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1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(11): 1038-1044, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34809744

RESUMO

Metabolic reprogramming plays a very important role in the immunoregulatory process, and T cells, as the indispensable part in the immune response, realize the change of function and state through metabolic reprogramming. And endothelial cells exhibit similar metabolic reprogramming. This review explores the interaction between endothelial cells and T cells to reveal the mechanism of the former as non-professional antigen presenting cells to recruit and activate the latter and the specific mechanism of cytokines produced by the latter in inflammatory response to regulate the function and state of the former, aiming to find the potential therapeutic targets for chronic inflammation and provide new ideas for the treatment.

2.
Biomed Res Int ; 2021: 9968907, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34734089

RESUMO

The study aimed to investigate the effect of erdosteine on middle ear effusion in rats through mediating the Toll-like receptor 4 (TLR4) signaling pathway. Rats were injected with endotoxin to prepare the model of acute secretory otitis media (SOM). Then, they were divided into an acute SOM model group (model group, n = 15) and erdosteine treatment group (18 mg/kg, gavage, treatment group, n = 15). Besides, a normal group (n = 15) was set up. Two weeks later, routine biochemical indicators such as aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected. The inflammatory effusion due to otitis media was scored. The content of myeloperoxidase (MPO), matrix metalloproteinase (MMP), and tumor necrosis factor-beta (TNF-ß) in middle ear lavage fluid was detected via enzyme-linked immunosorbent assay (ELISA). Additionally, histomorphological changes were observed with the help of hematoxylin-eosin (HE) staining, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assays were carried out to measure the expression levels of TLR4 pathway genes and proteins as well as the messenger ribonucleic acid (mRNA) expression levels of key factors for otitis media (mucin 2 (MUC2) and MUC5A). In the model group, the levels of AST, ALP, and glutamic-pyruvic transaminase (GPT) were significantly increased (p < 0.05). Besides, the content of MPO, MMP, and TNF-ß was overtly raised in the model group (p < 0.05), while it was notably lowered in the treatment group (p < 0.05). In the treatment group, the cilia were slightly swollen, and inflammatory cells were fewer. The mRNA levels of MUC2, MUC5A, and pathway genes TLR4 and c-Jun N-terminal kinase (JNK) were elevated in the model group. In addition, the protein assay results revealed that the protein levels of TLR4 and JNK were evidently increased in the model group. Erdosteine can treat the middle ear effusion in rats by repressing the activation of the TLR4 signaling pathway.

3.
Front Microbiol ; 12: 759198, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659193

RESUMO

Hantavirus can cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome (HPS) in America, with high mortality and unknown mechanisms. Innate immunity is the host's first-line defense to bridge the acquired immunity against viral infections. However, hantavirus has evolved various strategies in both molecular and cellular aspects to evade the host's natural immune surveillance. The Interferon-I (IFN-I) signaling pathway, a central link of host defense, induces various antiviral proteins to control the infection. This paper summarizes the molecular mechanisms of hantavirus evasion mechanisms of the IFN signaling pathway and cellular processes such as regulated cell death and cell stress. Besides, hantavirus could also evade immune surveillance evasion through cellular mechanisms, such as upregulating immune checkpoint molecules interfering with viral infections. Understanding hantavirus's antiviral immune evasion mechanisms will deepen our understanding of its pathogenesis and help us develop more effective methods to control and eliminate hantavirus.

4.
J Hazard Mater ; 423(Pt B): 127139, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34537653

RESUMO

Accurate determination of antibiotic resistance genes (ARGs) in environmental DNA molecules (eDNA) is challenging owing to its low abundance in the aquatic environment. Here we report a facile and cost-efficient approach to extract trace amount of eDNAs in the aquatic environment using LnPO4 nanomaterials. Among the nanomaterials, less crystalline TbPO4 nanoneedles was identified as the most prominent candidate for long stranded DNA and short stranded DNA with adsorption efficiency above 97%. The adsorbed DNA was washed off from TbPO4 nanoneedles by optimized eluant (85% PBS, 15% EtOH, 4 g/L glycine, pH 10.0) with an optimal DNA recovery of 78.83%. Our approach showed a comparable or better eDNA extraction efficiency than a commercial extraction method for different environmental samples, but 89% less cost. The high purity of the extracted eDNA was demonstrated by a high A260/280 ratio. Using qPCR experiment, the occurrence of six common ARGs in the eDNA were detected with abundance ranging from 4.06 × 103 to 3.51 × 109 copies/L in river samples. This specific DNA capturer is valuable for the evaluation of spatial and temporal dynamic of ARGs pollution to provide insight into the potential risk with regard to the human health.

5.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(9): 769-774, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34533122

RESUMO

Objective To investigate the effects of nucleotide binding oligomerization domain-like receptor family caspase recruitment domain containing 3 (NLRC3) on the proliferation, migration and invasion of human colon cancer HCT116 and LoVo cells. Methods NLRC3 was knocked down in HCT116 and LoVo cells by NLRC3-specific siRNA (si-NLRC3). NLRC3 mRNA and protein expression was detected by real-time quantitative PCR and Western blotting. The proliferation ability of cancer cells was detected by CCK-8 assay; the clone formation ability was detected by clone formation assay; the invasion ability was detected by TranswellTM assay; the migration ability was detected by cell scratch healing assay. Results The transfection of si-NLRC3 down-regulated the expression of NLRC3 in HCT116 and LoVo cells. After NLRC3 knockdown, the proliferation and invasion ability of colon cancer cells were significantly strengthened and the cell migration was not significantly changed. Conclusion Knockdown of NLRC3 in HCT116 and LoVo cells can enhance cell proliferation and invasion ability, but has no effects on cancer cell migration.


Assuntos
Neoplasias do Colo , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , RNA Mensageiro , RNA Interferente Pequeno/genética
6.
J Hazard Mater ; 416: 125867, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492814

RESUMO

Neurodegenerative diseases may be caused by air pollution, such as PM2.5. However, particles still need to be elucidated the mechanism of synergistic neurotoxicity induced by pollutant-loading PM2.5. In this study, we used a reductionist approach to study leading role of lead (Pb) in PM2.5-induced hippocampal neuronal apoptosis and synaptic damage both in vivo and in vitro. Pb in PM2.5 caused neurotoxicity: 1) by increasing ROS levels and thus causing apoptosis in neuronal cells and 2) by decreasing the expression of PSD95 via interfering with the calcium signaling pathway through cAMP/CREB/pCREB/BDNF/PSD95 pathway and reducing the synapse length by 50%. This study clarifies a key factor in PM2.5-induced neurotoxicity and provides the experimental basis for reducing PM2.5-induced neurotoxicity.


Assuntos
Hipocampo , Chumbo , Apoptose , Chumbo/toxicidade , Material Particulado/toxicidade , Sinapses
7.
BMC Vet Res ; 17(1): 303, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503504

RESUMO

BACKGROUND: Interferon regulatory factor 2 (IRF2) is an important transcription factor, which can regulate the IFN response and plays a role in antiviral innate immunity in teleost. RESULTS: In the present study, the full-length cDNA sequence of IRF2 (CcIRF2) was characterized in common carp (Cyprinus carpio L.), which encoded a protein containing a conserved DNA-binding domain (DBD) and an IRF-associated domain (IAD). Phylogenetic analysis showed that CcIRF2 was most closely related with IRF2 of Ctenopharyngodon idella. CcIRF2 transcripts were detectable in all examined tissues, with higher expression in the gills, spleen and brain. CcIRF2 expression was upregulated in immune-related tissues of common carp upon polyinosinic:polycytidylic acid (poly (I:C)) and Aeromonas hydrophila stimulation and induced by poly (I:C), lipopolysaccharide (LPS), peptidoglycan (PGN) and flagellin in the peripheral blood leucocytes (PBLs) and head kidney leukocytes (HKLs). In addition, overexpression of CcIRF2 decreased the expression of IFN and IFN-stimulated genes (ISGs), and a dual-luciferase reporter assay revealed that CcIRF2 could increase the activation of NF-κB. CONCLUSIONS: These results indicate that CcIRF2 participates in antiviral and antibacterial immune response and negatively regulates the IFN response, which provide a new insight into the regulation of IFN system in common carp, and are helpful for the prevention and control of infectious diseases in carp farming.


Assuntos
Carpas/genética , Carpas/imunologia , Fator Regulador 2 de Interferon/genética , Fator Regulador 2 de Interferon/imunologia , Interferons/imunologia , NF-kappa B/imunologia , Transdução de Sinais/imunologia , Animais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia
8.
Front Immunol ; 12: 725150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504499

RESUMO

TRIF, an important adaptor downstream of Toll-like receptor signaling, plays a critical role in the innate immune response. In this study, the full-length coding sequence of TRIF from common carp (Cyprinus carpio L.) was cloned and characterized. Bioinformatics analysis showed that common carp TRIF exhibited a conserved TIR domain and had the closest relationship with grass carp TRIF. Expression analysis revealed that TRIF was constitutively expressed in the examined tissues of common carp, with the highest expression in the spleen and the lowest expression in the head kidney, and could be upregulated under Aeromonas hydrophila and poly(I:C) stimulation in vivo and under poly(I:C), LPS, PGN, flagellin, and Pam3CSK4 stimulation in vitro. Laser confocal microscopy showed that common carp TRIF colocalized with the Golgi apparatus. A luciferase reporter assay showed that carp TRIF elicited the activity of ifn-1 and nf-κb through the C-terminal domain. Additionally, crystal violet staining and qPCR assays revealed that carp TRIF inhibited the replication of SVCV in epithelioma papulosum cyprini (EPC) cells. Then, the signaling downstream of carp TRIF was investigated. Coimmunoprecipitation and Western blotting analysis demonstrated that carp TRIF interacted with TBK1 and augmented the expression of TRAF6 and phosphorylation of TBK1. Overexpression of carp TRIF significantly enhanced the expression of interferon-stimulated genes and inflammatory cytokines. Furthermore, flow cytometric (FCM) analysis suggested that carp TRIF induced apoptosis through the activation of caspase-8. In summary, our study indicated that TRIF plays an essential role in the innate immune responses of common carp against bacterial and viral infection.

9.
Bioengineered ; 12(1): 4868-4877, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34346829

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disease with global health and economic impact. 1-methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and oxidative stress are reported to participate in the pathological mechanism of PD. Ramelteon is a novel oral hypnotic agent that has recently been reported to display neuronal protective effects. However, it is unknown whether Ramelteon possesses a beneficial effect in PD. In this study, we aimed to examine the potential function of Ramelteon in MPP+-challenged neurons. We found that Ramelteon rescued the cell viability reduced by MPP+-stimulation. Further, oxidative stress in MPP+-challenged SH-SY5Y cells was mitigated by Ramelteon as verified by the upregulated levels of mitochondrial reactive oxygen species (ROS) and protein carboxyl, and the upregulation of NADPH oxidase 4 (NOX-4). Furthermore, the declined mitochondrial membrane potential (ΔΨm) caused by MPP+ was reversed by Ramelteon. Importantly, Ramelteon attenuated MPP+-induced apoptosis, accompanied by a decreased ratio of Bax/Bcl-2, inhibition of cytochrome C release, and downregulation of cleaved caspase-3. For the first time, we conclude that Ramelteon might ameliorate MPP+-induced neurotoxicity in neuronal cells in a mitochondrial-dependent pathway.

10.
Front Immunol ; 12: 692509, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335602

RESUMO

Hantaan virus (HTNV) infects humans and causes hemorrhagic fever with renal syndrome (HFRS). The development of well-characterized animal models of HFRS could accelerate the testing of vaccine candidates and therapeutic agents and provide a useful tool for studying the pathogenesis of HFRS. Because NLRC3 has multiple immunoregulatory roles, we investigated the susceptibility of Nlrc3-/- mice to HTNV infection in order to establish a new model of HFRS. Nlrc3-/- mice developed weight loss, renal hemorrhage, and tubule dilation after HTNV infection, recapitulating many clinical symptoms of human HFRS. Moreover, infected Nlrc3-/- mice showed higher viral loads in serum, spleen, and kidney than wild type C57BL/6 (WT) mice, and some of them manifested more hematological disorders and significant pathological changes within multiple organs than WT mice. Our results identify that HTNV infected Nlrc3-/- mice can develop clinical symptoms and pathological changes resembling patients with HFRS, suggesting a new model for studying the pathogenesis and testing of candidate vaccines and therapeutics.

11.
Vet Res ; 52(1): 88, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34130754

RESUMO

Toll-like receptor 19 (Tlr19) is a fish-specific TLR that plays a critical role in innate immunity. In the present study, we aimed to identify tlr19 from common carp (Cyprinus carpio L.) and explored its expression profile, localization, adaptor, and signaling pathways. A novel tlr19 cDNA sequence (Cctlr19) was identified in common carp. Phylogenetic analysis revealed that CcTlr19 was most closely related to Danio rerio Tlr19. Subcellular localization analysis indicates that CcTlr19 was synthesized in the free ribosome and then transported to early endosomes. Cctlr19 was constitutively expressed in all the examined tissues, with the highest expression in the brain. After poly(I:C) and Aeromonas hydrophila injection, the expression of Cctlr19 was significantly upregulated in immune-related organs. In addition, the expression of Cctlr19 was upregulated in head kidney leukocytes (HKL) upon stimulation with different ligands. Immunofluorescence and luciferase analyses indicate that CcTlr19 recruited TRIF as an adaptor. Furthermore, CcTlr19 can activate the expression of ifn-1 and viperin. Taken together, these findings lay the foundation for future research to investigate the mechanisms underlying fish tlr19.


Assuntos
Carpas/genética , Carpas/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Aeromonas hydrophila , Animais , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Infecções por Bactérias Gram-Negativas , Interferons/genética , Filogenia , Poli I-C , Análise de Sequência de DNA/veterinária , Transdução de Sinais , Receptores Toll-Like/química
12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(7): 596-601, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34140070

RESUMO

Objective To clarify the expression and clinical significance of ARHGAP11A in lung adenocarcinoma. Methods The expression of ARHGAP11A in lung adenocarcinoma and normal tissue was obtained and analyzed by searching online databases such as Oncomine, and bioinformatic analysis was carried out on the relevant clinicopathological parameters and survival data of lung cancer patients. PrognoScan prognostic analysis database was used to analyze the relationship between ARHGAP11A gene expression and prognosis of lung adenocarcinoma. STRING database was used to construct ARHGAP11A and its function-related gene network. Results Compared with normal tissue, ARHGAP11A was highly expressed in lung adenocarcinoma, and the later the clinical stage and the worse the differentiation, the higher the expression of ARHGAP11A and the worse the prognosis. Conclusion ARHGAP11A is highly expressed in lung adenocarcinoma and is related to poor prognosis of lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Prognóstico
13.
Commun Biol ; 4(1): 652, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34079056

RESUMO

Hantaan viruses (HTNVs) are zoonotic pathogens transmitted mainly by rodents and capable of infecting humans. Increasing knowledge of the human response to HTNV infection can guide the development of new preventative vaccines and therapeutic strategies. Here, we show that HTNV can infect CD8+ T cells in vivo in patients diagnosed with hemorrhagic fever with renal syndrome (HFRS). Electron microscopy-mediated tracking of the life cycle and ultrastructure of HTNV-infected CD8+ T cells in vitro showed an association between notable increases in cytoplasmic multivesicular bodies and virus production. Notably, based on a clinical cohort of 280 patients, we found that circulating HTNV-infected CD8+ T cell numbers in blood were proportional to disease severity. These results demonstrate that viral infected CD8+ T cells may be used as an adjunct marker for monitoring HFRS disease progression and that modulating T cell functions may be explored for new treatment strategies.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Vírus Hantaan/imunologia , Vírus Hantaan/patogenicidade , Febre Hemorrágica com Síndrome Renal/imunologia , Febre Hemorrágica com Síndrome Renal/virologia , Doença Aguda , Adulto , Linfócitos T CD8-Positivos/ultraestrutura , Micropartículas Derivadas de Células/ultraestrutura , Micropartículas Derivadas de Células/virologia , Citocinas/sangue , Progressão da Doença , Feminino , Vírus Hantaan/fisiologia , Febre Hemorrágica com Síndrome Renal/sangue , Humanos , Técnicas In Vitro , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Modelos Biológicos , Vírion/imunologia , Vírion/patogenicidade , Replicação Viral
14.
ACS Appl Mater Interfaces ; 13(18): 21272-21285, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33940792

RESUMO

Although eco-friendly amidoxime-based adsorbents own an excellent uranium (U)-adsorption capacity, their U-adsorption efficiency is commonly reduced and even damaged by the biological adhesion from bacteria/microorganisms in an aqueous environment. Herein, we present an antibiofouling ultrathin poly(amidoxime) membrane (AUPM) with highly enhanced U-adsorption performance, through dispersing the quaternized chitosan (Q-CS) and poly(amidoxime) in a cross-linked sulfonated cellulose nanocrystals (S-CNC) network. The cross-linked S-CNC not only can elevate the hydrophilicity to improve the U-adsorption efficiency of AUPM but also can enhance the mechanical strength to form a self-supporting ultrathin membrane (17.21 MPa, 10 µm thickness). More importantly, this AUPM owns a good antibiofouling property, owing to the broad-spectrum antibacterial quaternary ammonium groups of the Q-CS. As a result, within the 1.00 L of low-concentration (100 ppb) U-added pure water (pH ≈ 5) and seawater (pH ≈ 8) for 48 h, 30 mg of AUPM can recover 93.7% U and 91.4% U, respectively. Furthermore, compared with the U-absorption capacity of a blank membrane without the Q-CS, that of AUPM can significantly increase 37.4% reaching from 6.39 to 8.78 mg/g after being in natural seawater for only 25 d. Additionally, this AUPM can still maintain almost constant tensile strength during 10 cycles of adsorption-desorption, which indicates the relatively long-term usability of AUPM. This AUPM will be a promising candidate for highly efficient and large-scale U-recovery from both U-containing waste freshwater/seawater and natural seawater, which will be greatly helpful to deal with the U-pollution and enrich U for the consumption of nuclear power. More importantly, the work will provide a new convenient but universal strategy to fabricate new highly enhanced low-cost U-adsorbents, through the introduction of both an antibacterial property and a high mechanical performance, which will be a good reference for the design of new highly efficient U-adsorbents.


Assuntos
Incrustação Biológica/prevenção & controle , Membranas Artificiais , Oximas/química , Polímeros/química , Água do Mar/química , Urânio/isolamento & purificação , Águas Residuárias/química , Adsorção , Urânio/química
15.
ACS Omega ; 6(11): 7771-7777, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33778288

RESUMO

BACKGROUND AND PURPOSE: Cerebral ischemia-reperfusion injury is commonly induced during the treatment of ischemic stroke and is reported to be related to the blood-brain barrier destruction and brain vascular endothelial cell dysfunction. Anagliptin is a novel antidiabetic agent recently reported to protect neurons from oxidative stress. In the present study, we aim to investigate the protective property of anagliptin against oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury on endothelial cells and clarify the potential underlying mechanism. METHODS: OGD/R modeling was established on bEnd.3 brain endothelial cells. Cell viability was detected using the MTT assay, and the mitochondrial reactive oxygen species (ROS) level was measured using the mitoses red staining assay. The endothelial monolayer permeability was determined using an FITC-dextran permeation assay. The expression levels of NOX-4 and ZO-1 were evaluated using qRT-PCR and Western blot assays. The expressions of MLC-2, p-MLC-2, and myosin light chain kinase (MLCK) were determined using Western blot. RESULTS: First, the decreased cell viability, upregulated NOX-4, and elevated mitochondrial ROS level in the endothelial cells induced by OGD/R were reversed by treatment with anagliptin. Second, the enlarged endothelial permeability and the decreased expression level of ZO-1 in the endothelial cells induced by OGD/R were alleviated by anagliptin. Third, the downregulation of ZO-1 and enlarged brain endothelial monolayer permeability induced by OGD/R were ameliorated by an MLCK inhibitor, ML-7. Lastly, the elevated expressions of MLCK and p-MLC-2 induced by OGD/R were suppressed by anagliptin. CONCLUSION: Anagliptin protected against hypoxia/reperfusion-induced brain vascular endothelial permeability by increasing the expression ZO-1, mediated by inhibition of the MLCK/MLC-2 signaling pathway.

16.
Bone Marrow Transplant ; 56(7): 1635-1641, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33608657

RESUMO

Hepatic veno-occlusive disease or sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present prospective study, we aimed to investigate the incidence, management, and outcome of VOD/SOS in patients with thalassemia major (TM) who received allo-HSCT. VOD/SOS was diagnosed and classified based on the modified Seattle criteria. The prophylactic regimen for VOD/SOS was a combination treatment of dalteparin and lipo-PGE1. VOD/SOS was managed through an approach consisting of adequate supportive measures, short-term withdrawal of calcineurin inhibitors (CNIs), and the use of methylprednisolone and basiliximab for graft-versus-host disease prophylaxis. VOD/SOS was found in 54 of 521 patients (10.4%) at a median time of 12 days after allo-HSCT. The cumulative incidence of all-grade and moderate VOD/SOS was 10.4% and 4.2%, respectively. Among the 54 VOD/SOS patients, no patient developed severe grade and died from VOD/SOS. Besides, the cumulative incidence of transplant-related mortality on day 100 for patients with or without VOD/SOS was 0% vs. 4.0% (P = 0.187), respectively, and the 3-year overall survival rates were 94.3% vs. 93.2% (P = 0.707), respectively. Collectively, we concluded that appropriate symptomatic therapy and short-term withdrawal of CNIs safely mitigated the mortality of VOD/SOS in TM patients who underwent allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Talassemia beta , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Incidência , Polidesoxirribonucleotídeos/uso terapêutico , Estudos Prospectivos
17.
ACS Appl Mater Interfaces ; 13(2): 3246-3258, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33406816

RESUMO

Uranium is an extremely abundant resource in seawater that could supply nuclear fuel for over the long-term, but it is tremendously difficult to extract. Here, a new supramolecular poly(amidoxime) (PAO)-loaded macroporous resin (PLMR) adsorbent has been explored for highly efficient uranium adsorption. Through simply immersing the macroporous resin in the PAO solution, PAOs can be firmly loaded on the surface of the nanopores mainly by hydrophobic interaction, to achieve the as-prepared PLMR. Unlike existing amidoxime-based adsorbents containing many inner minimally effective PAOs, almost all the PAOs of PLMR have high uranium adsorption efficiency because they can form a PAO-layer on the nanopores with molecular-level thickness and ultrahigh specific surface area. As a result, this PLMR has highly efficient uranium adsorbing performance. The uranium adsorption capacity of the PLMR was 157 mg/g (the UPAO in the PLMR was 1039 mg/g), in 32 ppm uranium-spiked seawater for 120 h. Additionally, uranium in 1.0 L 100 ppb U-spiked both water and seawater can be removed quickly and the recovery efficiency can reach 91.1 ± 1.7% and 86.5 ± 1.9%, respectively, after being filtered by a column filled with 200 mg PLMR at 300 mL/min for 24 h. More importantly, after filtering 200 T natural seawater with 200 g PLMR for only 10 days, the uranium-uptake amount of the PLMR reached 2.14 ± 0.21 mg/g, and its average uranium adsorption speed reached 0.214 mg/(g·day) which is very fast among reported amidoxime-based adsorbents. This new adsorbent has great potential to quickly and massively recover uranium from seawater and uranium-containing wastewater. Most importantly, this work will provide a simple but general strategy to greatly enhance the uranium adsorption efficiency of amidoxime-functionalized adsorbents with ultrahigh specific surface area via supramolecular interaction, and even inspire the exploration of other adsorbents.

18.
Hum Gene Ther ; 32(9-10): 481-494, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33256481

RESUMO

ß-Thalassemia is one of the most prevalent genetic diseases worldwide. The current treatment for ß-thalassemia is allogeneic hematopoietic stem cell transplantation, which is limited due to lack of matched donors. Gene therapy has been developed as an alternative therapeutic option for transfusion-dependent ß-thalassemia (TDT). However, successful gene therapy for ß-thalassemia patients in China has not been reported. Here, we present the results of preclinical studies of an optimally designed lentiviral vector (LV) named LentiHBBT87Q in hematopoietic stem and progenitor cells (HSPCs) derived from Chinese TDT patients. LentiHBBT87Q was selected from a series of LVs with optimized backbone and de novo cloning strategy. It contains an exogenous T87Q ß-globin gene (HBBT87Q) driven by a specific reconstituted locus control region, and efficiently expresses HBB mRNA and HBB protein in erythroblasts derived from cord blood HSPCs. To facilitate clinical transformation, we manufactured clinical-grade LentiHBBT87Q (cLentiHBBT87Q) and optimized its transduction procedure. Importantly, transduction of cLentiHBBT87Q restored expression of HBB monomer and adult hemoglobin tetramer to relatively normal level in erythroblasts from bone marrow HSPCs of Chinese TDT patients that carry the most common mutation types and cover various genotypes, including ß0/ß0. Furthermore, viral integration sites (VISs) of cLentiHBBT87Q were similar to other LVs safely used in previous clinical trials, and gene-ontology (term) analysis of VIS targeted genes suggests that no tumor-associated pathways were enriched in treated samples. Taken together, we have engineered the cLentiHBBT87Q that can restore ß-globin expression in the HSPCs-derived erythroblasts of Chinese TDT patients with minimal risk of tumorigenesis, providing a favorable starting point for future clinical application.

19.
Int J Oncol ; 57(6): 1368-1380, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33174013

RESUMO

Hepatocellular carcinoma (HCC) is an invasive malignant neoplasm with a poor prognosis. The development of chemoresistance severely obstructs the chemotherapeutic efficiency of HCC treatment. Therefore, understanding the mechanisms of chemoresistance is important for improving the outcomes of patients with HCC. Eukaryotic translation initiation factor 5A2 (eIF5A2), which is considered to be an oncogene, has been reported to mediate chemoresistance in various types of cancer; however, its precise role in HCC remains unclear. Accumulating evidence has suggested that autophagy serves a dual role in cancer chemotherapy. The present study aimed to investigate the role of autophagy in eIF5A2­mediated doxorubicin resistance in HCC. High expression levels of eIF5A2 in human HCC tissues were observed by immunohistochemistry using a tissue microarray, which was consistent with the results of reverse transcription­quantitative PCR analysis in paired HCC and adjacent healthy tissues. HCC patient­derived tumor xenograft mouse model was used for the in vivo study, and knockdown of eIF5A2 effectively enhanced the efficacy of doxorubicin chemotherapy compared with that in the control group. Notably, eIF5A2 served as a repressor in regulating autophagy under chemotherapy. Silencing of eIF5A2 induced doxorubicin sensitivity in HCC cells by triggering lethal autophagy. In addition, 5­ethynyl­2'­deoxyuridine, lactate dehydrogenase release assay and calcein­AM/PI staining were used to determine the enhanced autophagic cell death induced by the silencing of eIF5A2 under doxorubicin treatment. Suppression of autophagy attenuated the sensitivity of HCC cells to doxorubicin induced by eIF5A2 silencing. The results also demonstrated that knockdown of the Beclin 1 gene, which is an autophagy regulator, reversed the enhanced autophagic cell death and doxorubicin sensitivity induced by eIF5A2 silencing. Taken together, these results suggested eIF5A2 may mediate the chemoresistance of HCC cells by suppressing autophagic cell death under chemotherapy through a Beclin 1­dependent pathway, and that eIF5A2 may be a novel potential therapeutic target for HCC treatment.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Hepáticas/tratamento farmacológico , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Adulto , Idoso , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Doxorrubicina/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Fatores de Iniciação de Peptídeos/genética , Proteínas de Ligação a RNA/genética , Transdução de Sinais/genética , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
20.
BMC Vet Res ; 16(1): 450, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213475

RESUMO

BACKGROUND: Interferon (IFN) regulatory factors (IRFs), as transcriptional regulatory factors, play important roles in regulating the expression of type I IFN and IFN- stimulated genes (ISGs) in innate immune responses. In addition, they participate in cell growth and development and regulate oncogenesis. RESULTS: In the present study, the cDNA sequence of IRF10 in common carp (Cyprinus carpio L.) was characterized (abbreviation, CcIRF10). The predicted protein sequence of CcIRF10 shared 52.7-89.2% identity with other teleost IRF10s and contained a DNA-binding domain (DBD), a nuclear localization signal (NLS) and an IRF-associated domain (IAD). Phylogenetic analysis showed that CcIRF10 had the closest relationship with IRF10 of Ctenopharyngodon idella. CcIRF10 transcripts were detectable in all examined tissues, with the highest expression in the gonad and the lowest expression in the head kidney. CcIRF10 expression was upregulated in the spleen, head kidney, foregut and hindgut upon polyinosinic:polycytidylic acid (poly I:C) and Aeromonas hydrophila stimulation and induced by poly I:C, lipopolysaccharide (LPS) and peptidoglycan (PGN) in peripheral blood leucocytes (PBLs) and head kidney leukocytes (HKLs) of C. carpio. In addition, overexpression of CcIRF10 was able to decrease the expression of the IFN and IFN-stimulated genes PKR and ISG15. CONCLUSIONS: These results indicate that CcIRF10 participates in antiviral and antibacterial immunity and negatively regulates the IFN response, which provides new insights into the IFN system of C. carpio.


Assuntos
Carpas/genética , Carpas/imunologia , Fatores Reguladores de Interferon/genética , Aeromonas hydrophila/imunologia , Animais , Carpas/metabolismo , DNA Complementar , Proteínas de Peixes , Lipopolissacarídeos/imunologia , Peptidoglicano/imunologia , Filogenia , Poli I-C/imunologia , Análise de Sequência de DNA , Distribuição Tecidual
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