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1.
Artigo em Inglês | MEDLINE | ID: mdl-35029830

RESUMO

This study reports the release behaviors, enrichment characteristics, contamination level, and health risk of twenty-one elements in biomass, when dry distillation, incomplete combustion, and sufficient combustion. Results indicate that the element concentration in different kinds of biomass varies greatly. Even for the same kind of biomass, concentration in three products of dry distillation, incomplete combustion, and sufficient combustion is also different: fifteen elements (K, Ca, Mg, Al, Fe, Mn, B, Cu, Zn, Mo, Cd, Cr, Pb, Sb, Sn) have no significant difference in concentration but other six elements (As, Co, Ni, V, Na, P) are the opposite. Multivariate statistical approaches were used to assess five significant factors which affect element concentration, suggesting the contributes from biomass type, moisture content, soil, biomass age or organ, and disposal methods. Disposal methods and biomass type result in significant differences in element enrichment factor. More elements will release during sufficient combustion rather than dry distillation. The increasing of supplied oxygen during disposal process may increase the overall toxicity from elements release. The data of excess lifetime cancer risk (ELCR) suggests that Cr, Ni, Co, Cd, and Pb are the largest contributors to cancer risks during biomass application.

2.
Sci Total Environ ; 803: 149933, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34482141

RESUMO

To ensure global food security, agriculture must increase productivity while reducing environmental impacts associated with chemical nitrogen (N) fertilisation. This necessitates towards more sustainable practices such as recycling organic waste to substitute chemical fertiliser N inputs. However, hitherto how such strategy controls the succession of microbial communities and their relationship with crop yields and environmental impacts have not been comprehensively investigated. We conducted a field experiment with vegetable production in China examining partial substitution (25-50%) of chemical fertiliser with organic forms (pig manure or municipal sludge compost) considering key sustainability metrics: productivity, soil health, environmental impacts and microbial communities. We demonstrate that partial organic substitution improved crop yields, prevented soil acidification and improved soil fertility. Treatments also reduced detrimental environmental impacts with lower N2O emission, N leaching and runoff, likely due to reduced inorganic nitrogen surplus. Microbial communities, including key genes involved in the N cycle, were dynamic and time-dependent in response to partial organic substitution, and were also important in regulating crop yields and environmental impacts. Partial organic substitution increased bacterial diversity and the relative abundance of several specific microbial groups (e.g. Sphingomonadales, Myxococcales, Planctomycetes, and Rhizobiales) involved in N cycling. Additionally, partial organic substitution reduced the number of bacterial ammonia oxidizers and increased the number of denitrifiers, with the proportion of N2O-reducers being more pronounced, suggesting a mechanism for reducing N2O emissions. Comprehensive economic cost-benefit evaluation showed that partial organic substitution increased economic benefit per unit area by 37-46%, and reduced agricultural inputs and environmental impacts per unit product by 22-44%. Among them, 50% substitution of pig manure was the most profitable strategy. The study is crucial to policy-making as it highlights the potential advantages of shifting towards systems balancing chemical and organic fertilisers with economic benefits for farmers, reduced environmental damage and an efficient way for organic waste disposal.


Assuntos
Agricultura , Fertilizantes , Animais , Fertilizantes/análise , Esterco , Nitrogênio , Solo , Suínos
3.
Bioorg Chem ; 119: 105559, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34952244

RESUMO

Stimuli-responsive drug delivery systems (DDSs) based on amphiphilic polymers have attracted much attention. In this study, we reported an innovative H2O2-responsive amphiphilic polymer (TBP), bearing a H2O2-sensitive phenylboronic ester, AIE fluorophore tetraphenylethene (TPE) hydrophobic, and polyethylene glycol hydrophilic (PEG) moieties. TBP could self-assemble into micelles with an encapsulation efficiency as high as 74.9% for doxorubicin (DOX) in aqueous solution. In the presence of H2O2, TBP micelles was decomposed by oxidation, hydrolysis and rearrangement, leading to almost 80% DOX release from TBP@DOX micelles. TBP and the corresponding degradation products were biocompatible, while TBP@DOX micelles only displayed obvious toxicity toward cancer cells. Drug delivery process was clearly monitored by confocal laser scanning microscopic (CLSM) and flow cytometry (FCM) analysis. Moreover, in vivo anticancer study showed that TBP@DOX micelles were accumulated in tumor region of nude mice and effectively inhibited tumor growth. The results suggested that the reported H2O2-responsive amphiphilic polymer displayed great potential in drug delivery and tumor therapy.

4.
Front Genet ; 12: 790426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956331

RESUMO

Atrial septal defects (ASDs) are the most common types of cardiac septal defects in congenital heart defects. In addition to traditional therapy, interventional closure has become the main treatment method. However, the molecular events and mechanisms underlying the repair progress by occlusion device remain unknown. In this study, we aimed to characterize differentially expressed genes (DEGs) in the blood of patients treated with occlusion devices (metal or poly-L-lactic acid devices) using RNA-sequencing, and further validated them by qRT-PCR analysis to finally determine the expression of key mediating genes after closure of ASD treatment. The result showed that total 1,045 genes and 1,523 genes were expressed differently with significance in metal and poly-L-lactic acid devices treatment, respectively. The 115 overlap genes from the different sub-analyses are illustrated. The similarities and differences in gene expression reflect that the body response process involved after interventional therapy for ASDs has both different parts that do not overlap and the same part that crosses. The same portion of body response regulatory genes are key regulatory genes expressed in the blood of patients with ASDs treated with closure devices. The gene ontology enrichment analysis showed that biological processes affected in metal device therapy are immune response with CXCR4 genes and poly-L-lactic acid device treatment, and the key pathways are nuclear-transcribed mRNA catabolic process and proteins targeting endoplasmic reticulum process with ribosomal proteins (such as RPS26). We confirmed that CXCR4, TOB1, and DDIT4 gene expression are significantly downregulated toward the pre-therapy level after the post-treatment in both therapy groups by qRT-PCR. Our study suggests that the potential role of CXCR4, DDIT4, and TOB1 may be key regulatory genes in the process of endothelialization in the repair progress of ASDs, providing molecular insights into this progress for future studies.

5.
Acta Biomater ; 2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34936938

RESUMO

The heart is a highly complex, multicellular solid organ with energy-demanding processes that require a dense vascular network, extensive cell-cell interactions, and extracellular matrix (ECM)-mediated crosstalk among heterogeneous cell populations. Here, we describe the regeneration of left ventricular (LV) wall using decellularized whole rabbit heart scaffolds recellularized exclusively with human induced pluripotent stem cell-derived endothelial cells, cardiomyocytes, and other cardiac cell types. Cells were sequentially delivered to the scaffold using an optimized endothelial cell:cardiomyocyte media. Macroscopic assessment after 60 days showed that the LV wall of recellularized hearts was anatomically restored to full thickness from base to apex and endocardium to epicardium. Histologic analysis of the recellularized LV wall revealed a heterogeneous pool of cardiac cells containing aligned cardiac troponin T-positive cells in close contact with ECM; vessels varied from large artery-like, surrounded by smooth muscle actin+ cells, to capillary-like. Vessel patency was demonstrated after perfusion of recellularized hearts transplanted into the femoral artery bed of a pig. The construct exhibited visible beating and responded to chronotropic drug administration. These results demonstrate the ability to tissue engineer a vascularized, full-thickness LV wall with an unparalleled level of microanatomical organization and multicellular composition, using decellularized ECM and human cardiomyocytes, endothelial cells, and other cardiac cell types. STATEMENT OF SIGNIFICANCE: : Decellularized extracellular matrix (ECM) is a bioactive template for tissue engineering, but recellularizing acellular whole heart scaffolds is challenging. Here, we successfully revascularized and repopulated a large, full-thickness portion of a ventricle using human induced pluripotent stem cell-derived endothelial and cardiac cells. At 60 days, histologic studies showed that the microanatomical organization and cellular composition of this region was similar to that of the native heart. The recellularized heart showed visible beating and responded appropriately to heartbeat-altering drugs. Vessels surrounded by smooth muscle cells and endothelial cells supported blood flow through the vessels of a recellularized heart that was surgically connected to a pig femoral artery. These findings move this approach closer to the possibility of clinical translation.

6.
Mikrochim Acta ; 188(10): 354, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570272

RESUMO

A capillary-based SERS sensor was fabricated for ultrasensitive and selective detection of Hg2+ in water. Au@Ag core-shell NPs embedded with 4-mercaptobenzoic acid (4-MBA) (Au@4-MBA@Ag) were prepared by a seed growth method and fixed on the inner wall of the glass capillary to obtain the sensor. Owing to the amalgamation between Ag and Hg, the capillary-based SERS sensor can specifically recognize the reduced Hg2+ without any recognition element, and the resulted Ag/Hg amalgam can weaken the SERS activity of Ag shell; thus, the SERS intensity of the embedded 4-MBA at 1075 cm-1 gradually decreased with the increase of Hg2+ concentration. Under the optimum condition, the fabricated sensor can sensitively determine Hg2+ in water with a limit of detection (LOD) as low as 0.03 nM. The capillary-based SERS sensor offers the advantages of simple preparation, superior stability, and high selectivity, which is promising for rapid and on-site detection of Hg2+ in water combined with a portable Raman device.

7.
Bioorg Chem ; 116: 105299, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34454300

RESUMO

The development of cationic polymers as non-viral gene vectors has been hurdled by their high toxicity, thus degradable and biocompatible polymers are urgently demanded. Herein, five polyesters (B3a-B3e) were synthesized based on the ring-opening copolymerization between α-allyl-δ-valerolactone and δ-valerolactone derivatives decorated with alkyl or alkoxyl chains of different lengths, followed by the modification with 1,5,9-triazacyclododecyl ([12]aneN3) through thiol-ene click reactions. The five polyesters effectively condensed DNA into nanoparticles. Of them, B3a with a shorter alkyl chain and B3d with more positive charged units showed stronger DNA condensing performance and can completely retard the migration of DNA at N/P = 1.6 in the presence of DOPE. B3b/DOPE with a longer alkyl chain exhibited the highest transfection efficiency in HeLa cells with 1.8 times of 25 kDa PEI, while B3d/DOPE with more positive charged units exhibited highest transfection efficiency in A549 cells with 2.3 times of 25 kDa PEI. B3b/DOPE and B3d/DOPE successfully delivered pEGFP into zebrafish, which was superior to 25 kDa PEI (1.5 folds and 1.1 folds, respectively). The cytotoxicity measurements proved that the biocompatibility of these polyesters was better than 25 kDa PEI, due to their degradable property in acid environment. The results indicated that these cationic polyesters can be developed as potential non-viral gene vectors for DNA delivery.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34131853

RESUMO

The enrichment of heavy metals in air-borne particulate matters poses a great threat to health. In order to understand the mineralogical characteristics and sources of heavy metals in atmospheric particulate matter in coal mining cities, PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 µm), PM10 (particulate matter with an aerodynamic diameter less than 10 µm) and TSP (total suspended particulates) were sampled from Huainan city, China in December 2016 and May 2017. The contents of heavy metals in TSP are the highest, while those in PM2.5 are the lowest. Zn, Mn, and Pb are the main components of heavy metals in Huainan atmospheric particulates. Straw burning activities may result in relatively higher atmospheric particulate matter content in summer than that in winter. The proportion of mineral particles in the studied particulate matters was the highest (40.79%), followed by soot aggregates (35.55%) and coal fly ash (19.74%). The results of energy spectrum analysis show that the main component of soot aggregates is C, and other contents are contributed by elements such as O and Si. Coal fly ash mainly contains C, O, Si, and a small amount of Al and Na. As, Cd, and Hg are the most easily enriched heavy metals. Industrial emissions, traffic discharges, coal combustion and dust emissions were found to be the main sources of heavy metals in atmospheric particulates.

9.
Bioorg Chem ; 113: 104983, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34029935

RESUMO

Two-photon fluorescent Acenaphtho[1,2-b]quinoxaline (ANQ) and the hydrophilic di-(triazole-[12]aneN3) moieties were combined through an alkyl chain (ANQ-A-M) or a ß-hairpin motif with two aromatic γ-amino acid residues (ANQ-H-M) to explore their capabilities for in vitro and in vivo gene delivery and tracing. ANQ-A-M and ANQ-H-M showed the same maximum absorption at 420 nm, and their fluorescent intensities around 650 nm were varied in different solvents and became poor in the protic solvents. Gel electrophoresis assays indicated that both compounds completely retarded the migration of pDNA at 20 µM in the presence of DOPE. However, the DNA condensation with ANQ-H-M was not reversible, and the particle size of the corresponding complexes were larger indicated from the SEM and DLS measurements. In vitro transfections indicated ANQ-A-M/DOPE achieved Luciferase and GFP expressions were to be 7.9- and 5.7-fold of those by Lipo2000 in A549 cells respectively. However, ANQ-H-M showed very poor transfection efficiency in Luciferase expression. With the help of single/two-photon fluorescence imaging it clearly demonstrated that the successful transfection of ANQ-A-M was attributed to its cellular uptake, apparent lysosomal escape, and reversible release of DNA; and the poor transfection of ANQ-H-M was resulted from the aggregation of the DNA complexes which prevented them from the cellular uptake, and also the strong binding ability which is not easy to release DNA. ANQ-A-M/DOPE also exhibited robust gene silencing (83% knockdown of Luciferase) and GFP expression (2.47-fold higher) efficiency compared with Lipo2000 in A549 and zebrafish, respectively. The work demonstrated that the linkage structure between fluorescent and di(triazole-[12]aneN3) played the important role for their gene delivery performance, and that ANQ-A-M represents a vector with the strong transfection efficiency in vitro and in vivo as well as the efficient real time bioimaging properties, which is potential for the development in biomedical research.


Assuntos
Compostos de Anilina/química , DNA/genética , Corantes Fluorescentes/química , Técnicas de Transferência de Genes , Imagem Óptica , Fótons , Quinoxalinas/química , RNA Interferente Pequeno/genética , Compostos de Anilina/síntese química , Corantes Fluorescentes/síntese química , Vetores Genéticos/síntese química , Vetores Genéticos/química , Quinoxalinas/síntese química
10.
Front Pharmacol ; 12: 664123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967809

RESUMO

Cancer is a life-threatening disease, and there is a significant need for novel technologies to treat cancer with an effective outcome and low toxicity. Photothermal therapy (PTT) is a noninvasive therapeutic tool that transports nanomaterials into tumors, absorbing light energy and converting it into heat, thus killing tumor cells. Gold nanorods (GNRs) have attracted widespread attention in recent years due to their unique optical and electronic properties and potential applications in biological imaging, molecular detection, and drug delivery, especially in the PTT of cancer and other diseases. This review summarizes the recent progress in the synthesis methods and surface functionalization of GNRs for PTT. The current major synthetic methods of GNRs and recently improved measures to reduce toxicity, increase yield, and control particle size and shape are first introduced, followed by various surface functionalization approaches to construct a controlled drug release system, increase cell uptake, and improve pharmacokinetics and tumor-targeting effect, thus enhancing the photothermal effect of killing the tumor. Finally, a brief outlook for the future development of GNRs modification and functionalization in PTT is proposed.

11.
Org Biomol Chem ; 19(19): 4359-4363, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-33908557

RESUMO

A series of unnatural tripeptides, each consisting of two aromatic γ-amino acid residues and an ϖ-amino acid residue, are designed to probe their folding into hairpin conformations. The ϖ-amino acid residues, with aliphatic or aromatic spacers of different sizes, serve as the loop of the hairpins. Studies based on one-dimensional (1D) 1H NMR performed at different concentrations, solvent polarity, and temperature, along with 2D-NMR studies, demonstrated that the doubly H-bonded aromatic γ-amino acid residues play important roles in driving these tripeptides into the hairpin conformation. The loop based on 5-aminovaleric acid, which offers a four-carbon (CH2)4 spacer, enhanced the stability of the corresponding hairpin, while loops having a shorter, a longer and a more rigid spacer disfavored the formation of the hairpins. Results from computational studies are in good agreement with the experimental observations. Furthermore, the crystal structure of peptide 1b revealed the expected hairpin conformation in the solid state. This turn motif, which contains H-bonded aromatic γ-amino acid residues as the core unit and an ϖ-amino acid residue serving as the loop, provides a new platform that can be used to obtain a variety of turn conformations by incorporating diverse amino acids into the loops.

12.
Int J Oral Sci ; 13(1): 9, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727527

RESUMO

Issues caused by maxillofacial tumours involve not only dealing with tumours but also repairing jaw bone defects. In traditional tumour therapy, the systemic toxicity of chemotherapeutic drugs, invasive surgical resection, intractable tumour recurrence, and metastasis are major threats to the patients' lives in the clinic. Fortunately, biomaterial-based intervention can improve the efficiency of tumour treatment and decrease the possibility of recurrence and metastasis, suggesting new promising antitumour therapies. In addition, maxillofacial bone tissue defects caused by tumours and their treatment can negatively affect the physiological and psychological health of patients, and investment in treatment can result in a multitude of burdens to society. Biomaterials are promising options because they have good biocompatibility and bioactive properties for stimulation of bone regeneration. More interestingly, an integrated material regimen that combines tumour therapy with bone repair is a promising treatment option. Herein, we summarized traditional and biomaterial-mediated maxillofacial tumour treatments and analysed biomaterials for bone defect repair. Furthermore, we proposed a promising and superior design of dual-functional biomaterials for simultaneous tumour therapy and bone regeneration to provide a new strategy for managing maxillofacial tumours and improve the quality of life of patients in the future.


Assuntos
Materiais Biocompatíveis , Qualidade de Vida , Regeneração Óssea , Osso e Ossos , Humanos
13.
Schizophr Bull ; 47(3): 615-623, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33159208

RESUMO

Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%-98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%-96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%-87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%-100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.


Assuntos
Exossomos/metabolismo , Metaboloma/fisiologia , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Adulto , Biomarcadores/metabolismo , Cromatografia Líquida , Feminino , Humanos , Masculino , Metabolômica , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
14.
J Hazard Mater ; 405: 124280, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33268202

RESUMO

Mercury (Hg) stable isotopes have a great potential to track coal combustion Hg emissions, but mass-dependent fractionation (MDF) during Hg adsorption onto fly ash particles could significantly alter isotope signatures of emitted Hg species. The detailed processes causing this MDF, however, are not well understood. Here, we simulated how isotopes fractionate during gaseous Hg0 adsorption onto fly ash at different times and temperatures. Kinetic MDF that preferably transfers light Hg isotopes to fly ash dominated Hg0 adsorption processes. The magnitude of MDF during Hg0 adsorption was invariable in the time-series experiment but increased significantly with increasing temperature in the temperature-series experiment. The external mass transfer and chemisorption are suggested to be the controlling processes for isotopic fractionation. Relative to diffusion-driven Hg0 adsorption, chemisorption is suggested to be a more important Hg0 adsorption step causing MDF, especially at high temperatures. The chemisorption involves Hg redox change from Hg0 to HgII and is likely enhanced with increasing temperature (50-180 °C). The proposed kinetic MDF model reveals that MDF in modern coal-fired power plants is likely driven by temperature-induced redox processes during Hg0 adsorption, and has great implications for developing MDF models in coal-fired boilers and tracing coal combustion Hg emissions.

15.
Front Oral Health ; 2: 673449, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35048017

RESUMO

Background: Dental caries is a long-standing oral health problem for children all over the world. The available evidence shows that the association between maternal smoking during pregnancy and childhood caries is still controversial. Therefore, the aim of this systematic review and meta-analysis was to determine whether there was a correlation of prenatal smoking and dental caries in children. Methods: PubMed, EMBASE, Cochrane, Web of Science, and Scopus databases were searched for observational studies assessing the relationship between maternal smoking during the pregnancy and childhood caries. According to the predesigned eligibility criteria and items, studies selection, and data extraction were conducted, respectively. The effect estimates were pooled using a fixed-effect model or a random-effect model. Newcastle-Ottawa Scale (NOS) was adopted to evaluate the methodological quality of the included studies. All analyses were carried out through Stata 12.0 software. Results: Our systematic review included a total of 11 studies, of which 6 cross-sectional studies and 3 longitudinal studies were included in the final meta-analysis. The pooled estimates indicated maternal smoking during pregnancy was significantly associated with dental caries in children both in cross-sectional studies (OR = 1.57, 95% CI = 1.47-1.67) and longitudinal studies (RR = 1.26, 95% CI = 1.07-1.48). Sensitivity analyses confirmed the overall effect estimates were robust. Conclusions: There is a significant correlation of maternal smoking during pregnancy and childhood caries. However, the causal relationship between them cannot be determined. More prospective and extensive studies on this theme is needed for verification. Even so, it is necessary for pregnant women and women of reproductive age to quit smoking. Strategies must be developed to raise public awareness about the impact of prenatal smoking on children's oral health.

16.
Cell Mol Bioeng ; 13(6): 633-645, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33281992

RESUMO

Introduction: Recellularization of organ decellularized extracellular matrix (dECM) offers a potential solution for organ shortage in allograft transplantation. Cell retention rates have ranged from 10 to 54% in varying approaches for reseeding cells in whole organ dECM scaffolds. We aimed to improve recellularization by using soluble gelatin as a cell carrier to deliver endothelial cells to the coronary vasculature and cardiomyocytes to the parenchyma in a whole decellularized rat heart. Methods: Rat aortic endothelial cells (RAECs) were perfused over decellularized porcine aorta in low (1%) and high (5%) concentrations of gelatin to assess attachment to a vascular dECM model. After establishing cell viability and proliferation in 1% gelatin, we used 1% gelatin as a carrier to deliver RAECs and neonatal rat cardiomyocytes (NRCMs) to decellularized adult rat hearts. Immediate cell retention in the matrix was quantified, and recellularized hearts were evaluated for visible contractions up to 35 days after recellularization. Results: We demonstrated that gelatin increased RAEC attachment to decellularized porcine aorta; blocking integrin receptors reversed this effect. In the whole rat heart gelatin (1%) increased retention of both RAECs and NRCMs respectively, compared with the control group (no gelatin). Gelatin was associated with visible contractions of NRCMs within hearts (87% with gelatin vs. 13% control). Conclusions: Gelatin was an effective cell carrier for increasing cell retention and contraction in dECM. The gelatin-cell-ECM interactions likely mediated by integrin.

17.
Front Chem ; 8: 530083, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134269

RESUMO

Factors responsible for the persistent adoption of hairpin conformations by hybrid oligopeptides, each having a central ß/α dipeptide segment flanked by aromatic γ-amino acid (γAr) residues, are probed. Our recent studies revealed that tetrapeptide 1 and 2, having central dipeptide segments consisting of ß-alanine (ß-Ala) and glycine (Gly), and L-ß-homophenylalanine (L-ß-homoPhe) and Gly residues, respectively, that are flanked by γAr residues, fold into well-defined, expanded ß-turns with doubly H-bonded γAr residues. Replacing the γAr residues of 1 and 2 with L-Val and L-Leu residues results in tetrapetides 1 ' and 2 ' that fail to fold into defined conformations, which confirms the decisive role played by the H-bonded γAr residues in the promoting folding of 1 and 2. Attaching L-Val and L-Leu residues to the termini of 1 affords hexapeptide 1a. With an additional H-bond between its L-Val and L-Leu residues, peptide 1a folds into a hairpin with higher stability than that of 1, indicating that the expanded ß-turn can nucleate and stabilize ß-hairpin with longer ß-strands. Attaching L-Val and L-Leu residues to the termini of 2 affords hexapeptide 2a. Substituting the L-ß-homoPhe residue of 2a with a D-ß-homoPhe residue gives hexapeptide 2b. Surprisingly, hexapeptide 2a fold into a hairpin showing the similar stability as those of tetrapeptides 1 and 2. Hexapeptide 2b, with its combination of a D-ß-homoPhe residue and the L-Val/L-Leu pair, fold into a hairpin that is significantly more stable than the other hybrid peptides, demonstrating that a combination of hetero-chirality between the ß-amino acid residue of the dipeptide loop and the α-amino acid residues of the ß-strands enhances the stability of the resultant ß-hairpin.

18.
Oxid Med Cell Longev ; 2020: 9187195, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963705

RESUMO

Huntington's disease (HD) is a hereditary autosomal dominant neurodegenerative disease. Although studies have shown that blood oxidative stress markers are dysregulated in HD patients, clinical data on the blood oxidative stress markers of HD patients is inconsistent. To better understand the pathogenesis of HD, we performed a systematic review and meta-analysis of blood oxidative stress markers in HD patients and healthy control (HC) subjects. A database search from PubMed and Web of Science identified 12 studies with 375 HD patients and 447 HC subjects in this meta-analysis. A random-effects meta-analysis showed that blood lipid peroxidation products (Hedges' g = 0.883, 95%CI = 0.637 to 1.130, p < 0.001), 8-hydroxyguanosine (Hedges' g = 1.727, 95%CI = 0.489 to 2.965, p = 0.006) levels, and the activity of glutathione peroxidase (Hedges' g = 2.026, 95%CI = 0.570 to 3.482, p = 0.006) were significantly increased in HD patients compared to controls. In contrast, reduced glutathione levels were lower in HD patients than in controls (Hedges' g = -0.611, 95%CI = -1.016 to - 0.207, p = 0.003). However, blood superoxide dismutase, cholesterol, high-density lipoproteins, low-density lipoproteins, and triglycerides did not show significant differences between cases and controls. Taken together, this study clarified the associations between blood oxidative stress markers and HD, supporting the clinical evidence that HD is accompanied by increased oxidative stress.


Assuntos
Biomarcadores/sangue , Doença de Huntington/sangue , Doença de Huntington/patologia , Estresse Oxidativo , Adulto , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Exp Ther Med ; 20(4): 3837-3845, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32855734

RESUMO

Doxorubicin (DOX) has been widely employed to treat cancer, particularly solid tumors and hematological malignancies, owing to its high efficacy; however, chemotherapy has been indicated to be cardiotoxic and induce adverse effects, including mitochondrial dysfunction and DNA damage, which limits its application. The mitochondria-associated protein leucine-rich pentatricopeptide repeat-containing (LRPPRC) has been reported to serve critical regulatory roles in physiological processes via regulating mitochondrial function. The aim of the present study was to investigate the possible protective effects of LRPPRC against DOX-induced cardiac injury. In a DOX-induced cardiotoxicity model in H9C2 cells, LRPPRC was indicated to be transcriptionally upregulated and stabilize Bcl-2 and Bax. LRPPRC overexpression exhibited protective effects against proliferation and both apoptotic and non-apoptotic cell death following DOX treatment, but not under normal conditions. It was additionally observed that overexpressed LRPPRC reversed the decreases in ATP synthesis, mitochondrial mass and transcriptional activity, which were induced by DOX exposure. Overexpressed LRPPRC also decreased the accumulation of reactive oxygen species (ROS) under DOX treatment and inhibited cell death to a similar extent as N-acetyl-L-cysteine, which is a known ROS scavenger, indicating that LRPPRC potentially exerts protective effects via inhibiting ROS accumulation. Moreover, LRPPRC overexpression protected H9C2 cells against oxidative stress induced by H2O2, which also indicated its ROS-scavenging function. The present study demonstrated for the first time, to the best of our knowledge, that DOX-induced LRPPRC may exert cardioprotective effects via inhibiting ROS accumulation, thereby maintaining mitochondrial function.

20.
ACS Appl Mater Interfaces ; 12(36): 40094-40107, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32805811

RESUMO

Although a plethora of nonviral gene vectors have been developed for potential gene therapy, imageable gemini surfactants with stimuli-responsiveness and high transfection efficiency are still scarce for gene delivery. Herein, three gemini amphiphiles (DEDPP-4/8/12) consisting of an aggregation-induced emission (AIE) central fluorophore: 5,6-diphenylpyrazine-2,3-diester (DEDPP), decorated with triazole-[12]aneN3 as the hydrophilic moiety and alkyl chains of various lengths as the hydrophobic moiety, were designed and synthesized for trackable gene delivery via optical imaging. All three amphiphiles exhibited ultralow critical micelle concentrations (CMCs) (up to 3.40 × 10-6 M), prominent two-photon absorption properties, and solvatochromic fluorescence. Gel electrophoresis assays demonstrated that the migration of plasmid DNA was completely retarded after condensation with these gemini amphiphiles at low concentrations (up to 10 µM). In addition, the ester bond in these amphiphiles may facilitate vector degradation and DNA release, in response to esterase and the acidic environment inside cells. Upon self-assembly with DOPE to form liposomes, DEDPP-8/DOPE achieved the best transfection efficiency in four cell lines, and the transfection efficiency of DEDPP-8/DOPE in HeLa cell lines was 23.5-fold higher than that of Lipo2000, which is unusually high for small organic molecule-based nonviral vectors. Furthermore, excellent transfection efficiency of DEDPP-8/DOPE was obtained in the presence of serum, and the red fluorescence protein (RFP) gene was successfully transfected in zebrafish embryos. Both one- and two-photon fluorescence imaging clearly demonstrated the delivery process of plasmid DNA. This study demonstrated that gemini-type amphiphiles composed of a two-photon fluorophore core conjugated with triazole-[12]aneN3 via an ester bond afforded an unprecedentedly high transfection efficiency with excellent biocompatibility, which may provide new insights for the design and development of multifunctional nonviral gene vectors for imageable gene delivery.


Assuntos
Calcitriol/análogos & derivados , Corantes Fluorescentes/química , Técnicas de Transferência de Genes , Imagem Óptica , Pirazinas/química , Tensoativos/química , Calcitriol/síntese química , Calcitriol/química , Células Cultivadas , Corantes Fluorescentes/síntese química , Células HEK293 , Humanos , Estrutura Molecular , Tamanho da Partícula , Fótons , Pirazinas/síntese química , Propriedades de Superfície , Tensoativos/síntese química
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