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1.
J Am Chem Soc ; 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31955572

RESUMEN

Understanding the role of oxidation state of Cu surface and surface-adsorbed intermediate species in electrochemical CO2 reduction is crucial for the development of selective CO2-to-fuel electrocatalysts. In this study, the electrochemical CO2 reduction mechanism over the Cu catalysts with various oxidation states was studied by using in situ surface-enhanced infrared absorption spectroscopy (SEIRAS), in situ soft X-ray absorption spectroscopy (Cu L-edge) and on-line gas chromatography measurements. The atop-adsorbed CO (COatop) intermediate is obtained on the electrodeposited Cu surface which primarily has the oxidation state of Cu(I). COatop is further reduced, followed by the formation of C1 product such as CH4. The residual bridge-adsorbed CO (CObridge) is formed on the as-prepared Cu surface with Cu(0) which inhibits hydrocarbon formation. In contrast, the CV-treated Cu electrode prepared by oxidizing the as-prepared Cu surface contains different amount of Cu(I) and Cu(0) states. The major theme of this work is that in situ SEIRAS results show the coexistence of COatop and CObridge as the reaction intermediates during CO2 reduction and the selectivity of CO2-to-ethylene conversion is further enhanced in the CV-treated Cu electrode. The Cu catalysts modulated by electrochemical method exhibit different oxidation states and reaction intermediates as well as the electrocatalytic properties.

2.
Food Chem ; 313: 126162, 2020 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-31951884

RESUMEN

The aim of this study was to assess the effects of the phosphorylation levels of glycogen phosphorylase on its activity in mutton sarcoplasmic protein samples during incubation at 4 °C. Samples of sarcoplasmic proteins from mutton longissimus thoracis muscles were prepared and separated into three treatment groups to obtain glycogen phosphorylase with different phosphorylation levels, which were (1) treated with protein kinase A, (2) treated with alkaline phosphatase, and (3) left untreated (control). Glycogen phosphorylase phosphorylation levels and activity as well as the levels of related endogenous substances were assessed. The results showed that phosphorylation of glycogen phosphorylase in mutton promoted its activity during incubation at 4 °C. The activity of glycogen phosphorylase was also influenced by other factors (glycogen, glucose, glucose 6-phosphate, ATP, etc.) in vitro. The combined effects of phosphorylation and endogenous substances on glycogen phosphorylase activity varied at different incubation times.

3.
Hu Li Za Zhi ; 67(1): 89-97, 2020 Feb.
Artículo en Chino | MEDLINE | ID: mdl-31960400

RESUMEN

BACKGROUND & PROBLEMS: Dermatitis associated with incontinence was the cause of 55% of the total of 386 skin lesion cases in our unit between July and December 2016 and 40.3% of the skin lesion cases in our unit during March and April 2017, indicating the importance of this issue. Our survey showed that the nurses in our unit scored an average of 78.9% on knowledge related to the prevention of incontinence-associated dermatitis and only 58.2% on knowledge related to incontinence-associated dermatitis care. The main reasons for the high incidence of incontinence-associated dermatitis included: incorrect implementation of care, no discussion with the medical team, no incontinence care standards, no continue education, lack of related equipment for preventing incontinence-associated dermatitis, unit patient characteristics, and drugs used. PURPOSE: To reduce the incidence of incontinence-associated dermatitis from 40.3% to 32.0%. RESOLUTION: A care-bundle in treating incontinence-associated dermatitis was implemented by designing an assessment flow chart for evaluating incontinence-associated dermatitis, by setting standard guidelines for incontinence-associated dermatitis care, by distributing reminder cards, special toolboxes, and by changing how the little diapers were wrapped. In-service education lessons, inter-professional collaborative practice, and regular internal audit were also executed. RESULTS: After project implementation, the knowledge score of nurses increased from 78.9% to 95.7%; the correctness of care score, as retested in November 2017, increased from 58.2% to 91.5%; and the incidence of incontinence-associated dermatitis dropped to 18.5%. These improvements achieved the goals of this project. Furthermore, the sustained effect of the project measures was confirmed, with the incidence of incontinence-associated dermatitis determined as 17.9% at three months after completion of the project. CONCLUSIONS: Formulating care procedures and cooperating with medical team personnel to provide creative care measures were shown to effectively decrease the incidence of incontinence-associated dermatitis and improve overall quality of care. The findings of this project support the revision by hospitals of regulations and procedures related to adult incontinence-associated dermatitis to provide caregivers with basis-of-care standards and uniform care procedures and standards in support of effective patient skin care regimens.

4.
Mol Immunol ; 118: 182-190, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31896494

RESUMEN

Preeclampsia, a pregnancy-specific disorder, is characterized by abnormal vascular remodeling of the spiral arteries due to deficient trophoblast invasion. Lipopolysaccharide (LPS) administration to pregnant rats on day 5 of pregnancy could induce excessive immune response at the maternal-fetal interface contributing to poor early placentation that culminate in the preeclampsia-like syndrome. Furthermore, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a critical tumor suppressor, is markedly increased in the placentas of patients with preeclampsia. Our goal was to investigate the association of PTEN with preeclampsia and the pathways involved using human-trophoblast-derived cell line (HTR-8/SVneo) stimulated with LPS. We found that the expression of PTEN was significantly increased in the placentas of patients with severe preeclampsia and preeclamptic rat model induced by LPS. In vitro trophoblasts results showed that significantly differential expression of PTEN with corresponding changes in JunB/FosB (subunits of AP-1) and NF-κB activity after LPS stimulation. We further demonstrated that LPS-induced PTEN expression was dependent on AP-1 and NF-κB in trophoblasts. The trophoblasts with enforced expression of PTEN showed a reduced ability to invasion. Taken together, LPS may undermine remodelling of the human-trophoblast-derived HTR-8/SVneo cells by increasing PTEN, acting in part through the AP-1 and NF-κB pathways.

5.
Arch Biochem Biophys ; 680: 108244, 2020 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-31904363

RESUMEN

HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) is a long non-coding RNA (lncRNA) that is highly specific for maturing myeloid cells. Dysregulation of HOTAIRM1 has been found to be implicated in the development of acute myeloid leukemia (AML). However, the role of HOTAIRM1 in the drug resistance in AML remains unknown. The present study aimed to investigate the effect of HOTAIRM1 on the cytarabine (Ara-C) resistance in leukemia cell lines and to explore the underlying mechanism. The leukemia cell lines, HL60 and THP-1, were transfected with HOTAIRM1 specific siRNA (si-HOTAIRM1) or control siRNA (si-ctrl), and then treated with Ara-C for 48 h. The mRNA levels of HOTAIRM1 and platelet-type phosphofructokinase (PFKP) were measured using RT-PCR. Cell viability was evaluated by MTT assay. Apoptosis was determined using flow cytometry and caspase-3/7 activity assay. Glycolysis was evaluated by determining the glucose consumption and lactate production. To activate the Wnt/ß-catenin signaling pathway, HL60 and THP-1 cells were transfected with ß-catenin overexpressing plasmid (pcDNA-ß-catenin). Protein levels of PFKP, ß-catenin, and c-Myc were examined using western blot analysis. The results showed that knockdown of HOTAIRM1 enhanced Ara-C-induced reduction of cell viability and increase of cell apoptosis. HOTAIRM1 knockdown suppressed the glucose consumption and lactate production, as well as the expression of PFKP in AML cells. Besides, HOTAIRM1 knockdown resulted in a significant inhibitory effect on the Wnt/ß-catenin pathway. Furthermore, activating Wnt/ß-catenin pathway mitigated the effects of HOTAIRM1 knockdown on glycolysis and Ara-C cytotoxicity in AML cells. In conclusion, knockdown of HOTAIRM1 enhanced Ara-C cytotoxicity through regulating the Wnt/ß-catenin/PFKP signaling pathway. These findings suggested that HOTAIRM1 might be a therapeutic target for overcoming the Ara-C resistance in AML.

6.
BMJ Open ; 10(1): e032096, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31948986

RESUMEN

INTRODUCTION: Essential tremor (ET), a tremor disorder, is one of the most common movement disorders. Only oral drugs (propranolol, primidone, topiramate, etc)are still the first-line treatment recommended by the Food and Drug Administration. Propranolol is thought to potentially reduce upper limb action tremor. However, it has a poor effect on axial tremor symptoms, such as essential head tremor and voice tremor. Studies have shown that tremor severity develops over time, possibly producing other clinical tremors and neurological soft signs (such as memory loss, gait abnormalities, balance disorders, etc), which further increases the difficulty of treating tremors. However, some recent studies provide emerging evidence for oral propranolol on subgroups of ET, which is based on the anatomical distribution of ET (lower extremities, head, sound, tongue, etc). This systematic review aims to synthesise these new data to improve the efficacy of propranolol in ET subgroups. METHODS AND ANALYSIS: We will search for randomised controlled trials from the PubMed, MEDLINE, EMBASE, Cochrane Library, UptoDate and PEDro databases from inception to June 2019. All data will be extracted independently by two reviewers and compared at the end of the review. The two reviewers will screen the study quality, and the Cochrane Collaboration's tool in Review Manager (RevMan) V.5.3.3 will be used to evaluate risk of bias. Our primary outcome will be the functional disability component related to tremors, as measured by the Fahn-Tolosa-Marin Tremor Rating Scale subscales B and C. Secondary outcomes will include severity of tremors and quality of life. Narrative and meta-analytical syntheses are planned. ETHICS AND DISSEMINATION: Published aggregated data will be used in this review analysis and therefore no ethical approval is required. The results will be published in peer-reviewed journals, and proliferation activities will include diverse social stakeholders, non-academic groups and patients. PROSPERO REGISTRATION NUMBER: CRD42018112580.

7.
Acta Haematol ; : 1-5, 2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-31962320

RESUMEN

Thymoma is an uncommon neoplasia derived from the epithelial cells of the thymus, which leads to immune dysregulation and is associated with a series of autoimmune diseases. However, the concurrence of these disease entities is rare, and the exact mechanisms of these diseases are still unclear. We have admitted several cases who were diagnosed with thymoma, autoimmune haemolytic anaemia, and pure red cell aplasia. These cases were the first to report the concurrence of these three disorders. After thymectomy, anaemia improved, haemolytic cells decreased, and haemoglobin was normalized.

8.
J Hum Genet ; 2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-31965062

RESUMEN

NGLY1 deficiency is the first and only autosomal recessive congenital disorder of N-linked deglycosylation (NGLY1-CDDG). To date, no patients with NGLY1 deficiency has been reported from mainland China or East Asia in English literature. Here, we present six patients with a diagnosis of NGLY1-CDDG on the basis of clinical phenotype, genetic testing, and functional studies. We retrospectively analyzed clinical phenotypes and NGLY1 genotypes of six cases from four families. Informed consent was obtained for diagnosis and treatment. In-silico tools and in vitro enzyme activity assays were used to determine pathogenicity of NGLY1 varaints. All patients had typical features of NGLY1-CDDG, including global developmental delay, microcephaly, hypotonia, hypertransaminasemia, alacrimia, and feeding difficulty. Dysmorphic features found in our patients include flat nasal bridge, loose and hollow cheeks, short stature, malnutrition, and ptosis. Pachylosis could be a novel cutaneous feature that may be explained by lack of sweat. We found three novel variants, including one missense (c.982C > G/p.Arg328Gly), one splice site (c.1003+3A > G), and one frame-shift (c.1637-1652delCATCTTTTGCTTATAT/p.Ser546PhefsTer) variant. All mutations were predicted to be disease causing with in-silico prediction tools, and affected at least one feature of gene splicing. Protein modeling showed missense variants may affect covalent bonding within the protein structure, or interrupt active/binding amino-acid residues. In vitro studies indicated that proteins carrying missense variants (p.Arg328Gly and p.Tyr342Cys) lost the enzyme activity. We expanded clinical phenotype and genetic mutation spectrum of NGLY1-CDDG by reporting six cases, three novel variants, and novel clinical features from mainland China.

10.
Food Chem ; 312: 126122, 2020 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-31901825

RESUMEN

This study investigated how l-lysine/l-arginine/l-cysteine improved cured sausage color. Visible detection showed that Mb(Fe2+)NO did not form when MetMb(Fe3+) was treated with a combination of l-lysine and NaNO2, l-arginine and NaNO2, or l-cysteine and NaNO2. Visible spectra and electron paramagnetic resonance (EPR) detection together indicated formation of Mb(Fe2+)O2 when MetMb(Fe3+) was treated with l-lysine, l-arginine, or l-cysteine; Mb(Fe2+)NO was formed when MetMb(Fe3+) was treated with a combination of l-lysine and NO, l-arginine and NO, or l-cysteine and NO. Visible, EPR, and fourier transform infrared results suggested formation of a complex of Mb(Fe2+) and l-cysteine by the coordination of sulfydryl and ferrous porphyrin. Therefore, l-lysine, l-arginine, or l-cysteine can promote the formation of Mb(Fe2+)NO by reducing MetMb(Fe3+) to Mb(Fe2+)O2, and l-cysteine promotes formation of a complex of Mb(Fe2+) and l-cysteine via coordination of sulfydryl and ferrous porphyrin, which may improve cured sausage color.

11.
Artículo en Inglés | MEDLINE | ID: mdl-31928231

RESUMEN

We recently introduced a novel approach to assessing atherosclerosis: popliteal artery wall analysis from knee MRI. Specifically, the Osteoarthritis Initiative (OAI) is a multicenter, prospective cohort study of knee osteoarthritis (NCT00080171) acquiring multiple biomarkers longitudinally in 4,796 subjects for a decade, including serial high-resolution 3D double-echo steady-state MRI of the knee. The popliteal artery wall is well-seen in these high-quality MR images, allowing quantitative assessment of atherosclerotic progression/regression. However, the large number of images poses a formidable challenge. Manual segmentation of one knee/artery across 60 axial slices takes about 3-4 hours for an expert human reader, so around two decades of continuous effort would be needed to manually segment all three million slices in the OAI database.

12.
Chem Commun (Camb) ; 2020 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-31935003

RESUMEN

Pyridines containing adjacent C[triple bond, length as m-dash]C bonds were utilized as ligand units and integrated into the skeleton of conjugated microporous polymers. The resultant Pd-CMP-1 was first applied as a highly efficient heterogeneous catalytic system for Pd-catalyzed allene hydrosilylation towards a wide range of allenes to produce branched allylsilanes with high regioselectivity. The ligand units of the polymer, along with the confinement effect of the porous structure, jointly regulated the regioselectivity. The parts-per-million (ppm) levels of Pd, coordinated with the recyclable heterogeneous ligand, show promise for industrial applications. This work opens a new front of using CMP as an intriguing platform for developing highly efficient catalysts to control the regioselectivities in allene hydrosilylation.

13.
Obes Facts ; : 1-18, 2020 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-31935731

RESUMEN

OBJECTIVE: To investigate the anorexigenic and anti-obesity effectiveness of electroacupuncture (EA) on high-fat-diet-induced (HFDI) obese rats with insulin resistance (IR) and to reveal the possible mechanisms of EA affecting SIRT1 (silent mating type information regulation 2 homolog 1) in the central nervous system (CNS). METHODS: We divided 60 rats into 6 groups. All interventions, including EA and intracerebroventricular administration, were performed after 8 weeks of model establishment. We tested obesity phenotypes like body weight (BW) gain; food intake; and IR levels including glucose infusion rate, intraperitoneal insulin tolerance test (IPITT), and intraperitoneal glucose tolerance test (IPGTT) during treatment. We detected protein expression and microscopic locations in hypothalamic SIRT1, the transcription factor FOXO1 (forkhead box protein O1), acetylated FOXO1 (Ac-FOXO1), pro-opiomelanocortin (POMC), and neuropeptide Y (NPY) via Western blotting and immunofluorescence, and monitored gene expression by real-time polymerase chain reaction. RESULTS: Like the SIRT1 agonist, EA suppressed BW gain and IR levels in obese rats, but this was only partially blocked by the SIRT1 antagonist. EA could upregulate protein expression of hypothalamic SIRT1 and downregulate the acetylation level of FOXO1 in the hypothalamic arcuate nucleus (ARC), which decreased gene expression of NPY and increased that of POMC. The agonist targeted the hypothalamic SIRT1 gene, unlike EA, which targeted posttranscriptional regulation. CONCLUSION: EA could improve obesity in HFDI rats with IR via its anorectic effect. This effect targeted posttranscriptional regulation of the SIRT1 gene, which induced upregulation of ARC FOXO1 deacetylation and mediated the gene expression of POMC and NPY.

14.
Sensors (Basel) ; 20(2)2020 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-31936424

RESUMEN

A silk fibroin composite film that can simultaneously scavenge and probe H2O2 in situ was developed for possibly examining local concentrations of H2O2 for biomedical applications. A multi-functional composite film (GDES) that consists of graphene oxide (G), a photothermally responsive element that was blended with polydopamine (PDA, D)/horseradish peroxidase (HRP, E) (or DE complex), and then GDE microaggregates were coated with silk fibroin (SF, S), a tyrosine-containing protein. At 37 °C, the H2O2-scavenging ability of a GDES film in solution at approximately 7.5 × 10-3 µmol H2O2/mg film was the highest compared with those of S and GS films. The intensities of UV-excitable blue fluorescence of a GDES film linearly increased with increasing H2O2 concentrations from 4.0 µM to 80 µM at 37 °C. Interestingly, after a GDES film scavenged H2O2, the UV-excitable blue fluorescent film could be qualitatively monitored by eye, making the film an eye-probe H2O2 sensor. A GDES film enabled to heat H2O2-containing samples to 37 °C or higher by the absorption of near-IR irradiation at 808 nm. The good biocompatibility of a GDES film was examined according to the requirements of ISO-10993-5. Accordingly, a GDES film was developed herein to scavenge and eye-probe H2O2 in situ and so it has potential for biomedical applications.

15.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(1): 109-115, 2020 Jan 15.
Artículo en Chino | MEDLINE | ID: mdl-31939245

RESUMEN

Objective: To separate peripheral blood mesenchymal stem cells (PBMSC) and peripheral blood endothelial progenitor cells (PBEPC) from peripheral blood, and investigate the biological characteristics of composite cell sheets of PBMSC and PBEPC. Methods: The peripheral blood of healthy adult New Zealand white rabbits was extracted and PBMSC and PBEPC were separated by density gradient centrifugation. Morphological observation and identification of PBMSC and PBEPC were performed. The 3rd generation of PBMSC and PBEPC were used to construct a composite cell sheet at a ratio of 1∶1, and the 3rd generation of PBMSC was used to construct a single cell sheet as control. The distributions of cells in two kinds of cell sheets were observed by HE staining. In addition, the expression of alkaline phosphatase (ALP), osteocalcin (OCN), and vascular endothelial growth factor (VEGF) in the supernatants of cell sheets were observed by ELISA at 1, 5, and 10 days after osteogenic induction. Results: The morphology of PBMSC was spindle-shaped or polygonal, and PBMSC had good abilities of osteogenic and adipogenic differentiation. The morphology of PBEPC was paved stone-like, and the tube-forming test of PBEPC was positive. Two kinds of cell sheets were white translucent. The results of HE staining showed that the composite cell sheet had more cell layers and higher cell density than the single cell sheet. The expressions of ALP, OCN, and VEGF in the supernatant of the two groups of cell sheets increased with the time of induction. The expression of OCN in the group of composite cell sheet was significantly higher than that in the group of single cell sheet on the 5th and 10th day, ALP on the 10th day was significantly higher than that in the group of single cell sheet, VEGF expression on the 1st, 5th, and 10th day was significantly higher than that in the group of single cell sheet, all showing significant differences ( P<0.05), and there was no significant difference between the two groups at other time points ( P>0.05). Conclusion: PBMSC have stable differentiation ability, and they have good application prospects because of their minimally invasive access. Composite cell membranes constructed by co-culture of two kinds of cells and induction of membrane formation provides a new idea and exploration for tissue defect repair.

16.
Crit Care Med ; 48(2): e123-e132, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31939811

RESUMEN

OBJECTIVES: Trauma predisposes to systemic sterile inflammation (systemic inflammatory response syndrome) as well as infection, but the mechanisms linking injury to infection are poorly understood. Mitochondrial debris contains formyl peptides. These bind formyl peptide receptor-1, trafficking neutrophils to wounds, initiating systemic inflammatory response syndrome, and wound healing. Bacterial formyl peptides, however, also attract neutrophils via formyl peptide receptor-1. Thus, mitochondrial formyl peptides might suppress neutrophils antimicrobial function. Also, formyl peptide receptor-1 blockade used to mitigate systemic inflammatory response syndrome might predispose to sepsis. We examined how mitochondrial formyl peptides impact neutrophils functions contributing to antimicrobial responses and how formyl peptide receptor-1 antagonists affect those functions. DESIGN: Prospective study of human and murine neutrophils and clinical cohort analysis. SETTING: University research laboratory and level 1 trauma center. PATIENTS: Trauma patients, volunteer controls. ANIMAL SUBJECTS: C57Bl/6, formyl peptide receptor-1, and formyl peptide receptor-2 knockout mice. INTERVENTIONS: Human and murine neutrophils functions were activated with autologous mitochondrial debris, mitochondrial formyl peptides, or bacterial formyl peptides followed by chemokines or leukotrienes. The experiments were repeated using formyl peptide receptor-1 antagonist cyclosporin H, "designer" human formyl peptide receptor-1 antagonists (POL7178 and POL7200), or anti-formyl peptide receptor-1 antibodies. Mouse injury/lung infection model was used to evaluate effect of formyl peptide receptor-1 inhibition. MEASUREMENTS AND MAIN RESULTS: Human neutrophils cytosolic calcium, chemotaxis, reactive oxygen species production, and phagocytosis were studied before and after exposure to mitochondrial debris, mitochondrial formyl peptides, and bacterial formyl peptides. Mitochondrial formyl peptide and bacterial formyl peptides had similar effects on neutrophils. Responses to chemokines and leukotrienes were suppressed by prior exposure to formyl peptides. POL7200 and POL7178 were specific antagonists of human formyl peptide receptor-1 and more effective than cyclosporin H or anti-formyl peptide receptor-1 antibodies. Formyl peptides inhibited mouse neutrophils responses to chemokines only if formyl peptide receptor-1 was present. Formyl peptide receptor-1 blockade did not inhibit neutrophils bacterial phagocytosis or reactive oxygen species production. Cyclosporin H increased bacterial clearance in lungs after injury. CONCLUSIONS: Formyl peptides both activate and desensitize neutrophils. Formyl peptide receptor-1 blockade prevents desensitization, potentially both diminishing systemic inflammatory response syndrome and protecting the host against secondary infection after tissue trauma or primary infection.

17.
Cerebrovasc Dis ; : 1-9, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31940632

RESUMEN

BACKGROUND: Emerging evidence indicates a beneficial effect of mesenchymal stem cell (MSC) transplantation in subarachnoid hemorrhage (SAH). Chronic hydrocephalus is a common complication after SAH, which is associated with subarachnoid fibrosis promoted by transforming growth factor-ß1 (TGF-ß1). This study investigated the effect of human umbilical cord derived MSCs (hUC-MSCs) with TGF-ß1 knockdown on chronic hydrocephalus after SAH. METHODS: About 0.5 mL autologous blood was injected into the cerebellomedullaris cistern of 6-week SD rats to establish SAH model. hUC-MSCs or hUC-MSCs carrying TGF-ß1 knockdown (1 × 105 cells) were intraventricularly transplanted at 1 day before surgery and at P10. Neurological behavior score and water maze test were performed to assess neurological functions. Hydrocephalus was evaluated by Nissl staining. Concentrations of proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. The levels of TGF-ß1, p-Smad2/3, and Smad2/3 were measured using western blotting. RESULTS: Intraventricular hUC-MSCs transplantation significantly attenuated SAH-induced chronic hydrocephalus, upregulation of inflammatory cytokines, and behavioral impairment. Knockdown of TGF-ß1 in hUC-MSCs enhanced these effects. hUC-MSCs also reduced the upregulation of TGF-ß1 levels and Smad2/3 phosphorylation after SAH, and this effect was also enhanced by TGF-ß1 knockdown. CONCLUSION: Transplantation of hUC-MSCs exerts beneficial effect after SAH, possibly be through inhibiting TGF-ß1/Smad2/3 signaling pathway. Knockdown of TGF-ß1 in hUC-MSCs enhanced these effects.

18.
NMR Biomed ; : e4216, 2020 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-31943383

RESUMEN

Spinal cord injuries (SCIs) are a leading cause of disability and can severely impact the quality of life. However, to date, the processes of spontaneous repair of damaged spinal cord remain incompletely understood, partly due to a lack of appropriate longitudinal tracking methods. Noninvasive, multiparametric magnetic resonance imaging (MRI) provides potential biomarkers for the comprehensive evaluation of spontaneous repair after SCI. In this study in rats, a clinically relevant contusion injury was introduced at the lumbar level that impairs both hindlimb motor and sensory functions. Quantitative MRI measurements were acquired at baseline and serially post-SCI for up to 2 wk. The progressions of injury and spontaneous recovery in both white and gray matter were tracked longitudinally using pool-size ratio (PSR) measurements derived from quantitative magnetization transfer (qMT) methods, measurements of water diffusion parameters using diffusion tensor imaging (DTI) and intrasegment functional connectivity derived from resting state functional MRI. Changes in these quantitative imaging measurements were correlated with behavioral readouts. We found (a) a progressive decrease in PSR values within 2 wk post-SCI, indicating a progressive demyelination at the center of the injury that was validated with histological staining, (b) PSR correlated closely with fractional anisotropy and transverse relaxation of free water, but did not show significant correlations with behavioral recovery, and (c) preliminary evidence that SCI induced a decrease in functional connectivity between dorsal horns below the injury site at 24 h. Findings from this study not only confirm the value of qMT and DTI methods for assessing the myelination state of injured spinal cord but indicate that they may also have further implications on whether therapies targeted towards remyelination may be appropriate. Additionally, a better understanding of changes after SCI provides valuable information to guide and assess interventions.

19.
Circulation ; 2020 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-31910649

RESUMEN

Background: Cardiac magnetic resonance (CMR) is a recommended imaging test for patients with heart failure (HF), however there is a lack of evidence showing incremental benefit over transthoracic echocardiography. Hypothesis: Routine use of CMR will yield more specific diagnoses in non-ischemic HF. Secondary hypothesis: Routine use of CMR will improve patient outcomes. Methods: Patients with non-ischemic HF were randomized to Routine versus Selective CMR. Patients in the Routine strategy underwent echo and CMR whereas those assigned to Selective use underwent echo with or without CMR according to the clinical presentation. HF etiology was classified from the imaging data as well as by the treating physician at 3 months (primary outcome). Clinical events were collected for 12 months. Results: 500 patients (344 male), mean age 59±13, were randomized. The Routine and Selective CMR strategies had similar rates of specific HF etiologies at 3 months clinical follow-up, 44% vs. 50% respectively, p=0.22. At image interpretation, rates of specific HF etiology were also not different between Routine and Selective CMR, 34% vs. 30% respectively, p=0.34. However, 24% of patients in the Selective group underwent a non-protocol CMR. Patients with specific HF etiologies had more clinical events than those with non-specific etiologies based on imaging classification, 19% vs. 12% respectively, p=0.02, but not on clinical assessment, 15% vs. 14%, p=0.49. Conclusions: In patients with non-ischemic HF, Routine CMR does not yield more specific HF etiologies on clinical assessment. Patients with specific HF etiologies from imaging had worse outcomes whereas HF etiologies defined clinically did not. Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique Identifier: NCT01281384.

20.
Eur J Med Genet ; : 103855, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31972369

RESUMEN

We report a genetic assessment of autosomal dominant, nonsyndromic, progressive sensorineural hearing loss in a Chinese family, combining whole-exome sequencing and genome-wide linkage analysis. A novel missense mutation, c.626G > C, in the SCD5 gene was identified in this family. The heterozygous missense mutation could segregate hearing loss cases among family members, and was predicted to be deleterious by Polyphen-2, LRT and Mutation Taster. SCD5 is an endoplasmic reticulum enzyme, catalyzing the formation of monounsaturated fatty acids (MUFAs) from saturated fatty acids (SFAs). It plays a crucial role in regulating lipid metabolism. The SCD5 protein is expressed in inner and outer hair cells of the organ of Corti, the stria vascularis, cells of the lateral cochlear wall behind the spiral prominence, and more strongly in spiral ganglion cells of guinea pig and human fetal cochleas. SCD5 protein was also expressed in the brain, consistent with the hearing loss feature: the patients had a poor speech discrimination score at young age and mild hearing loss as evaluated by pure tone audiometry. In summary, we identified SCD5 as a novel gene responsible for autosomal dominant nonsyndromic deafness.

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