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1.
Curr Pharm Des ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31663471

RESUMO

Traumatic brain injury (TBI) can cause disorders of consciousness (DOC) by impairing the neuronal circuits of the ascending reticular activating system (ARAS) structures, including the hypothalamus, which are responsible for the maintenance of the wakefulness and awareness. Current awakening therapies for TBI-induced DOC comprise, among others, the regulation of excitatory and inhibitory neurotransmitters and the stimulation of the peripheral or central nervous system (CNS). However, the effects of these awakening therapies are still not satisfactory. Hypothalamus has been identified as a sleep/wake center, and its anterior and posterior regions have diverse roles in the regulation of the sleep/wake function. In particular, posterior hypothalamus (PH) possesses several types of neurons, including the orexin neurons in the lateral hypothalamus (LH) with widespread projections to other wakefulness-related regions of the brain. Orexins have been known to affect feeding and appetite, and recently their profound effect on sleep disorders and DOC has been identified. Orexin antagonists are used for the treatment of insomnia, and orexin agonists can be used for narcolepsy. Additionally, several studies demonstrated that the agonists of orexin might be effective in the treatment of DOC, providing novel therapeutic opportunities in this field.

2.
Int J Mol Sci ; 20(19)2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31581639

RESUMO

Wheat stem rust caused by Puccinia graminis f. sp. tritici (Pgt) had been a devastating foliar disease worldwide during the 20th century. With the emergence of Ug99 races, which are virulent to most stem rust resistance genes deployed in wheat varieties and advanced lines, stem rust has once again become a disease threatening global wheat production. Sr52, derived from Dasypyrum villosum and mapped to the long arm of 6V#3, is one of the few effective genes against Ug99 races. In this study, the wheat-D. villosum Robertsonian translocation T6AS·6V#3L, the only stock carrying Sr52 released to experimental and breeding programs so far, was crossed with a CS ph1b mutant to induce recombinants with shortened 6V#3L chromosome segments locating Sr52. Six independent homozygous recombinants with different segment sizes and breakpoints were developed and characterized using in situ hybridization and molecular markers analyses. Stem rust resistance evaluation showed that only three terminal recombinants (1381, 1380, and 1392) containing 8%, 22%, and 30% of the distal segment of 6V#3L, respectively, were resistant to stem rust. Thus, the gene Sr52 was mapped into 6V#3L bin FL 0.92-1.00. In addition, three molecular markers in the Sr52-located interval of 6V#3L were confirmed to be diagnostic markers for selection of Sr52 introgressed into common wheat. The newly developed small segment translocation lines with Sr52 and the identified molecular markers closely linked to Sr52 will be valuable for wheat disease breeding.

3.
Med Sci Monit ; 25: 7443-7450, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584038

RESUMO

BACKGROUND Knee stability has an important role in the gait of hemiplegic stroke patients. However, factors affecting knee stability have not been assessed concerning gait. The purpose of this study was to explore whether co-contraction of the lower limb muscles contributes to the knee stability during the stance phase of the gait cycle in hemiplegic stroke patients. MATERIAL AND METHODS A total of 30 hemiplegic stroke patients, ages 36-79 years, were instructed to walk at their natural speed. The root mean square of surface electromyography was used to measure activities of the biceps femoris and rectus femoris muscles, while the co-contraction ratio was computed based on the root mean squares. The peak angle of knee extension was acquired in the stance phase by 3D kinematic analyses. Lower limb function was evaluated using the Fugl-Meyer scale for lower limb motor assessment. RESULTS A statistically significant increase of the muscle co-contraction ratio of the involved extremity was observed compared with that of the uninvolved extremity (t=-4.066, P<0.05). The muscle co-contraction ratio was significantly correlated with the peak angle of knee extension (r=0.387, P=0.035), Fugl-Meyer scale (r=-0.522, P=0.003), and Modified Ashworth Scale (r=0.404, P=0.027) during the stance phase of the gait cycle. CONCLUSIONS Our results showed that co-contraction of the rectus femoris muscle contributes to the stability of the knee and lower limb function in hemiplegic stroke patients, and suggests that co-contraction should be considered in the rehabilitation of knee stability during gait in hemiplegic stroke patients. Appropriate rehabilitation assessment planning with hemiplegic stroke patients, such as muscle co-contraction or knee stability of, might be created based on our results.

4.
Life Sci ; 239: 116966, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31626790

RESUMO

AIMS: Enhanced aerobic glycolysis is an essential hallmark of malignant cancer. Blocking the glycolytic pathway has been suggested as a therapeutic strategy to impair the proliferation of tumor cells. Metformin, a widely used anti-diabetes drug, exhibits anti-tumor properties. However, the underlying molecular mechanism of its action linking glucose metabolism with the suppression of proliferation has not been fully clarified. MAIN METHODS: Stable isotope tracing technology and gas chromatography-mass spectrometry method were utilized to analyze the effect of metformin on glycolytic flux in HCC cells. Western blot and immunohistochemistry were utilized to analyze the expression of phosphofructokinase-1 (PFK1) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in HCC cells or xenograft tumor tissues. Lactate measurement and glucose uptake assay were used to analyze the level of lactate and glucose in the presence of frucose-2,6-diphosphate (F2,6BP) in HCC cells treated with metformin. KEY FINDINGS: We found that metformin significantly impaired hepatoma cell proliferation by inhibiting the glycolytic flux via PFK1 blockade. Interestingly, activation of PFK1 by F2,6BP reverses the inhibitory effect of metformin on hepatoma cell proliferation and glycolysis. Mechanistically, PFKFB3,a potent allosteric activator of PFK1, was markedly suppressed through inhibiting hypoxia-induced factor 1 (HIF-1α) accumulation mediated by metformin. SIGNIFICANCE: Taken together these data indicate that HIF-1α/PFKFB3/PFK1 regulatory axis is a vital determinant of glucose metabolic reprogramming in hepatocellular carcinoma, which gives new insights into the action of metformin in combatting liver cancer.

5.
Drug Chem Toxicol ; : 1-8, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31656113

RESUMO

Acetyl-11-keto-ß-boswellic acid (AKBA), a triterpenoid from Boswellia serrate, is regarded as an angiogenesis inhibitor. However, its toxicity is unknown. The aim of this study was to examine its developmental toxicity and cardiotoxicity. A developmental toxicity assay in zebrafish embryos/larvae from 4 to 96 hours post-fertilization (hpf) was performed and a cardiotoxicity assay was designed from 48 to 72 hpf. Markers of oxidative stress and related genes were selected to access the possible mechanisms. According to the results, AKBA induced pericardium edema, yolk-sac edema, abnormal melanin, spinal curvature, hatching inhibition and shortened body length. Further, increased SV-BA distance, reduced heart rate, increased pericardium area and decreased blood flow velocity were detected in AKBA treated groups. The inhibition of cardiac progenitor gene expression, such as Nkx2.5 and Gata4, may be related to cardiotoxicity. The activities of antioxidant enzymes were decreased and the content of MDA was increased. In addition, AKBA treatment decreased the expression levels of Mn-Sod, Cat, and Gpx. These results suggested that AKBA induced developmental toxicity and cardiotoxicity through oxidative stress. As far as we know, this is the first report on the toxicity of AKBA. It reminds us to pay attention to developmental toxicity and cardiotoxicity of AKBA.

6.
Int Immunopharmacol ; 76: 105908, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31622861

RESUMO

Neuroinflammation is a general pathological feature of central nervous system (CNS) diseases, primarily caused by activation of astrocytes and microglia, as well as the infiltration of peripheral immune cells. Inhibition of neuroinflammation is an important strategy in the treatment of brain disorders. Dopamine (DA) receptor, a significant G protein-coupled receptor (GPCR), is classified into two families: D1-like (D1 and D5) and D2-like (D2, D3 and D4) receptor families, according to their downstream signaling pathways. Traditionally, DA receptor forms a wide variety of psychological activities and motor functions, such as voluntary movement, working memory and learning. Recently, the role of DA receptor in neuroinflammation has been investigated widely, mainly focusing on nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, renin-angiotensin system, αB-crystallin, as well as invading peripheral immune cells, including T cells, dendritic cells, macrophages and monocytes. This review briefly outlined the functions and signaling pathways of DA receptor subtypes as well as its role in inflammation-related glial cells, and subsequently summarized the mechanisms of DA receptors affecting neuroinflammation. Meaningfully, this article provided a theoretical basis for drug development targeting DA receptors in inflammation-related brain diseases.

7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 533-539, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31642231

RESUMO

OBJECTIVE: To investigate the protective effect of (2R, 3R)-dihydroquercetin 7-O-ß-D-glucopyranose (C1) extracted from Coreopsis tinctoria Nutt. in a mouse model of alcoholic acute pancreatitis (FAEE-AP) induced byfatty acid ethyl ester (FAEE). METHODS: The 30 healthy SPF mice were randomly divided into control group, model group, low dose group, middle dose group and high dose group, 6 in each group. Alcoholic pancreatitis was induced by ethanol and palmitoleic acid administration (1.75 g/kg ethanol, 200 mg/kg palmitoleic acid, 2 times peritoneal injections). The three treatment groups were given C1 (0 h, 4 h, 8 h) at the dose of 12.5, 25 and 50 mg/kg, respectively. After 24 h of molding, the serum amylase, lipase and IL-6 levels were detected. The trypsin level in pancreatic tissue and myeloperoxidase (MPO) level in pancreatic and lung tissue were detected. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of pancreatic tissue and immunohistochemical (IHC) staining was used to detect the expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) in pancreatic tissue. RESULTS: The pancreatic histopathological scores, serum amylase and lipase activity, trypsin level in pancreatic tissue, serum IL-6 level, MPO level of pancreas and lung were significantly higher in the model group than in the control group (P < 0.01). Compared with the model group, the pancreatic histopathologies of the low dose group was significantly improved (P < 0.05), as well as the serum amylase and lipase activity, trypsin level of pancreas, serum IL-6 level, the pancreas andthe lung's MPO level decreased significantly (P < 0.05), and up-regulate that expression of Nrf2 in pancreatic tissue. CONCLUSION: 12.5 mg/kg of (2R, 3R) -dihydroquercetin 7-O-ß-D-glucopyranose (C1) improved the expression of Nrf2, reduced the expression of inflammatory factor IL-6, and protected acute pancreatitis caused by FAEE.

9.
Theranostics ; 9(20): 5854-5868, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534524

RESUMO

Rationale: Diabetes can lead to cerebral and cutaneous vascular dysfunction. However, it is still unclear how vascular function changes with the development of diabetes and what differences exist between cerebral and cutaneous vascular dysfunction. Thus, it is very important to monitor changes in cerebral and cutaneous vascular function responses in vivo and study their differences during diabetes development. Methods: With the assistance of newly developed skull and skin optical clearing techniques, we monitored the responses of sodium nitroprusside (SNP)- and acetyl choline (ACh)-induced cerebral and cutaneous vascular blood flow and blood oxygen in diabetic mice in vivo during the development of type 1 diabetes (T1D) by combining laser speckle contrast imaging with hyperspectral imaging. We then compared the differences between cerebral and cutaneous vascular responses and explored the reasons for abnormal changes induced in response to different vascular beds. Results: In the early stage of diabetes (T1D-1 week), there were abnormal changes in the cerebral vascular blood flow and blood oxygen responses to SNP and ACh as well as cutaneous vascular blood oxygen. The cutaneous vascular blood flow response also became abnormal from T1D-3 weeks. Additionally, the T1D-induced abnormal blood flow response was associated with changes in vascular myosin light chain phosphorylation and muscarinic acetylcholine receptor M3 levels, and the aberrant blood oxygen response was related to an increase in glycated hemoglobin levels. Conclusion: These results suggest that the abnormal cutaneous vascular blood oxygen response occurred earlier than the blood flow response and therefore has the potential to serve as a good assessment indicator for revealing cerebrovascular dysfunction in the early stage of diabetes.

10.
Langmuir ; 35(40): 13031-13039, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31537058

RESUMO

The increasing application of gold nanoparticles (AuNPs) in biomedicine requires extensive investigation of surface modification and stabilization to maximize their advantages for the diversity of more challenging biological utilization. Herein, a thiol-mediated multifunctional phospholipid ligand was designed while disclosing a zwitterionic nature to AuNPs. The ligand was synthesized by attachment to two bidentate lipoic acid (LA) anchor groups and incorporation of a zwitterionic phosphatidylcholine (PC) group, allowing for excellent hydrophilicity. As demonstrated through ultraviolet-visible spectroscopy, appropriate 7 nm diameter AuNPs modified with a 1,2-dilipoyl-sn-glycero-3-phosphorylcholine (di-LA-PC) compact ligand exhibited the best colloidal stability in a high NaCl concentration of up to 217 mM, different temperatures, and a wide range of pH values from 3 to 11 when compared to the traditional surfactants or thiol-contained amino acid surface modification cases. These AuNPs are also stable without specific interaction to positively/negatively charged proteins, possibly leading to prolonged blood circulation after in vivo administration. Moreover, much more resistance to ligand competition of dithiothreitol was found than other thiol-coated AuNPs, which further highlighted their affinity in an aqueous system. Biocompatibility of the zwitterionic ligand di-LA-PC-modified AuNPs was finally evaluated by hemolysis and cytotoxicity tests. Cumulatively, the remarkable stability and biocompatibility of AuNPs, multicoordinated with a di-LA-PC ligand, potentially motivated them as a practical alternative for surface tailoring in biotechnology.

11.
ACS Appl Mater Interfaces ; 11(41): 37411-37420, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31556583

RESUMO

Liposomes are the most valuable nanocarriers in clinical use because of their biocompatibility, biodegradation, and effective encapsulation of hydrophilic or hydrophobic drugs. However, their applications are limited by the structure and functions of the most common phospholipids used as the main component of the liposomes. In this work, novel series of thioether phosphatidylcholines (S-PCs) and S-PC-based liposomes (S-LPs) were developed for reactive oxygen species (ROS)-responsive drug release. First of all, S-PCs with different chain lengths were synthesized by a combination of click reaction and heterogeneous esterification. Differential scanning calorimetry studies indicated that S-PCs had different phase transition temperatures depending on their chain lengths. Their critical aggregation concentrations were measured by the fluorescence probe technique indicating the self-assembly ability. After that, S-PC-based stealth liposomes (S-LPs) containing DSPE-PEG2000 and cholesterol were prepared via a classic thin-film method. Doxorubicin (DOX) as a model drug was loaded in the stealth liposomes (DOX/S-LPs) by using the ammonium sulfate gradient method with high encapsulation efficiency. DOX/S-LPs were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), and cryogenic TEM, confirming their spherical structure with the bilayer thickness of about 4 nm. The ROS sensitivity of S-PCs and S-LPs was carefully evaluated in the presence of H2O2 by means of mass spectrometry, DLS, TEM, and ultraviolet spectroscopy and release study. The results indicated the significant structural change of S-LPs after H2O2 treatment, which demonstrated that S-LPs possessed an efficient ROS-triggered disintegration because of thioether oxidation of S-PCs. Finally, in vitro and in vivo anticancer efficiency assays revealed the improved drug potency of DOX/S-LPs, which can be attributed to ROS-triggered destruction of S-LPs after the uptake by tumor cells followed by rapid release of DOX. All together, as alternatives of traditional phosphatidylcholines, S-PC-based stealth liposomes are promising ROS-responsive carriers for the controlled delivery of drugs.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31560154

RESUMO

Herein the novel tetraphenylethylene (TPE) derivative 1 was designed with an integration of aggregation-induced emission (AIE), multi-state mechanochromism and self-recovery photochromism. The molecule was susceptible to grinding, heating and vapor fuming and showed corresponding transition of its emission colors. The heated powder or single crystal of 1 exhibited reversible photochromism. After a short period of UV irradiation, it showed a bright red color, but recovered to its original white appearance within 1 min. The photochromism is due to the formation of photocyclization intermediates upon UV irradiation, while the eversible mechanochromism is attributed to the weak molecular interactions derived from head-to-tail stacking of the molecules. This reversible multi-state, high-contrasted and rapid responsive mechanochromic and photochromic property cooperatively provide double enhancement of a multimode guarantee in advanced anti-counterfeiting.

13.
J Hazard Mater ; 381: 121010, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31425914

RESUMO

Porous nitrogen-doped reduced graphene oxide (NRGO) is successfully synthesized from graphene oxide via the combination of CO2 activation and nitrogen doping with ammonia. The performances of the carbon materials are evaluated by catalytic activation of perroxymonosulfate (PMS) for phenol degradation. The effect of the treatment sequence of CO2 activation and nitrogen doping on the catalytic activity of the derived product is investigated. The material obtained by CO2 activation-nitrogen doping (P-NRGO) shows better activity than the one obtained from nitrogen doping-CO2 activation (N-PRGO). The activation mechanisms are also investigated by radical scavenging test, and the P-NRGO/PMS system is unveiled to rely on the nonradical oxidation pathway. The turnover frequencies (TOFs) of these RGOs are also calculated, and the P-NRGO has the largest TOF of 58.39. Based on the analysis of synthesis method and catalytic activity, it is proposed that new catalytic sites are generated on P-NRGO. Density functional theory (DFT) calculations also illustrated that the most reactive sites are the structure vacancies with two nitrogen atoms, which is consistent with the results. The conclusion in this study provides new insights into the synergistic effect of N-doping and structural defects of carbon materials and the induced nonradical pathway in advanced oxidation.

14.
J Trace Elem Med Biol ; 56: 81-89, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31442958

RESUMO

INTRODUCTION: Environmental risk factors regrading rheumatoid arthritis (RA) have not been explored extensively. Selenium (Se), zinc (Zn) and copper (Cu) nutrients were reported to associate with RA, but the results were inconsistent. Therefore, we conduct present study to meta-analyze the relationship between serum Se, Zn and Cu and RA and review the potential mechanisms. METHODS: PubMed, Web of Science and Cochrane Library were comprehensively searched till October 1, 2018 for pertinent studies. Standard mean differences (SMDs) and 95% confident intervals (CIs) were calculated according to random effects model. RESULTS: Finally 41 literatures were included. Meta-analysis of 16 studies involving 806 RA patients and 959 health controls showed that serum Se (SMD = -1.04, 95% CI = -1.58 to -0.50) was decreased in RA patients, and 23 literatures with 1398 patients and 1299 controls reported serum Zn (SMD = -1.20, 95% CI = -1.74 to -0.67) was decreased. But serum Cu (SMD = 1.26, 95% CI = 0.63 to -1.89) was increased with 26 studies including 1723 patients and 1451 controls. Meta-regression reported that steroid use was positively related to serum level of Se in RA (ß = 0.041, 95% CI = 0.002 to 0.079). Differences in serum Se, Zn and Cu between rheumatoid arthritis patients and controls were all related with the geographical distribution. CONCLUSIONS: Patients with RA have significant decreased serum Se and Zn and increased serum Cu than health controls, suggesting potential roles of Se, Zn and Cu in the pathogenesis of RA. Patients and rheumatologist should give enough attention to the monitor of these elements during follow up.

15.
Libyan J Med ; 14(1): 1652058, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31405338

RESUMO

Objective: To investigate the effect of the duration of gonadotropin releasing hormone agonist (GnRH-a) use on the outcome of in vitro fertilization and embryo transfer (IVF-ET) during the short-acting long-term hyperstimulation cycle. Methodology: Clinical data from 776 patients receiving controlled ovarian stimulation (COS) after short-term regimen downregulation were retrospectively analyzed. According to the duration of GnRH-a, the patients were divided into 3 groups: Group A, 14 days for GnRH-a; Group B, 15-17 days for GnRH-a; and Group C, >18 days for GnRH-a. The clinical data, treatment and clinical outcomes were compared among the groups. Results: There were no significant differences in fertilization rate, implantation rate, clinical pregnancy rate, abortion rate, ovarian hyperstimulation syndrome (OHSS) rate(P > 0.05). The total costs in group A were significantly less than those in group B and C(P < 0.001). The number of eggs and quality embryos generated in group A was significantly higher than that in groups B and C (P = 0.014, P = 0.005). Conclusions: In the short-acting GnRH agonist long protocol, satisfactory IVF-ET pregnancy outcome was obtained with the use of GnRH-a for 14 days under the premise of lowering the receptor-regulating standard. Excessive application of GnRH-a will affect the number of eggs and embryos and increase the cost of medical treatment.

16.
Nat Commun ; 10(1): 3849, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31451698

RESUMO

Measurement of electron transfer at single-molecule level is normally restricted by the detection limit of faraday current, currently in a picoampere to nanoampere range. Here we demonstrate a unique graphene-based electrochemical microscopy technique to make an advance in the detection limit. The optical signal of electron transfer arises from the Fermi level-tuned Rayleigh scattering of graphene, which is further enhanced by immobilized gold nanostars. Owing to the specific response to surface charged carriers, graphene-based electrochemical microscopy enables an attoampere-scale detection limit of faraday current at multiple individual gold nanoelectrodes simultaneously. Using the graphene-based electrochemical microscopy, we show the capability to quantitatively measure the attocoulomb-scale electron transfer in cytochrome c adsorbed at a single nanoelectrode. We anticipate the graphene-based electrochemical microscopy to be a potential electrochemical tool for in situ study of biological electron transfer process in organelles, for example the mitochondrial electron transfer, in consideration of the anti-interference ability to chemicals and organisms.

17.
Cell Rep ; 28(9): 2386-2396.e5, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461653

RESUMO

It is known that lethal viruses profoundly manipulate host metabolism, but how the metabolism alternation affects the immediate host antiviral immunity remains elusive. Here, we report that the O-GlcNAcylation of mitochondrial antiviral-signaling protein (MAVS), a key mediator of interferon signaling, is a critical regulation to activate the host innate immunity against RNA viruses. We show that O-GlcNAcylation depletion in myeloid cells renders the host more susceptible to virus infection both in vitro and in vivo. Mechanistically, we demonstrate that MAVS O-GlcNAcylation is required for virus-induced MAVS K63-linked ubiquitination, thereby facilitating IRF3 activation and IFNß production. We further demonstrate that D-glucosamine, a commonly used dietary supplement, effectively protects mice against a range of lethal RNA viruses, including human influenza virus. Our study highlights a critical role of O-GlcNAcylation in regulating host antiviral immunity and validates D-glucosamine as a potential therapeutic for virus infections.

18.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2662-2666, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359674

RESUMO

Bupleuri Radix has both liver protection and hepatotoxicity. Saponins are the main pharmacodynamic and toxic components of Bupleuri Radix. Based on zebrafish physical model and the model of alcoholic fatty liver( AFL) pathology,the liver toxic and protective effect of saikosaponin a( SSa) were assessed. The results indicated that 1. 77 µmol·L-1 SSa showed protective effect to AFL zebrafish. 5. 30 µmol·L-1 SSa was hepatotoxic to healthy zebrafish,but it showed protective effect to AFL zebrafish. 5. 62 µmol·L-1 SSa was hepatotoxic to healthy and AFL zebrafish. This study is benefit for clinical safety of saikosaponin a.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Fígado Gorduroso Alcoólico/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Saponinas/toxicidade , Animais , Ácido Oleanólico/farmacologia , Ácido Oleanólico/toxicidade , Peixe-Zebra
19.
Luminescence ; 2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31328371

RESUMO

Hypoxanthine riboside (HXR) is a nucleoside essential for wobble base pairs to translate the genetic code. In this work, an absorption and luminescence study showed that HXR and human serum albumin (HSA) formed a new complex through hydrogen bonds and van der Waals forces at ground state. Fluorescence probe experiments indicated that HXR entered the first subdomain of domain II in HSA and was fixed by amino acid residues in site I defined by Sudlow, and after competing with a known site marker. The recognition interaction featured negative ΔHÏ´ , ΔSÏ´ and ΔGÏ´ thermodynamic parameters. Fluorescence and circular dichroism spectra described the polarity of residues and α-helix and ß-strand content changed because of HXR binding. The most rational structure for the HXR-HSA complex was recommended by the molecular docking method, in which the binding location, molecular orientation, adjacent amino acid residues, and hydrogen bonds were included. In addition, the influence of ß-cyclodextrin and some essential metal ions on the balance of the HSA-HXR system interaction was measured. The study gained comprehensive information on the transportation mechanism for HXR in blood, and was of great significance in understanding the theory of HXR biotransformation and in discussing its clinical in vivo half-life.

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