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1.
Chem Commun (Camb) ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36661386

RESUMO

We developed a circular bivalent aptamer (CBA) to precisely activate membrane receptor-mediated regenerative signaling for liver repair in vivo. The CBA showed enhanced biostability and receptor binding avidity, achieving effective pathway activation and satisfactory treatment in an acetaminophen-induced liver injury model. This work expands aptamer-based molecular engineering in regenerative medicine.

2.
Org Biomol Chem ; 21(3): 514-519, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36594355

RESUMO

Munronin V (1), isolated from Munronia henryi Harms, is the first example, to the best of our knowledge, of an unprecedented 7/7/6 tricarbocyclic framework featuring an unusual A,B-seco-limonoid ring. The structures of munronin V were established from extensive spectroscopic and electronic circular dichroism (ECD) analyses. The novel A,B-seco with two seven-membered lactones was formed as a result of Baeyer-Villiger oxidation. Compound 1 activated autophagy and inhibited Tau pathology as revealed by flow cytometric analyses, confocal imaging analysis and western blotting, and this effect was mediated by transcription factor EB (TFEB). These findings suggested that 1 might have potential as a compound for combating Alzheimer's disease.


Assuntos
Limoninas , Proteínas tau , Humanos , Doença de Alzheimer , Autofagia , Limoninas/química , Limoninas/farmacologia , Extratos Vegetais/química , Meliaceae/química
3.
Artigo em Inglês | MEDLINE | ID: mdl-36689577

RESUMO

Natural biopolymers can be controllably in situ synthesized in organisms and play important roles in biological activities. Inspired by this, the manipulation of in situ biosynthesis of functional polymers in vivo will be an important way to obtain materials for meeting biological requirements. Herein, in situ biosynthesis of functional conjugated polymer at the tumor site was achieved via the utilization of specific tumor microenvironment (TME) characteristics for the first time. Specially, a water-soluble aniline dimer derivative (N-(3-sulfopropyl) p-aminodiphenylamine, SPA) was artfully in situ polymerized into polySPA (PSPA) nanoparticles at the tumor site, which was activated via the catalysis of hydrogen peroxide (H2O2) overexpressed in TME to produce hydroxyl radical (•OH) by coinjected horseradish peroxidase (HRP). Benefiting from outstanding near-infrared (NIR)-II absorption of PSPA, the in situ polymerization process can be validly monitored by photoacoustic (PA) signal at the NIR-II region. Meanwhile, in situ polymerization would induce the size of polymeric materials from small to large, improving the distribution and retention of PSPA at the tumor site. On the combination of NIR-II absorption of PSPA and the size variation induced by polymerization, such polymerization can be applied for tumor-specific NIR-II light mediated PA image and photothermal inhibition of tumors, enhancing the precision and efficacy of tumor phototheranostics. Therefore, the present work opens the way to manipulate TME-activated in situ biosynthesis of functional conjugated polymer at the tumor site for overcoming formidable challenges in tumor theranostics.

4.
Dalton Trans ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36691961

RESUMO

Three copper(II) complexes C1-C3 were synthesized and fully characterized as chemodynamic therapy (CDT) anticancer agents. C1-C3 showed greater cytotoxicity than their ligands toward SK-OV-3 and T24 cells. Particularly, C2 showed high cytotoxicity toward T24 cells and low cytotoxicity toward normal human HL-7702 and WI-38 cells. Mechanistic studies demonstrated that C2 oxidized GSH to GSSG and produced ˙OH, which induced mitochondrial dysfunction and ER stress, finally leading to apoptosis of T24 cells. In addition, C2 inhibited autophagy by blocking autophagy flow, thereby closing the self-protection pathway of oxidative stress to enhance CDT. Importantly, C2 significantly inhibited T24 tumor growth with 57.1% inhibition in a mouse xenograft model. C2 is a promising lead as a potential CDT anticancer agent.

5.
J Int Med Res ; 51(1): 3000605221149879, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36694984

RESUMO

We herein report two cases involving children who died of influenza A (H3N2) virus infection-associated encephalopathy/encephalitis (IAE). Both children developed convulsions and impaired consciousness within a relatively short period and eventually died of brainstem failure. Patient 1 presented with high fever, vomiting, and diarrhea. Laboratory tests indicated persistently high lactate, alanine aminotransferase, and urea nitrogen concentrations in the blood as well as a high protein concentration in the cerebrospinal fluid. Patient 2 presented with persistent hyperthermia and progressive disturbance of consciousness, but the cerebrospinal fluid remained normal during the disease course. Both patients were actively given oseltamivir antiviral treatment after diagnosis of influenza virus infection. However, the disease progressed and invasive mechanical ventilation was performed. Both children's condition quickly progressed to IAE, and they eventually died. IAE is a rare complication of influenza virus infection with high mortality, and its pathogenesis remains unclear. The purpose of this report is to draw attention to the serious central nervous system complications of influenza infection and raise awareness of the fatal consequences of this disease among pediatricians.


Assuntos
Encefalopatias , Encefalite , Influenza Humana , Infecções por Orthomyxoviridae , Humanos , Criança , Influenza Humana/diagnóstico , Vírus da Influenza A Subtipo H3N2 , Encefalopatias/complicações , Encefalopatias/diagnóstico , Oseltamivir/uso terapêutico
6.
Biosens Bioelectron ; 224: 115052, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36603285

RESUMO

Toxicity screening and risk assessment of an overwhelmingly large and ever-increasing number of chemicals are vitally essential for ecological safety and human health. Genotoxicity is particularly important because of its association with mutagenicity, carcinogenicity and cancer. Phosphorylated histone H2AX (γH2AX) is an early sensitive genotoxic biomarker. It is therefore highly desirable to develop analytical methods for the detection of trace γH2AX to enable screening and assessment of genotoxicity. Here, we developed a novel cathodic photoelectrochemical (PEC) immunoassay with dual signal amplification for the rapid and ultrasensitive detection of γH2AX in cell lysates. A sandwich immuno-reaction targeting γH2AX was first carried out on a 96-well plate, using a secondary antibody/gold nanoparticle/glucose oxidase conjugate as the labeled detection antibody. The conjugate increased the production of H2O2 and thus provided the first mechanism of signal amplification. The immuno-reaction product containing H2O2 was then detected on a photocathode prepared from Bi2+xWO6 rich in oxygen vacancies, with H2O2 acting as electron acceptor. The oxygen vacancies acted as both adsorption and activation sites of H2O2 and thus enhanced the photocurrent, which provided another mechanism of signal amplification. As a result, an ultrasensitive immunoassay for γH2AX determination was established with a limit of detection of 6.87 pg/mL (S/N = 3) and a wide linear range from 0.01 to 500 ng/mL. The practicability of this assay was verified by detecting γH2AX in cell lysates exposed to known genotoxic chemicals. Our work offers a promising tool for the screening of genotoxic chemicals and opening a new avenue toward environmental risk assessment.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Humanos , Peróxido de Hidrogênio , Ouro , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Biomarcadores , Dano ao DNA , Técnicas Eletroquímicas/métodos , Limite de Detecção
7.
Sci Total Environ ; 867: 161344, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36610630

RESUMO

Multi-metal contaminated soil has received extensive attention. The biochar and bentonite-supported nano zero-valent iron (nZVI) (BC-BE-nZVI) composite was synthesized in this study by the liquid-phase reduction method. Subsequently, the BC-BE-nZVI composite was applied to immobilize cadmium (Cd), chromium (Cr), and lead (Pb) in simulated contaminated soil. The simultaneous immobilization efficiencies of Cd, Cr(VI), Crtotal, and Pb were achieved at 70.95 %, 100 %, 86.21 %, and 100 %, respectively. In addition, mobility and bioavailabilities of Cd, Cr, and Pb were significantly decreased and the risk of iron toxicity was reduced. Stabilized metal species in the contaminated soil (e.g., Cd(OH)2, Cd-Fe-(OH)2, CrxFe1-xOOH, CrxFe1-x(OH)3, PbO, PbCrO4, and Pb(OH)2) were formed after the BC-BE-nZVI treatment. Thus, the immobilization mechanisms of Cd, Cr, and Pb, including adsorption, reduction, co-precipitation, and complexation co-exist with the metals. More importantly, bacterial richness, bacterial diversity, soil enzyme activities (dehydrogenase, urease, and fluorescein diacetate hydrolase), and microbial activity were enhanced by applying the BC-BE-nZVI composite, thus increasing the soil metabolic function. Over all, this work applied a promising procedure for remediating multi- metal contaminated soil by using the BC-BE-nZVI composite.

8.
Environ Technol ; : 1-31, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36647685

RESUMO

High-cyclic polycyclic aromatic hydrocarbons (PAHs), with complex fused aromatic structures, are widespread, refractory and harmful in soil, but the current remediation technologies for high-cyclic PAHs are often inefficient and costly. This study focused on the biodegradation process of high-cyclic benzo[a]pyrene by Trametes versicolor crude enzymes. The crude enzymes exhibited high laccase activity (22112 U/L) and benzo[a]pyrene degradation efficiency (42.21%) within a short reaction time. Through the actual degradation and degradation kinetics, the degradation efficiency of PAHs decreased with the increase of aromatic rings. And the degradation conditions (temperature, pH, Cu2+ concentration, mediator) were systematically optimized. The optimum degradation conditions (1.5 mM Cu2+, 28℃ and pH 6) showed significant degradation efficiency for the low and medium concentrations of benzo[a]pyrene. In addition, complete degradation of benzo[a]pyrene could be achieved using only 0.2 mM of HBT mediator compared with crude enzymes alone. Collectively, these results showed the high-cyclic PAHs degradation potential of Trametes versicolor crude enzymes, and provided references to evaluate applicable prospects of white rot fungus crude enzymes in PAHs-contaminated soils.

9.
ACS Appl Mater Interfaces ; 15(2): 3253-3265, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36598330

RESUMO

Phototheranostics has attracted considerable attention in the fields of cancer diagnosis and treatment. However, the complete eradication of solid tumors using traditional phototheranostics is difficult because of the limited depth and range of laser irradiation. New phototheranostics enabling precise phototherapy and post-treatment imaging-guided programmed therapy for residual tumors is urgently required. Accordingly, this study developed a novel transformable phototheranostics by assembling hyaluronic acid (HA) with copper-nitrogen-coordinated carbon dots (CDs). In this transformable nanoplatform, named copper-nitrogen-CDs@HA, the HA component enables the specific targeting of cluster determinant (CD) 44-overexpressing tumor cells. In the tumor cells, redox glutathione converts Cu(II) (cupric ions) into Cu(I) (cuprous ions), which confers the novel transformable functionality to phototheranostics. Both in vitro and in vivo results reveal that the near-infrared-light-photoactivated CuII-N-CDs@HA could target CD44-overexpressing tumor cells for precise synergistic photothermal therapy and photodynamic therapy. This study is the first to observe that CuII-N-CDs@HA could escape from lysosomes and be transformed in situ into CuI-N-CDs@HA in tumor cells, with the d9 electronic configuration of Cu(II) changing to the d10 electronic configuration of Cu(I), which turns on their fluorescence and turns off their photothermal properties. This transformable phototheranostics could be used for post-treatment imaging-guided photodynamic therapy on residual tumor cells. Thus, the rationally designed copper-nitrogen-coordinated CDs offer a simple in situ transformation strategy for using multiple-stimulus-responsive precise phototheranostics in post-treatment monitoring of residual tumor cells and imaging-guided programmed therapy.


Assuntos
Nanopartículas , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Carbono , Neoplasia Residual , Cobre/farmacologia , Fototerapia , Linhagem Celular Tumoral , Nanopartículas/uso terapêutico
10.
Environ Technol ; : 1-11, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36579925

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) contaminated soil severely and are difficult to remediate. In this study, acid-modified chestnut inner shell biochar with abundant pore channels was used as the main raw materials for the immobilization of white-rot fungal crude enzyme. The maximum immobilization rate of crude enzymes (97.25%±6.20%) could be achieved under the optimal conditions of 24 h immobilization of 10 U/mL crude enzymes by 1 g biochar at 25℃ and pH = 5. Meanwhile, immobilization improved the stability of the crude enzyme. The relative activity of the immobilized crude enzyme increased by 59.32% and 49.73% (compared to the free crude enzymes) after 5 weeks of storage at 4°C and 25°C, respectively. It has been verified that chestnut-based immobilized crude enzyme can degrade 37% of benzo[a]pyrene in 10 days for PAHs-contaminated soils. An efficient, feasible, and low-cost remediation method for PAHs-contaminated soils was explored, which provides technical support for the application of crude enzymes in organic contaminated soils.

11.
Biochem Biophys Res Commun ; 640: 80-87, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36502635

RESUMO

Deficiency in human coagulation factor VIII (FVIII) causes hemophilia A (HA). Patients with HA may suffer from spontaneous bleeding, which can be life-threatening. Recombinant FVIII (rFVIII) is an established treatment and prevention agent for bleeding in patients with HA. Human plasma-derived FVIII (pdFVIII), commonly used in clinical practice, is relatively difficult to prepare. In this study, we developed a novel B-domain-deleted rFVIII, produced and formulated without the use of animal or human serum-derived components. rFVIII promoted the generation of activated factor X and downstream thrombin, and, similar to that of other available FVIII preparations, its activity was inhibited by FVIII inhibitors. In addition, rFVIII has ideal binding affinity to human von Willebrand factor. Activated FVIII (FVIIIa) could be degraded by activated protein C and lose its procoagulant activity. In vitro, commercially available recombinant FVIII (Xyntha) and pdFVIII were used as controls, and there were no statistical differences between rFVIII and commercial FVIII preparations, which demonstrates the satisfactory efficacy and potency of rFVIII. In vivo, HA mice showed that infusion of rFVIII rapidly corrected activated partial thromboplastin time, similar to Xyntha. Moreover, different batches of rFVIII were comparable. Overall, our results demonstrate the potential of rFVIII as an effective strategy for the treatment of FVIII deficiency.


Assuntos
Fator VIII , Hemofilia A , Humanos , Animais , Camundongos , Fator VIII/uso terapêutico , Fator VIII/metabolismo , Fatores de Coagulação Sanguínea , Hemofilia A/tratamento farmacológico , Hemorragia , Modelos Animais , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico
12.
J Inorg Biochem ; 240: 112093, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36525715

RESUMO

Three new synthetic terpyridine copper(II) complexes were characterized. The copper(II) complexes induced apoptosis of three cancer cell lines and arrested T-24 cell cycle in G1 phase. The complexes were accumulated in mitochondria of T-24 cells and caused significant reduction of the mitochondrial membrane potential. The complexes increased both intracellular ROS and Ca2+ levels and activated the caspase-3/9 expression. The apoptosis was further confirmed by Western Blotting analysis. Bcl-2 was down-regulated and Bax was upregulated after treatment with complexes 1-3. The in vivo studies showed that complexes 1-3 obviously inhibited the growth of tumor without significant toxicity to other organs.

13.
Dalton Trans ; 52(2): 269-280, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36519582

RESUMO

Designing novel anticancer non-platinum metal agents is fully challenging. Herein, a series of little-known indium (In) 2-acetylpyridine thiosemicarbazone compounds as potential anticancer agents were designed, synthesized, and characterized. The hydrogen atoms at the N-4 position with the alkyl of the In compounds significantly increased cellular uptake and cytotoxicity. In(III) compounds showed significantly higher cytotoxicity toward cisplatin-resistant cell lines than cisplatin. More importantly, C4 greatly inhibited A549DDP tumor growth in a vaccinated mouse model. C4 exerted cytotoxic effects via a multitarget mechanism. First, it activated p53 and blocked the cell cycle at the S phase, which then led to weak expression levels of cyclin and related kinases and upregulation of the expression levels of cyclin-dependent kinase inhibitors. C4 also depolarized the mitochondrial membrane potential and regulated the expression of the Bcl-2 family, which then released cyt-c and activated caspase-3/8/9 to execute apoptotic pathways. Then, it inhibited telomerase through the inhibition of the expression of the c-Myc regulator gene and expression of the human telomerase reverse transcriptase. Furthermore, C4 showed excellent antimetastatic activity.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Apoptose , Caspases , Linhagem Celular Tumoral , Cisplatino/farmacologia , Índio , Neoplasias Pulmonares/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos
14.
J Med Chem ; 66(1): 793-803, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36544423

RESUMO

To develop a next-generation anticancer metal-based drug, realize the multi-targeted combination therapy of protein drug and metal-based drug for cancer, solve their co-delivery challenges, and improve their in vivo targeting ability, we proposed to develop a multi-targeted anticancer metal-based agent exploiting the properties of the tumor microenvironment (TME) and of lactoferrin (LF). To this end, we optimized a series of gallium (Ga, III) isopropyl-2-pyridyl-ketone thiosemicarbazone compounds to obtain a Ga compound (C4) with remarkable cytotoxicity and then constructed a new LF-C4 nanoparticle (LF-C4 NP) delivery system. In vivo studies showed that LF-C4 NPs not only had a greater capacity for inhibiting tumor growth than LF or C4 alone but also solved the co-delivery problems of LF and C4 and improved their targeting ability. Furthermore, free C4 and LF-C4 NPs inhibited tumor growth through multiple synergistic actions on the TME: killing cancer cell, inhibiting tumor angiogenesis, and activating immune system.


Assuntos
Antineoplásicos , Gálio , Nanopartículas , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos , Lactoferrina/farmacologia , Lactoferrina/uso terapêutico , Gálio/farmacologia , Microambiente Tumoral , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
15.
Gastroenterol Rep (Oxf) ; 10: goac071, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457375

RESUMO

Background: Pediatric perianal fistula is a common disorder. It is more difficult to detect the fistula tract and internal opening (IO) in children than in adults. This study aimed to evaluate the clinical diagnostic value of transcutaneous perianal ultrasound for children with perianal fistula. Methods: A retrospective review was conducted by analysing the preoperative transcutaneous perianal ultrasound and intraoperative exploration results of 203 consecutive patients who were <3 years old and diagnosed with perianal fistula. Analyses were conducted to evaluate the accuracy and consistency of utilizing the transcutaneous perianal ultrasound in the diagnosis of the complexity and location of the IO of perianal fistulas. Results: Compared with intraoperative exploration, the preoperative transcutaneous perianal ultrasonography has almost perfect agreement (Kappa = 0.881, P < 0.001) in the diagnosis of fistula tract complexity and IO with a sensitivity of 92% and a specificity of 97%. In addition, both intraoperative exploration and transcutaneous perianal ultrasound diagnosis showed high consistency in the identification of the IO of perianal fistulas (Quadrant I Kappa = 0.831, Quadrant II Kappa = 0.773, Quadrant III Kappa = 0.735, Quadrant IV Kappa = 0.802, all P < 0.01). The IOs were mainly distributed in Quadrants IV and II in both simple and complex fistulas. Conclusions: Transcutaneous perianal ultrasound, as a non-invasive and simple imaging technique, showed high accuracy in the diagnosis and identification of the fistula classification and IO location. It could be considered a first-line diagnostic instrument for evaluating perianal fistulas among children.

17.
Phytochemistry ; 206: 113530, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36455653

RESUMO

Seven undescribed triterpenoids were obtained from the ethanol extract of the dried stems of Uncaria macrophylla Wall. (Rubiaceae).All of the isolates were urs-28-oic acid or olean-28-oic acid skeletons, including three triterpenoids with rare 3ß,23-(1R-4-hydroxy-butyl-1,1-dioxy) or 23-(2R-tetrahydrofuran-2-oxy) substituents. Five triterpenoids showed promising inhibitory activity against erastin-induced ferroptosis in PC12 cells, while 3ß,6α,23-trihydroxy-olean-12-en-28-oic acid was the most significant inhibitor to resist ferroptosis by activating the Nrf2/SLC7A11/GPx4 axis with an EC50 value of 4.2 ± 0.7 µM.

18.
Microb Ecol ; 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36585489

RESUMO

Inland saline-alkaline wetlands distributed in the mid-high latitude have repeatedly experienced freezing and thawing. However, the response of greenhouse gas (GHG) emission and microbially-mediated carbon and nitrogen cycle to freezing and thawing remains unclear. We monitored the GHG flux in an inland saline-alkaline wetland and found that, compared with the growth period, the average CO2 flux decreased from 171.99 to 76.61-80.71 mg/(m2‧h), the average CH4 flux decreased from 10.72 to 1.96-3.94 mg/(m2‧h), and the average N2O flux decreased from 56.17 to - 27.14 to - 20.70 µg/(m2‧h). Freezing and thawing significantly decreased the relative abundance of functional genes involved in carbon and nitrogen cycles. The aceticlastic methanogenic pathway was the main methanogenic pathway, whereas the Candidatus Methylomirabilis oxyfera was the most abundant methane oxidizer in the wetland. Ammonia-oxidizing archaea and denitrifier belonging to proteobacteria was the major microbial N2O source, while bacteria within clade II nosZ was the major microbial N2O sink. Freezing and thawing reduced the relative abundance of these genes, leading to a decrease in GHG flux.

19.
Sci Total Environ ; 865: 161262, 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36586290

RESUMO

Anaerobic membrane bioreactor (AnMBR) is a promising treatment technique for various types of wastewaters, and is preferred over other conventional aerobic and anaerobic methods. However, membrane fouling is considered a bottleneck in AnMBR system, which technically blocks membrane pores by numerous inorganics, organics, and other microbial substances. Various materials can be added in AnMBR to control membrane fouling and improve anaerobic digestion, and studies reporting the materials addition for this purpose are hereby systematically reviewed. The mechanism of membrane fouling control including compositional changes in extracellular polymeric substances (EPSs) and soluble microbial products (SMPs), materials properties, stimulation of antifouling microbes and alteration in substrate properties by material addition are thoroughly discussed. Nonetheless, this study opens up new research prospects to control membrane fouling of AnMBR, engineered by material, including compositional changes of microbial products (EPS and SMP), replacement of quorum quenching (QQ) by materials, and overall improvement of reactor performance. Regardless of the great research progress achieved previously in membrane fouling control, there is still a long way to go for material-mediated AnMBR applications to be undertaken, particularly for materials coupling, real scale application and molecular based studies on EPSs and SMPs, which were proposed for future researches.

20.
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