RESUMEN
CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% [95% CI, 44.1-78.1] vs. 67.6% [95% CI, 57.5-76.9], p = 0.210), leukaemia-free survival (LFS) (62.3% [95% CI, 44.6-78.4] vs. 62.0% [95% CI, 51.8-71.7], p = 0.548), non-relapse mortality (NRM) rates (32.0% [95% CI, 19.0-54.0] vs. 25.3% [95% CI, 17.9-35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0-26.0] vs. 15.8% [95% CI, 9.8-25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.
Asunto(s)
Antígenos CD7 , Trasplante de Células Madre Hematopoyéticas , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Inducción de Remisión , Humanos , Masculino , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Adulto , Adolescente , Persona de Mediana Edad , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Adulto Joven , Niño , Recurrencia , Trasplante Homólogo , Receptores Quiméricos de Antígenos/uso terapéutico , Resultado del Tratamiento , Preescolar , Tasa de SupervivenciaRESUMEN
While the use of chimeric antigen receptor-T (CAR-T) therapy for T-cell malignancies is in the early stage of clinical trials, it exhibits substantial potential to offer long-term remission for patients with refractory/relapsed (R/R) T-cell malignancies. In our phase I/II clinical trials, 65 pediatric and adult patients with R/R T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T-ALL/LBL) were enrolled (NCT04572308 and NCT04916860). Of these, 60 participants (T-ALL 35, T-LBL 25) received a single dose of naturally selected anti-CD7 CAR (NS7CAR) T cells at three levels: a low dose (5 × 105 /kg), a medium dose (1 to 1.5 × 106 /kg), and a high dose (2 × 106 /kg). On day 28, 94.4% of patients achieved deep complete remission (CR) in bone marrow. Among the 32 patients with extramedullary disease, 78.1% showed response, with 56.3% in CR and 21.9% in partial remission. The 2-year overall survival and progression-free survival (PFS) were 63.5% (95% CI 47.7-79.4) and 53.7% (95% CI, 38.9-68.6), with no difference between pediatric and adult patients. PFS was significantly higher among the 37 CR patients who proceeded with consolidation transplant than the 10 patients who did not with 1-year PFS 67.2% (95% CI 51.9-82.4) versus 15.0% (95% CI 0-40.2), p < .0001. Of the 10 CR patients without transplants, eight relapsed, while two sustained CR on day 128, and day 180, respectively. Cytokine release syndrome occurred in 91.7% of patients (grade 1/2 in 80.0%, grade 3/4 in 11.7%) and 5% of patients had neurotoxicity. NS7CAR-T therapy is effective in treating R/R T-ALL/LBL patients with promising PFS while maintaining a manageable safety profile.
Asunto(s)
Linfoma de Células T Periférico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Receptores Quiméricos de Antígenos , Adulto , Humanos , Niño , Receptores Quiméricos de Antígenos/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Inmunoterapia Adoptiva/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Linfocitos T , Linfoma de Células T Periférico/tratamiento farmacológico , Recurrencia , Tratamiento Basado en Trasplante de Células y Tejidos , Antígenos CD19RESUMEN
Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad Aguda , Basiliximab/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Estudios Retrospectivos , Esteroides/uso terapéuticoRESUMEN
BACKGROUND: Three-dimensional computed tomography bronchography and angiography (3D-CTBA) provides detailed imaging information for pulmonary segmentectomy. This study was performed to verify the feasibility of 3D-CTBA-guided thoracoscopic segmentectomy for the treatment of pulmonary nodules. METHODS: A retrospective analysis was performed on all patients who underwent 3D-CTBA-guided uniport thoracoscopic segmentectomies or subsegmentectomies for pulmonary nodules in the period from May 2019 to May 2020. All of the information related to perioperative management and surgical operations was retrieved from the medical records and operating notes for detailed analysis. RESULTS: A total of 104 eligible operations involving the resection of 110 nodules with diameters in the range of 5-20 mm were included. Under 3D-CTBA guidance, the pulmonary nodules were located with an accuracy of 100% (110/110) and the median resection margin was 24.3 mm (17-33 mm). Additionally, the segmental (subsegmental) bronchi, arteries, and veins were identified with accuracy rates of 100% (104/104), 96.2% (100/104), and 94.2% (98/104), respectively. The postoperative complications consisted of 3 cases of pulmonary infection (2.9%), 6 cases of arrhythmia (5.8%), 2 cases of hemoptysis (1.9%), 4 cases of air leak (3.8%), and 2 cases of subcutaneous emphysema (1.9%). No perioperative death occurred. CONCLUSION: 3D-CTBA-guided thoracoscopic segmentectomy is an effective surgical approach for the management of pulmonary nodules.
Asunto(s)
Broncografía , Neoplasias Pulmonares , Angiografía/métodos , Humanos , Imagenología Tridimensional/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Mastectomía Segmentaria , Neumonectomía/métodos , Estudios Retrospectivos , Cirugía Torácica Asistida por Video/métodos , Tomografía Computarizada por Rayos XRESUMEN
There are a limited number of studies comparing outcomes of busulfan (BU)-based myeloablative hematopoietic stem cell transplantation using unmanipulated haploidentical donors (HIDs), HLA-matched unrelated donors (MUDs), and HLA-matched sibling related donors (MSDs) in acute myeloid leukemia (AML) patients with complete remission (CR) status. With this background, we compared outcomes among 377 cases of CR following consecutive HID-HSCT for AML (CR) to 86 MUD and 92 MSD-HSCT cases. All patients received BU-based myeloablative conditioning and an unmanipulated graft within the same period. The median patient age was 23 years (range 1.1 to 65 years), and 230 patients (41.4%) were under age18. Among the 555 patients, 432 (77.8%) were of intermediate cytogenetic risk and 123 (22.2%) were of adverse risk. A total of 113 patients (20.5%) had FLT3-ITD+ AML, 425 patients (76.6%) were in first complete remission (CR1) post-transplant, and 130 (23.4%) patients were in second CR (CR2). GVHD prophylaxis included mycophenolate mofetil (MMF), cyclosporine-A (CSA) with short-term methotrexate (MTX) for HID, and MUD-HSCT. MMF is not used for MSD-HSCT. The median survival follow-up time was 42 months (range 18-91 months). The 3-year leukemia-free survival (LFS) among the HID, MUD, and MSD cohorts was 73.8% ± 4.8%, 66.4% ± 8.5%, 74.5% ± 2.4%, respectively (P = 0.637). Three-year overall survival (OS) was 74.9% ± 2.4%, 81.8% ± 4.3%, and 77.5% ± 4.5% among the HID, MUD, and MSD cohorts, respectively (P = 0.322). There were no difference among the relapse rate among the HID, MUD, and MSD donor cohorts (14.3% ± 4.0% vs 20.3% ± 6.4% vs 14.5% ± 2.2, respectively; P = 0.851) or the non-relapse mortality (NRM) (12.3% ± 3.5% vs 9.5% ± 3.2% vs 14.0% ± 1.8%, respectively; P = 0.441). Multivariate analyses showed that MRD-positive pre-HSCT was the only risk factor associated with a lower OS and LFS and higher risk of relapse among all 555 patients. Compared with the use of a MUD or MSD, an HID for HSCT had similar outcomes among AML patients with CR states who underwent an allo-HSCT with BU-based myeloablative conditioning. MFC-MRD-positive pre-HSCT was an independent negative factor impact on outcomes for AML patients in CR. We conclude that for AML patients who do not have a MSD or if an urgent transplant is required, HSCT from an HID is a valid option.
Asunto(s)
Busulfano/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Hermanos , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Donante no Emparentado , Adulto JovenRESUMEN
Prior studies have suggested that for leukemia patients with high-risk features, haplo-identical-hematopoietic stem cell transplantation (HID-HSCT) has a stronger anti-leukemia effect compared with HSCT using an identical sibling donor (ISD-HSCT). However, it is unclear whether an HID-HSC transplant also augments the graft-versus-leukemia (GVL) effect among refractory/relapsed (R/R) acute myeloid leukemia (AML) patients who are not in remission (NR). We conducted a retrospective analysis of 124 R/R AML patients with NR status who underwent HID-HSCT between April 2012 and December 2016 and compared these to 27 R/R AML patients who underwent an ISD-HSCT within the same timeframe. Among all of the patients, 68 (45.0%) had primary induction failure (PIF) and 83 (54.9%) were relapsed and had failed to respond to at least one cycle of salvage combination chemotherapy. Myeloablative conditioning regimens were administered to all patients. Here, we present a retrospective multivariate analysis of pre-transplantation risk factors and characteristics of all 151 patients and developed a predictive scoring system to predict patient survival. The median period of follow-up was 46 months for all patients. The HID cohort had a higher 5-year overall survival (OS) compared with the ISD cohort (48.6% ± 4.6% vs 25.9% ± 8.4, respectively; P = 0.017) and higher LFS (leukemia-free survival) (41.6% ± 7.5% vs 25.9% ± 8.4%, respectively; P = 0.019). There was no difference in the 5-year cumulative incidence of non-relapse mortality (NRM) (18.0% ± 3.8% and 34.9% ± 12.6%, respectively; P = 0.212) between the two group. However, the 5-year cumulative incidence of relapse (CIRs) was lower in the HID group compared with the ISD group (55.4% ± 8.9% vs 67.3% ± 9.9%, respectively; P = 0.021). Multivariate analysis showed three risk factors associated with OS and LFS: (1) ISD-HSCT, (2) use of a standardized conditioning regimen, and (3) less than 50% proportional reduction of blast cells in the bone marrow (BM). Based on these three risk factors, we developed a predictive scoring system for R/R AML patients undergoing HSCT. Patients who had a predictive score of 0 and 1 had a 66.6% ± 4.5% and 44.1% ± 3.6% OS rate at 5 years, respectively. Patients with a score ≥ 2 had only a 4.4 ± 0.2% OS rate at 5 years. An HID-HSCT had a better anti-leukemia effect among R/R AML patients with an NR status compared with an ISD-HSCT. We also identified pre-transplantation risk factors to delineate subgroups that could derive maximal benefit from HSCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Donadores Vivos , Hermanos , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/tendencias , Prueba de Histocompatibilidad/métodos , Prueba de Histocompatibilidad/tendencias , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/tendencias , Trasplante Haploidéntico/tendencias , Resultado del Tratamiento , Adulto JovenRESUMEN
The current study aimed to examine both gray matter and functional activity changes in schizophrenia by combing both structural and task-related functional magnetic resonance imaging (fMRI). Nineteen patients with schizophrenia and 17 controls were recruited. The fMRI scan was performed while performing a working memory (WM) task. In terms of task performance, accuracy did not differ between groups, but there were significant differences in reaction time. Compared with controls, patients exhibited decreased functional activation in prefrontal areas, insula, lingual gyrus, and superior temporal gyrus during different phases of WM. The subcallosal cortex showed increased activation. Intriguingly, a structural-functional correlation was found in the left dorsolateral prefrontal cortex, anterior cingulate cortex, and subcallosal cortex in patients when performing high-load WM task. This study demonstrated both impaired gray matter volume and functional activation during WM in schizophrenia, suggesting structural and functional impairments. The structural-functional correlation in schizophrenia suggested that structural damage in schizophrenia might induce a decreased ability to modulate functional response in accordance with increasing task difficulty.
Asunto(s)
Corteza Cerebral , Disfunción Cognitiva , Memoria a Corto Plazo/fisiología , Neuroimagen , Esquizofrenia , Adulto , Mapeo Encefálico , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología , Disfunción Cognitiva/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esquizofrenia/complicaciones , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/patología , Esquizofrenia/fisiopatologíaRESUMEN
Salvage haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is considered in patients with severe aplastic anemia (SAA) if a matched unrelated donor (MUD) is unavailable. However, studies on haplo- and MUD transplantation in SAA are lacking. The present study retrospectively analyzed the outcomes of 89 young SAA patients who underwent unmanipulated alternative HSCT between September 2012 and September 2016 at our single center. Forty-one patients received haploidentical donors and forty-eight patients MUDs for HSCT. Most were heavily transfused and refractory to previous immunotherapy. The median durations for myeloid engraftment in the haplo- and MUD cohorts were 14 (range, 10 to 21) and 13 (range, 10 to 18) days, respectively. Compared with the MUD cohort, haplo-HSCT cohorts had an increased cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV (43.9% ± 7.8% versus 12.5% ± 4.8%, P = .001) and grades III to IV (21.1% ± 6.7% versus 6.6% ± 3.7%, P = .045) and similar limited chronic GVHD (47.7% ± 8.5% versus 38.5% ± 7.3%, P = .129) and extensive chronic GVHD (12.1% ± 6.8% versus 9.1% ± 4.3%, P = .198). The median follow-up time of the surviving patients was 26 months (range, 6 to 45). No significant differences were observed between haplo-HSCT and MUD HSCT cohorts in 3-year overall survival (80.3% ± 5.1% versus 89.6% ± 7.0%, P = .210), disease-free survival (76.4% ± 5.1% versus 89.4% ± 7.7%, P = .127), and GVHD-free failure-free survival (79.0% ± 8.6% versus 71.6% ± 9.3%, P = .976). Thus, haplo-HSCT, as salvage therapy, achieved similar outcomes as MUD HSCT in young SAA patients, thereby rendering it as an effective and safe option for SAA.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Anemia Aplásica/patología , Niño , Preescolar , Femenino , Humanos , Masculino , Resultado del Tratamiento , Donante no Emparentado , Adulto JovenRESUMEN
Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Berberine is a natural medicine with multiple beneficial biological activities. In this study, we explored the mechanisms underlying the neuroprotective action of berberine in mice subjected transient middle cerebral artery occlusion (tMCAO). Male mice were administered berberine (25, 50 mg/kg/d, intragastric; i.g.), glycyrrhizin (50 mg/kg/d, intraperitoneal), or berberine (50 mg/kg/d, i.g.) plus glycyrrhizin (50 mg/kg/d, intraperitoneal) for 14 consecutive days before tMCAO. The neurological deficit scores were evaluated at 24 h after tMCAO, and then the mice were killed to obtain the brain samples. We showed that pretreatment with berberine dose-dependently decreased the infarct size, neurological deficits, hispathological changes, brain edema, and inflammatory mediators in serum and ischemic cortical tissue. We revealed that pretreatment with berberine significantly enhanced uptake of 18F-fluorodeoxyglucose of ischemic hemisphere comparing with the vehicle group at 24 h after stroke. Furthermore, pretreatment with berberine dose-dependently suppressed the nuclear-to cytosolic translocation of high-mobility group box1 (HMGB1) protein, the cytosolic-to nuclear translocation of nuclear factor kappa B (NF-κB) and decreased the expression of TLR4 in ischemic cortical tissue. Moreover, co-administration of glycyrrhizin and berberine exerted more potent suppression on the HMGB1/TLR4/NF-κB pathway than berberine or glycyrrhizin administered alone. These results demonstrate that berberine protects the brain from ischemia-reperfusion injury and the mechanism may rely on its anti-inflammatory effects mediated by suppressing the activation of HMGB1/TLR4/NF-κB signaling.
Asunto(s)
Berberina/uso terapéutico , Proteína HMGB1/antagonistas & inhibidores , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Subunidad p50 de NF-kappa B/antagonistas & inhibidores , Fármacos Neuroprotectores/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Animales , Encéfalo/patología , Edema Encefálico/tratamiento farmacológico , Regulación hacia Abajo , Ácido Glicirrínico/uso terapéutico , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Infarto de la Arteria Cerebral Media/etiología , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones Endogámicos C57BL , Subunidad p50 de NF-kappa B/genética , Subunidad p50 de NF-kappa B/metabolismo , Daño por Reperfusión/complicaciones , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
A rapid method was developed and validated by ultra-performance liquid chromatography-triple quadrupole mass spectroscopy with ultraviolet detection (UPLC-UV-MS) for simultaneous determination of paris saponin I, paris saponin II, paris saponin VI and paris saponin VII. Partial least squares discriminant analysis (PLS-DA) based on UPLC and Fourier transform infrared (FT-IR) spectroscopy was employed to evaluate Paris polyphylla var. yunnanensis (PPY) at different harvesting times. Quantitative determination implied that the various contents of bioactive compounds with different harvesting times may lead to different pharmacological effects; the average content of total saponins for PPY harvested at 8 years was higher than that from other samples. The PLS-DA of FT-IR spectra had a better performance than that of UPLC for discrimination of PPY from different harvesting times.
Asunto(s)
Cromatografía Liquida/métodos , Liliales/química , Espectrometría de Masas/métodos , Espectrofotometría Ultravioleta/métodos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Análisis de los Mínimos Cuadrados , Estándares de ReferenciaRESUMEN
Gentiana rigescens, an ethnomedicine, is widely cultivated in Yunnan province of China. Although a wide range of metabolites including iridoid glycosides, flavonoids and triterpenoids have been reported in this ethnomedicine, the data on accumulation and distribution of metabolites in certain parts are limited. In this study, targeted metabolic fingerprinting of iridoid glycosides based on liquid chromatography-ultraviolet detection-tandem mass spectrometry (LC-UV-MS/MS) was developed to investigate the metabolic similarities and differences in different parts and origins. Thirty-one compounds, including iridoid glycosides and flavonoids, were detected from targeted metabolite profiling and plausibly assigned to the different parts of G. rigescens. Multivariate statistical analysis was designed to reveal close chemical similarities between all the selected samples and to identify key metabolites characteristic of the standard. The results suggested that accumulation and distribution of metabolites in aerial and underground parts were different. Moreover, root samples tended to be grouped on the basis of the geographical closeness of region. Five metabolites can be considered as potential markers for the classification of underground parts from different regions. These results provided chemical information on the potential pharmaceutical value for further research, making G. rigescens ideal for the rational usage of different parts and exploitation of the source.
Asunto(s)
Cromatografía Liquida/métodos , Gentiana/química , Extractos Vegetales/química , Espectrometría de Masas en Tándem/métodos , Flavonoides/análisis , Flavonoides/química , Glicósidos Iridoides/análisis , Glicósidos Iridoides/química , Medicina Tradicional , Análisis MultivarianteRESUMEN
INTRODUCTION: Gentianaceae species which widely occur all over the world are used as folk medicine and raw food material with bitter properties. Although comparative analysis on metabolites in several Gentianaceae species has been reported, metabolic similarities used for chemotaxonomic studies are not yet clear. OBJECTIVE: To systematically characterise the variations of holistic metabolome and characteristic metabolites (iridoid glycosides and phenols) in nine Gentianaceae species from western China. METHODOLOGY: Fourier transform infrared (FT-IR) spectroscopy was applied to determine the variations of holistic metabolome. A targeted metabolic profiling using liquid chromatography with tandem mass spectrometry (LC-MS/MS) was established for determination of seven characteristic metabolites and identification of their derivatives. Both FT-IR and LC-MS/MS data were subjected to chemometrics analysis for exploring variations in iridoid glycosides and phenols within these species. RESULTS: Holistic metabolome in genera Gentiana and Swertia was largely different. Diversity of the biosynthetic pathway of iridoid glycosides was also observed in these species. Principal component analysis (PCA) showed a clear separation according to infrageneric classifications of genus Gentiana. Some secondary metabolites, such as mangiferin, rhodenthoside A-C, isoorientin, isovitexin, amarogentin, and swertianolin would serve as potential chemotaxonomic markers to differentiate Gentianaceae species. Furthermore, the accumulation of the six major metabolites seems to depend on geographical regions in Sect. Monopodiae and Sect. Cruciata. CONCLUSIONS: The combination of LC-MS/MS and FT-IR would provide some potential evidence on chemotaxonomic studies of Gentianaceae. Copyright © 2016 John Wiley & Sons, Ltd.
Asunto(s)
Gentianaceae/química , Glicósidos Iridoides/clasificación , Metaboloma , Fenoles/clasificación , Extractos Vegetales/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Espectrometría de Masas en Tándem/métodos , Biomarcadores/química , Biomarcadores/metabolismo , Vías Biosintéticas , China , Cromatografía Liquida/métodos , Gentiana/química , Gentiana/metabolismo , Gentianaceae/metabolismo , Glicósidos Iridoides/química , Glicósidos Iridoides/metabolismo , Medicina Tradicional , Metabolómica , Estructura Molecular , Fenoles/química , Fenoles/metabolismo , Metabolismo Secundario , Especificidad de la Especie , Swertia/química , Swertia/metabolismoRESUMEN
Medicinal and edible plant Maca is rich in various nutrients and owns great medicinal value. Based on near infrared diffuse reflectance spectra, 139 Maca samples collected from Peru and Yunnan were used to identify their geographical origins. Multiplication signal correction (MSC) coupled with second derivative (SD) and Norris derivative filter (ND) was employed in spectral pretreatment. Spectrum range (7,500-4,061 cm⻹) was chosen by spectrum standard deviation. Combined with principal component analysis-mahalanobis distance (PCA-MD), the appropriate number of principal components was selected as 5. Based on the spectrum range and the number of principal components selected, two abnormal samples were eliminated by modular group iterative singular sample diagnosis method. Then, four methods were used to filter spectral variable information, competitive adaptive reweighted sampling (CARS), monte carlo-uninformative variable elimination (MC-UVE), genetic algorithm (GA) and subwindow permutation analysis (SPA). The spectral variable information filtered was evaluated by model population analysis (MPA). The results showed that RMSECV(SPA) > RMSECV(CARS) > RMSECV(MC-UVE) > RMSECV(GA), were 2. 14, 2. 05, 2. 02, and 1. 98, and the spectral variables were 250, 240, 250 and 70, respectively. According to the spectral variable filtered, partial least squares discriminant analysis (PLS-DA) was used to build the model, with random selection of 97 samples as training set, and the other 40 samples as validation set. The results showed that, R²: GA > MC-UVE > CARS > SPA, RMSEC and RMSEP: GA < MC-UVE < CARS Asunto(s)
Lepidium/química
, Plantas Medicinales/química
, Espectroscopía Infrarroja Corta
, Algoritmos
, China
, Análisis de los Mínimos Cuadrados
, Modelos Teóricos
, Método de Montecarlo
, Perú
, Análisis de Componente Principal
RESUMEN
The harvest time of traditional Chinese medicine (TCM) is a very essential part for the production and quality of TCM which is the prerequisite for safe and effective clinical use of TCM. It is of great importance to carry out the research of timely harvest time of TCM. With Fourier transform infrared spectroscopy (FTIR) to study harvest time of Seventy-two Gentiana Rigescens samples. First derivative, second derivative, standard normal variate, multiplicative scatter correction and Savitaky-Golay(15,3) smoothing of all original spectra were pretreated with TQ8.0 software. Samples were divided into calibration set and prediction set at the ratio of 3â¶1. Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) model were established. The result indicated that after removing noise spectrum, the spectra range was from 1 800 to 600 cm-1, the method SNV combined with SD and SG present the best result of spectra pretreatment. The contribution rates of first three principal components were 92.47% with PCA. Small differences were found for the samples harvested in May, September and October. Same spectrum range was chosen and PLS-DA was applied to establish the model. The R2 and RMSEE were 0.967 8, 0.086 0, respectively, and the prediction accuracy is 100%. The methods of PCA and PLS-DA have good ability to classify and identify different harvest time of Gentiana Rigescens. It provided a basis for the identification of different harvest time of TCM.
RESUMEN
Multiple cropping systems are the way to cope with the shortage of traditional Chinese medicine (TCM) resources and enhance the utilization ratio of land. The aim of this study was to investigate seventy Gentiana rigescens Franch samples which were planted in slope and in multiple cropping system mixed with Juglans regia, Alnus nepalensis, Eucalyptus robusta, Alnus nepalensis, Camellia sinensis, Chaenomeles sinensis using Fourier transform infrared (FTIR) spectroscopy. The pretreatments such as baseline correction, normalization and second derivative of all the original spectra were performed with Omnic 8.0 software. Moreover, second derivative spectra of samples and gentiopicroside standard were analyzed. In addition, two spectral databases were set up based on the average spectra of every variety with Omnic 8.0 software. The first library (Lib1) which included the spectra region from 1 800 to 600 cm-1 had the algorithm of expert retrieve while the correlation retrieve and square differential retrieve were dealt with the second library (Lib2) in the full spectral range. The results indicated that it is difficult to identify the infrared spectra of samples directly because they had high similarities. There were multiple common peaks between spectra of samples and gentiopicroside standards. The absorption peaks of 1 611 and 1 076 cm-1 of gentiopicroside were the two main characteristic peaks in the second derivative spectra. The difference of peak shape of every sample in the wave number of 1 076 cm-1 was small. By comparing peak area at 1 611 cm-1, the samples planted with J. regia contained highest content of gentiopicroside while the content of this effective constituent was the lowest in the samples which were planted in the slope and in the multiple cropping systems mixed with C sinensis. The differences of effective components in the samples with different planting patterns were represented by the variances of spectral matching values. The difference of matching values of samples planted with J. regia, A. nepalensis, E. Robusta and A. nepalensis were lower than that with slope and C. Sinensis. The number of misjudgment of expert retrieval, correlation retrieve and square differential retrieve were 11, 4 and 9, respectively. The discrimination result of correlation retrieve was the best in the full spectral range and the correct recognition rate was 94.29%. Fourier transforms infrared (FTIR) spectroscopy combined with second derivative and retrieval had good ability to discriminate G. rigescens with different cropping systems. It could provide a basis for the discrimination of different planting patterns of TCM
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Gentiana , Espectroscopía Infrarroja por Transformada de Fourier , Algoritmos , Bases de Datos Factuales , Glucósidos Iridoides , Programas InformáticosRESUMEN
Fourier-transform infrared spectroscopy combined with partial least squares discriminate analysis (PLS-DA) and hierarchical cluster analysis (HCA) were used to rapidly discriminate the Swertia davidi Franch which collected from different origins. The original infrared spectra data of different parts of all the 70 samples which collected from four different regions were preprocessed by automatic calibration, automatic smoothing, the first derivative and the,second derivative. Then the processed data were imported into OMNIC 8.2 and the absorption peaks were compared; PLS-DA was performed by SIMCA-P⺠10.0 and the effect of discrimination of different origins was compared by 3D score plot of the first three principal components; the infrared spectral data were imported into SPSS 19. 0 for HCA to compare classification results of different parts by the dendrogram. The results showed that: (1) There were differences among the spectra of the roots of different origins in the spectral peaks in 1,739, 1,647, 1,614, 1,503, 1,271, 1,243, 1,072 cm⻹. The spectra of the stems of different origins showed differentiation in the wavelength in 1 503, 1 270, 1 246 cm⻹; (2) The characteristic peaks of different parts of the same origin were different; (3) PLS-DA indicated that the data which were processed by automatic correction, automatic smoothing and second derivative have showed the best classification. In addition, the discrimination of roots which collected from different origins could be the best; (4) Tree diagram of HCA showed that the accuracy rate of cluster in roots, stems and leaves were 83%, 56%, and 70%, respectively. In conclusion: FTIR combined with PLS-DA and HCA can rapidly and accurately differentiate S. davidi that collected from different origins, the origin discrimination effect of different parts was clearly different that the classification of roots is the best, the second derivative could enhance the specificity of the samples, the classification in 3D score plot could be visualized and obvious.
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Plantas Medicinales/clasificación , Swertia/clasificación , Análisis de los Mínimos Cuadrados , Plantas Medicinales/química , Espectroscopía Infrarroja por Transformada de Fourier , Swertia/químicaRESUMEN
The application of traditional Chinese medicine (TCM) and their preparations have a long history. With the deepening of the research, the market demand is increasing. However, wild resources are so limited that it can not meet the needs of the market. The development of wild and cultivated samples and research on accumulation dynamics of chemical component are of great significance. In order to compare composition difference of different parts (root, stem, and leaf) of wild and cultivated G. rigescens, Fourier infrared spectroscopy (FTIR) and second derivative spectra were used to analyze and evaluate. The second derivative spectra of 60 samples and the rate of affinity (the match values) were measured automatically using the appropriate software (Omnic 8.0). The results showed that the various parts of wild and cultivated G. rigescens. were high similar the peaks at 1732, 1 643, 1 613, 1 510, 1 417, 1 366, 1 322, 1 070 cm(-1) were the characteristic peak of esters, terpenoids and saccharides, respectively. Moreover, the shape and peak intensity were more distinct in the second derivative spectrum of samples. In the second derivative spectrum range of 1 800-600 cm(-1), the fingerprint characteristic peak of samples and gentiopicroside standards were 1 679, 1 613, 1 466, 1 272, 1 204, 1 103, 1 074, 985, 935 cm(-1). The characteristic peak intensity of gentiopicroside of roots of wild and cultivated samples at 1 613 cm(-1) (C-C) was higher than stems and leaves which indicated the higher content of gentiopicroside in root than in stem and leaves. Stems of wild samples at 1 521, 1 462 and 1 452 cm(-1) are the skeletal vibration peak of benzene ring of lignin, and the stem of cultivated sample have stronger peak than other samples which showed that rich lignin in stems. The iInfrared spectrum of samples were similar with the average spectral of root of wild samples, and significant difference was found for the correlation between second derivative spectrum of samples and average spectral of wild samples root, and the sequence of similarity was root > stem > leaf. Therefore, FTIR combined with second derivative spectra was an express and comprehensive approach to analyze and evaluate in the imperceptible differences among different parts of wild and cultivated of G. rigescens.
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Gentiana/química , Fitoquímicos/análisis , Espectroscopía Infrarroja por Transformada de Fourier , Glucósidos Iridoides/análisis , Hojas de la Planta/química , Raíces de Plantas/química , Tallos de la Planta/química , Programas Informáticos , Espectrofotometría InfrarrojaRESUMEN
The Processing of traditional Chinese medicine (TCM) is the key to clinical application of TCM, and processing has functions such as enhancing the efficacy, attenuating the toxicity andmoderating medicine property. In order to the realizing safe, reasonable and effective use of medicine in clinical, research on identification of TCM processed products is of great significance. The Gentiana rigescens samples which processed with five different methods were discriminated by Fourier transform infrared spectroscopy (FTIR). Baseline correction and normalization were used to pretreat all original spectra and the noise was cut off. The spectra range was from 3 400 to 600 cm-1. The effect of multiple scattering correction and standard normal variable on the model were observed and compared. Samples were divided into calibration set and prediction set at the ratio of 3â¶1. The principal component analysis (PCA) was applied to reduce data dimensionality and discriminant analysis model was established. The result indicated that the main absorption peaks of samples were 3 378, 2 922, 1 732, 1 610, 1 417, 1 366, 1 316, 1 271, 1 068, 1 048 cm- 1 which 1 738, 1 643, 1 613, 1 420, 1 051 cm-1 as to gentiopicrin; 1 068, 1 048, 935 cm-1 as to carbohydrate. The accumulation contribution rate of first three principal components is 94.05%. Most of the information reflected the original data. There were differences among different samples. The result of discriminant analysis showed that the recognition rate of G. rigescens samples could achieve to 100% based on baseline correction and normalization treatment combined with MSC with the precondition of principal component scores being 10. In conclusion, FTIR is a feasible, rapid and non-destructive method to discriminate G. rigescens samples wtih different processing methods. It also provided reference for discrimination of processed products of medicine materials.
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Gentiana , Espectroscopía Infrarroja por Transformada de Fourier , Calibración , Análisis Discriminante , Glucósidos Iridoides , Análisis de Componente PrincipalRESUMEN
The Panax notoginseng is an important Chinese herbal medicine (CHM) and the quality is affected by growing environment. UV spectra approach was used to study the relationships between UV spectra of P. notoginseng and locations, rapidly. The UV spectra of fifty P. notoginseng samples which collected from ten regions were obtained and processed by using mean value, smoothing and derivative. The numbers of common peaks of chloroform, ethanol and water extractions were compared, respectively and the best extraction solvent was confirmed. The differences and relationships of P. notoginseng samples from different locations were investigated by comparing the characteristics of UV spectra combined with partial least square discriminant analysis (PLS-DA). The results showed that the extract ratio was the best in chloroform and the RSD% of precision, repeatability and stability in 30 h were 0.00ï½0.42, 0.00ï½0.54 and 0.00ï½0.60, respectively. The spectra of samples collected from different areas were similar except the absorbance. It could display the fingerprint characteristics. The common peaks of UV spectra were 194, 200, 204, 210 and 218 nm and the peaks absorption value ranged from 0.00 to 4.00. It showed that the main constituent had low correlation with collection regions while the content may be affected by the collection areas. The PLS-DA score plots could show the relationships among the P. notoginseng from different locations. In conclusion, this qualitative method could evaluate P. notoginseng samples from different locations rapidly and exactly. Moreover, it could provide the reference for source discrimination of CHM.
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UV-Vis and HPLC fingerprint of different harvest time of the leaves of Alstonia scholaris (L.) R. Br. were establish the for identification and quality evaluation to promote the development of Dai Medicine modernization. The optimal extraction condition was used to obtain UV - vis data of different harvest time which were deducted background and eight spot smooth, were collected to make the principal component analysis in SIMCA-P(+)11.5, identifying the samples quickly with the first three principal component three-dimensional diagram. The HPLC fingerprint were obtained with Agilent ZORBAX Eclipse XDB C18 (250×4.6 mm, 5 µm) chromatographic column with the mobile phase of acetonitrile (B) - water (contain 0.1% formic acid) (A) for gradient elution (0ï½5 min, 5% B; 5ï½35 min, 5% Bâ26% B; 35ï½40 min, 26% Bâ56% B). The wavelength was set at 287 nm and the column temperature was maintained at 30 â. The flow rate was 1.0 mL·min-1 and the injection volume was 7 µL. The HPLC fingerprint of different harvest time of the leaves of Alstonia scholaris (L.) R. Br. was analysised by cluster analysis to quality evaluation. Research findings showing: (1) The UV-Vis spectrogram of different harvest time of the leaves of Alstonia scholaris (L.) R. Br. were divided into three parts according to the absorption peak position and amplitude of variation. The first was 235 to 400 nm, the second was 400 to 500 nm, and the third was 500 to 800 nm. In the first part, absorption peak were focused on 270, 287 and 325 nm, which can reflect the fingerprint character for the high absorbance and amplitude of variation. Absorption peak were distributed in 410 and 464 nm in the second part, absorbance and amplitude of variation were lower than the first part. There was a bigger absorption peak at 665 nm in the third part, but the absorbance had no difference. The UV-Vis data of different harvest time were gathered to make the principal component analysis, the result was that the samples of same month were concentrated distribution, but different month samples were dispersed distribution. (2) HPLC fingerprint were divided into three categories through hierarchical cluster analysis, 3, 4, 5 and 7 month were the first category, 6, 8, 9 month samples were second category, the others were third category. Chemical composition and content of the same category samples were similar, but the different category samples had a obvious difference, more important is that the third category samples content was the highest. Combining UV-Vis FP and HPLC FP can identify and evaluate quickly the samples of different harvest time of the leaves of Alstonia scholaris (L.) R. Br. The optimal harvest time of Alstonia scholaris (L.) R. Br. was from October to next February, which was the coldest season in the Dai calendar.