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1.
Nano Lett ; 24(12): 3614-3623, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38497742

RESUMO

Broad-spectrum antiviral platforms are always desired but still lack the ability to cope with the threats to global public health. Herein, we develop a poly aptamer encoded DNA nanocatcher platform that can trap entire virus particles to inhibit infection with a broad antiviral spectrum. Ultralong single-stranded DNA (ssDNA) containing repeated aptamers was synthesized as the scaffold of a nanocatcher via a biocatalytic process, wherein mineralization of magnesium pyrophosphate on the ssDNA could occur and consequently lead to the formation of nanocatcher with interfacial nanocaves decorated with virus-binding aptamers. Once the viruses were recognized by the apatmers, they would be captured and trapped in the nanocaves via multisite synergistic interactions. Meanwhile, the size of nanocatchers was optimized to prevent their cellular uptake, which further guaranteed inhibition of virus infection. By taking SARS-CoV-2 variants as a model target, we demonstrated the broad virus-trapping capability of a DNA nanocatcher in engulfing the variants and blocking the infection to host cells.


Assuntos
Aptâmeros de Nucleotídeos , Vírus , Aptâmeros de Nucleotídeos/farmacologia , DNA de Cadeia Simples , Antivirais/farmacologia
2.
Cancer Sci ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38476086

RESUMO

Long noncoding RNAs (lncRNAs) have emerged as important molecules and potential new targets for human cancers. This study investigates the function of lncRNA CTBP1 antisense RNA (CTBP1-AS) in prostate cancer (PCa) and explores the entailed molecular mechanism. Aberrantly expressed genes potentially correlated with PCa progression were probed using integrated bioinformatics analyses. A cohort of 68 patients with PCa was included, and their tumor and para-cancerous tissues were collected. CTBP1-AS was highly expressed in PCa tissues and cells and associated with poor patient prognosis. By contrast, tumor protein p63 (TP63) and S100 calcium binding protein A14 (S100A14) were poorly expressed in the PCa tissues and cells. CTBP1-AS did not affect TP63 expression; however it blocked the TP63-mediated transcriptional activation of S100A14, thereby reducing its expression. CTBP1-AS silencing suppressed proliferation, apoptosis resistance, migration, invasion, and tumorigenicity of PCa cell lines, while its overexpression led to inverse results. The malignant phenotype of cells was further weakened by TP63 overexpression but restored following artificial S100A14 silencing. In conclusion, this study demonstrates that CTBP1-AS plays an oncogenic role in PCa by blocking TP63-mediated transcriptional activation of S100A14. This may provide insight into the management of PCa.

3.
Phytomedicine ; 123: 155252, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056145

RESUMO

BACKGROUND: Acute kidney injury (AKI) has high morbidity and mortality, which is manifested by inflammation and apoptosis. Effective treatment methods for AKI are currently lacking. OBJECTIVE: This study demonstrated the protecting effects of Madecassoside (MA) in the cisplatin- and hypoxia-reoxygenation-induced renal tubular epithelial cells in vitro and AKI mice in vivo. METHODS: In vivo AKI mouse models were established by inducing them with cisplatin and renal ischemia-reperfusion. In vitro injury models of mouse renal tubular epithelial cells were established by inducing them with cisplatin and hypoxia and reoxygenation, respectively. The mechanism of MA effects was further explored using molecular docking and RNA-sequencing. RESULTS: MA could significantly reduce kidney injury in the cisplatin-and renal ischemia-reperfusion (IRI)-induced AKI. Further validation in the two cellular models also showed that MA had protect effects. MA can alleviate AKI in vitro and in vivo by inhibiting inflammation, cell apoptosis, and oxidative stress. MA exhibited high permeability across the Caco-2 cell, can enter cells directly. Through RNA-seq and molecular docking analysis, this study further demonstrated that MA inhibits its activity by directly binding to JNK kinase, thereby inhibiting c-JUN mediated cell apoptosis and improving AKI. In addition, MA has better renal protective effects compared to curcumin and JNK inhibitor SP600125. CONCLUSION: The results demonstrate that MA might be a potential drug for the treatment of AKI and act through the JNK/c-JUN signaling pathway.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Triterpenos , Humanos , Camundongos , Animais , Cisplatino/efeitos adversos , Células CACO-2 , Simulação de Acoplamento Molecular , Injúria Renal Aguda/induzido quimicamente , Apoptose , Rim , Estresse Oxidativo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Isquemia , Inflamação/metabolismo , Hipóxia , Camundongos Endogâmicos C57BL
4.
Pharmacol Res ; 197: 106950, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37820854

RESUMO

Kidney disease can be caused by various internal and external factors that have led to a continual increase in global deaths. Current treatment methods can alleviate but do not markedly prevent disease development. Further research on kidney disease has revealed the crucial function of epigenetics, especially acetylation, in the pathology and physiology of the kidney. Histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyllysine readers jointly regulate acetylation, thus affecting kidney physiological homoeostasis. Recent studies have shown that acetylation improves mechanisms and pathways involved in various types of nephropathy. The discovery and application of novel inhibitors and activators have further confirmed the important role of acetylation. In this review, we provide insights into the physiological process of acetylation and summarise its specific mechanisms and potential therapeutic effects on renal pathology.


Assuntos
Nefropatias , Humanos , Acetilação , Nefropatias/tratamento farmacológico , Rim , Epigênese Genética , Epigenômica
5.
Sci Adv ; 9(35): eadi3602, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37647403

RESUMO

CRISPR-Cas9 has been explored as a therapeutic agent for down-regulating target genes; the controlled delivery of Cas9 ribonucleoprotein (RNP) is essential for therapeutic efficacy and remains a challenge. Here, we report cascade dynamic assembly/disassembly of DNA nanoframework (NF) that enables the controlled delivery of Cas9 RNP. NF was prepared with acrylamide-modified DNA that initiated cascade hybridization chain reaction (HCR). Through an HCR, single-guide RNA was incorporated to NF; simultaneously, the internal space of NF was expanded, facilitating the loading of Cas9 protein. NF was designed with hydrophilic acylamino and hydrophobic isopropyl, allowing dynamic swelling and aggregation. The responsive release of Cas9 RNP was realized by introducing disulfide bond-containing N,N-bis(acryloyl)cystamine that was specifically in response to glutathione of cancer cells, triggering the complete disassembly of NF. In vitro and in vivo investigations demonstrated the high gene editing efficiency in cancer cells, the hypotoxicity in normal cells, and notable antitumor efficacy in a breast cancer mouse model.


Assuntos
Sistemas CRISPR-Cas , DNA , Animais , Camundongos , DNA/genética , Acrilamida , Proteína 9 Associada à CRISPR/genética , Cistamina , Ribonucleoproteínas
6.
Environ Pollut ; 335: 122249, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37487872

RESUMO

The tanning sludge (TS) and other tanning solid wastes are produced in significant quantities by the leather industry. To evaluate the combustion properties, acid gaseous pollutant conversion, and ash management, co-firing of TS with various wastes was investigated in a bubbling fluidized bed. TG-FTIR test indicated that tanning solid wastes had superior combustion properties and include more gaseous pollutants than TS. The leather mixed solid waste (LMSW) formed by mixing had better fuel characteristics than TS. The conversion rates of SO2 and HCl of LMSW incineration were 67% and 40%, respectively. The co-combustion of TS and solid wastes reduces the conversion rate of acid gas. Increasing the proportion of high-inorganic chlorine raw material could further reduce the conversion rate and increase the ash fusion temperature appropriately. Because ash and slag were primarily composed of Ca and Fe elements, the addition of calcium carbonate (CaCO3) can increase ash melting point while reducing acid gas emissions. When CaCO3 was added at a calcium to sulfur (Ca/S) ratio of 2, the acid gas emission was reduced by more than 80% and the softening temperature was raised by 90 °C. When Ca/S is greater than 2, the economics of adding CaCO3 decreased.


Assuntos
Poluentes Ambientais , Resíduos Sólidos , Resíduos Sólidos/análise , Incineração , Gases , Cloro , Esgotos , Cinza de Carvão/análise
7.
Biomed Pharmacother ; 165: 115166, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37473682

RESUMO

Signal transducer and activator of transcription 3 (STAT3) is a cell-signal transcription factor that has attracted considerable attention in recent years. The stimulation of cytokines and growth factors can result in the transcription of a wide range of genes that are crucial for several cellular biological processes involved in pro- and anti-inflammatory responses. STAT3 has attracted considerable interest as a result of a recent upsurge in study because of their role in directing the innate immune response and sustaining inflammatory pathways, which is a key feature in the pathogenesis of many diseases, including renal disorders. Several pathological conditions which may involve STAT3 include diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and renal cell carcinoma. STAT3 is expressed in various renal tissues under these pathological conditions. To better understand the role of STAT3 in the kidney and provide a theoretical foundation for STAT3-targeted therapy for renal disorders, this review covers the current work on the activities of STAT3 and its mechanisms in the pathophysiological processes of various types of renal diseases.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Nefrite Lúpica , Humanos , Fator de Transcrição STAT3/metabolismo , Rim/patologia , Nefrite Lúpica/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia
8.
J Biomater Appl ; 38(1): 73-84, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37142296

RESUMO

Urinary tract infections caused by catheter insertion are prevalent in hospital clinics, which can induce serious complications such as bacteriuria and sepsis, and even lead to patient death. The disposable catheters currently used in clinical practice suffer from poor biocompatibility and high infection rate. In this paper, we developed a polydopamine (PDA)-carboxymethylcellulose (CMC)-Ag nanoparticles (AgNPs) coating with both good antibacterial and anti-adhesion properties to bacteria on the surfaces of a disposable medical latex catheter by a simple dipping method. The antibacterial efficiency of the coated catheters against Gram-negative E. coli and Gram-positive S. aureus bacteria was evaluated with both inhibition zone tests and fluorescence microscopy. Compared with the untreated catheter, the PDA-CMC-AgNPs coated catheters showed both good antibacterial and anti-adhesion properties to bacteria, which inhibited the adhesion of live bacteria and dead bacteria by 99.0% and 86.6%, respectively. This novel PDA-CMC-AgNPs composite hydrogel coating has great potential in applications in catheters and other biomedical devices to reduce infections.


Assuntos
Carboximetilcelulose Sódica , Nanopartículas Metálicas , Humanos , Cateteres Urinários , Escherichia coli , Staphylococcus aureus , Hidrogéis , Prata/farmacologia , Antibacterianos/farmacologia
9.
Br J Pharmacol ; 180(20): 2641-2660, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37248964

RESUMO

BACKGROUND AND PURPOSE: Necroptosis plays an essential role in acute kidney injury and is mediated by receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed lineage kinase domain-like pseudokinase (MLKL). A novel RIPK3 inhibitor, compound 42 (Cpd-42) alleviates the systemic inflammatory response. The current study was designed to investigate whether Cpd-42 exhibits protective effects on acute kidney injury and reveal the underlying mechanisms. EXPERIMENTAL APPROACH: The effects of Cpd-42 were determined in vivo through cisplatin- and ischaemia/reperfusion (I/R)-induced acute kidney injury and in vitro through cisplatin- and hypoxia/re-oxygenation (H/R)-induced cell damage. Transmission electron microscopy and periodic acid-Schiff staining were used to identify renal pathology. Cellular thermal shift assay and RIPK3-knockout mouse renal tubule epithelial cells were used to explore the relationship between Cpd-42 and RIPK3. Molecular docking and site-directed mutagenesis were used to determine the binding site of RIPK3 with Cpd-42. KEY RESULTS: Cpd-42 reduced human proximal tubule epithelial cell line (HK-2) cell damage, necroptosis and inflammatory responses in vitro. Furthermore, in vivo, cisplatin- and I/R-induced acute kidney injury was alleviated by Cpd-42 treatment. Cpd-42 inhibited necroptosis by interacting with two key hydrogen bonds of RIPK3 at Thr94 and Ser146, which further blocked the phosphorylation of RIPK3 and mitigated acute kidney injury. CONCLUSION AND IMPLICATIONS: Acting as a novel RIPK3 inhibitor, Cpd-42 reduced kidney damage, inflammatory response and necroptosis in acute kidney injury by binding to sites Thr94 and Ser146 on RIPK3. Cpd-42 could be a promising treatment for acute kidney injury.


Assuntos
Injúria Renal Aguda , Cisplatino , Camundongos , Animais , Humanos , Cisplatino/farmacologia , Necroptose , Simulação de Acoplamento Molecular , Injúria Renal Aguda/metabolismo , Proteínas Quinases/metabolismo , Camundongos Knockout , Apoptose , Proteína Serina-Treonina Quinases de Interação com Receptores
10.
Langmuir ; 39(4): 1562-1572, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36661856

RESUMO

Slippery silicone-oil-infused (SOI) surfaces have recently emerged as a promising alternative to conventional anti-infection coatings for urinary catheters to combat biofilm and encrustation formation. Benefiting from the ultralow low hysteresis and slippery behavior, the liquid-like SOI coatings have been found to effectively reduce bacterial adhesion under both static and flow conditions. However, in real clinical settings, the use of catheters may also trigger local inflammation, leading to release of host-secreted proteins, such as fibrinogen (Fgn) that deposits on the catheter surfaces, creating a niche that can be exploited by uropathogens to cause infections. In this work, we report on the fabrication of a silicone oil-infused silver-releasing catheter which exhibited superior durability and robust antibacterial activity in aqueous conditions, reducing biofilm formation of two key uropathogens Escherichia coli and Proteus mirabilis by ∼99%, when compared with commercial all-silicone catheters after 7 days while remaining noncytotoxic toward L929 mouse fibroblasts. After exposure to Fgn, the oil-infused surfaces induced conformational changes in the protein which accelerated adsorption onto the surfaces. The deposited Fgn blocked the interaction of silver with the bacteria and served as a scaffold, which promoted bacterial colonization, resulting in a compromised antibiofilm activity. Fgn binding also facilitated the migration of Proteus mirabilis over the catheter surfaces and accelerated the deposition and spread of crystalline biofilm. Our findings suggest that the use of silicone oil-infused silver-releasing urinary catheters may not be a feasible strategy to combat infections and associated complications arising from severe inflammation.


Assuntos
Cateterismo Urinário , Cateteres Urinários , Animais , Camundongos , Cateteres Urinários/microbiologia , Óleos de Silicone , Prata/farmacologia , Biofilmes , Silicones
11.
Artigo em Inglês | MEDLINE | ID: mdl-36673805

RESUMO

With the increase in global environmental pollution, it is important to understand the concentration characteristics and correlations with other pollutants of atmospheric particulate matter as affected by relevant policies. The data presented in this paper were obtained at monitoring stations in Xi'an, China, in the years from 2016 to 2020, and the spatial distribution characteristics of the mass and quantity concentrations of particulate matter in the atmosphere, as well as its correlation with other pollutants, were analyzed in depth. The results showed that the annual average concentrations of PM10 and PM2.5 decreased year by year from 2016 to 2020. The annual concentrations of PM2.5 decreased by 20.3 µg/m3, and the annual concentrations of PM10 decreased by 47.3 µg/m3. The days with concentrations of PM10 exceeding the standards decreased by 82 days, with a decrease of 66.7%. The days with concentrations of PM2.5 exceeding the standards decreased by 40 days, with a decrease of 35.4%. The concentration values of PM10 and PM2.5 were roughly consistent with the monthly and daily trends. The change in monthly concentrations was U-shaped, and the change in daily concentrations showed a double-peak behavior. The highest concentrations of particulate matter appeared at about 8:00~9:00 am and 11:00 pm, and they were greatly affected by human activity. The proportion of particles of 0~1.0 µm decreased by 1.94%, and the proportion of particles of 0~2.5 µm decreased by 2.00% from 2016 to 2020. A multivariate linear regression model to calculate the concentrations of the pollutants was established. This study provides a reference for the comprehensive analysis and control of air pollutants in Xi'an and even worldwide.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Humanos , Material Particulado/análise , Poluentes Ambientais/análise , Monitoramento Ambiental/métodos , Estações do Ano , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Políticas
12.
Environ Pollut ; 314: 120261, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36155219

RESUMO

The control of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from the flue gas in hazardous waste incinerators (HWIs) is an intractable problem. To figure out the formation mechanism of PCDD/Fs and reduce the emission, a field study was carried out in a full-scale HWI. Ca(OH)2 & (NH4)H2PO4 or CH4N2S & (NH4)H2PO4 were injected into the quench tower, and the detailed inhibition effect on PCDD/Fs formation by the inhibitors coupled with quench tower was studied. Gas and ash samples were collected to analyze PCDD/Fs. XPS, EDS characterization and Principal component analysis were adopted to further analyze the de novo and precursors synthesis. The PCDD/Fs emissions reduced from 0.135 ng I-TEQ/Nm3 to 0.062 or 0.025 ng I-TEQ/Nm3 after the injection of Ca(OH)2 & (NH4)H2PO4 or CH4N2S & (NH4)H2PO4, respectively. The quench tower was found mainly hindering de novo synthesis by reducing reaction time. CP-route was the dominant formation pathway of PCDD/Fs in quench tower ash. Ca(OH)2 & (NH4)H2PO4 effectively inhibit precursors synthesis and reduce proportions of organic chlorine from 4.11% to 2.86%. CH4N2S & (NH4)H2PO4 show good control effects on both de novo and precursors synthesis by reducing chlorine content and inhibiting metal-catalysts. Sulfur-containing inhibitors can cooperate well with the quench tower to inhibit PCDD/Fs formation and will be effective to reduce dioxins formation in high chlorine flue gas. The results pave the way for further industrial application of inhibition to reduce PCDD/Fs emissions in the HWIs flue gas.


Assuntos
Poluentes Atmosféricos , Benzofuranos , Dioxinas , Dibenzodioxinas Policloradas , Resíduos Perigosos/análise , Dibenzofuranos/análise , Dibenzodioxinas Policloradas/análise , Dioxinas/análise , Cloro/análise , Poluentes Atmosféricos/análise , Benzofuranos/análise , Monitoramento Ambiental , Incineração/métodos , Enxofre/análise , Dibenzofuranos Policlorados/análise
13.
Int J Clin Pract ; 2022: 5734387, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36177365

RESUMO

Background: The purpose of this study was to determine whether oxybuprocaine hydrochloride gel could alleviate pain during male catheterization. Methods: Between September 2021 and March 2022, a randomized controlled trial was conducted at the Urology Department of Harbin Medical University Cancer Hospital (China). A total of 192 adult male patients requiring catheterization were enrolled and randomly assigned to one of two groups: 96 in the test group and 96 in the control group. The test group included patients who received oxybuprocaine hydrochloride gel as urethral lubricant, while patients in the control group received liquid paraffin. The preoperative and postoperative pain scores were compared using nonparametric tests. Results: At the baseline, there was no significant difference between the two groups. There was no significant difference in preoperative pain scores between the test group (mean ± SD = 20.04 ± 2.68 mm) and the control group (mean ± SD = 20.21 ± 3.23 mm) (p=0.694). Postoperative pain scores increased significantly in the test (mean ± SD = 31.98 ± 2.57 mm, p < 0.001) and control groups (mean ± SD = 38.96 ± 2.02 mm, p < 0.001) groups. Postoperative pain scores were significantly lower in the test group (mean ± SD = 31.98 ± 2.57 mm) than those in the control group (mean ± SD = 38.96 ± 2.02 mm (p < 0.001). Conclusions: The use of oxybuprocaine hydrochloride gel significantly reduced pain during male urethral catheterization. The study provides evidence for clinicians to use oxybuprocaine hydrochloride gel during male catheterization.


Assuntos
Anestésicos Locais , Cateterismo Urinário , Adulto , Anestésicos Locais/efeitos adversos , Humanos , Lubrificantes , Masculino , Óleo Mineral , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Procaína/análogos & derivados , Cateterismo Urinário/efeitos adversos
14.
Front Microbiol ; 13: 880258, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847100

RESUMO

Hantaan virus (HTNV) is the main cause of hemorrhagic fever with renal syndrome (HFRS) around the world, which results in profound morbidity and mortality. However, there are currently no FDA-approved therapeutics or vaccines against HFRS. To find new anti-HTNV drugs, the inhibitory activity of 901 small molecule kinase inhibitors against HTNV is analyzed. Among these compounds, compound 8G1 inhibits HTNV with a relatively high inhibition rate and lower toxicity. The viral titer and nucleocapsid protein of HTNV are reduced after compound 8G1 treatment in a dose-dependent manner at concentrations ranging from 1 to 20 µM. In addition, the administration of compound 8G1 at the early stage of HTNV infection can inhibit the replication of HTNV. The molecular docking result reveals that compound 8G1 forms interactions with the key amino acid residues of serine/threonine-protein kinase B (Akt), which is responsible for the observed affinity. Then, the mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E (eIF4E) signaling pathways are inhibited. Our results may help to design novel targets for therapeutic intervention against HTNV infection and to understand the anti-HTNV mechanism of protein kinase inhibitors.

15.
Kidney Int ; 102(4): 828-844, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35752325

RESUMO

The novel biomarker, insulin-like growth factor binding protein 7 (IGFBP7), is used clinically to predict different types of acute kidney injury (AKI) and has drawn significant attention as a urinary biomarker. However, as a secreted protein in the circulation of patients with AKI, it is unclear whether IGFBP7 acts as a key regulator in AKI progression, and if mechanisms underlying its upregulation still need to be determined. Here we found that IGFBP7 is highly expressed in the blood and urine of patients and mice with AKI, possibly via a c-Jun-dependent mechanism, and is positively correlated with kidney dysfunction. Global knockout of IGFBP7 ameliorated kidney dysfunction, inflammatory responses, and programmed cell death in murine models of cisplatin-, kidney ischemia/reperfusion-, and lipopolysaccharide-induced AKI. IGFBP7 mainly originated from kidney tubular epithelial cells. Conditional knockout of IGFBP7 from the kidney protected against AKI. By contrast, rescue of IGFBP7 expression in IGFBP7-knockout mice restored kidney damage and inflammation. IGFBP7 function was determined in vitro using recombinant IGFBP7 protein, IGFBP7 knockdown, or overexpression. Additionally, IGFBP7 was found to bind to poly [ADP-ribose] polymerase 1 (PARP1) and inhibit its degradation by antagonizing the E3 ubiquitin ligase ring finger protein 4 (RNF4). Thus, IGFBP7 in circulation acts as a biomarker and key mediator of AKI by inhibiting RNF4/PARP1-mediated tubular injury and inflammation. Hence, over-activation of the IGFBP7/PARP1 axis represents a promising target for AKI treatment.


Assuntos
Injúria Renal Aguda , Inibidor Tecidual de Metaloproteinase-2 , Adenosina Difosfato Ribose , Animais , Biomarcadores , Cisplatino/toxicidade , Inflamação , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Lipopolissacarídeos , Camundongos , Camundongos Knockout , Ubiquitina-Proteína Ligases/metabolismo
16.
Angew Chem Int Ed Engl ; 61(36): e202207770, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35731026

RESUMO

Coupling materials chemistry systems to biological processes is a promising way to rationally modulate lysosomal functions. A proton-driven dynamic assembly of a DNA nanoframework inside cells coupled with the lysosome-mediated endocytosis pathways/lysosomal maturation, gives the rational modulation of lysosomal functions, which we term "lysosome interference". Through lysosome-mediated endocytosis, the DNA nanoframework with acid-responsive semi-i-motif enters the lysosome and assembles into an aggregate in a process triggered by lysosomal acidity. The aggregate is suitable for long-term retention. The consumption of protons resulted in lysosomal acidity reduction and hydrolase activity attenuation, thus hindering the degradation of nucleic acid drugs in the lysosome and improving gene silencing effects. This study shows a new way to achieve lysosome interference by coupling the subcellular microenvironment with a precisely programmable assembly system.


Assuntos
Ácidos Nucleicos , Prótons , DNA/metabolismo , Endocitose , Lisossomos/metabolismo , Ácidos Nucleicos/metabolismo
17.
J Imaging ; 8(5)2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35621893

RESUMO

Digital images are usually stored in compressed format. However, image classification typically takes decompressed images as inputs rather than compressed images. Therefore, performing image classification directly in the compression domain will eliminate the need for decompression, thus increasing efficiency and decreasing costs. However, there has been very sparse work on image classification in the compression domain. In this paper, we studied the feasibility of classifying images in their JPEG compression domain. We analyzed the underlying mechanisms of JPEG as an example and conducted classification on data from different stages during the compression. The images we used were malaria-infected red blood cells and normal cells. The training data include multiple combinations of DCT coefficients, DC values in both decimal and binary forms, the "scan" segment in both binary and decimal form, and the variable length of the entire bitstream. The result shows that LSTM can successfully classify the image in its compressed form, with accuracies around 80%. If using only coded DC values, we can achieve accuracies higher than 90%. This indicates that images from different classes can still be well separated in their JPEG compressed format. Our simulations demonstrate that the proposed compression domain-processing method can reduce the input data, and eliminate the image decompression step, thereby achieving significant savings on memory and computation time.

18.
Chem Asian J ; 17(13): e202200310, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35468254

RESUMO

Branched DNA with multibranch-like anisotropic topology serves as a promising and powerful building block in constructing multifunctional-integrated nanomaterials in a programmable and controllable manner. Recently, a series of branched DNA-based functional nanomaterials were developed by elaborate molecular design. In this review, we focused on the construction of branched DNA-based nanostructures for biological and biomedical applications. First, the molecular design and synthesis method of branched DNA monomer were briefly described. Then, the construction strategies of branched DNA-based nanostructures were categorially discussed, including target-triggered polymerization, enzymatic extension and hybrid assembly. Finally, the biological and biomedical applications including diagnosis, therapeutics and protein engineering were summarized. We envision that the review will contribute to the further development of branched DNA-based nanomaterials with great application potential in the field of biomedicine, thus building a new bridge between material chemistry and biomedicine.


Assuntos
Nanoestruturas , DNA/química , Nanoestruturas/química , Polimerização , Engenharia de Proteínas
19.
Small ; 18(16): e2106269, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35266630

RESUMO

Exploring appropriate precursors has been proposed to be a promising strategy for the creation of artificial enzymes that are emerging as alternatives of natural enzymes. Herein, inspired by the catalytic activities of ribose nucleic acid, using ribonucleosides as precursors including adenosine, guanosine, cytidine, and uridine, respectively, four carbonic aggregates, namely, carbon dots (A-CDs, G-CDs, C-CDs, and U-CDs) to mimic artificial enzymes are synthesized. All the CDs show a planar graphene-like structure and thus can intercalatively bind with DNA double helix. Different from the other three CDs, the uridine-derived U-CDs exhibit unique catalytic property, which can mediate the topological transformation of DNA from supercoiled to nicked open-circular conformation. U-CDs can catalyze oxidation of O2 to generate singlet oxygen 1 O2 via a Haber-Weiss reaction, and consequently mediate oxidative cleavage of phosphate backbone in DNA and release the torsional energy stored in supercoiled DNA. Explorations reveal that the unique highly active oxygenated species, namely, quinone groups that are on the edge of U-CDs, play a key role in the catalytic production of 1 O2 . This work represents a new insight that using natural biomolecules in living systems as precursors can create new species beyond life.


Assuntos
Grafite , Pontos Quânticos , Ribonucleosídeos , Carbono/química , Catálise , Pontos Quânticos/química , Uridina
20.
J Am Chem Soc ; 144(10): 4667-4677, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35254064

RESUMO

Constructing artificial dynamic architectures inside cells to rationally interfere with organelles is emerging as an efficient strategy to regulate the behaviors and fate of cells, thus providing new routes for therapeutics. Herein, we develop an intracellular K+-mediating dynamic assembly of DNA tetrahedrons inside cells, which realizes efficient mitochondrial interference and consequent regulation on the energy metabolism of living cells. In the designer DNA tetrahedron, one vertex was modified with triphenylphosphine (TPP) for mitochondrial targeting, and the other three vertexes were tethered with guanine-rich sequences that could realize K+-mediating formation of intermolecular G-quadruplexes, which consequently led to the assembly of DNA tetrahedrons to form aggregates in the cytoplasm. The DNA aggregates specially targeted mitochondria and served as a polyanionic barrier for substance communication, thus generating a significant inhibition effect on the aerobic respiration function of mitochondria and the associated glycolysis process, which consequently reduced the production of intracellular adenosine triphosphate (ATP). The lack of ATP impeded the formation of lamellipodium that was essential for the movement of cells, consequently resulting in a significant inhibitory effect on cell migration. Remarkably, the migration capacity was suppressed by as high as 50% for cancer cells. This work provides a new strategy for the manipulation of organelles via the endogenous molecule-mediating dynamic assembly of exogenous artificial architectures inside living cells, which is envisioned to have great potential in precise biomedicine.


Assuntos
Mitocôndrias , Nanoestruturas , Trifosfato de Adenosina/metabolismo , DNA/metabolismo , Metabolismo Energético , Mitocôndrias/metabolismo
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