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1.
J Endocrinol ; 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32031966

RESUMO

Over a half of the diabetic individuals develop macrovascular complications that cause high mortality. Oxidative stress (OS) promotes endothelial dysfunction (ED) which is a critical early step toward diabetic macrovascular complications. Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular antioxidant defense system and combats diabetes-induced OS. Previously, we found that impaired NRF2 antioxidant signaling contributed to diabetes-induced endothelial OS and dysfunction in mice. The present study has investigated the effect of microRNA-200a (miR-200a) on NRF2 signaling and diabetic ED. In aortic endothelial cells (ECs) isolated from C57BL/6 wild-type (WT) mice, high glucose (HG) reduced miR-200a level and increased the expression of kelch-like ECH-associated protein 1 (Keap1) - a target of miR-200a and a negative regulator of NRF2. This led to inactivation of NRF2 signaling and exacerbation of OS and inflammation. MiR-200a mimic (miR-200a-M) or inhibitor modulated KEAP1/NRF2 antioxidant signaling and manipulated OS and inflammation under HG condition. These effects were completely abolished by knockdown of Keap1, indicating that Keap1 mRNA is a major target of miR-200a. Moreover, the protective effect of miR-200a-M was completely abrogated in aortic ECs isolated from C57BL/6 Nrf2 knockout (KO) mice, demonstrating that NRF2 is required for miR-200a's actions. In vivo, miR-200a-M inhibited aortic Keap1 expression, activated NRF2 signaling, and attenuated hyperglycemia-induced OS, inflammation and ED in the WT, but not Nrf2 KO, mice. Therefore, the present study has uncovered a miR-200a/KEAP1/NRF2 signaling that controls aortic endothelial antioxidant capacity that protects against diabetic ED.

2.
Genomics ; 112(3): 2550-2563, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32057915

RESUMO

P-type ATPases are integral membrane transporters that play important roles in transmembrane transport in plants. However, a comprehensive analysis of the P-type ATPase gene family has not been conducted in Chinese white pear (Pyrus bretschneideri) or other Rosaceae species. Here, we identified 419 P-type ATPase genes from seven Rosaceae species (Pyrus bretschneideri, Malus domestica, Prunus persica, Fragaria vesca, Prunus mume, Pyrus communis and Pyrus betulifolia). Structural and phylogenetic analyses revealed that P-type ATPase genes can be divided into five subfamilies. Different subfamilies have different conserved motifs and cis-acting elements, which may lead to functional divergence within one gene family. Dispersed duplication and whole-genome duplication may play critical roles in the expansion of the P-type ATPase family. Purifying selection was the primary force driving the evolution of P-type ATPase family genes. Based on the dynamic transcriptome analysis and transient transformation of Chinese white pear fruit, Pbr029767.1 in the P3A subfamily were found to be associated with malate accumulation during pear fruit development. Using a co-expression network, we identified several transcription factors that may have regulatory relationships with the P-type ATPase gene family. Overall, this study lays a solid foundation for understanding the evolution and functions of P-type ATPase genes in Chinese white pear and six other Rosaceae species.

3.
Diabetes Ther ; 11(3): 633-642, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31955370

RESUMO

INTRODUCTION: The aim of our study was to determine the effect of metformin administration on juvenile type 1 diabetes mellitus and atherosclerosis in apolipoprotein E null (ApoE-/-) mice and to explore the mechanism involved. METHODS: Eighteen male ApoE-/- mice were injected with streptozotocin to induce diabetes (diabetic group) and 18 mice who received no streptozotocin injection were assigned to the control (non-diabetic) group. Six mice in each group were then orally administered metformin, simvastatin, or vehicle, respectively, following which the mice were euthanized and tissue samples collected. RESULTS: Fasting plasma glucose, low-density lipoprotein-cholesterol, and triglyceride concentrations were significantly higher in the three diabetic groups than in the three non-diabetic groups. Plasma N∈-(carboxymethyl)lysine and N∈-(carboxyethyl)lysine concentrations were higher in the diabetic mice than in the non-diabetic mice, but metformin treatment reduced these concentrations more effectively than simvastatin. All three diabetic groups demonstrated obvious arterial plaques, but these were largest in the vehicle-treated diabetic group. The expression of extracellular nitric oxide synthase was highest in the simvastatin-treated non-diabetic group, and in diabetic mice it was higher in the simvastatin-treated group than in the other two groups. No significant expression of AMP-activated protein kinase (AMPK) was measured in the three diabetic groups, but a low level of AMPK expression was detected in the non-diabetic groups. CONCLUSIONS: Metformin can limit the development of atherosclerosis secondary to diabetes in young diabetic mice. A possible mechanism is the removal of methylglyoxal, thereby reducing the formation of advanced glycation endproducts, rather than by lowering the blood glucose level. FUNDING: This work was supported by the National Natural Science Foundation of China (81901106) and Jinan clinical medical science and technology innovation plan (201907002).

4.
Talanta ; 209: 120535, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892060

RESUMO

The integration of highly-purity, dense and monodisperse plasmonic nanoparticles (NPs) on two-dimensional (2D) graphene-like support possesses great potential for optimizing surface-enhanced Raman spectroscopy (SERS). Based on ultraviolet (UV) laser-induced modified photochemical reaction, we report an ingenious and green strategy to support highly dispersed Au NPs with controllable distribution on graphene oxide (GO). Without using any stabilizing agents or other complex chemical additives, the GO with abundant oxygen-containing functional groups can be effectively excited by 375 nm laser irradiation in HAuCl4 solution, resulting in controlled reduction of Au ions and then overgrowth of highly-purity Au NPs. Highly dense and monodisperse Au NPs with uniform diameter of ~20 nm formed on GO supports can be achieved by 30 min irradiation, which can offer maximized SERS activity in comparison with GO/Au NPs obtained by other irradiation times. The optimized GO/Au NPs give rise to ultralow SERS analyses of (10-14 M) methylene blue (MB), (10-13 M) rhodamine 6G (R6G) and (10-13 M) malachite green (MG), respectively. More importantly, it can also simultaneously analyze these three aromatic dyes in a mixture condition at detection limits as low as nano-mole level (10-9-10-11 M), achieving the urgent requirement of mutually independent SERS trace detection. Therefore, the obtained GO/Au NPs with extremely high SERS activity and superior spectroscopic identification will be a prominent candidate for widespread SERS applications in real-word scenarios.

5.
Drug Dev Res ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904877

RESUMO

Tuberculosis (TB), a chronic infectious disease, is one of the greatest risks to human beings and 10 million people were diagnosed with TB and 1.6 million died from this disease in 2017. In addition, with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the TB situation has become even worse, which has aggravated the mortality and spread of this disease. To overcome this problem, research into novel antituberculosis agents with enhanced activities against MDR-TB, reduced toxicity, and shortened duration of therapy is of great importance. Fortunately, many novel potential anti-TB drug candidates with five-membered rings, which are most likely to be effective against sensitive and resistant strains, have recently entered clinical trials. Different five-membered rings such as furans, pyranoses, thiazoles, pyrazolines, imidazoles, oxazolidinone, thiazolidins, isoxazoles, triazoles, oxadiazoles, thiadiazoles, and tetrazoles have been designed, prepared, and evaluated for their antimycobacterial activity against Mycobacterium tuberculosis. In this article, we highlight the recent advances made in the discovery of novel five-membered ring compounds and focus on their antitubercular activities, toxicity, structure-activity relationships, and mechanisms of action.

6.
Gene ; 726: 144226, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669644

RESUMO

Hereditary spherocytosis is a congenital red blood cell disorder. Typical clinical manifestations include anemia, jaundice and splenomegaly, which overlap with the thalassemia phenotype. Therefore, in high prevalence thalassemia regions, hereditary spherocytosis cases are often misdiagnosed. Here, a case once diagnosed as thalassemia, based on preliminary clinical examinations, underwent genetic testing in our laboratory, where analysis of globin gene mutations proved negative. We conducted both clinical and genetic analyses on the patient and his family. We collected clinical data, performed erythrocyte membrane protein analysis by SDS-PAGE and sequenced the ANK1 gene. We also investigated pathogenic mechanisms through cDNA sequencing and literature studies. From patient clinical data, we diagnosed the patient with moderate to severe hereditary spherocytosis, rather than thalassemia. SDS-PAGE data showed that Ankyrin protein expression was reduced. Sequencing of genomic DNA identified a frameshift mutation (ANK1:c.2394_2397del CAGT). cDNA sequencing showed that the expression of a mutant allele was significantly decreased. Our study corrected a clinical misdiagnosis and confirmed the diagnosis of hereditary spherocytosis in this patient. Identification of such causative mutations is important for accurate downstream patient therapy and is critically important for the prevention/detection of another affected birth. Additionally, the disruption of mRNA transcribed from the mutant allele resulted in a significant reduction in Ankyrin expression and was speculatively considered the pathogenic mechanism behind this mutation.


Assuntos
Anquirinas/genética , Nucleotídeos/genética , Deleção de Sequência/genética , Esferocitose Hereditária/diagnóstico , Esferocitose Hereditária/genética , Alelos , Criança , Erros de Diagnóstico , Mutação da Fase de Leitura/genética , Humanos , Masculino , Mutação/genética , Fenótipo , RNA Mensageiro/genética , Talassemia/genética
7.
Bioorg Chem ; 94: 103475, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791683

RESUMO

Two series of novel 4″-O-aralkylacetylhydrazineacyl azithromycin derivatives were synthesized and evaluated for their in vitro antibacterial activities. Among them, compound B4, B5, B13 and B18 were found to display significantly improved activity than control drugs (MIC > 128 µg/mL) against methicillin-resistant strain S. aureus ATCC 43,300 with an MIC value 2-4 µg/mL. Remarkably, compound B5 and B13 showed potent activity against penicillin-resistant S. aureus ATCC31007 (MIC = 4 µg/mL) and methicillin-resistant S. aureus ATCC 43,300 (MIC = 2 µg/mL).

8.
Clin Exp Pharmacol Physiol ; 47(4): 599-608, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31821581

RESUMO

Diabetic nephropathy (DN) is the major microvascular complication of diabetes mellitus and the most important cause of end-stage renal disease worldwide. Metformin is the preferred oral hypoglycaemic drug for type 2 diabetes mellitus (T2DM). Recent studies have shown that besides lowering blood glucose, metformin also has protective effects on renal function, but its mechanism is not clear. In this study, we established a diabetic rat model by high-fat feeding combined with intraperitoneal injection of streptozotocin. Their changes of renal function, oxidative stress, histopathology and structure, and autophagy were observed after 8 weeks of metformin treatment at different dose. Sirt1 inhibitor EX527 and metformin were used to observe whether the protective effect of metformin on DN kidney was achieved through the Sirt1/FoxO1 autophagic signalling pathway. The results showed that metformin could protect renal function by up-regulating autophagy level, alleviating oxidative stress level of renal tissue and pathological and structural changes of glomeruli, and inhibiting the expression of extracellular matrix. Sirt1 inhibitor could block the protective effect of metformin on kidney of diabetic rats, suggesting that metformin could alleviate kidney injury in diabetic rats by inducing Sirt1/FoxO1 autophagy signal axis. So metformin could alleviate renal injury in diabetic rats, which may be achieved by regulating Sirt1/FoxO1 autophagic signalling pathway and inducing renal autophagy.

9.
Int J Biol Macromol ; 143: 602-609, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31837362

RESUMO

We report the inclusion of cyclolipopeptides (CL) from Bacillus subtilis in the production of an easily removed alginate coating for the preservation of vulnerable berries. The sodium alginate-CL (SA-CL) coating films exhibited potent antifungal and freshness-maintaining properties during the storage of blueberries, the 3% CL-added film decreased total fungal count to 2.5 × 103 cfu/g at the end of the storage. The SA-CL films had poor mechanical properties (i.e., tensile strength and elongation at break), low water vapor permeability and high water solubility. The addition of CL (3%) decreased the tensile strength and elongation at break of the SA-CL film to 0.37 mPa and 2.57%, respectively, and increased the water solubility to 28.92%. But the water vapor permeability of the 3% film was lowered to 398.10 g/m2/day. These results implied the film was suitable for the coating of vulnerable berries. Further research revealed that ionic and hydrogen bonding interactions between CL and alginate stabilized the network of the coating film while the fatty acid moiety weakened the strength and crystallinity and restricted the water transfer of the coating film. Our findings provide an effective route to an easily washed alginate coating film through inclusion of amphiphilic antifungal substances.

10.
J Musculoskelet Neuronal Interact ; 19(4): 516-520, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31789303

RESUMO

OBJECTIVE: To study the effect of comprehensive nursing based on the concept of feedforward control on postoperative FMA (Fugl-Meyer Assessment) and SF-36 (health status questionnaire) in patients with femoral trochanteric fracture. METHODS: 114 patients with femoral intertrochanteric fracture were enrolled in the study. Patients were divided into control group and observation group according to order of admission, 57 cases in each group. Both groups of patients received proximal femoral nail antirotation surgery, conventional nursing and feedforward control based comprehensive nursing. Nursing effects of the two groups of patients were compared. RESULTS: Anus first exhaust time, the time of getting out of bed and hospitalization time, and after nursing, SAS (Self-Rating Anxiety) and SDS (Self-Rating Depression) score of the observation group were significantly lower than those of the control group (p<0.05). FMA and SF-36 score of the observation group after surgical nursing were significantly higher than those of the control group (p<0.05). The total incidence of complications in the observation group was lower than that in the control group (p<0.05). CONCLUSIONS: Comprehensive care based on the concept of feedforward control has a better nursing effect for patients with intertrochanteric fracture, which can shorten the time of patient getting out of bed and hospitalization and reduce the incidence of post-complications.

11.
Emerg Microbes Infect ; 8(1): 1574-1583, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31682177

RESUMO

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has become an important re-emerging pathogen with its rapid spread to many non-endemic areas. The lack of effective vaccines and antiviral agents is largely attributed to the elusive infection and dissemination dynamics in vivo. In this study, we designed and developed a novel, replication-competent, CHIKV reporter virus (CHIKV-iRFP) encoding a near infrared fluorescent protein (iRFP). In vitro and in vivo characterization demonstrated that CHIKV-iRFP retained similar replication and virulence phenotypes to its parental virus. Neonatal BABL/c mice and IFNAR-/- A129 mice were highly susceptible to CHIKV-iRFP infection. Following intracranial (i.c.) inoculation, CHIKV-iRFP efficiently replicated and disseminated into whole body, resulting in rapid death in an age-dependent manner. Remarkably, upon footpad injection, CHIKV-iRFP readily disseminated from footpad to head and whole skeleton, with a specific tropism for bone marrow. Taken together, this novel reporter virus provides a powerful tool to track real time CHIKV replication and to test the in vivo efficacy of vaccines and antiviral therapeutics.


Assuntos
Febre de Chikungunya/virologia , Vírus Chikungunya/fisiologia , Animais , Vírus Chikungunya/genética , Vírus Chikungunya/patogenicidade , Feminino , Fluorescência , Genes Reporter , Humanos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Virulência , Replicação Viral
12.
Opt Express ; 27(20): A1601-A1614, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684591

RESUMO

Optical polarization characteristics and light extraction behavior of deep-ultraviolet (DUV) light-emitting diode (LED) flip-chip with full-spatial omnidirectional reflector (FSODR) have been investigated. FSODR is fabricated to be simultaneously covered on the whole flip-chip, except the sapphire surface. It is found that the FSODR greatly enhance both transverse-electric (TE) and transverse-magnetic (TM) mode light extraction at every space angle, resulting in total enhancement of 73.1% and 79.8%, respectively. Moreover, the four individual ODR structures separated from FSODR, which are covered on the surface of n-AlGaN, the interface of p-GaN/p-AlGaN, the sidewall of mesa and the sidewall of n-AlGaN/AlN, respectively, show considerably different optical polarization characteristics and extraction behaviors between each other. The achievements of FSODR cannot be obtained by any separated ODR, and all of the individual ODRs can contribute to the FSODR. Especially, the synergy effect of TM extraction behavior obviously exists in FSODR. As a result, the light extraction efficiency (LEE) enhancement of FSODR is approximately 60% at a high current density of 140A/cm2. This study is significant for understanding and modulating the extraction behavior of polarized light to realize high efficiency AlGaN-based DUV LEDs.

13.
J Recept Signal Transduct Res ; 39(4): 304-311, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31755335

RESUMO

The α-fetoprotein transcription factor (FTF) is a member of the nuclear receptor NR5A subfamily, which is involved in the pathogenesis of liver cancer and some other gastrointestinal cancers. The protein's transcriptional activity is regulated by binding TIF-2 coactivator at its coactivator-interacting site (CIS); suppression of the transcriptional activity has been recognized as a potential therapeutic strategy against cancer. Previously, small-molecule antagonists have been developed to target the ligand-binding site (LBS) of FTF ligand-binding domain, which simply occupy the site to exclusively block natural ligand entry (type-I antagonists) or destabilize the agonist conformation of activation helix 12 of the domain (type-II antagonists). Here, we describe the use of small-molecule competitors (type-III antagonists) to directly disrupt FTF-TIF-2 interaction by competitively targeting FTF CIS site. High-throughput virtual screening is performed against a structurally diverse, commercially available compound library to identify FTF CIS binders as competitor candidates, from which 12 hits are manually selected and their competitive potency with TIF-2 core binding sequence for FTF CIS site is tested with CC50 values up to 2.5 µM. Structural modeling analysis revealed that the competitive ligands can form a complicated network of noncovalent interactions to specifically or nonspecifically pack against FTF CIS site, thus preventing TIF-2 from binding to the site.

14.
Biochem Biophys Res Commun ; 520(1): 41-46, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31564416

RESUMO

Alzheimer's disease (AD) is a chronic neurodegenerative disease and mitochondrial impairment is a key feature of AD. The mitochondrial DNA (mtDNA) epigenetic mechanism is a relatively new field compared to nuclear DNA. The relationship between mtDNA epigenetic mechanism and AD hasn't been established. So we analyzed the mtDNA methylation in D-loop region and 12 S rRNA gene in the hippocampi in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice by bisulfite pyrosequencing. Mitochondrial DNA copy number and gene expression were studied by quantitative real-time PCR (qRT-PCR). We observed a decrease in the displacement loop (D-loop) methylation and an increase in 12 S rRNA gene methylation, while both the mtDNA copy number and the mitochondrial gene expression were reduced in APP/PS1 transgenic mice. In summary, the present finding suggest that mtDNA methylation may play a role in AD pathology, which warrants larger future investigations.

15.
Microb Pathog ; 137: 103739, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31513896

RESUMO

Helicobacter pylori infection can cause a wide range of digestive diseases. Gene hp0788 encodes an outer membrane protein HofF, which can reduce the bacterial adherence to the GES-1 cells and affect pathogenesis of H. pylori. In this study, the role of hp0788 in H. pylori infection was further analyzed. RNA-seq data showed that two genes (hp0523 and hp0539), located on the cagPAI, were down-regulated in Δ0788 mutant. The changes were confirmed through qRT-PCR, and the expression of these two genes will be almost recovered to the normal level in complemented strain. These two genes, hp0523 and hp0539, are known to be necessary for integrated T4SS, which related to CagA translocation and IL-8 induction. In H. pylori infected assay, lower amount of phosphorylated CagA and lower induction of IL-8 were both detected in GES-1 cells infected by Δ0788 mutant, compared with the wild type strain. Meanwhile, these reductions almost recovered to the wild-type level in complemented strain. These results reveal that there is a correlation between hp0788 disruption and CagA/IL-8 decline. Deletion of CagA-encoding gene (hp0547) in Δ0788 mutant was further constructed. The double deleted mutant shows lower IL-8-inducing capability than Δ0788 mutant, indicated the correlation between deficiency of CagA and reduced IL-8 production. These results together imply that disruption of hp0788 might affect the efficiency of T4SS and CagA injection, then weaken the induction of IL-8 in infected GES-1 cells.

16.
Nanotechnology ; 30(50): 505706, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31491778

RESUMO

In this study, we designed the luminescent enhanced composites by combining upconversion nanoparticles (UCNPs) and photonic crystals (PCs), and prepared multi-mode coding patterns through utilizing the optical properties of both materials, respectively. We prepared UCNPs with different luminescence and the composite materials can be quickly obtained by spin-coating the UCNPs on the surface of the PCs. We discover that the composite materials have significant luminescent enhancement and the enhancement of upconversion is attributed to the Bragg reflection of the photonic band gap. We fabricated upconversion luminescent lattices based on the surface of the PCs by dropping and endowed with the meaning of the Morse code so that it can have more information in different modes. In addition, we further obtained the cipher table pattern according to the structural color of the PCs and the luminescence of the UCNPs. The results reveal great potential applications in the field of multi-mode optical imaging and anti-counterfeiting.

17.
Opt Express ; 27(17): 23981-23995, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31510294

RESUMO

The blue laser beam-excited surface-enhanced Raman scattering (SERS)-based pH sensing holds great promise for avoiding undesired thermal heating effect on some special temperature-vulnerable molecules, as compared to the vast majority studies by exciting in the red or near-infrared (NIR). Herein, we report an ingenious approach to support core-shell Au@Ag nanodendrites (NDs) on TiO2 nanowires, which can possess enhanced SERS activity under 473 nm laser excitation, owing to the improved charge-transfer effect on modified TiO2 support by inserting plasmonic Au@Ag. By using pH-indicating 4-mercaptobenzoic acid (4-MBA), the obtained TiO2/Au@Ag NDs can not only exhibit high sensitive linear-responses of pH changes ranging from pH 4.0 to 9.0 in different solutions (deionized water, NaCl, CaCl2, and MgCl2) but also provide excellent temperature stability under 4°C, 25°C and 37°C temperatures as well as good time stability after storage for 10 days. The established SERS-pH sensing by using shorter wavelength laser excitation is highly desirable for understanding physiological process in temperature-vulnerable microenvironment.

18.
Int J Biochem Cell Biol ; 115: 105591, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31442607

RESUMO

GATA-6 is a transcription factor that participates in cell lineage differentiation and organogenesis in many tissue types. The abnormal expression of GATA-6 is associated with the development of diverse cancers. GATA-6 acts as an oncogene or tumor suppressor based on tumor origin. Here, we investigated the effects of GATA-6 on lung squamous cell carcinoma (LSCC). We found that GATA-6 was significantly reduced in LSCC tissues compared with the paired normal tissues. The overexpression of GATA-6 inhibited LSCC cell proliferation and migration. Importantly, a luciferase reporter assay and chromatin immunoprecipitation assay demonstrated that GATA-6 negatively regulated the expression of sonic hedgehog (Shh) by directly binding to its promoter region. Furthermore, N-Shh stimulation rescued the inhibition of LSCC cell proliferation and migration upon GATA-6 overexpression. Thus, GATA-6 inhibited the proliferation and migration of LSCC cells by transcriptionally inhibiting the expression of Shh, indicating that targeting GATA-6 may be a potential approach for LSCC therapy.

19.
Ann Palliat Med ; 8(4): 483-489, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31431023

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory colonic disease strongly associated with intestinal epithelial cell (IEC) death. Necroptosis is characterized by a newly programmed cell death through a caspase-independent pathway. Receptor interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) are very important in the pathway of necroptosis. However, their expression in UC remains unelucidated. This study aimed to investigate the expression of RIP3 and MLKL in patients with UC, along with its correlation with disease activity. METHODS: Colonic tissue samples were taken from 22 UC patients and 19 healthy controls. RIP3 and MLKL expression levels were evaluated by immunohistochemical staining and western blotting. RESULTS: RIP3 and MLKL were upregulated in inflamed tissues of UC (P<0.01). No variations were observed in healthy control subjects and non-inflamed colons (P>0.05). RIP3 and MLKL were positively correlated with UC disease activity (P<0.01). CONCLUSIONS: Our results suggest that necroptosis is strongly associated with intestinal inflammation in patients with UC. Further studies of necroptosis may be helpful in future treatments of UC.

20.
ACS Omega ; 4(6): 11163-11172, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31460216

RESUMO

Fuel cells hold great promise for clean and sustainable energy, whereas their widespread commercialization strongly depends on the development of highly efficient and stable electrocatalysts. Herein, three-dimensional fluffy PtPd nanocorals (NCs) loaded on two-dimensional (2D) hexagonal boron nitride (h-BN) supports were successfully achieved by a simple one-step strategy based on ultraviolet (UV) laser-excited photochemical reaction. As for alcohol oxidation reaction, the h-BN/PtPd NCs with unique nanoporous surface provide more enhanced electrocatalytic performances than many previous nanocatalysts, owing to abundant active sites and plentiful charge-transfer channels formed on high electrode-electrolyte contact area. Especially, the mass activity of h-BN/PtPd NCs is about 962.8 mA mgPtPd -1 in methanol oxidation reaction in alkaline solution, which can be maintained at ∼274.9 mA mgPtPd -1 (28.6% of the initial one) even after a 5 × 104 s durability test. The present work not only offers an advanced electrocatalyst for long-term fuel cells but also provides a versatile route for construction of complex metallic nanocomposites on 2D supports, holding great potential for diverse energy-related applications.

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