Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 115
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Mol Med ; 30(1): 152, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289602

RESUMEN

VEXAS syndrome, an uncommon yet severe autoimmune disorder stemming from a mutation in the UBA1 gene, is the focus of this paper. The overview encompasses its discovery, epidemiological traits, genetic underpinnings, and clinical presentations. Delving into whether distinct genotypes yield varied clinical phenotypes in VEXAS patients, and the consequent adjustment of treatment strategies based on genotypic and clinical profiles necessitates thorough exploration within the clinical realm. Additionally, the current therapeutic landscape and future outlook are examined, with particular attention to the potential therapeutic roles of IL-6 inhibitors and JAK inhibitors, alongside an elucidation of prevailing limitations and avenues for further research. This study contributes essential theoretical groundwork and clinical insights for both diagnosing and managing VEXAS syndrome.


Asunto(s)
Interleucina-6 , Inhibidores de las Cinasas Janus , Enzimas Activadoras de Ubiquitina , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Inhibidores de las Cinasas Janus/uso terapéutico , Enzimas Activadoras de Ubiquitina/genética , Enzimas Activadoras de Ubiquitina/antagonistas & inhibidores , Mutación , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/diagnóstico
2.
J Environ Manage ; 367: 121973, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39067336

RESUMEN

Commonly high lipid in food waste confronts anaerobic digestion with improved energy production and also inhibition risk from the intermediate long chain fatty acids (LCFAs). Combined with operation challenges from anaerobic digestion of food waste itself, coping strategies are necessitated to ensure stable operation for oily food waste (OFW). A parallel thermophilic (TD) and mesophilic digestion (MD) of high-solid OFW was conducted and operated continuously for a long term. It was clarified that challenges were mainly from acidification, trace metal deficiency and LCFA inhibition. Acidification resulted in an abrupt pH decline to even below 6.00, and over 75% drop of biogas production rate. In addition to the requirements of saturated strong alkali to maintain an appropriate range, supplementation of trace metals were proven effective in counteracting the sharp decrease of biogas production rate. The TD was observed more competent in coping with the acidification than the MD, while the TD needed more supplementation of trace metals at approximately 0.10 mg Fe/g chemical oxygen demand (COD)added, 0.01 mg Co/g CODadded and 0.01 mg Ni/g CODadded. The TD was more adaptable in LCFA conversion due to the stronger ability of overcoming the palmitic acid (C16:0) accumulation. The MD experienced a prolonged recovery period owing to LCFA inhibition shortly after acidification. Similar operation performance was ultimately achieved for the TD and MD by the counteractions, with a methane yield and volatile solids (VS) removal efficiency at about 0.60 L/g VSadded and 75.0%, respectively. In summary, combined pH control and trace metal supplementation, and prevention and recovery of LCFA inhibition were necessary for the stability insurance of a long-term continuous digestion of oily food waste.


Asunto(s)
Alimentos , Anaerobiosis , Residuos Sólidos , Biocombustibles , Ácidos Grasos/metabolismo , Concentración de Iones de Hidrógeno , Alimento Perdido y Desperdiciado
3.
J Cell Physiol ; 238(2): 355-365, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36571294

RESUMEN

Wound healing is a complex and error-prone process. Wound healing in adults often leads to the formation of scars, a type of fibrotic tissue that lacks skin appendages. Hypertrophic scars and keloids can also form when the wound-healing process goes wrong. Leptin (Lep) and leptin receptors (LepRs) have recently been shown to affect multiple stages of wound healing. This effect, however, is paradoxical for scarless wound healing. On the one hand, Lep exerts pro-inflammatory and profibrotic effects; on the other hand, Lep can regulate hair follicle growth. This paper summarises the role of Lep and LepRs on cells in different stages of wound healing, briefly introduces the process of wound healing and Lep and LepRs, and examines the possibility of promoting scarless wound healing through spatiotemporal, systemic, and local regulation of Lep levels and the binding of Lep and LepRs.


Asunto(s)
Cicatriz Hipertrófica , Leptina , Humanos , Cicatriz Hipertrófica/patología , Leptina/metabolismo , Receptores de Leptina/metabolismo , Piel/metabolismo , Cicatrización de Heridas , Animales
4.
J Environ Manage ; 335: 117573, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36840995

RESUMEN

Long chain fatty acids (LCFAs) are the key intermediate of anaerobic digestion of oily food waste, not completely soluble in a water-dominant anaerobic system due to their long hydrocarbon chains with hydrophobic property. Their effective concentration affects release of high methanogenic potential and system stability. A long-term continuous anaerobic digestion of oily food waste demonstrated excess methane production of even more than feedstock in an anaerobic continuous stirred tank reactor (CSTR). Assuming feedstock COD at 100%, approximately 120% of COD as methane could be achieved. Oil floating and crystallization with Ca salt resulting from the distribution heterogeneity of LCFAs in the CSTR were found responsible for the excess methane production. Moreover, slow conversion and accumulation of saturated LCFAs with relatively lower solubility played an important role as well. Compared with unsaturated oleic (C18:1) and linoleic acids (C18:2), around twice slower methane production rate and longer lag time could be observed for those saturated LCFAs. Mixing intensity was proved to be a critical controlling factor for methanogenesis and stability possibly by affecting interaction between oil/LCFAs and anaerobes to change effective lipid loading.


Asunto(s)
Alimentos , Metano , Eliminación de Residuos , Anaerobiosis , Ácidos Grasos , Aceites , Eliminación de Residuos/métodos
5.
Sheng Li Xue Bao ; 75(1): 17-26, 2023 Feb 25.
Artículo en Zh | MEDLINE | ID: mdl-36859831

RESUMEN

Previous studies have shown that long-term spermatogonial stem cells (SSCs) have the potential to spontaneously transform into pluripotent stem cells, which is speculated to be related to the tumorigenesis of testicular germ cells, especially when p53 is deficient in SSCs which shows a significant increase in the spontaneous transformation efficiency. Energy metabolism has been proved to be strongly associated with the maintenance and acquisition of pluripotency. Recently, we compared the difference in chromatin accessibility and gene expression profiles between wild-type (p53+/+) and p53 deficient (p53-/-) mouse SSCs using the Assay for Targeting Accessible-Chromatin with high-throughput sequencing (ATAC-seq) and transcriptome sequencing (RNA-seq) techniques, and revealed that SMAD3 is a key transcription factor in the transformation of SSCs into pluripotent cells. In addition, we also observed significant changes in the expression levels of many genes related to energy metabolism after p53 deletion. To further reveal the role of p53 in the regulation of pluripotency and energy metabolism, this paper explored the effects and mechanism of p53 deletion on energy metabolism during the pluripotent transformation of SSCs. The results of ATAC-seq and RNA-seq from p53+/+ and p53-/- SSCs revealed that gene chromatin accessibility related to positive regulation of glycolysis and electron transfer and ATP synthesis was increased, and the transcription levels of genes encoding key glycolytic enzymes and regulating electron transport-related enzymes were markedly increased. Furthermore, transcription factors SMAD3 and SMAD4 promoted glycolysis and energy homeostasis by binding to the chromatin of the Prkag2 gene which encodes the AMPK subunit. These results suggest that p53 deficiency activates the key enzyme genes of glycolysis in SSCs and enhances the chromatin accessibility of genes associated with glycolysis activation to improve glycolysis activity and promote transformation to pluripotency. Moreover, SMAD3/SMAD4-mediated transcription of the Prkag2 gene ensures the energy demand of cells in the process of pluripotency transformation and maintains cell energy homeostasis by promoting AMPK activity. These results shed light on the importance of the crosstalk between energy metabolism and stem cell pluripotency transformation, which might be helpful for clinical research of gonadal tumors.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Espermatogonias , Proteína p53 Supresora de Tumor , Animales , Ratones , Cromatina , Metabolismo Energético , Eliminación de Gen , Células Madre , Proteína p53 Supresora de Tumor/genética , Espermatogonias/citología , Masculino
6.
J Org Chem ; 87(23): 16039-16046, 2022 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-36379013

RESUMEN

Pd-catalyzed borylation of fluorobenzene was theoretically studied. DFT calculations revealed that the reaction occurs through an unprecedented 3 + 6-membered ring transition state, in which one LiHMDS (HMDS = hexamethyldisilazane) acts as a ligand and another LiHMDS is essential to provide Li···N and Li···F interactions, overcoming the large destabilization of the strong phenyl-F bond distortion. The characteristic feature of LiHMDS was elucidated by comparing it with HMDS and NaHMDS analogues.


Asunto(s)
Fluorobencenos , Paladio , Paladio/química , Modelos Moleculares , Ligandos
7.
J Sci Food Agric ; 102(10): 4200-4209, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-35018645

RESUMEN

BACKGROUND: Because many common foods are emulsions (mayonnaise, margarine, salad dressing, etc.), a better understanding of lipid oxidation is crucial for the formulation, production, and storage of the relevant consumer products. We prepared oil-in-water (O/W) and water-in-oil (W/O) emulgels, and their architecture was characterized before monitoring lipid oxidation under thermally accelerated conditions to systematically compare the effect of emulsion type, oil composition, and oil fraction on the structure and lipid oxidation in thee biphasic emulgel systems. RESULTS: Higher susceptibility of lipids to oxidation (>2.5 times) was observed in the biphasic O/W and W/O emulgels than in soybean oil owing to an interfacial region. In the heterogeneous emulsion systems, W/O emulgels had oxidation resistance than O/W emulgels did. Compared with the oil-phase composition of high oleic sunflower, soybean, and flaxseed oils, oxidation sensitivity of emulsified lipids was significantly raised as the degree of unsaturation increased from 100.72 to 203.07. Moreover, increasing oil fraction from 75% to 85% led to an obvious increase in total oxidation in O/W emulgels but a decrease in W/O emulgels. In addition to emulsion size and oil unsaturation, viscoelasticity had a remarkable effect on the low-unsaturated oil oxidation (e.g. high oleic sunflower oil). CONCLUSION: Physical and structural phenomena played important roles in lipid oxidation based on a mass transport principle. These findings provide novel information for designing the structures of emulsion gels for controlling lipid oxidation through the cooperation of both formulation and architecture principles. © 2022 Society of Chemical Industry.


Asunto(s)
Aceites , Agua , Emulsiones/química , Geles/química , Aceites/química , Viscosidad , Agua/química
8.
Acta Pharmacol Sin ; 42(4): 518-528, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32724177

RESUMEN

GM1 ganglioside is particularly abundant in the mammalian central nervous system and has shown beneficial effects on neurodegenerative diseases. In this study, we investigated the therapeutic effect of GM1 ganglioside in experimental models of Parkinson's disease (PD) in vivo and in vitro. Mice were injected with MPTP (30 mg·kg-1·d-1, i.p.) for 5 days, resulting in a subacute model of PD. PD mice were treated with GM1 ganglioside (25, 50 mg·kg-1·d-1, i.p.) for 2 weeks. We showed that GM1 ganglioside administration substantially improved the MPTP-induced behavioral disturbance and increased the levels of dopamine and its metabolites in the striatal tissues. In the MPP+-treated SH-SY5Y cells and α-synuclein (α-Syn) A53T-overexpressing PC12 (PC12α-Syn A53T) cells, treatment with GM1 ganglioside (40 µM) significantly decreased α-Syn accumulation and alleviated mitochondrial dysfunction and oxidative stress. We further revealed that treatment with GM1 ganglioside promoted autophagy, evidenced by the autophagosomes that appeared in the substantia nigra of PD mice as well as the changes of autophagy-related proteins (LC3-II and p62) in the MPP+-treated SH-SY5Y cells. Cotreatment with the autophagy inhibitor 3-MA or bafilomycin A1 abrogated the in vivo and in vitro neuroprotective effects of GM1 ganglioside. Using GM1 ganglioside labeled with FITC fluorescent, we observed apparent colocalization of GM1-FITC and α-Syn as well as GM1-FITC and LC3 in PC12α-Syn A53T cells. GM1 ganglioside significantly increased the phosphorylation of autophagy regulatory proteins ATG13 and ULK1 in doxycycline-treated PC12α-Syn A53T cells and the MPP+-treated SH-SY5Y cells, which was inhibited by 3-MA. Taken together, this study demonstrates that the anti-PD role of GM1 ganglioside resulted from activation of autophagy-dependent α-Syn clearance.


Asunto(s)
Autofagia/efectos de los fármacos , Gangliósido G(M1)/uso terapéutico , Neuroprotección/efectos de los fármacos , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , alfa-Sinucleína/metabolismo , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/metabolismo , Línea Celular Tumoral , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Ratones Endogámicos C57BL , Enfermedad de Parkinson Secundaria/inducido químicamente , Ratas
9.
J Asian Nat Prod Res ; 23(2): 150-162, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32102552

RESUMEN

The PDGF receptor is mock-coupled with a known active compound, and 14 novel skeleton candidate compounds were designed and synthesized. The structure was confirmed by 1H NMR, 13C NMR and MS. The in vitro cytotoxicity of the two cancer cell lines (SGC-7901 and A549) was evaluated by MTT assay. PDGF receptor protein inhibition assays were performed on I6 and II4 using fluorescence polarization immunoassay (FPIA). [Formula: see text].


Asunto(s)
Antineoplásicos , Ácido Oleanólico , Antineoplásicos/farmacología , Línea Celular , Línea Celular Tumoral , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Ácido Oleanólico/farmacología , Receptores del Factor de Crecimiento Derivado de Plaquetas/farmacología , Relación Estructura-Actividad
10.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5064-5071, 2021 Oct.
Artículo en Zh | MEDLINE | ID: mdl-34738402

RESUMEN

The present study investigated the effects of chikusetsu saponin Ⅳa(CHS Ⅳa) on isoproterenol(ISO)-induced myocardial hypertrophy in rats and explored the underlying molecular mechanism. ISO was applied to establish a rat model of myocardial hypertrophy, and CHS Ⅳa(5 and 15 mg·kg~(-1)·d~(-1)) was used for intervention. The tail artery blood pressure was measured. Cardiac ultrasound examination was performed. The ratio of heart weight to body weight(HW/BW) was calculated. Morphological changes in the myocardial tissue were observed by HE staining. Collagen deposition in the myocardial tissue was observed by Masson staining. The mRNA expression of myocardial hypertrophy indicators(ANP and BNP), autophagy-related genes(Atg5, P62 and beclin1), and miR199 a-5 p was detected by qRT-PCR. Atg5 protein expression was detected by Western blot. The results showed that the model group exhibited increased tail artery blood pressure and HW/BW ratio, thickened left ventricular myocardium, enlarged myocardial cells, disordered myocardial fibers with widened interstitium, and a large amount of collagen aggregating around the extracellular matrix and blood vessels. ANP and BNP were largely expressed. Moreover, P62 expression was up-regulated, while beclin1 expression was down-regulated. After intervention by CHS Ⅳa at different doses, myocardial hypertrophy was ameliorated and autophagy activity in the myocardial tissue was enhanced. Meanwhile, miR199 a-5 p expression declined and Atg5 expression increased. As predicted by bioinformatics, Atg5 was a target gene of miR199 a-5 p. CHS Ⅳa was capable of preventing myocardial hypertrophy by regulating autophagy of myocardial cells through the miR-199 a-5 p/Atg5 signaling pathway.


Asunto(s)
Ácido Oleanólico , Saponinas , Animales , Cardiomegalia/inducido químicamente , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/genética , Isoproterenol , Miocardio , Miocitos Cardíacos , Ácido Oleanólico/análogos & derivados , Ratas , Saponinas/farmacología
11.
Biochem Biophys Res Commun ; 531(2): 118-124, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-32782145

RESUMEN

There is increasing evidence that the sympathetic nervous system (SNS) plays an important role in adipose tissue development. However, the underlying molecular mechanism(s) associated with this remains unclear. SNS innervation of white adipose tissue (WAT) is believed to be necessary and sufficient to elicit WAT lipolysis. In this current study, mice with Schwann cell (SC)-specific inactivation of phosphatase and tensin homolog (Pten) displayed enlarged inguinal white adipose tissue (iWAT). This serendipitous observation implicates the role of SCs in mediating SNS activity associated with mouse adipose tissue development. Mice with SC-specific Pten inactivation displayed enlarged iWAT. Interestingly, the SNS activity in iWAT of SC-specific Pten-deficient mice was reduced as demonstrated by decreased tyrosine hydroxylase (TH) expression level and neurotransmitters, such as norepinephrine (NE) and histamine (H). The lipolysis related protein, phosphorylated hormone sensitive lipase (pHSL), was also decreased. As expected, AKT-associated signaling pathway was hyperactivated and hypothesized to induce enlarged iWAT in SC-specific Pten-deficient mice. Moreover, preliminary experiments using AKT inhibitor AZD5363 treatment ameliorated the enlarged iWAT condition in SC-specific Pten-deficient mice. Taken together, SCs play an essential role in the regulation of SNS activity in iWAT development via the AKT signaling pathway. This novel role of SCs in SNS function allows for better understanding into the genetic mechanisms of peripheral neuropathy associated obesity.


Asunto(s)
Tejido Adiposo Blanco/crecimiento & desarrollo , Fosfohidrolasa PTEN/metabolismo , Células de Schwann/metabolismo , Sistema Nervioso Simpático/metabolismo , Adipocitos/citología , Adipocitos/metabolismo , Adiposidad , Animales , Tamaño de la Célula , Conducto Inguinal/anatomía & histología , Ratones , Neurotransmisores/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirimidinas/farmacología , Pirroles/farmacología , Regulación hacia Arriba , Vía de Señalización Wnt
12.
J Org Chem ; 85(12): 7694-7703, 2020 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-32469518

RESUMEN

The first example of gold-catalyzed formal intermolecular [4 + 2 + 1] cycloaddition was developed using 1,3-dien-8-yne as C4 and C2 units and diazo ester as the C1 unit, which provides expedient access to a series of structurally complicated [5.3.0] bicyclic adducts in moderate yields with moderate to high diastereoselectivities. The key route involved a cascade process of dienyne cycloisomerization, cyclopropyl gold carbene's trapping, and subsequent divinyl cyclopropane (DVCP) Cope rearrangement.

13.
Environ Res ; 191: 110035, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32827519

RESUMEN

Hyperthermophilic anaerobic digestion, especially at 70 °C, has drawn wide attention. In order to acquire the inoculum and digestion characteristics, batch acclimation and continuous operation experiments were conducted under hyperthermophilic (70 °C), thermophilic (55 °C) and mesophilic (35 °C) conditions, respectively. Archaea at each temperature was successfully enriched from the sole-source waste activated sludge (WAS). Hyperthermophilic digestion achieved higher archaea diversity, close to the Shannon index 2.23 for the thermophilic digestion, but the population were not improved, at a 16S rRNA genes 5.99 × 105 copies mL-1. Hydrogenotrophic methanogens, Methanospirillum and Methanothermobacter, dominated in the hyperthermophilic digester, accounting for 27.15%, while the primary phylum Firmicutes was promoted to 36.31%, with the proteolytic genus Coprothermobacter in Firmicutes at 19.50%. Refractory organic fractions were converted more with a higher digestion temperature, which was demonstrated by the fact that the COD/VS increased to 5.8, 5.2 and 4.2 at 70 °C, 55 °C and 35 °C, respectively, at the end of batch acclimation. In addition, the most solubilization for the dominant fraction protein in the WAS occurred at 70 °C as well. Similar hydrolysis ratio, over 10%, and specific hydrolysis rate, around 0.025 g COD (g VSS·d)-1, were achieved at 70 °C and 55 °C. The higher hydrolysis for hyperthermophilic digestion even resulted in a higher methane yield than that for the mesophilic digestion. Nevertheless, contrary to higher hydrolysis, methanogenesis limited hyperthermophilic digestion in WAS degradation, with an ultimate methane yield 71.2 mL g-1 VSadded, despite an almost complete VFA conversion through the continuous operation.


Asunto(s)
Microbiota , Aguas del Alcantarillado , Anaerobiosis , Archaea/genética , Reactores Biológicos , Metano , ARN Ribosómico 16S/genética , Temperatura
14.
BMC Anesthesiol ; 20(1): 190, 2020 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-32746864

RESUMEN

BACKGROUND: The efficacy and safety of spinal anesthesia by intrathecal dexmedetomidine (DEX) for parturients undergoing cesarean section are still lack of evidence. This aim of our study was to evaluate the efficacy and safety of intrathecal DEX for parturients undergoing cesarean section to provide more data evidence for intrathecal applications. METHODS: Three hundred parturients undergoing cesarean section under spinal anesthesia were randomly assigned into three groups: group B: 9.0 mg (1.2 ml) of 0.75% bupivacaine with saline (1 ml); group FB: 9.0 mg (1.2 ml) of 0.75% bupivacaine with 20 µg of fentanyl (1 ml); group DB: 9.0 mg (1.2 ml) of 0.75% bupivacaine with 5 µg of DEX (1 ml). Intraoperative block characteristics, parturients' postoperative quality of recovery, maternal and neonatal outcomes and the plasma concentration of DEX were measured. All parturients were followed up for 30 days to determine whether nerve injury occurred. RESULTS: Compared with group B, the duration of sensory block in group FB and group DB were significantly prolonged (108.4 min [95% Confidence Interval (CI) = 104.6-112.3] in group B, and 122.0 min [95% CI = 116.8-127.3] in group FB, 148.2 min [95% CI = 145.3-151.1] in group DB). The overall score of quality recovery in group DB (71.6 [95% CI = 71.0-72.2]) was significantly higher than that in group FB (61.5 [95% CI = 60.8-62.2]) and group B (61.7 [95% CI = 61.0-62.4]). There was no statistically significant difference among the three groups for PH, PaO2, and PaCO2 of newborn. The plasma concentration of DEX in umbilical artery and umbilical vein was low and cannot be detected. The 30-days follow-up of parturients did not show any new onset of back, buttock or leg pain or paresthesia. CONCLUSIONS: DEX is a potential local anesthetic adjuvant that the intrathecal combination of 5 µg DEX can safely exhibit a facilitatory block effect and improve parturients' recovery quality. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration number # ChiCTR1900022019 ; Date of Registration on March 20th, 2019).


Asunto(s)
Anestesia Obstétrica/métodos , Bupivacaína/administración & dosificación , Cesárea/métodos , Dexmedetomidina/administración & dosificación , Adulto , Anestesia Raquidea/métodos , Anestésicos Locales/administración & dosificación , Dexmedetomidina/efectos adversos , Método Doble Ciego , Femenino , Fentanilo/administración & dosificación , Estudios de Seguimiento , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Recién Nacido , Inyecciones Espinales , Bloqueo Nervioso/métodos , Embarazo , Estudios Prospectivos
15.
J Asian Nat Prod Res ; 22(7): 689-700, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31122063

RESUMEN

Based on the simulation of the docking of survivin protein with known small molecule inhibitors, the active groups which can bind to target proteins were analyzed by the techniques of computer-aided drug design (CADD). These active groups were introduced into the A-ring of asiatic acid and their C-28 sites were reconstructed simultaneously. Ten asiatic acid derivatives were designed and synthesized, and their structures were confirmed by MS and NMR. The inhibitory activities of the asiatic acid derivatives against HepG2 and SGC7901 cell lines were evaluated and confirmed by the tetrazolium bromidesalt (MTT) assay. The results showed that compounds I6 and II4 exhibited more potent cytotoxicity than the positive control drug gefitinib, which was comparable to that of adriamycin.[Formula: see text].


Asunto(s)
Antineoplásicos , Línea Celular Tumoral , Proliferación Celular , Diseño de Fármacos , Simulación del Acoplamiento Molecular , Estructura Molecular , Triterpenos Pentacíclicos , Relación Estructura-Actividad
16.
J Asian Nat Prod Res ; 22(4): 359-369, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30829054

RESUMEN

Eighteen uronic acid derivatives were designed and synthesized, and the cytotoxicities in vitro of two cancer cell lines (BEL7402 and SGC7901) were evaluated by MTT assay. The results showed that the inhibitory rate of the compounds on both cell lines was significantly higher than the parent compound. The IC50 of compounds II4, II6, III4, and III6 are comparable or stronger than the positive control drug, the interactions between compounds II4, II6, III4, III6, and NF-κB were also studied by docking simulations.


Asunto(s)
Antineoplásicos , Línea Celular Tumoral , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Relación Estructura-Actividad , Triterpenos , Ácido Ursólico
17.
Molecules ; 25(16)2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32824166

RESUMEN

Tricin, a flavone isolated from rice bran, has been shown to be chemopreventive in a colorectal cancer (CRC) mouse model. This study aimed to illustrate the inhibitory activities of tricin in colon cancer cells and in a metastatic CRC mouse model. BALB/c mice injected with mouse Colon26-Luc cells into the rectum wall were treated with tricin (37.5 mg/kg) daily for 18 days. Orthotopic colon tumor growth and metastasis to lungs were assessed by in vivo bioluminescence imaging. Results showed that tricin suppressed Colon-Luc cells motility and downregulated phosphorylated Akt, Erk1/2 and NF-κB expressions of human colon cancer HT-29 cells. While tricin treatment suppressed tumor growth and lung metastasis as well as altered the populations of myeloid-derived suppressor cells and regulatory T cells in spleens. In summary, the tumor microenvironment modulatory and anti-metastatic effects of tricin in colon cancer mouse model were shown for the first time, suggesting the potential development of tricin-containing food supplements for CRC patients.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Grano Comestible/química , Flavonas/farmacología , Flavonoides/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Animales , Apoptosis , Proliferación Celular , Neoplasias Colorrectales/patología , Humanos , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Biochem Biophys Res Commun ; 515(1): 50-56, 2019 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-31122699

RESUMEN

The neuromuscular junction (NMJ) is formed by motor nerve terminals, post-junctional muscle membranes, and terminal Schwann cells (SCs). The formation of NMJ requires complex and dynamic molecular interactions. Nerve- and muscle-derived molecules have been well characterized but the mechanistic involvement of SC in NMJ development remains poorly understood. SC-specific phosphatase and tensin homolog (Pten) inactivation and epidermal growth factor receptor (EGFR) overexpression (Dhh-Cre; Cnp-EGFR; Ptenflox/flox or DET) mice were used and NMJ malformation was observed in these mice. Acetylcholine receptors (AChRs) were distorted and varicose presynaptic nerve terminals appeared in the tibialis anterior (TA) muscle of DET mice. Agrin signaling related to NMJ development, was downregulated in TA muscle. Both RAS/MEK/ERK and PI3K/AKT/mTOR signaling pathways were activated in the sciatic nerves of DET mice. In addition, autophagy was downregulated in these sciatic nerves. Interestingly, the use of Torin 2, an mTOR inhibitor, rescued the phenotype. The downregulated-autophagy might account for Agrin signaling abnormity, which induced NMJ malformation. Taken together, our results indicate that SCs-specific Pten and EGFR cooperation are essential for NMJ development.


Asunto(s)
Agrina/metabolismo , Autofagia , Receptores ErbB/metabolismo , Unión Neuromuscular/metabolismo , Unión Neuromuscular/patología , Fosfohidrolasa PTEN/metabolismo , Células de Schwann/metabolismo , Transducción de Señal , Animales , Femenino , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Naftiridinas/farmacología , Unión Neuromuscular/efectos de los fármacos , Terminales Presinápticos/efectos de los fármacos , Terminales Presinápticos/metabolismo , Receptores Colinérgicos/metabolismo , Células de Schwann/efectos de los fármacos , Células de Schwann/patología , Nervio Ciático/efectos de los fármacos , Nervio Ciático/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo
19.
Int J Qual Health Care ; 31(7): 568-574, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-30388240

RESUMEN

QUALITY PROBLEM OR ISSUE: Chinese medical institutions need clinical guidelines to improve healthcare quality. Unfamiliarity with clinical methodology and procedures leads to poor quality. INITIAL ASSESSMENT: This study examined 327 clinical guidelines made in China during the period of 2006-10 and found these clinical guidelines have many problems in terms of guideline making procedures-compliant process, conflicts of interest disclosure. CHOICE OF SOLUTION: Chinese Medical Association organized a working group in 2014 to make a national [Guideline for Clinical Guidelines Constitution/Amendment] and invited multidiscipline experts to prove its possibility. IMPLEMENTATION: Experts investigated and reviewed numerous domestic and foreign published literature within the past 2 years, concluded that a clinical guideline should have following seven components: I. Objective; II. General Principle; III. Procedure and Methodology; IV. Confirmation, Publication and Dissemination; V. Update and Amendment; VI. Implementation and Outcome Validation; VII. Reference. EVALUATION: The [Guideline for Clinical Guidelines Constitution/Amendment] will improve the quality of Chinese clinical guidelines and regulate applications, as well as outcome evaluations of clinical guidelines in China. LESSONS LEARNED: Standardized methodology and procedures are important for constituting high-quality clinical guidelines.


Asunto(s)
Guías de Práctica Clínica como Asunto/normas , China
20.
Molecules ; 24(3)2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30717158

RESUMEN

Bioactive metabolites in Codonopsis pilosula are of particular interest as an immunostimulant. Methyl jasmonate (MeJA) plays an important role in the elicitation of metabolite biosynthesis. Here, we explored the response of metabolites to MeJA elicitation in C. pilosula adventitious roots and multiple shoots. The results showed that the biomass, polysaccharide, and lobetyolin content of adventitious roots exhibited the highest increases with 100 µmol·L-1 MeJA at the 16th day of subculture, whereas the atractylenolide III (a terpenoid) content increased extremely with 50 µmol·L-1 MeJA treatment at the 7th day of subculture. In addition, the biomass and lobetyolin content significantly increased at the 4th day after treatment. Similarly, the polysaccharide and lobetyolin content increased in multiple shoots. Further identification of different metabolites responding to MeJA by ¹H-NMR showed an extremely significant increase of the lobetyolinin level, which coincided with lobetyolin. Accordingly, the precursor, fatty acids, showed a highly significant decrease in their levels. Furthermore, a significant increase in ß-d-fructose-butanol glycoside was detected, which was accompanied by a decrease in the sucrose level. Accordingly, the enzyme genes responsible for terpenoid and carbohydrate biosynthesis, CpUGPase, and CpPMK, were up regulated. In conclusion, MeJA promoted culture growth and accelerated bioactive metabolite accumulation by regulating the expression of the metabolite biosynthesis related genes, CpUGPase and CpPMK in C. pilosula.


Asunto(s)
Acetatos/farmacología , Codonopsis/efectos de los fármacos , Ciclopentanos/farmacología , Regulación de la Expresión Génica de las Plantas , Oxilipinas/farmacología , Reguladores del Crecimiento de las Plantas/farmacología , Proteínas de Plantas/genética , Biomasa , Codonopsis/genética , Codonopsis/crecimiento & desarrollo , Codonopsis/metabolismo , Ácidos Grasos/biosíntesis , Lactonas/metabolismo , Redes y Vías Metabólicas/efectos de los fármacos , Redes y Vías Metabólicas/genética , Fosfotransferasas (Aceptor del Grupo Fosfato)/genética , Fosfotransferasas (Aceptor del Grupo Fosfato)/metabolismo , Proteínas de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/genética , Brotes de la Planta/crecimiento & desarrollo , Brotes de la Planta/metabolismo , Poliinos/metabolismo , Sesquiterpenos/metabolismo , UTP-Glucosa-1-Fosfato Uridililtransferasa/genética , UTP-Glucosa-1-Fosfato Uridililtransferasa/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA