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1.
Artigo em Inglês | MEDLINE | ID: mdl-34628849

RESUMO

The earth-abundant iron and nitrogen doped carbon (Fe-N-C) catalyst has great potential to substitute noble metal catalysts for oxygen reduction reaction (ORR) in H2-O2 proton exchange membrane fuel cells (PEMFCs). Herein, we report the preparation of Fe-N4 moiety doped carbon nanotubes (CNTs) by ball milling and two-step pyrolysis with dual metal-organic frameworks (MOFs) as the precursor. This catalyst shows high ORR catalytic performance and stability. Different from traditional inorganic iron sources, the MOF structure can effectively prevent the iron metal from aggregating during pyrolysis. In PEMFC, the catalyst shows high current density (0.39 A/cm2 at 0.7 V) and power density (850 mW/cm2). Such a method brings inspiration for the reasonable design of FeNC catalysts with high catalytic activity for H2-O2 PEMFCs.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34628856

RESUMO

The oxygen evolution reaction (OER) is crucial for hydrogen production from water splitting and rechargeable metal-air batteries. However, the four-electron mechanism results in slow reaction kinetics, which needed to be accelerated by efficient catalysts. Herein, a hybrid catalyst of novel nickel-iron layered double hydroxide (NiFe LDH) on porous indium tin oxide (ITO) is presented to lower the overpotential of the OER. The as-prepared NiFe LDH@ITO catalyst showed superior catalytic activity toward the OER with an overpotential of only 240 mV at a current density of 10 mA/cm2. The catalyst also offered high stability with almost no activity decay after more than 200 h of chronopotentiometry test. Furthermore, the applications of NiFe LDH@ITO in (flexible) rechargeable zinc-air batteries exhibited a better performance than commercial RuO2 and can remain stable in cycling tests. It is supposed that the superior catalytic behavior originates from the ITO conductive framework, which prevents the agglomeration and facilitates the electron transfer during the OER process.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34596819

RESUMO

Salvinorin A (SA), a highly selective kappa opioid receptor agonist, has been shown to reduce brain infarct volume and improve neurological function after ischemic stroke. However, the underlying mechanisms have not been fully understood yet. Therefore, we explored whether SA provides neuroprotective effects by regulating the immune response after ischemic stroke both in the central nervous system (CNS) and peripheral circulation. In this study, adult male mice were subjected to transient Middle Cerebral Artery Occlusion (tMCAO) and then were treated intranasally with SA (50 µg/kg) or with the vehicle dimethyl sulfoxide (DMSO). Multiple behavioral tests were used to evaluate neurofunction. Flow cytometry and immunofluorescence staining were used to evaluate the infiltration of peripheral immune cells into the brain. The tracer cadaverine and endogenous immunoglobulin G (IgG) extravasation were used to detect blood brain barrier leakage. We observed that SA intranasal administration after ischemic stroke decreased the expression of pro-inflammatory factors in the brain. SA promoted the polarization of microglia/macrophages into a transitional phenotype and decreased the pro-inflammatory phenotype in the brain after tMCAO. Interestingly, SA treatment scarcely altered the number of peripheral immune cells but decreased the macrophage and neutrophil infiltration into the brain at 24 h after tMCAO. Furthermore, SA treatment also preserved BBB integrity, reduced long-term brain atrophy and white matter injury, as well as improved the long-term neurofunctional outcome in mice. In this study, intranasal administration of SA improved long-term neurological function via immuno-modulation and by preserving blood-brain barrier integrity in a mouse ischemic stroke model, suggesting that SA could potentially serve as an alternative treatment strategy for ischemic stroke.

4.
China CDC Wkly ; 3(11): 221-225, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-34594854

RESUMO

What is already known on this topic?: Iron deficiency (ID) is the most widespread micronutrient deficiency and have several adverse effects on health. Consequences of ID among children include delayed psychomotor development and impaired cognitive performance, which makes it important to monitor the iron status of children. What is added by this report?: In this study, the serum ferritin (SF) level was 56.6 (95% CI: 56.0-57.2) ng/mL in 65,293 children aged 6-17 years old in the National Nutrition and Health Surveillance in China in 2016-2017. ID prevalence varied significantly in children stratified by sex, age, and regions ranging from 1.0% to 28.1% judged by the standard of SF<15 ng/mL and SF<25 ng/mL. ID prevalence in females aged 12-17 years was the highest among children aged 6-17 years. What are the implications for public health practice?: Understanding iron status of school children could provide evidence and data for developing policies and strategies for ID and iron deficiency anemia (IDA) control and prevention. Females aged 12-17 years showed high ID prevalence, and iron-rich food interventions are strongly recommended.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34687898

RESUMO

OBJECTIVE: We investigated the effect of berberine, a natural plant product that can activate AMP-activated protein kinase (AMPK), on OA development and associated pain in mice. DESIGN: Human primary knee chondrocytes were utilized to investigate how AMPK is activated by berberine. Both global knockout (KO) of AMPKα1 and congenic wild type (WT) mice were subjected to the post-traumatic OA through destabilization of medial meniscus (DMM) surgery. Two weeks after surgery, the mice were randomly divided into two groups with one group receiving berberine chloride daily via drinking water and were sacrificed at 6 and 12 weeks after surgery. OA severity was assessed by histological and histomorphometric analyses of cartilage degradation, synovitis, and osteophyte formation. OA-associated pain behavior was also determined. Immunohistochemistry (IHC) analyses were carried out to examine changes in AMPK signaling. RESULTS: Berberine induced phosphorylation of AMPKα (Thr172) via liver kinase B1 (LKB1), the major upstream kinase of AMPK, in chondrocytes in vitro. Both WT and AMPKα1KO developed OA and associated pain post DMM surgery. However, treatment with berberine significantly reduced severity of OA and associated pain in WT but not AMPKα1KO mice. IHC analysis of WT DMM knee cartilage further revealed that berberine inhibited concomitant loss of expression and phosphorylation of AMPKα and expression of SIRT1 and SIRT3, suggesting an important role of activation of AMPK signaling in mediating beneficial effect of berberine. CONCLUSIONS: Berberine acts through AMPK to reduce joint structural damage and pain associated with post-traumatic OA in mice in vivo.

6.
Front Oncol ; 11: 747608, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604092

RESUMO

Triple-negative breast cancer (TNBC) has inadequate treatment approaches and a poor prognosis. It is urgent to develop new treatment approaches for TNBC. The combination of photothermal therapy (PTT) and chemotherapy is a very effective potential therapy for TNBC. However, asynchronous accumulation, unclear efficacy, and toxic side effects hinder the further promotion of this method. Therefore, we designed and constructed a new type of nanocarriers, the cascade release near-infrared imaging (NIFI) & thermal-chemo combination nanoparticles (CNC NPs), that can release drugs through the cascade of ultrasound triggering and pH responding to achieve the synchronous tumor accumulation, monitoring and synergistic treatment of two functional molecules. The key material of CNC NPs is the polydopamine (PDA), which, through self-assembling, forms a rigid shell that contains doxorubicin (DOX) and NIF fluorescent dye IR780 on the surface of the perfluorohexane (PFH) microbubbles. The results show that CNC NPs have a hollow core-shell structure with an average particle size of 97.3 ± 27.2 nm and have exceptional colloidal stability and photothermal conversion efficiency. The NPs can effectively perform cascade drug release through ultrasound triggering and pH responding. CNC NPs have good in vivo biological safety and excellent fluorescence imaging, drug delivery, and therapeutic abilities in the TNBC models. These results provide an experimental basis for the development of new clinical treatment methods for TNBC.

7.
Cell Death Discov ; 7(1): 256, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548476

RESUMO

Alzheimer's disease (AD) is characterized by aberrant accumulation of extracellular ß-amyloid (Aß) peptides in the brain. Soluble Aß oligomers are thought to be the most neurotoxic species and are correlated with cognitive dysfunction in early AD. However, there is still no effective treatment so far. We determined that Pep63, a small peptide, had a neuroprotective effect on synaptic plasticity and memory in our previous study. Here, we developed novel and multifunctional liposomes targeting both Aß oligomers and fibrils based on a liposome delivery system. Transferrin-Pep63-liposomes (Tf-Pep63-Lip), possessing the ability for blood-brain barrier targeting, were also incorporated with phosphatidic acid (PA) and loaded with neuroprotective Pep63. We discovered that administration of Tf-Pep63-Lip could significantly reduce the Aß burden in the hippocampus, and improve cognitive deficits in 6-month-old APP/PS1 mice in the Morris-Water maze task and fear-conditioning test with the combined effects of PA and Pep63. Tf-Pep63-Lip could capture Aß oligomers or fibrils and then facilitated microglial chemotaxis nearby for clearance. Simultaneously, Tf-Pep63-Lip hindered Aß1-42 aggregation and disaggregated Aß1-42 assembly due to multivalent PA-Aß. Pep63 effectively inhibited the binding between EphB2 and Aß oligomers after release from liposomes and rescued NMDA receptors trafficking, the basis of synaptic plasticity. No side effects were observed in either APP/PS1 or wild-type mice, indicating that Tf-Pep63-Lip might be safe under the dosing regimen used in our experiment. Taken together, our results suggested that Tf-Pep63-Lip may serve as a safe and efficient agent for AD combination therapy.

8.
J Pharm Pharmacol ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570873

RESUMO

OBJECTIVES: This study was designed to test our hypothesis that angiotensin II (Ang II) upregulates endothelin (ET) receptors in vascular smooth muscle cells (VSMCs). METHODS: Rat superior mesenteric artery (SMA) without endothelium was cultured in serum-free medium for 24 h in the presence of Ang II with or without metformin or nicotinamide. In vivo, rats were implanted subcutaneously with a mini-osmotic pump infusing AngII (500 ng/kg/min) for 4 weeks. The level of protein expression was determined using Western blotting. The contractile response to ET receptor agonists was studied using sensitive myography. Caudal artery blood pressure (BP) was measured using non-invasive tail-cuff plethysmography. KEY FINDINGS: The results showed that Ang II significantly increased ET receptors and decreased phosphorylated-adenosine monophosphate-activated protein kinase α (p-AMPKα) in SMA. Furthermore, metformin significantly inhibited Ang II-upregulated ET receptors and upregulated Ang II-decreased sirtuin 1 (Sirt1). However, this effect was reversed by nicotinamide. Moreover, the in-vivo results showed that metformin not only inhibited Ang II-induced upregulation of ET receptors but also recovered Ang II-decreased p-AMPKα and Sirt1. In addition, metformin significantly inhibited Ang II-elevated BP. However, the effect was reversed by nicotinamide, except for p-AMPKα. CONCLUSIONS: Ang II upregulated ET receptors in VSMCs to elevate BP by inhibiting AMPK, thereby inhibiting Sirt1.

9.
Front Immunol ; 12: 618367, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552580

RESUMO

Novel systemic agents and effective treatment strategies for recurrence adenoid cystic carcinoma (ACC) of the head and neck are still worthy of further exploration. Here, we analyzed the mutations and expression profiles of 75 Chinese ACC patients, characterized the prognostic value of the immune signature for recurrence or distant metastasis, and explored the potential of immunotherapeutic biomarkers in ACC. In general, MYB fusion and somatic mutations accounted for a high proportion, which was 46.7% (35/75). ACCs displayed an overall low mutation burden and lack of programmed cell death ligand-1 (PD-L1) expression. The antigen-presenting machinery (APM) expression score and immune infiltration score (IIS) were the lowest among ACC patients, compared with other cancer types. For 61 primary cases, the locoregional recurrence-free survival (LRRFS) was statistically significantly correlated with the IIS [univariate analysis; hazard ratio (HR) = 0.32; 95% CI, 0.11-0.92; p = 0.035] and T-cell infiltration score (TIS) (univariate analysis; HR = 0.33; 95% CI, 0.12-0.94; p = 0.037]. Patients with lower IIS (log-rank p = 0.0079) or TIS (log-rank p = 0.0079) had shorter LRRFS. Additionally, solid pattern was also a prognostic factor related to locoregional recurrence, whereas postoperative radiotherapy (PORT) exerted its beneficial effects. We further evaluated the pretreatment immune profile of five ACC patients treated with PD-1 inhibitors. Patients who responded to camrelizumab or pembrolizumab observed elevated APM and TIS, compared with patients with progressive disease. Our study highlights the immune infiltration pattern and messenger RNA (mRNA) signatures of Chinese ACC patients, which has the potential value for prognosis and immunotherapy.

10.
Front Mol Biosci ; 8: 721990, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568427

RESUMO

Esophageal cancer (EC) is a common malignant disease in eastern countries. However, a study of the metabolomic characteristics associated with other biological factors in esophageal squamous cell carcinoma (ESCC) is limited. Interleukin enhancer binding factor 2 (ILF2) and ILF3, double-stranded RNA-binding proteins, have been reported to contribute to the occurrence and development of various types of malignancy. Nevertheless, the underlying functions of ILF2 and ILF3 in ESCC metabolic reprogramming have never been reported. This study aimed to contribute to the metabolic characterization of ESCC and to investigate the metabolomic alterations associated with ILF2 and ILF3 in ESCC tissues. Here, we identified 112 differential metabolites, which were mainly enriched in phosphatidylcholine biosynthesis, fatty acid metabolism, and amino acid metabolism pathways, based on liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry approaches using ESCC tissues and paired para-cancer tissues from twenty-eight ESCC patients. In addition, ILF2 and ILF3 expression were significantly elevated in EC tissues compared to the histologically normal samples, and closely associated with PI3K/AKT and MAPK signaling pathways in ESCC. Moreover, in ESCC tissues with a high ILF2 expression, several short-chain acyl-carnitines (C3:0, C4:0, and C5:0) related to the BCAA metabolic pathway and long-chain acyl-carnitines (C14:0, C16:0, C16:0-OH, and C18:0) involved in the oxidation of fatty acids were obviously upregulated. Additionally, a series of intermediate metabolites involved in the glycolysis pathway, including G6P/F6P, F1,6BP, DHAP, G3P, and 2,3BPG, were remarkably downregulated in highly ILF3-expressed ESCC tissues compared with the corresponding para-cancer tissues. Overall, these findings may provide evidence for the roles of ILF2 and ILF3 during the process of ESCC metabolic alterations, and new insights into the development of early diagnosis and treatment for ESCC. Further investigation is needed to clarify the underlying mechanism of ILF2 and ILF3 on acyl-carnitines and the glycolysis pathway, respectively.

11.
Front Cell Infect Microbiol ; 11: 696186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485176

RESUMO

Objective: Frailty is a common geriatric syndrome that is diagnosed and staged based mainly on symptoms. We aimed to evaluate frailty-related alterations of the intestinal permeability and profile fecal microbiota of healthy and frail older adults to identify microbial biomarkers of this syndrome. Methods: We collected serum and fecal samples from 94 community-dwelling older adults, along with anthropometric, medical, mental health, and lifestyle data. Serum inflammatory cytokines IL-6 and HGMB1 and the intestinal permeability biomarker zonulin were measured using enzyme-linked immunosorbent assays. The 16S rRNA amplicon sequencing method was performed to determine the fecal composition of fecal microbiota. We analyzed the diversity and composition differences of the gut microbiota in the two groups and assessed the relationship between the changes in microbiota structure and clinical biomarkers. Results: Older adults with frailty showed higher concentrations of IL-6, HGMB1, and zonulin. Although there were no statistically significant differences in the diversity index and evenness indices or species richness of fecal microbiota between the two groups, we found significant microbiota structure differences. Compared with the control group, fecal samples from the frail group had higher levels of Akkermansia, Parabacteroides, and Klebsiella and lower levels of the commensal genera Faecalibacterium, Prevotella, Roseburia, Megamonas, and Blautia. Spearman's correlation analysis showed that the intergenus interactions were more common in healthy controls than older adults with frailty. Escherichia/Shigella, Pyramidobacter, Alistipes, and Akkermansia were positively correlated with IL-6, while Faecalibacterium, Prevotella, and Roseburia were negatively correlated with IL-6. Alistipes were found to be positively correlated with HGMB1. Akkermansia and Alistipes were linked to the increased serum level of inflammatory factors and intestinal permeability. Conclusions: Frailty is associated with differences in the composition of fecal microbiota. These findings might aid in the development of probiotics or microbial-based therapies for frailty.


Assuntos
Fragilidade , Microbioma Gastrointestinal , Microbiota , Idoso , Fezes , Humanos , RNA Ribossômico 16S/genética
12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 659-662, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494541

RESUMO

The incidence of endophthalmitis after vitrectomy is extremely low,especially lower in silicone oil-filled eyes.Silicone oil exerts a toxic effect on the cell membranes of microorganisms and leads to the lack of nutrients.It is thus believed to inhibit the growth of bacteria and fungi.Endophthalmitis induced by mixed bacteria in silicone oil-filled eye has been rarely reported.We reviewed the clinical manifestations,diagnosis,and treatment of a patient with endophthalmitis caused by mixed infection of Morganella morganii and Staphylococcus epidermidis in the silicone oil-filled eye,aiming to improve the understanding and diagnosis of mixed infections.


Assuntos
Coinfecção , Endoftalmite , Bactérias , Humanos , Óleos de Silicone/efeitos adversos , Vitrectomia
13.
Br J Neurosurg ; : 1-10, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34553657

RESUMO

PURPOSE: The preferred surgical method for treating adults with moyamoya disease (MMD) remains controversial. The purpose of this study was to compare the efficacy of different surgical methods in the treatment of adults with ischaemic-type MMD. METHODS: We retrospectively analyzed the data of patients with ischaemic-type MMD who underwent indirect bypass (IB), direct bypass (DB), or combined bypass (CB) at the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2019. Postoperative complications, improvements in neurological function, haemodynamics, recurrent stroke and neovascularization were compared. RESULTS: A total of 310 adults (371 hemispheres) with ischaemic-type MMD were included in our study. Ninety, 127, and 154 hemispheres underwent IB, DB and CB, respectively. A total of 24 (6.5%) ischaemic events and 8 (2.8%) symptomatic hyperperfusion events occurred after the operations. There was no significant difference in postoperative complications among the three types of surgery (p = 0.300). During the follow-up period, there were 21 cases (5.7%) of recurrent ischaemia and 12 cases (3.2%) of recurrent haemorrhage. Kaplan-Meier survival analysis showed that the ischaemia-free survival of the CB group was significantly longer than that of the IB group (p = 0.047), but there was no significant difference in haemorrhage-free survival among the three groups (p = 0.660). Six months after the operation, DB and CB were superior to IB in improving cerebral blood flow and neovascularization (p = 0.002), but there was no significant difference in the improvement of neurological function among the three groups at the last follow-up (p = 0.784). CONCLUSION: The three surgical methods achieved satisfactory results in the treatment of ischaemic-type MMD. DB and CB can significantly improve haemodynamics and reduce recurrent stroke. In terms of improving neurological function, the curative effect of the three surgical methods remains to be further explored.

14.
Se Pu ; 39(10): 1118-1127, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34505434

RESUMO

The late endosomal/lysosomal adaptor MAPK and mTOR activator 1 (LAMTOR1) is an important regulator protein in the response to energy stress. Public gene expression data shows that the expression of LAMTOR1 is abnormally high in nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC); hence, LAMTOR1 may play an important role in the development of NASH and HCC. Therefore, exploring the LAMTOR1 regulatory mechanism in the progression of NASH and malignant transformation of liver inflammation may be crucial for translational medicine. First, a NASH mouse model was established by feeding a methionine choline-deficient (MCD) diet. Hematoxylin-eosin staining of liver tissues showed successful modeling of inflammatory injury in the mouse liver. Immunoblot analysis confirmed LAMTOR1- and LAMTOR1-mediated protein expression in LAMTOR1 specifically depleted mouse livers. Subsequently, metabolic profiling of liver tissues was performed using an ultra-performance liquid chromatography-time-of-flight mass spectrometry strategy. Based on the retention time, m/z value, and tandem mass spectra, 134 metabolites were identified. Among these, the levels of 45 metabolite were significantly influenced by hepatic LAMTOR1 depletion. According to the metabolomics results, uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) was significantly upregulated in LAMTOR1-depleted (LAMTOR1LKO) hepatocyte tissues. As the final product of the hexosamine biosynthetic pathway (HBP), alteration in UDP-GlcNAc levels may regulate LAMTOR1 and metabolic regulatory genes downstream of HBP. Moreover, there was an obvious increase in the levels of several methylation-related metabolites. Thus, upregulated S-adenosylmethionine, S-adenosylhomocysteine, and N6,N6,N6-trimethyl-L-lysine indicated that LAMTOR1 may regulate the process of DNA or protein methylation. In addition, downregulation of 9-oxo-octadecadienoate, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) was also observed in LAMTOR1LKO mice liver tissues. Alterations in polyunsaturated fatty acids, such as EPA and DHA, link LAMTOR1 to inflammatory and immune processes, which are known to play important roles in NASH pathogenesis. These metabolic disorders demonstrated that LAMTOR1 significantly contributed to the metabolic mechanism of NASH. Furthermore, gene expression correlations were analyzed to interpret the regulatory role of LAMTOR1 from the perspective of genetic networks. Owing to a paucity of liver whole-transcriptome studies in NASH, correlation analysis was performed based on HCC transcriptome data from public databases. First, a negatively regulated relationship was observed between LAMTOR1 and MAT1A (R=-0.47). MAT1A encodes methionine adenosyltransferase 1A, an essential enzyme that catalyzes the formation of S-adenosylmethionine. Based on the upregulation of UDP-GlcNAc under hepatocyte LAMTOR1 depletion, it was predicted that LAMTOR1 positively influenced MGAT1 (R=0.47), a gene encoding alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase. Together with changes in succinyladenosine caused by hepatocyte LAMTOR1 deletion, predicted correlation results showed that LAMTOR1 may also participate in the pathogenesis through the positive regulatory relationship with ADSL (R=0.59). The ADSL gene provides instructions for making an enzyme called adenylosuccinate lyase, which can dephosphorylate the substrate succinyladenosine. In this study, LAMTOR1 was identified to specifically regulate multiple key metabolic pathways based on both NASH mouse models and gene expression correlations. These results illustrate the important role of LAMTOR1 in the progression of NASH and malignant transformation of liver inflammation, which provides a theoretical basis for the diagnosis and treatment of NASH or possible NASH-driven HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Cromatografia Líquida , Modelos Animais de Doenças , Inflamação , Fígado , Espectrometria de Massas , Metionina , Camundongos
15.
Adv Sci (Weinh) ; : e2102666, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523247

RESUMO

Necrosis induces strong inflammation with undesirable implications in clinics compared with apoptosis. Fortunately, the switch between necrosis and apoptosis could be realized by tailoring the appropriate structural properties of gold nano rods (GNRs) that could precisely modulate cell death pathways. Herein, the intracellular interaction between GNRs and organelles is monitored and it is found that lysosomes dominates necrosis/apoptosis evoking. Then the surface molecule density of GNRs, which is first defined as ρsurf. molecule (Nsurf. molecules /(a × π × Diameter × Length)), mediates lysosome activities as the membrane permeabilization (LMP), the Cathepsin B and D release, the cross-talk between lysosome and different organelles, which selectively evokes apoptosis or necrosis and the production of TNF-α from macrophages. GNRs with small ρsurf. molecule mainly induce apoptosis, while with large ρsurf. molecule they greatly contribute to necrosis. Interestingly, necrosis can be suppressed by GNRs with higher ρsurf. molecule due to the overexpression of key protease caspase 8, which cleaves the RIP1-RIP3 complex and activates caspase 3 followed by necrosis to apoptosis transition. This investigation indicates that the ρsurf. molecule greatly affects the utility of nanomaterials and different structural properties of nanomaterials have different implications in clinics.

16.
Biochem Biophys Res Commun ; 578: 21-27, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34534741

RESUMO

Serine and arginine-rich splicing factor 3 (SRSF3), the smallest member of the Ser/Arg-rich (SR) RNA-binding protein family, regulates multiple aspects of post-transcriptional gene expression program. Although SRSF3 is essential for early embryo development, reprogramming, and pluripotency maintenance, the RNA targets and specificity of RNA recognition of SRSF3 are not well understood in human pluripotent stem cells. In this study, we used inducible TRIBE (targets of RNA binding sites by editing) to identify RNA targets and binding motifs of SRSF3 in human embryonic stem cells (hESCs). We identified 3888 confident binding sites of SRSF3, corresponding to 1222 gene targets. Our results showed that nearly half of the binding sites were distributed in exons, reflecting the alternative splicing function of SRSF3. Motif analysis demonstrated that two of the SRSF3 recognition sequences were the same as the motifs identified in mouse embryonic stem cells, suggesting the recognition sequences of SRSF3 may be conserved in mammals. Overall, our analyses revealed the RNA targets of SRSF3 and uncovered its RNA recognition specificity, providing a valuable resource for understanding the function of SRSF3 in human embryonic stem cells.

17.
Biosens Bioelectron ; 194: 113594, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34474280

RESUMO

Gastric cancer cell-derived exosomes as biomarkers have a very high application potential to the non-invasive detection of early-stage gastric cancer. However, the small size of exosomes (30-150 nm) results in huge challenges in separating and detecting them from complex media (e.g., plasma, urine, saliva, and cell culture supernatant). Here we proposed a highly integrated exosome separation and detection (ExoSD) chip to immunomagnetic separate exosomes from cell culture supernatant in a manner of continuous flow, and to immunofluorescence detect gastric cancer cell-derived exosomes with high sensitivity. The ExoSD chip has achieved a high exosome recovery (>80%) and purity (>83%) at the injection rate of 4.8 mL/h. Furthermore, experimental results based on clinical serum samples of patients with gastric cancer (stages I and II) show that the detection rate of the ExoSD chip is as high as 70%. The proposed ExoSD chip has been successfully demonstrated as a cutting-edge platform for exosomes separation and detection. It can be served as a versatile platform to extend to the applications of separation and detection of the other cell-derived exosomes or cells.


Assuntos
Técnicas Biossensoriais , Exossomos , Neoplasias Gástricas , Detecção Precoce de Câncer , Humanos , Separação Imunomagnética , Neoplasias Gástricas/diagnóstico
18.
Cancer Lett ; 524: 42-56, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34582976

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has the highest fatality rate of any solid tumor, with a five-year survival rate of only 10% in the USA. PDAC is characterized by early metastasis. More than 50% of patients present with distant metastases at the time of diagnosis, and the majority of patients will develop metastasis within 4 years after tumor resection. Despite extensive studies, the molecular mechanisms underlying PDAC metastasis remain unclear. The polyoma enhancer activator protein (PEA3) subfamily was reported to play a vital role in the initiation and progression of multiple tumors. Herein, we found that ETS variant 4 (ETV4) was highly expressed in PDAC tissues and associated with poor survival. Univariate and multivariate analyses revealed that ETV4 expression was an independent prognostic factor for patient survival. Further experiments showed that ETV4 overexpression promoted PDAC invasion and metastasis both in vitro and in vivo. For the first time, we demonstrated that, mechanistically, ETV4 increased CXCR5 expression by directly binding to the CXCR5 promoter region. Knockdown of CXCR5 significantly reversed ETV4-mediated PDAC migration and invasion, while CXCR5 overexpression exerted the opposite effects. Intriguingly, we found that CXCL13, a specific ligand of CXCR5, increased ETV4 expression and promoted PDAC invasion and metastasis by activating the ERK1/2 pathway. ETV4 knockdown significantly abrogated the enhanced migratory and invasive abilities induced by the CXCL13/CXCR5 axis. In addition, a CXCR5 neutralizing antibody disrupted the CXCL13/ETV4/CXCR5 positive feedback loop and inhibited cell migration and invasion. Overall, in this study, we demonstrated that ETV4 plays a vital role in PDAC metastasis and defined a novel CXCL13/ETV4/CXCR5 positive feedback loop. Targeting this pathway has implications for potential therapeutic strategies for PDAC treatment.

19.
J Food Sci Technol ; 58(10): 3780-3789, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34471301

RESUMO

This work proposes a novel potential source of antiallergens based on bioactive peptides. Cashew-nut protein hydrolysate with antiallergic activity was prepared from cashew nuts through protease treatment. The change in the antiallergic activity of cashew-nut protein hydrolysate during in vitro simulated digestion was investigated. Cashew-nut protein hydrolysates were prepared through treatment using five different enzymes, namely, Alcalase, Protamex, Neutrase, papain, and bromelin. According to the results of molecular weight distribution, more small molecular weight peptides could be obtained by selecting Alcalase protease than other proteases, and the degree of hydrolysis, trichloroacetic acid-soluble peptide yield and hyaluronidase inhibitory rate of the hydrolysate were 17.0 ± 61.52%, 26.28 ± 0.13% and 62.06% ± 5.07%, which were significantly higher than those of other proteases. Therefore, Alcalase is the most suitable protease for the preparation of cashew-nut hydrolysates. Cashew-nut protein hydrolysates prepared with Alcalase under optimum conditions were fractionated through ultrafiltration. Fractions with low molecular weight exhibited the highest hyaluronidase inhibitory rate (90.57%) among all fractions. The inhibition of hyaluronidase activity during digestion showed that cashew-nut protein hydrolysate III (CPH III) has persistent antiallergic activity. Therefore, CPH III could serve as a potential source of functional peptides with health-promoting effects.

20.
Pharmacol Res ; 172: 105857, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34461223

RESUMO

Opioid relapse is generally caused by the recurrence of context-induced memory reinstatement of reward. However, the internal mechanisms that facilitate and modify these processes remain unknown. One of the key regions of the reward is the nucleus accumbens (NAc) which receives glutamatergic projections from the dorsal hippocampus CA1 (dCA1). It is not yet known whether the dCA1 projection to the NAc shell regulates the context-induced memory recall of morphine. Here, we used a common model of addiction-related behavior conditioned place preference paradigm, combined with immunofluorescence, chemogenetics, optogenetics, and electrophysiology techniques to characterize the projection of the dCA1 to the NAc shell, in context-induced relapse memory to morphine. We found that glutamatergic neurons of the dCA1 and gamma aminobutyric acidergic (GABA) neurons of the NAc shell are the key brain areas and neurons involved in the context-induced reinstatement of morphine memory. The dCA1-NAc shell glutamatergic input pathway and the excitatory synaptic transmission of the dCA1-NAc shell were enhanced via the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) when mice were re-exposed to environmental cues previously associated with drug intake. Furthermore, chemogenetic and optogenetic inactivation of the dCA1-NAc shell pathway decreased the recurrence of long- and short-term morphine-paired context memory in mice. These results provided evidence that the dCA1-NAc shell glutamatergic projections mediated the context-induced memory recall of morphine.

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