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2.
J Mater Chem B ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31589215

RESUMO

Hypertrophic scarring is a widespread skin disorder that affects a patient's confidence and quality of life. Intralesional injection of bleomycin is one of the most commonly employed treatments for hypertrophic scars, which, however, always brings pain and requires long-term treatment. To overcome these limitations, new methods for bleomycin delivery enabling painlessness, self-administration, the fast onset of action, and good bioavailability are urgently needed. In this study, we developed bleomycin-loaded dissolving microneedles (BMN) made up of hyaluronic acid (HA) with excellent aqueous solubility and enhanced efficacy for inhibiting hypertrophic scars. The as-obtained BMN possesses sufficient mechanical strength to pierce porcine skin ex vivo with an insertion depth of over 300 µm. Moreover, BMN can dissolve rapidly and release 20% of loaded bleomycin within 1 min and 52% within 10 min, and the BMN-treated skin could recover to its original status within 3 h, demonstrating good biocompatibility. Besides, the HA matrix also maintains the stability and activity of bleomycin. Furthermore, we show that BMN consisting of HA and bleomycin can inhibit the proliferation of human hypertrophic scar fibroblasts (hHSFs) and the secretion of transforming growth factor-ß (TGF-ß1) in vitro. Therefore, bleomycin-loaded dissolving HA microneedles provide a potential route to treat hypertrophic scars in a convenient, efficient, and minimally invasive manner.

3.
Medicine (Baltimore) ; 98(39): e17354, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574878

RESUMO

INTRODUCTION: The incidence, mortality, and treatment costs of sepsis are high and, thus, present a major challenge for critical care medicine. Our previous studies suggest that intestinal metabolite granisetron has a potential therapeutic effect on sepsis. Granisetron is a clinically widely used antiemetic, which is safe, inexpensive, and reliable. However, its value in the treatment of sepsis remains unclear. This study aims to explore the efficacy and safety of granisetron in the treatment of sepsis. METHODS AND ANALYSIS: A single-center, single-blind, randomized, controlled clinical trial will be conducted on 154 patients with sepsis. Patients who meet sepsis 3.0 diagnostic criteria, aged ≥18 and ≤80 years, with PCT ≥ 2 ng/mL will be recruited. Patients will be randomized to receive intravenous granisetron 3 mg every 8 hours (n = 77) or an equal volume of normal saline (n = 77) for a treatment period of 4 days or to ICU discharge. The primary outcome is 28-day all-cause mortality. Secondary outcome measures include requirements for organ function support, changes of organ function, changes in infection biomarkers, changes in inflammatory and immune biomarkers, and the proportion of new organ failure. Adverse events and serious adverse events also will be observed closely. ETHICS AND DISSEMINATION: The study was approved by the Clinical Ethics Committee of Zhujiang Hospital of Southern Medical University (2018-ZZJHZX-009). The trial results will be disseminated at national and international conferences and through peer-reviewed journal. TRIAL REGISTRATION: NCT03924518.URL: www.clinicaltrials.gov. PROTOCOL DATE: 1 May 2019. version 2.1.


Assuntos
Granisetron/administração & dosagem , Sepse/tratamento farmacológico , Antagonistas da Serotonina/administração & dosagem , Choque Séptico/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/mortalidade , Choque Séptico/mortalidade , Método Simples-Cego , Resultado do Tratamento , Adulto Jovem
4.
Oncogene ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501523

RESUMO

TRIM family proteins are defined as E3 ubiquitin ligases because of their RING-finger domains. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) encodes a 15-kDa protein, that is implicated in the posttranslational modification of diverse proteins. Both TRIM29 and ISG15 play both pro-tumoral and anti-tumoral functions in cancer cells derived from different histology. In the current study, we demonstrated that correlation expression of TRIM29 and ISG15 in pancreatic ductal adenocarcinomas (PDACs). The current study demonstrated that TRIM29 knockdown destabilized ISG15 protein via promoting its processing by calpain 3 (CAPN3). Importantly, the current study found that TRIM29 knockdown suppressed cancer stem cell-like features of PDACs, which can be rescued by ISG15 independent of its conjugation function. In addition, the current study demonstrated that extracellular free ISG15 played an important role in maintenance of cancer stem cell-like features of PDACs. Thereby, the current study displayed a novel mechanism by which TRIM29 modulates ISG15 stability via CAPN3-mediated processing, and subsequently extracellular ISG15 maintains the cancer stem cell-like features of PDAC via autocrine mode of action.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31520808

RESUMO

OBJECTIVES: The rapid spread of Klebsiella spp. is recognized as a major threat to public health owing to a rise in the number of both healthcare- and community acquired infections. Here we report the draft genome sequence of a high carbapenem-resistant strain Klebsiella quasipneumoniae subsp. quasipneumoniae Cln185 isolated from an HIV patient with pneumonia. METHODS: Classical microbiological methods were applied to isolate and identify the strain, genomic DNA was sequenced using an Illumina HiSeq platform and the reads were de novo assembled into contigs using CLC Genomics Workbench. The assembled contigs was annotated and whole genome sequencing (WGS) analysis was performed. RESULTS: WGS analysis revealed the genome comprised a circular chromosome of 5,406,774 bp with a G-C content of 57.73 %. Three important antibiotic resistance genes, IMP-38, OKP-B-6, and DHA-1, were detected. In addition, genes conferring resistance to aminoglycosides, macrolides, sulfonamide, fluoroquinolones, and tetracycline were also identified. CONCLUSION: The draft genome sequence reported herein will lay the foundation for future research for antibiotic resistance mechanisms and pathogenic mechanisms in Klebsiella quasipneumoniae subsp. quasipneumoniae, and also will promote the comparative analysis with genomic features among different sources of clinically important multidrug resistance strains.

6.
Sci Rep ; 9(1): 13007, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506476

RESUMO

Diploid strawberry (Fragaria vesca 'Baiguo') is a model plant for studying functional genomics in Rosaceae. Adventitious shoot regeneration is essential for functional genomics by Agrobacterium tumefaciens-mediated transformation. An efficient shoot regeneration method using diploid strawberry leaf explants was conducted on 1/2MS + 1/2B5 medium that contained 2.0 mg L-1 TDZ over 14 days of dark culture; this induced the maximum percentage of shoot regeneration (96.44 ± 1.60%) and the highest number of shoots per explant (23.46 ± 2.14) after 11 weeks of culture. The explants considerably enlarged after 12 days; then, turned greenish brown after 30 days, yellowish brown after 36 days, and completely brown and necrotic after 48 days. Large numbers of adventitious shoots were produced from 48 to 66 days, and the shoots elongated from 66 to 78 days; this represents a critical period of reinvigoration, which included 30 days for leaf explant chlorosis, 36 days for adventitious shoot appearance, and 48 days for generation of numerous shoots. During the reinvigoration process, higher expressions of the hormone synthesis-related genes Ciszog1, CKX2, CKX3, CKX7, YUC2, YUC6, YUC10, YUC9, and GA2ox were detected from 30 to 48 days. Our results indicate that these genes may regulate reinvigoration of shoot regeneration.

7.
Hum Mutat ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489982

RESUMO

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene variant. We aimed to provide the characteristics of G6PD deficiency and G6PD gene variant distribution in a large Chinese newborn screening population. We investigated the prevalence of G6PD in China from 2013 to 2017. Then, we examined G6PD activity and G6PD gene in representative Chinese birth cohort to explore the distribution of G6PD gene variant in 2016. We then performed multicolor melting curve analysis to classify G6PD gene variants in 10,357 neonates with activity-confirmed G6PD deficiency, and DNA Sanger sequencing for G6PD coding exons if hot site variants were not found. The screened population, organizations, and provinces of G6PD deficiency were increased from 2013 to 2017 in China. The top five frequency of G6PD gene variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, and c.871G>A and varied in different provinces, with regional and ethnic features, and four pathogenic variant sites (c.152C>T, c.290A>T, c.697G>C, and c.1285A>G) were first reported. G6PD deficiency mainly occurs in South China, and the frequency of G6PD gene variant varies in different regions and ethnicities.

8.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(10): 1234-1238, 2019 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-31544431

RESUMO

Objective: To investigate the association between the tip apex distance (TAD) and migration of helical blade in the femoral head of geriatric intertrochanteric fractures. Methods: A retrospective study of intertrochanteric fractures treated with the proximal femoral nail antirotation (PFNA) between June 2015 and June 2018 was performed. There were 32 males and 55 females with an average age of 84.7 years (range, 80-101 years). All of them were unilateral fresh closed intertrochanteric fractures caused by low energy injury. According to AO/Orthopaedic Trauma Association (AO/OTA) classification, 33 cases belonged to type 31-A1, 35 cases to type 31-A2, and 19 cases to type 31-A3. The time interval from injury to operation was 1-16 days (mean, 3.7 days). The TAD was measured according to immediate postoperative X-ray films. The cases were divided into two groups: group A with TAD less than 20 mm and group B with TAD greater than 20 mm. The difference of fracture healing and migration of helical blade between the two groups were observed. Results: According to the TAD value immediately after operation, 49 patients in group A had TAD of 8.9-19.7 mm, with an average of 18.6 mm; 38 patients in group B had TAD of 20.1-41.4 mm, with an average of 27.7 mm. The 87 patients were followed up for an average of 11.7 months, ranging from 4 to 28 months. Three cases (all in group B) underwent screw blade cutting and displacement, which resulted in internal fixation failure, including 1 case with femoral head cut upward and 2 cases with femoral head penetrated inward. The remaining 84 cases had bone healing without internal fixation related complications such as fracture of internal fixator and fracture of femoral shaft. There was significant difference in the incidence of internal fixation failure between group A and group B ( P=0.049). Conclusion: Reducing the TAD value of helical blade appropriately (15-20 mm) in PFNA internal fixation for intertrochanteric fracture patients over 80 years old can increase initial stability without increasing the risk of helical blade migration.

9.
Aging Clin Exp Res ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471892

RESUMO

BACKGROUND: Postoperative delirium is common in older patients after spinal surgery. Many reports investigating the risk factors for delirium after spinal surgery have been published recently. METHODS: A literature search was performed using the Cochrane Library, Web of Science, PubMed, Embase, and Springer databases from inception to February 2019. Relevant studies involving patients with delirium who underwent spinal surgery were included if the studies contained data about blood transfusion or other related factors, such as haemoglobin, haematocrit, and blood loss levels. The Newcastle-Ottawa Scale was used for the study-quality evaluation. The pooled odds ratios or (standard) mean differences of the individual risk factors were estimated using the Mantel-Haenszel or inverse-variance methods. RESULTS: Fifteen observational studies met the inclusion criteria; the studies included a total of 583,290 patients (5431 patients with delirium and 577,859 patients without delirium). In addition to an advanced age, the results of the meta-analyses showed that living in an institution, diabetes, cerebral vascular diseases, pulmonary diseases, opioid use, length of surgery, intraoperative blood loss, blood transfusions, intraoperative infusion, preoperative albumin, postoperative albumin, preoperative haematocrit, postoperative haematocrit, preoperative haemoglobin, postoperative haemoglobin, preoperative sodium, postoperative sodium, Mini-Mental State Examination score, inability to ambulate, depression, number of medications, and treatment with multiple drugs (> three types) were significantly associated with delirium. CONCLUSION: The above-mentioned risk factors can be used to identify high-risk patients, and the appropriate prophylaxis strategies should be implemented to prevent delirium after spinal surgery.

10.
Sci Signal ; 12(600)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551295

RESUMO

Although brain-derived neurotrophic factor (BDNF) is implicated in the nociceptive signaling of peripheral sensory neurons, the underlying mechanisms remain largely unknown. Here, we elucidated the effects of BDNF on the neuronal excitability of trigeminal ganglion (TG) neurons and the pain sensitivity of rats mediated by T-type Ca2+ channels. BDNF reversibly and dose-dependently enhanced T-type channel currents through the activation of tropomyosin receptor kinase B (TrkB). Antagonism of phosphatidylinositol 3-kinase (PI3K) but not of its downstream target, the kinase AKT, abolished the BDNF-induced T-type channel response. BDNF application activated p38 mitogen-activated protein kinase (MAPK), and this effect was prevented by inhibition of PI3K but not of protein kinase A (PKA). Antagonism of either PI3K or p38 MAPK prevented the BDNF-induced stimulation of PKA activity, whereas PKA inhibition blocked the BDNF-mediated increase in T-type currents. BDNF increased the rate of action potential firing in TG neurons and enhanced the pain sensitivity of rats to mechanical stimuli. Moreover, inhibition of TrkB signaling abolished the increased mechanical sensitivity in a rat model of chronic inflammatory pain, and this effect was attenuated by either T-type channel blockade or knockdown of the channel Cav3.2. Together, our findings indicate that BDNF enhances T-type currents through the stimulation of TrkB coupled to PI3K-p38-PKA signaling, thereby inducing neuronal hyperexcitability of TG neurons and pain hypersensitivity in rats.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31553048

RESUMO

BACKGROUND: To assess the associations between family characteristics and influenza vaccination coverage among children. METHODS: Data were used from the National Health Interview Survey 2011-2016. RESULTS: The number of children ranged from 10 720 to 12 991 per year from 2011 to 2016. After adjustment for the high-risk status of influenza complications, sex, age, region, race and office visits of children, children of adults who received influenza vaccination were 3.83-4.79 times (the lowest and the highest odds ratios from 2011 to 2016) more likely to be immunized for influenza. Health insurance (1.36-1.61) was also associated with vaccination in children. However, the education level of family adults (0.59-0.79) and marital status of being widowed/divorced/separated (0.74-0.79) were negatively associated with vaccination uptake in children. The following characteristics were not major concerns with influenza vaccination in children: class of worker, years on the job, physical activity, drinking, smoking, hepatitis B immunization, number of family members aged ≥65 years and the ratio of family income to the poverty threshold. Overall, results from the pooled analysis (2011-2016) were consistent with the above-mentioned findings. CONCLUSIONS: Promoting parental influenza immunization and access to health insurance may be the most effective tools to promote the coverage of influenza vaccine among children.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31562937

RESUMO

BACKGROUND & AIMS: Toll-like receptor 2 (TLR2) and TLR3 regulate hepatic immunity under pathological conditions, but their functions and potential drug targets in alcoholic liver disease (ALD) remain poorly understood. METHODS: ALD-associated liver injury were induced in TLR2 knockout (TLR2-/-), TLR3-/-, TLR2-/- bone marrow transplanted (BMT), TLR3-/- BMT, IL-10-/- mice, and their wild-type littermates through ethanol challenge with or without co-administered epigallocatechin-3-gallate (EGCG). Moreover, Kupffer cells were depleted by GdCl3 injection to evaluate their pathogenic roles in ALD. RESULTS: We identified that deficiency of TLR2 and TLR3 significantly alleviated and aggravated ALD-induced liver injury, respectively. Mechanistically, Kupffer cell inactivation, M1 to M2 polarization, and IL-10 production via STAT3 activation contributed to hepatic protection mediated by concurrent TLR2 inhibition and TLR3 agonism. These findings were further confirmed in TLR2 and TLR3 BMT mice. We also identified a novel ALD-protective agent EGCG which directly interacted with Kupffer cell TLR2/3 to induce IL-10 production. Deficiency of IL-10 aggravated ALD injury and blunted EGCG-mediated hepatoprotection while depletion of Kupffer cells partially recovered liver injury but abolished EGCG's actions. CONCLUSIONS: Altogether, our results illustrate the divergent roles of Kupffer cells TLR2/3 in ALD progression via anti-inflammatory cytokine IL-10 production.

15.
Biosens Bioelectron ; 144: 111626, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31494510

RESUMO

Intracellular action potential signals reveal enriched physiological information. Patch clamp techniques have been widely used to measure intracellular potential. Despite their high signal fidelity, they suffer from low throughput. Recently, 3D nanoelectrodes have been developed for intracellular potential recording. However, they are limited by scalability, yield, and cost, directly constraining their use in monitoring large number of cells and high throughput applications. In this paper, we demonstrate intracellular potential monitoring of cardiomyocytes using simple 2D planar electrode array in a standard CMOS process without patch clamps or post fabricated 3D nanoelectrodes. This is enabled by our unique cardiomyocytes/fibroblasts co-culturing technique and electroporation. The co-cultured fibroblasts promote tight sealing of cardiomyocytes on electrodes and enable high-fidelity intracellular potential monitoring based on 2D planar electrode. Compared to existing technologies, our platform has a unique potential to achieve an unprecedented combination of throughput, spatiotemporal resolution, and a tissue-level field-of-view for cellular electrophysiology monitoring.

16.
J Basic Microbiol ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549433

RESUMO

Oenococcus oeni is the main bacteria extensively used in malolactic fermentation due to its high tolerance against stress factors in wine production. Among these, ethanol is one of the main challenges to O. oeni, and its ethanol tolerance mechanism remains unclear. In this study, the puuE gene related to ethanol tolerance from O. oeni SD-2a was heterologously expressed in Lactobacillus plantarum WCFS1. Results showed that the recombinant strain (W-pMG36epuuE) exhibited better growth performance and survival rate compared to the control strain (W-pMG36e) under ethanol-stress conditions. In addition, it was found that the activities of superoxide dismutase and the concentration of glutathione of W-pMG36epuuE were significantly higher than those of W-pMG36e. This resulted in the decrease of intracellular reactive oxygen species (ROS) accumulation (10.34% lower than control). Moreover, heterologous expression of puuE in WCFS1 exhibited improved activities of two ATPases in membrane, increasing the cell membrane integrity (37.67% higher than control). These results revealed the role of the puuE gene in improving ethanol tolerance in O. oeni by decreasing ROS accumulation and enhancing cell membrane integrity.

17.
PLoS Genet ; 15(9): e1008368, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31518356

RESUMO

Telomere shortening is associated with aging and age-associated diseases. Additionally, telomere dysfunction resulting from telomerase gene mutation can lead to premature aging, such as apparent skin atrophy and hair loss. However, the molecular signaling linking telomere dysfunction to skin atrophy remains elusive. Here we show that dysfunctional telomere disrupts BMP/pSmad/P63 signaling, impairing epidermal stem cell specification and differentiation of skin and hair follicles. We find that telomere shortening mediated by Terc loss up-regulates Follistatin (Fst), inhibiting pSmad signaling and down-regulating P63 and epidermal keratins in an ESC differentiation model as well as in adult development of telomere-shortened mice. Mechanistically, short telomeres disrupt PRC2/H3K27me3-mediated repression of Fst. Our findings reveal that skin atrophy due to telomere dysfunction is caused by a previously unappreciated link with Fst and BMP signaling that could be explored in the development of therapies.

18.
Nanoscale ; 11(37): 17401-17406, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31528930

RESUMO

A highly selective and sensitive electroanalysis strategy has been developed for sensing histamine (HTA) and histidine (His) with "turn-on" signal outputs using copper nanocomposites (Cu NCs) of reduced copper metal-organic frameworks (Cu MOFs). It was discovered that the Cu NC-modified electrodes could display the sharp and stable oxidation peaks of solid-state CuCl electrochemistry at a low potential (about -0.10 V). More interestingly, once HTA or His was introduced, the peaking currents of the electrodes would increase due to the specific interaction between Cu2+ and imidazole groups of HTA or His. A highly selective electroanalysis method was thereby developed for the detection of both HTA and His in the concentration range of 0.010-100 µM. Besides, the application feasibility of the developed electroanalysis strategy was demonstrated for the evaluation of HTA and His separately in red wine and urine samples. Such an electroanalysis candidate for HTA and His holds great potential for wide applications in the fields of food analysis and clinical disease diagnosis.

19.
Chem Commun (Camb) ; 55(80): 12008-12011, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31532419

RESUMO

Mussel-inspired enhancement of Fe3O4 catalysis was discovered towards a highly selective and sensitive colorimetric strategy for the magnetic separation-based evaluation of dopamine and/or levodopa in urine, in which the specific interaction of bis-catechol-containing analytes and mesoporous Fe3O4 NPs would form highly stable complexes of bis-catechol-Fe coordination.

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