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1.
Front Pharmacol ; 15: 1347316, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38482055

RESUMEN

Background: Radix Bupleuri, a kind of Chinese herbal medicine with great clinical use, is often confused with its adulterants, and it is difficult to identify it without certain knowledge. The existing identification methods have their own drawbacks, so a new method is needed to realize the identification of Radix Bupleuri and its adulterants. Methods: We used Micro Computed Tomography (Micro-CT) to perform tomography scans on Radix Bupleuri and its adulterants, performed data screening and data correction on the obtained DICOM images, and then applied 3D reconstruction, data augmentation, and ResNext deep learning model for the classification study. Results: The DICOM images after data screening, data correction, and 3D reconstruction can observe the differences in the microstructure of Radix Bupleuri and its adulterants, thus enabling effective classification and analysis. Meanwhile, the accuracy of classification using the ResNext model reached 75%. Conclusion: The results of this study showed that Micro-CT technology is feasible for the authentication of Radix Bupleuri. The pre-processed and 3D reconstructed tomographic images clearly show the microstructure and the difference between Radix Bupleuri and its adulterants without damaging the internal structure of the samples. This study concludes that Micro-CT technology provides important technical support for the reliable identification of Radix Bupleuri and its adulterants, which is expected to play an important role in the quality control and clinical application of herbs.

2.
J Ethnopharmacol ; 321: 117490, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38030025

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoqinglong decoction (XQLD), first recorded in Shang Han Lun, is a traditional Chinese medicine prescribed for the treatment of allergic rhinitis (AR). XQLD alleviates the clinical symptoms of AR by inhibiting the occurrence of an inflammatory response, but the specific regulatory mechanism remains unclear. AIM OF THE STUDY: NLRP3-mediated pyroptosis is closely related to AR pathogenesis. Hence, this study aimed to explore the potential role of NLRP3-mediated pyroptosis pathway in the AR-associated pharmacological mechanism of XQLD. MATERIALS AND METHODS: BALB/C mice models of AR was established by using ovalbumin (OVA) and aluminum hydroxide sensitization. After intragastric administration of different dosages of XQLD, nasal allergic symptoms were observed. The expression of OVA-sIgE and Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum was detected by ELISA. The histopathological morphology and expression of inflammatory factors in nasal mucosa along with pyroptosis were investigated. Molecular docking was performed to analyze the binding of representative compounds of XQLD with NLRP3. Activation of the NLRP3 inflammasome was detected by immunofluorescence and western blotting. RESULTS: XQLD significantly improved the nasal allergic symptoms of mice, reduced the degree of goblet cell proliferation, mast cell infiltration, and collagen fiber hyperplasia in nasal mucosa. Meanwhile, it could downregulate the expression of Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum and nasal mucosa. XQLD significantly reduced the number of GSDMD and TUNEL double-positive cells and IL-1ß and IL-18 expression. Molecular docking confirmed that seven representative compounds of XQLD had good binding properties with NLRP3 and were able to inhibit the activation of the NLRP3 inflammasome. CONCLUSIONS: The representative compounds of XQLD might inhibit pyroptosis in nasal mucosa mediated by the NLRP3 inflammasome to helping the recovery of AR, which provides a new modern pharmacological proof for XQLD to treat AR.


Asunto(s)
Proteína con Dominio Pirina 3 de la Familia NLR , Rinitis Alérgica , Ratones , Animales , Inflamasomas/metabolismo , Interleucina-13 , Ratones Endogámicos BALB C , Piroptosis , Interleucina-4 , Interleucina-5 , Simulación del Acoplamiento Molecular , Rinitis Alérgica/tratamiento farmacológico , Modelos Animales de Enfermedad , Ovalbúmina
3.
Phytother Res ; 37(11): 5243-5278, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37795775

RESUMEN

As a worldwide public health issue, cancer-induced cachexia can result in decreasing physical function and survival rate. However, the therapeutic effects of conventional approaches, including pharmacotherapy, exercise and nutritional intervention, are far from satisfactory. Herbal medicines (HMs), especially Traditional Chinese Medicine (TCM), are reported to effectively treat cachexia for centuries. The inclusion criteria of all participants in this study pointed to the diagnosis of cachexia, the trial group used herbal medicine (HM) in complementary and alternative medicine, etc. Twelve databases, including EMbase, PubMed, Web of science, Cochrane CENTRAL, CINAHL, CINAHLPlus, PsycINFO, AMED, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Chongqing VIP (CQVIP) were retrieved from inception to March 28, 2022. We conducted the meta-analysis utilizing RevMan 5.3. A trial sequential analysis (TSA) was conducted to assess the adequacy of the sample size for the outcomes. We have registered the protocol and the registration number was CRD42022336446. A total of 66 studies were included, containing 3654 patients diagnosed with cancer cachexia, of which 1833 patients were assigned to the trial group and 1821 patients were treated in the control group. Outcomes cover the primary indicator KPS (RR = 1.84, 95%CI = [1.61, 2.09], p < 0.00001), and other outcomes including adverse events rate (RR = 0.37, 95%CI = [0.23, 0.58], p < 0.0001), albumin (MD = 2.14, 95%CI = [1.56, 2.71], p < 0.00001), haemoglobin (MD = 4.88, 95%CI = [3.26, 6.50], p < 0.00001), TCM syndrome effect (MD = 1.47, 95%CI = [1.31, 1.65], p < 0.00001), effect of weight (RR = 1.62, 95%CI = [1.34, 1.95], p < 0.00001), effect of appetite (RR = 1.23, 95%CI = [1.13, 1.34], p < 0.00001), FAACT (RR = 7.81, 95%CI = [6.12, 9.50], p < 0.00001), PG-SGA (MD = -2.16, 95%CI = [-2.65, -1.67], p < 0.00001) and QOL (MD = 5.76, 95%CI = [4.04, 7.48], p < 0.00001), suggesting that HMs or HMs combined with conventional treatment have an ameliorating effect on cachexia in each respect. Subgroup analysis showed that the five HMs with the best effect on improving KPS and their optimal doses were Coicis Semen (Yiyiren) in 10 g group, Citri Reticulatae Pericarpium (Chenpi) in 15 g group, Dioscoreae Rhizoma (Shanyao) in 10 g group, Ophiopogonis Radix (Maidong) in 10 g group and Ginseng Radix Et Rhizoma (Renshen) in 20 g group. In addition, there were HM combinations of levels 2-6. Egger's test showed publication bias for five outcomes. HMs have a significant effect on improving cancer cachexia on FAACT, TCM syndrome, KPS, QOL, appetite, nutritional status (evaluated by PG-SGA scale), weight, levels of albumin and haemoglobin. And the Adverse events rate is less than that of Western Medicine. The herbs with the best curative effect and their optimal dose were Dioscoreae R. (10 g), Citri R.P. (15 g), Coicis S. (10 g), Ophiopogonis R. (10 g) and Ginseng R.E.R. (20 g). Due to the quality of included studies is not high, further high-quality studies are needed to firmly establish the clinical efficacy of HM.


Asunto(s)
Medicamentos Herbarios Chinos , Neoplasias , Plantas Medicinales , Humanos , Calidad de Vida , Caquexia/etiología , Caquexia/inducido químicamente , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Albúminas , Hemoglobinas
4.
Zhongguo Zhong Yao Za Zhi ; 48(9): 2368-2378, 2023 May.
Artículo en Chino | MEDLINE | ID: mdl-37282866

RESUMEN

This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 µmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Pronóstico , Biología Computacional
5.
CNS Neurosci Ther ; 29(4): 1094-1108, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36627822

RESUMEN

BACKGROUND: A growing body of research shows that drug monomers from traditional Chinese herbal medicines have antineuroinflammatory and neuroprotective effects that can significantly improve the recovery of motor function after spinal cord injury (SCI). Here, we explore the role and molecular mechanisms of Alpinetin on activating microglia-mediated neuroinflammation and neuronal apoptosis after SCI. METHODS: Stimulation of microglia with lipopolysaccharide (LPS) to simulate neuroinflammation models in vitro, the effect of Alpinetin on the release of pro-inflammatory mediators in LPS-induced microglia and its mechanism were detected. In addition, a co-culture system of microglia and neuronal cells was constructed to assess the effect of Alpinetin on activating microglia-mediated neuronal apoptosis. Finally, rat spinal cord injury models were used to study the effects on inflammation, neuronal apoptosis, axonal regeneration, and motor function recovery in Alpinetin. RESULTS: Alpinetin inhibits microglia-mediated neuroinflammation and activity of the JAK2/STAT3 pathway. Alpinetin can also reverse activated microglia-mediated reactive oxygen species (ROS) production and decrease of mitochondrial membrane potential (MMP) in PC12 neuronal cells. In addition, in vivo Alpinetin significantly inhibits the inflammatory response and neuronal apoptosis, improves axonal regeneration, and recovery of motor function. CONCLUSION: Alpinetin can be used to treat neurodegenerative diseases and is a novel drug candidate for the treatment of microglia-mediated neuroinflammation.


Asunto(s)
Flavonas , Enfermedades Neuroinflamatorias , Traumatismos de la Médula Espinal , Animales , Ratas , Apoptosis/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Janus Quinasa 2/efectos de los fármacos , Janus Quinasa 2/metabolismo , Lipopolisacáridos , Microglía , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Ratas Sprague-Dawley , Transducción de Señal , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismo , Flavonas/farmacología , Flavonas/uso terapéutico , Factor de Transcripción STAT3/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo
6.
Food Funct ; 13(23): 12051-12066, 2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36342232

RESUMEN

Resveratrol (RES) has many beneficial effects on the human body, but it is always unstable, resulting in low oral bioavailability, especially in the gastrointestinal tract. In this study, we developed an oral intestine-specific released hydrogel carrier for targeted RES release in the intestinal tract, which was composed of alginate (ALG) with a specific ratio of α-L-guluronic (G blocks) and ß-D-mannuronic (M blocks) and low methoxyl pectin (LMP). The encapsulation efficiency and loading capacity of RES was 92.04 ± 0.32% and 6.41 ± 0.022 mg g-1 samples, respectively. Positioning release kinetics were investigated in vivo and in vitro. Also, this hydrogel carrier provides good protection for RES against the stomach. 94.71% of RES could be transported to the intestines in two hours after oral administration and released mainly in the small intestine and colon. Thus, the hydrogel carrier is conducive to RES, which is absorbed through the intestinal barrier rather than the stomach after oral administration. Moreover, the hydrogel carrier could load other health factors with expected encapsulation efficiencies, such as curcumin (93.52%), ascorbic acid (90.33%), ginsenoside Rg3 (81.54%), and EGCG (92.27%). These also implied that the hydrogel carrier holds general applicability in disease management.


Asunto(s)
Alginatos , Pectinas , Humanos , Hidrogeles , Resveratrol , Intestinos , Portadores de Fármacos
7.
Food Res Int ; 160: 111739, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36076467

RESUMEN

Threeoligosaccharides, namely single clove garlic (SGOS), purple garlic (PGOS), and Cangshan hybrid garlic (HGOS), were prepared by water extraction and ethanol precipitation. The chemical composition and molecular weight of garlic oligosaccharides were elucidated by gas chromatograph, high-performance liquid chromatography,Fourier-transform infrared (FTIR), and nuclear magnetic resonance (NMR) analyses. Moreover, fortified dough was prepared by adding garlic oligosaccharides at different proportions to evaluate the interaction of the obtained oligosaccharides with gluten proteins. Additionally, the microcosmic, mesoscopic, and macroscopic characteristics of the fortified dough were investigated in terms of the physical and rheological properties, thermodynamic parameters, moisture distribution, morphology, and protein secondary structure using texture profile analysis, rheology, differential scanning calorimetry, low-field NMR, scanning electron microscopy, confocal laser scanning microscopy and FTIR analyses. The results indicated that SGOS was mainly composed of galactose. SGOS fraction had a slightly higher molecular weight (3.00 × 103 Da) compared to the HGOS and PGOS fractions (2.90 × 103 Da), which showed the most compatibility with the dough matrix, thereby improving the dough quality. The present study results can provide a theoretical basis for the application of garlic oligosaccharides in the development of flour-based products.


Asunto(s)
Pan , Ajo , Pan/análisis , Harina/análisis , Oligosacáridos , Triticum/química
8.
Int Immunopharmacol ; 111: 109163, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35994851

RESUMEN

BACKGROUND: Spinal cord injury (SCI) can cause severe motor impairment. Post-SCI treatment has focused primarily on secondary injury, with neuroinflammation and neuronal apoptosis as the primary therapeutic targets. Aucubin (Au), a Chinese herbal medicine, exerts anti-inflammatory and neuroprotective effects. The therapeutic effects of Aucubin in SCI have not been reported. METHODS: In this study, we carried out an in vivo SCI model and a series of in vitro experiments to explore the therapeutic effect of Aucubin. Western Blotting and immunofluorescence were used to study the effect of Aucubin on microglial polarization and neuronal apoptosis and its underlying mechanism. RESULTS: We found that Aucubin can promote axonal regeneration by reducing neuroinflammation and neuronal apoptosis, which is beneficial to motor recovery after spinal cord injury in rats. Our further in vitro experiments showed that Aucubin can activate the toll-like receptor 4 (TLR4)/myeloid differentiation protein-88 (MyD88)/IκBα/nuclear factor kappa B (NF-κB) signaling pathway to reduce neuroinflammation and reverse mitochondrial dysfunction to reduce neuronal apoptosis. CONCLUSIONS: In summary, these results suggest that Aucubin may ameliorate secondary injury after SCI by reducing neuroinflammation and neuronal apoptosis. Therefore, Au may be a promising post-SCI therapeutic drug.


Asunto(s)
Traumatismos de la Médula Espinal , Animales , Apoptosis , Inflamación/metabolismo , Glucósidos Iridoides , FN-kappa B/metabolismo , Neuronas , Ratas , Ratas Sprague-Dawley , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/tratamiento farmacológico
9.
Pharm Biol ; 60(1): 255-273, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35148221

RESUMEN

CONTEXT: Xinbao pill (XBW), a traditional Chinese herbal formula, is widely used in clinical treatment for cardiovascular diseases; however, the therapeutic effect of XBW on myocardial ischaemia-reperfusion injury (MI/RI) is unclear. OBJECTIVE: This study evaluates the cardioprotective effect and molecular mechanism of XBW against MI/RI. MATERIALS AND METHODS: A phytochemistry-based network pharmacology analysis was used to uncover the mechanism of XBW against MI/RI. Ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was used to identify chemicals. MI/RI-related targets of XBW were predicted using TargetNet database, OMIC database, etc. Sprague-Dawley (SD) rats under anterior descending artery ligation model were divided into Sham, MI/RI and XBW (180 mg/kg, intragastric administration). After 30 min ischaemia and 24 h reperfusion, heart tissues were collected for measurement of myocardial infarct size. After oxygen glucose deprivation for 6 h, H9c2 cells were treated with XBW (60, 240 and 720 µg/mL) and diazoxide (100 µM) for 18 h of reperfusion. RESULTS: Thirty-seven chemicals were identified in XBW; 50 MI/RI-related targets of XBW were predicted using indicated databases. XBW significantly reduced infarct size and creatine kinase MB (CK-MB) level after MI/RI; XBW protected H9c2 cells against OGD/R injury. Gene ontology (GO) and KEGG pathway enrichment analyses by String database showed that the cardioprotective effect of XBW was associated with autophagy and apoptosis signalling pathways. Experimental investigation also verified that XBW suppressed apoptosis, autophagy and endoplasmic reticulum (ER) stress. CONCLUSIONS: XBW showed therapeutic effects against MI/RI mainly via attenuating apoptosis though suppressing excessive autophagy and ER stress.


Asunto(s)
Cardiotónicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Cardiotónicos/administración & dosificación , Línea Celular , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Estrés del Retículo Endoplásmico/efectos de los fármacos , Masculino , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Farmacología en Red , Ratas , Ratas Sprague-Dawley
10.
J Agric Food Chem ; 70(1): 184-195, 2022 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-35016506

RESUMEN

The mechanisms of coffee against Parkinson disease (PD) remained incompletely elucidated. Numerous studies suggested that gut microbiota played a crucial role in the pathogenesis of PD. Here, we explored the further mechanisms of coffee against PD via regulating gut microbiota. C57BL/6 mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce a PD mouse model, then treated with coffee for 4 consecutive weeks. Behavioral tests consisting of the pole test and beam-walking test were conducted to evaluate the motor function of mice. The levels of tyrosine hydroxylase (TH) and α-synuclein (α-syn) were assessed for dopaminergic neuronal loss. The levels of occludin, glial fibrillary acidic protein (GFAP), Bcl-2, Bax, cleaved caspase-3, and cytochrome c (Cyt c) were detected. Moreover, microbial components were measured by 16s rRNA sequencing. Our results showed that coffee significantly improved the motor deficits and TH neuron loss, and reduced the level of α-syn in the MPTP-induced mice. Moreover, coffee increased the level of BBB tight junction protein occludin and reduced the level of astrocyte activation marker GFAP in the MPTP-induced mice. Furthermore, coffee significantly decreased the levels of proapoptotic proteins, including Bax, cleaved caspase-3, and cytochrome c, while it increased the level of antiapoptotic protein Bcl-2, consequently preventing MPTP-induced apoptotic cascade. Moreover, coffee improved MPTP-induced gut microbiota dysbiosis. These findings suggested that the neuroprotective effects of coffee on PD were involved in the regulation of gut microbiota, which might provide a novel option to elucidate the effects of coffee on PD.


Asunto(s)
Microbioma Gastrointestinal , Fármacos Neuroprotectores , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Café , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas , Ratones , Ratones Endogámicos C57BL , ARN Ribosómico 16S
11.
J Ethnopharmacol ; 282: 114611, 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-34537280

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Ilex pubescens (I. pubescens), has been widely used to treat cardiovascular disease (CVD) in South China. Several studies have revealed aspect of its phytochemistry and pharmacological activities in cardiovascular diseases, but its active compounds and mechanisms of action are still unclear. The aim of this study was to search for the active compounds and the pharmacological mechanisms of I. pubescens for myocardial ischemia-reperfusion injury (MI/RI) by an integrative pharmacology-based investigation. MATERIALS AND METHODS: The main targets of compounds in I. pubescens were predicted using the TargetNet webserver (http://targetnet.scbdd.com). The network between compounds and predicted targets related to MI/RI and compounds was constructed. Functional enrichment analysis was performed to investigate the specific functions and pathways involved in the candidate I. pubescens targets acting on MI/RI, which were further validated by in vitro and in vivo experiments. RESULTS: A total of 191 targets were predicted for 64 chemical compounds in I. pubescens. Following Venn's analysis, we found that 38 candidate targets of I. pubescens were associated with protective effects against MI/RI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these targets were related to estrogen signaling pathway. Importantly, the cardioprotective effects of I. pubescens and its active compounds were evaluated and the regulatory effects on key targets of heat shock protein 90 alpha family class A member 1 (HSP90AA1) and Estrogen receptor 1 (ESRα) in estrogen signaling pathway were validated in vitro and in vivo. CONCLUSION: Our discoveries revealed that I. pubescens ameliorated MI/RI by regulating HSP90AA1 and ESRα in estrogen signaling pathway.


Asunto(s)
Ilex/química , Isquemia Miocárdica/complicaciones , Miocitos Cardíacos/efectos de los fármacos , Extractos Vegetales/farmacología , Daño por Reperfusión/tratamiento farmacológico , Animales , Línea Celular , Supervivencia Celular , Masculino , Potencial de la Membrana Mitocondrial , Miocitos Cardíacos/metabolismo , Farmacología en Red , Óxido Nítrico , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley
12.
Angew Chem Int Ed Engl ; 60(45): 24096-24106, 2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-34608723

RESUMEN

We report herein the development of stereodivergent syntheses of enantioenriched homoallylic alcohols using chiral nonracemic α-CH2 Bpin-substituted crotylboronate. Chiral phosphoric acid (S)-A-catalyzed asymmetric allyl addition with the reagent gave Z-anti-homoallylic alcohols with excellent enantioselectivities and Z-selectivities. When the enantiomeric acid catalyst (R)-A was utilized, the stereoselectivity was completely reversed and E-anti-homoallylic alcohols were obtained with high E-selectivities and excellent enantioselectivities. By pairing the chirality of the boron reagent with the catalyst, two complementary stereoisomers of chiral homoallylic alcohols can be obtained selectively from the same boron reagent. DFT computational studies were conducted to probe the origins of the observed stereoselectivity. These reactions generate highly enantioenriched homoallylic alcohol products that are valuable for rapid construction of polyketide structural frameworks.

15.
Clin Toxicol (Phila) ; 58(11): 1015-1022, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32609548

RESUMEN

Introduction: Amatoxin leads to the majority of deaths by mushroom poisoning around the world. Amatoxin causes gastrointestinal disturbances and multiple organ dysfunction, including liver and renal failure. As a potential treatment for amatoxin poisoning, N-acetylcysteine (NAC) has been used for decades but its benefit is still unproven.Objectives: We undertook a systematic review to evaluate the performance and safety of N-acetylcysteine on patients suffering amatoxin intoxication.Methods: We searched Pubmed, EMBASE, CENTRAL and SinoMed databases, from inception to August 31, 2019. Articles were eligible if there were five or more patients with amatoxin poisoning and N-acetylcysteine was included in the therapeutic regimen. Mortality rate including liver transplant cases (MRLTi) was the primary outcome. Mortality rate not including liver transplant cases, liver and renal function, clinical complications, as well as any adverse reactions to intravenous NAC were secondary outcomes.Results: Thirteen studies with a total of 506 patients were included. The MRLTi of amatoxin-poisoning patients with NAC treatment was 11% (57/506), and a MRLTe of 7.9% (40/506) and a liver transplantation rate of 4.3% (22/506). Transaminase concentrations generally peaked around 3 days after ingestion, prothrombin time/International Normalized Ratio (PT/INR) generally worsened during the first 3-4 days after ingestion before returning to normal four to 7 days after ingestion, and Factor V levels normalized in about 4-5 days after ingestion in patients treated with NAC. Renal failure was reported in 3% (3/101) and acute kidney injury was reported in 19% (5/27). Gastrointestinal bleeding occurred in 21% (15/71). Anaphylactoid reactions were the principle adverse reaction to NAC treatment in amatoxin-poisoning patients with an incidence of 5% (4/73).Conclusions: NAC treatment combined with other therapies appears to be beneficial and safe in patients with amatoxin poisoning. Until further data emerge, it is reasonable to use NAC in addition to other treatments for amatoxin poisoning.


Asunto(s)
Acetilcisteína/uso terapéutico , Amanitinas/envenenamiento , Acetilcisteína/efectos adversos , Lesión Renal Aguda/etiología , Hemorragia Gastrointestinal/etiología , Humanos , Hígado/fisiopatología , Trasplante de Hígado/mortalidad , Trasplante de Hígado/estadística & datos numéricos
16.
Food Chem ; 322: 126766, 2020 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-32305873

RESUMEN

A simple, rapid, and effective method based on salting-out extraction and LC-MS/MS techniques was developed for the determination of 39 plant growth regulator (PGR) residues in two of the most common root and rhizome Chinese herbs, Codonopsis Radix (Dangshen) and Notoginseng Radix et Rhizoma (Sanqi). The extraction process was performed with acetonitrile-water (5:1) and citrate buffer extraction salt. The performance of the method was validated in accordance with the analytical quality control criteria of SANTE/11813/2017 guidelines. Analyte recoveries of 79.49-109.41% (Dangshen) and 80.17-102.81% (Sanqi) were achieved. The limit of quantifications (LOQs) were determined with the consideration of accuracy and precision. LOQs were lower than the lowest residue limits in EU pesticide regulation (10 µg/kg) for most PGRs. Moreover, the method was successfully applied in the analysis of 35 batches of Dangshen, and 60 batches of Sanqi products. The concentration of eleven PGRs were determined in analyzed samples.


Asunto(s)
Medicamentos Herbarios Chinos/análisis , Reguladores del Crecimiento de las Plantas/análisis , Cromatografía Líquida de Alta Presión/métodos , Codonopsis/química , Medicamentos Herbarios Chinos/química , Reproducibilidad de los Resultados , Rizoma/química , Espectrometría de Masas en Tándem/métodos
17.
J Chromatogr A ; 1613: 460674, 2020 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-31733897

RESUMEN

To fully capture the chemo-diversity of medicinal plants is very essential for understanding of their pharmacological activities and guiding scientific quality control. Aiming to facilitate chemical characterization and novel natural products discovery, the present study proposed an integrated approach based on two-dimensional liquid chromatography coupled with quadrupole-Orbitrap mass spectrometer (2D LC/Q-Orbitrap MS). An offline comprehensive two-dimensional (2D) LC system was constructed to cover and separate multi-type constituents by combining hydrophilic interaction chromatography (HILIC) and conventional reversed phase C18. A two-step mass defect filtering-induced exclusion list-data dependent acquisition was developed to increase MS/MS coverage and selectivity. Additionally, an efficient interpretation strategy, combining an automatic matching algorithm and molecular networking (MN), was introduced for rapid recognition of known compounds and efficient elucidation of unreported ones. As a case study, the integrated approach was tentatively applied for comprehensive characterization of complex multi-type components in Lonicerae Japonicae Flos (LJF), a traditional Chinese medicine. Consequently, a total of 537 compounds were characterized from LJF, including a large number of potential novel structures. It was demonstrated that the integrated approach is powerful in deep investigation on chemical diversity of medicinal plants and discovery of novel structures. Its application could also be extended for global profiling of other complicated chemical systems, such as Chinese medicinal formulas.


Asunto(s)
Técnicas de Química Analítica/métodos , Lonicera/química , Plantas Medicinales/química , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Medicina Tradicional China , Espectrometría de Masas en Tándem
18.
World Neurosurg ; 124: e748-e754, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30677571

RESUMEN

BACKGROUND: For patients undergoing lumbar spinal surgery, many surgeons routinely perform laboratory tests within 3 days after surgery. However, few studies have reported the necessity for routine laboratory tests for patients with uncomplicated cases within 3 days after surgery. METHODS: We performed a retrospective study of patients with lumbar degenerative disease who had undergone lumbar spinal surgery from May 2014 to May 2017. The perioperative patient information was recorded. The abnormal postoperative laboratory tests were recorded. Finally, the incidence and risk factors for patients requiring postoperative clinical treatment were analyzed. RESULTS: A total of 1915 patients were included in the present study. Postoperative laboratory tests had been ordered for 870 patients (45.43%). Of these patients, only a small proportion had required postoperative clinical intervention to treat abnormal serum hemoglobin (2.53%), albumin (1.95%), serum potassium (0.92%), or serum calcium (6.55%) levels. Multivariate logistic regression analysis showed that female gender and operative time were risk factors for the need for blood transfusion after lumbar spinal surgery. Age and operative time were risk factors for patients requiring albumin supplementation after lumbar spinal surgery. Finally, intraoperative blood loss and operative time were independent risk factors for patients requiring calcium supplementation after surgery. CONCLUSIONS: Owing to the small number of postoperative clinical interventions for abnormal laboratory test results, we believe that the use of routine laboratory tests within 3 days after lumbar spinal surgery for patients with uncomplicated cases are unnecessary. Our results showed that operative time is a potential risk factor for the necessity for clinical treatment after lumbar spinal surgery.

19.
ACS Appl Mater Interfaces ; 10(10): 8436-8442, 2018 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-29457450

RESUMEN

Nowadays, two-dimensional (2D) materials have attracted extensive attention as cancer drug delivery platforms owing to their unparalleled physicochemical properties and superior specific surface area. Graphdiyne (GDY) is a novel 2D carbon material. Compared with graphene, GDY not only has benzene rings composed of sp2-hybridized carbon atoms but also has acetylene units composed of sp-hybridized carbon atoms; therefore, it possesses multiple conjugated electronic structures. Herein, we used doxorubicin (DOX) as a model drug to develop a GDY nanosheet-based drug delivery platform for a photothermal/chemotherapy combination in living mice. With a high photothermal conversion ability and drug loading efficiency, GDY/DOX under 808 nm laser irradiation showed a much higher cancer inhibition rate compared with solo therapy both in vitro and in vivo. Furthermore, GDY exhibited great biocompatibility and no obvious side effects, as shown by histopathological examination and serum biochemical analysis. For the first time, our work demonstrated a successful example of GDY for efficient photothermal/chemotherapy and suggests both safety and great promise for GDY in cancer treatment.


Asunto(s)
Nanoestructuras , Animales , Antineoplásicos , Doxorrubicina , Sistemas de Liberación de Medicamentos , Grafito , Ratones , Neoplasias , Fototerapia
20.
ACS Appl Mater Interfaces ; 9(28): 23497-23507, 2017 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-28661121

RESUMEN

Cancer stem cells (CSCs) have been identified as a new target for therapy in diverse cancers. Traditional therapies usually kill the bulk of cancer cells, but are often unable to effectively eliminate CSCs, which may lead to drug resistance and cancer relapse. Herein, we propose a novel strategy: fabricating multifunctional magnetic Fe3O4@PPr@HA hybrid nanoparticles and loading it with the Notch signaling pathway inhibitor N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycinet-butylester (DAPT) to eliminate CSCs. Hyaluronic acid ligands greatly enhance the accumulation of the hybrid nanoparticles in the tumor site and in the CSCs. Both hyaluronase in the tumor microenvironment and the magnetic hyperthermia effect of the inner magnetic core can accelerate the release of DAPT. This controlled release of DAPT in the tumor site further enhances the ability of the combination of chemo- and magnetohyperthermia therapy to eliminate cancer stem cells. With the help of polypyrrole-mediated photoacoustic and Fe3O4-mediated magnetic resonance imaging, the drug release can be precisely monitored in vivo. This versatile nanoplatform enables effective elimination of the cancer stem cells and monitoring of the drugs.


Asunto(s)
Células Madre Neoplásicas , Liberación de Fármacos , Humanos , Hipertermia Inducida , Nanopartículas , Fototerapia
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