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1.
Colloids Surf B Biointerfaces ; 240: 113968, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38788472

RESUMO

Due to the unique structure, carbon nanomaterials could convert near-infrared (NIR) light into heat efficiently in tumor ablation using photothermal therapy (PTT). However, none of them has been applied in clinical treatment, because they have not been approved for clinical evaluations and the precise temperature control facility is scarce. In this study, we designed a temperature-responsive controller for PTT and used carbon nanoparticles-Fe(II) complex (CNSI-Fe) as photothermal conversion agent (PTA) for PTT of tumor in vitro and in vivo. CNSI-Fe was an innovative drug under the evaluations in clinical trials. CNSI-Fe showed excellent photothermal conversion ability in water to increase the water temperature by 40 °C within 5 min under irradiation of 808 nm laser at 0.5 W/cm2. The temperature was precisely controlled at 52 °C for both in vitro and in vivo tumor inhibition. CNSI-Fe with NIR irradiation showed higher tumor cell inhibition than CNSI. In tumor bearing mice, CNSI-Fe with NIR irradiation achieved an inhibition rate of 84.7 % and 71.4 % of them were completely cured. Mechanistically, CNSI-Fe under NIR irradiation induced the radical generation, oxidative damage and ferroptosis to kill tumor. In addition, CNSI-Fe showed good biosafety during PTT according to hematological, serum biological and histopathological examinations. These results indicated that the combination of chemotherapy and PTT provided higher antitumor efficiency using CNSI-Fe as PTA.


Assuntos
Carbono , Nanopartículas , Terapia Fototérmica , Animais , Carbono/química , Camundongos , Nanopartículas/química , Humanos , Camundongos Nus , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos Endogâmicos BALB C , Raios Infravermelhos , Compostos Ferrosos/química , Compostos Ferrosos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Tamanho da Partícula , Ensaios de Seleção de Medicamentos Antitumorais
2.
J Bone Miner Res ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38624186

RESUMO

BACKGROUND: The relationship between socio-economic status and bone-related diseases is attracting increasing attention. Therefore, a bidirectional Mendelian randomization (MR) analysis was performed in this study. METHODS: Genetic data on factors associated with socio-economic status (average total household income before tax, years of schooling completed and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fracture (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses, and multivariable MR was performed to enhance the robustness of our findings. RESULTS: A higher educational attainment was associated with an increased level of eBMD (beta:0.06, 95% CI:0.01-0.10, P = 7.24 × 10-3), and decreased risk of osteoporosis (OR:0.78, 95% CI:0.65-0.94, P = 8.49 × 10-3), spine fracture (OR:0.76, 95% CI:0.66-0.88, P = 2.94 × 10-4), femur fracture (OR:0.78, 95% CI:0.67-0.91, P = 1.33 × 10-3), lower leg-ankle fracture (OR:0.79, 95% CI:0.70-0.88, P = 2.05 × 10-5), foot fracture (OR:0.78, 95% CI:0.66-0.93, P = 5.92 × 10-3) and wrist-hand fracture (OR:0.83, 95% CI:0.73-0.95, P = 7.15 × 10-3). Further, material deprivation seemed to harm the spine fracture (OR:2.63, 95% CI:1.43-4.85, P = 1.91 × 10-3). A higher level of FN-BMD positively affected increased household income (beta:0.03, 95% CI:0.01-0.04, P = 6.78 × 10-3). All these estimates were adjusted for body mass index (BMI), type 2 diabetes, smoking initiation, and frequency of alcohol intake. CONCLUSIONS: The Mendelian randomization analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings offer valuable insights into the formulation of health guidelines and policy development.


We conducted stratified analyses to explore the causal links between socio-economic status and osteoporosis and various fractures and observed that education significantly reduced risk of osteoporosis and lower eBMD. It also lowered the risks of fractures of spine, femur, lower leg-ankle, foot, and wrist-hand, while material deprivation exhibited positive associations with spine fracture risk. Bidirectional MR analysis showed that an elevated score of FN-BMD was associated with a higher income level. Our study shows the importance of conducting routine BMD estimations and osteoporosis screening, to enhance knowledge and awareness among individuals to promote bone health and prevent fractures.

3.
Environ Sci Technol ; 58(13): 5856-5865, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38516968

RESUMO

Measuring the quantum yield and reactivity of triplet-state dissolved organic matter (3DOM*) is essential for assessing the impact of DOM on aquatic photochemical processes. However, current 3DOM* quantification methods require multiple fitting steps and rely on steady-state approximations under stringent application criteria, which may introduce certain inaccuracies in the estimation of DOM photoreactivity parameters. Here, we developed a global kinetic model to simulate the reaction kinetics of the hv/DOM system using four DOM types and 2,4,6-trimethylphenol as the probe for 3DOM*. Analyses of residuals and the root-mean-square error validated the exceptional precision of the new model compared to conventional methods. 3DOM* in the global kinetic model consistently displayed a lower quantum yield and higher reactivity than those in local regression models, indicating that the generation and reactivity of 3DOM* have often been overestimated and underestimated, respectively. The global kinetic model derives parameters by simultaneously fitting probe degradation kinetics under different conditions and considers the temporally increasing concentrations of the involved reactive species. It minimizes error propagation and offers insights into the interactions of different species, thereby providing advantages in accuracy, robustness, and interpretability. This study significantly advances the understanding of 3DOM* behavior and provides a valuable kinetic model for aquatic photochemistry research.


Assuntos
Matéria Orgânica Dissolvida , Processos Fotoquímicos , Fotoquímica , Fotólise
4.
J Mater Chem B ; 12(10): 2559-2570, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38362614

RESUMO

Pathologic myopia has seriously jeopardized the visual health of adolescents in the past decades. The progression of high myopia is associated with a decrease in collagen aggregation and thinning of the sclera, which ultimately leads to longer eye axis length and image formation in front of the retina. Herein, we report a fibroblast-loaded hydrogel as a posterior scleral reinforcement (PSR) surgery implant for the prevention of myopia progression. The fibroblast-loaded gelatin methacrylate (GelMA)-poly(ethylene glycol) diacrylate (PEGDA) hydrogel was prepared through bioprinting with digital light processing (DLP). The introduction of the PEGDA component endowed the GelMA-PEGDA hydrogel with a high compression modulus for PRS surgery. The encapsulated fibroblasts could consistently maintain a high survival rate during 7 days of in vitro incubation, and could normally secrete collagen type I. Eventually, both the hydrogel and fibroblast-loaded hydrogel demonstrated an effective shortening of the myopic eye axis length in a guinea pig model of visual deprivation over three weeks after implantation, and the sclera thickness of myopic guinea pigs became significantly thicker after 4 weeks, verifying the success of sclera remodeling and showing that myopic progression was effectively controlled. In particular, the fibroblast-loaded hydrogel demonstrated the best therapeutic effect through the synergistic effect of cell therapy and PSR surgery.


Assuntos
Miopia , Esclera , Animais , Cobaias , Modelos Animais de Doenças , Esclera/patologia , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Miopia/tratamento farmacológico , Miopia/prevenção & controle , Miopia/patologia , Fibroblastos/patologia , Impressão Tridimensional
5.
J Pediatr Nurs ; 75: 31-40, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38101309

RESUMO

PROBLEM: Most rare diseases occur in childhood and are difficult to diagnose and treat. The caregivers are faced with the challenge of providing care to the children afflicted with these rare diseases, resulting in a significant burden of care and an altered family dynamic. ELIGIBILITY CRITERIA: A meta-synthesis review was conducted to explore the caregivers' experience of children with rare diseases using eight electronic databases PubMed, Web of Science, the Cochrane Library, EMBASE, VIP database, Wan Fang, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure from each database's inception to October 5, 2023. SAMPLE: 4207 records were identified and 20 eligible studies were included. RESULTS: Three themes emerged: (1) Life is changed by "rare"; (2) many unmet needs; (3) Strive to adapt and grow. CONCLUSIONS: Caregivers of children with rare diseases are full of stress and challenges in the process of caring for them, and their lives have changed greatly due to "rare". Appropriate measures need to be taken to reduce the burden on caregivers. IMPLICATIONS: According to the findings, both the medical and health systems, as well as society, should pay attention to the care load and unmet requirements of carers of children with rare diseases, and offer them with practical supportive services. Finally, it can improve the quality of life for caregivers and families of children with rare diseases, as well as stimulate the development of rare diseases.


Assuntos
Cuidadores , Qualidade de Vida , Criança , Humanos , Pesquisa Qualitativa , Doenças Raras
6.
J Nanobiotechnology ; 21(1): 315, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667298

RESUMO

Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment.


Assuntos
Exossomos , MicroRNAs , Calcificação Vascular , Animais , Camundongos , Células Endoteliais , Fibroblastos , Fósforo , MicroRNAs/genética , Receptores de Proteínas Morfogenéticas Ósseas
7.
Pharmaceutics ; 15(8)2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37631359

RESUMO

A carbon nanotube-doped octapeptide self-assembled hydrogel (FEK/C) and a hydrogel-based polycaprolactone PCL composite scaffold (FEK/C3-S) were developed for cartilage and subchondral bone repair. The composite scaffold demonstrated modulated microstructure, mechanical properties, and conductivity by adjusting CNT concentration. In vitro evaluations showed enhanced cell proliferation, adhesion, and migration of articular cartilage cells, osteoblasts, and bone marrow mesenchymal stem cells. The composite scaffold exhibited good biocompatibility, low haemolysis rate, and high protein absorption capacity. It also promoted osteogenesis and chondrogenesis, with increased mineralization, alkaline phosphatase (ALP) activity, and glycosaminoglycan (GAG) secretion. The composite scaffold facilitated accelerated cartilage and subchondral bone regeneration in a rabbit knee joint defect model. Histological analysis revealed improved cartilage tissue formation and increased subchondral bone density. Notably, the FEK/C3-S composite scaffold exhibited the most significant cartilage and subchondral bone formation. The FEK/C3-S composite scaffold holds great promise for cartilage and subchondral bone repair. It offers enhanced mechanical support, conductivity, and bioactivity, leading to improved tissue regeneration. These findings contribute to the advancement of regenerative strategies for challenging musculoskeletal tissue defects.

9.
Cell Mol Immunol ; 20(10): 1232-1250, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37644166

RESUMO

SEL1L-mediated endoplasmic reticulum-associated degradation (ERAD) plays critical roles in controlling protein homeostasis by degrading misfolded or terminal unfolded proteins. However, it remains unclear how SEL1L regulates peripheral T-cell survival and homeostasis. Herein, we found that SEL1L deficiency led to a greatly reduced frequency and number of mature T cells, which was further validated by adoptive transfer experiments or bone marrow chimera experiments, accompanied by the induction of multiple forms of cell death. Furthermore, SEL1L deficiency selectively disrupted naïve CD8+ T-cell homeostasis, as indicated by the severe loss of the naïve T-cell subset but an increase in the memory T-cell subset. We also found that SEL1L deficiency fueled mTORC1/c-MYC activation and induced a metabolic shift, which was largely attributable to enhanced expression of the IL-15 receptor α and ß chains. Mechanistically, single-cell transcriptomic profiling and biochemical analyses further revealed that Sel1l-/- CD8+ T cells harbored excessive ER stress, particularly aberrant activation of the PERK-ATF4-CHOP-Bim pathway, which was alleviated by supplementing IL-7 or IL-15. Importantly, PERK inhibition greatly resolved the survival defects of Sel1l-/- CD8+ T cells. In addition, IRE1α deficiency decreased mTORC1 signaling in Sel1l-/- naïve CD8+ T cells by downregulating the IL-15 receptor α chain. Altogether, these observations suggest that the ERAD adaptor molecule SEL1L acts as an important checkpoint for preserving the survival and homeostasis of peripheral T cells by regulating the PERK signaling cascade and IL-15 receptor-mediated mTORC1 axis.


Assuntos
Degradação Associada com o Retículo Endoplasmático , Proteínas Serina-Treonina Quinases , Linfócitos T CD8-Positivos/metabolismo , Sobrevivência Celular , Endorribonucleases/metabolismo , Homeostase , Proteínas Serina-Treonina Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Camundongos
10.
J Nanobiotechnology ; 21(1): 226, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37461031

RESUMO

Medial arterial calcification (MAC), a systemic vascular disease different from atherosclerosis, is associated with an increased incidence of cardiovascular events. Several studies have demonstrated that ambient temperature is one of the most important factors affecting cardiovascular events. However, there has been limited research on the effect of different ambient temperatures on MAC. In the present study, we showed that cold temperature exposure (CT) in mice slowed down the formation of vitamin D (VD)-induced vascular calcification compared with room temperature exposure (RT). To investigate the mechanism involved, we isolated plasma-derived exosomes from mice subjected to CT or RT for 30 days (CT-Exo or RT-Exo, respectively). Compared with RT-Exo, CT-Exo remarkably alleviated the calcification/senescence formation of vascular smooth muscle cells (VSMCs) and promoted autophagy by activating the phosphorylation of AMP-activated protein kinase (p-AMPK) and inhibiting phosphorylation of mammalian target of rapamycin (p-mTOR). At the same time, CT-Exo promoted autophagy in ß-glycerophosphate (ß-GP)-induced VSMCs. The number of autophagosomes and the expression of autophagy-related proteins ATG5 and LC3B increased, while the expression of p62 decreased. Based on a microRNA chip microarray assay and real-time polymerase chain reaction, miR-320a-3p was highly enriched in CT-Exo as well as thoracic aortic vessels in CT mice. miR-320a-3p downregulation in CT-Exo using AntagomiR-320a-3p inhibited autophagy and blunted its anti-calcification protective effect on VSMCs. Moreover, we identified that programmed cell death 4 (PDCD4) is a target of miR-320a-3p, and silencing PDCD4 increased autophagy and decreased calcification in VSMCs. Treatment with CT-Exo alleviated the formation of MAC in VD-treated mice, while these effects were partially reversed by GW4869. Furthermore, the anti-arterial calcification protective effects of CT-Exo were largely abolished by AntagomiR-320a-3p in VD-induced mice. In summary, we have highlighted that prolonged cold may be a good way to reduce the incidence of MAC. Specifically, miR-320a-3p from CT-Exo could protect against the initiation and progression of MAC via the AMPK/mTOR autophagy pathway.


Assuntos
Aterosclerose , MicroRNAs , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Antagomirs , Serina-Treonina Quinases TOR , Autofagia , MicroRNAs/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
11.
Front Pharmacol ; 14: 1112484, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37169000

RESUMO

Introduction: Necroptosis is an alternative, caspase-independent programmed cell death that appears when apoptosis is inhibited. A gowing number of studies have reflected the link between necroptosis and tumors. However, only some systematical bibliometric analyses were focused on this field. In this study, we aimed to identify and visualize the cooperation between countries, institutions, authors, and journals through a bibliometric analysis to help understand the hotspot trends and emerging topics regarding necroptosis and cancer research. Methods: The articles and reviews on necroptosis and cancer were obtained from the Web of Science Core Collection on 16 September 2022. Countries, institutions, authors, references, and keywords in this field were visually analyzed by CtieSpace 5.8.R3, VOSviewer 1.6.18, and R package "bibliometrix." Results: From 2006 to 2022, 2,216 qualified original articles and reviews on necroptosis in tumors were published in 685 academic journals by 13,009 authors in 789 institutions from 75 countries/regions. Publications focusing on necroptosis and cancer have increased violently in the past 16 years, while the citation number peaked around 2008-2011. Most publications were from China, while the United States maintained the dominant position as a "knowledge bridge" in necroptosis and cancer research; meanwhile, Ghent University and the Chinese Academy of Sciences were the most productive institutions. Moreover, only a tiny portion of the articles were multiple-country publications. Peter Vandenabeele had the most significant publications, while Alexei Degterev was most often co-cited. Peter Vandenabeele also gets the highest h-index and g-index in this research field. Cell Death and Disease was the journal with the most publications on necroptosis and cancer, which was confirmed to be the top core source by Bradford's Law. At the same time, Cell was the leading co-cited journal, and the focus area of these papers was molecular, biology, and immunology. High-frequency keywords mainly contained those that are molecularly related (MLKL, NF-kB, TNF, RIPK3, RIPK1), pathological process related (necroptosis, apoptosis, cell-death, necrosis, autophagy), and mechanism related (activation, expression, mechanisms, and inhibition). Conclusion: This study comprehensively overviews necroptosis and cancer research using bibliometric and visual methods. Research related to necroptosis and cancer is flourishing. Cooperation and communication between countries and institutions must be further strengthened. The information in our paper would provide valuable references for scholars focusing on necroptosis and cancer.

12.
Molecules ; 28(7)2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37049746

RESUMO

As a substitute for banned brominated flame retardants (BFRs), the use of organophosphate esters (OPEs) increased year by year with the increase in industrial production and living demand. It was inevitable that OPEs would be discharged into wastewater in excess, which posed a great threat to the health of human beings and aquatic organisms. In the past few decades, people used various methods to remove refractory OPEs. This paper reviewed the photocatalysis method, the adsorption method with wide applicability, and the biological method mainly relying on enzymolysis and hydrolysis to degrade OPEs in water. All three of these methods had the advantages of high removal efficiency and environmental protection for various organic pollutants. The degradation efficiency of OPEs, degradation mechanisms, and conversion products of OPEs by three methods were discussed and summarized. Finally, the development prospects and challenges of OPEs' degradation technology were discussed.


Assuntos
Retardadores de Chama , Água , Humanos , Retardadores de Chama/análise , Adsorção , Organofosfatos , Ésteres , Monitoramento Ambiental , China
13.
Graefes Arch Clin Exp Ophthalmol ; 261(10): 2729-2741, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36862203

RESUMO

Optical coherence tomography (OCT) is a revolutionary in vivo imaging technology that presents real-time information on ocular structures. Angiography based on OCT, known as optical coherence tomography angiography (OCTA), is a noninvasive and time-saving technique originally utilized for visualizing retinal vasculature. As devices and built-in systems have evolved, high-resolution images with depth-resolved analysis have assisted ophthalmologists in accurately localizing pathology and monitoring disease progression. With the aforementioned advantages, application of OCTA has extended from the posterior to anterior segment. This nascent adaptation showed good delineation of the vasculature in the cornea, conjunctiva, sclera, and iris. Thus, neovascularization of the avascular cornea and hyperemia or ischemic changes involving the conjunctiva, sclera, and iris has become prospective applications for AS-OCTA. Although traditional dye-based angiography is regarded as the gold standard in demonstrating vasculature in the anterior segment, AS-OCTA is expected to be a comparable but more patient-friendly alternative. In its initial stage, AS-OCTA has exhibited great potential in pathology diagnosis, therapeutic evaluation, presurgical planning, and prognosis assessments in anterior segment disorders. In this review of AS-OCTA, we aim to summarize scanning protocols, relevant parameters, and clinical applications as well as limitations and future directions. We are sanguine about its wide application in the future with the development of technology and refinement in built-in systems.


Assuntos
Angiografia , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Vasos Retinianos , Iris/irrigação sanguínea , Córnea , Angiofluoresceinografia/métodos
14.
Int J Nanomedicine ; 18: 933-948, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36852185

RESUMO

Background: Nanomaterials exhibited intrinsic enzyme-like properties due to the unique properties compared with natural enzyme. Carbon dots (CDs) are an important kind of quantum-sized nanomaterials, which have enormous application potential in bio-imaging, drug carrier, and nanosystems. Carbon dots possess intrinsic enzyme-like properties, such as glutathione (GSH) oxidase or peroxidase activities. Methods: A co-delivery nanosystem that could carry siRNA and doxorubucin (DOX) simultaneously has been studied in this work. The co-delivery based on carbon dots was surface-modified with poly-ethylenimine (PEI) and loaded the siMRP1 with chemotherapeutics on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI was raw materials and passivator during the reaction process that makes CDs exhibit excellent optical property. Results: The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumors and releasing them synchronously in cells in an acid-triggered manner. The particles exhibited GSH oxidase-like catalytic property, oxidizing GSH to oxidized glutathione with concomitant increase of reactive oxygen species (ROS). We found that silencing of MRP1 by co-delivery system antagonized chemoresistance by increasing DOX accumulation and significantly enhancing the inhibitory effect of cell viability induced by CD-PEI-DOX. The co-delivery system dramatically inhibited tumor growth in xenograft model, and CDs counteracted MRP1 function by siRNA-mediated knockdown of MRP1. Conclusion: Taken together, we uncover the potential role of CDs with a combination of siRNA and chemotherapeutics in overcoming chemoresistance of lung cancer by suppressing MRP1 and oxidation of GSH. Our findings imply its potential of antagonizing chemoresistance to enhance therapeutic efficiency of doxorubicin in clinical practices of lung cancer treatment.


Assuntos
Neoplasias Pulmonares , Humanos , Carbono , Doxorrubicina/farmacologia , Glutationa , Neoplasias Pulmonares/tratamento farmacológico , Oxirredutases , RNA Interferente Pequeno , Resistencia a Medicamentos Antineoplásicos
15.
Anal Bioanal Chem ; 415(9): 1733-1740, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36840810

RESUMO

ω-Transaminases (ω-TAs) are widely available for the production of chiral amines and unnatural amino acids. Herein, a rapid spectrophotometric method was developed for screening ω-TAs based on the colored products that can be generated from transamination reactions between aliphatic α-diketones and amino donors catalyzed by ω-TAs. The possible mechanism of the formation of the colored product was investigated according to LC-Q-TOF-MS analysis. Among seven diketones, 2,3-butanedione was selected as the most suitable amino acceptor for colorimetric screening of ω-TAs with high efficiency, high sensitivity, and low background interference. Meanwhile, the absorbance of the colored product generated by 2,3-butanedione catalyzed by ω-TAs in this method was linearly correlated with the results by HPLC analysis. This method was also confirmed to effectively screen ω-TA mutants with high activity towards isopropylamine.


Assuntos
Ensaios de Triagem em Larga Escala , Transaminases , Transaminases/química , Transaminases/metabolismo , Colorimetria , Diacetil , Aminoácidos , Aminas , Cetonas
16.
Biomater Sci ; 11(3): 840-853, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36512317

RESUMO

Segmental bone defects over the self-healing threshold are a major challenge for orthopedics. Despite the advancements in clinical practice, traditional tissue engineering methods are limited by the addition of heterogeneous cells and cytokines, leading to carcinoma or other adverse effects. Here, we present a cell-free and cytokine-free strategy using an ECM-mimetic self-assembling peptide hydrogel (SAPH)- polycaprolactone (PCL) composite scaffold. The hydrophilic SAPH endows the rigid PCL scaffold with excellent biocompatibility and preference for osteogenesis induction. The autologous cells around the bone defect site immediately grew, proliferated, and secreted ECM and cytokines after contacting the implanted SAPH-PCL composite scaffold, and the bone repair of rabbit ulnar segmental bone defect was achieved in just six months. Quantitative proteomic analysis reveals that the SAPH-PCL composite scaffold accelerates osteoblastogenesis, osteoclastogenesis, and angiogenesis with moderate immune responses and negligible effects on pathological fibrosis. These findings have important implications for the potential clinical applications of the SAPH-PCL composite scaffold in patients with segmental bone defects and identify the mechanisms of action for accelerated segmental bone defect repair.


Assuntos
Hidrogéis , Alicerces Teciduais , Animais , Coelhos , Proteômica , Engenharia Tecidual/métodos , Osteogênese , Poliésteres/farmacologia , Peptídeos
17.
Sci Total Environ ; 858(Pt 2): 159942, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36343828

RESUMO

Average climatic events describe the occurrence of weather or climate at an average value, whereas extreme events are defined as events that exceed the upper or lower threshold value of statistical or observational average climatic events. This study investigated the impacts of both average climate change (ACC) (i.e., average precipitation, temperature, and potential evapotranspiration [PET]) and extreme climate change (ECC) (i.e., five precipitation and five temperature extremes) on dryland vegetation based on the Normalized Difference Vegetation Index (NDVI). The spatial divergences of ACC and ECC in affecting changes in NDVI over drylands were determined using the geographical detector model. In this study, the growth of vegetation in 40.29 % of global drylands was driven by average precipitation and this dominant effect also occurred in all the plant species, particularly shrubs. However, the sensitivity of grassland to average precipitation exceeded that of most of the woody vegetation. The average temperature and PET controlled 28.64 % and 31.07 % of the changes in NDVI, respectively. Precipitation extremes (except for consecutive dry days and consecutive wet days) and warm temperature extremes (WTE) had positive influences on dryland vegetation, and the effect of WTE on NDVI exceeded that of the remaining temperature extremes. Temperature extremes exerted more significant effects than precipitation extremes for changes in the grassland NDVI. In contrast, the variations in shrub NDVI were primarily dominated by precipitation extremes. We also found that the impacts of parts of average and extreme climatic factors on vegetation had changed over time. Furthermore, temperature extremes had far exceeded the average temperature in affecting vegetation growth at the spatial scale, and this action gradually intensified from 1982 to 2015. The influences of all precipitation extremes were weaker than those of the average precipitation. Those can offer scientific references for ecosystem protection in drylands.


Assuntos
Mudança Climática , Ecossistema , Plantas , Temperatura , Tempo (Meteorologia) , China
18.
J Agric Food Chem ; 70(48): 15178-15188, 2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36424346

RESUMO

Five plant-derived uridine diphosphate glycosyltransferases (UGTs) that catalyzed the glucosylation of stevia glycosides (SGs) were uncovered as the result of sequence mining considering the catalytic residues and conserved motifs of the known UGTs. Thereinto, LbUGT from Lycium barbarum with high activity toward rubusoside has been enzymatically characterized. The recombinant LbUGT was demonstrated to catalyze the ß-1,6-glucosylation at C19 of rubusoside, producing a monoglucosyl derivative 13-[(O-ß-d-glucopyranosyl) oxy] ent-kaur-16-en-19-oic acid-[(6-O-ß-d-glucopyranosyl-ß-d-glucopyranosyl) ester], which was then submitted to a ß-1,2-glucosylation by LbUGT, resulting in a diglucosyl derivative 13-[(O-ß-d-glucopyranosyl) oxy] ent-kaur-16-en-19-oic acid-[(2-O-ß-d-glucopyranosyl-6-O-ß-d-glucopyranosyl-ß-d-glucopyranosyl) ester]. The di-glycosylated product of rubusoside showed an obvious increase in sweetness intensity (134 times sweeter than 5% sucrose) and almost eliminated the unpleasant bitter taste. This work will provide a reference for the taste improvement of SGs.


Assuntos
Stevia , Difosfato de Uridina , Glicosídeos , Glicosiltransferases/genética , Ésteres
19.
ACS Omega ; 7(41): 36672-36678, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36278039

RESUMO

With the rapid progress of agriculture and aquaculture, waste shells are harming the environment because of large production, and highly valued recycling is now holding more attention. However, there are still no good ways for simultaneously solving the poor mechanical and antibacterial performance during the recycling process. In this work, antibacterial shell-grafting-Ag powders/polylactic acid (shell-g-Ag/PLA) biocompatible composites, with comparable mechanical properties to industrial polymer counterparts, were prepared via the in situ reduction of Ag ions on surfaces of polydopamine-modified shell powders. The introduction of Ag particles increases the compatibility on the interface and endows the composites with antibacterial performance by inheriting the prominent characteristic from Ag. Without scarifying the mechanical properties by improving the crystallinity and interface, the loaded Ag particles in the composites endowed the composites with valorized antibacterial performance, evidenced by a bacterial inhibition width from 0 to ∼3.29 mm. The biofriendly composites, together with comparable mechanical properties to industrial PLA products, can serve as a sustainable material to be applied in the field of disposable packaging.

20.
Front Endocrinol (Lausanne) ; 13: 863708, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784574

RESUMO

Histone methylation is an epigenetic change mediated by histone methyltransferase, and has been connected to the beginning and progression of several diseases. The most common ailments that affect the elderly are cardiovascular and cerebrovascular disorders. They are the leading causes of death, and their incidence is linked to vascular calcification (VC). The key mechanism of VC is the transformation of vascular smooth muscle cells (VSMCs) into osteoblast-like phenotypes, which is a highly adjustable process involving a variety of complex pathophysiological processes, such as metabolic abnormalities, apoptosis, oxidative stress and signalling pathways. Many researchers have investigated the mechanism of VC and related targets for the prevention and treatment of cardiovascular and cerebrovascular diseases. Their findings revealed that histone lysine methylation modification may play a key role in the various stages of VC. As a result, a thorough examination of the role and mechanism of lysine methylation modification in physiological and pathological states is critical, not only for identifying specific molecular markers of VC and new therapeutic targets, but also for directing the development of new related drugs. Finally, we provide this review to discover the association between histone methylation modification and VC, as well as diverse approaches with which to investigate the pathophysiology of VC and prospective treatment possibilities.


Assuntos
Lisina , Calcificação Vascular , Idoso , Histonas/metabolismo , Humanos , Metilação , Estudos Prospectivos , Calcificação Vascular/genética , Calcificação Vascular/patologia
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