was evaluated. A highly ß-selective glycosylation reaction was achieved by using thioglycosides that were protected by 4-nitrophenyl (NP) groups, which were introduced by using the corresponding diaryliodonium triflate. Analysis of the stereoselectivities of several glycosyl donors indicated that the ß-glycosides were obtained through an SN 2-type displacement from the corresponding α-glycosyl triflate. The NP group could be removed by reduction of the nitro group and acylation, followed by oxidation with ceric ammonium nitrate (CAN).