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1.
Cereb Cortex ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35512283

RESUMO

Despite ambiguous environmental inputs, top-down attention biases our subjective perception toward the preferred percepts, via modulating prestimulus neural activity or inducing prestimulus sensory templates that carry concrete internal sensory representations of the preferred percepts. In contrast to frequent changes of behavioral goals in the typical cue-target paradigm, human beings are often engaged in a prolonged task state with only 1 specific behavioral goal. It remains unclear how prestimulus neural signals and sensory templates are modulated in the latter case. To answer this question in the present electroencephalogram study on human subjects, we manipulated sustained task demands toward one of the 2 possible percepts in the bistable Ternus display, emphasizing either temporal integration or segregation. First, the prestimulus peak alpha frequency, which gated the temporal window of temporal integration, was effectively modulated by task demands. Furthermore, time-resolved decoding analyses showed that task demands biased neural representations toward the preferred percepts after the full presentation of bottom-up stimuli. More importantly, sensory templates resembling the preferred percepts emerged even before the bottom-up sensory evidence were sufficient enough to induce explicit percepts. Taken together, task demands modulate both prestimulus alpha frequency and sensory templates, to eventually bias subjective perception toward the preferred percepts.

2.
Front Neurosci ; 16: 810553, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431792

RESUMO

Background: The motor imagery brain computer interface (MI-BCI) is now available in a commercial product for clinical rehabilitation. However, MI-BCI is still a relatively new technology for commercial rehabilitation application and there is limited prior work on the frequency effect. The MI-BCI has become a commercial product for clinical neurological rehabilitation, such as rehabilitation for upper limb motor dysfunction after stroke. However, the formulation of clinical rehabilitation programs for MI-BCI is lack of scientific and standardized guidance, especially limited prior work on the frequency effect. Therefore, this study aims at clarifying how frequency effects on MI-BCI training for the plasticity of the central nervous system. Methods: Sixteen young healthy subjects (aged 22.94 ± 3.86 years) were enrolled in this randomized clinical trial study. Subjects were randomly assigned to a high frequency group (HF group) and low frequency group (LF group). The HF group performed MI-BCI training once per day while the LF group performed once every other day. All subjects performed 10 sessions of MI-BCI training. functional near-infrared spectroscopy (fNIRS) measurement, Wolf Motor Function Test (WMFT) and brain computer interface (BCI) performance were assessed at baseline, mid-assessment (after completion of five BCI training sessions), and post-assessment (after completion of 10 BCI training sessions). Results: The results from the two-way ANOVA of beta values indicated that GROUP, TIME, and GROUP × TIME interaction of the right primary sensorimotor cortex had significant main effects [GROUP: F (1,14) = 7.251, P = 0.010; TIME: F (2,13) = 3.317, P = 0.046; GROUP × TIME: F (2,13) = 5.676, P = 0.007]. The degree of activation was affected by training frequency, evaluation time point and interaction. The activation of left primary sensory motor cortex was also affected by group (frequency) (P = 0.003). Moreover, the TIME variable was only significantly different in the HF group, in which the beta value of the mid-assessment was higher than that of both the baseline assessment (P = 0.027) and post-assessment (P = 0.001), respectively. Nevertheless, there was no significant difference in the results of WMFT between HF group and LF group. Conclusion: The major results showed that more cortical activation and better BCI performance were found in the HF group relative to the LF group. Moreover, the within-group results also showed more cortical activation after five sessions of BCI training and better BCI performance after 10 sessions in the HF group, but no similar effects were found in the LF group. This pilot study provided an essential reference for the formulation of clinical programs for MI-BCI training in improvement for upper limb dysfunction.

3.
Clin Nutr ; 41(3): 599-609, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35124467

RESUMO

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) is a new framework to evaluate nutritional status. It has been validated mostly by retrospective studies, which often failed to follow the framework as recommended due to their retrospective nature. This study aims to validate GLIM with a large prospective study and investigate its role in predicting short-term surgical outcomes. METHODS: Patients who underwent abdominal surgery for digestive cancer in our center were prospectively included between January 2020 and December 2020. Data collected included demographic information, clinical and pathological information, lab results, and computed tomography scans. Muscle strength, physical performances, quality of life and cancer symptom burden were evaluated upon admission. Multiple tools for nutritional risk screening were used. Nutritional status was evaluated with Subjective Global Assessment (SGA) and GLIM. Postoperative outcomes collected included return of gastrointestinal function, postoperative length of stay, complications, 30-day readmission and 30-day mortality. RESULTS: A total of 1115 patients were evaluated with GLIM criteria. Inter-rater reliability was good [k = 0.76, 95% confidence interval (CI): 0.72-0.80]. The accuracy of GLIM diagnosis compared to the semi-gold standard SGA varied with the screening method used. GLIM with MNA-SF screening [area under the curve (AUC): 0.78] and GLIM without screening (AUC: 0.77) were the two most accurate protocols, and there was no significant difference between the two from a clinical perspective. GLIM can predict preoperative nutritional status, functional status, symptom burden and quality of life. It can also predict complications after surgery [odds ratio (OR) = 2.31, 95% CI: 1.67-3.21], especially infection related complications (OR = 2.19, 95% CI: 1.38-3.49) and wound healing related complications (OR = 2.54, 95% CI: 1.38-4.71). CONCLUSIONS: GLIM malnutrition criteria showed good inner-rater reliability and moderate agreement with SGA. GLIM can be used to predict preoperative nutritional status, functional status, cancer related symptoms, and quality of life. It can also predict postoperative outcomes especially complications that are related to infection and wound healing. In surgical candidates, the screening process could potentially be skipped so that GLIM assessment can be faster, more accessible, and more sensitive.


Assuntos
Desnutrição , Neoplasias , Humanos , Liderança , Desnutrição/etiologia , Neoplasias/complicações , Avaliação Nutricional , Estado Nutricional , Estudos Prospectivos , Qualidade de Vida , Reprodutibilidade dos Testes , Estudos Retrospectivos
4.
Front Nutr ; 9: 794576, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35178421

RESUMO

BACKGROUND: Skeletal muscle mass deterioration is common in gastric cancer (GC) patients and is linked to poor prognosis. However, information regarding the effect of skeletal muscle mass changes in the postoperative period is scarce. This study was to investigate the link between postoperative loss of skeletal muscle mass and survival following GC surgery. METHODS: Patients who underwent GC surgery between January 2015 and December 2016 were recruited into the study. Computed tomography at L3 vertebral level was used to examine skeletal muscle index prior to surgery and about 6 months after surgery. Skeletal muscle index changes were categorized as presence or absence of ≥5% loss. Overall survival (OS) and disease-free survival (DFS) were analyzed, and Cox proportional hazard models used to identify their predictors. RESULTS: The study comprised of 318 gastric cancer patients of which 63.5% were male. The group's mean age was 58.14 ± 10.77 years. Sixty-five patients experienced postoperative skeletal muscle index loss ≥5% and had poorer OS (P = 0.004) and DFS (P = 0.020). We find that postoperative skeletal muscle index loss ≥ 5% predicts OS [hazard ratio (HR): 2.769, 95% confidence interval (CI): 1.865-4.111; P < 0.001] and DFS (HR: 2.533, 95% CI: 1.753-3.659; P < 0.001). CONCLUSIONS: Loss of skeletal muscle mass postoperatively is linked to poor survival following GC surgery. Further studies are needed to determine whether stabilizing or enhancing skeletal muscle mass after surgery improves survival.

5.
Front Neurosci ; 16: 807045, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185457

RESUMO

BACKGROUND: Mirror visual feedback (MVF) has been widely used in neurological rehabilitation. Due to the potential gain effect of the MVF combination therapy, the related mechanisms still need be further analyzed. METHODS: Our self-controlled study recruited 20 healthy subjects (age 22.150 ± 2.661 years) were asked to perform four different visual feedback tasks with simultaneous functional near infrared spectroscopy (fNIRS) monitoring. The right hand of the subjects was set as the active hand (performing active movement), and the left hand was set as the observation hand (static or performing passive movement under soft robotic bilateral hand rehabilitation system). The four VF tasks were designed as RVF Task (real visual feedback task), MVF task (mirror visual feedback task), BRM task (bilateral robotic movement task), and MVF + BRM task (Mirror visual feedback combined with bilateral robotic movement task). RESULTS: The beta value of the right pre-motor cortex (PMC) of MVF task was significantly higher than the RVF task (RVF task: -0.015 ± 0.029, MVF task: 0.011 ± 0.033, P = 0.033). The beta value right primary sensorimotor cortex (SM1) in MVF + BRM task was significantly higher than MVF task (MVF task: 0.006 ± 0.040, MVF + BRM task: 0.037 ± 0.036, P = 0.016). CONCLUSION: Our study used the synchronous fNIRS to compare the immediate hemodynamics cortical activation of four visual feedback tasks in healthy subjects. The results showed the synergistic gain effect on cortical activation from MVF combined with a soft robotic bilateral hand rehabilitation system for the first time, which could be used to guide the clinical application and the future studies.

6.
J Inflamm Res ; 15: 603-612, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35115808

RESUMO

BACKGROUND: Allergic rhinitis (AR) is a common inflammatory airway disease, and allergen-specific immunotherapy (AIT) is the only disease-modifying treatment for it. However, not all AR patients respond to AIT, and early prediction of patient response is extremely important. This study aimed to example serum levels of multiple cytokines in AR and explore their association with the efficacy of AIT. METHODS: A total of 74 AR patients treated with sublingual immunotherapy (SLIT) were prospectively recruited. Serum samples were obtained before the onset of SLIT and cytokine levels detected by multiplex analysis. All patients were followed for >1 year, and associations between cytokine levels and the early efficacy of SLIT were evaluated. Significantly distinctive cytokines were further verified in another independent cohort. RESULTS: Sixty patients completed the visit schedule set: 35 patients were put into a responder group and 25 a nonresponder group. Multiple-cytokine profiling showed that cytokine levels differed significantly between the two groups. The responder group had higher concentrations of BAFF and CCL11 and lower levels of CCL2, CCL7, IFNγ, IL8, IL10, IL16, and IL33 than the nonresponder group (P<0.05). Receiver-operating characteristic curves highlighted that serum BAFF, IFNγ, IL10, and IL33 levels were strongly predictive of the efficacy of SLIT (area under the curve <0.7, P<0.05). Serum IL10 and IL33 were overexpressed in nonresponders in the validation cohort. Patients in the responder group exhibited significantly higher IL10 levels and lower IL33 post-SLIT than pre-SLIT (P<0.05), but no statistical difference was found in nonresponders (P<0.05). CONCLUSION: Our data indicated that serum multiple-cytokine profiling was associated with response to SLIT and that IL10 and IL33 might serve as novel biomarkers for early prediction of efficacy and be involved in the therapeutic mechanisms of SLIT in AR patients.

7.
J Plant Physiol ; 270: 153635, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35124291

RESUMO

NAC transcription factors have multiple biological functions in plants. In this study, a new NAC transcription factor, LpNAC6, was cloned from Lilium pumilum, and its salt and drought resistance functions were identified. We treated LpNAC6 transgenic tobacco plants with different intensities of alkali and drought stress. Results showed that LpNAC6 transgenic tobacco had enhanced alkali tolerance, but decreased drought tolerance. Antioxidant enzyme (SOD, POD, CAT) activity, chlorophyll content, proline content, and photosynthetic capacity of transgenic tobacco were significantly higher than those of wild-type tobacco, while the contents of MDA, H2O2, and O2- were significantly lower than those of wild-type tobacco. The expression level of stress-related genes in transgenic tobacco increased significantly, and the alkali tolerance was enhanced, but the opposite was true under drought stress. Our findings suggest that LpNAC6 has a reverse regulatory effect on alkaline and drought tolerance in plants, which is of great significance for plant screening and stress tolerance regulation of transgenic plants in arid saline-alkali land.

8.
PLoS One ; 17(2): e0263389, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35113961

RESUMO

OBJECTIVE: Fermented sausage is popular all over the world for its rich nutrition and unique flavor. Sausage casing is one of the key factors affecting the quality of fermented sausage. However, there is little information involved in this field. METHODS: In this study, collagen casings were used as a wrapping material, and natural casings (pig casings) were used as a control. The effects of the two types of casings on biogenic amine content and other quality characteristics of fermented sausage were analyzed with increasing the storage time. RESULTS: The results showed that with storage time increasing, the hardness and gumminess of fermented sausage in collagen casing (CC) group were higher than those in pig casing (PC) group (P<0.05), while the elasticity in CC group was lower than that in PC group (P<0.05). In the processing and storage period, there was no significant difference in the type and content of flavor substances between the two groups. More importantly, the contents of tryptamine, putrescine, cadaverine, histamine, tyramine and phenyethylamine in fermented sausage of CC group were lower than those in PC group (P<0.05). CONCLUSION: In conclusion, this study revealed that CC could improve the quality characteristics of fermented sausage and reduce the content of biogenic amines in fermented sausage, which provides a theoretical basis for the choice of casings in industrial production in the future.


Assuntos
Colágeno/química , Análise de Alimentos/métodos , Manipulação de Alimentos/métodos , Produtos da Carne/análise , Aminas , Animais , Aminas Biogênicas/análise , Reatores Biológicos , Cadaverina/análise , Fermentação , Histamina/análise , Concentração de Íons de Hidrogênio , Fenetilaminas/análise , Putrescina/análise , Ovinos , Triptaminas/análise , Tiramina/análise
9.
Mater Sci Eng C Mater Biol Appl ; : 112651, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35034817

RESUMO

Porous titanium implants were popularly fabricated to promote bone formation. A desirable porous scaffold was recommended to be with porosity of >60% or/and pore size of >300 µm for better osteointegration. However, whether the pore size and porosity could be randomly selected within the recommended values? And what is the correlation between pore size and porosity for accelerating osteointegration? In this study, porous titanium with cubic cell structure was produced by selective laser melting. The designed porosities of scaffolds with 700-µm pore size were 40%, 70% and 90%; and the pore sizes of scaffolds with 70% porosity were 400, 700 and 900 µm. The in vitro osteogenic potential and in vivo bone formation were investigated. Results showed that porosity and pore size could be tuned by altering strut size, which was further directly responsible for mechanical properties. Besides, pore size and porosity synergistically contributed to osteogenic activity in vitro and new bone formation in vivo. In regard to pore sizes herein, the optimized one for better osteogenic response and bone forming ability was ~600-700 µm (p70). Too smaller or too larger pore size might more or less hinder cellular behaviors and bone regeneration, even if both pore size (300-900 µm) and porosity (70%) were within the recommended value range. At a constant pore size (~600-700 µm), p70 and p90 with higher porosity was more conductive to biological effects, compared with p40. As a result, pore-size variation revealed more significant influence on osteogenesis, compared with variation of porosity within recommended values. However, the applicable porosity within recommended values should be designed with the consideration of specific load-bearing conditions. This study helps to provide guidance for designing porous scaffolds with appropriate mechanical strengths and effective bone-forming ability, so as to develop better custom-made bone substitutes.

10.
Chem Commun (Camb) ; 58(11): 1804-1807, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35040445

RESUMO

We present the finding of a dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization. It has a binding affinity of 16 nM for the SARS-CoV-2 spike RBD, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC50 of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC50 of 2.4 µM. Our study should provide a new insight for the optimization of peptide-based anti-SARS-CoV-2 inhibitors.


Assuntos
Antivirais/farmacologia , Fragmentos de Peptídeos/farmacologia , Peptidomiméticos/farmacologia , SARS-CoV-2/efeitos dos fármacos , Sequência de Aminoácidos , Enzima de Conversão de Angiotensina 2/química , Antivirais/síntese química , Antivirais/metabolismo , Linhagem Celular Tumoral , Humanos , Testes de Sensibilidade Microbiana , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/metabolismo , Peptidomiméticos/síntese química , Peptidomiméticos/metabolismo , Ligação Proteica , Domínios Proteicos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo
11.
Res Vet Sci ; 144: 34-43, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35038674

RESUMO

Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus, causes lethal watery diarrhea to the piglets, which poses significant economic losses and public health concerns. The nsp10 protein of PEDV is essential regulatory subunits that are critical for virus replication. Since PEDV nsp10 is a crucial regulator of viral RNA synthesis, it is promising that nsp10 might become anti-virus drugs target or candidate for rapid diagnosis of PEDV infection. In this study, the PEDV nsp10 was inserted into pMAL-c2x-MBP / pET-28a vector, efficiently and stably expressed in E.coli system. Then the purified nsp10 protein was found to mediate potent antibody responses in immunized mice. The antibodies of immunized mice and PEDV infection swine strongly recognized purified nsp10 protein from cell lysates. Furthermore, cytokines test revealed that the expression of IL-2, IL-4, IL-10, TNF-α, IFN-γ were significantly higher than those in control group, indicated that purified nsp10 protein induce the cellular immune response mechanism in mice. Using modified seroneutralization test, we also demonstrated that sera from nsp10-immunized mice inhibited PEDV replication to some extent. These findings suggest that nsp10 has a high immunogenicity. This study may have implications for future development of PEDV detection or anti-virus drugs for swine.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Roedores , Doenças dos Suínos , Animais , Anticorpos Antivirais , Infecções por Coronavirus/veterinária , Camundongos , RNA Viral , Suínos , Replicação Viral
12.
Anim Biosci ; 35(4): 614-623, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34991228

RESUMO

OBJECTIVE: The objective of this study was to investigate the effects of sheep slaughter age on myogenic characteristics in skeletal muscle satellite cells (SMSCs). METHODS: Primary SMSCs were isolated from hind leg biceps femoris muscles of Wurank lambs (slaughtered at three months, Mth-3) and adults (slaughtered at fifteen months, Mth-15). SMSCs were selected by morphological observation and fluorescence staining. Myogenic regulatory factors (MRF) and myosin heavy chain (MyHC) expressions of SMSCs were analyzed on days 1, 3, 4, and 5. RESULTS: The expressions of myogenic factor 5 (Myf5), myogenic differentiation (MyoD), Myf6, and myogenin (MyoG) in Mth-15 were significantly higher in Mth-15 than in Mth-3 on days 1, 3, and 4 (p<0.05). However, MyoG expression in Mth-15 was significantly lower than in Mth-3 on day 5 (p<0.05). The expressions of MyHC I, MyHC IIa, and MyHC IIx in Mth-15 were significantly higher than in Mth-3 on days 1 and 3 (p<0.05), and MyHC IIb were significantly lower than in Mth-3 on days 3 and 4 (p<0.05). In contrast, the expression of MyHC IIx in Mth-15 was significantly lower and MyHC IIb was significantly higher than in Mth-3 on days 5 (p<0.05). CONCLUSION: The slaughter age altered the expression of MRFs and MyHCs in SMSCs while differentiation, which caused the variation of myogenic characteristics, and thus may affect the meat quality of Wurank sheep.

13.
Microb Pathog ; 162: 105195, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34571150

RESUMO

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is an enveloped positive-sense ssRNA virus which is highly lethal to piglets, causing enormous economic losses to swine industry worldwide. Nsp15 protein is an endoribonuclease of PEDV and plays an indispensable role in the viral proliferation. We reported the transcription files of nsp15 transfected IPEC-J2 cells for the first time to broaden our understanding of PEDV pathogenesis. METHODS: RNA-seq was performed to compare gene expression profiles between pCAGGS-HA-nsp15 transfected IPEC-J2 cells and pCAGGS-HA (empty vector) transfected IPEC-J2 cells. Immune-related genes and pathways were identified and analyzed to deepen our understanding of nsp15 for PEDV pathogenicity. IPEC-J2 cells transfected with pCAGGS-HA-CCL5/CXCL8/CXCL10 were infected with CV777 and the virus load of PEDV was detected by qRT-PCR. RESULTS: A total of 21,654 genes were obtained by RNA-Seq and 415 differential expressed genes (DEGs) were identified, including 136 up-regulated and 279 down-regulated genes. A number of effect genes involved in immune responses and inflammation were differentially expressed. GO and KEGG enrichment analysis showed that 32 GO terms were significantly enriched and the DEGs were mainly enriched in immune-related pathways such as TNF signaling pathway, RIG-I-like receptor signaling pathway and Cytosolic DNA-sensing pathway. qRT-PCR results indicated the overexpression of selected chemokines, CCL5/CXCL8/CXCL10, can inhibit PEDV proliferation in IPEC-J2 cells. CONCLUSIONS: Our transcriptome profile illustrated a number of genes involving in immune responses and inflammation were inhibited by nsp15, such as CCL5, CXCL8, CXCL10, OAS, MXs, STAT1 and IRF9. The results suggested that nsp15 can antagonize IFNs and block chemokine system to provide an adequate intracellular environment for viral proliferation.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Animais , Linhagem Celular , Infecções por Coronavirus/genética , Infecções por Coronavirus/veterinária , Células Epiteliais , Perfilação da Expressão Gênica , Imunidade , Vírus da Diarreia Epidêmica Suína/genética , Suínos
15.
Org Lett ; 24(1): 53-57, 2022 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-34894695

RESUMO

We report a new pattern of a bicyclic helical peptide constructed through head-to-tail cross-linking. The described bicyclic helical peptide has a head-to-tail cross-linking arm and a C-terminal i, i + 4 cross-linking arm. This scaffold will provide a promising scaffold for designing a proteolytically resistant helix-constrained peptide.


Assuntos
Peptídeos
16.
Toxicology ; 466: 153066, 2022 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-34919984

RESUMO

In order to overcome the weakness of conventional approaches for cell culture, and provide cells with more in vivo-like microenvironment for studying hepatotoxicity of drugs, "multiple-in-one" strategy was adopted to fabricate a 3D scaffold of silk fibroin/hydroxyapatite/poly lacticco-glycolic acid (SF/HA/PLGA), where HepG2 cells were cultivated and the toxicity of drugs to the cells was investigated. The prepared 3D scaffold proves to bear proper porosity, excellent mechanical property, steady pH environment and good biocompatibility for cell culture. Furthermore, the validity of the developed 3D-SF/HA/PLGA-scaffold based platform was verified by probing the toxicity of a known drug-induced liver injury (DILI) concern acetaminophen (APAP) to HepG2 cells. Eventually, an application of the platform to dioscin (a medicinal plant extract) reveals the hepatotoxicity of dioscin, which involves the inhibition of the expression of CYP3A4 mRNA in the cells. The developed 3D-SF/HA/PLGA-scaffold platform may become a universal avenue for safety evaluation of drugs.


Assuntos
Acetaminofen/toxicidade , Técnicas de Cultura de Células/métodos , Resinas Compostas/química , Avaliação Pré-Clínica de Medicamentos/métodos , Tecidos Suporte/química , Diferenciação Celular , Proliferação de Células , Doença Hepática Induzida por Substâncias e Drogas , Sistema Enzimático do Citocromo P-450/metabolismo , Diosgenina/análogos & derivados , Diosgenina/toxicidade , Glucose/metabolismo , Células Hep G2 , Humanos , Preparações Farmacêuticas
17.
J Colloid Interface Sci ; 607(Pt 2): 1239-1252, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34583031

RESUMO

Tissue adhesives have received much attention for their effectiveness in sealing wounds or incisions in clinical surgery, especially in minimally invasive surgery. To meet the safe and smart wound management requirements, ideal tissue adhesives are expected to have high biocompatibility, and be able to accelerate wound closing and healing, and monitor wound healing process. However, few adhesives fit all of the above descriptions. It has been demonstrated that inorganic nanoparticles can directly glue biological tissue based on nano-bridging effect. In this study, self-luminescence porous silicon (LPSi) particles were prepared with degradable and biocompatible properties. In addition, the self-luminescence property of LPSi particles was discovered by In Vivo Imaging System (IVIS) for the first time, which can avoid the limitations of photoluminescence imaging. Due to the oxidation and degradation reaction, LPSi particles not only can be degraded completely in several days, but also showed satisfactory biocompatibility. And their degradation product could promote tube formation of HUVECs. Moreover, owing to the high specific surface area and the outer oxide layer of LPSi particles, LPSi tissue adhesive exhibited strong adhesive strength to pig livers. Furthermore, this adhesive closed wound rapidly, promoted angiogenesis and epidermal regeneration, and facilitated wound healing in a mouse skin incision model. Importantly, the wound healing ratio can be monitored by measuring the self-luminescence intensity of LPSi particles in the wound site. This study reveals that LPSi particles could be employed as a safe and smart wound management tissue adhesive for wound closure, as well as accelerating and monitoring wound healing.


Assuntos
Adesivos Teciduais , Animais , Luminescência , Camundongos , Porosidade , Silício , Suínos , Cicatrização
18.
Int J Biol Macromol ; 193(Pt B): 2021-2028, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34767883

RESUMO

Mg alloys are increasingly being investigated as a versatile and economical alternative for developing bone repair implants because of their high mechanical strength, wide availability, adjustable structure and properties. In this study, magnesium alloy WE43 is coated on both sides with gelatin nanosphere/chitosan (GNs/CTS), a coating enhanced by incorporating simvastatin (SIM). SIM-loaded GNs/CTS coated magnesium alloy can promote the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). BMSCs and human umbilical vein endothelial cells (HUVECs) are co-cultured through transwell systems. The release of SIM from the coating is found to increase the secretion of chemokine and angiogenic factors from BMSCs, which promote the migration and tube formation of HUVECs, respectively. Bone morphogenetic protein secreted by HUVECs is seen to increase by the release of SIM from the coating, promoting the osteogenic differentiation of BMSCs. The secretion of chemokines from HUVECs promote the migration of BMSCs. The coated magnesium alloy substrate loaded with SIM is found to regulate the osteogenic differentiation of BMSCs. The study of the paracrine interaction between BMSCs and HUVECs proves that the applied coating promotes both osteogenic differentiation and vascularization, thus demonstrating a new approach for the design of bone repair materials based on magnesium alloys.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Quitosana/farmacologia , Gelatina/farmacologia , Magnésio/química , Nanosferas/química , Osteogênese/efeitos dos fármacos , Sinvastatina/farmacologia , Ligas/farmacologia , Indutores da Angiogênese/farmacologia , Osso e Ossos/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura/métodos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos
19.
Oncol Lett ; 22(6): 839, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34712363

RESUMO

Non-small cell lung cancer (NSCLC) is the most common cause of cancer-associated mortality worldwide. Our previous study revealed that circular RNA (circRNA)-FOXO3 is highly expressed in lung cancer and inhibits cell proliferation. However, to the best of our knowledge, at present, no study has focused on the specific mechanism of circRNA-FOXO3 in drug resistance. Therefore, the present study aimed to provide novel perspectives on the role of circRNA-FOXO3 in cisplatin (DDP) resistance in NSCLC. A Cell Counting Kit-8 assay was used to determine the viability of cells overexpressed with circRNA-FOXO3 and under DDP treatment. Glycolysis was analyzed by measuring glucose consumption and lactate production. The interaction of circRNA-FOXO3, microRNA 543 (miR-543) and Foxo3 was confirmed using a dual-luciferase reporter assay. It was revealed that circRNA-FOXO3 improved cell sensitivity to DDP and repressed glycolysis in DDP-sensitive and DDP-resistant NSCLC cells. Bioinformatics analysis, luciferase reporter assays, quantitative PCR and RNA pull-down assays were employed to verify the binding of circRNA-FOXO3 to miR-543. Functionally, inhibition of miR-543 could sensitize NSCLC cells to DDP, and overexpression of miR-543 at least partially abolished the circRNA-FOXO3-induced decrease in chemoresistance. Furthermore, it was revealed that Foxo3 was a direct target of miR-543. Notably, the inhibitory action of miR-543 silencing on DDP resistance and glycolysis was reversed by overexpression of Foxo3 in DDP-sensitive and DDP-resistant NSCLC cells. In conclusion, the present study demonstrated that circRNA-FOXO3 promoted DDP sensitivity in NSCLC cells by regulating the miR-543/Foxo3 axis-mediated glycolysis balance. The present findings may provide novel perspectives for the treatment of patients with NSCLC resistant to DDP.

20.
mBio ; 12(5): e0229821, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34579580

RESUMO

Polyketides are one of the largest categories of secondary metabolites, and their biosynthesis is initiated by polyketide synthases (PKSs) using coenzyme A esters of short fatty acids (acyl-CoAs) as starter and extender units. In this study, we discover a universal regulatory mechanism in which the starter and extender units, beyond direct precursors of polyketides, function as ligands to coordinate the biosynthesis of antibiotics in actinomycetes. A novel acyl-CoA responsive TetR-like regulator (AcrT) is identified in an erythromycin-producing strain of Saccharopolyspora erythraea. AcrT shows the highest binding affinity to the promoter of the PKS-encoding gene eryAI in the DNA affinity capture assay (DACA) and directly represses the biosynthesis of erythromycin. Propionyl-CoA (P-CoA) and methylmalonyl-CoA (MM-CoA) as the starter and extender units for erythromycin biosynthesis can serve as the ligands to release AcrT from PeryAI, resulting in an improved erythromycin yield. Intriguingly, anabolic pathways of the two acyl-CoAs are also suppressed by AcrT through inhibition of the transcription of acetyl-CoA (A-CoA) and P-CoA carboxylase genes and stimulation of the transcription of citrate synthase genes, which is beneficial to bacterial growth. As P-CoA and MM-CoA accumulate, they act as ligands in turn to release AcrT from those targets, resulting in a redistribution of more A-CoA to P-CoA and MM-CoA against citrate. Furthermore, based on analyses of AcrT homologs in Streptomyces avermitilis and Streptomyces coelicolor, it is believed that polyketide starter and extender units have a prevalent, crucial role as ligands in modulating antibiotic biosynthesis in actinomycetes. IMPORTANCE Numerous antibiotics are derived from polyketides, whose biosynthesis is accurately controlled by transcriptional regulators that respond to diverse physiological or environmental signals. It is generally accepted that antibiotics or biosynthetic intermediates serve as effectors to modulate their production in actinomycetes. Our study unprecedentedly demonstrates that the direct precursors of polyketide, propionyl-CoA and methylmalonyl-CoA, play a role as ligands to modulate erythromycin biosynthesis in Saccharopolyspora erythraea. More importantly, the two acyl-CoAs as ligands could adjust their own supplies by regulating the acetyl-CoA metabolic pathway so as to well settle the relationship between cellular growth and secondary metabolism. Significantly, polyketide starter and extender units have a universal role as ligands to coordinate antibiotic biosynthesis in actinomycetes. These findings not only expand the understanding of ligand-mediated regulation for antibiotic biosynthesis but also provide new insights into the physiological functions of polyketide starter and extender units in actinomycetes.


Assuntos
Antibacterianos/biossíntese , Eritromicina/biossíntese , Saccharopolyspora/metabolismo , Acil Coenzima A/genética , Acil Coenzima A/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Vias Biossintéticas , Ligantes , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Regiões Promotoras Genéticas , Saccharopolyspora/enzimologia , Saccharopolyspora/genética
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