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1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554098

RESUMO

Biofilms are communities of microorganisms that play a significant role as virulence factors in disease transmission. The ability to attach to surfaces is an important feature which facilitates both host colonization and survival in the environment. To attach to a wide array of biotic and abiotic surfaces, biofilm-dwelling bacterial cells need to produce specific adhesion molecules. The causative agent of pandemic cholerae, Vibrio cholerae, forms biofilms dependent on Vibrio polysaccharide (VPS), the primary component of the biofilm matrix, which makes a significant contribution to the structural integrity of the biofilm. In addition to VPS, the biofilm matrix contains proteins and nucleic acids; together these components play an important role in maintaining the integrity of the biofilm. The three main proteins of the biofilm matrix are RbmA, RbmC and Bap1. In this study we focus on RbmC and Bap1, which are considered adhesion proteins with overlapping but distinct functions. Both proteins share sequence identity and core structural features: a ß-propeller domain, and a ß-prism domain. RbmC contains two functional ß-prism domains which bind with high affinity to the core of complex N-glycans, while Bap1 has only one domain which appears to have lost the ability to bind glycans. Our study finds that the two adhesins differ in the adhesive properties of the ß-prism domains that interface with the external environment. The current study combines insights from prior crystallographic work with functional assays in V. cholerae biofilms to demonstrate the modular nature of Bap1 and RbmC and how V. cholerae utilizes these two biofilm-specific adhesins to achieve robust adhesion to various types of surfaces. We also propose a model for how V. cholerae biofilms recognize host surfaces specifically during infection while retaining adhesion to abiotic surfaces. This emphasizes the critical need to develop new biofilm elimination strategies, both from abiotic surfaces and post-infection as an alternative to antibiotics due to the development of antibiotic resistance.

2.
Front Mol Neurosci ; 15: 877263, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571375

RESUMO

It has been widely demonstrated by numerous preclinical studies and clinical trials that the neonates receiving repeated or long-time general anesthesia (GA) could develop prolonged cognitive dysfunction. However, the definite mechanism remains largely unknown. Epigenetics, which is defined as heritable alterations in gene expression that are not a result of alteration of DNA sequence, includes DNA methylation, histone post-translational modifications, non-coding RNAs (ncRNAs), and RNA methylation. In recent years, the role of epigenetic modifications in neonatal GA-induced neurotoxicity has been widely explored and reported. In this review, we discuss and conclude the epigenetic mechanisms involving in the process of neonatal anesthesia-induced cognitive dysfunction. Also, we analyze the wide prospects of epigenetics in this field and its possibility to work as treatment target.

3.
Comput Math Methods Med ; 2022: 7982023, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572824

RESUMO

Objective: To explore the effect of Yiqi Huayu Pinggan Zishen recipe combined with valsartan in the treatment of hypertension and its effect on MMP-9, Ang II, and MCP-1. Methods: About 100 patients with hypertension treated in our hospital from March 2020 to April 2021 were enrolled. All patients were arbitrarily assigned to the control group and the study group. The former group was cured with valsartan, and the latter group was cured with Yiqi Huayu Pinggan Zishen recipe combined with valsartan. The curative effect, blood pressure level, renal function index, serum matrix metalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), angiotensin II (Ang II) level, traditional Chinese medicine (TCM) syndrome score, and the incidence of adverse reactions were compared. Results: First of all, we compared the curative effects; the study group exhibited remarkably effective in 44 cases and effective in 6 cases, and the effective rate was 100.00%, while in the control group, 24 cases were markedly effective, 16 cases were effective, and 5 cases were ineffective; the effective rate was 90.00%. The curative effect in the study group was higher (P < 0.05). Secondly, we compared the blood pressure level. Before treatment, there was no remarkable difference (P > 0.05). After treatment, the blood pressure of the two groups decreased. The systolic blood pressure and diastolic blood pressure of the study group were lower (P < 0.05). In terms of renal function indexes, the levels of blood urine nitrogen (BUN), Cr, and ß 2-MG in the study group were lower, while the level of eGFR in the study group was higher (P < 0.05). The serum levels of MMP-9, MCP-1, and Ang II decreased. Of note, the levels of serum MMP-9, MCP-1, and Ang II in the study group were lower (P < 0.05). After treatment, the TCM syndrome scores decreased, and the study group was lower (P < 0.05). Finally, we compared the incidence of adverse reactions. The incidence of adverse reactions in the study group was lower (P < 0.05). Conclusion: Yiqi Huayu Pinggan Zishen recipe combined with valsartan in the treatment of hypertension can remarkably reduce the clinical symptoms, enhance the renal function, strengthen the therapeutic effect, promote the ability of independent movement, and reduce the levels of serum MMP-9, MCP-1, and Ang II with high safety, which has the value of clinical application.

5.
Acta Clin Belg ; : 1-9, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35587164

RESUMO

BACKGROUND: We carried out a systematic review and meta-analysis to assess the safety and effectiveness of hepatic arterial infusion chemotherapy (HAIC) compared with transarterial chemoembolization (TACE) for patients with unresectable hepatocellular carcinoma (uHCC). METHODS: Eligible studies were searched by MEDLINE, the Cochrane Library, Embase, and Web of Science from January 1995 to January 2022, investigating eligible literature comparing HAIC and TACE for patients with HCC. The main outcome measures included progression-free survival (PFS), overall survival (OS), adverse events (AEs), objective response rate (ORR), and diseases control rate (DCR). RESULTS: Eight literature and 1028 patients were enrolled in this meta-analysis. The pooled PFS, OS, ORR, and DCR were HR = 0.89 (95% CI, 0.81-0.98), HR = 0.84 (95% CI, 0.75-0.93), OR = 2.77 (95% CI, 2.01-3.80), and OR = 4.64 (95% CI, 2.40-8.99), respectively. The adverse events of HAIC were lower than TACE. CONCLUSION: Our meta-analysis revealed that HAIC can achieve a better effect and survival benefits than TACE in patients with uHCC.

6.
Zhongguo Zhen Jiu ; 42(5): 525-32, 2022 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-35543943

RESUMO

OBJECTIVE: To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism. METHODS: A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR. RESULTS: Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05). CONCLUSION: Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.


Assuntos
Hipotireoidismo , Moxibustão , Pontos de Acupuntura , Animais , Depressão/genética , Depressão/terapia , Hipocampo/metabolismo , Hidrocortisona/metabolismo , Hipotireoidismo/complicações , Hipotireoidismo/metabolismo , Hipotireoidismo/terapia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Glucocorticoides/metabolismo , Receptores de Mineralocorticoides/metabolismo , Serotonina , Tireotropina/metabolismo , Triticum/metabolismo
7.
Food Chem X ; 14: 100329, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35601211

RESUMO

This study investigated the combined effects of calcium lactate (CA-L, 3 g L-1) and shortwave ultraviolet (UV-C, 4.0 kJ m-2) irradiation on quality attributes and antioxidant defense capacity of fresh-cut kiwifruits at refrigerated storage for 7 d. The results indicated that CA-L and UV-C joint treatment, compared to either treatment alone, alleviated microbial load, showed higher quality on ascorbic acid (AsA), green color, total chlorophyll, flesh hardness, total sugar, total acid and malonaldehyde (MDA) content. Besides, it inhibited O 2 · - and •OH generation, induced H2O2 production, improved the activity of antioxidant enzymes (SOD, CAT and APX), activated critical enzymes (PAL, C4H and 4CL) in phenylpropanoid metabolism pathway and further enhanced total phenolic and proanthocyanidin content. Above results demonstrated that UV-C together with CA-L treatment could synergistically maintain overall quality and improve antioxidant capacity of kiwifruit slices. Therefore, the combination of CA-L and UV-C treatment showed a potential practical application in fresh-cut kiwifruits.

8.
Anal Chem ; 94(20): 7425-7432, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35543487

RESUMO

In vivo, endothelial cells are permanently subjected to dynamic cyclic stretch and adapt to it through the release of vasoactive substances. Among them, reactive oxygen species (ROS) and nitric oxide (NO) are indispensable redox molecules, the contents of which and their ratio are closely implicated with endothelial redox homeostasis. However, simultaneous and quantitative monitoring of ROS and NO release in endothelial mechanotransduction remains a great challenge. Herein, a stretchable electrochemical device is developed with a dual electrode based on gold nanotubes decorated with uniform and tiny platinum nanoparticles. This hybrid nanostructure endows the sensor with high sensitivity toward both hydrogen peroxide (H2O2) (as the most stable ROS) and NO electrooxidation. Importantly, the two species can be well discriminated by applying different potentials, which allows simultaneous monitoring of H2O2 and NO release in stretch-induced endothelial mechanotransduction by the same device. The results of quantitative analysis suggest that endothelial redox homeostasis and its alteration are strongly related to vascular biomechanical and biochemical milieus. Further investigation reveals that the interplay of ROS and NO signaling has an important role in the regulation of endothelial redox state. This work will greatly facilitate the deep understanding of the molecular mechanism of endothelial dysfunction and vascular disorder.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35518345

RESUMO

Gandan oral liquid (GOL) is a mixture of crude extracts from licorice and Radix isatidis. Clinically, it has been widely used in the treatment of exudative pneumonia (EP) in animals. But the molecular mechanism of these effects is unclear. Therefore, antibacterial activity and therapeutic effect were tested in vitro and in vivo. Exudative pneumonia was established with the intraperitoneal injection of LPS, followed by continuous intranasal inoculation of Klebsiella pneumoniae (KP). After that, Gandan oral liquid, acetylcysteine, and levofloxacin were given through the intragastric route for five days, and clinical symptoms were observed and counted. The bacterial content of alveolar lavage fluid was determined, hematology analysis was performed, and lung histology examination was performed. Western blotting, immunohistochemistry, and immunofluorescence were used to detect the expression levels of AQP3, AQP5, and MUC5AC in lung tissues. ELISA kit was used to detect serum and BALF cytokines levels. The results showed that GOL (242 mg/mL) had no antibacterial activity on Klebsiella pneumonia (KP), and the effect was significantly worse than levofloxacin. However, the therapeutic test in vivo of the rat model of bacterial EP showed different results. After treatment, GOL administration ameliorated EP and increased the expression of mucoprotein -5AC (MUC5AC), and GOL promoted water secretion of the respiratory tract by increasing the expression of aquaporin-5 (AQP5) and decreasing the levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1ß). Conclusion. GOL accelerates the water secretion of respiratory tract, inhibits the inflammatory response, induces removal of bacteria of respiratory tract via the AQPs/MUC pathway, and ultimately ameliorates EP.

10.
J Transl Med ; 20(1): 193, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35509104

RESUMO

PURPOSE: We develop a new risk score to predict patients with stroke-associated pneumonia (SAP) who have an acute intracranial hemorrhage (ICH). METHOD: We applied logistic regression to develop a new risk score called ICH-LR2S2. It was derived from examining a dataset of 70,540 ICH patients between 2015 and 2018 from the Chinese Stroke Center Alliance (CSCA). During the training of ICH-LR2S2, patients were randomly divided into two groups - 80% for the training set and 20% for model validation. A prospective test set was developed using 12,523 patients recruited in 2019. To further verify its effectiveness, we tested ICH-LR2S2 on an external dataset of 24,860 patients from the China National Stroke Registration Management System II (CNSR II). The performance of ICH-LR2S2 was measured by the area under the receiver operating characteristic curve (AUROC). RESULTS: The incidence of SAP in the dataset was 25.52%. A 24-point ICH-LR2S2 was developed from independent predictors, including age, modified Rankin Scale, fasting blood glucose, National Institutes of Health Stroke Scale admission score, Glasgow Coma Scale score, C-reactive protein, dysphagia, Chronic Obstructive Pulmonary Disease, and current smoking. The results showed that ICH-LR2S2 achieved an AUC = 0.749 [95% CI 0.739-0.759], which outperforms the best baseline ICH-APS (AUC = 0.704) [95% CI 0.694-0.714]. Compared with the previous ICH risk scores, ICH-LR2S2 incorporates fasting blood glucose and C-reactive protein, improving its discriminative ability. Machine learning methods such as XGboost (AUC = 0.772) [95% CI 0.762-0.782] can further improve our prediction performance. It also performed well when further validated by the external independent cohort of patients (n = 24,860), ICH-LR2S2 AUC = 0.784 [95% CI 0.774-0.794]. CONCLUSION: ICH-LR2S2 accurately distinguishes SAP patients based on easily available clinical features. It can help identify high-risk patients in the early stages of diseases.


Assuntos
Pneumonia , Acidente Vascular Cerebral , Glicemia , Proteína C-Reativa , Hemorragia Cerebral/complicações , Humanos , Hemorragias Intracranianas/complicações , Pneumonia/complicações , Prognóstico , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações
11.
Eur J Med Chem ; 236: 114313, 2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35390712

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive, high recurrence and metastatic breast cancer subtype. There are few safe and effective therapeutic drugs for treatment of TNBC. The marine natural product MHO7 has been determined to be a potential antitumor agent. However, its moderate activity and complex structure hampered its clinical application. In this study, a series of novel derivatives with modification on C24 of MHO7 were first synthesized. Some of the analogues were significantly more potent than MHO7 against all selected breast cancer cell lines. Among them, compound 4m had the best activity, and its IC50 value against TNBC was up to 0.51 µM. A whole-genome transcriptomic analysis shown that the mechanism of compound 4m against TNBC cells was similar with that of parent compound MHO7. Subsequent cellular mechanism studies showed that compound 4m could induce apoptosis of MDA-MB-231 cells through mitochondria pathway and cause G1 phase arrest. Moreover, 4m could disrupt the expressions of MAPK/Akt pathway-associated proteins (p-p38 and p-Akt) and remarkably increase the ratio of Bax to Bcl-2 and activate cleaved caspase 3/9/PARP. Importantly, 4m could influence the expression of Smad 7, and p-Smad 3 to inhibit TNBC cells metastasis. Stability assays in rat plasma and liver microsomes indicated that 4m still have room for further optimization. And the results of the online molinspiration software predicted that 4m has desirable physicochemical properties but some properties still have violation from the Lipinski rule of five. Overall, the modification on C24 of MHO7 was a promising way for developing novel anti-TNBC agents with considerable potential for optimization.

12.
Front Endocrinol (Lausanne) ; 13: 862545, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399943

RESUMO

Aims/Introduction: Renal function impairment related to type 2 diabetes (T2DM) presents serious threat to public health. Previous studies suggest that vascular endothelial growth factor-B (VEGF-B) might contribute to renal injury. Therefore, this study investigated the association of serum VEGF-B level with the risk of renal function impairment in T2DM patients. Materials and Methods: Serum VEGF-B levels were measured in 213 patients with type 2 diabetes and 31 healthy participants. Participants with type 2 diabetes were further divided into a group of 112 participants with eGFR<90 mL/min/1.73m2 and 101 participants with eGFR≥ 90 mL/min/1.73m2. Clinical data were collected, and a binary logistic regression model was employed to test the association between potential predictors and eGFR. Results: Serum VEGF-B levels evaluated in type 2 diabetes patients compared with healthy controls. In patients with type 2 diabetes, serum VEGF-B level was positively correlated with triglyceride, serum creatinine and cystatin C while negatively correlated with HDL-C and eGFR. Binary logistic regression showed that serum VEGF-B level was an independent risk factor of eGFR<90 mL/min/1.73m2. Conclusions: Serum VEGF-B level is associated with renal function impairment in patients with type 2 diabetes and may be a potential drug target for diabetic kidney disease.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Renal , Fator B de Crescimento do Endotélio Vascular , Nefropatias Diabéticas/etiologia , Taxa de Filtração Glomerular , Humanos , Rim/fisiologia , Fator B de Crescimento do Endotélio Vascular/sangue
13.
J Integr Plant Biol ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35442564

RESUMO

Here, through single-molecule real-time (SMRT) sequencing, we present a high-quality genome sequence of the Japanese larch (Larix kaempferi), a conifer species with great value for wood production and ecological afforestation. The assembled genome is 10.97 Gb in size, harboring 45,828 protein-coding genes. 66.8% of the genome consists of repeat sequences, of which LTR-RTs are dominant and make up 69.86%. We find that tandem duplications have been responsible for the expansion of genes involved in transcriptional regulation and stress responses, unveiling their crucial roles in adaptive evolution. Population transcriptome analysis reveals that lignin content in L. kaempferi is mainly determined by the process of monolignols polymerization. The expression values of six genes (LkCOMT7, LkCOMT8, LkLAC23, LkLAC102, LkPRX148 and LkPRX166) have significantly positive correlations with lignin content. These results indicated that the increased expression of these six genes might be responsible for the high lignin content of the larches' wood. Overall, this study provides new genome resources for investigating the evolution and biological function of conifer trees, and also offers new insights into wood properties of larches. This article is protected by copyright. All rights reserved.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35460152

RESUMO

AIMS: To introduce and compare the modified laparoscopic Vecchietti and Davydov techniques for vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Moreover, the long-term treatment of vaginal agenesis was followed-up. METHODS: This comparative retrospective cohort study enrolled a total of 53 women with MRKH syndrome. The patients underwent surgical creation of a neovagina including 32 patients who underwent the modified laparoscopic Vecchietti technique, and 21 patients who underwent the modified laparoscopic Davydov technique from January 2009 to February 2019. The perioperative parameters, complications, anatomical, and functional outcomes of the two groups were compared. Patients' sexual functions were evaluated over a long-term follow-up using the female sexual function index (FSFI) and the revised female sexual distress scale (FSDS-R). RESULTS: The medians (25th-75th) of the surgery duration for modified Vecchietti procedures was 50.0 (40.0-59.0) minutes, comparing to 135.0 (117.5-162.5) min for Davydov procedures (p < 0.001). The intraoperative blood loss was 20 (7.5-20.0) mL versus 50.0 (50.0-100.0) mL using the modified Vecchietti and Davydov approaches (p < 0.001), respectively. In the 39 follow-up cases, the lengths of the neovagina of the patients for Vecchietti group versus Davydov group were 7.9 ± 1.0 cm versus 8.6 ± 1.2 cm at 6 months after the vaginoplasty and 8.3 ± 0.7 cm versus 8.5 ± 0.9 cm after 2 years. There was no statistical difference in the FSFI and FSDS-R scores between the two groups. CONCLUSIONS: Both the modified Davydov and Vecchietti laparoscopic procedures successfully achieved optimal anatomic and functional outcomes in treatments of vaginal agenesis. The modified Vecchietti technique is relatively simpler than the modified Davydov technique.

15.
NPJ Regen Med ; 7(1): 26, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35474221

RESUMO

Tendon regeneration highly relies on biomechanical and biochemical cues in the repair microenvironment. Herein, we combined the decellularized bovine tendon sheet (DBTS) with extracellular matrix (ECM) from tendon-derived stem cells (TDSCs) to fabricate a biomechanically and biochemically functional scaffold (tECM-DBTS), to provide a functional and stem cell ECM-based microenvironment for tendon regeneration. Our prior study showed that DBTS was biomechanically suitable to tendon repair. In this study, the biological function of tECM-DBTS was examined in vitro, and the efficiency of the scaffold for Achilles tendon repair was evaluated using immunofluorescence staining, histological staining, stem cell tracking, biomechanical and functional analyses. It was found that tECM-DBTS increased the content of bioactive factors and had a better performance for the proliferation, migration and tenogenic differentiation of bone marrow-derived stem cells (BMSCs) than DBTS. Furthermore, our results demonstrated that tECM-DBTS promoted tendon regeneration and improved the biomechanical properties of regenerated Achilles tendons in rats by recruiting endogenous stem cells and participating in the functionalization of these stem cells. As a whole, the results of this study demonstrated that the tECM-DBTS can provide a bionic microenvironment for recruiting endogenous stem cells and facilitating in situ regeneration of tendons.

16.
Regen Biomater ; 9: rbac020, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480863

RESUMO

Developing highly bioactive scaffold materials to promote stem cell migration, proliferation and tissue-specific differentiation is a crucial requirement in current tissue engineering and regenerative medicine. Our previous work has demonstrated that the decellularized tendon slices (DTSs) are able to promote stem cell proliferation and tenogenic differentiation in vitro and show certain pro-regenerative capacity for rotator cuff tendon regeneration in vivo. In this study, we present a strategy to further improve the bioactivity of the DTSs for constructing a novel highly bioactive tendon-regenerative scaffold by surface modification of tendon-specific stem cell-derived extracellular matrix (tECM), which is expected to greatly enhance the capacity of scaffold material in regulating stem cell behavior, including migration, proliferation and tenogenic differentiation. We prove that the modification of tECM could change the highly aligned surface topographical cues of the DTSs, retain the surface stiffness of the DTSs and significantly increase the content of multiple ECM components in the tECM-DTSs. As a result, the tECM-DTSs dramatically enhance the migration, proliferation as well as tenogenic differentiation of rat bone marrow-derived stem cells compared with the DTSs. Collectively, this strategy would provide a new way for constructing ECM-based biomaterials with enhanced bioactivity for in situ tendon regeneration applications.

17.
Food Chem ; 389: 133083, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35487082

RESUMO

Barley grass polysaccharides (BGPs) are some of the major bioactive constituents of barley (Hordeum vulgare L.) grass (BG). They exhibit favorable biological activities and health benefits. In this study, seven BGPs were extracted from BG, which was harvested at three different growth stages (e.g., seedling, tillering, and stem elongation), by alkaline-extraction method. Their physicochemical properties, structural characteristics, and biological activities were investigated and compared. Results demonstrated that the extraction yields, chemical compositions, monosaccharide constituents, and molecular weights of the seven BGPs obtained at different growth stages varied obviously. These BGPs had similar preliminary structural characteristics but different microstructures and thermal properties. Furthermore, the BGPs (BGP-Z12 and BGP-Z21) obtained at the seedling stage possessed stronger in vitro antioxidant potentials, cholic acid binding activity, and immunological activity than other BGPs. Therefore, these results indicated that that the seedling stage of BG was the preferable harvest time for preparing highly bioactive BGPs.


Assuntos
Hordeum , Antioxidantes/farmacologia , Hordeum/química , Monossacarídeos , Polissacarídeos/química , Polissacarídeos/farmacologia , Plântula
18.
Adv Mater ; : e2109517, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388551

RESUMO

Systemic immunosuppression mediated by tumor-derived exosomes is an important cause for the resistance of immune checkpoint blockade (ICB) therapy. Herein, self-adaptive platelet (PLT) pharmacytes are engineered to mediate cascaded delivery of exosome-inhibiting siRNA and anti-PD-L1 (aPDL1) toward synergized antitumor immunity. In the pharmacytes, polycationic nanocomplexes (NCs) assembled from Rab27 siRNA (siRab) and a membrane-penetrating polypeptide are encapsulated inside the open canalicular system of PLTs, and cytotoxic T lymphocytes (CTLs)-responsive aPDL1 nanogels (NGs) are covalently backpacked on the PLT surface. Upon systemic administration, the pharmacytes enable prolonged blood circulation and active accumulation to tumors, wherein PLTs are activated to liberate siRab NCs, which efficiently transfect tumor cells, silence Rab27a, and inhibit exosome secretion. The immunosuppression is thus relieved, leading to the activation, proliferation, and tumoral infiltration of cytotoxic T cells, which trigger latent aPDL1 release. As such, the competitive aPDL1 exhaustion by PD-L1-expressing exosomes is minimized to sensitize ICB. Synergistically, siRab and aPDL1 induce strong antitumor immunological response and memory against syngeneic murine melanoma. This study reports a bioinspired mechanism to resolve the blood circulation/cell internalization contradiction of polycationic siRNA delivery systems, and renders an enlightened approach for the spatiotemporal enhancement of antitumor immunity.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35457322

RESUMO

The arctic region is a remote area with relatively few anthropogenic inputs, but there is increasing concern over toxic trace metal contamination in the Arctic Ocean. In this study, distribution characteristics of eight trace metals in the surface sediment of the Pacific Sector of the Arctic Ocean and Bering Strait are analyzed. The geochemical baseline value of each metal element is explored using the relative cumulative frequency curve method; the enrichment factor (EF), geo-accumulation index (Igeo) and potential ecological risk index (RI) are applied to assess the ecological risk level of the trace metals. According to the results, Cu, As and Hg had a little more content variation, and their contents in some areas were significantly higher than the previous reports. EF values show an obvious enrichment of element As, followed by Cr element with the moderate enrichment; the enrichment of the other six elements are not related to human activity. The Igeo value shows a moderately contaminated to heavily contaminated level of As and a moderately contaminated level of Cr. According to the potential ecological risk indexes in each site, most sites are at a low ecological risk level except five sites with RI/baseline values exceeding 150 which are at a moderate ecological risk level.


Assuntos
Metais Pesados , Oligoelementos , Poluentes Químicos da Água , China , Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Humanos , Metais Pesados/análise , Medição de Risco , Oligoelementos/análise , Poluentes Químicos da Água/análise
20.
Food Res Int ; 155: 111125, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35400410

RESUMO

Hyperlipidemia is associated with lipid metabolic disorders, chronic inflammation, and intestinal dysbiosis. Previous studies have shown that the metabolic improvement of high-fat diet (HFD)-induced mice by buckwheat is correlated with gut microbiota; however, the anti-hyperlipidemia effects and potential mechanism of probiotics-fermented rice buckwheat (FRB) are not well understood. Here, we aimed to investigate the lipid-lowering and gut microbiota regulation of FRB in HFD-induced hyperlipidemic mice. We observed that probiotic fermentation markedly increased the contents of γ-aminobutyric acid, rutin, total polyphenols, and total flavonoids in rice buckwheat. FRB supplementation over eight weeks significantly reduced body weight gain and visceral obesity, as well as alleviating dyslipidemia in HFD-fed mice. Moreover, FRB treatment effectively ameliorated oxidative stress and chronic inflammation. We further demonstrated that FRB intervention significantly inhibited hepatic cholesterol synthesis and lipogenesis, and promoted lipolysis. More important, FRB treatment reversed HFD-induced gut dysbiosis by decreasing the ratio of Firmicutes to Bacteroidetes and increasing the abundance of SCFA-producing bacteria such as Bacteroides, Lactobacillus, and Blautia, along with increasing the total SCFAs contents. Overall, these results show that FRB is a beneficial nutraceutical for hyperlipidemia amelioration.


Assuntos
Fagopyrum , Microbioma Gastrointestinal , Hiperlipidemias , Doenças Metabólicas , Oryza , Probióticos , Animais , Dieta Hiperlipídica/efeitos adversos , Disbiose , Hiperlipidemias/tratamento farmacológico , Inflamação , Lipídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Probióticos/farmacologia
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