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1.
Meat Sci ; 214: 109532, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38733667

RESUMO

This study aimed to clarify the effect of electrostatic spraying of lactic acid (LE) and ascorbic acid (AE) on vacuum-packaged beef aged at 10 °C. The physicochemical attributes, flavor profiles, and microbial diversities were evaluated. Beef steaks were electrostatically sprayed twice with 4% LE, 0.5% AE, or a mixture of them (LAE). Afterward, the beef was vacuum-packaged and aged. All treated beef exhibited a decrease in quality and sensory scores over time. At the end of the study period, the total viable count (TVC) and the total volatile basic nitrogen values in the control group (7.34 log CFU/g and 15.52 mg/100 g, respectively) were higher than those in the acid-treated groups. The LAE group exhibited the best color stability and the lowest TVC and Enterobacteriaceae counts after aging. High-throughput sequencing analysis revealed that acid types and electrostatic spray could change the microbiota structure. Leuconostoc was the dominant bacteria in the AE and LAE groups, while Enterococcus became the predominant bacteria in the NLE and LE groups with aging. This indicates that electrostatic spray combined with acid treatment can ensure beef quality and microbiological safety at mild temperatures.

2.
Int J Biol Macromol ; 263(Pt 2): 129887, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38383251

RESUMO

Infected wound management is a great challenge to healthcare, especially in emergencies such as accidents or battlefields. Hydrogels as wound dressings can replace or supplement traditional wound treatment strategies, such as bandages or sutures. It is significant to develop novel hydrogel-based wound dressings with simple operation, inexpensive, easy debridement, effective antibacterial, biocompatibility, etc. Here, we designed a novel gelatin-based hydrogel wound dressing Gel-TA-Fe3+. The hydrogels used tannic-modified gelatin as the main body and Fe3+ as the crosslinking agent to achieve a controllable rapid sol-gel transition. The hydrogels exhibited tough mechanical properties, excellent antibacterial ability, biocompatibility and an acceptable temperature response to near-infrared light (NIR). Moreover, the hydrogels could promote the healing process of MRSA-infected skin wound in rats. This multifunctional hydrogel was thought to have potential for emergency treatment of bacterial infected wound.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecção dos Ferimentos , Animais , Ratos , Gelatina/farmacologia , Cicatrização , Suplementos Nutricionais , Antibacterianos/farmacologia , Hidrogéis/farmacologia , Infecção dos Ferimentos/tratamento farmacológico
3.
Cancer Med ; 13(2): e6942, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38376003

RESUMO

OBJECTIVE: The purpose of this study is to explore the biological mechanism of Schizandrin A (SchA) inducing non-small cell lung cancer (NSCLC) apoptosis. METHODS: The reverse molecular docking tool "Swiss Target Prediction" was used to predict the targets of SchA. Protein-protein interaction analysis was performed on potential targets using the String database. Functional enrichment analyses of potential targets were performed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The conformation of SchA binding to target was simulated by chemical-protein interactomics and molecular docking. The effect of SchA on the expression and phosphorylation level of EGFR was detected by Western blot. Lipofectamine 3000 and EGFR plasmids were used to overexpress EGFR. Apoptosis was tested with Annexin V-FITC and propidium iodide staining, and cell cycle was detected by propidium iodide staining. RESULTS: The "Swiss Target Prediction" database predicted 112 and 111 targets based on the 2D and 3D structures of SchA, respectively, of which kinases accounted for the most, accounting for 24%. Protein interaction network analyses showed that molecular targets such as ERBB family and SRC were at the center of the network. Functional enrichment analyses indicated that ERBB-related signaling pathways were enriched. Compound-protein interactomics and molecular docking revealed that SchA could bind to the ATP-active pocket of the EGFR tyrosine kinase domain. Laboratory results showed that SchA inhibited the phosphorylation of EGFR. Insulin could counteract the cytotoxic effect of SchA. EGFR overexpression and excess EGF or IGF-1 had limited impacts on the cytotoxicity of SchA. CONCLUSIONS: Network pharmacology analyses suggested that ERBB family members may be the targets of SchA. SchA can inhibit NSCLC at least in part by inhibiting EGFR phosphorylation, and activating the EGFR bypass can neutralize the cytotoxicity of SchA.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Ciclo-Octanos , Lignanas , Neoplasias Pulmonares , Compostos Policíclicos , Humanos , Apoptose , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Ciclo-Octanos/farmacologia , Receptores ErbB/genética , Lignanas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Simulação de Acoplamento Molecular , Compostos Policíclicos/farmacologia
4.
ACS Appl Mater Interfaces ; 16(4): 4449-4461, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38252958

RESUMO

The phenylborate-ester-cross-linked hydrogel microneedle patch (MNP) was promising in the diabetic field for the glucose-responsive insulin-delivering property and simple fabrication process. However, the unfit design of the charging microneedle network limited the improvement of blood-glucose regulating performances. In this work, insulin-loaded phenylborate-ester-cross-linked MNPs, with the polyzwitterion property, were constructed based on the modified ε-polylysine and poly(vinyl alcohol). The relationship between the charging nature of the MNP network and insulin release was verified by regulating the content of postprotonated positively charged amino groups. The elaborately designed MNP possessed improved glucose-responsive insulin-delivering performance. The in vivo study revealed the satisfactory results on blood-glucose regulation by the optimized MNP under the mimic three-meal-per-day mode. Moreover, the insulin bioactivity in the MNP could be maintained for 2 weeks under 25 °C. In summary, this work developed an effective strategy to improve the glucose-responsive phenylborate-ester-cross-linked MNP and enhance its potential for clinical transformation.


Assuntos
Glicemia , Sistemas de Liberação de Medicamentos , Eletricidade Estática , Sistemas de Liberação de Medicamentos/métodos , Glucose , Insulina , Agulhas , Ésteres
5.
Foods ; 13(2)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38254499

RESUMO

The aim of this study was to explore the potential of commercial lactic acid bacteria (LAB) as probiotic starters in fermented sausages. We initially investigated the growth activity, acid production capability, and tolerance to fermentation conditions of Lactobacillus sakei, Lactiplantibacillus plantarum, and Pediococcus pentosaceus. All three LAB strains proved viable as starters for fermented sausages. Subsequently, we explored their potential as probiotics based on their antibacterial and antioxidant capabilities. L. plantarum exhibited stronger inhibition against Escherichia coli and Staphylococcus aureus. All three strains displayed antioxidant abilities, with cell-free supernatants showing a higher antioxidant activity compared to intact cells and cell-free extracts. Moreover, the activities of superoxide dismutase, glutathione peroxidase, and catalase were stronger in the cell-free supernatant, cell-free extract, and intact cell, respectively. Finally, we individually and collectively inoculated these three LAB strains into sausages to investigate their impact on quality during the fermentation process. External starters significantly reduced pH, thiobarbituric acid reactive substances, and sodium nitrite levels. The improvements in color and texture had positive effects, with the L. plantarum inoculation achieving higher sensory scores. Overall, all three LAB strains show promise as probiotic fermentation starters in sausage production.

6.
Commun Biol ; 6(1): 1298, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129665

RESUMO

Biallelic mutations of the chromatin regulator SMARCAL1 cause Schimke Immunoosseous Dysplasia (SIOD), characterized by severe growth defects and premature mortality. Atherosclerosis and hyperlipidemia are common among SIOD patients, yet their onset and progression are poorly understood. Using an integrative approach involving proteomics, mouse models, and population genetics, we investigated SMARCAL1's role. We found that SmarcAL1 interacts with angiopoietin-like 3 (Angptl3), a key regulator of lipoprotein metabolism. In vitro and in vivo analyses demonstrate SmarcAL1's vital role in maintaining cellular lipid homeostasis. The observed translocation of SmarcAL1 to cytoplasmic peroxisomes suggests a potential regulatory role in lipid metabolism through gene expression. SmarcAL1 gene inactivation reduces the expression of key genes in cellular lipid catabolism. Population genetics investigations highlight significant associations between SMARCAL1 genetic variations and body mass index, along with lipid-related traits. This study underscores SMARCAL1's pivotal role in cellular lipid metabolism, likely contributing to the observed lipid phenotypes in SIOD patients.


Assuntos
Síndromes de Imunodeficiência , Animais , Humanos , Camundongos , Cromatina , DNA Helicases/genética , DNA Helicases/metabolismo , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/metabolismo , Metabolismo dos Lipídeos/genética , Lipídeos
7.
Adv Colloid Interface Sci ; 319: 102982, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37597358

RESUMO

Injectable hydrogel adhesives have gained widespread attention due to their ease of use, fast application time, and suitability for minimally invasive procedures. Several biomedical applications depend on tough adhesion between hydrogel adhesives and tissues, including wound closure and healing, hemostasis, tissue regeneration, drug delivery, and wearable electronic devices. Compared with bulk hydrogel adhesives formed ex situ, injectable hydrogel adhesives are more difficult to achieve strong adhesion strength due to a further balance of cohesion and adhesion while maintaining their flowability. In this review, the critical principles in designing tough adhesion of injectable hydrogel adhesives are summarized, including simultaneously enhancing their intrinsic interfacial toughness (Γ0inter) and mechanical dissipation (ΓDinter). Thereafter, various design strategies to enhance the Γ0inter and ΓDinter are discussed and evaluated respectively, involving multiple noncovalent/covalent interactions, topological connections, and polymer network structures. Furthermore, targeted biomedical applications of injectable hydrogel adhesives for specific tissue needs are systematically highlighted. In the end, this review outlines the challenges and trends in producing next-generation multifunctional injectable hydrogels for both practical and translational applications.


Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis , Polímeros , Cicatrização
8.
PLoS One ; 18(8): e0290725, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37651373

RESUMO

INTRODUCTION: Tranexamic acid (TXA) has been proven to prevent thrombolysis and reduce bleeding and blood transfusion requirements in various surgical settings. However, the optimal dose of TXA that effectively reduce intraoperative bleeding and blood product infusion in patients undergoing neurosurgical resection of meningioma with a diameter ≥ 5 cm remains unclear. METHODS: This is a single-center, randomized, double-blinded, paralleled-group controlled trial. Patients scheduled to receive elective tumor resection with meningioma diameter ≥ 5 cm will be randomly assigned the high-dose TXA group, the low-dose group, and the placebo. Patients in the high-dose TXA group will be administered with a loading dose of 20 mg/kg TXA followed by continuous infusion TXA at a rate of 5 mg/kg/h. In the low-dose group, patients will receive the same loading dose of TXA followed by a continuous infusion of normal saline. In the control group, patients will receive an identical volume of normal saline. The primary outcome is the estimated intraoperative blood loss calculated using the following formula: collected blood volume in the suction canister (mL)-the volume of flushing (mL) + the volume from the gauze tampon (mL). Secondary outcomes include calculated intraoperative blood loss, intraoperative coagulation function assessed using thromboelastogram (TEG), intraoperative cell salvage use, blood product infusion, and other safety outcomes. DISCUSSION: Preclinical studies suggest that TXA could reduce intraoperative blood loss, yet the optimal dose was controversial. This study is one of the early studies to evaluate the impact of intraoperative different doses infusion of TXA on reducing blood loss in neurological meningioma patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05230381. Registered on February 8, 2022.


Assuntos
Neoplasias Meníngeas , Meningioma , Ácido Tranexâmico , Humanos , Perda Sanguínea Cirúrgica/prevenção & controle , Ácido Tranexâmico/uso terapêutico , Meningioma/cirurgia , Solução Salina , Neoplasias Meníngeas/cirurgia , Encéfalo , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Biomater Sci ; 11(16): 5410-5438, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37395463

RESUMO

Glucose-sensitive microneedle systems (GSMSs) as an intelligent strategy for treating diabetes can well solve the problems of puncture pain, hypoglycemia, skin damage, and complications caused by the subcutaneous injection of insulin. According to the various functions of each component, herein, therapeutic GSMSs are reviewed based on three parts (glucose-sensitive models, diabetes medications, and microneedle body). Moreover, the characteristics, benefits, and drawbacks of three types of typical glucose-sensitive models (phenylboronic acid based polymer, glucose oxidase, and concanavalin A) and their drug delivery models are reviewed. In particular, phenylboronic acid-based GSMSs can provide a long-acting drug dose and controlled release rate for the treatment of diabetes. Moreover, their painless, minimally invasive puncture also greatly improves patient compliance, treatment safety, and potential application prospects.


Assuntos
Glicemia , Diabetes Mellitus , Humanos , Glucose , Ácidos Borônicos , Sistemas de Liberação de Medicamentos
10.
ACS Appl Mater Interfaces ; 15(31): 37214-37231, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37498537

RESUMO

Currently, antibiotics are the most common treatment for bacterial infections in clinical practice. However, with the abuse of antibiotics and the emergence of drug-resistant bacteria, the use of antibiotics has faced an unprecedented challenge. It is imminent to develop nonantibiotic antimicrobial agents. Based on the cation-π structure of barnacle cement protein, a polyphosphazene-based polymer poly[(N,N-dimethylethylenediamine)-g-(N,N,N,N-dimethylaminoethyl p-ammonium bromide (ammonium bromide)-g-(N,N,N,N-dimethylaminoethyl acetate ethylammonium bromide)] (PZBA) with potential adhesion and inherent antibacterial properties was synthesized, and a series of injectable antibacterial adhesive hydrogels (PZBA-PVA) were prepared by cross-linking with poly(vinyl alcohol) (PVA). PZBA-PVA hydrogels showed good biocompatibility, and the antibacterial rate of the best-performed hydrogel reached 99.81 ± 0.04% and 98.80 ± 2.16% against Staphylococcus aureus and Escherichia coli within 0.5 h in vitro, respectively. In the infected wound model, the healing rate of the PZBA-PVA-treated group was significantly higher than that of the Tegaderm film group due to the fact that the hydrogel suppressed inflammatory responses and modulated the infiltration of immune cells. Moreover, the wound healing mechanism of the PZBA-PVA hydrogel was further evaluated by real-time polymerase chain reaction and total RNA sequencing. The results indicated that the process of hemostasis and tissue development was prompted and the inflammatory and immune responses were suppressed to accelerate wound healing. Overall, the PZBA-PVA hydrogel is shown to have the potential for infected wound healing application.


Assuntos
Infecções Estafilocócicas , Adesivos Teciduais , Humanos , Hidrogéis/farmacologia , Hidrogéis/química , Antibacterianos/farmacologia , Antibacterianos/química
11.
ACS Appl Mater Interfaces ; 15(26): 31330-31343, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37339143

RESUMO

It was greatly significant, but difficult, to develop stimulus-responsive polymeric nanoparticles with efficient protein-loading and protein-delivering properties. Crucial obstacles were the ambiguous protein/nanoparticle-interacting mechanisms and the corresponding inefficient trial-and-error strategies, which brought large quantities of experiments in design and optimization. In this work, a molecular docking-guided universal "segment-functional group-polymer" process was proposed to simplify the previous laborious experimental step. The insulin-delivering glucose-responsive polymeric nanoparticles for diabetic treatments were taken as the examples. The molecular docking study obtained insights from the insulin/segment interactions. It was then experimentally confirmed in six functional groups for insulin-loading performances of their corresponding polymers. The optimization formulation was further proved effective in blood-glucose stabilization on the diabetic rats under the "three-meal-per-day" mode. It was believed that the molecular docking-guided designing process was promising in the protein-delivering field.


Assuntos
Diabetes Mellitus Experimental , Nanopartículas , Ratos , Animais , Glicemia , Glucose , Simulação de Acoplamento Molecular , Diabetes Mellitus Experimental/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Insulina/uso terapêutico , Polímeros/uso terapêutico
12.
Cell Genom ; 3(5): 100304, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37228746

RESUMO

Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank and genome-scale CRISPR-Cas9 knockout and activation screening, we substantially improve the identification of genes whose disruption alters serum LDL-C levels. We identify 21 genes in which rare coding variants significantly alter LDL-C levels at least partially through altered LDL-C uptake. We use co-essentiality-based gene module analysis to show that dysfunction of the RAB10 vesicle transport pathway leads to hypercholesterolemia in humans and mice by impairing surface LDL receptor levels. Further, we demonstrate that loss of function of OTX2 leads to robust reduction in serum LDL-C levels in mice and humans by increasing cellular LDL-C uptake. Altogether, we present an integrated approach that improves our understanding of the genetic regulators of LDL-C levels and provides a roadmap for further efforts to dissect complex human disease genetics.

13.
Macromol Rapid Commun ; 44(13): e2300084, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37002643

RESUMO

As a common oxidizer, ammonium perchlorate (AP) is an important component in composite solid propellants (CSPs). Ferrocene (Fc)-based compounds are often selected as burning rate catalysts (BRCs) to catalyze AP decomposition owing to their excellent catalytic behavior. However, one of the drawbacks of Fc-based BRCs is migration in CSPs. In this study, five Fc-terminated dendrimers are designed and synthesized to improve the anti-migration properties, and their chemical structures are confirmed systemically by the related spectra characterization techniques. Moreover, the redox performance, catalytic effect on AP decomposition, combustion performance, and mechanical properties in CSPs are also studied. The shapes of the prepared propellant samples are observed via scanning electron microscopy. The obtained Fc-based BRCs have good redox performance, a positive effect on promoting AP decomposition, excellent combustion catalytic performance, and good mechanical properties. Meanwhile, they have a higher anti-migration ability than catocene (Cat) and Fc. This study demonstrates that Fc-terminated dendrimers have great potential to be applied as anti-migration BRCs in CSPs.


Assuntos
Dendrímeros , Metalocenos , Catálise , Índio
14.
ACS Biomater Sci Eng ; 9(5): 2534-2544, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37027835

RESUMO

Diabetes patients cannot complete effective blood glucose regulation due to their impaired pancreatic function. At present, subcutaneous insulin injection is the only treatment for patients with type 1 and severe type 2 diabetes. However, long-term subcutaneous injection will cause patients with intense physical pain and lasting psychological burden. In addition, subcutaneous injection will lead to hypoglycemia risk to a large extent because of the uncontrollable release of insulin. In this work, we developed a glucose-sensitive microneedle patch based on phenylboronic acid (PBA)-modified chitosan (CS) particles and poly(vinyl alcohol) (PVA)/poly(vinylpyrrolidone) (PVP) hydrogel for the efficient delivery of insulin. Meanwhile, through the double glucose-sensitive response process of CS-PBA particle and external hydrogel, the sudden release of insulin was well restrained, and a more persistent blood glucose control was achieved. Finally, the painless, minimally invasive, and efficient treatment effect of the glucose-sensitive microneedle patch indicated its great advantages as a new generation of injection therapy.


Assuntos
Diabetes Mellitus Tipo 2 , Insulina , Humanos , Insulina/uso terapêutico , Glucose , Preparações de Ação Retardada/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hidrogéis
15.
Bioinformatics ; 39(4)2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37018146

RESUMO

SUMMARY: We developed the eccDB database to integrate available resources for extrachromosomal circular DNA (eccDNA) data. eccDB is a comprehensive repository for storing, browsing, searching, and analyzing eccDNAs from multispecies. The database provides regulatory and epigenetic information on eccDNAs, with a focus on analyzing intrachromosomal and interchromosomal interactions to predict their transcriptional regulatory functions. Moreover, eccDB identifies eccDNAs from unknown DNA sequences and analyzes the functional and evolutionary relationships of eccDNAs among different species. Overall, eccDB offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher the molecular regulatory mechanisms of eccDNAs. AVAILABILITY AND IMPLEMENTATION: eccDB is freely available at http://www.xiejjlab.bio/eccDB.


Assuntos
Cromatina , DNA Circular , Cromatina/genética , Cromossomos , DNA , Sequência de Bases
16.
bioRxiv ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36711952

RESUMO

Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank and genome-scale CRISPR-Cas9 knockout and activation screening, we have substantially improved the identification of genes whose disruption alters serum LDL-C levels. We identify 21 genes in which rare coding variants significantly alter LDL-C levels at least partially through altered LDL-C uptake. We use co-essentiality-based gene module analysis to show that dysfunction of the RAB10 vesicle transport pathway leads to hypercholesterolemia in humans and mice by impairing surface LDL receptor levels. Further, we demonstrate that loss of function of OTX2 leads to robust reduction in serum LDL-C levels in mice and humans by increasing cellular LDL-C uptake. Altogether, we present an integrated approach that improves our understanding of genetic regulators of LDL-C levels and provides a roadmap for further efforts to dissect complex human disease genetics.

17.
ACS Appl Mater Interfaces ; 14(47): 52643-52658, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36382579

RESUMO

The high level of reactive oxygen species (ROS) and bacterial infection impede wound healing of the diabetic wound. Here, benefiting from the antioxidation effects of tannic acid (TA) and ROS-responsive phenylborate ester (PBAE), a series of ROS-responsive anti-inflammatory TA-conjugated nanoparticle hydrogels (PPBA-TA-PVA) can be obtained by conveniently mixing TA, phenylboric acid modified polyphosphazene (PPBA), and poly(vinyl alcohol) (PVA). The obtained PPBA-TA-PVA hydrogels could effectively inhibit the growth of Escherichia coli (antibacterial rate = 93.1 ± 1.1%) within 4 h and effectively scavenge both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and •OH radicals in vitro. Besides, the cell migration rate of HDFa cells treated with PPBA-TA-PVA hydrogels (84.2 ± 4.6%) was twice the rate of normal cells (43.8 ± 8.1%) after 24 h of cocultivation. The clinical relevance was demonstrated further by assessing the PPBA-TA-PVA hydrogels in full-thickness excisional wounds in a streptozotocin (STZ)-induced diabetic rat model. The PPBA-TA-PVA hydrogels could act as effective ROS-scavenging agents to alleviate inflammation and accelerate wound closure by decreasing the proinflammatory cytokines (IL-6, IL-1ß) and increasing the gene expression of TGF-ß1, COL-1, and COL-3, which resulted in faster re-epithelialization and increased formation of granulation tissue.


Assuntos
Diabetes Mellitus , Pró-Fármacos , Ratos , Animais , Hidrogéis/farmacologia , Hidrogéis/química , Polifenóis/farmacologia , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Cicatrização , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Taninos/farmacologia , Taninos/uso terapêutico
18.
J Control Release ; 352: 527-539, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36341933

RESUMO

Nocturnal blood glucose regulation was one of the key challenges in diabetic treatments. However, development of the smart insulin complexes with mild and glucose-responsive delivering performances was mostly relied on experience of the senior researchers and numerous confirmation experiments. In this work, a series of bioinspired fatty-acid-modified glucose-responsive insulin-delivering polymeric nanoparticles were designed. The molecular docking technique was utilized to efficiently screen the fatty-acid-derived functional groups. The results provided the basis for polymer functionalization and simplified the optimization experiments. For the optimized formulation (C10MS), insulin-loaded C10MS successfully fulfilled the nocturnal-glycemic-controlling requirement of the diabetic rats with lower occurrence of hypoglycemia than the conventional insulin injection schemes. Such formulation also possessed good biocompatibility with the moderate elimination kinetics in vivo, which matched the demand of bio-safety in the daily treatments. Overall, this work opened up a new path for efficient design of functional polymeric materials.


Assuntos
Diabetes Mellitus Experimental , Nanopartículas , Ratos , Animais , Insulina , Glucose , Simulação de Acoplamento Molecular , Diabetes Mellitus Experimental/tratamento farmacológico , Glicemia , Polímeros , Hipoglicemiantes/uso terapêutico
19.
Circ Res ; 131(12): 1004-1017, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36321446

RESUMO

BACKGROUND: Genome-wide association studies have discovered a link between genetic variants on human chromosome 15q26.1 and increased coronary artery disease (CAD) susceptibility; however, the underlying pathobiological mechanism is unclear. This genetic locus contains the FES (FES proto-oncogene, tyrosine kinase) gene encoding a cytoplasmic protein-tyrosine kinase involved in the regulation of cell behavior. We investigated the effect of the 15q26.1 variants on FES expression and whether FES plays a role in atherosclerosis. METHODS AND RESULTS: Analyses of isogenic monocytic cell lines generated by CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing showed that monocytes with an engineered 15q26.1 CAD risk genotype had reduced FES expression. Small-interfering-RNA-mediated knockdown of FES promoted migration of monocytes and vascular smooth muscle cells. A phosphoproteomics analysis showed that FES knockdown altered phosphorylation of a number of proteins known to regulate cell migration. Single-cell RNA-sequencing revealed that in human atherosclerotic plaques, cells that expressed FES were predominately monocytes/macrophages, although several other cell types including smooth muscle cells also expressed FES. There was an association between the 15q26.1 CAD risk genotype and greater numbers of monocytes/macrophage in human atherosclerotic plaques. An animal model study demonstrated that Fes knockout increased atherosclerotic plaque size and within-plaque content of monocytes/macrophages and smooth muscle cells, in apolipoprotein E-deficient mice fed a high fat diet. CONCLUSIONS: We provide substantial evidence that the CAD risk variants at the 15q26.1 locus reduce FES expression in monocytes and that FES depletion results in larger atherosclerotic plaques with more monocytes/macrophages and smooth muscle cells. This study is the first demonstration that FES plays a protective role against atherosclerosis and suggests that enhancing FES activity could be a potentially novel therapeutic approach for CAD intervention.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Placa Aterosclerótica , Proteínas Proto-Oncogênicas c-fes , Animais , Humanos , Camundongos , Artérias/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Estudo de Associação Genômica Ampla , Miócitos de Músculo Liso/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Proteínas Proto-Oncogênicas c-fes/genética , Proteínas Proto-Oncogênicas c-fes/metabolismo
20.
PLoS One ; 17(10): e0275286, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36219595

RESUMO

We calculate the embodied carbon emissions of China's through the multiregional input-output (MRIO) method, then we construct the interprovincial embodied carbon flow networks of China's exports based on the mean threshold, and the application of complex network analysis to conduct a detailed examination of the overall characteristics, key nodes and edges, and community structure of China's interprovincial embodied carbon flow network. We extended the embodied carbon flow network analysis at the provincial level. The results demonstrated the following: (1) The interprovincial embodied carbon flow network of China's exports has small-world and scale-free characteristics. The node degree probability distribution curves for the networks obviously conformed to a decreasing power law distribution, indicating that a few industrial sectors carry a large amount of embodied carbon and suggesting that reducing the embodied carbon of China's exports could yield twice the results with half the effort as long as attention is paid to a few sectors. (2) The key nodes and edges in the networks show that industrial sectors and production chains such as the power and heat production and supply industry, the petroleum processing, coking, and nuclear fuel processing industry, and the metal smelting and calendering industry play the role of key "bridges" in the entire network, among which Guangdong, Hebei, Jiangsu, Inner Mongolia, and Shanxi are important node provinces and the main flow paths for the generation of embodied carbon in national exports. These industrial sectors and production chains should bolster their policies to encourage the innovation of carbon emission reduction technologies and decrease carbon emissions, so as to reduce the embodied carbon of national exports on a large scale. (3) The number of communities firstly increased then decreased from 2007 to 2017, while the aggregation coefficient of the node and correlation density within first community displayed firstly downward then upward trends, reflecting firstly decentralization then centralization of the interprovincial embodied carbon flow.


Assuntos
Carbono , Petróleo , Carbono/análise , Dióxido de Carbono/análise , China , Desenvolvimento Econômico , Indústrias , Petróleo/análise
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