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A three-dimensional convolutional neural network model was developed to classify the severity of chronic kidney disease (CKD) using magnetic resonance imaging (MRI) Dixon-based T1-weighted in-phase (IP)/opposed-phase (OP)/water-only (WO) imaging. Seventy-three patients with severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2, CKD stage G4-5); 172 with moderate renal dysfunction (30 ≤ eGFR < 60 mL/min/1.73 m2, CKD stage G3a/b); and 76 with mild renal dysfunction (eGFR ≥ 60 mL/min/1.73 m2, CKD stage G1-2) participated in this study. The model was applied to the right, left, and both kidneys, as well as to each imaging method (T1-weighted IP/OP/WO images). The best performance was obtained when using bilateral kidneys and IP images, with an accuracy of 0.862 ± 0.036. The overall accuracy was better for the bilateral kidney models than for the unilateral kidney models. Our deep learning approach using kidney MRI can be applied to classify patients with CKD based on the severity of kidney disease.
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Tasa de Filtración Glomerular , Riñón , Imagen por Resonancia Magnética , Redes Neurales de la Computación , Insuficiencia Renal Crónica , Índice de Severidad de la Enfermedad , Humanos , Insuficiencia Renal Crónica/diagnóstico por imagen , Insuficiencia Renal Crónica/patología , Imagen por Resonancia Magnética/métodos , Femenino , Masculino , Persona de Mediana Edad , Riñón/diagnóstico por imagen , Riñón/patología , Anciano , Adulto , Aprendizaje Profundo , Imagenología Tridimensional/métodosRESUMEN
Dysgonomonas capnocytophagoides shows multidrug resistance to antibiotics and causes opportunistic infections in immunocompromised hosts. The drug resistance mechanisms of D. capnocytophagoides have not yet been identified. In this work, we analyzed D. capnocytophagoides isolated from a fatal case of peritonitis to clarify its drug resistance mechanisms. Whole genome sequencing revealed that our isolate harbored a chromosomally encoded metallo-beta-lactamase (designated blaDYB-1) and a chromosomally encoded ermFS gene. Phylogenetic analysis, primary sequence comparison, and structural modeling analysis of DYB-1 showed it was highly similar to CfiA in Bacteroides fragilis and belonged to the B1 MBL family. Transformation analysis into Escherichia coli TOP10 showed that a recombinant plasmid containing blaDYB-1 increased the minimum inhibitory concentration of beta-lactams, including carbapenem. We identified a novel chromosomally encoded class B1 metallo-beta-lactamase gene designated blaDYB-1 and an ermFS gene that contributed to multidrug resistance. This study indicates the importance of further surveillance for D. capnocytophagoides harboring blaDYB-1.
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OBJECTIVE: To determine the long-term survival of patients receiving home hemodialysis (HHD) through self-punctured arteriovenous access. METHODS: We conducted an observational study of all patients receiving HHD at our facility between 2001 and 2020. The primary outcome was treatment survival, and it was defined as the duration from HHD initiation to the first event of death or technique failure. The secondary outcomes were the cumulative incidence of technique failure and mortality. Cox proportional hazard models were used to identify the predictive factors for treatment survival. RESULTS: A total of 77 patients (mean age, 50.7 years; 84.4% male; 23.4% with diabetes) were included. The median dialysis duration was 18 hours per week, and all patients self-punctured their arteriovenous fistula. During a median follow-up of 116 months, 30 treatment failures (11 deaths and 19 technique failures) were observed. The treatment survival was 100% at 1 year, 83.5% at 5 years, 67.2% at 10 years, and 34.6% at 15 years. Age (adjusted hazard ratio [aHR], 1.07) and diabetes (aHR, 2.45) were significantly associated with treatment survival. Cardiovascular disease was the leading cause of death, and vascular access-related issues were the primary causes of technique failure, which occurred predominantly after 100 months from HHD initiation. CONCLUSION: This study showed a favorable long-term prognosis of patients receiving HHD. HHD can be a sustainable form of long-term kidney replacement therapy. However, access-related technique failures occur more frequently in patients receiving it over the long term. Therefore, careful management of vascular access is crucial to enhance technique survival.
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Hemodiálisis en el Domicilio , Humanos , Masculino , Femenino , Persona de Mediana Edad , Hemodiálisis en el Domicilio/métodos , Hemodiálisis en el Domicilio/mortalidad , Adulto , Derivación Arteriovenosa Quirúrgica , Anciano , Modelos de Riesgos Proporcionales , Fallo Renal Crónico/terapia , Fallo Renal Crónico/mortalidad , Estudios RetrospectivosRESUMEN
BACKGROUND: Information of short-term prognosis after hemodialysis (HD) introduction is important for elderly patients with chronic kidney disease (CKD) and their families choosing a modality of renal replacement therapy. Therefore, we developed a risk score to predict early mortality in incident elderly Japanese hemodialysis patients. MATERIALS AND METHODS: We analyzed data of incident elderly HD patients from a nationwide cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) to develop a prognostic risk score. Candidate risk factors for early death within 1 year was evaluated using multivariate logistic regression analysis. The risk score was developed by summing up points derived from parameter estimate values of independent risk factors. The association between risk score and early death was tested using Cox proportional hazards models. This risk score was validated twice by using an internal validation cohort derived from the JRDR and an external validation cohort collected for this study. RESULTS: Using the development cohort (n = 2,000), nine risk factors were retained in the risk score: older age (>85), yes = 2, no = 0; sex, male = 2, female = 0; lower body mass index (<20), yes = 2, no = 0; cancer, yes = 1, no = 0; dementia, yes = 3, no = 0; lower creatinine (<6.5 mg/dL), yes = 1, no = 0; lower albumin (<3.0 g/dL), yes = 3, no = 0; normal or high calcium (≥8.5 mg/dL), yes = 1, no = 0; and higher C reactive protein (>2.0 mg/dL), yes = 2, no = 0. In the internal and external validation cohorts (n = 739, 140, respectively), the medium- and high-risk groups (total score, 6 to 10 and 11 or more, respectively) showed significantly higher risk of early death than the low-risk group (total score, 0 to 5) (p<0.001). CONCLUSION: We developed a prognostic risk score predicting early death within 1 year in incident elderly Japanese HD patients, which may help detect elderly patients with a high-risk of early death after HD introduction.
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Fallo Renal Crónico , Humanos , Masculino , Femenino , Anciano , Pronóstico , Estudios de Cohortes , Fallo Renal Crónico/terapia , Japón/epidemiología , Diálisis Renal , Factores de RiesgoRESUMEN
We herein report a case of diffuse large B-cell lymphoma (DLBCL) involving multiple renal and bone infiltrations presenting with giant cell arteritis-like (GCA)-like manifestations. One month prior, the present patient had left-sided temporal headache, jaw claudication, and renal failure. The patient was diagnosed with DLBCL based on a renal biopsy. After rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus intrathecal methotrexate/cytarabine/prednisone and rituximab, high-dose methotrexate, and cytarabine (R-MA) chemotherapy, the patient's clinical manifestations improved, and complete remission was achieved. DLBCL rarely but occasionally presents with GCA-like manifestations or multiple renal and bone infiltrations, highlighting the need for prompt and aggressive combination chemotherapy.
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We developed a 3D convolutional neural network (CNN)-based automatic kidney segmentation method for patients with chronic kidney disease (CKD) using MRI Dixon-based T1-weighted in-phase (IP)/opposed-phase (OP)/water-only (WO) images. The dataset comprised 100 participants with renal dysfunction (RD; eGFR < 45 mL/min/1.73 m2) and 70 without (non-RD; eGFR ≥ 45 mL/min/1.73 m2). The model was applied to the right, left, and both kidneys; it was first evaluated on the non-RD group data and subsequently on the combined data of the RD and non-RD groups. For bilateral kidney segmentation of the non-RD group, the best performance was obtained when using IP image, with a Dice score of 0.902 ± 0.034, average surface distance of 1.46 ± 0.75 mm, and a difference of - 27 ± 21 mL between ground-truth and automatically computed volume. Slightly worse results were obtained for the combined data of the RD and non-RD groups and for unilateral kidney segmentation, particularly when segmenting the right kidney from the OP images. Our 3D CNN-assisted automatic segmentation tools can be utilized in future studies on total kidney volume measurements and various image analyses of a large number of patients with CKD.
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Redes Neurales de la Computación , Insuficiencia Renal Crónica , Humanos , Imagen por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Riñón/diagnóstico por imagen , Insuficiencia Renal Crónica/diagnóstico por imagenRESUMEN
CCN2/connective tissue growth factor (CTGF) potentially serves as a therapeutic target for chronic kidney disease. Here we investigated CCN2 module-4, encoded by Ccn2 exon 5, through the generation of Ccn2 exon 5 knockout mice (Ex5-/- mice). To investigate renal fibrosis pathogenesis, Ex5-/- mice were employed to model unilateral ureteral obstruction (UUO), unilateral ischemic-reperfusion injury (UIRI), and 5/6 nephrectomy. Interstitial fibrosis was significantly attenuated in the Ex5-/- mice in the three models. Furthermore, phosphorylated focal adhesion kinase (FAK) levels in tubular epithelial cells were significantly lower in the kidneys of the UUO- and UIRI-Ex5-/- mice than those of the Ex5+/+ mice. Moreover, CCN2 module 4-mediated renal tubule FAK and promoted fibrosis. These findings indicate that CCN2 module-4-FAK pathway components will serve as therapeutic targets for effectively attenuating renal fibrosis.
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INTRODUCTION: While recent investigations show that klotho exerts renoprotective actions, it has not been fully addressed whether klotho protein supplementation reverses renal damage. METHODS: The impacts of subcutaneous klotho supplementation on rats with subtotal nephrectomy were examined. Animals were divided into 3 groups: group 1 (short remnant [SR]): remnant kidney for 4 weeks, group 2 (long remnant [LR]): remnant kidney for 12 weeks, and group 3 (klotho supplementation [KL]): klotho protein (20 µg/kg/day) supplementation on the remnant kidney. Blood pressure, blood and urine compositions with conventional methods such as enzyme-linked immunosorbent assay and radioimmunoassay, kidney histology, and renal expressions of various genes were analyzed. In vitro studies were also performed to support in vivo findings. RESULTS: Klotho protein supplementation decreased albuminuria (-43%), systolic blood pressure (-16%), fibroblast growth factor (FGF) 23 (-51%) and serum phosphate levels (-19%), renal angiotensin II concentration (-43%), fibrosis index (-70%), renal expressions of collagen I (-55%), and transforming growth factor ß (-59%) (p < 0.05 for all). Klotho supplementation enhanced fractional excretion of phosphate (+45%), glomerular filtration rate (+76%), renal expressions of klotho (+148%), superoxide dismutase (+124%), and bone morphogenetic protein (BMP) 7 (+174%) (p < 0.05 for all). CONCLUSION: Our data indicated that klotho protein supplementation inactivated renal renin-angiotensin system, reducing blood pressure and albuminuria in remnant kidney. Furthermore, exogenous klotho protein supplementation elevated endogenous klotho expression to increase phosphate excretion with resultant reductions in FGF23 and serum phosphate. Finally, klotho supplementation reversed renal dysfunction and fibrosis in association with improved BMP7 in remnant kidney.
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Albuminuria , Enfermedades Renales , Animales , Ratas , Albuminuria/metabolismo , Suplementos Dietéticos , Fibrosis , Riñón/patología , Enfermedades Renales/patología , Proteínas Klotho/uso terapéutico , Fosfatos/metabolismoRESUMEN
During the treatment of a patient on hemodialysis with severe coronavirus disease 2019 (COVID-19), the patient was weaned from extracorporeal membrane oxygenation, which was used to treat severe COVID-19 pneumonia. However, the patient's condition worsened after the peak infection phase of COVID-19 because of acute respiratory distress syndrome with suspected hemophagocytic lymphohistiocytosis (HLH). After a bone marrow biopsy confirmed the diagnosis, methylprednisolone pulse therapy, followed by combination therapy (including oral prednisolone and cyclosporine) was immediately administered, and the patient survived. Because HLH can occur a month or more after the onset of COVID-19, even if the viral load is reduced to the point of being undetectable by reverse transcriptase-polymerase chain reaction, it can be considered to correspond to the "post-acute COVID-19 syndrome," which has recently been proposed. Early intervention is necessary, because HLH can be fatal. Therefore, it is important to know that HLH can occur at any stage of COVID-19 and to pay attention to the patient's progress over time, including checking the HScore.
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COVID-19 , Linfohistiocitosis Hemofagocítica , Humanos , COVID-19/complicaciones , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/terapia , Médula Ósea/patología , BazoRESUMEN
INTRODUCTION: The prognosis of patients with acute kidney injury (AKI) caused by type 1 cardiorenal syndrome (CRS) requiring continuous renal replacement therapy (CRRT) is unclear. We investigated the in-hospital mortality and prognostic factors in these patients. METHODS: We retrospectively identified 154 consecutive adult patients who received CRRT for AKI caused by type 1 CRS between January 1, 2013, and December 31, 2019. We excluded patients who underwent cardiovascular surgery and those with stage 5 chronic kidney disease. The primary outcome was in-hospital mortality. Cox proportional hazards analysis was performed to analyze independent predictors of in-hospital mortality. RESULTS: The median age of patients at admission was 74.0 years (interquartile range: 63.0-80.0); 70.8% were male. The in-hospital mortality rate was 68.2%. Age ≥80 years (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.21-2.87; p = 0.004), previous hospitalization for acute heart failure (HR, 1.67; 95% CI, 1.13-2.46; p = 0.01), vasopressor or inotrope use (HR, 5.88; 95% CI, 1.43-24.1; p = 0.014), and mechanical ventilation at CRRT initiation (HR, 2.24; 95% CI, 1.46-3.45; p < 0.001) were associated with in-hospital mortality. CONCLUSION: In our single-center study, the use of CRRT for AKI due to type 1 CRS was associated with high in-hospital mortality.
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Lesión Renal Aguda , Síndrome Cardiorrenal , Terapia de Reemplazo Renal Continuo , Adulto , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Femenino , Estudios Retrospectivos , Terapia de Reemplazo Renal , Síndrome Cardiorrenal/complicaciones , Síndrome Cardiorrenal/terapia , Pronóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapiaRESUMEN
Renal interstitial fibrosis is the final common pathway in the process of all kidney diseases, and it results in chronic kidney disease. CCN2 is an important factor in the pathogenesis of renal interstitial fibrosis, and analysis of its function can lead to treatments for chronic kidney disease. Since CCN2 knockout mice are developmentally lethal, generation of conditional knockout mice is essential for in vivo analysis. Since CCN2 is expressed in a variety of cells in the kidney, including podocytes, mesangial cells, pericytes, and tubular epithelial cells, it is necessary to perform cell-specific verification of the cells that play a central role in fibrosis. However, cell-specific validation using the Cre/loxP system in vivo has only been performed in mesangial cells. In our research program, we are focusing on the role of CCN2 in tubular epithelial cells in renal fibrogenesis. In this report, we introduce the creation of a tubular epithelial cell-specific knockout model and method of its analysis.
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Riñón , Insuficiencia Renal Crónica , Ratones , Animales , Riñón/metabolismo , Fibrosis , Ratones Noqueados , Insuficiencia Renal Crónica/metabolismo , Epitelio/metabolismoRESUMEN
A 75-year-old woman with colon cancer and distant metastases was treated with fluorouracil, levofolinate, and irinotecan (FOLFIRI) plus bevacizumab postoperatively. During the 32nd course, the patient developed massive proteinuria, and only bevacizumab was discontinued; the proteinuria improved rapidly over time. However, more than six months later, the patient developed massive proteinuria again, and her renal function declined. Renal biopsy revealed glomerular microangiopathy with prominent foam cell infiltration into the glomerulus, which was thought to be caused by chronic endothelial cell damage to the glomerular capillaries. Endothelial cell damage is thought to be caused not only by the inhibition of vascular endothelial growth factor action of bevacizumab in the glomerular capillary but also by the cytotoxicity of the concomitant anticancer drugs and coexisting clinical conditions such as dyslipidemia and hypertension. After discontinuing anticancer agents and intensifying diet and antihypertensive therapy, proteinuria and dyslipidemia slowly improved; however, it became difficult to continue adequate chemotherapy, and the tumor marker levels worsened. Combination therapies, including molecular targeted agents, have become common, and the side effects of anticancer agents are expected to continue to be complicated. To prevent the onset and severity of renal complications, management of blood pressure, lipid level, and glucose metabolism, as well as multidisciplinary medical management, including dietary therapy, is required.
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We evaluated a multiclass classification model to predict estimated glomerular filtration rate (eGFR) groups in chronic kidney disease (CKD) patients using magnetic resonance imaging (MRI) texture analysis (TA). We identified 166 CKD patients who underwent MRI comprising Dixon-based T1-weighted in-phase (IP)/opposed-phase (OP)/water-only (WO) images, apparent diffusion coefficient (ADC) maps, and T2* maps. The patients were divided into severe, moderate, and control groups based on eGFR borderlines of 30 and 60 mL/min/1.73 m2. After extracting 93 texture features (TFs), dimension reduction was performed using inter-observer reproducibility analysis and sequential feature selection (SFS) algorithm. Models were created using linear discriminant analysis (LDA); support vector machine (SVM) with linear, rbf, and sigmoid kernels; decision tree (DT); and random forest (RF) classifiers, with synthetic minority oversampling technique (SMOTE). Models underwent 100-time repeat nested cross-validation. Overall performances of our classification models were modest, and TA based on T1-weighted IP/OP/WO images provided better performance than those based on ADC and T2* maps. The most favorable result was observed in the T1-weighted WO image using RF classifier and the combination model was derived from all T1-weighted images using SVM classifier with rbf kernel. Among the selected TFs, total energy and energy had weak correlations with eGFR.
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Imagen por Resonancia Magnética , Insuficiencia Renal Crónica , Humanos , Riñón/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Insuficiencia Renal Crónica/diagnóstico por imagen , Reproducibilidad de los Resultados , Estudios Retrospectivos , Máquina de Vectores de SoporteRESUMEN
Purpose: Nephrologists have empirically predicted renal function from renal morphology. In diagnosing a case of renal dysfunction of unknown course, acute kidney injury and chronic kidney disease are diagnosed from blood tests and an imaging study including magnetic resonance imaging (MRI), and an examination/treatment policy is determined. A framework for the estimation of renal function from water images obtained using the Dixon method is proposed to provide information that helps clinicians reach a diagnosis by accurately estimating renal function on the basis of renal MRI. Approach: The proposed framework consists of four steps. First, the kidney area is extracted by MRI using the Dixon method with a U-net by deep learning. Second, the extracted renal region is registered with the target mask. Third, the kidney features are calculated based on the target mask classification information created by a specialist. Fourth, the estimated glomerular filtration rate (eGFR) representing the renal function is estimated using a regression support vector machine from the calculated features. Results: For the accuracy evaluation, we conducted an experiment to estimate the eGFR when MRI was performed and the eGFR slope, which is the annual rate of decline in eGFR. When the accuracy was evaluated for 165 subjects, the eGFR was estimated to have a root mean square error (RMSE) of 11.99 and a correlation coefficient of 0.83. Moreover, the eGFR slope was estimated to have an RMSE of 4.8 and a correlation coefficient of 0.5. Conclusions: Therefore, the proposed method shows the possibility of estimating the prognosis of renal function based on water images obtained by the Dixon method.
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Magnetic resonance imaging (MRI) is playing an increasingly important role in evaluating chronic kidney disease (CKD). It has the potential to be used not only for evaluation of physiological and pathological states, but also for prediction of disease course. Although different MRI sequences have been employed in renal disease, there are few studies that have compared the different sequences. We compared several multiparametric MRI sequences, and compared their results with the estimated glomerular filtration rate. Principal component analysis showed a similarity between T1 values and tissue perfusion (arterial spin labelling), and between fractional anisotropy (diffusion tensor imaging) and apparent diffusion coefficient values (diffusion-weighted imaging). In multiple regression analysis, only T2* values, derived from the blood oxygenation level-dependent (BOLD) MRI sequence, were associated with estimated glomerular filtration rate slope after adjusting for degree of proteinuria, a classic prognostic factor for CKD. In receiver operating characteristic curve analysis, T2* values were a good predictor of rapid deterioration, regardless of the degree of proteinuria. This suggests further study of the use of BOLD-derived T2* values in the workup of CKD, especially to predict the disease course.
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Riñón/patología , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Insuficiencia Renal Crónica/patología , Anciano , Imagen de Difusión por Resonancia Magnética/métodos , Progresión de la Enfermedad , Femenino , Fibrosis/patología , Tasa de Filtración Glomerular/fisiología , Humanos , Laboratorios , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Magnetic resonance imaging (MRI) is indispensable in clinical medicine for the morphological and tomographic evaluation of many parenchymal organs. With varied imaging methods, diverse biological information, such as the perfusion volume and measurements of metabolic products, can be obtained. In addition to conventional MRI for morphological assessment, diffusion-weighted MRI/diffusion tensor imaging is used to evaluate white matter structures in the brain; arterial spin labeling is used for cerebral blood flow evaluation; magnetic resonance elastography for fatty liver and cirrhosis evaluation; magnetic resonance spectroscopy for evaluation of metabolites in specific regions of the brain; and blood oxygenation level-dependent imaging for neurological exploration of eating behavior, obesity, and food perception. This range of applications will continue to expand in the future. Nutritional science is a multidisciplinary and all-inclusive field of research; therefore, there are many different applications of MRI. We present a literature review of MRI techniques that can be used to evaluate the nutritional status, particularly in patients on dialysis. We used MEDLINE as the information source, conducted a keyword search in PubMed, and found that, as a nutritional evaluation method, MRI has been used frequently to comprehensively and quantitatively evaluate muscle mass for the determination of body composition.
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Imagen por Resonancia Magnética , Estado Nutricional , Diálisis Renal , Composición Corporal , Distribución de la Grasa Corporal , Encéfalo/diagnóstico por imagen , Circulación Cerebrovascular , Imagen de Difusión Tensora , Diagnóstico por Imagen de Elasticidad , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Músculo Esquelético/diagnóstico por imagen , Tamaño de los Órganos , Insuficiencia Renal Crónica/diagnóstico por imagen , Insuficiencia Renal Crónica/terapiaRESUMEN
BACKGROUND: Klotho interacts with various membrane proteins, such as transforming growth factor-ß (TGFß) and insulin-like growth factor (IGF) receptors. The renal expression of klotho is diminished in chronic kidney disease. METHOD: In this study, we assessed the effects of klotho supplementation on a murine model of IgA nephropathy. Twenty-four-week-old hyper serum IgA (HIGA) mice were subcutaneously injected daily with recombinant human klotho protein (20âµg/kg per day) or the vehicle. After 2 months, the mice were killed using an anesthesia overdose and their kidneys were harvested for analysis. RESULTS: Supplementation of exogenous klotho protein reduced SBP, albuminuria, 8-epi-prostaglandin F2α excretion, glomerular filtration rate, renal angiotensin II concentration, and angiotensinogen expression in HIGA mice. Additionally, it enhanced renal expression of superoxide dismutase (SOD) and renal klotho itself. The findings using laser-manipulated microdissection demonstrated that klotho supplementation reduced the glomerular expression of TGFß, fibronectin, and IGF, and increased the glomerular expression of connexin (Cx) 40. CONCLUSION: These results indicate that klotho supplementation reduces blood pressure by suppressing the renin--angiotensin system in HIGA mice. Klotho inhibits IGF signaling to preserve glomerular Cx40 levels, ameliorating albuminuria in HIGA mice. Klotho protein supplementation attenuates mesangial expansion by inhibiting TGFß signaling in HIGA mice.
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Glomerulonefritis por IGA , Glucuronidasa , Albuminuria , Animales , Presión Sanguínea , Suplementos Dietéticos , Modelos Animales de Enfermedad , Glomerulonefritis por IGA/tratamiento farmacológico , Proteínas Klotho , RatonesRESUMEN
Cyst nematodes (Globodera spp. and Heterodera spp.) are highly evolved sedentary endoparasites that are considered as harmful pests worldwide. The hatching of the dormant eggs of cyst nematodes occurs in response to hatching factors (HFs), which are compounds that are secreted from the roots of host plants. Solanoeclepin A (SEA), a triterpene compound, has been isolated as HF for potato cyst nematode (PCN) eggs, whereas other compounds, such as steroidal glycoalkaloids (SGAs), are also known to show weak hatching stimulation (HS) activity. However, the structures of both compounds are different and the HF-mediated hatching mechanism is still largely unknown. In the present study, we observed specific hatching of PCN eggs stimulated by the hairy root culture media of potato and tomato, revealing the biosynthesis and secretion of HFs. SGAs, such as α-solanine, α-chaconine, and α-tomatine, showed significant HS activity, despite being remarkably less activities than that of SEA. Then, we evaluated the contribution of SGAs on the HS activities of the hairy root culture media. The estimated SGAs content in the hairy root culture media were low and nonconcordant with the HS activity of those, suggesting that the HS activity of SGAs did not contribute much. The analysis of structure-activity relationship revealed that the structural requirements of the HS activity of SGAs are dependent on the sugar moieties attached at the C3-hydoroxyl group and the alkaloid property of their aglycones. The stereochemistry in the EF rings of their aglycone also affected the strength of the HS activity.