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1.
Ecotoxicol Environ Saf ; 282: 116694, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971101

RESUMO

In this study, a microcosm experiment was conducted to investigate the effects of Na2S2O8 preoxidation combined with biostimulation on petroleum-contaminated soil remediation. The response of microbial community during this process was explored using BIOLOG ECO microplate carbon utilization method and 16 s rDNA high-throughput sequencing. The results showed that use of 10 mg/g Na2S2O8 removed 19.8 % of the petroleum hydrocarbons, reduced soil biotoxicity and did not affect soil microbial activity compared to other concentrations. Therefore, sodium persulfate of ca. 10 mg/g was used to oxidize petroleum in soil before the biostimulation experiment with organic and inorganic fertilizers. Our finding showed that the content of total petroleum hydrocarbons (TPHs) in soil was reduced by 43.3 % in inorganic fertilizer treatment after 60 days. The results of BIOLOG ECO microplate carbon utilization analysis and 16 S rDNA high-throughput sequencing further confirmed that biostimulation quickly restored the microbial activities in oxidant treated soil. The main marker bacteria in chemical oxidation combined with biostimulation remediation were Arthrobacter and Paenarthrobacter, and their relative abundances were both significantly negatively correlated with the content of petroleum hydrocarbons in soil.

2.
ACS Appl Mater Interfaces ; 16(26): 33021-33037, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38888460

RESUMO

Hypoxia can lead to liver fibrosis and severely limits the efficacy of photodynamic therapy (PDT). Herein, carbon nitride (CN)-based hybrid nanoparticles (NPs) VPSGCNs@TSI for light-driven water splitting were utilized to solve this problem. CNs were doped with selenide glucose (Se-glu) to enhance their red/NIR region absorption. Then, vitamin A-poly(ethylene glycol) (VA-PEG) fragments and aggregation-induced emission (AIE) photosensitizers TSI were introduced into Se-glu-doped CN NPs (VPSGCNs) to construct VPSGCNs@TSI NPs. The introduction of VA-PEG fragments enhanced the targeting of the NPs to activated hepatic stellate cells (HSCs) and reduced their toxicity to ordinary liver cells. VPSGCN units could trigger water splitting to generate O2 under 660 nm laser irradiation, improve the hypoxic environment of the fibrosis site, downregulate HIF-1α expression, and activate HSC ferroptosis via the HIF-1α/SLC7A11 pathway. In addition, generated O2 could also increase the reactive oxygen species (ROS) production of TSI units in a hypoxic environment, thereby completely reversing hypoxia-triggered PDT resistance to enhance the PDT effect. The combination of water-splitting materials and photodynamic materials showed a 1 + 1 > 2 effect in increasing oxygen levels in liver fibrosis, promoting ferroptosis of activated HSCs and reversing PDT resistance caused by hypoxia.


Assuntos
Ferroptose , Células Estreladas do Fígado , Cirrose Hepática , Nanopartículas , Fotoquimioterapia , Nanopartículas/química , Animais , Ferroptose/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Camundongos , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Nitrilas/química , Nitrilas/farmacologia , Humanos , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Espécies Reativas de Oxigênio/metabolismo
3.
Pharmacol Res ; 205: 107253, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38862072

RESUMO

Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates a variety of key processes like inhibiting angiogenesis by reducing vascular endothelial growth factor levels and protecting the blood-retinal barrier (BRB) integrity by enhancing tight junction proteins and pericyte coverage. Melatonin also maintains cell health by modulating autophagy via the Sirt1/mTOR pathways, reduces inflammation, promotes antioxidant enzyme activity, and regulates intraocular pressure fluctuations. Additionally, melatonin protects retinal ganglion cells by modulating aging and inflammatory pathways. Understanding melatonin's multifaceted functions in ocular health could expand the knowledge of ocular pathogenesis, and shed new light on therapeutic approaches in ocular diseases. In this review, we summarize the current evidence of ocular functions and therapeutic potential of melatonin and describe its roles in angiogenesis, BRB integrity maintenance, and modulation of various eye diseases, which leads to a conclusion that melatonin holds promising treatment potential for a wide range of ocular health conditions.


Assuntos
Oftalmopatias , Melatonina , Melatonina/uso terapêutico , Melatonina/metabolismo , Melatonina/farmacologia , Humanos , Animais , Oftalmopatias/tratamento farmacológico , Oftalmopatias/metabolismo , Olho/metabolismo , Olho/irrigação sanguínea , Olho/efeitos dos fármacos , Barreira Hematorretiniana/metabolismo , Barreira Hematorretiniana/efeitos dos fármacos
4.
ACS Appl Mater Interfaces ; 16(25): 32762-32772, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38867400

RESUMO

Currently, the development of hydrogels with excellent mechanical properties (elasticity, fatigue resistance, etc.) and conductive properties can better meet their needs in the field of flexible sensor device applications. Generally, hydrogels with a denser cross-linking density tend to have better mechanical properties, but the improvement in mechanical properties comes at the expense of reduced electrical conductivity. Directly generating CaCO3 in the hydrogel prepolymer can not only increase the cross-linking density of its network but also introduce additional ions to enhance its internal ionic strength, which is beneficial to improving the conductivity of the hydrogel. It is still a big challenge to directly generate CaCO3 in the static prepolymer solution and ensure its uniform dispersion in the hydrogel. Herein, we adopted an improved preparation method to ensure that the directly generated CaCO3 particles can be evenly dispersed in the static prepolymer solution until the polymerization is completed. Finally, a PAM/PVA/CaCO3 hydrogel with supertensile, compressive, toughness, and fatigue resistance properties was prepared. In addition, the presence of free Na+ and Cl- gives the hydrogel excellent conductivity and sensing performance to monitor daily human activities. On the basis of the application of hydrogels in information communication, we have further deepened this application by combining the characteristics of hydrogels themselves. Combined with ASCII code, the hydrogel can also be applied in information exchange and information encryption and decryption, achieving the antitheft function in smart locks. A variety of excellent performance integrated PAM/PVA/CaCO3 hydrogels have broad application prospects for flexible sensors, highlighting great potential in human-computer interaction and intelligent information protection.

5.
Front Cardiovasc Med ; 11: 1377095, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832316

RESUMO

Objective: To explore the clinical value of echocardiography in detecting fetal cardiac axis abnormalities during middle pregnancy for diagnosing conus arteriosus malformation, and to compare and analyze the genetic diagnosis results, in order to provide evidence for clinical diagnosis and intervention. Methods: Four hundred twenty-one fetuses with conus arteriosus malformation from January 2020 to October 2023 were included as the conus arteriosus malformation group, and 917 healthy fetuses (all single fetuses) matched at the same gestational age were selected as the healthy group. Results: There was no significant difference in gestational weeks between two groups (P > 0.05). The age of pregnant women in conus arteriosus malformation group was lower compared to healthy group (P < 0.05), and the fetal cardiac axis in conus arteriosus malformation group was significantly higher compared to healthy group (P < 0.05). Among the fetuses with conus arteriosus malformation, tetralogy of Fallot (TOF), transposition of the great arteries (TGA) and double outlet right ventricle (DORV) had the highest proportions, accounting for 38.00%, 18.29% and 17.58%, respectively. Among all types of conus arteriosus malformations, atresia pulmonary valve syndrome associated with TOF, persistent truncus arteriosus and DORV exhibited higher proportions of fetal cardiac axis abnormalities, at 75.00%, 36.84% and 27.03%, respectively, while TGA and interrupted aortic arch associated with B-type interruption had lower proportions of fetal cardiac axis abnormalities, at 2.60% and 4.55%, respectively. Genetic testing was conducted on 73 cases (17.34%) of fetuses with conus arteriosus malformation in this study. Among them, fetal cardiac axis abnormalities were considered positive for genetic results due to factors such as aneuploidy, copy number abnormalities, and single-gene pathogenicity. A total of 31 cases tested positive for genetic anomalies, with a positive rate of approximately 42.47%. Conclusion: In the middle pregnancy, the fetal cardiac axis in cases of conus arteriosus malformation was significantly higher than in normal fetuses. Moreover, there were variations in fetal cardiac axis among different types of conus arteriosus malformations, and these differences were notably associated with genetic diagnostic results.

6.
Heliyon ; 10(8): e29159, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38644860

RESUMO

Acute kidney injury (AKI) is a clinical syndrome with high morbidity and mortality caused by various factor. The specific strategies for AKI are still lacking. GSK3ß is widely expressed in the kidneys. In acute models of injury, GSK3ß promotes the systemic inflammatory response, increases the proinflammatory release of cytokines, induces apoptosis, and alters cell proliferation. We screened a series of 3-(4-pyridyl)-5-(4-sulfamido-phenyl)-1,2,4-oxadiazole derivatives which are recognized as new GSK3ß inhibitors, and found that 5n had the least toxicity and the best cell protection. We then tested the anti-inflammatory and reno-protective effect of 5n in cisplatin-treated tubular epithelial cells. 5n had anti-inflammation effect indicated by phosphor-NF-κB detection. Finally, we found that 5n ameliorated renal injury and inflammation in cisplatin-induced AKI mouse model. Silencing GSK3ß inhibited cell injury and inflammation induced by cisplatin. We found that GSK3ß interacted with PP2Ac to modulate the activity of NF-κB. In conclusion, 5n, the novel GSK3ß inhibitor, protects against AKI via PP2Ac-dependent mechanisms which may provide a potential strategy for the treatment of AKI in clinic.

7.
MedComm (2020) ; 5(3): e504, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38469551

RESUMO

The circadian clock system orchestrates daily behavioral and physiological rhythms, facilitating adaptation to environmental and internal oscillations. Disruptions in circadian rhythms have been linked to increased susceptibility to various diseases and can exacerbate existing conditions. This review delves into the intricate regulation of diurnal gene expression and cell function by circadian clocks across diverse tissues. . Specifically, we explore the rhythmicity of gene expressions, behaviors, and functions in both immune and non-immune cells, elucidating the regulatory effects and mechanisms imposed by circadian clocks. A detailed discussion is centered on elucidating the complex functions of circadian clocks in regulating key cellular signaling pathways. We further review the circadian regulation in diverse diseases, with a focus on inflammatory diseases, cancers, and systemic diseases. By highlighting the intimate interplay between circadian clocks and diseases, especially through clock-controlled cell function, this review contributes to the development of novel disease intervention strategies. This enhanced understanding holds significant promise for the design of targeted therapies that can exploit the circadian regulation mechanisms for improved treatment efficacy.

8.
Toxics ; 12(2)2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38393240

RESUMO

1,4-dioxane is a potential carcinogen in water and is difficult to deal with due to its robust cycloether bond and complete miscibility with water. To remove 1,4-dioxane in an economically viable and environmentally friendly way, a series of carbon aerogels were synthesized as adsorbents for 1,4-dioxane. The experiment results showed that adsorption performances were closely related to the preparation conditions of carbon aerogels, such as the molar ratio, heating rate, pyrolysis temperature and residence time, which were carefully controlled. Scanning electron microscope analysis revealed the presence of a three-dimensional porous network structure in carbon aerogels. Brunauer-Emmett-Teller analysis results demonstrated an increase in specific surface area (673.89 m2/g) and total pore volume after carbonization, with an increase in mesoporous porosity and a decrease in microporosity. When considering each variable individually, the highest specific surface area of prepared carbon aerogels was achieved at a pyrolysis temperature of 800 °C, a holding time of 1 h, and a heating rate of 2 °C/min. Under optimal experimental conditions, the adsorption removal of 1,4-dioxane by carbon aerogels exceeded 95%, following quasi-second-order kinetics and Langmuir isothermal adsorption isotherms, indicating that monolayer adsorption on the surface of carbon aerogels occurred. The maximum adsorption capacity obtained was 67.28 mg/g at a temperature of 318 K, which was attributed to the presence of a large proportion of mesopores and abundant micropores simultaneously in carbon aerogels. Furthermore, with the interference of chlorinated solvents such as trichloroethylene (TCE), the removal efficiency of 1,4-dioxane had no obvious inhibition effect. Regeneration experiments showed that after five continuous cycles, the carbon aerogels still kept a comparable adsorption capacity, which illustrates its potential application in 1,4-dioxane-polluted water purification.

9.
Nat Commun ; 15(1): 1213, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38332012

RESUMO

Dysfunction of invariant natural killer T (iNKT) cells contributes to immune resistance of tumors. Most mechanistic studies focus on their static functional status before or after activation, not considering motility as an important characteristic for antigen scanning and thus anti-tumor capability. Here we show via intravital imaging, that impaired motility of iNKT cells and their exclusion from tumors both contribute to the diminished anti-tumor iNKT cell response. Mechanistically, CD1d, expressed on macrophages, interferes with tumor infiltration of iNKT cells and iNKT-DC interactions but does not influence their intratumoral motility. VCAM1, expressed by cancer cells, restricts iNKT cell motility and inhibits their antigen scanning and activation by DCs via reducing CDC42 expression. Blocking VCAM1-CD49d signaling improves motility and activation of intratumoral iNKT cells, and consequently augments their anti-tumor function. Interference with macrophage-iNKT cell interactions further enhances the anti-tumor capability of iNKT cells. Thus, our findings provide a direction to enhance the efficacy of iNKT cell-based immunotherapy via motility regulation.


Assuntos
Células T Matadoras Naturais , Neoplasias , Humanos , Ativação Linfocitária , Neoplasias/terapia , Neoplasias/metabolismo , Imunoterapia/métodos , Macrófagos/metabolismo , Antígenos CD1d/metabolismo
10.
Arch Insect Biochem Physiol ; 115(1): e22070, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38288484

RESUMO

DNA barcoding is a useful addition to the traditional morphology-based taxonomy. A ca. 650 bp fragment of the 5' end of mitochondrial cytochrome c oxidase subunit I (hereafter COI-5P) DNA barcoding was sued as a practical tool for Gampsocleis species identification. DNA barcodes from 889 specimens belonging to 8 putative Gampsocleis species was analyzed, including 687 newly generated DNA barcodes. These barcode sequences were clustered/grouped into Operational Taxonomic Units (OTUs) using the criteria of five algorithms, namely Barcode Index Number (BIN) System, Assemble Species by Automatic Partitioning (ASAP), a Java program uses an explicit, determinate algorithm to define Molecular Operational Taxonomic Unit (jMOTU), Generalized Mixed Yule Coalescent (GMYC), and Bayesian implementation of the Poisson Tree Processes model (bPTP). The Taxon ID Tree grouped sequences of morphospecies and almost all MOTUs in distinct nonoverlapping clusters. Both long- and short-winged Gampsocleis species are reciprocally monophyletic in the Taxon ID Tree. In BOLD, 889 barcode sequences are assigned to 17 BINs. The algorithms ASAP, jMOTU, bPTP and GMYC clustered the barcode sequences into 6, 13, 10, and 23 MOTUs, respectively. BIN, ASAP, and bPTP algorithm placed three long-winged species, G. sedakovii, G. sinensis and G. ussuriensis within the same MOTU. All species delimitation algorithms split two short-winged species,G. fletcheri and G. gratiosa into at least two MOTUs each, except for ASAP algorithm. More detailed molecular and morphological integrative studies are required to clarify the status of these MOTUs in the future.


Assuntos
Código de Barras de DNA Taxonômico , Ortópteros , Animais , Teorema de Bayes , Ortópteros/genética , Filogenia , DNA
11.
Small ; 20(2): e2302765, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37679056

RESUMO

Corneal neovascularization (CoNV) is a major cause of visual impairment worldwide. Currently, available treatment options have limited efficacy and are associated with adverse effects due to biological barriers and clearance mechanisms. To address this challenge, a novel topical delivery system is developed-Gel 2_1&Eylea-an aflibercept-loaded eye-drop hydrogel mediated with cell-penetrating peptide 1. Gel 2_1&Eylea demonstrates superior membrane permeability, increased stability, and prolonged drug retention time on the ocular surface, and thus may improve drug efficacy. In a rabbit CoNV model, Gel 2_1&Eylea significantly reduces the density of neovascularization with no adverse effects on normal corneoscleral limbal vessels, demonstrating high efficacy and biocompatibility. This work identifies a promising treatment for CoNV which has the potential to benefit other ocular neovascular diseases.


Assuntos
Peptídeos Penetradores de Células , Neovascularização da Córnea , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Animais , Coelhos , Neovascularização da Córnea/tratamento farmacológico , Hidrogéis , Soluções Oftálmicas/uso terapêutico
12.
Heliyon ; 9(11): e21231, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027630

RESUMO

Cisplatin is a chemotherapeutant widely used in treating solid tumors, with the common side effect of acute kidney injury (AKI). Developing effective useful agent for preventing or treating cisplatin-induced AKI is of great importance. In this study, we investigate the protective effect of vaccarin, a chemical entity of flavonoid glycoside, against cisplatin-induced AKI. Cisplatin-treated C57BL/6J mice and human kidney-2 (HK-2) cells were used as the model of cisplatin-induced AKI. The levels of blood urea nitrogen (BUN) and creatine (Cr) levels and periodic acid-Schiff staining (PAS) scores decreased when vaccarin was administrated. Vaccarin had no impact on renal platinum accumulation, which was detected by the ICP-MS 6 h after cisplatin injection. Moreover, vaccarin can significantly alleviate the product of reactive oxygen species and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) in cisplatin-induced AKI, both in vivo and in vitro. In addition, vaccarin decreased the receptor-interacting protein kinase 1 (RIPK1) related programmed necrosis (necroptosis), cell apoptosis (shown by the protein levels of cleaved-caspase3 and flow cytometry) and inflammation (shown by the decreased levels of NLRP3, p-P65 and the mRNA of several inflammatory factors). NOX4 inhibitor GLX351322 (GLX) and NOX4 kowndown by siRNA have equivalent protective effect of vaccarin in vitro. When vaccarin was administered together with GLX or NOX4 siRNA, this protective effect of vaccarin did not further increase, as indicating by the index of oxidative stress, cell viability, necroptosis and apoptosis. In conclusion, vaccarin can alleviate cisplatin-induced AKI via inhibiting NOX4.

13.
Protein Pept Lett ; 30(10): 854-867, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37921157

RESUMO

BACKGROUND: It has been reported that activation of glutamate kainate receptor subunit 2 (GluK2) subunit-containing glutamate receptors and the following Fas ligand(FasL) up-regulation, caspase-3 activation, result in delayed apoptosis-like neuronal death in hippocampus CA1 subfield after cerebral ischemia and reperfusion. Nitric oxide-mediated S-nitrosylation might inhibit the procaspase activation, whereas denitrosylation might contribute to cleavage and activation of procaspases. OBJECTIVES: The study aimed to elucidate the molecular mechanisms underlying procaspase-3 denitrosylation and activation following kainic acid (KA)-induced excitotoxicity in rat hippocampus. METHODS: S-nitrosylation of procaspase-3 was detected by biotin-switch method. Activation of procaspase-3 was shown as cleavage of procaspase-3 detected by immunoblotting. FasL expression was detected by immunoblotting. Cresyl violets and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining were used to detect apoptosis-like neuronal death in rat hippocampal CA1 and CA3 subfields. RESULTS: KA led to the activation of procaspase-3 in a dose- and time-dependent manner, and the activation was inhibited by KA receptor antagonist NS102. Procaspase-3 was denitrosylated at 3 h after kainic acid administration, and the denitrosylation was reversed by SNP and GSNO. FasL ASODNs inhibited the procaspase-3 denitrosylation and activation. Moreover, thioredoxin reductase (TrxR) inhibitor auranofin prevented the denitrosylation and activation of procaspase-3 in rat hippocampal CA1 and CA3 subfields. NS102, FasL AS-ODNs, and auranofin reversed the KAinduced apoptosis and cell death in hippocampal CA1 and CA3 subfields. CONCLUSIONS: KA led to denitrosylation and activation of procaspase-3 via FasL and TrxR. Inhibition of procaspase-3 denitrosylation by auranofin, SNP, and GSNO played protective effects against KA-induced apoptosis-like neuronal death in rat hippocampal CA1 and CA3 subfields. These investigations revealed that the procaspase-3 undergoes an initial denitrosylation process before becoming activated, providing valuable insights into the underlying mechanisms and possible treatment of excitotoxicity.


Assuntos
Auranofina , Ácido Caínico , Ratos , Animais , Ácido Caínico/toxicidade , Ácido Caínico/metabolismo , Caspase 3/metabolismo , Auranofina/metabolismo , Auranofina/farmacologia , Ratos Sprague-Dawley , Hipocampo/metabolismo
15.
Nano Converg ; 10(1): 37, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37561270

RESUMO

With a high specific capacity and low electrochemical potentials, metal anode batteries that use lithium, sodium and zinc metal anodes, have gained great research interest in recent years, as a potential candidate for high-energy-density storage systems. However, the uncontainable dendrite growth during the repeated charging process, deteriorates the battery performance, reduces the battery life and more importantly, raises safety concerns. With their unique properties, two-dimensional (2D) materials, can be used to modify various components in metal batteries, eventually mitigating the dendrite growth, enhancing the cycling stability and rate capability, thus leading to safe and robust metal anodes. In this paper, we review the recent advances of 2D materials and summarize current research progress of using 2D materials in the applications of (i) anode design, (ii) separator engineering, and (iii) electrolyte modifications by guiding metal ion nucleation, increasing ion conductivity, homogenizing the electric field and ion flux, and enhancing the mechanical strength for safe metal anodes. The 2D material modifications provide the ultimate solution for obtaining dendrite-free metal anodes, realizes the high energy storage application, and indicates the importance of 2D materials development. Finally, in-depth understandings of subsequent metal growth are lacking due to research limitations, while more advanced characterizations are welcome for investigating the metal deposition mechanism. The more facile and simplified preparation of 2D materials possess great prospects in high energy density metal anode batteries, and thus fulfils the development of EVs.

16.
Adv Healthc Mater ; 12(29): e2301485, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37463681

RESUMO

Hypoxia is an important feature, which can upregulate the hypoxia-inducible factor-1α (HIF-1α) expression and promote the activation of hepatic stellate cells (HSCs), leading to liver fibrosis. Currently, effective treatment for liver fibrosis is extremely lacking. Herein, a safe and effective method is established to downregulate the expression of HIF-1α in HSCs via targeted delivery of VA-PEG-modified CNs-based nanosheets-encapsulated (VA-PEG-CN@GQDs) HIF-1α small interfering RNA (HIF-1α-siRNA). Due to the presence of lipase in the liver, the reversible release of siRNA can be promoted to complete the transfection process. Simultaneously, VA-PEG-CN@GQD nanosheets enable trigger the water splitting process to produce O2 under near-infrared (NIR) irradiation, thereby improving the hypoxic environment of the liver fibrosis site and maximizing the downregulation of HIF-1α expression to improve the therapeutic effect, as demonstrated in liver fibrosis mice. Such combination therapy can inhibit the activation of HSCs via HIF-1α-mediated TGF-ß1/Smad pathway, achieving outstanding therapeutic effects in liver fibrosis mice. In conclusion, this study proposes a novel strategy for the treatment of liver fibrosis by regulating the hypoxic environment and the expression of HIF-1α at lesion site.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Fator de Crescimento Transformador beta1 , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , RNA Interferente Pequeno/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Cirrose Hepática/terapia , Hipóxia
17.
J Leukoc Biol ; 114(4): 335-346, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37479674

RESUMO

CD8+ invariant natural killer T (iNKT) cells are functionally different from other iNKT cells and are enriched in human but not in mouse. To date, their developmental pathway and molecular basis for fate decision remain unclear. Here, we report enrichment of CD8+ iNKT cells in neonatal mice due to their more rapid maturation kinetics than CD8- iNKT cells. Along developmental trajectories, CD8+ and CD8- iNKT cells separate at stage 0, following stage 0 double-positive iNKT cells, and differ in HIVEP3 expression. HIVEP3 is lowly expressed in stage 0 CD8+ iNKT cells and negatively controls their development, whereas it is highly expressed in stage 0 CD8- iNKT cells and positively controls their development. Despite no effect on IFN-γ, HIVEP3 inhibits granzyme B but promotes interleukin-4 production in CD8+ iNKT cells. Together, we reveal that, as a negative regulator for CD8+ iNKT fate decision, low expression of HIVEP3 in stage 0 CD8+ iNKT cells favors their development and T helper 1-biased cytokine responses as well as high cytotoxicity.

18.
Sheng Wu Gong Cheng Xue Bao ; 39(4): 1548-1561, 2023 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-37154322

RESUMO

Foot-and-mouth disease (FMD) is an acute, severe, and highly contagious infectious disease caused by foot-and-mouth disease virus (FMDV), which seriously endangers the development of animal husbandry. The inactivated FMD vaccine is the main product for the prevention and control of FMD, which has been successfully applied to control the pandemic and outbreak of FMD. However, the inactivated FMD vaccine also has problems, such as the instability of antigen, the risk of spread of the virus due to incomplete inactivation during vaccine production, and the high cost of production. Compared with traditional microbial and animal bioreactors, production of antigens in plants through transgenic technology has some advantages including low cost, safety, convenience, and easy storage and transportation. Moreover, since antigens produced from plants can be directly used as edible vaccines, no complex processes of protein extraction and purification are required. But, there are some problems for the production of antigens in plants, which include low expression level and poor controllability. Thus, expressing the antigens of FMDV in plants may be an alternative mean for production of FMD vaccine, which has certain advantages but still need to be continuously optimized. Here we review the main strategies for expressing active proteins in plants, as well as the research progress on the expression of FMDV antigens in plants. We also discuss the current problems and challenges encountered, with the aim to facilitate related research.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Vacinas Virais , Animais , Vírus da Febre Aftosa/genética , Febre Aftosa/prevenção & controle , Antígenos Virais/genética
19.
Exp Eye Res ; 232: 109518, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37257714

RESUMO

The aim of the study is to reveal the expression profiling and clinical significance of peripheral blood mononuclear cell (PBMC) tRNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) of premature infants with treatment-requiring retinopathy of prematurity (ROP). Significantly altered tsRNAs and miRNAs were screened using small RNA sequencing. RT-qPCR was used to verify the altered RNAs identified by small RNA transcriptomics. The target genes, their enriched functions, and possibly involved signaling pathways were identified by bioinformatics analyses. According to the small RNA sequencing, 125 tsRNAs and 205 miRNAs were significantly altered in PBMCs obtained from infants with treatment-requiring ROP compared with the premature controls without retinopathy. We preliminarily validated the significant alterations of 6 tsRNAs and 9 miRNAs. The target genes for those tsRNAs were enriched for cellular macromolecule metabolic process, intracellular anatomical structure, transcription regulatory region nucleic acid binding, and Th17 cell differentiation; those of the altered miRNAs were enriched for the developmental process, cell junction, DNA-binding transcription activator activity, and FoxO signaling pathway. By verification with the extended sample size, we identified tsRNAs and miRNAs that could be potential biomarkers with clinical values. The study recognized the alterations and clinical significance of changed tsRNA/miRNA profiles in PBMCs from premature infants with ROP. These significantly altered tsRNAs and miRNAs might be useful as potential diagnostic biomarkers and molecular targets for treatment-requiring ROP.


Assuntos
MicroRNAs , Retinopatia da Prematuridade , Recém-Nascido , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Leucócitos Mononucleares/metabolismo , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/genética , Retinopatia da Prematuridade/metabolismo , Relevância Clínica , Biomarcadores/metabolismo
20.
Cell Prolif ; 56(10): e13443, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36941019

RESUMO

Developing a nanosystem that can perform multimodal imaging-guided combination therapy is highly desirable but challenging. In this study, we introduced multifunctional nanoparticles (NPs) consisting of graphene oxide-grafted hollow mesoporous organosilica loaded with the drug doxorubicin (DOX) and photosensitizers tetraphenylporphyrin (TPP). These NPs were encapsulated by thermosensitive liposomes that release their contents once the temperature exceeds a certain threshold. Metal oxide NPs grown on the graphene oxide (GO) surface served multiple roles, including enhancing photothermal efficiency, acting as contrast agents to improve magnetic resonance imaging, increasing the sensitivity and specificity of photoacoustic imaging, and catalysing hydrogen peroxide for the generation of reactive oxygen species (ROS). When locally injected, the HMONs-rNGO@Fe3 O4 /MnOx@FA/DOX/TPP NPs effectively enriched in subcutaneous Hela cell tumour of mice. The photothermal/photodynamic/chemo combination therapy triggered by near-infrared (NIR) successfully suppressed the tumour without noticeable side effects. This study presented a unique approach to develop multimodal imaging-guided combination therapy for cancer.


Assuntos
Grafite , Nanopartículas , Humanos , Animais , Camundongos , Fototerapia , Células HeLa , Doxorrubicina/farmacologia , Linhagem Celular Tumoral
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