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1.
Life Sci ; 253: 117750, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32380078

RESUMO

AIM: Osteoarthritis (OA) is the main cause of disability and joint replacement surgery in the elderly. As a crucial cell survival mechanism, autophagy has been reported to decrease in OA. PHF23 is a new autophagy inhibitor which was first reported by us previously. This study aimed to explore the anti-autophagic mechanism of PHF23 to make it a possible therapeutic target of OA. MAIN METHOD: Lentiviral vectors specific to PHF23 were used on chondrocytes (C28/I2) to establish PHF23 overexpressed or knockdown stable cell strains. Interleukin (IL)-1ß (10 ng/mL) and chloroquine (CQ, 25 uM) were used as an inducer of OA and inhibitor of lysosome, respectively. Autophagy was evaluated by autophagosome formation using transmission electron microscopy (TEM) and western blot analysis of P62 and LC3B on different groups of cells. Effects of PHF23 on OA were evaluated by collagen II immunofluorescent staining and western blot analysis of OA-associated proteins MMP13 and ADAMTS5. Effects of PHF23 on AMPK and mTOR/S6K pathways and mitophagy were determined by western blot analysis. KEY FINDINGS: Knockdown of PHF23 enhanced IL-1ß-induced autophagy, while overexpression of PHF23 exerted the opposite effect. Knockdown of PHF23 protected chondrocytes against IL-1ß-induced OA by decreasing the levels of OA-associated proteins and increasing expression of Collagen II. Knockdown of PHF23 also increased mitophagy level and altered the phosphorylation levels of AMPK, mTOR, and S6K. SIGNIFICANCE: PHF23 downregulates autophagy, mitophagy in IL-1ß-induced OA-like chondrocytes and alters the activities of AMPK and mTOR/S6K, which suggests that PHF23 may be a possible therapeutic target for OA.

3.
Poult Sci ; 99(5): 2349-2361, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32359570

RESUMO

There have been several genome-wide association study (GWAS) reported for carcass, growth, and meat traits in chickens. Most of these studies have been based on single SNPs GWAS. In contrast, haplotype-based GWAS reports have been limited. In the present study, 2 Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) and genotyped with the chicken 60K SNP chip were used to perform a haplotype-based GWAS. The lean and fat chicken lines were selected for abdominal fat content for 11 yr. Abdominal fat weight was significantly different between the 2 lines; however, there was no difference for body weight between the lean and fat lines. A total of 132 haplotype windows were significantly associated with abdominal fat weight. These significantly associated haplotype windows were primarily located on chromosomes 2, 4, 8, 10, and 26. Seven candidate genes, including SHH, LMBR1, FGF7, IL16, PLIN1, IGF1R, and SLC16A1, were located within these associated regions. These genes may play important roles in the control of abdominal fat content. Two regions on chromosomes 3 and 10 were significantly associated with testis weight. These 2 regions were previously detected by the single SNP GWAS using this same resource population. TCF21 on chromosome 3 was identified as a potentially important candidate gene for testis growth and development based on gene expression analysis and the reported function of this gene. TCF12, which was previously detected in our SNP by SNP interaction analysis, was located in a region on chromosome 10 that was significantly associated with testis weight. Six candidate genes, including TNFRSF1B, PLOD1, NPPC, MTHFR, EPHB2, and SLC35A3, on chromosome 21 may play important roles in bone development based on the known function of these genes. In addition, several regions were significantly associated with other carcass and growth traits, but no candidate genes were identified. The results of the present study may be helpful in understanding the genetic mechanisms of carcass and growth traits in chickens.

4.
Food Funct ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32400831

RESUMO

Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibits potential renoprotective properties. Here, we examined the protective effects of GAS on carbon tetrachloride (CCl4)-induced kidney inflammation and fibrosis in mice, and explored its underlying mechanisms. Our research findings revealed that GAS improved CCl4-induced renal damage in mice. GAS inhibited kidney fibrosis and the deposition of collagen and α-smooth muscle actin (α-SMA). GAS suppressed CCl4-induced inflammation in kidney tissue, as indicated by the decreased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The renoprotective effects of GAS were associated with inhibiting oxidative stress by regulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling and increasing adenosine 5'-monophosphate activated protein kinase (AMPK) activation. Furthermore, GAS supplementation inactivated the receptor for advanced glycation end products (RAGE) and the high-mobility group box-1 (HMGB1) pathway. GAS inhibited the activation of Toll-like receptors (TLRs), nuclear factor-kappa B (NF-κB) and transforming growth factor (TGF)-ß. Collectively, this study clarified that GAS attenuates CCl4-induced kidney inflammation and fibrosis via the AMPK/Nrf2/HMGB1 pathway.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32412228

RESUMO

Constructing highly efficient and low-cost transition-metal-based electrocatalysts with a large number of interfaces to increase their active site densities constitutes major advancements in the development of water splitting technology. Herein, a bimetallic phosphide composite (Co2P@NC-Fe2P) is successfully synthesized from a ferric hydroxyphosphate-zeolitic imidazolate framework hybrid precursor (FeHP-ZIF-67). Benefitting from morphology and composition regulations, the FeHP-ZIF-67 precursor is prepared by a room-temperature solution synthesis method, which exhibits an optimal morphology where FeHP microspheres are coated with excess ZIF-67 nanoparticles. During the annealing of FeHP-ZIF-67, FeHP serves as a source of phosphorus to form Fe2P and Co2P simultaneously, where Co2P nanoparticles coated with a N-doped carbon (NC) matrix derived from ZIF-67 are partially adsorbed onto the surface of Fe2P microspheres, forming numerous NC-Fe2P interfaces. The optimal Co2P@NC-Fe2P composite has an overpotential of 260 mV at a current density of 10 mA cm-2, a small Tafel slope of 41 mV dec-1 and a long-term stability of over 35 h in an alkaline medium for oxygen evolution reaction (OER). Such a superior OER performance is attributed to the active NC-Fe2P interfaces in the Co2P@NC-Fe2P composite. This work provides a new strategy to optimize transition metal phosphides with effective interfaces for OER electrocatalysis.

6.
Opt Lett ; 45(10): 2704-2707, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32412446

RESUMO

Observing microvasculature in its native environment provides invaluable information to understand the initiation and development of microcirculatory related diseases. However, the lack of a high-resolution three-dimensional (3D) imaging technique hinders in vivo investigation of the microvasculature. Recently, we found that the red blood cells can emit autofluorescence signals with short-wavelength two-photon excitation. In this study, we exploited this property and developed a time-resolved two-photon excitation microscopy system using a homemade 520 nm femtosecond fiber laser as the excitation source. Using this system, we could achieve intravital high-resolution 3D imaging of a microvascular network noninvasively. In a mouse tumor model, tumorous blood vessels could be observed and distinguished clearly from the normal vessels.

7.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 137-141, 2020 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-32376569

RESUMO

ObjectiveTo explore the mediating effect of rumination on coping style and insomnia in college students.MethodWe surveyed 767 college students from a university in Sichuan Province using Insomnia Severity Index (ISI), Ruminative Responses Scale (RRS), and Trait Coping Style Questionnaire (TCSQ).ResultsThe prevalence of insomnia was 36.6% in the surveyed college students. Positive coping style was negatively correlated with the total score and scores in each dimension of RRS (r=-0.127~-0.116, P < 0.001), and was negatively correlated with the total score of ISI (r=-0.159, P < 0.001). Negative coping style was positively correlated with the total score and the scores in each dimension of RRS (r=0.298-0.334, P < 0.001), and was positively correlated with the total score of ISI (r=0.264, P < 0.001). The total score and the scores in each dimension of RRS were positively correlated with the total score of ISI (r=0.251-0.281, P < 0.001). Rumination had a partial mediating effect on both positive and negative coping style and insomnia.ConclusionCoping style affects insomnia in college students not only directly but also indirectly through the mediating effect of rumination.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32385713

RESUMO

Since the discovery of the first mammalian Wnt proto-oncogene in virus-induced mouse mammary tumors almost four decades ago, Wnt signaling pathway and its involvement in cancers have been extensively investigated. Activation of this evolutionarily conserved pathway promotes cancer development via diverse mechanisms. Cancer is a complex disease and one outstanding conceptual framework for understanding its biology is the "Hallmarks of Cancer". In this review, we focus on the involvement of Wnt signaling in the ten hallmarks of human cancer. These widespread roles of Wnt signaling in human cancers highlight the importance and feasibility of targeting this signaling pathway for cancer treatment.

9.
Virus Res ; : 198024, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32425279

RESUMO

Discovered in 2017, swine enteric alphacoronavirus (SeACoV), also known as swine acute diarrhea syndrome coronavirus (SADS-CoV) or porcine enteric alphacoronavirus (PEAV), is the fifth porcine CoV identified in diarrheal piglets. The presumed name "SADS-CoV" may not be appropriate since current studies have not provided strong evidence for high pathogenicity of the virus. SeACoV was the most recently recognized CoV of potential bat origin prior to the novel human severe acute respiratory syndrome CoV 2 (SARS-CoV-2), associated with the pandemic CoV disease 2019 (COVID-19). Although SeACoV is recognized as a regional epizootic virus currently, it possesses the most extensive cell species tropism in vitro among known CoVs. This review summarizes the emergence of SeACoV and updates the research progress made from 2017 to early 2020, mainly focusing on the etiology, epidemiology, evolutionary perspective, potential for interspecies transmission, pathogenesis and diagnosis.

11.
Cell Res ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350394

RESUMO

Programmed death ligand-1 (PD-L1 or B7-H1) is well known for its role in immune checkpoint regulation, but its function inside the tumor cells has rarely been explored. Here we report that nuclear PD-L1 is important for cancer cell sister chromatid cohesion. We found that depletion of PD-L1 suppresses cancer cell proliferation, colony formation in vitro, and tumor growth in vivo in immune-deficient NSG mice independent of its role in immune checkpoint. Specifically, PD-L1 functions as a subunit of the cohesin complex, and its deficiency leads to formation of multinucleated cells and causes a defect in sister chromatid cohesion. Mechanistically, PD-L1 compensates for the loss of Sororin, whose expression is suppressed in cancer cells overexpressing PD-L1. PD-L1 competes with Wing Apart-Like (WAPL) for binding to PDS5B, and secures proper sister chromatid cohesion and segregation. Our findings suggest an important role for nuclear PD-L1 in cancer cells independent of its function in immune checkpoint.

12.
Pharmazie ; 75(5): 200-203, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32393429

RESUMO

Timosaponin B-II (TB-II; (25S)-26-(ß-D-glucopyranosyloxy)-3ß-[(2-O-ß-D-glucopyranosyl-ß-D-galactopyranosyl) oxy]-5ß-furostan-22-ol is extracted from Anemarrhena. Its anti-inflammation, anti-oxidation, and anti-asthma properties have been widely explored. However, its effect on the heart has not been reported. In this study, we used zebrafish as a research model to determine the effects of TB-II on the heart and its toxic and anti-inflammatory effects. To explore the cause of cardioprotective effects of TB-II, we used transgenic zebrafish with macrophages and neutrophils labeled with fluorescent protein. We found for the first time that TB-II had a protective effect on the zebrafish heart. It did not affect the survival and hatching rates of zebrafish embryos, indicating its low toxicity. Results showed that TB-II may have cardioprotective effects, which might be related to its anti-inflammatory effects.

13.
Aging (Albany NY) ; 122020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427575

RESUMO

Although androgen deprivation therapy may initially be effective in prostate cancer, the disease can gradually progress to castration-resistant prostate cancer, at which point chemotherapy becomes the major clinical strategy. In this study, we demonstrated the anti-cancer potential of a novel 3',5'-diprenylated chalcone (C10), which selectively inhibited the proliferation of PC3 cells in vitro and in vivo. C10 treatment elevated the proportion of PC3 cells in sub-G1 phase and induced programmed cell death. Interestingly, C10 elicited concurrent Caspase-dependent apoptotic and gasdermin E-dependent pyroptotic events. RNA-Seq and bioinformatics analyses revealed a strong correlation between protein kinase C delta (PKCδ) and mitogen-activated protein kinase pathway activation in prostate cancer. PKCδ silencing in PC3 cells suppressed the activation of the JNK pathway and the expression of its downstream genes, including Bax, interleukin-6 and interleukin-1ß, which are involved in apoptotic and pyroptotic processes. Moreover, in PC3 cell xenograft tumor tissues, C10 treatment inhibited tumor growth and upregulated PKCδ. These findings suggest that C10 treatment induces the PKCδ/JNK pathway, thereby activating Caspase-3 and inducing the cleavage of PARP and gasdermin E to execute apoptosis and cell-lytic pyroptosis in prostate cancer cells.

14.
Zhen Ci Yan Jiu ; 45(4): 305-9, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32333536

RESUMO

OBJECTIVE: To observe the effect of moxibustion and acupoint catgut embedding (ACE) at "Tianshu"(ST25) "Dachangshu"(BL25) and "Shangjuxu"(ST37) on changes of body mass, stool property, histopathological conditions and expression levels of interleukin 6 (IL-6) in colonic mucosa of ulcerative colitis (UC) rats, so as to reveal its anti-inflammatory mechanisms underlying improvement of UC. METHODS: SD rats were randomized into normal, model, moxibustion, ACE and moxibustion+ACE groups (n=6 in each group). The UC model was established by enema of trinitro-benzene-sulfonic acid and ethanol. Moxibustion was applied to bilateral ST25, BL25 and ST37 for 10 min, once daily for 14 days, and ACE applied to the same 3 acupoints, once a week for two weeks. After the treatment, the rats' general conditions were observed, and the severity of UC was assessed by using disease activity index (DAI) score. Colonic mucosal pathological changes were observed under microscope after hematoxylin eosin (H.E.) stain, and the expression levels of IL-6 in the colonic mucosa tissue detected by using immunohistochemical stain and Western blot, respectively. RESULTS: After modeling, the DAI score, and expression level of colonic IL-6 protein detected by immunohistochemistry and Western blot were obviously increased in the model group relevant to the normal group (P<0.01). Following the intervention, the increase of DAI score and IL-6 expression were reversed in moxibustion, ACE and moxibustion+ACE groups (P<0.01, P<0.05). The therapeutic effects of moxibustion+ACE were considerably superior to those of simple ACE and simple moxibustion in down-regulating the levels of DAI score and IL-6 expression (P<0.01). H.E. staining showed severe defect of the colonic mucosal epithelium with infiltration of a large number of inflammatory cells in the model group, which was milder in moxibustion, ACE and moxibustion+ACE groups. CONCLUSION: Moxibustion combined with ACE is able to improve the inflammatory injury of colonic mucosa in UC rats, which may be related with its effect in suppressing the expression of colonic IL-6; and the efficacy of moxibustion+ACE is apparently superior to that of moxibustion and ACE alone.

15.
Free Radic Biol Med ; 153: 122-131, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32344103

RESUMO

The microRNA-based mechanisms underlying the antioxidant action(s) of co-existing flavonoids in response to oxidative stress are of high interest. This study aimed to extend the existing knowledge and provide insights into the potential regulatory network in response to oxidative stress and the co-presence of quercetin and catechin antioxidants, via a preclinical approach using H2O2-stimulated HepG2 cells. It was confirmed that BACH1 serves as an essential and direct negative regulator of the Keap1-Nrf2 signaling pathway and the antioxidant synergism between quercetin and catechin. BACH1 promoted reactive oxygen species (ROS) accumulation while inhibiting cell growth, which could be reversed by the synergistic action of let-7a-5p and miR-25-3p in the co-presence of quercetin and catechin. Both let-7a-5p and miR-25-3p could directly regulate the expression and function of BACH1 (e.g. upregulation of the two miRNAs could rescue largely overexpression of BACH1). Although these molecular interactions likely represented only some aspects of the overall regulatory network, this research confirms the feasibility of the combined uses of dietary flavonoids with chemopreventive properties in synergy during multiple-target interactions and multiple-pathway regulation.

16.
ACS Appl Mater Interfaces ; 12(17): 19834-19839, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32250112

RESUMO

DNA nanostructures are a new type of technology for constructing nanomaterials that has been developed in recent years. By relying on the complementary pairing of DNA molecules to form a double-stranded property, DNA molecules can construct a variety of nanoscale structures of 2D and 3D shapes. However, most of the previously reported DNA nanostructures rely solely on hydrogen bonds to maintain structural stability, resulting in DNA structures that can be maintained only at low temperature and in the presence of Mg2+, which greatly limits the application of DNA nanostructures. This study designed a DNA nanonetwork structure (nanonet) and changed its topological structure to DNA nanomesh by using DNA topoisomerase to make it thermally stable, while escaping the dependence on Mg2+, and the stability of the structure can be maintained in a nonsolution state. Moreover, the nanomesh also has a large amount of ssDNA (about 50%), providing active sites capable of exerting biological functions. Using the above characteristics, we prepared the nanomesh into a device capable of adsorbing specific DNA molecules, and used the device to enrich DNA. We also tried to mount antibodies using DNA probes. Preliminary results show that the DNA nanomesh also has the ability to enrich specific proteins.

17.
Pediatr Dermatol ; 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32301528

RESUMO

Topical corticosteroids are an emerging cause of allergic contact dermatitis in children that may often be missed. It is important to consider patch testing with corticosteroids to detect allergic contact dermatitis in patients with persistent or worsening of dermatitis despite topical corticoseroid treatment. However, delayed reactions (>7 days) to topical corticosteroids may occur, leading to false-negative reactions and misdiagnosis. Herein, we report a case of an 8-year-old girl who developed a positive reaction to budesonide on day 12 of patch testing.

18.
Signal Transduct Target Ther ; 5(1): 15, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32296035

RESUMO

The incidence of lymphoma has gradually increased over previous decades, and it ranks among the ten most prevalent cancers worldwide. With the development of targeted therapeutic strategies, though a subset of lymphoma patients has become curable, the treatment of refractory and relapsed diseases remains challenging. Many efforts have been made to explore new targets and to develop corresponding therapies. In addition to novel antibodies targeting surface antigens and small molecular inhibitors targeting oncogenic signaling pathways and tumor suppressors, immune checkpoint inhibitors and chimeric antigen receptor T-cells have been rapidly developed to target the tumor microenvironment. Although these targeted agents have shown great success in treating lymphoma patients, adverse events should be noted. The selection of the most suitable candidates, optimal dosage, and effective combinations warrant further investigation. In this review, we systematically outlined the advances in targeted therapy for malignant lymphoma, providing a clinical rationale for mechanism-based lymphoma treatment in the era of precision medicine.

19.
ACS Appl Mater Interfaces ; 12(18): 20321-20330, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32293862

RESUMO

Metal-organic frameworks (MOFs) have been identified as promising materials for the delivery of therapeutics to cure cancer owing to their intrinsic porous structure. However, in a majority of cases, MOFs act as only a delivery cargo for anticancer drugs while little attention has been focused on the utilization of their intriguing physical and chemical properties for potential anticancer purposes. Herein for the first time, an ultrathin (16.4 nm thick) ferrocene-based MOF (Zr-Fc MOF) nanosheet has been synthesized for synergistic photothermal therapy (PTT) and Fenton reaction-based chemodynamic (CDT) therapy to cure cancer without additional drugs. The Zr-Fc MOF nanosheet acts not only as an excellent photothermal agent with a prominent photothermal conversion efficiency of 53% at 808 nm but also as an efficient Fenton catalyst to promote the conversion of H2O2 into hydroxyl radical (•OH). As a consequence, an excellent therapeutic performance has been achieved in vitro as well as in vivo through this combinational effect. This work aims to construct an "all-in-one" MOF nanoplatform for PTT and CDT treatments without incorporating any additional therapeutics, which may launch a new era in the investigation of MOF-based synergistic therapy platforms for cancer therapy.

20.
Dev Cell ; 53(3): 272-286.e7, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32275888

RESUMO

Extreme weather events can cause heat stress that decreases crop production. Recent studies have demonstrated that protein degradation and rRNA homeostasis as well as transcription factors are involved in the thermoresponse in plants. However, how RNA modifications contribute to temperature stress response in plant remains largely unknown. Herein, we identified OsNSUN2 as an RNA 5-methylcytosine (m5C) methyltransferase in rice. osnsun2 mutant displayed severe temperature- and light-dependent lesion-mimic phenotypes and heat-stress hypersensitivity. Heat stress enhanced the OsNSUN2-dependent m5C modification of mRNAs involved in photosynthesis and detoxification systems, such as ß-OsLCY, OsHO2, OsPAL1, and OsGLYI4, which increased protein synthesis. Furthermore, the photosystem of osnsun2 mutant was vulnerable to high ambient temperature and failed to undergo repair under tolerable heat stress. Thus, OsNSUN2 mutation reduced photosynthesis efficiency and accumulated excessive reactive oxygen species upon heat treatment. Our findings demonstrate an important mechanism of mRNA m5C-dependent heat acclimation in rice.

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