RESUMEN
Cucurbitacin B (CuB) is a natural triterpenoid with diverse pharmacological effects including potent anticancer activity. However, its oral bioavailability is hampered by limited metabolism in vivo. We characterized CuB's in vivo metabolism in rats to uncover bioactive metabolites retaining therapeutic potential, using a robust UHPLC-Q-TOF-MS/MS workflow. This workflow combined molecular networking, fragmentation filtering, and mass defect filtering to identify CuB metabolites in rat urine, plasma, and feces following oral administration. Thirteen metabolites were identified and seven were confirmed. Major phase I transformations involved hydrolysis, reduction, epoxidation, and amination. Phase II conjugation included cysteine, glutathione, glucuronide, and gluconic acid conjugates. Notably, one of the main metabolites formed was the cysteine conjugate CuB-Cys. CuB-Cys maintained similar in vitro antiproliferative activity to CuB on HepG2, MCF-7, and PANC-1 cancer cell lines. However, it demonstrated lower cytotoxicity towards non-cancerous L02 cells, highlighting improved therapeutic selectivity. Mechanistically, CuB-Cys induced greater apoptotic signaling in HepG2 cells than CuB via enhanced caspase activation and disrupted BAX-Bcl-2 balance. This represents the first systematic characterization of CuB's in vivo metabolic pathway. The identification and confirmation of CuB-Cys provide insight for drug development efforts aiming to maintain therapeutic efficacy while reducing toxicity, via metabolite-based approaches. Our findings shed light on strategies for improving CuB's clinical potential.
RESUMEN
A systematic investigation combined with a Global Natural Products Social (GNPS) molecular networking approach, was conducted on the metabolites of the deep-sea-derived fungus Samsoniella hepiali W7, leading to the isolation of three new fusaric acid derivatives, hepialiamides A-C (1-3) and one novel hybrid polyketide hepialide (4), together with 18 known miscellaneous compounds (5-22). The structures of the new compounds were elucidated through detailed spectroscopic analysis. as well as TD-DFT-based ECD calculation. All isolates were tested for anti-inflammatory activity in vitro. Under a concentration of 1 µM, compounds 8, 11, 13, 21, and 22 showed potent inhibitory activity against nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells, with inhibition rates of 34.2%, 30.7%, 32.9%, 38.6%, and 58.2%, respectively. Of particularly note is compound 22, which exhibited the most remarkable inhibitory activity, with an IC50 value of 426.2 nM.
Asunto(s)
Ácido Fusárico , Paecilomyces , Ácido Fusárico/farmacología , Macrófagos , Antiinflamatorios , Estructura MolecularRESUMEN
BACKGROUND: Sarcopenia is one of the early pathological manifestations of cancer cachexia. This change in quality and function has a general and special impact on the prognosis of many types of tumors. However, there are few studies to evaluate the overall impact of sarcopenia on the prognosis of gynecological tumors in sufficient follow-up period. METHODS: This study systematically searched PubMed, EMBASE, web of science, and MEDLINE databases for related studies and related references since April 15, 2021. The 1-year, 5-year overall survival (OS), progression-free survival (PFS), hazard ratio (HR), and 95% confidence interval (CI) were analyzed by Stata 14.0.(CRD 42021236036). RESULTS: A total of 23 observational studies involving 3495 female patients were included in the analysis, with an average prevalence of 46.9% (38.5%-55.3%). Meta-analysis showed that the 1-year OS (RR: 1.60, 95% CI = [1.04, 2.46]) of patients with sarcopenia was significantly lower than that of patients without sarcopenia, and then this effect gradually decreased. The results showed that sarcopenia was an independent predictor of OS (HR: 1.78, 95% CI = [1.38, 2.30]) and PFS (HR: 1.32, 95% CI = [1.02, 1.70]) in gynecological cancer patients. Subgroup analysis showed that sarcopenia was significant in Asian population (HR: 1.93, 95% CI = [1.18, 3.17]) and cervical cancer patients (HR: 5.07, 95% CI = [2.82, 9.56]). CONCLUSION: The survival and recurrence outcome of patients with sarcopenia independently related to surgery, and its impact is very obvious in the short term. In addition, Asian participants with sarcopenia face a greater risk of death than Western participants.
Asunto(s)
Sarcopenia , Neoplasias del Cuello Uterino , Femenino , Humanos , Prevalencia , Pronóstico , Modelos de Riesgos Proporcionales , Sarcopenia/epidemiología , Neoplasias del Cuello Uterino/epidemiologíaRESUMEN
The pericarp of Herpetospermum pedunculosum (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl4-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD50 and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD50) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD50 of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components.
RESUMEN
BACKGROUND: Prostate lymphoma has no characteristic clinical symptomatology, is often misdiagnosed, and currently, clinical case reports of this disease are relatively rare. The disease develops rapidly and is not sensitive to conventional treatment. A delay in the treatment of hydronephrosis may lead to renal function injury, often causing physical discomfort and rapid deterioration with the disease. This paper presents two patients with lymphoma of prostate origin, followed by a summary of the literature concerning the identification and treatment of such patients. CASE SUMMARY: This paper reports on the cases of two patients with prostate lymphoma admitted to the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, one of whom died of the disease 2 mo after diagnosis, while the other was treated promptly, and his tumor was significantly reduced at the 6-mo follow-up. CONCLUSION: The literature shows that prostate lymphoma is often seen as a benign prostate disease during its pathogenesis, even though primary prostate lymphoma enlarges rapidly and diffusely with the invasion of surrounding tissues and organs. In addition, prostate-specific antigen levels are not elevated and are not specific. There are no significant features in single imaging either, but during dynamic observation of imaging, it can be found that the lymphoma is diffusely enlarged locally and that systemic symptoms metastasize rapidly. The two cases of rare prostate lymphoma reported herein provide a reference for clinical decision making, and the authors conclude that early nephrostomy to relieve the obstruction plus chemotherapy is the most convenient and effective treatment option for the patient.
RESUMEN
Trichlorfon, one of the most widely used organophosphate insecticides, is commonly employed in aquaculture and agriculture to combat parasitic infestations. However, its inherent instability leads to rapid decomposition into dichlorvos (DDVP), increasing its toxicity by eightfold. Therefore, the environmental effects of trichlorfon in real-world scenarios involve the combined effects of trichlorfon and its degradation product, DDVP. In this study, we systematically investigated the degradation of trichlorfon in tap water over time using HPLC and LC-MS/MS analysis. Subsequently, an experiment was conducted to assess the acute toxicity of trichlorfon and DDVP on goldfish (Carassius auratus), employing a 1H NMR-based metabolic approach in conjunction with serum biochemistry, histopathological inspection, and correlation network analysis. Exposure to trichlorfon and its degradation product DDVP leads to increased lipid peroxidation, reduced antioxidant activity, and severe hepatotoxicity and nephrotoxicity in goldfish. Based on the observed pathological changes and metabolite alterations, short-term exposure to trichlorfon significantly affected the liver and kidney functions of goldfish, while exerting minimal influence on the brain, potentially due to the presence of the blood-brain barrier. The changes in the metabolic profile indicated that trichlorfon and DDVP influenced several pathways, including oxidative stress, protein synthesis, energy metabolism, and nucleic acid metabolism. This study demonstrated the applicability and potential of 1H NMR-based metabonomics in pesticide environmental risk assessment, providing a feasible method for the comprehensive study of pesticide toxicity in water environments.
Asunto(s)
Insecticidas , Plaguicidas , Animales , Triclorfón/análisis , Diclorvos/toxicidad , Diclorvos/análisis , Carpa Dorada/metabolismo , Cromatografía Liquida , Espectroscopía de Protones por Resonancia Magnética , Espectrometría de Masas en Tándem , Insecticidas/análisis , Plaguicidas/análisis , Agua/metabolismoRESUMEN
Previous studies have found that deficiency in nuclear receptor-related factor 1 (Nurr1), which participates in the development, differentiation, survival, and degeneration of dopaminergic neurons, is associated with Parkinson's disease, but the mechanism of action is perplexing. Here, we first ascertained the repercussion of knocking down Nurr1 by performing liquid chromatography coupled with tandem mass spectrometry. We found that 231 genes were highly expressed in dopaminergic neurons with Nurr1 deficiency, 14 of which were linked to the Parkinson's disease pathway based on Kyoto Encyclopedia of Genes and Genomes analysis. To better understand how Nurr1 deficiency autonomously invokes the decline of dopaminergic neurons and elicits Parkinson's disease symptoms, we performed single-nuclei RNA sequencing in a Nurr1 LV-shRNA mouse model. The results revealed cellular heterogeneity in the substantia nigra and a number of activated genes, the preponderance of which encode components of the major histocompatibility II complex. Cd74, H2-Ab1, H2-Aa, H2-Eb1, Lyz2, Mrc1, Slc6a3, Slc47a1, Ms4a4b, and Ptprc2 were the top 10 differentially expressed genes. Immunofluorescence staining showed that, after Nurr1 knockdown, the number of CD74-immunoreactive cells in mouse brain tissue was markedly increased. In addition, Cd74 expression was increased in a mouse model of Parkinson's disease induced by treatment with 6-hydroxydopamine. Taken together, our results suggest that Nurr1 deficiency results in an increase in Cd74 expression, thereby leading to the destruction of dopaminergic neurons. These findings provide a potential therapeutic target for the treatment of Parkinson's disease.
RESUMEN
BACKGROUND: Levodopa (L-DOPA) is considered the most reliable drug for treating Parkinson's disease (PD) clinical symptoms. Regrettably, long-term L-DOPA therapy results in the emergence of drug-induced abnormal involuntary movements (AIMs) in most PD patients. The mechanisms underlying motor fluctuations and dyskinesia induced by L-DOPA (LID) are still perplexing. METHODS: Here, we first performed the analysis on the microarray data set (GSE55096) from the gene expression omnibus (GEO) repository and identified the differentially expressed genes (DEGs) using linear models for microarray analysis (Limma) R packages from the Bioconductor project. 12 genes (Nr4a2, Areg, Tinf2, Ptgs2, Pdlim1, Tes, Irf6, Tgfb1, Serpinb2, Lipg, Creb3l1, Lypd1) were found to be upregulated. Six genes were validated on quantitative polymerase chain reaction and subsequently, Amphiregulin (Areg) was selected (based on log2 fold change) for further experiments to unravel its involvement in LID. Areg LV_shRNA was used to knock down Areg to explore its therapeutic role in the LID model. RESULTS: Western blotting and immunofluorescence results show that AREG is significantly expressed in the LID group relative to the control. Dyskinetic movements in LID mice were alleviated by Areg knockdown, and the protein expression of delta FOSB, the commonly attributable protein in LID, was decreased. Moreover, Areg knockdown reduced the protein expression of P-ERK. In order to ascertain whether the inhibition of the ERK pathway (a common pathway known to mediate levodopa-induced dyskinesia) could also impede Areg, the animals were injected with an ERK inhibitor (PD98059). Afterward, the AIMs, AREG, and ERK protein expression were measured relative to the control group. A group treated with ERK inhibitor had a significant decrease of AREG and phosphorylated ERK protein expression relative to the control group. CONCLUSION: Taken together, our results indicate unequivocal involvement of Areg in levodopa-induced dyskinesia, thus a target for therapy development.
Asunto(s)
Discinesia Inducida por Medicamentos , Enfermedad de Parkinson , Ratones , Animales , Levodopa/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Oxidopamina/toxicidad , Antiparkinsonianos/uso terapéutico , Anfirregulina/genética , Anfirregulina/uso terapéutico , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Discinesia Inducida por Medicamentos/genética , Discinesia Inducida por Medicamentos/metabolismo , Modelos Animales de EnfermedadRESUMEN
Because sarcopenia is widely distributed in patients with acute ischemic stroke (AIS) and has not attracted enough attention, this study aims to explore the relationship between sarcopenia defined by temporal muscle thickness (TMT) and physical function and prognosis of patients with AIS. A total of 265 hospitalized nonsurgical AIS patients from 2015 to 2018, with an age range of 28 ~ 92, were analyzed retrospectively. The median value of TMT was used as the risk classification index of sarcopenia. The main results were the relationship between sarcopenia and Essen Stroke Risk Score, National Institutes of Health Stroke Scale, modified Rankin Score, water swallow test, venous thromboembolism assessment of medical inpatients, activities of daily living assessed by Barthel Index, and the relationship between TMT and final survival outcome. The mean TMT of men in the study cohort was higher than that of women. The measured values of TMT among different researchers had good consistency (intraclass correlation coefficient, 0.980; P < .001). After adjusting for confounding variables, logistic regression showed that sarcopenia was associated with Essen Stroke Risk Score (odds ratio, 1.89; P < .05) and Barthel Index (odds ratio, 1.67; P < .05). Kaplan-Meier analysis showed that the survival time of low TMT group was significantly lower than that of high TMT group (36 vs 49 months; P < .001). Multivariate Cox regression showed that there was causal correlation between sarcopenia and patient death (hazard ratio, 3.54; 95% confidence interval, 1.46-8.58; P < .01). As a potential comprehensive index, thickness of temporal muscle can be included in baseline evaluation to show the physical status, stroke recurrence, and survival prognosis of AIS patients.
Asunto(s)
Accidente Cerebrovascular Isquémico , Sarcopenia , Accidente Cerebrovascular , Actividades Cotidianas , Femenino , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Sarcopenia/complicaciones , Accidente Cerebrovascular/etiologíaRESUMEN
Congenital pure red cell aplasia, also known as Diamond-Blackfan anemia (DBA), is a hereditary disease characterized by pure red cell aplasia and congenital malformation. Its main clinical features are anemia, dysplasia, and tumor susceptibility. Ribosomal protein (RP) gene mutation is the main pathogenesis of DBA. The most common type of gene mutation is RPS19 gene mutation. Heterozygous mutations in as many as 19 RP genes and other non-RP genes mutations have been identified in DBA. This review summarized briedfly the latest research advances in the pathogenesis of DBA.
Asunto(s)
Anemia de Diamond-Blackfan , Humanos , Mutación , RibosomasRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: 25 flavors of the turquoise pill, a traditional Tibetan medicine for the treatment of various types of hepatitis, has not been investigated on its safety, especially the component mineral turquoise, which is believed to be essential but worried for its potential toxicity. AIM OF THE STUDY: To explore the potential acute toxicity and function of 25 flavors of the turquoise pill and turquoise, the possible mechanism of the effects of turquoise and 25 flavors of the turquoise pill were systematically studied based on 1H NMR metabolomics. MATERIALS AND METHODS: The rats were administered with turquoise and 25 flavors of the turquoise pill by gavage for 7 days, and samples of serum, liver, and kidney were collected. The potential toxicity and function of turquoise and 25 flavors of the turquoise pill on the liver and kidney of SD rats were evaluated by 1H NMR metabonomics, histopathology, and biochemical indexes. RESULTS: The results demonstrated that 25 flavors of the turquoise pill could scavenge free oxygen radicals, strengthen aerobic respiration and inhibit glycolysis in the liver. It did not cause oxidative stress in the kidney with no obvious damage. By modulation of branched-chain amino acids (BCAAs), 25 flavors of the turquoise pill can improve the utilization of glucose and promote aerobic respiration of the kidney. CONCLUSION: Considering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys.
Asunto(s)
Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Medicina Tradicional Tibetana/efectos adversos , Minerales/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Aromatizantes/química , Depuradores de Radicales Libres/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Glucosa/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Medicina Tradicional Tibetana/métodos , Metabolómica , Minerales/aislamiento & purificación , Minerales/farmacología , Ratas Sprague-Dawley , Medición de Riesgo , Pruebas de Toxicidad AgudaRESUMEN
OBJECTIVE: The purposes of this study were to evaluate whether a novel radiographic technique, diffraction-enhanced radiographic imaging, would render high-contrast images of mouse livers, hearts, and kidneys and to determine whether blood vessels and bile ducts can be differentiated on images of mouse livers. MATERIALS AND METHODS: For imaging of the bile ducts, mouse livers were excised 20 or 35 days after ligation of the common bile duct. Livers, hearts, and kidneys of control mice also were excised for imaging. The diffraction-enhanced imaging experiments were performed with a silicon 333 crystal diffraction plane and an 18-keV x-ray beam. The beam incident to the sample measured 20 mm (horizontal) x 11 mm (vertical). Images were acquired with the analyzer crystal set at different positions of the rocking curve. RESULTS: Only dilated bile ducts, no normal bile ducts, were found. With diffraction-enhanced imaging without a contrast agent, the blood vessels of the liver, heart, and kidney were visualized to a scale of tens of micrometers. CONCLUSION: Diffraction-enhanced imaging with a silicon 333 crystal plane had excellent contrast in the detection of blood vessels and pathologically dilated bile ducts and may be a promising radiographic technique for basic medical research.
Asunto(s)
Conducto Colédoco/diagnóstico por imagen , Intensificación de Imagen Radiográfica/métodos , Tecnología Radiológica/métodos , Animales , Corazón/diagnóstico por imagen , Técnicas In Vitro , Riñón/irrigación sanguínea , Riñón/diagnóstico por imagen , Hígado/irrigación sanguínea , Hígado/diagnóstico por imagen , Ratones , Difracción de Rayos X/métodosRESUMEN
BACKGROUND: The main endemic areas of alveolar echinococcosis (AE) are in Central Europe and Western China. Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE. AIM: To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim. METHODS: Consecutively, five experienced examiners evaluated contrast-enhanced abdominal computed tomography (CT) scans for 200 patients with hepatic AE of each of four locations (n = 50) in Germany, France and China. Therefore, we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center, performed because of hepatic AE from September 21, 2007 to March 21, 2018. AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT (EMUC-CT). Distant extrahepatic manifestations were documented either by whole body positron emission tomography-CT or with the addition of thoracic CT and cranial magnetic resonance imaging. Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion. Statistical analysis was performed using SAS Version 9.4 (SAS Institute Inc., Cary, NC, United States). RESULTS: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (P = 0.0091). A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size (P = 0.0075). Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe (P < 0.0001), and vascular/biliary involvement depended on lesion size. Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations: Vascular/biliary involvement as a function of lesions primary morphology ranged from 5.88% of type IV liver lesions to 100% among type III lesions. Type IV differed significantly in these associations from types I, II, and III (P < 0.0001). With respect to extrahepatic disease, the primary morphology types IV and V of liver lesions were not associated with any case of distant extrahepatic disease. In contrast, distant extrahepatic manifestations in types I-III were found to varying degrees, with a maximum of 22% for type III. CONCLUSION: Different CT morphological patterns of hepatic AE lesions influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations. There are intercontinental differences regarding the characteristics of AE manifestation.
Asunto(s)
Equinococosis Hepática , Equinococosis , Animales , China/epidemiología , Equinococosis Hepática/diagnóstico por imagen , Equinococosis Hepática/epidemiología , Europa (Continente) , Francia , Alemania , Humanos , Estudios RetrospectivosRESUMEN
Objective: To make full usage of resource and turn waste into treasure, the chemical constituents and bioactivity were firstly investigated on Damask rose (Rosa damascena) flower residue (DRFR). Methods: DPPH and ABTS experiments were applied to assess the antioxidant activity of DRFR. Then, column chromatography was used to purify compounds from an antioxidation extract (DRFR-A), and the chemical structure was identified using NMR. The total phenolic acid content was measured by Folin-Ciocalteu colorimetric method, and the content of gallic acid of the indicator ingredient was detected by HPLC. Results: DRFR-A was found to show a high activity both on DPPH (IC50: 2.760 µg/mL) and ABTS (IC50: 2.258 µg/mL) compared to positive control VC. Ten compounds were isolated and identified as quercetin (1), kaempferol (2), gallic acid (3), protocatechuic acid (4), pyrogallic acid (5), 2-phenylethyl 3,4,5-trihydroxybenzoate (6), methyl gallate (7), p-hydroxybenzoic acid (8), p-hydroxyphenethyl alcohol (9) and astragalin (10) from DRFR-A. Among them, pyrogallic acid, 2-phenylethyl-3, 4, 5-trihydroxybenzoate, p-hydroxybenzoic acid and p-hydroxyphenethyl alcohol are obtained from the plant for the first time. The content of total phenolic acids and gallic acid, main ingredient in DRFR-A was determined as 63.73% and 24.67%, respectively. Conclusion: This study provides a reliable data and lays the foundation for the development and utilization of rose residue, and hence for the full utilization of rose resources.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodiae Rhizoma (GR), a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating headache, dizziness, tetanus, epilepsy, and etc., has been proven to relieve chronic atrophic gastritis (CAG). Due to its complex ingredients, the active fractions responsible for the treatment of CAG remain largely unknown. AIM OF THE STUDY: To explore the underlying material and interpret its underlying mechanism, the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG was studied based on the 1H NMR metabolomics. MATERIALS AND METHODS: The rat model of CAG was established by autoimmune method. The modeled CAG rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of Gastrodiae Rhizoma for 21 consecutive days. The stomach and serum samples were collected and then subjected to histopathology observation, biochemical measurement (MDA, SOD, GSH, NO, XOD and pepsin), 1H NMR metabolic profiling and multivariate/univariate statistical analysis. RESULTS: The results showed that T1 had the best therapeutic effect, T2 the second, and T3 and T4 the poorest with no obvious therapeutic effect, demonstrating that the effective components of Gastrodiae Rhizoma should be compounds of high polarity. T1 achieved good therapeutic effects due to the anti-inflammatory and anti-oxidant activities, and by rectifying the disturbed energy and amino acid metabolism in CAG model. CONCLUSION: This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means.
Asunto(s)
Gastritis Atrófica/prevención & control , Gastrodia/química , Metabolómica , Extractos Vegetales/farmacología , Animales , Interacciones Hidrofóbicas e Hidrofílicas , Masculino , Extractos Vegetales/química , Espectroscopía de Protones por Resonancia Magnética , Ratas , Rizoma/química , Solventes/químicaRESUMEN
The Herpetospermum caudigerum Wall (HCW) is a traditional Tibetan medicine and is widely used in clinical practice. However, the shell of the HCW (SHCW) has rarely been studied, and some researchers have suggested that the SHCW may be toxic. Therefore, in this study, SHCW was administered to rats at two doses (0.1 and 0.33â¯g/kg) once a day for 21 days. The hepatic stimuli induced by SHCW in rats were investigated for the first time by 1H-NMR-based metabolomics combined with histopathological observation and biochemical detection. Histopathological sections showed a certain degree of hepatocyte edema and hepatic sinus congestion in the liver tissue of the rats in the drug-administered group. Serum biochemical indicators revealed a significant increase in ALT, AST, and MDA, and a significant decrease in SOD. Metabolomic results showed that the metabolites in rats were changed after gavage administration of extracts from SHCW. By multivariate statistical analysis and univariate analysis, it was found that SHCW could cause the disorder of energy metabolism, oxidative stress and amino acid metabolism in rats, leading to liver damage. This comprehensive metabolomics approach demonstrates its ability to describe the global metabolic state of an organism and provides a powerful and viable tool for exploring drug-induced toxicity or side effects.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Cucurbitaceae/toxicidad , Medicina Tradicional Tibetana/efectos adversos , Metabolómica/métodos , Extractos Vegetales/toxicidad , Espectroscopía de Protones por Resonancia Magnética , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Modelos Animales de Enfermedad , Etanol/química , Humanos , Pruebas de Función Hepática/métodos , Masculino , Extractos Vegetales/aislamiento & purificación , RatasRESUMEN
The relationships between the leaf chlorophyll content (LCC) of Pinus massoniana at different growth stages and their chlorophyll content were analyzed. 7 of 36 red edge-based parameters were finally selected as the typical spectral response parameters which held the most significant statistical relationship with LCC, and then the hyperspectral assessment model for retrieving the LCC was built based on stepwise regression analysis method and B-P neural network, respectively. In the same way, four different vegetation indices (VIs) were selected as typical spectral parameters, in the meantime, the first four components of the principal component analysis (PCA) transformed from original spectral measurements were inputted into the B-P neural network, and then the hyperspectral assessment model for retrieving the LCC was built based on stepwise regression analysis method and B-P neural network, respectively. The results showed that R2 of the red edge-based stepwise regression model and the red edge-based B-P neural network model were 0.5205 and 0.7253, RMSE were 0.1004 and 0.0848, and relative errors were 6.3% and 5.7%, respectively. R2 of the VIs-based stepwise regression model and the VIs-based B-P neural network model were 0.5392 and 0.7064, RMSE were 0.0978 and 0.0871, and relative errors were at 6.2% and 6.0%, respectively. The prediction effect of PCA-based B-P neural network model was the best, R2 was 0.7475, RMSE was 0.0540, and the relative error was 4.8%.
Asunto(s)
Clorofila , Redes Neurales de la Computación , Pinus , Hojas de la Planta , Análisis EspectralRESUMEN
OBJECTIVE: Using a pulsating coronary artery phantom at high heart rate settings, we investigated the efficacy of a motion correction algorithm (MCA) to improve the image quality in dual-energy spectral coronary CT angiography (CCTA). MATERIALS AND METHODS: Coronary flow phantoms were scanned at heart rates of 60-100 beats/min at 10-beats/min increments, using dual-energy spectral CT mode. Virtual monochromatic images were reconstructed from 50 to 90 keV at 10-keV increments. Two blinded observers assessed image quality using a 4-point Likert Scale (1 = non-diagnostic, 4 = excellent) and the fraction of interpretable segments using MCA versus conventional algorithm (CA). Comparison of variables was performed with the Wilcoxon rank sum test and McNemar test. RESULTS: At heart rates of 70, 80, 90, and 100 beats/min, images with MCA were rated as higher image scores compared to those with CA on monochromatic levels of 50, 60, and 70 keV (each p < 0.05). Meanwhile, at a heart rate of 90 beats/min, image interpretability was improved by MCA at a monochromatic level of 60 keV (p < 0.05) and 70 keV (p < 0.05). At a heart rate of 100 beats/min, image interpretability was improved by MCA at monochromatic levels of 50 keV (from 69.4% to 86.1%, p < 0.05), 60 keV (from 55.6% to 83.3%, p < 0.05) and 70 keV (from 33.3% to 69.3%, p < 0.05). CONCLUSION: Low-keV monochromatic images combined with MCA improves image quality and image interpretability in CCTAs at high heart rates.
Asunto(s)
Algoritmos , Angiografía por Tomografía Computarizada/métodos , Vasos Coronarios/diagnóstico por imagen , Frecuencia Cardíaca/fisiología , Angiografía por Tomografía Computarizada/instrumentación , Vasos Coronarios/fisiología , Humanos , Interpretación de Imagen Radiográfica Asistida por Computador , Reproducibilidad de los ResultadosRESUMEN
To determine whether body weight and concentration dependent contrast medium (CM) injection protocols can improve patient to patient CT value uniformity more than the conventional injection protocols with fixed injection parameters in coronary CT angiography (CCTA), one hundred and sixty patients who underwent CCTA were prospectively randomized into two groups. Group A (n = 80) used individualized-protocol with adjusted injection rate based on patient weight and contrast medium concentration to obtain constant iodine load of 280 mgI/kg while group B (n = 80) followed the conventional contrast injection protocol with total injection volume of 80ml and constant injection rate of 5.5ml/s. For both groups, patients were further divided into four subgroups with different CM concentrations: A1, B1 (300 mg I/ml); A2, B2 (320 mg I/ml); A3, B3 (350 mg I/ml) and A4 and B4 (370 mg I/ml). For each patient, the CT values of the ascending aorta, left ventricle and coronary arteries were measured. One-way analysis of variance was used to compare CT values among subgroups. Among the subgroups of A, sufficient attenuation of greater than 300HU was obtained in all target vessels with no difference among them. Among the subgroups of B, the CT values had significant difference in left ventricle, left circumflex branch, proximal and distal segment of the right coronary artery (all p < 0.05), and the attenuation with 300 mg I/ml CM concentration was significantly lower than that with 370 mg I/ml. Compared with group B, group A used less volume (62.83 ml vs. 80.00 ml, P<0.001) and lower rate (5.21 ml/s vs. 5.50 ml/s, P<0.001) of CM. Compared with the conventional contrast medium injection protocol with fixed volume and injection rate, the individualized-protocol based on patient weight and contrast concentration provides overall contrast dose reduction and achieves more homogenous attenuation among different coronary vessels and patients.