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1.
Nanoscale ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065202

RESUMO

The key to develop efficient catalysts is to improve the quantity and activity of catalytic sites of the catalysts through optimal structural and compositional design. Accordingly, open-mouth N-doped carbon nanoboxes embedded with mixed metal phosphide nanoparticles are fabricated from monodisperse Ni3[Fe(CN)6]2·H2O nanocubes through conformal Ni3[Co(CN)6]2·12H2O layer coating, ammonia etching, and thermal phosphorization, sequentially. The product catalyst exhibits highly efficient electrocatalytic performances, achieving low overpotentials of 204 and 129 mV for the oxygen evolution reaction and hydrogen evolution reaction, respectively, and a small working voltage of 1.57 V for the overall water splitting, all at 10 mA cm-2. Its long-term electrocatalytic stability is also outstanding, experiencing only minor chronopotentiometric decay after a 24 h operation at 10 mA cm-2. The enhanced electrocatalytic performance may be attributed to the synergistic effects between the mixed metal phosphides, the protective function offered by the chainmail catalyst design, and the fast mass transport channels for the electrolyte and gaseous products afforded by the large openings on the nanobox shell, as well as the easy access of the inner active sites of the nanobox. The ingenious open-mouth nanobox structure together with embedded mixed metal phosphide nanoparticles is a unique design for improving the quantity and activity of catalytic sites of the catalyst for high efficiency electrolytic water splitting. The present design concept can be readily applied to the fabrication of other heterogeneous catalysts.

2.
Neuro Oncol ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32055852

RESUMO

Gliomas are the most common primary central nervous system tumors occurring in children and adults with neurofibromatosis type I (NF1). Over the past decade, discoveries of the molecular basis of low-grade gliomas (LGGs) have led to new approaches for diagnosis and treatments. However, these new understandings have not been fully applied to the management of NF1-associated gliomas. A consensus panel consisting of experts in NF1 and gliomas was convened to review the current molecular knowledge of NF1-associated low grade "transformed" and high-grade gliomas; insights gained from mouse models of NF1-LGGs; challenges in diagnosing and treating older patients with NF1-associated gliomas; and advances in molecular targeted treatment and potential immunologic treatment of these tumors. Next steps are recommended to advance the management and outcomes for NF1-associated gliomas.

3.
Anal Chem ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32020800

RESUMO

Mercury (Hg), as a highly harmful environmental pollutant, poses severe ecological and health risks even at low concentrations. Accurate and sensitive methods for detecting Hg2+ ions in aquatic environments are highly needed. In this work, we developed a highly sensitive fluorescence sensor for Hg2+ detection with an integrated use of biosynthetic CdSe/CdS quantum dots (QDs) and liposome carrier signal amplification. To construct such a sensor, three single-stranded DNA probes were rationally designed based on the thymine-Hg2+-thymine (T-Hg2+-T) coordination chemical principles and by taking advantage of the biocompatibility and facile-modification properties of the biosynthetic QDs. Hg2+ could be determined in a range from 0.25 to 100 nM with a detection limit of 0.01 nM, which met the requirements of environmental sample detection. The sensor also exhibited a high selectivity for Hg2+ detection in the presence of other high-level metal ions. A satisfactory capacity of the sensor for detecting environmental samples including tap water, river water, and landfill leachate was also demonstrated. This work opens up a new application scenario for biosynthetic QDs and holds a great potential for environmental monitoring applications.

4.
BMC Pulm Med ; 20(1): 43, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066414

RESUMO

Descending necrotizing mediastinitis is a severe infection of the mediastinum. This syndrome manifests as fever and chest pain following cough and sputum production. A 49-year-old woman presented with fever and a 14-day history of pneumonia. CT showed mediastinal abscesses with a giant calcified mediastinal lymph node (21 × 18 mm) and pneumonia. Bronchoscopy by EBUS-TBNA under general anesthesia was performed. The pathogen found in the puncture culture was Streptococcus constellatus, and antibiotics (mezlocillin/sulbactam 3.375 IVGTT q8h) was administered. A proximal right main bronchial neoplasm, suspected lung cancer, was found and conformed to inflammatory granuloma. A total of 22 months post-discharge the patient was clinically stable. We also conducted a review of the literature for all Streptococcus constellatus descending necrotizing mediastinitis infections between 2011 and 2017.

6.
Pharm Dev Technol ; : 1-8, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32009511

RESUMO

Piperine (Pip) has been widely studied for its multiple activities such as antidepressant, anti-epileptic, and so forth. However, the poor water solubility coupled with low bioavailability may inevitably hinder the application of Pip in the clinical setting. In this study, a formulation strategy was proposed to spontaneously resolve the low bioavailability and dose dividing issue of Pip. The matrix pellets (Pip-SR-pellets) consisting of Pip solid dispersion (Pip-SD) and hydroxypropylmethyl cellulose-K100 were developed to achieve an increased and sustained release profile in vitro. The Pip-SR-pellets were compacted into fast disintegrating tablets (FDTs) with a blend of excipients comprising lactose, MCC, LS-HPC, and CMS-Na. The Pip-SD was characterized by solubility study and XRD. The evaluation of the cross-sectional morphology of the Pip-FDTs via scanning electron microscope proved that Pip-SR-pellets maintained its structural integrity during compression and were uniformly distributed in the Pip-FDTs. The release profile of Pip-SR-pellets was highly consistent with the Pip-FDTs. In vivo pharmacokinetics study demonstrated that the relative bioavailability of Pip-SR-pellets was approximately 2.70-fold higher than that of the pure drug, and 1.62-fold compared with that of Pip-SD. This work therefore showed a potential industrialized method could be applied to formulate poorly water-soluble drug that has dose-dividing requirement.

7.
Biotechnol Lett ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048128

RESUMO

Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Ex) are a promising tool for the repair of acute kidney injury (AKI) caused by cisplatin and ischemia/reperfusion. However, the roles of hucMSC-Ex in sepsis-associated AKI repair and its mechanism are largely unknown. Hence, we constructed a sepsis model through cecal ligation and puncture (CLP), testing the benefits of hucMSC-Ex in the sepsis in terms of survival rate, serum renal markers levels, morphological changes and apoptosis. Immunohistochemistry staining and immunofluorescence assay were used to investigate the role of NF-κB activity in the repair of sepsis-associated AKI with hucMSC-Ex. HK-2 cells were transfected with microRNA-146b (miR-146b) mimics and inhibitors, respectively, and the regulatory effect of miR-146b on NF-κB activity was studied. We found that hucMSC-Ex treatment significantly decreased the serum creatinine (Cr) and blood urea nitrogen (BUN) levels, ameliorated the morphological damage and inhibited renal tubular cells apoptosis. More importantly, the survival rate at 72 h was 28% in CLP group and 45% in hucMSC-Ex group, respectively. Treatment with hucMSC-Ex improved survival in mice with sepsis. These effects of hucMSC-Ex were mediated by the inhibition of NF-κB activity and the lessening of pro-inflammatory response. Furthermore, hucMSC-Ex significantly increased miR-146b expression in kidney tissues. Conversely, interleukin (IL)-1 receptor-associated kinase (IRAK1) level, which is the target gene of miR-146b, clearly decreased in hucMSC-Ex group. In brief, this study showed that treatment with hucMSC-Ex decreased IRAK1 expression through the up-regulation of miR-146b level, led to the inhibition of NF-κB activity, and eventually alleviated sepsis-associated AKI and improved survival in mice with sepsis. HucMSC-Ex may be a novel therapeutic agent for the reduction of sepsis-associated AKI.

8.
Anal Chem ; 92(3): 2697-2705, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31895543

RESUMO

Formaldehyde (HCHO) is the most abundant atmospheric carbonyl compound and plays an important role in the troposphere. However, HCHO detection via traditional incoherent broadband cavity enhanced absorption spectroscopy (IBBCEAS) is limited by short optical path lengths and weak light intensity. Thus, a new light-emitting diode (LED)-based IBBCEAS was developed herein to measure HCHO in ambient air. Two LEDs (325 and 340 nm) coupled by a Y-type fiber bundle were used as an IBBCEAS light source, which provided both high light intensity and a wide spectral fitting range. The reflectivity of the two cavity mirrors used herein was 0.99965 (1 - reflectivity = 350 ppm loss) at 350 nm, which corresponded with an effective optical path length of 2.15 km within a 0.84 m cavity. At an integration time of 30 s, the measurement precision (1σ) for HCHO was 380 parts per trillion volume (pptv), and the corresponding uncertainty was 8.3%. The instrument was successfully deployed for the first time in a field campaign and delivered results that correlated well with those of a commercial wet-chemical instrument based on Hantzsch fluorimetry (R2 = 0.769). The combined light source based on a Y-type fiber bundle overcomes the difficulty of measuring ambient HCHO via IBBCEAS in near-ultraviolet range, which may extend IBBCEAS technology to measure other atmospheric trace gases with high precision.

9.
Food Chem Toxicol ; 137: 111126, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31954714

RESUMO

Syringic acid (SA), a natural polyphenol found in fruits and vegetables, is claimed to show notable hepatoprotection. Nevertheless, low solubility and bioavailability hamper the application of SA. This study aimed to investigate the potential of TPGS/F127/F68 mixed polymeric micelles as a sustained and liver-targeting nanocarrier for SA. Herein, the prepared SA-loaded TPGS/F127/F68 mixed polymeric micelles (SA-TPGS-Ms) were spherically-shaped and homogeneously-distributed nanoparticles with high entrapment efficiency (94.67 ± 2.05%) and sustained release. Besides, in-vitro cell culture studies revealed that SA-TPGS-Ms substantially promoted cellular uptake with excellent biocompatibility. After oral administration, SA-TPGS-Ms demonstrated an increased bioavailability (2.3-fold) and delayed in-vivo elimination compared with the free SA. Furthermore, the alleviation of oxidative stress and amelioration of hepatic injury in CCl4-induced hepatotoxicity mice further demonstrated the excellent hepatoprotection of SA-TPGS-Ms. Collectively, SA-TPGS-Ms could be a promising nanocarrier for the utilization of SA in functional foods, with enhanced bioavailability and hepatoprotection.

10.
Theranostics ; 10(1): 74-90, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903107

RESUMO

Microglial activation participates in white matter injury after cerebral hypoperfusion. However, the underlying mechanism is unclear. Here, we explore whether activated microglia aggravate white matter injury via complement C3-C3aR pathway after chronic cerebral hypoperfusion. Methods: Adult male Sprague-Dawley rats (n = 80) underwent bilateral common carotid artery occlusion for 7, 14, and 28 days. Cerebral vessel density and blood flow were examined by synchrotron radiation angiography and three-dimensional arterial spin labeling. Neurobehavioral assessments, CLARITY imaging, and immunohistochemistry were performed to evaluate activation of microglia and C3-C3aR pathway. Furthermore, C3aR knockout mice were used to establish the causal relationship of C3-C3aR signaling on microglia activation and white matter injury after hypoperfusion. Results: Cerebral vessel density and blood flow were reduced after hypoperfusion (p<0.05). Spatial learning and memory deficits and white matter injury were shown (p<0.05). These impairments were correlated with aberrant microglia activation and an increase in the number of reactive microglia adhering to and phagocytosed myelin in the hypoperfusion group (p<0.05), which were accompanied by the up-regulation of complement C3 and its receptors C3aR (p<0.05). Genetic deletion of C3ar1 significantly inhibited aberrant microglial activation and reversed white matter injury after hypoperfusion (p<0.05). Furthermore, the C3aR antagonist SB290157 decreased the number of microglia adhering to myelin (p<0.05), attenuated white matter injury and cognitive deficits in chronic hypoperfusion rats (p<0.05). Conclusions: Our results demonstrated that aberrant activated microglia aggravate white matter injury via C3-C3aR pathway during chronic hypoperfusion. These findings indicate C3aR plays a critical role in mediating neuroinflammation and white matter injury through aberrant microglia activation, which provides a novel therapeutic target for the small vessel disease and vascular dementia.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31913590

RESUMO

Electrocatalytic hydrogen production driven by surplus electric energies is considered a promising sustainable process for hydrogen supply. The high overpotential and low energy-conversion efficiency caused by the slow kinetics of the four-electron transfer oxygen-evolution reaction (OER), however, hamper its competitiveness. Herein, a highly stable, efficient OER catalyst was developed, taking the effects of both composition and nanostructure into account for the catalyst design. N-doped carbon-armored mixed metal phosphide nanoparticles confined in N-doped porous carbon nanoboxes, a particle-in-box nanostructure, were synthesized from monodisperse Ni3[Fe(CN)6]2·H2O nanocubes through sequential conformal polydopamine coating, ammonia etching, and thermal phosphorization. The product exhibited outstanding catalytic abilities for the OER in 1.0 M KOH, delivering 10, 100, and 250 mA/cm2 at ultrasmall overpotentials of 203, 242, and 254 mV, respectively, with an ultrasmall Tafel slope of 38 mV/dec, outperforming most recently reported top-notch iron-group-based OER catalysts. The long-term stability was also excellent, showing a small chronopotentiometric decay of 2.5% over a 24 h operation at 50 mA/cm2. The enhanced catalytic efficiency and stability may be attributable to the unique particle-in-box structure as a nanoreactor offering a local, fast reaction environment, the conductive N-doped porous carbon shell for fast charge and mass transport, the synergistic effect between multicomponent metal phosphides for enhanced intrinsic activities, and the carbon protection layer to prevent/delay the catalyst core from being deactivated. This combined particle-in-box and chainmail design concept for electrocatalysts is unique and advantageous and may be readily applied to the general field of heterogeneous reactions.

12.
Ying Yong Sheng Tai Xue Bao ; 31(1): 72-82, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31957382

RESUMO

Photosynthetically active radiation (PAR) is a key environmental factor affecting the change of net ecosystem exchange (NEE) during the daytime. However, the coordinate system of PAR measured by horizontal radiometers over sloping terrain does not match that of NEE after tilt-corrected of the ultrasonic anemometer. Using the temperate deciduous broad-leaved forest at the Maoershan site with an average slope of 9° and a azimuth of 296° as a case, we investigated the diurnal variations in NEE and its driving factors in the growing season (May to September) of 2016. We assessed the differences in estimating light response parameters and the explanations of NEE by other environmental factors between the PAR measured by horizontal and slope-parallel radiometers. The results showed that the diurnal change of NEE in each month of the growing season presented a morning-afternoon asymmetrically unimodal curve: the value was negative (net carbon absorption) about 2.5 h after sunrise, reached the peak around 12:00, then approached zero again at two hours before sunset. The daily net uptake maximized in July and minimized in May. During the whole growing season, the time-lag and difference in the PAR measured by the horizontal versus slope-parallel radiometers led to that the PAR values measured by the horizontal radiometer increased photosynthetic quantum yield (α) and daytime respiration rate (Rd) by 13.3% and 11.5%, respectively, and decreased the maximum photosynthetic efficiency (Amax) by 7.7%. The light response curves of NEE were asymmetrical in the morning and afternoon, with Rd and Amax in the afternoon being greater than that in the morning. Weather conditions affected light response parameters: on cloudy days, Amax was higher than that in sunny days, the α and Rd were lower versus those in sunny days for most conditions. However, the monthly Amax and Rd were generally higher for horizontally measured PAR than for slope-parallelly measured PAR, especially for Amax in the cloudy afternoon. The radiometer-orientation affected the explanation of daytime NEE by air temperature (Ta) and vapor pressure deficit (VPD). The correlation of NEE residual based on the slope-parallel radiometer with Ta and VPD (r ranged: 0.013 to 0.197, 0.098 to 0.224) was tighter than that based on the horizontal radiometer (r ranged: 0.082 to 0.219, 0.162 to 0.282) when the negative correlations with Ta for September was excluded. Our results indicated that the measurements of PAR on the inclined terrains could cause errors in the environmental interpretations of NEE. Such findings had implications for the radiometric measurement of mountain vegetation and the reasonable interpretation of carbon exchange in terrestrial ecosystems.


Assuntos
Carbono , Ecossistema , Dióxido de Carbono , China , Florestas , Fotossíntese , Estações do Ano
13.
Int J Pharm ; 575: 118980, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31899320

RESUMO

Cardiac glycosides (CGs) have been used to treat cancer for hundreds of years. However, the narrow therapeutic window and system toxicity have hindered their wide clinical applications. Herein, the small molecule prodrug strategy and nanotechnology were integrated into one drug delivery system with enhanced therapeutic effect. Using periplocymarin (PPM) as a target agent, we designed a novel redox-responsive prodrug conjugated with linoleic acid (PPM-ss-LA), which was capable of self-assembling independent of exogenous excipients. This prodrug could co-assemble with DSPE2k to form PEGylated prodrug nanoparticles (PPM-ss-LA/DSPE2k-NPs) with enhanced colloidal stability and blood circulation. Compared with free PPM, PPM-ss-LA/DSPE2k-NPs retained high anti-proliferative activity and showed increased cell uptake and therapeutic efficacy. Furthermore, the PPM-ss-LA/DSPE2k-NPs acquired a greatly enhancement of 50% lethal dose (LD50) in mice and reduced system toxicity compared with the free drug. Overall, the on-demand release of nanoprodrug delivery system could improve the therapeutic window and anticancer efficacy of CGs.

14.
Medicine (Baltimore) ; 99(4): e18835, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977879

RESUMO

The treatment strategy for elderly patients with locally advanced rectal cancer (LARC) remains controversial. The aim of this study was to identify the significance of adjuvant chemotherapy (AC) for elderly patients with LARC after neoadjuvant chemoradiotherapy (nCRT) and surgical resection. Between February 2002 and December 2012, a total of 43 patients aged ≥70 years with LARC following nCRT and surgery were retrospectively reviewed. The median follow-up time was 51 months (range 15-161 months). All patients completed the programmed chemoradiotherapy, of which 20 patients (46.5%) received 5-fluorouracil-based AC, and other 23 patients (53.5%) received no adjuvant chemotherapy. The 5-year overall survival and disease-free survival rates for AC group and non-adjuvant chemotherapy (NAC) group were 74.7% vs 63.4% (P = .562) and 73.4% vs 66.3% (P = .445), respectively. More patients in AC group suffered from severe leucopenia than that in NAC group (60% vs 17.4%, P = .004). For elderly patients with LARC following nCRT and surgery, AC may not benefit for survival, but increase treatment related leucopenia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Retais/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia , Quimioterapia Adjuvante/métodos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Retais/mortalidade , Estudos Retrospectivos
15.
Eur J Med Chem ; 186: 111864, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31767136

RESUMO

A series of indazolyl-substituted piperidin-4-yl-aminopyrimidines (IPAPYs) were designed from two potent HIV-1 NNRTIs piperidin-4-yl-aminopyrimidine 3c and diaryl ether 4 as the lead compounds by molecular hybridization strategy. The target molecules 5a-q were synthesized and evaluated for their anti-HIV activities and cytotoxicities in MT-4 cells. 5a-q displayed moderate to excellent activities against wild-type (WT) HIV-1 with EC50 values ranging from 1.5 to 0.0064 µM. Among them, 5q was regarded as the most excellent compound against WT HIV-1 (EC50 = 6.4 nM, SI = 2500). And also, it displayed potent activities against K103 N (EC50 = 0.077 µM), Y181C (EC50 = 0.11 µM), E138K (EC50 = 0.057 µM), and moderate activity against double mutants RES056 (EC50 = 8.7 µM). Moreover, the structure-activity relationships (SARs) were summarized, and the molecular docking was performed to investigate the binding mode of IPAPYs and HIV-1 reverse transcriptase.

16.
Mol Biol Rep ; 47(2): 1045-1056, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31741264

RESUMO

Inflammation can deregulate the testicular functions of steroidogenesis and spermatogenesis, consequently contributing to male infertility. Animals and cells treated with lipopolysaccharide (LPS) exhibit infection- and inflammation-induced testicular dysfunction. However, the precise mechanisms affecting steroidogenesis and spermatogenesis in response to LPS-treatment remain poorly understood. We isolated distinct testicular cells including spermatocytes, round spermatids and late spermatids to analyze distribution of peroxisome proliferator-activated receptor (PPAR) family, plays central roles in the regulation of metabolism. Our results suggested Pparα/Pparγ mRNA was highly expressed in late spermatids, while Pparß mRNA was highly expressed in round spermatids. To analyze the effect of LPS on testicular cells, we established an LPS infection model using primary Sertoli cells and testicular cell lines (TM4, GC2 and MLTC1). We observed that PPARγ and SIRT1 were concentrated in the nuclear region and that the mRNA expression levels of antioxidative enzymes (Cat and Homx1) and PPARγ were upregulated in primary Sertoli cells after LPS-treatment. Moreover, luciferase reporter gene assays of the testicular cell lines revealed that the activity of the PPAR response element (PPRE) was significantly increased. Importantly, the transcriptional activity of the androgen response element was significantly reduced, whereas activity of estrogen response element was strongly induced in LPS-treated TM4 cells, consistent with the RT-PCR results. Meanwhile, the qRT-PCR results revealed that the LPS-induced upregulation of Ar mRNA in MLTC1 cells and Erß mRNA in TM4 cells were significantly recovered after treatment with the specific PPARγ-antagonist GW9662. In addition, we also found that LPS induced alterations in enzymes involved in steroidogenesis in testicular cell lines. Taken together, our results revealed that LPS may induce PPAR transcriptional activity to disturb estrogen/androgen receptor expression and impair steroidogenesis and ROS metabolism in testicular cells.

17.
J Colloid Interface Sci ; 562: 42-51, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-31835020

RESUMO

N-doped carbon armored metal phosphides were anchored in-situ on backbones of nickel foam (NF), by using polydopamine as both carbon source and targeted precursor delivery vehicle. The product served as a highly efficient chainmail bi-functional catalyst toward electrolytic water splitting, requiring small operating cell voltages of only 1.65, 1.73, and 1.79 V at 50, 100, and 250 mA/cm2, respectively for overall water splitting. More importantly, the product catalyst also possessed excellent long-term stability, even tested at 250 mA/cm2. The excellent activity and durability may be ascribed to the positive synergistic effects between well-mixed metal phosphides, advantageous nanostructure of interwoven thin vertical nanosheets, protective and conductive N-doped carbon matrix, hydrophilic and aerophobic characteristics, and well dispersed and utilized active materials on skeleton surfaces of the highly conductive NF. This synergistic effect boosting and protective layer armored design for highly efficient and stable electrocatalysts is unique and scalable, suitable for large-scale applications not only in the field of electrocatalysis, but also in other heterogeneous catalysis.

18.
J Cell Physiol ; 235(2): 909-919, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31241766

RESUMO

MicroRNAs are a group of endogenous regulators that participate in several cellular physiological processes. However, the role of miR-137 in the osteogenic differentiation of human adipose-derived stem cells (hASCs) has not been reported. This study verified a general downward trend in miR-137 expression during the osteogenic differentiation of hASCs. MiR-137 knockdown promoted the osteogenesis of hASCs in vitro and in vivo. Mechanistically, inhibition of miR-137 activated the bone morphogenetic protein 2 (BMP2)-mothers against the decapentaplegic homolog 4 (SMAD4) pathway, whereas repressed lysine-specific histone demethylase 1 (LSD1), which was confirmed as a negative regulator of osteogenesis in our previous studies. Furthermore, LSD1 knockdown enhanced the expression of BMP2 and SMAD4, suggesting the coordination of LSD1 in the osteogenic regulation of miR-137. This study indicated that miR-137 negatively regulated the osteogenic differentiation of hASCs via the LSD1/BMP2/SMAD4 signaling network, revealing a new potential therapeutic target of hASC-based bone tissue engineering.

19.
Biosens Bioelectron ; 148: 111836, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731074

RESUMO

This work reports a customized methodology for the fabrication of 3D CdS nanosheet (NS)-enwrapped carbon fiber framework (CFF) and its utilization for sensitive split-type CuO-mediated PEC immunoassay. Specifically, the 3D CdS NS-CFF was fabricated via a solvothermal process, while the sandwich immunocomplexing was allowed in a 96 well plate with CuO nanoparticles (NPs) as the signaling labels. The subsequent release of the Cu2+ ions was directed to interact with the CdS NS, generating trapping sites and thus inhibiting its photocurrent generation. In such a protocol, the 3D CdS NS-CFF photoelectrode could not only guarantee its sufficient contact with the Cu2+-containing solution but also supply plenty CdS surface for the Cu2+ ions. Because of the target-dependent release of the Cu2+ ions and its proper coupling with the 3D CdS NS-CFF photoelectrode, a sensitive split-type PEC immunoassay was achieved for the detection of brain natriuretic peptide (BNP). This proposed system exhibited good stability and selectivity, and its applicability for real sample analysis was also demonstrated via comparison with the commercial BNP enzyme-linked immunosorbent assay (ELISA) kit. We expect this work could stimulate more interest in the design and utilization of 3D photoelectrodes for novel PEC bioanalysis.

20.
J Acquir Immune Defic Syndr ; 83(1): 81-89, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31809363

RESUMO

BACKGROUND: The intestinal microbiota contributes to the pathogenesis of obesity and metabolic disorders. People living with HIV (PLWH) have a higher risk for the development of visceral adiposity with accompanying worsened cardiovascular risk. SETTING: Convenience sample from an HIV clinic and research unit. METHODS: To understand the relationship between adiposity and intestinal dysbiosis, we compared the gut microbiota and inflammatory markers in a cross-sectional study of viscerally obese, generally obese, and lean PLWH. Fecal intestinal microbiota was characterized by 16S ribosomal DNA sequencing. Abdominal CTs quantified subcutaneous adipose tissue and visceral adipose tissue (SAT; VAT). Serum high sensitivity C-reactive protein, adiponectin, leptin, IL-6, MCP-1, and sCD14 were assayed. RESULTS: We studied 15, 9, and 11 participants with visceral obesity, general obesity, and lean body type, respectively. The generally obese group were all women and 2/3 African American, whereas the visceral obesity and lean groups were predominantly white and men who have sex with men. Markers of systemic inflammation and sCD14 were higher in general obesity compared with lean. sCD14 was positively correlated with VAT, but not SAT. Bacterial diversity was significantly reduced in participants with visceral and general obesity and composition of intestinal microbiota was significantly different from lean body types. Bacterial alpha diversity was negatively correlated with VAT area, waist/hip ratio, and sCD14, but not with SAT area. CONCLUSIONS: In this exploratory study, obesity in general was associated with dysbiotic intestinal microbiota. The relationships of VAT to bacterial diversity and sCD14 suggest that dysbiosis in viscerally obese PLWH could be associated with heightened inflammatory state.

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