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1.
PLoS One ; 19(4): e0301986, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38626158

RESUMEN

The production of sludge-based biochar to recover phosphorus (P) from wastewater and reuse the recovered phosphorus as agricultural fertilizer is a preferred process. This article mainly studied the removal of phosphate (PO4-P) from aqueous solution by synthesizing sludge-based biochar (MgSBC-0.1) from anaerobic fermentation sludge treated with magnesium (Mg)-loading-modification, and compared it with unmodified sludge-based biochar (SBC). The physicochemical properties, adsorption efficiency, and adsorption mechanism of MgSBC-0.1 were studied. The results showed that the surface area of MgSBC-0.1 synthesized increased by 5.57 times. The material surface contained MgO, Mg(OH)2, and CaO nanoparticles. MgSBC-0.1 can effectively remove phosphate in the initial solution pH range of 3.00-7.00, with a fitted maximum phosphorus adsorption capacity of 379.52 mg·g-1. The adsorption conforms to the pseudo second-order kinetics model and Langmuir isotherm adsorption curve. The characterization of the adsorbed composite material revealed the contribution of phosphorus crystal deposition and electrostatic attraction to phosphorus absorption.


Asunto(s)
Fosfatos , Contaminantes Químicos del Agua , Fosfatos/química , Magnesio , Aguas del Alcantarillado , Adsorción , Carbón Orgánico , Fósforo/química , Cinética , Contaminantes Químicos del Agua/análisis
2.
Nat Commun ; 14(1): 8281, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38092825

RESUMEN

Metabolic oligosaccharide engineering (MOE) is a classical chemical approach to perturb, profile and perceive glycans in physiological systems, but probes upon bioorthogonal reaction require accessibility and the background signal readout makes it challenging to achieve glycan quantification. Here we develop SeMOE, a selenium-based metabolic oligosaccharide engineering strategy that concisely combines elemental analysis and MOE,enabling the mass spectrometric imaging of glycome. We also demonstrate that the new-to-nature SeMOE probes allow for detection, quantitative measurement and visualization of glycans in diverse biological contexts. We also show that chemical reporters on conventional MOE can be integrated into a bifunctional SeMOE probe to provide multimodality signal readouts. SeMOE thus provides a convenient and simplified method to explore the glyco-world.


Asunto(s)
Selenio , Polisacáridos/metabolismo , Oligosacáridos/metabolismo , Ingeniería Metabólica , Espectrometría de Masas
3.
Anal Chem ; 94(27): 9636-9647, 2022 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-35763570

RESUMEN

Selenium, as an essential trace element of life, is closely related to human health and is required to produce selenoproteins, a family of important functional proteins in many living organisms. All selenoproteins contain a special amino acid, selenocysteine, which often serves as their active-site residue, and the expression and activity of selenoproteins are fine-tuned. However, the turnover dynamics of selenoproteome has never been systematically investigated, especially in a site-specific manner for selenocysteines. In the current work, we developed a chemical proteomic strategy named "SElenoprotein Turnover Rate by Isotope Perturbation (SETRIP)" to quantitatively monitor the turnover dynamics of selenoproteins at the proteomic level. The kinetic rates and half-lives of nine selenoproteins were accurately measured by combining Na274SeO3 metabolic labeling with pulse-chase chemoproteomics. The half-lives of selenoproteins were measured to range from 6 to 32 h with the housekeeping selenoprotein glutathione peroxidases (GPX4) showing a faster turnover rate, implying that the hierarchy regulation also exists in the turnover of selenoproteins in addition to expression and activity. Our study generated a global portrait of dynamic changes in the selenoproteome and provided important clues to study the roles of selenium in biology.


Asunto(s)
Selenio , Glutatión Peroxidasa , Humanos , Proteómica , Selenocisteína , Selenoproteínas/química , Selenoproteínas/metabolismo
4.
Int J Pharm ; 621: 121820, 2022 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-35569628

RESUMEN

Otitis media, mainly caused by bacteria, is prevalent in young children and can cause hearing loss and growth retardation. Antibiotics are the most widely utilized treatment for otitis media, however, they can cause drug resistance and harmful side effects. In this study, we reported an antibacterial nanocomposite in combination with sonodynamic therapy that consists of herbal antibacterial agents such as Curcumin (CUR) and Tanshinone IIA (TSIIA), as well as Chitosan (CS), for the treatment of acute otitis media. CUR/TSIIA/CS nanocomposite (NC) with ultrasonic irradiation demonstrated that it could eliminate Staphylococcus aureus. In vivo experiments revealed that NC-mediated sonodynamic therapy had excellent antibacterial and anti-inflammatory activity, displaying a consistent performance comparable to ofloxacin. The therapeutic efficiency was attributed to capturing bacteria through spider-web-like effect and destroying bacteria through the reactive oxygen species generated under ultrasonic irradiation. Significantly, NC did not induce bacterial resistance and showed good biocompatibility. This study provides a novel strategy to develop an ultrasound-assisted nanocomposite with an enhanced antibacterial effect. Further, it unlocks new doors for the substitute of antibiotics to combat otitis media by establishing efficient therapeutic systems.


Asunto(s)
Quitosano , Curcumina , Nanocompuestos , Otitis Media , Arañas , Infecciones Estafilocócicas , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias , Preescolar , Quitosano/farmacología , Curcumina/farmacología , Humanos , Otitis Media/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico
5.
Methods Enzymol ; 662: 241-258, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35101212

RESUMEN

Selenoproteins play crucial roles including protection and recovery from oxidative stress in organisms. Direct profiling of selenoproteins in proteomes is challenging due to their extremely low abundance. We have developed a computational algorithm termed selenium-encoded isotopic signature targeted profiling (SESTAR) to increase the sensitivity of detecting selenoproteins in complex proteomic samples. In this chapter, we briefly described the basic algorithm of SESTAR. We then introduced SESTAR++, an updated version of SESTAR, with accelerated computation speed and lowered false positive rate. We also provided a detailed workflow to apply SESTAR++ to proteomic profiling of selenoproteins, including the instruction of running the software and implementing it in a targeted profiling mode.


Asunto(s)
Selenio , Algoritmos , Isótopos , Proteómica , Selenoproteínas/análisis
6.
Front Med (Lausanne) ; 8: 756940, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34901069

RESUMEN

Background: Neuropathic pain (NP), a severe and disruptive symptom following many diseases, normally restricts patients' physical functions and leads to anxiety and depression. As an economical and effective therapy, exercise may be helpful in NP management. However, few guidelines and reviews focused on exercise therapy for NP associated with specific diseases. The study aimed to summarize the effectiveness and efficacy of exercise for various diseases with NP supported by evidence, describe expert recommendations for NP from different causes, and inform policymakers of the guidelines. Design: A systematic review and expert consensus. Methods: A systematic search was conducted in PubMed. We included systematic review and meta-analysis, randomized controlled trials (RCTs), which assessed patients with NP. Studies involved exercise intervention and outcome included pain intensity at least. Physiotherapy Evidence Database and the Assessment of Multiple Systematic reviews tool were used to grade the quality assessment of the included RCTs and systematic reviews, respectively. The final grades of recommendation were based on strength of evidence and a consensus discussion of results of Delphi rounds by the Delphi consensus panel including 21 experts from the Chinese Association of Rehabilitation Medicine. Results: Eight systematic reviews and 21 RCTs fulfilled all of the inclusion criteria and were included, which were used to create the 10 evidence-based consensus statements. The 10 expert recommendations regarding exercise for NP symptoms were relevant to the following 10 different diseases: spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, cervical radiculopathy, sciatica, diabetic neuropathy, chemotherapy-induced peripheral neuropathy, HIV/AIDS, and surgery, respectively. The exercise recommended in the expert consensus involved but was not limited to muscle stretching, strengthening/resistance exercise, aerobic exercise, motor control/stabilization training and mind-body exercise (Tai Chi and yoga). Conclusions: Based on the available evidence, exercise is helpful to alleviate NP intensity. Therefore, these expert consensuses recommend that proper exercise programs can be considered as an effective alternative treatment or complementary therapy for most patients with NP. The expert consensus provided medical staff and policymakers with applicable recommendations for the formulation of exercise prescription for NP. This consensus statement will require regular updates after five-ten years.

7.
Int J Biol Macromol ; 192: 1256-1265, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34673104

RESUMEN

Chinese quince (Chaenomeles sinensis) fruits offer a potential source of pectin and hemicellulose. However, the existence of lignin-carbohydrate complexes (LCCs) can negatively impact the extraction of pectin and hemicellulose. In this work, LCCs were sequentially fractionated from Chinese quince during the removal of pectin and hemicellulose. The structures of LCCs were characterized by HPAEC, FT-IR, GPC, Py-GC/MS, TGA and 2D HSQC NMR. The results showed that the carbohydrate content and molecular weight of LCCs was found to be changed significantly after the removal of hemicellulose (KSH). The lignin in Björkman LCCs was found to be linked mainly to galactan and fructan, whereas the lignin LCC-AcOHs was found to be linked mainly to arabinan after the removal of KSH. The isolation of carbonate-soluble pectin (NSP) increased thermal stability of Björkman LCC fraction, however, the isolation of chelator-soluble pectin (CSP) increased the thermal stability of LCC-AcOHs. The S/G ratios of LCC-AcOHs increased and large amounts of S-type lignin released during sequential fractionation of pectin and hemicellulose. These results will be beneficial for understanding the mechanisms of pectin and hemicellulose isolation, thereby facilitating the potential application of Chinese quince as a valuable natural resource for food and other industries.


Asunto(s)
Carbohidratos/química , Lignina/química , Sustancias Macromoleculares/química , Pectinas/química , Polisacáridos/química , Rosaceae/química , Fraccionamiento Químico , Peso Molecular , Pectinas/aislamiento & purificación , Polisacáridos/aislamiento & purificación , Análisis Espectral
8.
Artif Cells Nanomed Biotechnol ; 47(1): 3101-3109, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31343369

RESUMEN

Nanotechnology is creating a bang in each and every field of life science. Scientists are mounting their interest of research towards gold nanoparticles as they are capable with bigger and advanced properties.Traditionally nanoparticles have been manufactured by various chemical and physical methods but have negative impact on the environment and are also highly toxic. Synthesis of nanoparticles by using plant extracts is substituting the conventional methods and it is eco-friendly too. In the current study, we prepared gold nanoparticles (AuNPs) from Magnolia officinalis, which is identified as an eco-friendly and less toxic method. Incorporation of AuNPs was renowned by UV-absorbance and it shows peak values. Nanoparticle sizes are recognized by dynamic light scattering scrutiny and it shows a value of 128 nm. Besides, high resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray analysis (EDX) and atomic force microscopy (AFM) incorrigibly define the shape of the AuNPs which are present in the complex materials. Fourier-transform infrared spectroscopy (FTIR) findings display that the active molecules are positioned in the plane of the AuNPs. Similarly, anticancer efficacy of AuNPs have been assessed in A549 cells. our study show that AuNPs effectively provoke cytotoxicity, and apoptosis by inflecting apoptotic gene expressions in A549 cells.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Oro/química , Neoplasias Pulmonares/patología , Magnolia/química , Nanopartículas del Metal/química , Células A549 , Antineoplásicos/síntesis química , Técnicas de Química Sintética , Tecnología Química Verde , Humanos , Nanotecnología , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 44(8): 1715-1723, 2019 Apr.
Artículo en Chino | MEDLINE | ID: mdl-31090340

RESUMEN

Epimedii Folium,a commonly used traditional Chinese medicine,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism. However,in recent years,the number of reports on adverse reactions of Epimedii Folium and its Chinese patent medicines such as Xianling Gubao Capsules and Zhuanggu Guanjie Pills has been gradually increased,and the toxicity of Epimedii Folium has attracted more and more attention. In this article,the ancient and modern literature on Epimedii Folium was traced through a comprehensive and systematic literature analysis method. According to the 2015 edition of the Chinese Pharmacopoeia,Epimedii Folium refers to the dried leaves of Epimedii Folium brevicomu,E. sugittutum,E. pubescens or E. koreuuum. The Chinese Pharmacopoeia also includes E. wushanense of Wushan Epimedium,which is the same plant variety as Epimedium. The study showed that there were differences in the geographical distribution,composition and toxicity among five species of Epimedium. This paper also explained the toxicity mechanism as well as efficacy enhancing and toxicity reducing effects of Epimedii Folium,and reported its related adverse reaction cases. Through a retrospective comparative study on the toxicity of the modern Chinese patent medicines Xianling Gubao Capsules and Zhuanggu Guanjie Pills containing Epimedii Folium,it was believed that Epimedii Folium had cardiovascular system toxicity,neurotoxicity,hepatotoxicity,long-term toxicity,acute toxicity,genotoxicity and special toxicity; its safe medication factors included patient syndrome,doctor factors,drug factors,processing and compatibility factors. Meanwhile,strategies were proposed to improve patient safety medication awareness,standardize Epimedii Folium varieties and quality supervision,and the toxicity of Epimedii Folium was studied,hoping to draw attention from scholars to the safety of Epimedii Folium,improve the safe use of Epimedii Folium,and prevent adverse reactions.


Asunto(s)
Medicamentos Herbarios Chinos/efectos adversos , Epimedium/química , Humanos , Medicina Tradicional China , Hojas de la Planta/química , Estudios Retrospectivos
10.
J Am Chem Soc ; 141(22): 8951-8968, 2019 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-31060360

RESUMEN

Covalent probes can display unmatched potency, selectivity, and duration of action; however, their discovery is challenging. In principle, fragments that can irreversibly bind their target can overcome the low affinity that limits reversible fragment screening, but such electrophilic fragments were considered nonselective and were rarely screened. We hypothesized that mild electrophiles might overcome the selectivity challenge and constructed a library of 993 mildly electrophilic fragments. We characterized this library by a new high-throughput thiol-reactivity assay and screened them against 10 cysteine-containing proteins. Highly reactive and promiscuous fragments were rare and could be easily eliminated. In contrast, we found hits for most targets. Combining our approach with high-throughput crystallography allowed rapid progression to potent and selective probes for two enzymes, the deubiquitinase OTUB2 and the pyrophosphatase NUDT7. No inhibitors were previously known for either. This study highlights the potential of electrophile-fragment screening as a practical and efficient tool for covalent-ligand discovery.


Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Electrones , Células HEK293 , Humanos , Ligandos , Modelos Moleculares , Peso Molecular , Conformación Proteica , Factores de Tiempo
11.
Bioresour Technol ; 285: 121370, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31022576

RESUMEN

The effect of condensing temperature on composition of bio-oil obtained via fractional condensation was investigated by pyrolysis-condensation experiments of walnut shells at condensing temperatures from 290 K to 370 K. The condensing efficiency of the first stage condenser decreased from 0.59 to 0.12 with increasing temperature. Moisture of bio-oil decreased from 40% to 5%, but the C/O ratio increased from 0.50 to 1.50. Compared with contents observed at the lowest condensation temperature, the maximum content of each component increased by 50%-500%. Combined with variations in condensing efficiency and composition content, the optimum condensing temperature range for declining water in bio-oil was 340-350 K. The condensing temperature associated with the enrichment of acetic acid and furfural was 345 K. The 355 K optimum condensing temperature could be selected to achieve the maximum enrichment of guaiacol and its derivatives.


Asunto(s)
Biocombustibles , Juglans , Biomasa , Calor , Aceites de Plantas , Polifenoles , Pirólisis , Temperatura
12.
Drug Dev Ind Pharm ; 45(6): 995-998, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30892088

RESUMEN

Novel fatty acid-bile acid conjugates (1a-1k) were designed and synthesized by coupling of the fatty acids to the 3-OH of bile acids using lysine for linkage. In the conjugates, the 24-COOH of the bile acids was kept intact to preserve liver-specific recognition. The ability of the newly synthesized conjugates (at 100 mg/kg dosage) to reduce total cholesterol (TC) and triglyceride (TG) levels in mice fed with high-fat diet (HFD) was evaluated. Conjugates of stearic acid with cholic acid and palmitic acid with ursodeoxycholic acid (at dosages of 50, 100, and 200 mg/kg) were further evaluated to determine their ability to reduce aspartate aminotransferase (AST), alanine aminotransferase (ALT), TC, and TG levels in mice fed with HFD. All conjugates showed potent hypolipidemic activity. Further investigation revealed that compounds 1c and 1 g not only dose-dependently reduced serum levels of TC and TG, but also inhibited the elevation of serum AST and ALT levels in mice fed with HFD. Thus, compounds 1c and 1 g are promising hypolipidemic agents with hepatocyte protective effects against HFD-induced liver damage.


Asunto(s)
Ácidos y Sales Biliares/administración & dosificación , Ácidos Grasos/administración & dosificación , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/administración & dosificación , Hígado/efectos de los fármacos , Animales , Ácidos y Sales Biliares/química , Colesterol/sangre , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Ácidos Grasos/química , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/etiología , Hiperlipidemias/patología , Hipolipemiantes/química , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Pruebas de Función Hepática , Lisina/química , Ratones , Triglicéridos/sangre
13.
Chin J Integr Med ; 25(3): 203-209, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30552545

RESUMEN

OBJECTIVE: To investigate the effects of Ganoderma lucidum polysaccharides (GL-PS) on human fibroblasts and skin wound healing in Kunming male mice and to explore the putative molecular mechanism. METHODS: Primary human skin fibroblasts were cultured. The viability of fibroblasts treated with 0, 10, 20, 40, 80, and 160 µg/mL of GL-PS, respectively were detected by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-Htetrazolium bromide (MTT). The migration ability of fibroblasts treated with 0, 10, 20, and 40 µg/mL of GL-PS were measured by transwell assay. The secretion of the C-terminal peptide of procollagen type I (CICP) and transforming growth factor-ß1 (TGF-ß1) in the cell supernatant was tested by enzyme-linked immunosorbent assay. The expression of ß-catenin was detected by Western blot. Furthermore, the Kunming mouse model with full-layer skin resection trauma was established, and was treated with 10, 20, and 40 mg/mL of GL-PS, respectively as external use. The size of the wound was measured daily, complete healing time in each group was recorded and the percentage of wound contraction was calculated. RESULTS: Compared with the control group, 10, 20, and 40 µg/mL of GL-PS significantly increased the viability of fibroblasts, promoted the migration ability of fibroblasts, and up-regulated the expressions of CICP and TGF-ß1 in fibroblasts (Plt;0.05 or Plt;0.01). The expression of ß-catenin in fibroblasts treated with 20 and 40 µg/mL of GL-PS was significantly higher than that of the control group (Plt;0.01). Furthermore, after external use of 10, 20, and 40 mg/mL of GL-PS, the rates of wound healing in mice were significantly higher and the wound healing time was significantly less than the control group (Plt;0.05 or Plt;0.01). CONCLUSION: A certain concentration of GL-PS may promote wound healing via activation of the Wnt/ß-catenin signaling pathway and up-regulation of TGF-ß1, which might serve as a promising source of skin wound healing.


Asunto(s)
Polisacáridos/farmacología , Reishi/química , Piel/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Animales , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Colágeno Tipo I/biosíntesis , Fibroblastos/efectos de los fármacos , Humanos , Masculino , Ratones , Piel/lesiones , Factor de Crecimiento Transformador beta1/fisiología , beta Catenina/fisiología
14.
Artículo en Chino | WPRIM | ID: wpr-773178

RESUMEN

Epimedii Folium,a commonly used traditional Chinese medicine,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism. However,in recent years,the number of reports on adverse reactions of Epimedii Folium and its Chinese patent medicines such as Xianling Gubao Capsules and Zhuanggu Guanjie Pills has been gradually increased,and the toxicity of Epimedii Folium has attracted more and more attention. In this article,the ancient and modern literature on Epimedii Folium was traced through a comprehensive and systematic literature analysis method. According to the 2015 edition of the Chinese Pharmacopoeia,Epimedii Folium refers to the dried leaves of Epimedii Folium brevicomu,E. sugittutum,E. pubescens or E. koreuuum. The Chinese Pharmacopoeia also includes E. wushanense of Wushan Epimedium,which is the same plant variety as Epimedium. The study showed that there were differences in the geographical distribution,composition and toxicity among five species of Epimedium. This paper also explained the toxicity mechanism as well as efficacy enhancing and toxicity reducing effects of Epimedii Folium,and reported its related adverse reaction cases. Through a retrospective comparative study on the toxicity of the modern Chinese patent medicines Xianling Gubao Capsules and Zhuanggu Guanjie Pills containing Epimedii Folium,it was believed that Epimedii Folium had cardiovascular system toxicity,neurotoxicity,hepatotoxicity,long-term toxicity,acute toxicity,genotoxicity and special toxicity; its safe medication factors included patient syndrome,doctor factors,drug factors,processing and compatibility factors. Meanwhile,strategies were proposed to improve patient safety medication awareness,standardize Epimedii Folium varieties and quality supervision,and the toxicity of Epimedii Folium was studied,hoping to draw attention from scholars to the safety of Epimedii Folium,improve the safe use of Epimedii Folium,and prevent adverse reactions.


Asunto(s)
Humanos , Medicamentos Herbarios Chinos , Epimedium , Química , Medicina Tradicional China , Hojas de la Planta , Química , Estudios Retrospectivos
15.
Artículo en Inglés | MEDLINE | ID: mdl-30216996

RESUMEN

For decades, professional divisions have been represented as the main structural divisions in Western medicine throughout the world. In Taiwan, medical policymakers are also interested in designing professional divisions of traditional Chinese medicine (TCM). Therefore, this study evaluated the current status and potentiality of professional divisions of TCM in Taiwan using data from the year 2012 obtained from the National Health Insurance Research Database; the database provides information regarding age and gender of TCM physicians (TCMPs); total visit counts; contracted medical institution codes; groupings of diseases classified under International Classification of Diseases, Ninth Revision, Clinical Modification codes; numbers of children and female patients seeking treatment; and claim disposition codes used by each TCMP. The results indicated that there were 5522 TCMPs in 2012, and 4876 (90.3%) TCMPs practiced in primary clinics. The proportions of pediatric visits to these TCMPs were mostly below 0.2, and acupuncture or traumatology-related visit proportions were below 0.5. Only a few of the studied Taiwan-based TCMPs practiced gynecology and pediatrics, but most of them performed "internal medicine", or "acupuncture" or "traumatology" treatments. Thus, the number of TCM specialists practicing gynecology or pediatrics is insufficient, indicating that a policy that forms professional divisions of TCM practitioners in Taiwan should be reconsidered.


Asunto(s)
Medicina Tradicional China , Médicos , Terapia por Acupuntura , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Ginecología , Humanos , Medicina Interna , Masculino , Registros Médicos , Persona de Mediana Edad , Programas Nacionales de Salud , Pediatría , Taiwán
16.
Proc Natl Acad Sci U S A ; 115(26): E5896-E5905, 2018 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-29891721

RESUMEN

Obesity and related metabolic diseases are becoming worldwide epidemics that lead to increased death rates and heavy health care costs. Effective treatment options have not been found yet. Here, based on the observation that baicalin, a flavonoid from the herbal medicine Scutellaria baicalensis, has unique antisteatosis activity, we performed quantitative chemoproteomic profiling and identified carnitine palmitoyltransferase 1 (CPT1), the controlling enzyme for fatty acid oxidation, as the key target of baicalin. The flavonoid directly activated hepatic CPT1 with isoform selectivity to accelerate the lipid influx into mitochondria for oxidation. Chronic treatment of baicalin ameliorated diet-induced obesity (DIO) and hepatic steatosis and led to systemic improvement of other metabolic disorders. Disruption of the predicted binding site of baicalin on CPT1 completely abolished the beneficial effect of the flavonoid. Our discovery of baicalin as an allosteric CPT1 activator opens new opportunities for pharmacological treatment of DIO and associated sequelae.


Asunto(s)
Carnitina O-Palmitoiltransferasa/metabolismo , Hígado Graso , Flavonoides/farmacología , Hígado/enzimología , Mitocondrias Hepáticas/enzimología , Obesidad , Proteómica , Regulación Alostérica/efectos de los fármacos , Animales , Sitios de Unión , Dieta/efectos adversos , Activación Enzimática/efectos de los fármacos , Hígado Graso/inducido químicamente , Hígado Graso/enzimología , Hígado Graso/patología , Hígado Graso/prevención & control , Células HeLa , Humanos , Hígado/patología , Ratones , Mitocondrias Hepáticas/patología , Obesidad/inducido químicamente , Obesidad/enzimología , Obesidad/prevención & control
17.
Biochemistry ; 57(4): 451-460, 2018 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-29072073

RESUMEN

As one of the most intrinsically reactive amino acids, cysteine carries a variety of important biochemical functions, including catalysis and redox regulation. Discovery and characterization of cysteines with heightened reactivity will help annotate protein functions. Chemical proteomic methods have been used to quantitatively profile cysteine reactivity in native proteomes, showing a strong correlation between the chemical reactivity of a cysteine and its functionality; however, the relationship between the cysteine reactivity and its local sequence has not yet been systematically explored. Herein, we report a machine learning method, sbPCR (sequence-based prediction of cysteine reactivity), which combines the basic local alignment search tool, truncated composition of k-spaced amino acid pair analysis, and support vector machine to predict cysteines with hyper-reactivity based on only local sequence features. Using a benchmark set compiled from hyper-reactive cysteines in human proteomes, our method can achieve a prediction accuracy of 98%, a precision of 95%, and a recall ratio of 89%. We utilized these governing features of local sequence motifs to expand the prediction to potential hyper-reactive cysteines in other proteomes deposited in the UniProt database. We validated our predictions in Escherichia coli by activity-based protein profiling and discovered a hyper-reactive cysteine from a functionally uncharacterized protein, YecH. Biochemical analysis suggests that the hyper-reactive cysteine might be involved in metal binding. Our computational method provides a large inventory of potential hyper-reactive cysteines in proteomes and is highly complementary to other experimental approaches to guide systematic annotation of protein functions in the postgenome era.


Asunto(s)
Cisteína/química , Aprendizaje Automático , Proteómica , Secuencias de Aminoácidos , Cromatografía Liquida , Técnicas de Apoyo para la Decisión , Proteínas de Escherichia coli/química , Humanos , Proteínas Recombinantes/química , Alineación de Secuencia , Espectrometría de Masas en Tándem
18.
Molecules ; 22(8)2017 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-28820480

RESUMEN

The objectives of this study were to characterize the antioxidant capacities and phytochemicals such as phenolics and flavonoids in four parts of Euphorbia lathyris L. HPLC was employed to detect the type and content of phenolic acids and flavonoids in the root, stem, seed, and testa of the plant. The total phenolic content (TPC) and total flavonoid content (TFC) were different among various parts of E. lathyris. The highest TPC were found in the testa (290.46 ± 15.09 mg of gallic acid equiv/100 g dry weight (DW)). However, the root contained the highest TFC (215.68 ± 3.10 mg of rutin equiv/g DW). Of the different antioxidant activities detected, DPPH free radical scavenging activity was highest in the testa (61.29 ± 0.29 mmol Trolox/100 g DW), but the highest FRAP antioxidant activity was found in the seed (1131.25 ± 58.68 mg FeSO4/100 g DW of free compounds and 1927.43 ± 52.13 mg FeSO4/100 g DW of bound compounds). There was a positive correlation between the total phenolic contents and DPPH free radical scavenging activity in different parts of E. lathyris.


Asunto(s)
Antioxidantes/farmacología , Euphorbia/química , Fenoles/química , Extractos Vegetales/farmacología , Antioxidantes/química , Flavonoides/química , Flavonoides/clasificación , Flavonoides/aislamiento & purificación , Fenoles/farmacología , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales/química , Semillas/química
19.
Bioorg Med Chem ; 24(22): 6102-6108, 2016 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-27720557

RESUMEN

Protein lysine methyltransferase G9a is widely considered as an appealing antineoplastic target. Herein we present an integrated workflow combining shape-based virtual screening and structure-based molecular modification for the identification of novel G9a inhibitors. The shape-based similarity screening through ROCS overlay on the basis of the structure of UNC0638 was performed to identify CPUY074001 contained a 6H-anthra[1,9-cd]isoxazol-6-one scaffold as a hit. Analysis of the binding mode of CPUY074001 with G9a and 3D-QSAR results, two series compounds were designed and synthesized. The derivatives were confirmed to be active by in vitro assay and the SAR was explored by docking stimulations. Besides, several analogues showed acceptable anti-proliferative effects against several cancer cell lines. Among them, CPUY074020 displayed potent dual G9a inhibitory activity and anti-proliferative activity. Furthermore, CPUY074020 induced cell apoptosis in a dose-dependent manner and displayed a significant decrease in dimethylation of H3K9. Simultaneously, CPUY074020 showed reasonable in vivo PK properties. Altogether, our workflow supplied a high efficient strategy in the identification of novel G9a inhibitors. Compounds reported here can serve as promising leads for further study.


Asunto(s)
Descubrimiento de Drogas , Inhibidores Enzimáticos/farmacología , N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , Isoxazoles/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Antígenos de Histocompatibilidad/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Isoxazoles/síntesis química , Isoxazoles/química , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad
20.
Artículo en Inglés | MEDLINE | ID: mdl-25838832

RESUMEN

Increasing evidence shows that grains may play a role in disease prevention beyond the simple provision of energy and nutrients. It has been reported that some components contained in grains exert their functional effects on viral and bacterial infections and protect against various cancers. However, until now, hardly any intervention studies have investigated the effects of grains or grain based extracts on the inhibition of HIV-1 infection. In this study, the antiviral function of a zymolytic grain based extract (ZGE) was detected in vitro and in rats, and the antiviral mechanism was investigated. Results showed that ZGE had an inhibition effect on HIV-1 infection in vitro with low cytotoxic effects. The study of the mechanism demonstrated that this functional food possibly acted on the viral surface structure protein gp120 which is responsible for cell binding, as well as on the postattachment stage of the virus. The sera of model rats administrated with this food by gavage presented anti-infection abilities against HIV-1 in vitro during a serum concentration associated period of time. These findings provide valuable insights into the application of ZGE on the control of viral load, which may contribute to future anti-HIV treatment with less adverse effects.

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