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1.
BMC Urol ; 19(1): 106, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684918

RESUMO

BACKGROUND: Bilateral adrenal hemorrhage (BAH) is a rare but potentially catastrophic condition. Its clinical manifestation is often non-specific and sometimes difficult to be diagnosed in time. A 57-year-old woman, who presented with severe fatigue, nausea and vomiting after left hip arthroplasty due to her femoral neck fracture in a local hospital, was transferred to our medical center. Laboratory results revealed significant hyponatremia, low serum cortisol and elevated serum ACTH. Computed tomography (CT) showed a bilateral adrenal mass, measured 3.6 × 2.7 cm on the left and 3.4 × 2.3 cm on the right. Further magnetic resonance imaging (MRI) confirmed the diagnosis of BAH. The patient was prescribed with oral prednisolone acetate, 5 mg, tid, and her condition improved gradually. Nine months after, the patient was in good condition with 5 mg prednisolone acetate per day. CT revealed a clearly shrunken adrenal mass compared with 9 months ago. CONCLUSIONS: This case illustrates the difficulty in making the diagnosis of BAH with atypical presentation. Such cases necessitate greater alertness on the part of the clinician and require rapid diagnosis and prompt glucocorticoid replacement for better clinical outcomes.

2.
Brain Behav ; : e01460, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721481

RESUMO

INTRODUCTION: We previously reported transferring seventh cervical (C7) nerve from unaffected side to affected side in patients with spastic hemiplegia due to chronic cerebral injury, to improve function and reduce spasticity of paralyzed upper limb. In the clinics, some patients also reported changes of spasticity in their lower limb, which could not be detected by routine physical examinations. Pennation angle of muscle can indirectly reflect the condition of spasticity. The purpose of this study was to evaluate whether this upper limb procedure may affect spasticity of lower limb, using ultrasonography to detect changes of muscle pennation angle (PA). METHODS: Twelve spastic hemiplegia patients due to cerebral injury including stroke, cerebral palsy, and traumatic brain injury, who underwent C7 nerve transfer procedure, participated in this study. B-mode ultrasonography was used to measure PA of the gastrocnemius medialis (GM) muscle at rest preoperatively and postoperatively. The plantar load distribution of the lower limbs was evaluated using a Zebris FDM platform preoperatively and postoperatively. RESULTS: The PA of the GM was significantly smaller on the affected side than that of unaffected side before surgery. On the affected side, the postoperative PA was significantly larger than preoperative PA. On the unaffected side, the postoperative PA was not significantly different compared to preoperative PA. The postoperative plantar load distribution of the affected forefoot was significantly smaller than preoperative load distribution, which was consistent with ultrasonography results. CONCLUSIONS: This study indicates that C7 nerve transfer surgery for improving upper limb function can also affect muscle properties of lower limb in spastic hemiplegia patients, which reveals a link between the upper and lower limbs. The interlimb interactions should be considered in rehabilitation physiotherapy, and the regular pattern and mechanism need to be further studied.

3.
Acta Crystallogr C Struct Chem ; 75(Pt 11): 1517-1523, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31686663

RESUMO

The cyanide ligand can act as a strong σ-donor and an effective π-electron acceptor that exhibits versatile bridging abilities, such as terminal, µ2-C:N, µ3-C:C:N and µ4-C:C:N:N modes. These ligands play a key role in the formation of various copper(I) cyanide systems, including one-dimensional (1D) chains, two-dimensional (2D) layers and three-dimensional (3D) frameworks. According to the literature, numerous coordination polymers based on terminal, µ2-C:N and µ3-C,C,N bridging modes have been documented so far. However, systems based on the µ4-C:C:N:N bridging mode are relatively rare. In this work, a novel cyanide-bridged 3D CuI coordination framework, namely poly[(µ2-2,2'-biimidazole-κ2N3:N3')(µ4-cyanido-κ4C:C:N:N)(µ2-cyanido-κ2C:N)dicopper(I)], [Cu2(CN)2(C6H6N4)]n, (I), was synthesized hydrothermally by reaction of environmentally friendly K3[Fe(CN)6], CuCl2·2H2O and 2,2'-biimidazole (H2biim). It should be noted that cyanide ligands may act as reducing agents to reduce CuII to CuI under hydrothermal conditions. Compound (I) contains diverse types of bridging ligands, such as µ4-C:C:N:N-cyanide, µ2-C:N-cyanide and µ2-biimidazole. Interestingly, the [Cu2] dimers are bridged by rare µ4-C:C:N:N-mode cyanide ligands giving rise to the first example of a 1D dimeric {[Cu2(µ4-C:C:N:N)]n+}n infinite chain. Furthermore, adjacent dimer-based chains are linked by µ2-C:N bridging cyanide ligands, generating a neutral 2D wave-like (4,4) layer structure. Finally, the 2D layers are joined together via bidentate bridging H2biim to create a 3D cuprous cyanide network. This arrangement leads to a systematic variation in dimensionality from 1D chain→2D sheet→3D framework by different types of bridging ligands. Compound (I) was further characterized by thermal analysis, solid-state UV-Vis diffuse-reflectance and photoluminescence studies. The solid-state UV-Vis diffuse-reflectance spectra show that compound (I) is a wide-gap semiconductor with band gaps of 3.18 eV. The photoluminescence study shows a strong blue-green photoluminescence at room temperature, which may be associated with metal-to-ligand charge transfer.

4.
FASEB J ; 33(12): 14703-14716, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31693862

RESUMO

In female mammals, the majority of primordial follicles (PFs) are physiologically quiescent, and only a few of them are activated and enter the growing follicle pool. Specific molecules, such as mammalian target of rapamycin (mTOR) and the serine/threonine kinase Akt (AKT), have been proven to be important for PF activation. However, how the transcription of these genes is regulated is not clear. Although activators of mTOR or AKT have been successfully used to rescue the fertility of patients with premature ovarian insufficiency, the low efficacy and unclear safety profile of these drugs hinder their clinical use in the in vitro activation (IVA) of PFs. Here, sirtuin 1 (SIRT1), an NAD-dependent deacetylase, was demonstrated to activate mouse PFs independent of its deacetylase activity. SIRT1 was prominently expressed in pregranulosa cells (pGCs) and oocytes, and its expression was increased during PF activation. PF activation was achieved by either up-regulating SIRT1 with a specific activator or overexpressing SIRT1. Moreover, SIRT1 knockdown in oocytes or pGCs could significantly suppress PF activation. Further studies demonstrated that SIRT1 enhanced both Akt1 and mTOR expression by acting more as a transcription cofactor, directly binding to the respective gene promoters, than as a deacetylase. Importantly, we explored the potential clinical applications of targeting SIRT1 in IVA via short-term treatment of cultured ovaries from mice and human ovarian tissues to activate PFs by applying the SIRT1 activator resveratrol. RSV-induced IVA could be a candidate strategy to develop more efficient procedures for future clinical treatment of infertility.-Zhang, T., Du, X., Zhao, L., He, M., Lin, L., Guo, C., Zhang, X., Han, J., Yan, H., Huang, K., Sun, G., Yan, L., Zhou, B., Xia, G., Qin, Y., Wang, C. SIRT1 facilitates primordial follicle recruitment independent of deacetylase activity through directly modulating Akt1 and mTOR transcription.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31515879

RESUMO

RATIONALE: GW1929 is a potent PPAR-γactivator. To fully understand its mechanism of action, it is necessary to study the in vitro and in vivo metabolism. METHODS: For in vitro metabolism, GW1929 was incubated with rat hepatocytes at 37 o C for 2h. For in vivo metabolism, rats were orally administered with GW1929 at a single dose of 10 mg/kg and plasma, urinary and fecal samples were collected at defined time points. All the samples were analyzed by the developed ultra-high performance liquid chromatography combined with tandem mass spectrometry. The structures of metabolites were proposed according to their accurate masses and product ions. RESULTS: A total of 17 metabolites, seven glucuronide conjugates, were detected and structurally identified. M4 (hydroxylation), M13 (demethylation) and M14 (hydroxylation) were the most abundant metabolites. The metabolic pathways of GW1929 referred to hydroxylation, demethylation, deamination and glucuronidation. CONCLUSIONS: The present study provided new information on the in vitro and in vivo metabolic profiles of GW1929, which would be helpful for us to understand the mechanism of the elimination of GW1929.

6.
Med Biol Eng Comput ; 57(11): 2435-2447, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31515659

RESUMO

Conventional needle-based approaches in intravitreal drug delivery carry needle-stick-injury risk and could scare patients (belonephobia). Alternatively, our group has explored the application of an electromagnetic needleless injector in this paper. This work aims to improve intravitreal drug delivery, which in the future could assist physicians with automation and benefit patients by providing a needleless approach. Electromagnetic needleless intravitreal injections lack quantification studies. We investigate the delivery properties of the needleless injector where the characterization can be used to refine the design parameters of the prototype in subsequent iterations. Experiments were performed to characterize the injectant delivered from the electromagnetic needleless injector. Penetration tests were conducted to observe the influences of various injection barriers and tissues. Ultrasonic imaging modality was explored for future applications of the prototype. The dispersion of the injectant was controllable where injection depth and distribution is dependent on the input voltage. The synthetic barriers highlighted significant energy losses for penetration (maximum velocity falls from 4.46 to 1.57 mm/s with a 0.1-mm barrier). The biological barriers were difficult to penetrate with the current prototype. Our results indicate that the current electromagnetic injector offers controllable dispersion (depth and distribution) correlated with input voltages, which should have increased injection power for use with biological tissue. Ultrasonic imaging modality produced velocity profiles comparable to the optical approach which is promising for future in vivo studies. The influences of injection barriers should be further investigated in in vivo experiments with ultrasonic imaging modalities. Graphical abstract .

7.
Lancet Public Health ; 4(9): e473-e481, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31493844

RESUMO

BACKGROUND: The estimation of influenza-associated excess mortality in countries can help to improve estimates of the global mortality burden attributable to influenza virus infections. We did a study to estimate the influenza-associated excess respiratory mortality in mainland China for the 2010-11 through 2014-15 seasons. METHODS: We obtained provincial weekly influenza surveillance data and population mortality data for 161 disease surveillance points in 31 provinces in mainland China from the Chinese Center for Disease Control and Prevention for the years 2005-15. Disease surveillance points with an annual average mortality rate of less than 0·4% between 2005 and 2015 or an annual mortality rate of less than 0·3% in any given years were excluded. We extracted data for respiratory deaths based on codes J00-J99 under the tenth edition of the International Classification of Diseases. Data on respiratory mortality and population were stratified by age group (age <60 years and ≥60 years) and aggregated by province. The overall annual population data of each province and national annual respiratory mortality data were compiled from the China Statistical Yearbook. Influenza surveillance data on weekly proportion of samples testing positive for influenza virus by type or subtype for 31 provinces were extracted from the National Sentinel Hospital-based Influenza Surveillance Network. We estimated influenza-associated excess respiratory mortality rates between the 2010-11 and 2014-15 seasons for 22 provinces with valid data in the country using linear regression models. Extrapolation of excess respiratory mortality rates was done using random-effect meta-regression models for nine provinces without valid data for a direct estimation of the rates. FINDINGS: We fitted the linear regression model with the data from 22 of 31 provinces in mainland China, representing 83·0% of the total population. We estimated that an annual mean of 88 100 (95% CI 84 200-92 000) influenza-associated excess respiratory deaths occurred in China in the 5 years studied, corresponding to 8·2% (95% CI 7·9-8·6) of respiratory deaths. The mean excess respiratory mortality rates per 100 000 person-seasons for influenza A(H1N1)pdm09, A(H3N2), and B viruses were 1·6 (95% CI 1·5-1·7), 2·6 (2·4-2·8), and 2·3 (2·1-2·5), respectively. Estimated excess respiratory mortality rates per 100 000 person-seasons were 1·5 (95% CI 1·1-1·9) for individuals younger than 60 years and 38·5 (36·8-40·2) for individuals aged 60 years or older. Approximately 71 000 (95% CI 67 800-74 100) influenza-associated excess respiratory deaths occurred in individuals aged 60 years or older, corresponding to 80% of such deaths. INTERPRETATION: Influenza was associated with substantial excess respiratory mortality in China between 2010-11 and 2014-15 seasons, especially in older adults aged at least 60 years. Continuous and high-quality surveillance data across China are needed to improve the estimation of the disease burden attributable to influenza and the best public health interventions are needed to curb this burden. FUNDING: National Science Fund for Distinguished Young Scholars, National Science and Technology Major Project of China, National Institute of Health Research, the Harvard Center for Communicable Disease Dynamics from the National Institute of General Medical Sciences, and the China-US Collaborative Program on Emerging and Re-emerging Infectious Disease.

8.
Int Immunopharmacol ; 75: 105819, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421546

RESUMO

Although several therapies are approved, none promote re-myelination in multiple sclerosis (MS) patients, limiting their ability for sustained recovery. Thus, treatment development in MS has the opportunity to tackle the challenges, including experimental therapies targeting neuroprotection and re-myelination. Here, we provide a novel therapeutic target for Ginkgolide K (GK) that is now becoming a very critical natural compound to treat demyelination and neurodegeneration. GK improves behavioral dysfunction and demyelination in cuprizone (CPZ) model, followed by the migration and enrichment of astrocytes in the corpus callosum. Both in vitro and in vivo experiments demonstrates that GK triggers the upregulation of Nrf2/HO-1 in astrocytes and inhibition of p-NF-kB/p65, which is associated with the outcome of anti-inflammation and anti-oxidation by suppressing the production of IL-6 and TNFα as well as nitric oxide and iNOS in astrocytes. Further findings suggest that IGF/PI3K, but not BDNF, was induced in the corpus callosum after GK treatment, revealing that Nrf2 activation inhibited caspase-3 and apoptosis in O4+ oligodendrocytes possibly through IGF/PI3K signaling molecules. Since the current immunomodulatory therapies for MS have failed to prevent patients from entering the progressive phase of the disease, thus targeting Nrf2 in astrocytes with GK would be an ideal strategy for myelin protection and regeneration.

9.
J Agric Food Chem ; 67(34): 9510-9521, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31382738

RESUMO

Glutamate (Glu) is a critical nutritional regulator of intestinal epithelial homeostasis. In addition, intestinal stem cells (ISCs) at crypt bases are known to play important roles in maintaining the renewal and homeostasis of the intestinal epithelium, and the aspects of communication between Glu and ISCs are still unknown. Here, we identify Glu and mammalian target of rapamycin complex 1 (mTORC1) as essential regulators of ISC expansion. The results showed that extracellular Glu promoted ISC expansion, indicated by increased intestinal organoid forming efficiency and budding efficiency as well as cell proliferation marker Ki67 immunofluorescence and differentiation marker Keratin 20 (KRT20) expression. Moreover, the insulin receptor (IR) mediating phosphorylation of the insulin receptor substrate (IRS) and downstream signaling phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was involved in this response in ISCs. As expected, Glu-induced mTORC1 signaling activation was observed in the intestinal porcine enterocyte cell line (IPEC-J2), and Glu activated the PI3K/Akt/mTORC1 pathway. Accordingly, PI3K inhibition partially suppressed Glu-induced mTORC1 activation. In addition, Glu increased the phosphorylation levels of IR and IRS, and inhibiting IR downregulated the IRS/PI3K/Akt pathway. Collectively, our findings first indicate that extracellular Glu activates mTORC1 via the IR/IRS/PI3K/Akt pathway and stimulates ISC expansion, providing a new perspective for regulating the growth and health of the intestinal epithelium.


Assuntos
Ácido Glutâmico/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Mucosa Intestinal/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Insulina/metabolismo , Células-Tronco/metabolismo , Animais , Proteínas Substratos do Receptor de Insulina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Fosfatidilinositol 3-Quinases/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Receptor de Insulina/genética , Transdução de Sinais , Suínos
10.
Cell Death Dis ; 10(8): 597, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395857

RESUMO

Human adipose-derived stem cells (hADSCs) are increasingly presumed to be a prospective stem cell source for cell replacement therapy in various degenerative and/or traumatic diseases. The potential of trans-differentiating hADSCs into motor neuron cells indisputably provides an alternative way for spinal cord injury (SCI) treatment. In the present study, a stepwise and efficient hADSC trans-differentiation protocol with retinoic acid (RA), sonic hedgehog (SHH), and neurotrophic factors were developed. With this protocol hADSCs could be converted into electrophysiologically active motoneuron-like cells (hADSC-MNs), which expressed both a cohort of pan neuronal markers and motor neuron specific markers. Moreover, after being primed for neuronal differentiation with RA/SHH, hADSCs were transplanted into SCI mouse model and they survived, migrated, and integrated into injured site and led to partial functional recovery of SCI mice. When ablating the transplanted hADSC-MNs harboring HSV-TK-mCherry overexpression system with antivirial Ganciclovir (GCV), functional relapse was detected by motor-evoked potential (MEP) and BMS assays, implying that transplanted hADSC-MNs participated in rebuilding the neural circuits, which was further confirmed by retrograde neuronal tracing system (WGA). GFP-labeled hADSC-MNs were subjected to whole-cell patch-clamp recording in acute spinal cord slice preparation and both action potentials and synaptic activities were recorded, which further confirmed that those pre-conditioned hADSCs indeed became functionally active neurons in vivo. As well, transplanted hADSC-MNs largely prevented the formation of injury-induced cavities and exerted obvious immune-suppression effect as revealed by preventing astrocyte reactivation and favoring the secretion of a spectrum of anti-inflammatory cytokines and chemokines. Our work suggests that hADSCs can be readily transformed into MNs in vitro, and stay viable in spinal cord of the SCI mouse and exert multi-therapeutic effects by rebuilding the broken circuitry and optimizing the microenvironment through immunosuppression.

11.
Hypertens Res ; 42(10): 1536-1543, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31388123

RESUMO

The genetic factors related to early-onset hypertension are largely unknown. This study aimed to determine the spectrum of steroid metabolism gene variants and the clinical relationships of these variants to phenotypes in Chinese patients with early-onset hypertension. A total of 306 consecutive early-onset hypertensive patients were recruited. All coding exons and flanking intronic regions of KCNJ5, CYP11B1, and CYP17A1 were sequenced. Long-distance polymerase chain reaction was used to search for a CYP11B1/CYP11B2 chimeric gene. Pedigree investigations and genotype-phenotype analyses were performed for patients with rare variants. Nine rare variants were detected in eight patients (2.6%), but no CYP11B1/CYP11B2 chimeric gene was identified. One patient and two of her siblings were found to carry compound heterozygous mutations (C183Y and T390R) in CYP17A1 and were eventually diagnosed with atypical congenital adrenal hyperplasia. Patients with rare variants had younger ages of onset [17 (16, 20) vs. 30 (23, 35) years old, p = 0.010] and higher systolic blood pressure (148.5 ± 9.6 vs. 137.9 ± 17.8 mmHg, p = 0.021) than those without rare variants. Additionally, the patients and their relatives carrying rare variants exhibited increased serum free corticosterone [230.4 (7.4, 533.0) vs. 1.9 (0.9, 6.7)ng/ml, p = 0.001] and 11-deoxycorticosterone [16.16 (0.59, 33.23) vs. 0.77 (0.41, 0.96)ng/ml, p = 0.038] levels. Genetic testing is useful for the etiologic diagnosis of early-onset hypertension. Rare variants in steroid metabolism genes were associated with more severe clinical expression and abnormal circulating steroid metabolites in patients with early-onset hypertension.

12.
Mol Ther Nucleic Acids ; 17: 636-643, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31400606

RESUMO

Diabetic cardiomyopathy (DCM) is a vital cause of fatalities in diabetic patients. The programmed death of cardiomyocytes and inflammation critically contribute to cardiac hypertrophy and fibrosis in DCM. Furthermore, circular RNA (circRNA) is a key regulator of various diseases. However, the role of circRNAs in DCM remains to be elucidated. Our previous study found that pyroptosis was markedly activated in the cardiomyocytes subjected to high-glucose conditions, and miR-214-3p regulated the expression of caspase-1. The aim of this study was to elucidate whether circRNA is involved in DCM pyroptosis via the miR-214-3p/caspase-1 pathway. Herein, we identified that hsa_circ_0076631, named caspase-1-associated circRNA (CACR), was increased both in high-glucose-treated cardiomyocytes and in the serum of diabetic patients. CACR also sponged an endogenous miR-214-3p to sequester and inhibit its expression. CACR knockdown in cardiomyocytes counteracted high-glucose-induced caspase-1 activation. Conversely, miR-214-3p knockdown partially abolished the beneficial effects of CACR silencing on pyroptosis in cardiomyocytes. Therefore, this study elucidated that CACR might be a novel therapeutic target via the CACR/miR-214-3p/caspase-1 pathway in DCM.

13.
Nat Nanotechnol ; 14(8): 770-775, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31332345

RESUMO

Spin-orbit coupling is a fundamental mechanism that connects the spin of a charge carrier with its momentum. In the optical domain, an analogous synthetic spin-orbit coupling is accessible by engineering optical anisotropies in photonic materials. Both yield the possibility of creating devices that directly harness spin and polarization as information carriers. Atomically thin transition metal dichalcogenides promise intrinsic spin-valley Hall features for free carriers, excitons and photons. Here we demonstrate spin- and valley-selective propagation of exciton-polaritons in a monolayer of MoSe2 that is strongly coupled to a microcavity photon mode. In a wire-like device we trace the flow and helicity of exciton-polaritons expanding along its channel. By exciting a coherent superposition of K and K' tagged polaritons, we observe valley-selective expansion of the polariton cloud without either an external magnetic field or coherent Rayleigh scattering. The observed optical valley Hall effect occurs on a macroscopic scale, offering the potential for applications in spin-valley-locked photonic devices.

14.
Biomed Chromatogr ; 33(10): e4634, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31257625

RESUMO

Plasma concentrations of nicotine and its active metabolite cotinine are highly correlated with its biological effects. A UHPLC-MS/MS method was developed, validated and applied for nicotine and cotinine analysis in mice plasma. Chromatographic separation was achieved on a BEH HILIC column using acetonitrile (0.1% formic acid) and 10 mm ammonium formate as mobile phase. The gradient elution was performed at 0.4 mL/min with a run time of 3.6 min. The quantitative ion transition was m/z 163.1 > 130.0 for nicotine, m/z 177.1 > 80.0 for cotinine and m/z 167.1 > 134.0 for nicotine-D4 (internal standard, IS). For both nicotine and cotinine, the calibration range was 5-500 ng/mL with 5 ng/mL as the lower limit of quantitation, and the intra- and inter-day bias and imprecision were -4.61-12.00% and <11.12%. The IS normalized recovery was 90.62-98.95% for nicotine and 89.18-101.53% for cotinine, and the IS normalized matrix factor was 106.00-116.44% for nicotine and 100.34-109.85% for cotinine. Both nicotine and cotinine were stable under conventional storage conditions. The validated method has been applied to a pharmacokinetic study in mice to calculate the pharmacokinetic parameters for both analytes.

15.
J Am Soc Mass Spectrom ; 30(10): 2068-2081, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31332742

RESUMO

Zinc fingers are proteins that are characterized by the coordination of zinc ions by an amino acid sequence that commonly contains two histidines and two cysteines (2His-2Cys motif). Investigations of oligopeptides that contain the 2His-2Cys motif, e.g., acetyl-His1-Cys2-Gly3-Pro4-Tyr5-His6-Cys7, have discovered they exhibit pH-dependent Zn(II) chelation and have redox activities with Cu(I/II), forming a variety of metal complexes. To further understand how these 2His-2Cys oligopeptides bind these metal ions, we have undertaken a series of ion mobility-mass spectrometry and B3LYP/LanL2DZ computational studies of structurally related heptapeptides. Starting with the sequence above, we have modified the potential His, Cys, or C-terminus binding sites and report how these changes in primary structure affect the oligopeptides positive and negative charge states, conformational structure, collision-induced breakdown energies, and how effectively Zn(II) binds to these sequences. The results show evidence that the weak acid-base properties of Cys-His are intrinsically linked and can result in an intramolecular salt-bridged network that affects the oligopeptide properties.

16.
Food Funct ; 10(8): 5080-5090, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31361289

RESUMO

Acanthopanax trifoliatus (L.) Merr., an edible medicinal plant from Southeast Asia, exerts a wide range of bioactivities, such as anti-inflammatory activity. However, the anti-inflammatory mechanisms of its action and active constituents remain unclear. Herein, the effects of two triterpenoids, namely impressic acid (IA) and acankoreanogenin A (AA), from A. trifoliatus in both in vitro and in vivo chronic inflammation models were investigated. The results indicated that AA and IA reduced lipopolysaccharide (LPS)-induced production of nitroxide significantly in murine macrophage RAW246.7 cells. In addition, AA and IA down-regulated the activation of NF-κB and decreased the release of inflammatory mediators (iNOS, COX-2, TNF-α, and IL-6) and tumorigenesis-associated factors (MMP-9 and VEGF) in RAW246.7 cells. Furthermore, in a tetradecanoylphorbolacetate (TPA)-treated mouse model, AA and IA could effectively attenuate mouse ear edema and pathological damage and reduced levels of cytokines including iNOS, COX-2, TNF-α, and IL-1ß. Taken together, AA and IA, being of natural origin, are promising anti-inflammatory agents and may contribute to the overall anti-inflammatory effect of A. trifoliatus.

17.
J Sep Sci ; 42(17): 2788-2795, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31218807

RESUMO

With the explosive growth of the bioscience and biopharmaceuticals, the demand for high efficient analysis and separation of proteins is urgent. High-performance liquid chromatography is an appropriate technology for this purpose, and the stationary phase is the kernel to the separation efficiency. In this study, flow-through poly(styrene-co-divinylbenzene) microspheres characteristic of the binary pores, i.e. flow-through pores and mesopores, were synthesized; this special porous structure would benefit the convective mass transfer while guarantee the high specific surface area. Owing to the hydrophobic nature, poly(styrene-co-divinylbenzene) microspheres were suitable as the reversed-phase stationary phase for separation of proteins. For the high permeability of the poly(styrene-co-divinylbenzene) microspheres packed column, fast separation of the studied six proteins in ∼2 min was achieved. The recoveries of studied proteins were acceptable in the range of 79.0-99.4%. The proposed column had good pH stability of 1-13 and repeatability. Moreover, the column was applied for egg white fast separation, further demonstrating its applicability for complex bio-sample separation. The flow-through poly(styrene-co-divinylbenzene) microspheres were promising for fast separation of large molecules.

18.
Int J Biol Sci ; 15(5): 1010-1019, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31182921

RESUMO

Metformin is a widely used antidiabetic drug for type 2 diabetes that can play a cardioprotective role through multiple pathways. It is a recognized agonist of AMP-activated protein kinase (AMPK) that blocks mitochondrial complex I. The NLRP3 inflammasome has been demonstrated to be activated in diabetic cardiomyopathy (DCM). However, the role of metformin in regulating the NLRP3 signaling pathway in DCM remains unclear. It has been reported that AMPK can inhibit NLRP3 by activating autophagy. The aim of this study was to investigate whether metformin can inhibit the NLRP3 inflammasome by activating the AMPK/mTOR pathway in DCM. In this study, streptozotocin-induced C57BL/6 mice and high glucose-treated primary cardiomyocytes from neonatal mice were treated with metformin or an AMPK inhibitor compound C. Echocardiography, hematoxylin-eosin and Masson staining showed that the function and morphology of the diabetic hearts were improved after metformin treatment, whereas these parameters deteriorated after intervention with an AMPK inhibitor. Immunohistochemical staining, immunofluorescence staining and western blot assays indicated that the expression levels of mTOR, NLRP3, caspase-1, IL-1ß and GSDMD-N were decreased in the diabetic model treated with metformin and were reversed after the administration of an AMPK inhibitor in vivo and in vitro. Mechanistically, our results demonstrated that metformin can activate AMPK, thus improving autophagy via inhibiting the mTOR pathway and alleviating pyroptosis in DCM. Thus, we provide novel information for the treatment of DCM.

19.
Zhen Ci Yan Jiu ; 44(4): 264-9, 2019 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-31056879

RESUMO

OBJECTIVE: To observe and compare the effect of electroacupuncture (EA) of "Tianshu" (ST25) and "Dachangshu" (BL25) on intestinal sensitivity and the expression of M3 muscarinic acetylcholine receptor (M3R) and 5-hydroxytryptamine 3A receptor (5-HT3AR) in the colon tissue in irritable bowel syndrome (IBS) rats, so as to explore its mechanism underlying improvement of IBS. METHODS: Forty newborn Wistar rats were randomly divided into blank control, model, ST25 and BL25 groups (n=10 rats per group). The IBS model was established by joint application of maternal separation, acetic acid enema plus colorectal distension from day 8 to 21 after birth. At the age of 9 weeks, EA (2 Hz/100 Hz, 0.1-0.3 mA) was applied to ST25 and BL25 for 20 min, once every other day for 5 times. The modified method was used to record the abdominal withdrawal reflex (AWR), so as to evaluate the visceral sensitivity by referring to the modified Al-Chaer's and colleagues' methods. The threshold (initial wave), the number and peak-peak value of contraction waves (AWR) within 90 s were recorded. The immunoactivity of M3R and 5-HT3AR in the colon tissue was detected by immunohistochemistry. RESULTS: After modeling, the latency was obviously shortened, the number and peak-peak values of contraction waves of intestine were significantly increased, and the immunoactivity of M3R and 5-HT3AR was notably up-regulated in the model group compared with the blank control group (P<0.01). After the EA intervention, the latency was obviously prolonged, the peak-peak value in both ST25 and BL25 groups, and the number of contraction waves in the ST25 group were significantly decreased (P<0.01), and the expression levels of M3 and 5-HT3A R were considerably down-regulated in both ST25 and BL25 groups relevant to the model group (P<0.01). The therapeutic effects were significantly better in the ST25 group than in the BL25 group in prolonging the latency and reducing the contraction wave number, and in down-regulating the expression of colonic M3R and 5-HT3AR (P<0.05, P<0.01). CONCLUSION: EA at ST25 and BL25 can reduce the intestinal sensitivity in IBS rats, which is probably associated with its effects in down-regulating the expression of M3R and 5-HT3AR in the colon. The therapeutic effects of ST25 were obviously better than those of BL25 in suppressing intestinal sensitivity and expression of colonic M3R and 5-HT3AR.


Assuntos
Eletroacupuntura , Síndrome do Intestino Irritável , Pontos de Acupuntura , Animais , Colinérgicos , Privação Materna , Muscarina , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Receptores 5-HT3 de Serotonina , Serotonina
20.
Nature ; 569(7757): E7, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31065056

RESUMO

Change history: In this Letter, the following text has been added to the Acknowledgements section: "the scanning transmission electron microscopy measurements at the Molecular Foundry were supported by the Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under contract number DE-AC02-05CH11231". See accompanying Amendment.

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