RESUMO
OBJECTIVE. Diagnostic accuracy of core needle biopsy (CNB) for adipocytic tumors can be low because of sampling error from these often large, heterogeneous lesions. The purpose of this study was to evaluate the diagnostic accuracy of image-guided CNB for various adipocytic tumors in comparison with excisional pathology. MATERIALS AND METHODS. Adipocytic tumors (n = 77) of all adult patients undergoing image-guided CNB and subsequent surgical excision of an adipocytic tumor at a tertiary referral center between 2005 and 2019 were studied. To determine concordance, we compared pathologic diagnoses based on CNB to the reference standard of pathologic diagnoses after surgical excision. Tumors were divided into three categories (benign lipomatous tumors [lipoma, lipoma variants, hibernomas], atypical lipomatous tumors [ALTs] or well-differentiated liposarcomas [WDLs], and higher grade liposarcomas [myxoid, dedifferentiated, pleomorphic]), and diagnostic accuracy was calculated for each category. RESULTS. In 73 of 77 adipocytic tumors (95%), diagnosis at CNB and diagnosis after excision were concordant. Accuracy of diagnosis was poorer for ALTs and WDLs than for the other two categories, and the difference was statistically significant (p < .002). For the 29 benign lipomatous tumors and the 27 higher-grade liposarcomas, diagnoses at CNB and after excision were concordant in all cases (100%). Seventeen of the 21 tumors (81%) diagnosed as ALTs or WDLs at CNB had a concordant diagnosis after excision; four of the 21 were upgraded (dedifferentiated liposarcoma, n = 3; myxoid liposarcoma, n = 1). CONCLUSION. CNB provides high diagnostic accuracy for adipocytic tumors, particularly for benign lipomatous tumors and higher grade liposarcomas. However, though still high at 81%, diagnostic accuracy of CNB is not as high for tumors diagnosed as ALTs or WDLs. Awareness of this limitation is important when determining management, particularly of cases of ALT or WDL for which surgery is not planned.
Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Biópsia Guiada por Imagem/métodos , Neoplasias Lipomatosas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Lipoma/diagnóstico por imagem , Lipoma/patologia , Lipossarcoma/diagnóstico , Lipossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Lipomatosas/diagnóstico , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
This paper proposes and implements a lightweight, "real-time" localization system (SORLA) with artificial landmarks (reflectors), which only uses LiDAR data for the laser odometer compensation in the case of high-speed or sharp-turning. Theoretically, due to the feature-matching mechanism of the LiDAR, locations of multiple reflectors and the reflector layout are not limited by geometrical relation. A series of algorithms is implemented to find and track the features of the environment, such as the reflector localization method, the motion compensation technique, and the reflector matching optimization algorithm. The reflector extraction algorithm is used to identify the reflector candidates and estimates the precise center locations of the reflectors from 2D LiDAR data. The motion compensation algorithm predicts the potential velocity, location, and angle of the robot without odometer errors. Finally, the matching optimization algorithm searches the reflector combinations for the best matching score, which ensures that the correct reflector combination could be found during the high-speed movement and fast turning. All those mechanisms guarantee the algorithm's precision and robustness in the high speed and noisy background. Our experimental results show that the SORLA algorithm has an average localization error of 6.45 mm at a speed of 0.4 m/s, and 9.87 mm at 4.2 m/s, and still works well with the angular velocity of 1.4 rad/s at a sharp turn. The recovery mechanism in the algorithm could handle the failure cases of reflector occlusion, and the long-term stability test of 72 h firmly proves the algorithm's robustness. This work shows that the strategy used in the SORLA algorithm is feasible for industry-level navigation with high precision and a promising alternative solution for SLAM.
Assuntos
Robótica , Algoritmos , Movimento (Física) , MovimentoRESUMO
By establishing the preparation process of Scrophulariaceae Radix reference extract(SRRE) and calibrating it, we discussed its feasibility as a substitute for single reference substance in the quality control of Scrophulariae Radix. The SRREs were prepared by solvent extraction method and chromatographic separation technology, and then calibrated with the reference substances of harpagide, angoroside C and harpagoside. The HPLC content determination method of Scrophulariae Radixl was established with SRREs of the known content and the reference substances of harpagide, angoroside C and harpagoside respectively as the control ones. Then the content of three components in Scrophulariae Radix was determined, and the t-test method was used to compare the results of the two methods. With SRRE as references, harpagide, angoroside C and harpagoside were in a good linear relationship(r≥0.999 8) within each range, and the average recovery rate was 98.55% to 100.6%. The t-test results showed that the P values of two determination methods were 0.493, 0.155 and 0.171 for harpagide, angoroside C and harpagoside respectively, indicating no significant diffe-rence between the two methods of content determination. The SRRE can be used as a substitute for the reference in the quality control of Scrophulariaceae Radix. The SRRE can replace the corresponding reference substance for the quality control of Scrophulariae Radix. The results of this study provide new methods and new ideas for the quality evaluation of Scrophulariae Radix, and provide a scientific basis for the application of reference extracts in the quality research of traditional Chinese medicine.
Assuntos
Medicamentos de Ervas Chinesas , Scrophularia , Scrophulariaceae , Cromatografia Líquida de Alta Pressão , Controle de QualidadeRESUMO
The calibration of chromone reference extract(CRE) was conducted and a quality control method of Saposhnikoviae Radix(SR) was established based on CRE. Meanwhile, the quality control system of SR was improved and the feasibility of using reference extract as a substitute for single reference substance in quality control of Chinese medicine was discussed. In this study, the content of the prepared CRE was calibrated with prim-O-glucosylcimifugin, cimifugin, 4'-O-ß-D-glucosyl-5-O-methylvisamminol, and secO-glucosylhamaudol as indicators. Subsequently, an HPLC analytical method was developed to determine the content of four chromones in 20 batches of SR samples based on the CRE with known content as the standard substance. T-test was used for the comparison of the determination results of the two methods(single chemical component and CRE as reference substances, respectively), and the P values of prim-O-glucosylcimifugin, cimifugin, 4'-O-ß-D-glucosyl-5-O-methylvisamminol, and sec-O-glucosylhamaudol were 0. 16,0. 39, 0. 14, and 0. 42. The results demonstrated that there was no significant difference between the two methods. This study initially verified the feasibility that the CRE could be used as a substitute for single reference substance in quality control of SR. In conclusion,this study is expected to provide a scientific basis and a new research model for the application of reference extract in the quality control of Chinese medicine.
Assuntos
Apiaceae , Medicamentos de Ervas Chinesas , Calibragem , Cromatografia Líquida de Alta Pressão , Cromonas , Controle de QualidadeRESUMO
Chinese traditional medicine compound is the main form of Chinese medicine clinical application. The elucidation of the effective components of traditional Chinese medicine is one of the key scientific issues to promote the modernization of traditional Chinese medicine. At present, there are many research ideas on the effective components of traditional Chinese medicine compounds. By analyzing the current status and existing problems of existing research ideas, the author proposes a "double reduction network pharmacology"(2 R network pharmacology) research method based on "prediction of dominant components-potential target selection". Chemical components with good properties were selected by ADMET property prediction technology, and compared with the blood components and target organ components to determine the dominant components with potential therapeutic effect, that is "reducing constituents"; the potential core regulatory pathway of traditional Chinese medicine compound was enriched by RNA-Seq technology combined with network database, and then the target of traditional Chinese medicine compound was mined based on the signal pathway, that is "reducing targets". To improve the efficiency and accuracy of effective component screening, the network relationship of "component target" was established by the related technology of network pharmacology. The purpose of this study is to provide practical research ideas and methods for clarifying the effective components of traditional Chinese medicine, revealing the law of compatibility of traditional Chinese medicine and clarifying the target of drug action.
Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Bases de Dados Factuais , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Projetos de PesquisaRESUMO
Noble metal nanoparticles (NPs) and their hybrids have demonstrated a strong potential to mimic the catalytic activity of natural enzymes and diminish oxidative stress. There is a large space to explore the intrinsic catalytic activity of Rh NPs with respect to reactive oxygen species (ROS) scavenging. We found that Rh NPs can quench H2O2, â¢OH, O2â¢-, 1O2 and inhibit lipid peroxidation under physiological conditions. In vitro cell experiments proved that Rh NPs have great biocompatibility and protect cells from oxidative damage caused by H2O2. This study can provide important insights that could inform future biological applications.
Assuntos
Materiais Biocompatíveis/análise , Peroxidação de Lipídeos , Nanopartículas Metálicas/análise , Espécies Reativas de Oxigênio/química , Ródio/análise , Catálise , Citotoxinas/química , Peróxido de Hidrogênio/química , Hidróxidos/química , Oxigênio Singlete/químicaRESUMO
Fluorescent nitrogen and phosphorus co-doped carbon dots (NPCDs) were prepared via a hydrothermal method with citric acid and O-phosphorylethanolamine as precursors. The overlap between the absorption spectrum of riboflavin and the fluorescence emission spectrum of the NPCDs and the relative proximity of the NPCDs to riboflavin due to hydrogen bonding facilitated the formation of a NPCDs/riboflavin fluorescence resonance energy transfer (FRET) system. Thus, a ratiometric fluorescence method for the detection of riboflavin based on the formation of this NPCDs/riboflavin FRET system was developed. The method displayed a sensitive and selective response to riboflavin in the range 0.5-50 µmol/L with a detection limit of 0.17 µmol/L. It was also found to be suitable for the detection of riboflavin in milk and riboflavin pharmaceutical tablets. Graphical abstract Illustration of the preparation of NPCDs and the ratiometric fluorescence detection of riboflavin using the NPCDs/riboflavin FRET system.
Assuntos
Carbono/química , Transferência Ressonante de Energia de Fluorescência/métodos , Nitrogênio/química , Fósforo/química , Pontos Quânticos/química , Riboflavina/análise , Animais , Limite de Detecção , Leite/química , Modelos Moleculares , Preparações Farmacêuticas/análiseRESUMO
This experiment was performed to analyze and identify the chemical constituents of Lycii Cortex by UPLC-LTQ-OrbitrapMS. The analysis was performed on a Waters Xbridge Shield RP18( 4. 6 mm×250 mm,5 µm) column with the mobile phase of 0. 1%formic acid( A)-acetonitrile( B) under gradient conditions at a flow rate of 1. 0 m L·min-1 and the temperature maintained at 35 â ï¼Electrospray ionization ion trap time-off light multistage mass spectrometry was applied for qualitative analysis under positive and negative ion modes. The results indicated that 55 compounds consisted of 39 phenolic amides,6 organic acids,3 cyclic peptides,2 coumarins and 5 others. In conclusion,an UPLC-LTQ-Orbitrap-MS method was established to qualitative analysis of Lycii Cortex in this study,and the fragmentation rules of phenolic amides were summarized,which provides a good foundation for further study of Lycii Cortex.
Assuntos
Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão , Cumarínicos , Espectrometria de Massas , FenóisRESUMO
BACKGROUND/AIMS: Metformin, the common medication for type II diabetes, has protective effects on cerebral ischemia. However, the molecular mechanisms are far from clear. Mitotic arrest deficient 2-like protein 2 (MAD2B), an inhibitor of the anaphase-promoting complex (APC), is widely expressed in hippocampal and cortical neurons and plays an important role in mediating high glucose-induced neurotoxicity. The present study investigated whether metformin modifies the expression of MAD2B and to exert its neuroprotective effects in primary cultured cortical neurons during oxygen-glucose deprivation/reoxygenation (OGD/R), a widely used in vitro model of ischemia/reperfusion. METHODS: Primary cortical neurons were cultured, deprived of oxygen-glucose for 1 h, and then recovered with oxygen-glucose for 12 h and 24 h. Cell viability was measured by detecting the levels of lactate dehydrogenase (LDH) in culture medium. The levels of MAD2B, cyclin B and p-histone 3 were measured by Western blot. RESULTS: Cell viability of neurons was reduced under oxygen-glucose deprivation/reoxygenation (OGD/R). The expression of MAD2B was increased under OGD/R. The levels of cyclin B1, which is a substrate of APC, were also increased. Moreover, OGD/R up-regulated the phosphorylation levels of histone 3, which is the induction of aberrant re-entry of post-mitotic neurons. However, pretreatment of neurons with metformin alleviated OGD/R-induced injury. Metformin further decreased the expression of MAD2B, cyclin B1 and phosphorylation levels of histone 3. CONCLUSION: Metformin exerts its neuroprotective effect through regulating the expression of MAD2B in neurons under OGD/R.
Assuntos
Regulação para Baixo/efeitos dos fármacos , Glucose/deficiência , Proteínas Mad2/metabolismo , Metformina/farmacologia , Neurônios/patologia , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Oxigênio/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Ciclina B1/metabolismo , Modelos Biológicos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurotoxinas/toxicidade , Ratos Sprague-Dawley , Fase S/efeitos dos fármacosRESUMO
Background and aims: Previous research has underscored the association between oily fish intake and type 2 diabetes (T2DM), yet the causality remains elusive. Methods: A bidirectional univariable Mendelian Randomization (MR) analysis was employed to evaluate the causal effects of oily fish and non-oily fish intake on T2DM. Replication analysis and meta-analysis were conducted to ensure robust results. Multivariable MR analysis was utilized to assess confounders, and further mediation MR analysis discerned mediating effects. Linkage Disequilibrium Score (LDSC) analysis was undertaken to compute genetic correlations. Inverse variance weighted (IVW) was the primary method, complemented by a series of sensitivity analyses. Results: The LDSC analysis unveiled a significant genetic correlation between oily fish intake and T2DM (Genetic correlation: -0.102, p = 4.43 × 10-4). For each standard deviation (SD) increase in genetically predicted oily fish intake, the risk of T2DM was reduced by 38.6% (OR = 0.614, 95% CI 0.504 ~ 0.748, p = 1.24 × 10-6, False Discovery Rate (FDR) = 3.72 × 10-6). The meta-analysis across three data sources highlighted a persistent causal association (OR = 0.728, 95% CI 0.593 ~ 0.895, p = 0.003). No other causal effects were identified (all p > 0.5, FDR > 0.5). The main outcomes remained consistent in most sensitivity analyses. Both MVMR and mediation MR analyses emphasized the mediating roles of triglycerides (TG), body mass index (BMI), and 25-hydroxyvitamin D (25OHD) levels. Conclusion: To encapsulate, there's an inverse association between oily fish intake and T2DM risk, suggesting potential benefits of oily fish intake in T2DM prevention.
RESUMO
Since oxidative stress is often associated with neurodegenerative diseases, antioxidants are likely to confer protection against neurodegeneration. Despite an increasing number of food-derived peptides being identified as antioxidants, their antineurodegenerative potentials remain largely unexplored. Here, a sea cucumber peptide preparation - the peptide-rich fraction of <3 kDa (UF<3K) obtained by ultrafiltration from Apostichopus japonicus protein hydrolyzate - was found to protect PC12 cells and Caenorhabditis elegans from neurodegeneration by reducing oxidative stress and apoptosis, demonstrating its in vitro and in vivo neuroprotective effects. As many food-originated peptides are cryptides (cryptic peptides - short amino acid sequences encrypted in parent proteins) released in quantities by protein hydrolysis, UF<3K was subjected to sequencing analysis. As expected, a large repertoire of peptides were identified in UF<3K, establishing a sea cucumber cryptome (1238 peptides in total). Then 134 peptides were randomly selected from the cryptome (>10%) and analyzed for their antioxidant activities using a number of in silico bioinformatic programs as well as in vivo experimental assays in C. elegans. From these results, a novel antioxidant peptide - HoloPep#362 (FETLMPLWGNK) - was shown to not only inhibit aggregation of neurodegeneration-associated polygluatmine proteins but also ameliorate behavioral deficits in proteotoxicity nematodes. Proteomic analysis revealed an increased expression of several lysosomal proteases by HoloPep#362, suggesting proteostasis maintenance as a mechanism for its antineurodegenerative action. These findings provide an insight into the health-promoting potential of sea cucumber peptides as neuroprotective nutraceuticals and also into the importance of training in silico peptide bioactivity prediction programs with in vivo experimental data.
Assuntos
Antioxidantes , Caenorhabditis elegans , Fármacos Neuroprotetores , Estresse Oxidativo , Peptídeos , Pepinos-do-Mar , Animais , Caenorhabditis elegans/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Peptídeos/farmacologia , Peptídeos/química , Pepinos-do-Mar/química , Estresse Oxidativo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Células PC12 , Ratos , Doenças Neurodegenerativas/tratamento farmacológico , Simulação por ComputadorRESUMO
PURPOSE: Acellular porcine small intestinal submucosa (SIS) has been successfully used for esophagoplasty in dogs. However, this has not led to complete epithelialization and muscular regeneration. We undertook the present study to assess the effect of tissue-engineered esophagus generated by seeding bone marrow mesenchymal stem cells (BMSCs) onto an SIS scaffold (BMSCs-SIS) in a canine model. METHODS: We cultured, passaged, and measured autologous BMSCs and myoblasts with cell proliferation and immunohistochemical assays. We labeled the third passage of BMSCs with PKH-26, a fluorescent dye, before seeded it onto the SIS. We resected canine cervical esophagus to generate a defect 5 cm in length and 50% in circumference, which we repaired with BMSCs-SIS or SIS alone. RESULTS: Four weeks later, barium esophagram demonstrated that esophageal lumen surface of the patch graft was smoother in the BMSCs-SIS group compared with the SIS group. Histological examination suggested a strong similarity between BMSCs and esophageal myoblasts in terms of morphology and function. Although both BMSCs-SIS and SIS repaired the esophageal defects, we noted complete re-epithelialization with almost no inflammation only in the former group. By 12 wk after the surgery, we observed long bundles of skeletal muscles only in the BMSCs-SIS group, where the microvessel density was also much greater. CONCLUSIONS: Bone marrow mesenchymal stem cells on an SIS scaffold can promote re-epithelialization, revascularization, and muscular regeneration. This approach may provide an attractive option for esophageal regeneration.
Assuntos
Diferenciação Celular/fisiologia , Esôfago/citologia , Células-Tronco Mesenquimais/citologia , Modelos Animais , Engenharia Tecidual/métodos , Actinas/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Proliferação de Células , Células Cultivadas , Cães , Esôfago/fisiologia , Masculino , Células-Tronco Mesenquimais/fisiologia , Mioblastos de Músculo Liso/citologia , Mioblastos de Músculo Liso/metabolismo , Regeneração/fisiologia , Alicerces TeciduaisRESUMO
2D materials, such as graphene, MXenes (metal carbides and nitrides), graphdiyne (GDY), layered double hydroxides, and black phosphorus, are widely used as electrocatalyst supports for alcohol oxidation reactions (AORs) owing to their large surface area and unique 2D charge transport channels. Furthermore, the development of highly efficient electrocatalysts for AORs via tuning the structure of 2D support materials has recently become a hot area. This article provides a critical review on modification strategies to develop 2D material-based electrocatalysts for AOR. First, the principles and influencing factors of electrocatalytic oxidation of alcohols (such as methanol and ethanol) are introduced. Second, surface molecular functionalization, heteroatom doping, and composite hybridization are deeply discussed as the modification strategies to improve 2D material catalyst supports for AORs. Finally, the challenges and perspectives of 2D material-based electrocatalysts for AORs are outlined. This review will promote further efforts in the development of electrocatalysts for AORs.
RESUMO
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the popular seed cells for regenerative medicine, and there has been a rapid increase in the number of BM-MSC-based clinical trials. However, the safety of these cells should also be closely studied. In this study, spontaneous calcification of BM-MSCs from rats was evaluated in normoxia (20% O(2)) without osteogenic medium after continuous culture for 21 days; obvious mineralized nodules were observed, which were positive for Alizarin Red, collagen-I (Col-I), osteocalcin (OC) and alkaline phosphatase (ALP), and mainly consisted of C, O and Ca elements. Interestingly, hypoxia (2% O(2)) significantly inhibited this spontaneous calcification. In addition, the ALP and calcium content of rBM-MSCs were sharply reduced. Based on RT-PCR results, the expression of osteogenic genes (Cbfa1/Runx2, Col-I, ALP, and OC) was reduced compared to that in normoxia. These results demonstrate a natural and unique characterization of rat BM-MSCs in normoxia after continuous culture and highlight the inhibiting effects of hypoxia. Finally, this study contributes to the information regarding the application of BM-MSCs in the regeneration of various tissues.
Assuntos
Células da Medula Óssea/citologia , Calcificação Fisiológica , Hipóxia Celular , Células-Tronco Mesenquimais/citologia , Animais , Células da Medula Óssea/metabolismo , Meios de Cultura , Perfilação da Expressão Gênica , Imuno-Histoquímica , Células-Tronco Mesenquimais/metabolismo , Microscopia Eletrônica de Varredura , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Espectrometria por Raios XRESUMO
MSCs (mesenchymal stem cells) may be promising seed cells for tissue regeneration because of their self-renewal and multi-differentiation potential. Shh (sonic hedgehog) is involved in the skeletal formation during embryo development and skeletal regeneration. However, how Shh regulates the biological characteristics of BM-MSCs (bone marrow-derived MSCs) is poorly understood. We have investigated the effect of rShh-N (recombinant N-terminal Shh) on the proliferation and osteogenic differentiation of rBM-MSCs (rat BM-MSCs) in vitro. rBM-MSCs were treated with rShh-N at concentrations up to 200 ng/ml. Proliferation and colony-forming ability of rBM-MSCs were increased in a dose-dependent manner. rShh-N increased the ratio of cells in S and G2/M phase, as well as the number of Ki-67+ cells. In addition, ALP (alkaline phosphatase) activity and matrix mineralization were enhanced by 200 ng/ml rShh-N. Real-time PCR showed that rShh-N (200 ng/ml) up-regulated the expression of genes encoding Cbfa-1 (core-binding factor α1), osteocalcin, ALP and collagen type I in rBM-MSCs. This information reveals some potential of rShh-N in the therapeutics of bone-related diseases.
Assuntos
Células da Medula Óssea/efeitos dos fármacos , Proteínas Hedgehog/fisiologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Células da Medula Óssea/citologia , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/fisiologia , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Fatores de Ligação ao Core/genética , Fatores de Ligação ao Core/metabolismo , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Proteínas Hedgehog/farmacologia , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Células-Tronco Mesenquimais/citologia , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/fisiologia , Ratos , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Serine peptidase inhibitor Kazal type 2 (SPINK2) has been reported to be involved in certain cancers. We conducted an in-depth investigation on the role and mechanism of SPINK2 in acute myeloid leukemia (AML). METHODS: The relationship between SPINK2 expression and AML clinicopathologic characteristics was determined using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Concomitantly, we used Kaplan-Meier survival analysis, as well as univariate and multivariate regression analyses to evaluate SPINK2 as a prognostic marker of AML. Additionally, we annotated the enrichment and function of SPINK2 using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Sets Enrichment Analysis (GSEA). The CIBERSORT algorithm was used to analyze the relationship between SPINK2 expression and immune infiltration. RESULTS: SPINK2 expression was significantly higher in AML patients compared to healthy individuals (P<0.001). The area under receiver operating characteristic curve in the GSE9476 dataset was 0.660, whereas that in the Genotype-Tissue Expression (GTEx) and TCGA datasets was 0.935. In addition, GSEA also showed that several pathways were enriched in the group with high SPINK2 expression, such as PI3K-AKT signaling, PD-L1 expression, and checkpoint pathways. Analysis of immune infiltration showed that SPINK2 expression was correlated with certain immune infiltrating cells. Cox multivariate analysis revealed that the level of SPINK2 was an independent risk factor for the progression of AML (P<0.001). Moreover, age, M1, M5, M6, and CytoRisk-Poor also affected the progression of AML (P<0.05). The C-index of the nomogram in our internal validation was 0.702. CONCLUSION: The high expression of SPINK2 in AML suggests that SPINK2 may play an important role in the immune microenvironment and thus could be a biomarker for diagnosis and prognosis of AML.
RESUMO
Objective: To establish a reliable and sensitive method for evaluating quality of Yiqi Jiangzhi Granules (YQJZG). Methods: Ultra performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) was employed for simultaneous determination of eight marker components. Separation was performed on an AQUITY UPLC® HSS T3 column, the mobile phase consisted of acetonitrile as the organic phase and 0.1% (volume percentage) formic acid as the aqueous. Eight marker components, ginsenoside Rg1 (GRg1), ginsenoside Re (GRe), ginsenoside Rb1 (Gb1), typhaneoside (TEO), isorhamnetin-3-O-neohespeidoside (IN), hesperidin (HPD), aurantio-obtusin-6-O-ß-D-glucoside (AG) and curcumin (CCM), were detected by multiple reaction monitoring (MRM) mode. The Chinese Pharmacopoeia (2020 edition) was regarded as the guidance document for this method validation. Results: The method showed good linearity (R 2 ≥ 0.9990). The relative standard deviation (RSD) values for the instrument precision, intermediate precision and repeatability were less than 2.91%, 2.88%, and 3.54%, respectively. The average recovery varied from 91.08% to 103.89%, with RSD below 3.81%. Sample solutions were found to be stable within 24 h at 4 °C (RSD < 2.85%). Eight marker components were successfully determined from three batches of YQJZG. Conclusion: The proposed UPLC-ESI-MS/MS method was found to be simple, fast and sensitive, and can be used for the routine quality assessment of YQJZG. Simultaneously, this method may provide a new and powerful tool of quality control for other traditional Chinese medicine analogous formulae.
RESUMO
Cryptochlorogenic acid (4-CQA) is a phenolic acid that has antioxidant and anti-inflammatory activities. Our preliminary study found that 4-CQA has a good effect on isoproterenol (ISO)-induced myocardial hypertrophy, while the mechanism remains largely unknown. This study aimed at delineating the metabolites and metabolic pathways of 4-CQA using liquid mass spectrometry and molecular biotechnology, exploring possible active metabolites and the mechanism of myocardial hypertrophy amelioration in H9c2 cells, and finally, investigating the pharmacokinetics of 4-CQA and its active metabolites in vivo. In summary, 56 potential effective metabolites were distinguished in rat urine, feces, plasma samples and heart tissue after intragastric administration of 4-CQA, and the main metabolic reaction types of 4-CQA included hydrogenation, methylation, glucuronidation, sulfation, hydration and their composite reactions in in vivo biotransformation. Besides, 4-CQA and its main active metabolites, caffeic acid and 4-O-feruloylquinic acid, significantly ameliorated pathological cardiac hypertrophy of H9c2 cells treated with ISO based on the Akt/mTOR/HIF-1α pathway. In addition, this study demonstrated that the prototype drugs 4-CQA and 4-O-ferulylquinic acid generally exhibit similar pharmacokinetic characteristics and caffeic acid presents relatively late peak time and low peak concentration in rats, which make them suitable candidate drugs.
Assuntos
Cardiomegalia/prevenção & controle , Cardiotônicos/uso terapêutico , Ácido Clorogênico/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Cardiomegalia/induzido quimicamente , Cardiotônicos/farmacologia , Ácido Clorogênico/farmacologia , Modelos Animais de Doenças , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoproterenol , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
The surface contamination of SARS-CoV-2 is becoming a potential source of virus transmission during the pandemic of COVID-19. Under the cold environment, the infection incidents would be more severe with the increase of virus survival time. Thus, the disinfection of contaminated surfaces in both ambient and cold environments is a critical measure to restrain the spread of the virus. In our study, it was demonstrated that the 254 nm ultraviolet-C (UVC) is an efficient method to inactivate a coronavirus, mouse hepatitis virus strain A59 (MHV-A59). The inactivation rate to MHV-A59 coronavirus was up to 99.99% when UVC doses were 2.90 and 14.0 mJ/cm2 at room temperature (23 °C) and in cold environment (-20 °C), respectively. Further mechanistic study demonstrated that UVC could induce spike protein damage to partly impede virus attachment and genome penetration processes, which contributes to 12% loss of viral infectivity. Additionally, it can induce genome damage to significantly interrupt genome replication, protein synthesis, virus assembly and release processes, which takes up 88% contribution to viral inactivation. With these mechanistic understandings, it will greatly contribute to the prevention and control of the current SARS-CoV-2 transmissions in cold chains (low temperature-controlled product supply chains), public area such as airport, school, and warehouse.
RESUMO
BACKGROUND: Hereditary hearing loss (HHL) is the most common sensory deficit, which highly afflicts humans. With gene sequencing technology development, more variants will be identified and support genetic diagnoses, which is difficult for human experts to diagnose. This study aims to develop a machine learning-based genetic diagnosis model of HHL-related variants of GJB2, SLC26A4 and MT-RNR1. METHODS: This case-control study included 1898 subjects, among which 1354 were HHL patients and 544 were carriers. Risk assessment models were established based on variants at 144 sites in three genes related to HHL by building six machine learning (ML) models. We compared the ML models with the genetic risk score (GRS) and expert interpretation (EI) to verify the clinical performance. FINDINGS: Among the six ML models, the support vector machine (SVM) showed the best performance. For the prediction of HHL-related gene sites in subjects with variants, the area under the receiver operating characteristic (AUC) of the SVM model was 0.803 (0.680-0.814) in the 10-fold stratified cross-validation and 0.751 (0.635-0.779) in external validation. The predicted results were better than both EI and GRS. Furthermore, 11 sites were identified as the smallest feature set that can be accurately predicted. INTERPRETATION: The developed SVM model has great potential to be an efficient and effective tool for HHL prediction when high throughput sequencing data are available. FUNDING: This study was supported by the National Key Research and Development Program (2017YFC1001800).