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1.
Langmuir ; 38(51): 16112-16121, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36512764

RESUMO

The scientific community has shown a great deal of interest in sodium lauroyl glycine (SLG) and sodium lauroyl lactylate (SLL), two sustainable and eco-friendly substances that are considered as potential bio-friendly alternatives for petrochemical-based amphiphiles. In the present work, the formation of mixed micelle for SLG and SLL surfactant in water was investigated. Meanwhile, the surface interaction and thermodynamic parameters were calculated according to the surface tension curves. The results indicated that at certain ratios, SLG/SLL surfactant mixtures had synergistic effects that could yield higher surface activity and improve application performance. When the mole fraction of SLL (αSLL) was 0.4, γcmc achieved a minimum of 22.6 mN m-1 and displayed the best foaming properties. The mixed solution exhibited the best wetting ability when αSLL was 0.6. While αSLL was 0.8, the mixed solution showed the optimum dynamic adsorption properties. And it was found that the antibacterial property of SLG and SLL could be partially preserved after compounding. These results demonstrated for the first time that the mixed environmentally friendly surfactant SLG and SLL has a promising prospect for use in the personal care, detergent, and cosmetic industries.


Assuntos
Micelas , Tensoativos , Molhabilidade , Termodinâmica , Glicina , Sódio
2.
Diabetes Metab Syndr Obes ; 15: 3285-3301, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325432

RESUMO

Purpose: In this study, we aimed to investigate the effect of follistatin (FST) on hepatic steatosis in NAFLD and the underlying mechanism, which has rarely been reported before. Methods: Liver samples from NAFLD patients and normal liver samples (from liver donors) were collected to investigate hepatic FST expression in humans. Additionally, human liver cells (LO2) were treated with free fatty acid (FFA) to induce lipid accumulation. Furthermore, lentivirus with FST overexpression or knockdown vectors were used to generate stable cell lines, which were subsequently treated with FFA or FFA and rapamycin. In the animal experiments, male C57BL/6J mice were fed with a high-fat diet (HFD) to induce NAFLD, after which the adeno-associated virus (AAV) gene vectors for FST overexpression were administered. In both cell culture and mice, we evaluated morphological changes and the protein expression of sterol regulatory element-binding protein1 (SREBP1), acetyl-CoA carboxylase1 (ACC1), carbohydrate-responsive element-binding protein (ChREBP), fatty acid synthase (FASN), and Akt/mTOR signaling. The body weight and serum parameters of the mice were also measured. Results: Hepatic FST expression level was higher in NAFLD patients compared to normal samples. In LO2 cells, FST overexpression alleviated lipid accumulation and lipogenesis, whereas FST knockdown aggravated hepatic steatosis. FST could regulate Akt/mTOR signaling, and the mTOR inhibitor rapamycin abolished the effect of FST knockdown on hepatic de novo lipogenesis (DNL). Furthermore, FST expression was increased in HFD mice compared to the corresponding controls. FST overexpression in mice reduced body weight gain, hyperlipidemia, hepatic DNL, and suppressed Akt/mTOR signaling. Conclusion: Hepatic FST expression increases in NAFLD and plays a protective role in hepatic steatosis. FST overexpression gene therapy alleviates hepatic steatosis via the mTOR pathway.Therefore, gene therapy for FST is a promising treatment in NAFLD.

3.
Circ Res ; 131(10): 828-841, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36252121

RESUMO

BACKGROUND: Dysregulated BMP (bone morphogenetic protein) or TGF-ß (transforming growth factor beta) signaling pathways are imperative in idiopathic and familial pulmonary arterial hypertension (PAH) as well as experimental pulmonary hypertension (PH) in rodent models. MED1 (mediator complex subunit 1) is a key transcriptional co-activator and KLF4 (Krüppel-like factor 4) is a master transcription factor in endothelium. However, MED1 and KLF4 epigenetic and transcriptional regulations of the BMP/TGF-ß axes in pulmonary endothelium and their dysregulations leading to PAH remain elusive. We investigate the MED1/KLF4 co-regulation of the BMP/TGF-ß axes in endothelium by studying the epigenetic regulation of BMPR2 (BMP receptor type II), ETS-related gene (ERG), and TGFBR2 (TGF-ß receptor 2) and their involvement in the PH. METHODS: High-throughput screening involving data from RNA-seq, MED1 ChIP-seq, H3K27ac ChIP-seq, ATAC-seq, and high-throughput chromosome conformation capture together with in silico computations were used to explore the epigenetic and transcriptional regulation of BMPR2, ERG, and TGFBR2 by MED1 and KLF4. In vitro experiments with cultured pulmonary arterial endothelial cells (ECs) and bulk assays were used to validate results from these in silico analyses. Lung tissue from patients with idiopathic PAH, animals with experimental PH, and mice with endothelial ablation of MED1 (EC-MED1-/-) were used to study the PH-protective effect of MED1. RESULTS: Levels of MED1 were decreased in lung tissue or pulmonary arterial endothelial cells from idiopathic PAH patients and rodent PH models. Mechanistically, MED1 acted synergistically with KLF4 to transactivate BMPR2, ERG, and TGFBR2 via chromatin remodeling and enhancer-promoter interactions. EC-MED1-/- mice showed PH susceptibility. In contrast, MED1 overexpression mitigated the PH phenotype in rodents. CONCLUSIONS: A homeostatic regulation of BMPR2, ERG, and TGFBR2 in ECs by MED1 synergistic with KLF4 is essential for the normal function of the pulmonary endothelium. Dysregulation of MED1 and the resulting impairment of the BMP/TGF-ß signaling is implicated in the disease progression of PAH in humans and PH in rodent models.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Camundongos , Animais , Hipertensão Pulmonar/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Células Endoteliais/metabolismo , Epigênese Genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Artéria Pulmonar/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Hipertensão Arterial Pulmonar/genética , Endotélio Vascular/metabolismo , Fatores de Transcrição/metabolismo , Subunidade 1 do Complexo Mediador/genética , Subunidade 1 do Complexo Mediador/metabolismo
4.
World J Clin Cases ; 10(26): 9484-9492, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36159414

RESUMO

BACKGROUND: Salivary gland cancer is a rare disease in which cancer cells form in the tissues of the salivary glands. It mostly occurs in the glands that have secretion functions, such as the parotid gland, sublingual gland and submandibular gland. This is very rare when it occurs in other nonsecreting glands. Here, we report one case of salivary gland carcinoma occurring in the thymus and discuss related diagnoses and treatment progress. CASE SUMMARY: One 33-year-old middle-aged man presented with a thymus mass without any clinical symptoms when he underwent regular physical examination. Later, the patient was admitted to the hospital for further examination. Computed tomography (CT) showed that there was a mass of 3 cm × 2.8 cm × 1.5 cm in the thymus area. The patient had no symptom of discomfort or tumor- related medical history before. After completing the preoperative examinations, it was confirmed that the patient had indications for surgery. The surgeon performed a transthoracoscope "thymectomy + pleural mucostomy" for him. During the operation, the tumor tissue was quickly frozen, and the symptomatic section showed a malignant tumor. The final pathological result suggested thymus salivary gland carcinoma- mucoepidermoid carcinoma (MEC). In the second month after surgery, we performed local area radiotherapy for the patient, with a total radiation dose of 50.4 Gy/28Fx. After 12 mo of surgery, the patient underwent positron emission tomography-CT examination, which indicated that there was no sign of tumor recurrence or metastasis. After 16 mo of operation, CT scan re-examination showed that there was no sign of tumor recurrence or metastasis. As of the time of publication, the patient was followed up for one and a half years. He had no sign of tumor recurrence and continued to survive. CONCLUSION: The incidence of MEC in the thymus is low, and its diagnosis needs to be combined with clinical features and imaging methods. Histopathological analysis plays a key role in the diagnosis of the disease. Patients with early-stage disease have a good prognosis and long survival period. In contrast, patients with advanced-stage disease have a poor prognosis and short survival period. Combining radiotherapy and chemotherapy in inoperable patients may prolong survival.

5.
J Immunol ; 209(5): 855-863, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36130132

RESUMO

Effector CD8+ T cells are crucial players in adaptive immunity for effective protection against invading pathogens. The regulatory mechanisms underlying CD8+ T cell effector differentiation are incompletely understood. In this study, we defined a critical role of mediator complex subunit 1 (Med1) in controlling effector CD8+ T cell differentiation and survival during acute bacterial infection. Mice with Med1-deficient CD8+ T cells exhibited significantly impaired expansion with evidently reduced killer cell lectin-like receptor G1+ terminally differentiated and Ly6c+ effector cell populations. Moreover, Med1 deficiency led to enhanced cell apoptosis and expression of multiple inhibitory receptors (programmed cell death 1, T cell Ig and mucin domain-containing-3, and T cell immunoreceptor with Ig and ITIM domains). RNA-sequencing analysis revealed that T-bet- and Zeb2-mediated transcriptional programs were impaired in Med1-deficient CD8+ T cells. Overexpression of T-bet could rescue the differentiation and survival of Med1-deficient CD8+ effector T cells. Mechanistically, the transcription factor C/EBPß promoted T-bet expression through interacting with Med1 in effector T cells. Collectively, our findings revealed a novel role of Med1 in regulating effector CD8+ T cell differentiation and survival in response to bacterial infection.


Assuntos
Linfócitos T CD8-Positivos , Subunidade 1 do Complexo Mediador , Animais , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Diferenciação Celular , Subunidade 1 do Complexo Mediador/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Mucinas/metabolismo , RNA/metabolismo , Receptores Semelhantes a Lectina de Células NK/metabolismo , Proteínas com Domínio T/metabolismo
6.
Artigo em Inglês | MEDLINE | ID: mdl-36098912

RESUMO

Developing efficient and cost-effective non-noble metal catalysts for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) is of great importance. Herein, Co-promoted 1T-MoS2 nanoflowers were synthesized via a one-step hydrothermal method. The influence of Co content on the structure and catalytic performance of 1T-MoS2 was studied in detail. It was found that Co doping not only enhanced the electronic conductivity but also increased the hydrogen adsorption ability of 1T-MoS2. Meanwhile, the highest activity was achieved due to the synergy effect of Co-Mo-S and CoS2 active phase. In the catalytic reduction of 4-NP, the reaction rate constant of Co/1T-MoS2-0.3 was as high as 0.908 min-1 and the catalyst exhibited excellent stability after recycling five times. The present work provides new insights for the rational design of highly efficient metal-doped MoS2 catalysts towards 4-NP reduction in wastewater.

7.
Balkan Med J ; 39(6): 411-421, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36172827

RESUMO

Background: Increasing evidence revealed that circular RNAs (circRNAs) are involved in colorectal cancer progression. However, the potential function of circ_0001535 in colorectal cancer remains unclear. Aims: To investigate the mechanism of circ_0001535 by silencing circ_0001535 in colorectal cancer cells and nude mice. Study Design: A cell study. Methods: Expressions of circ_0001535, LIM and SH3 protein 1 (LASP1) mRNA, and miR-485-5p were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Western blot analyses of LASP1, PCNA, cleaved caspase 3, snail 1, and OCT4 protein expression were performed. CCK-8, EdU, flow cytometry, transwell assays, and sphere formation were conducted to evaluate colorectal cancer cell proliferation, apoptosis, invasion, and stemness. Luciferase reporter assays, RNA pull-down, and RIP validated binding. A nude mice xenograft model was constructed. Results: Circ_0001535 was significantly upregulated in colorectal tissues and cells. Circ_0001535 knockdown suppressed the malignant behavior of colorectal cells such as proliferation, invasion, stemness, and tumor growth in vivo. This knockdown also induced apoptosis by sponging miR-485-5p and upregulating LASP1 expression. Conclusion: Circ_0001535 promotes colorectal cancer cell development by absorbing miR-485-5p and upregulating LASP1.


Assuntos
Neoplasias Colorretais , Proteínas com Domínio LIM , MicroRNAs , RNA Circular , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética
8.
Front Immunol ; 13: 901566, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35874667

RESUMO

Acute liver injury (ALI) is a disease that seriously threatens human health and life, and a dysregulated inflammation response is one of the main mechanisms of ALI induced by various factors. Phosphatidylethanolamine binding protein 4 (PEBP4) is a secreted protein with multiple biological functions. At present, studies on PEBP4 exist mainly in the field of tumors and rarely in inflammation. This study aimed to explore the potential roles and mechanisms of PEBP4 on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALI. PEBP4 was downregulated after treatment with LPS/D-GalN in wild-type mice. PEBP4 hepatocyte-conditional knockout (CKO) aggravated liver damage and repressed liver functions, including hepatocellular edema, red blood cell infiltration, and increased aspartate aminotransferase (AST)/alanine aminotrans-ferase (ALT) activities. The inflammatory response was promoted through increased neutrophil infiltration, myeloperoxidase (MPO) activities, and cytokine secretions (interleukin-1ß, IL-1ß; tumor necrosis factor alpha, TNF-α; and cyclooxygenase-2, COX-2) in PEBP4 CKO mice. PEBP4 CKO also induced an apoptotic effect, including increasing the degree of apoptotic hepatocytes, the expressions and activities of caspases, and pro-apoptotic factor Bax while decreasing anti-apoptotic factor Bcl-2. Furthermore, the data demonstrated the levels of Toll-like receptor 4 (TLR4), phosphorylation-inhibitor of nuclear factor kappaB Alpha (p-IκB-α), and nuclear factor kappaB (NF-κB) p65 were upregulated, while the expressions of cytoplasmic IκB-α and NF-κB p65 were downregulated after PEBP4 CKO. More importantly, both the NF-κB inhibitor (Ammonium pyrrolidinedithiocarbamate, PDTC) and a small-molecule inhibitor of TLR4 (TAK-242) could inhibit TLR4/NF-κB signaling activation and reverse the effects of PEBP4 CKO. In summary, the data suggested that hepatocyte-conditional knockout of PEBP4 aggravated LPS/D-GalN-induced ALI, and the effect is partly mediated by activation of the TLR4/NF-κB signaling pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , NF-kappa B , Proteína de Ligação a Fosfatidiletanolamina , Animais , Doença Hepática Induzida por Substâncias e Drogas/genética , Galactosamina/toxicidade , Hepatócitos/metabolismo , Humanos , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/patologia , Camundongos , Camundongos Knockout , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-35786548

RESUMO

As a leading graph clustering technique, spectral clustering is one of the most widely used clustering methods to capture complex clusters in data. Some additional prior information can help it to further reduce the difference between its clustering results and users' expectations. However, it is hard to get the prior information under unsupervised scene to guide the clustering process. To solve this problem, we propose a self-constrained spectral clustering algorithm. In this algorithm, we extend the objective function of spectral clustering by adding pairwise and label self-constrained terms to it. We provide the theoretical analysis to show the roles of the self-constrained terms and the extensibility of the proposed algorithm. Based on the new objective function, we build an optimization model for self-constrained spectral clustering so that we can simultaneously learn the clustering results and constraints. Furthermore, we propose an iterative method to solve the new optimization problem. Compared to other existing versions of spectral clustering algorithms, the new algorithm can discover a high-quality cluster structure of a data set without prior information. Extensive experiments on benchmark data sets illustrate the effectiveness of the proposed algorithm.

10.
Viruses ; 14(5)2022 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-35632744

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) induces secretion of high mobility group box 1 (HMGB1) to mediate inflammatory response that is involved in the pulmonary injury of infected pigs. Our previous study indicates that protein kinase C-delta (PKC-delta) is essential for HMGB1 secretion in PRRSV-infected cells. However, the underlying mechanism in HMGB1 secretion induced by PRRSV infection is still unclear. Here, we discovered that the phosphorylation level of HMGB1 in threonine residues increased in PRRSV-infected cells. A site-directed mutagenesis study showed that HMGB1 phosphorylation at threonine-51 was associated with HMGB1 secretion induced by PRRSV infection. Co-immunoprecipitation (co-IP) of HMGB1 failed to precipitate PKC-delta, but interestingly, mass spectrometry analysis of the HMGB1 co-IP product showed that PRRSV infection enhanced HMGB1 binding to ribosomal protein S3 (RPS3), which has various extra-ribosomal functions. The silencing of RPS3 by siRNA blocked HMGB1 secretion induced by PRRSV infection. Moreover, the phosphorylation of HMGB1 at threonine-51 was correlated with the interaction between HMGB1 and RPS3. In vivo, PRRSV infection also increased RPS3 levels and nuclear accumulation in pulmonary alveolar macrophages. These results demonstrate that PRRSV may induce HMGB1 phosphorylation at threonine-51 and increase its interaction with RPS3 to enhance HMGB1 secretion. This finding provides insights into the pathogenesis of PRRSV infection.


Assuntos
Proteína HMGB1 , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Proteína HMGB1/metabolismo , Fosforilação , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Suínos , Treonina/metabolismo
12.
Am J Pathol ; 192(7): 1016-1027, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35461855

RESUMO

Mediator 1 (MED1), a key subunit of the mediator complex, interacts with various nuclear receptors and functions in lipid metabolism and energy homeostasis. Dilated cardiomyopathy-related ventricular dilatation and heart failure have been reported in mice with cardiomyocyte-specific Med1 deficiency. However, the contribution of macrophage-specific MED1 in cardiac remodeling remains unclear. In this study, macrophage-specific Med1 knockout (Med1ΔMac) mice were generated and exposed to isoproterenol (ISO) to induce cardiac fibrosis; these mice showed aggravated cardiac fibrosis compared with Med1fl/fl mice. The levels of expression of marker genes for myofibroblast transdifferentiation [α-smooth muscle actin (SMA)] and of profibrotic genes, including Col1a1, Col3a1, Postn, Mmp2, Timp1, and Fn1, were significantly increased in the cardiac tissues of Med1ΔMac mice with ISO-induced myocardial fibrosis. In particular, the transforming growth factor (TGF)-ß-Smad2/3 signaling pathway was activated. In bone marrow-derived and peritoneal macrophages, Med1 deficiency was also associated with elevated levels of expression of proinflammatory genes, including Il6, Tnfa, and Il1b. These findings indicate that macrophage-specific MED1 deficiency may aggravate ISO-induced cardiac fibrosis via the regulation of the TGF-ß-SMAD2/3 pathway, and the underlying mechanism may involve MED1 deficiency triggering the activation of inflammatory cytokines in macrophages, which in turn may stimulate phenotypic switch of cardiac fibroblasts and accelerate cardiac fibrosis. Thus, MED1 is a potential therapeutic target for cardiac fibrosis.


Assuntos
Isoproterenol , Macrófagos , Subunidade 1 do Complexo Mediador , Miócitos Cardíacos , Animais , Fibrose , Isoproterenol/toxicidade , Macrófagos/metabolismo , Subunidade 1 do Complexo Mediador/deficiência , Subunidade 1 do Complexo Mediador/genética , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/patologia , Miofibroblastos/metabolismo
13.
Neuroradiology ; 64(7): 1401-1410, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35462573

RESUMO

BACKGROUND AND OBJECTIVE: Cervical spondylosis (CS) is often accompanied by persistent cervical pain, and psychological complications including depression and anxiety, which aggravate pain. Past studies have revealed brain alterations in chronic pain patients. However, the cortical mechanism for NSAID (non-steroidal anti-inflammatory drug) responders relative to non-responders is still lacking. Therefore, we aimed to investigate the brain functional differences between responders to NSAID relative to non-responders using amplitude of low-frequency fluctuation (ALFF) and dynamic functional connectivity variance (DFCV). To our knowledge, our study is the first to investigate the DFCV in CS patients. MATERIALS AND METHODS: We first explored the differences in psychological inventories in CS patients who respond to NSAID vs non-responders. The voxel-wise ALFF was calculated and compared between CS patients and healthy controls. The ALFF within the resultant clusters were extracted and compared between responders and non-responders. DFCV among the resulting clusters was compared in responders vs non-responders. RESULTS: We found that (1) compared to responders, non-responders exhibited higher levels of anxiety and depression; (2) relative to healthy controls, CS patients exhibited altered ALFF within the middle cingulate cortice (MCC), cerebellum, and middle frontal gyrus (MFG); (3) moreover, compared with responders, non-responders exhibited lower ALFF within MCC; furthermore, non-responders also exhibited increased DFCV between MCC and cerebellum, and between MCC and MFG. CONCLUSION: Our data indicate that psychological comorbidities (e.g., anxiety) influence response to NSAID in CS patients. Relative to NSAID responders, non-responders had altered MCC function, which may be associated with anxiety in CS patients.


Assuntos
Imageamento por Ressonância Magnética , Espondilose , Anti-Inflamatórios , Anti-Inflamatórios não Esteroides/uso terapêutico , Encéfalo , Mapeamento Encefálico/métodos , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Espondilose/diagnóstico por imagem , Espondilose/tratamento farmacológico
14.
Front Chem ; 10: 857036, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35355786

RESUMO

In the critical situation of energy shortage and environmental problems, Si has been regarded as one of the most potential anode materials for next-generation lithium-ion batteries as a result of the relatively low delithiation potential and the eminent specific capacity. However, a Si anode is subjected to the huge volume expansion-contraction in the charging-discharging process, which can touch off pulverization of the bulk particles and worsens the cycle life. Herein, to reduce the volume change and improve the electrochemical performance, a novel Si@SiOx/C anode with a core-shell structure is designed by spray and pyrolysis methods. The SiOx/C shell not only ensures the structure stability and proves the high electrical conductivity but also prevents the penetration of electrolytes, so as to avoid the repetitive decomposition of electrolytes on the surface of Si particle. As expected, Si@SiOx/C anode maintains the excellent discharge capacity of 1,333 mAh g-1 after 100 cycles at a current density of 100 mA g-1. Even if the current density reaches up to 2,000 mA g-1, the capacity can still be maintained at 1,173 mAh g-1. This work paves an effective way to develop Si-based anodes for high-energy density lithium-ion batteries.

15.
Microbiol Spectr ; 10(2): e0114721, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35293806

RESUMO

The substantially increased prevalence of obesity and obesity-related diseases has generated considerable concern. Currently, synthetic biological strategies have played an essential role in preventing and treating chronic diseases such as obesity. A growing number of symbiotic bacteria used as vectors for genetic engineering have been applied to create living therapeutics. In this study, using Bacillus subtilis as a cellular chassis, we constructed the engineered butyrate-producing strain BsS-RS06551 with a butyrate yield of 1.5 g/liter. A mouse model of obesity induced by a high-fat diet (HFD) was established to study the long-term intervention effects of this butyrate-producing bacteria on obesity. Combined with phenotypic assay results, we found that BsS-RS06551 could effectively retard body weight gain induced by a high-fat diet and visceral fat accumulation of mice, whereas it could improve glucose tolerance and insulin tolerance, reducing liver damage. We explored the BsS-RS06551 mechanism of action on host function and changes in intestinal flora by integrating multiple omics profiling, including untargeted metabolomics and metagenomics. The results showed that 24 major differential metabolites were involved in the metabolic regulation of BsS-RS06551 to prevent obesity in mice, including bile acid metabolism, branch chain amino acids, aromatic amino acids, and other metabolic pathways. Continuous ingestion of BsS-RS06551 could regulate gut microbiota composition and structure and enhance intestinal flora metabolic function abundance, which was closely related to host interactions. Our results demonstrated that engineered butyrate-producing bacteria had potential as an effective strategy to prevent obesity. IMPORTANCE Obesity is a chronic metabolic disease with an imbalance between energy intake and energy expenditure, and obesity-related metabolic diseases have become increasingly common. There is an urgent need to develop effective interventions for the prevention and treatment of obesity. This study showed that long-term consumption of BsS-RS06551 had a significant inhibitory effect on obesity induced by a high-fat diet and was more potent in inhibiting obesity than prebiotic inulin. In addition, this study showed a beneficial effect on host glucose, lipid metabolism, and gut microbe composition. Considering its colonization potential, this engineered bacteria provided a new strategy for the effective and convenient treatment of obesity in the long term.


Assuntos
Microbioma Gastrointestinal , Doenças Metabólicas , Animais , Bactérias/genética , Bactérias/metabolismo , Butiratos/efeitos adversos , Butiratos/metabolismo , Microbioma Gastrointestinal/fisiologia , Glucose/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/terapia
16.
Animal Model Exp Med ; 5(1): 72-80, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35229996

RESUMO

BACKGROUND: Porcine pancreatic elastase (PPE) is successfully used to induce abdominal aortic aneurysm (AAA) in mice. However, differences between mouse strains in susceptibility to PPE induction have been reported. Kunming mouse is one of the most frequently used strains in China but whether it is suitable for induction of AAA by PPE application remains unclear. METHODS: PPE infusion (1.5 units/ml) in temporary controlled aorta was performed to induce AAAs in both C57BL/6J and Kunming mice. Phosphate-buffered saline (PBS) application was used as vehicle control. The aorta diameters of all mice were measured at days 0 and 14 after surgery to evaluate the AAA formation. RESULTS: After 14 days of PPE or PBS infusion, all mice were sacrificed and aorta tissues were collected for histological staining analysis. At the 14th day after infusion, PPE successfully induced aortic dilation in Kunming mice and typical AAA in C57BL/6J mice. The aorta diameter increased by 0.23 mm in Kunming mice after PPE infusion, while it was 0.72 mm in the C57BL/6J strain. PPE induced mild elastin degradation, smooth muscle cell (SMC) depletion and mural leucocyte infiltration in Kunming mice, but in PPE-sensitive C57BL/6J mice, it induced total loss of SMCs, elastin disappearance and diffused infiltrated leucocytes in aortic aneurysmal segments. The effects of PPE in inducing angiogenesis and upregulating matrix metalloproteinase 2 and 9 expression in Kunming mice were also weaker than that in C57BL/6J mice. CONCLUSION: At the reported dose of PPE, Kunming mouse is not as susceptible to AAA formation as C57BL/6J mice. The failure of PPE to induce AAA formation in Kunming mice may be associated to its inability to boost a strong inflammatory response.


Assuntos
Aneurisma da Aorta Abdominal , Elastase Pancreática , Animais , Aorta Abdominal , Aneurisma da Aorta Abdominal/induzido quimicamente , Modelos Animais de Doenças , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Elastase Pancreática/efeitos adversos , Suínos
17.
Oxid Med Cell Longev ; 2022: 3698219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222797

RESUMO

Hypertension is a high-risk factor for developing coronary heart disease and stroke. Endothelial dysfunction and arterial remodeling can lead to increased vascular wall thickness and arterial stiffness. Previous studies showed that microRNA-483 (miR-483) enhances endothelial cell (EC) function. Here, we investigated the protective role of miR-483 in hypertension. Data collected from two patient cohorts showed that the serum miR-483-3p level was associated with the progression of hypertension and positively correlated with vascular function. In cultured ECs, miR-483 targets a number of endothelial dysfunction-related genes, such as transforming growth factor-ß (TGF-ß), connective tissue growth factor (CTGF), angiotensin-converting enzyme 1 (ACE1), and endothelin-1 (ET-1). Overexpression of miR-483-3p in ECs inhibited Ang II-induced endothelial dysfunction, revealed by the decreased expression of TGF-ß, CTGF, ACE1, and ET-1. Furthermore, miR-483-3p secreted from ECs was taken up by smooth muscle cells (SMCs) via the exosome pathway, which also decreased these genes in SMCs. Additionally, telmisartan could increase the aortic and serum levels of miR-483-3p in hypertension patients and spontaneous hypertension rats (SHR). These findings suggest that miR-483-3p exerts a protective effect on EC function during the onset of hypertension and thus may be considered a potential therapeutic target for hypertension-related cardiovascular diseases.


Assuntos
Células Endoteliais/metabolismo , Hipertensão/metabolismo , MicroRNAs/metabolismo , Angiotensina II/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Exossomos/metabolismo , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Hipertensão/patologia , MicroRNAs/sangue , MicroRNAs/genética , Músculo Liso Vascular/metabolismo , Ratos , Ratos Endogâmicos SHR , Telmisartan/farmacologia , Telmisartan/uso terapêutico
18.
Proteome Sci ; 20(1): 1, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980145

RESUMO

BACKGROUND: Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, most of which are caused by atherosclerosis. Discerning processes that participate in macrophage-to-foam cell formation are critical for understanding the basic mechanisms underlying atherosclerosis. To explore the molecular mechanisms of foam cell formation, differentially expressed proteins were identified. METHODS: Human peripheral blood mononuclear cells were stimulated with macrophage colony-stimulating factor, and obtained macrophages were transformed into foam cells by oxidized low-density lipoprotein. Tandem mass tag (TMT) labeling combined with mass spectrometry was performed to find associations between foam cell transformation and proteome profiles. RESULTS: Totally, 5146 quantifiable proteins were identified, among which 1515 and 182 differentially expressed proteins (DEPs) were found in macrophage/monocyte and foam cell/macrophage, respectively. Subcellular localization analysis revealed that downregulated DEPs of macrophages/monocytes were mostly located in the nucleus, whereas upregulated DEPs of foam cells/macrophages were mostly extracellular or located in the plasma membrane. Functional analysis of DEPs demonstrated that cholesterol metabolism-related proteins were upregulated in foam cells, whereas immune response-related proteins were downregulated in foam cells. The protein interaction network showed that the DEPs with the highest interaction scores between macrophages and foam cells were mainly concentrated in lysosomes and the endoplasmic reticulum. CONCLUSIONS: Proteomics analysis suggested that cholesterol metabolism was upregulated, while the immune response was suppressed in foam cells. KEGG enrichment analysis and protein-protein interaction analysis indicated that DEPs located in the endoplasmic reticulum and lysosomes might be key drivers of foam cell formation. These data provide a basis for identifying the potential proteins associated with the molecular mechanism underlying macrophage transformation to foam cells.

19.
Cell Mol Gastroenterol Hepatol ; 13(4): 1161-1179, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34990887

RESUMO

BACKGROUND & AIMS: Cholesterol 25-hydroxylase (Ch25h), converting cholesterol to 25-hydroxycholesterol (25-HC), is critical in modulating cellular lipid metabolism and anti-inflammatory and antiviral activities. However, its role in nonalcoholic fatty liver disease remains unclear. METHODS: Ch25h expression was detected in livers of ob/ob mice and E3 rats fed a high-fat diet (HFD). Gain- or loss-of-function of Ch25h was performed using Ch25h+/+ (wild type [WT]) mice receiving AAV8-Ch25h or Ch25h knockout (Ch25h-/-) mice. WT mice fed an HFD were administered with 25-HC. The Ch25h-LXRα-CYP axis was measured in primary hepatocytes isolated from WT and Ch25h-/- mice. RESULTS: We found that Ch25h level was decreased in livers of ob/ob mice and E3 rats fed an HFD. Ch25h-/- mice fed an HFD showed aggravated fatty liver and decreased level of cytochrome P450 7A1 (CYP7A1), in comparison with their WT littermates. RNA-seq analysis revealed that the differentially expressed genes in livers of HFD-fed Ch25h-/- mice were involved in pathways of positive regulation of lipid metabolic process, steroid metabolic process, cholesterol metabolic process, and bile acid biosynthetic process. As gain-of-function experiments, WT mice receiving AAV8-Ch25h or 25-HC showed alleviated NAFLD, when compared with the control group receiving AAV8-control or vehicle control. Consistently, Ch25h overexpression significantly elevated the levels of primary and secondary bile acids and CYP7A1 but decreased those of small heterodimer partner and FGFR4. CONCLUSIONS: Elevated levels of Ch25h and its enzymatic product 25-HC alleviate HFD-induced hepatic steatosis via regulating enterohepatic circulation of bile acids. The underlying mechanism involves 25-HC activation of CYP7A1 via liver X receptor. These data suggest that targeting Ch25h or 25-HC may have therapeutic advantages against nonalcoholic fatty liver disease.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Ácidos e Sais Biliares , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/etiologia , Ratos , Esteroide Hidroxilases
20.
Anticancer Drugs ; 33(1): e409-e422, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34459455

RESUMO

Colorectal cancer (CRC) is a prevalent malignant tumor with a poor prognosis. Circular RNA (circRNA) circ_0007334 is related to cell proliferation in CRC. This study is designed to explore the role and mechanism of circ_0007334 in CRC progression. Circ_0007334, microRNA-577 (miR-577) and kruppel-like factor 12 (KLF12) levels were measured by real-time quantitative PCR (RT-qPCR). Exosomes were detected by a transmission electron microscope and nanoparticle tracking analysis (NTA). CD63, TSG101, matrix metallopeptidase-2 (MMP-2), MMP-9, VEGFA and KLF12 protein levels were examined by western blot assay. The binding relationship between miR-577 and circ_0007334 or KLF12 was predicted by circRNA interactome or Starbase and verified by a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell viability, colony number, migration, invasion and angiogenesis were detected by cell counting kit-8 (CCK-8), colony formation, wound healing, transwell and tube formation assays. The biological role of circ_0007334 was examined by the xenograft tumor model in vivo. Circ_0007334 and KLF12 were increased, and miR-577 was decreased in CRC tissues and cells. Also, circ_0007334 expression was upregulated in CRC cell-derived exosomes. Circ_0007334 deficiency repressed cell viability, colony formation, migration, invasion, and angiogenesis in CRC cells. Mechanically, circ_0007334 could regulate KLF12 expression by sponging miR-577. Circ_0007334 downregulation or exosomal circ_0007334 silencing blocked CRC tumor growth in vivo. These results presented that circ_0007334 deficiency exerts a tumor-suppressor by the miR-577/KLF12 axis in CRC, and indicated that exosomal circ_0007334 could hinder CRC tumor growth and angiogenesis in vivo. Our findings provided a novel therapeutic strategy for CRC.


Assuntos
Neoplasias Colorretais/patologia , Fatores de Transcrição Kruppel-Like/metabolismo , MicroRNAs/metabolismo , RNA Circular/metabolismo , RNA não Traduzido/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Exossomos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
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