Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 54
Filtrar
1.
Int Immunopharmacol ; 137: 112433, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38870879

RESUMO

BACKGROUND: Gastric cancer (GC) is a refractory malignant tumor with high tumor heterogeneity, a low rate of early diagnosis, and poor patient prognosis. Lipid metabolism reprogramming plays a critical role in tumorigenesis and progression, but its prognostic role and regulatory mechanism in GC are rarely studied. Thus, the identification of signatures related to lipid metabolism is necessary and may present a new avenue for improving the overall prognosis of GC. METHODS: Lipid metabolism-associated genes (LMAGs) with differential expression in tumor and tumor-adjacent tissue were acquired to identify lipid metabolism-associated subtypes. The differentially expressed genes (DEGs) between the two clusters were then utilized for prognostic analysis and signature construction. Additionally, pathway enrichment analysis and immune cell infiltration analysis were employed to identify the characteristics of the prognostic model. Further analyses were conducted at the single-cell level to better understand the model's prognostic mechanism. Finally, the prediction of immunotherapy response was used to suggest potential treatments. RESULTS: Two lipid metabolism-associated subtypes were identified and 9 prognosis-related genes from the DEGs between the two clusters were collected for the construction of the prognostic model named lipid metabolism-associated signature (LMAS). Then we found the low LMAS patients with favorable prognoses were more sensitive to ferroptosis in the Cancer Genome Atlas of Stomach Adenocarcinoma (TCGA-STAD). Meanwhile, the tumor cells exhibiting high levels of lipid peroxidation and accumulation of reactive oxygen species (ROS) in single-cell levels were primarily enriched in the low LMAS group, which was more likely to induce ferroptosis. In addition, endothelial cells and cancer-associated fibroblasts (CAFs) facilitated tumor angiogenesis, proliferation, invasion, and metastasis through endothelial-mesenchymal transition (EndMT), affecting the prognosis of the patients with high LMAS scores. Moreover, CD1C- CD141- dendritic cells (DCs) also secreted pro-tumorigenic cytokines to regulate the function of endothelial cells and CAFs. Finally, the patients with low LMAS scores might have better efficacy in immunotherapy. CONCLUSIONS: A LMAS was constructed to guide GC prognosis and therapy. Meanwhile, a novel anti-tumor effect was found in lipid metabolism reprogramming of GC which improved patients' prognosis by regulating the sensitivity of tumor cells to ferroptosis. Moreover, EndMT may have a negative impact on GC prognosis.


Assuntos
Ferroptose , Metabolismo dos Lipídeos , Neoplasias Gástricas , Microambiente Tumoral , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/imunologia , Ferroptose/genética , Humanos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Metabolismo dos Lipídeos/genética , Prognóstico , Regulação Neoplásica da Expressão Gênica , Transição Endotélio-Mesênquima , Reprogramação Metabólica
2.
Curr Med Chem ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38529602

RESUMO

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) emerged at the end of 2019, causing a highly infectious and pathogenic disease known as 2019 coronavirus disease. This disease poses a serious threat to human health and public safety. The SARS-CoV-2 main protease (Mpro) is a highly sought-after target for developing drugs against COVID-19 due to its exceptional specificity. Its crystal structure has been extensively documented. Numerous strategies have been employed in the investigation of Mpro inhibitors. This paper is primarily concerned with Fragment-based Drug Discovery (FBDD), which has emerged as an effective approach to drug design in recent times. Here, we summarize the research on the approach of FBDD and its application in developing inhibitors for SARS-CoV-2 Mpro.

3.
Front Cell Infect Microbiol ; 14: 1342684, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533384

RESUMO

Brucella consists of gram-negative bacteria that have the ability to invade and replicate in professional and non-professional phagocytes, and its prolonged persistence in the host leads to brucellosis, a serious zoonosis. Toll-like receptors (TLRs) are the best-known sensors of microorganisms implicated in the regulation of innate and adaptive immunity. In particular, TLRs are transmembrane proteins with a typical structure of an extracellular leucine-rich repeat (LRR) region and an intracellular Toll/interleukin-1 receptor (TIR) domain. In this review, we discuss Brucella infection and the aspects of host immune responses induced by pathogens. Furthermore, we summarize the roles of TLRs in Brucella infection, with substantial emphasis on the molecular insights into its mechanisms of action.


Assuntos
Brucella , Brucelose , Humanos , Receptores Toll-Like , Imunidade Inata
4.
Artigo em Inglês | MEDLINE | ID: mdl-38153832

RESUMO

In the process of rehabilitation treatment for stroke patients, rehabilitation evaluation is a significant part in rehabilitation medicine. Researchers intellectualized the evaluation of rehabilitation evaluation methods and proposed quantitative evaluation methods based on evaluation scales, without the clinical background of physiatrist. However, in clinical practice, the experience of physiatrist plays an important role in the rehabilitation evaluation of patients. Therefore, this paper designs a 5 degrees of freedom (DoFs) upper limb (UL) rehabilitation robot and proposes a rehabilitation evaluation model based on Belief Rule Base (BRB) which can add the expert knowledge of physiatrist to the rehabilitation evaluation. The motion data of stroke patients during active training are collected by the rehabilitation robot and signal collection system, and then the upper limb motor function of the patients is evaluated by the rehabilitation evaluation model. To verify the accuracy of the proposed method, Back Propagation Neural Network (BPNN) and Support Vector Machines (SVM) are used to evaluate. Comparative analysis shows that the BRB model has high accuracy and effectiveness among the three evaluation models. The results show that the rehabilitation evaluation model of stroke patients based on BRB could help physiatrists to evaluate the UL motor function of patients and master the rehabilitation status of stroke patients.


Assuntos
Robótica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Extremidade Superior , Robótica/métodos , Paresia/reabilitação , Recuperação de Função Fisiológica
5.
Mol Med Rep ; 28(6)2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37859616

RESUMO

Several studies have revealed that an imbalance of the intestinal microbiota is involved in intestinal inflammation associated with ulcerative colitis (UC). Therefore, regulating the homeostasis of gut microbiota is critical for treating UC. Dracocephalum moldavica L. (DML) extract, a common traditional Chinese medicine, has been demonstrated to possess numerous pharmacological effects, such as antioxidative, anti­inflammatory, and antibacterial properties. The aim of the present study was to evaluate the beneficial effects of DML extract and the probable mechanism of action in a dextran sulfate sodium­induced chronic colitis model. It was found that DML extract ameliorated UC by improving disease activity index, weight loss, colon length, and histological scoring. DML extract administration also enhanced the count of Lactobacillus and reduced the count of Romboutsia. Furthermore, the results of network pharmacology analysis revealed that the active ingredients (including luteolin, rosmarinic acid, oleanolic acid, ursolic acid, apigenin, acacetin, kaempferol, and isorhamnetin) in the DML extract were closely associated with anti­inflammatory activity via various signaling pathways, including the NF­κB, IL­17, TNF, and Toll­like receptor (TLR) signaling pathways. Western blot analysis further indicated that DML extract downregulated the expression of members of the TLR4/NF­κB signaling pathway, which was associated with colitis. Thus, it was hypothesized that DML extract exerted its anti­colitis effects by modulating the gut microbiota and inflammatory pathways.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Ratos , Camundongos , NF-kappa B , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
6.
Curr Med Chem ; 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37718522

RESUMO

Brucellosis remains one of the major zoonotic diseases worldwide. As a causative agent of brucellosis, it has many ways to evade recognition by the immune system, allowing it to replicate and multiply in the host, causing significant harm to both humans and animals. The pathogenic mechanism of Brucella has not been elucidated, making the identification of drug targets from the pathogenic mechanism a challenge. Metalloenzymatic targets and some protein targets unique to Brucella are exploitable in the development of inhibitors against this disease. The development of specific small molecule inhibitors is urgently needed for brucellosis treatment due to the antibiotic resistance of Brucella. This review summarizes the research on small molecule inhibitors of Brucella, which could be instructive for subsequent studies.

7.
Front Cell Infect Microbiol ; 13: 1136674, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37065189

RESUMO

Brucellosis is a common zoonotic disease that is widely spread worldwide and poses a major threat to human health. Clinically, it often presents with non-specific symptoms such as fever, excessive sweating, malaise, myalgia, arthralgia, loss of appetite, weight loss, and enlarged liver, spleen and lymph nodes. The disease has a long and recurrent course, often accumulating in multiple systems and organs. Of these, osteoarticular involvement is the most common complication, with a prevalence of approximately 2-77%, usually manifesting as spondylitis, sacroiliac arthritis and peripheral arthritis. Hepatosplenomegaly is seen in about 50% of patients with brucellosis, and gastrointestinal disturbances such as abdominal pain, nausea, and vomiting are common. Although respiratory involvement is less common, pneumonia, pleurisy, pleural effusion, and pulmonary nodules have been reported. Besides, approximately 2-20% of cases involve infections of the male genitourinary system, mainly manifesting as unilateral epididymal-orchitis and orchitis. The most serious complication facing brucellosis is cardiovascular involvement, and although the overall mortality rate of brucellosis is about 1% and the incidence of brucellosis endocarditis is less than 2%, more than 80% of deaths are associated with endocarditis. Furthermore, brucellosis is complicated by hematologic disease, with anemia occurring in approximately 20-53% of children during the acute phase. In addition, the neurological incidence of brucellosis is about 0.5-25%, mainly manifested as meningitis. In this study, we review the multisystem complications of brucellosis with the aim of improving early diagnosis, timely treatment and prevention of long-term complications.


Assuntos
Brucelose , Endocardite , Orquite , Derrame Pleural , Espondilartrite , Criança , Humanos , Masculino , Orquite/complicações , Brucelose/complicações , Brucelose/epidemiologia , Brucelose/diagnóstico , Espondilartrite/complicações , Endocardite/complicações
8.
Front Cardiovasc Med ; 10: 1143583, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37113698

RESUMO

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) that can identify pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). TLRs play an important role in the innate immune response, leading to acute and chronic inflammation. Cardiac hypertrophy, an important cardiac remodeling phenotype during cardiovascular disease, contributes to the development of heart failure. In previous decades, many studies have reported that TLR-mediated inflammation was involved in the induction of myocardium hypertrophic remodeling, suggesting that targeting TLR signaling might be an effective strategy against pathological cardiac hypertrophy. Thus, it is necessary to study the mechanisms underlying TLR functions in cardiac hypertrophy. In this review, we summarized key findings of TLR signaling in cardiac hypertrophy.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36833536

RESUMO

The rate of soil detachment by water flow indicates soil erosion intensity directly. The exact relation between soil detachment rate and actual sediment load in water flow, however, is still unclear, and the existing relationships have not been adequately tested. The aims of the present study were to investigate the response of soil detachment rate to sediment load using rill flume data with loessial soil and to quantitatively examine the soil detachment equations in the WEPP and EUROSEM soil erosion models. Six slopes were combined with seven flow discharges to measure detachment rates under seven sediment loads using a rill flume with a soil-feeding hopper. Significant differences were found among the soil detachment rate by different sediment loads in low sediment load levels, but an insensitive response of soil detachment rate to sediment load was found under high levels of sediment load. The soil detachment rate was proved to be negatively linearly correlated with sediment load. The rill detachment equation in the WEPP model predicted the soil detachment rate by rill flow very well under our experiment condition. The soil detachment equation in the EUROSEM model underestimated the detachment rates under controlled conditions, but removing the setting velocity from the equation greatly improved prediction. Further experiments that could reflect the dynamic convective detachment and deposition process need to be conducted to compare with the present examination results and to further understand rill erosion processes.


Assuntos
Sedimentos Geológicos , Solo , Erosão do Solo , Simulação por Computador , Água
10.
Exp Ther Med ; 24(2): 511, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35837060

RESUMO

Plague is an acute bacterial infection caused by Yersinia pestis. The three major clinical forms of plague are bubonic, pneumonic and septicemic, which have high case-mortality rates. Therefore, rapid and reliable diagnostic tools are crucial. Currently, bacteriological means and traditional serological assays are used for detecting infection with Y. pestis. However, such methods have their limitations. Polymerase chain reaction (PCR) is one of the most useful tools for rapid diagnosis of plague. The present review introduced the main PCR techniques and their applications for detecting and confirmation of Y. pestis. The advantages and disadvantages of the different PCR methods were also summarized.

11.
Environ Sci Pollut Res Int ; 29(53): 80705-80715, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35727511

RESUMO

The variations in hydrodynamic parameters at different polysaccharides rates and the relationships between sheet erosion modulus and hydrodynamic parameters were analyzed to reveal the hydrodynamic mechanism of sheet erosion on loessial slopes. Artificially simulated rainfall experiments were carried out under three slope gradients (10°, 15°, and 20°), three rainfall intensities (1.0, 1.5, and 2.0 mm·min-1), and four dry-spreading rates of polysaccharides (0, 1, 3, and 5 g·m-2). The results showed that (1) four hydrodynamic parameters (flow velocity, shear stress, stream power, and unit stream power) all increased with both rainfall intensities and slope gradients at four rates of polysaccharides. (2) Polysaccharides could effectively reduce hydrodynamic parameters. In contrast to the bare slope, the average flow velocity, shear stress, stream power, and unit stream power diminished by 27.11~41.18%, 9.53~18.67%, 31.82~50.24%, and 27.11~41.18%, respectively. (3) Polysaccharides could effectively reduce the growth rate of the sheet erosion modulus with hydrodynamic parameters, and there were few differences among the different rates (1, 3, and 5 g·m-2). The increasing rates of the sheet erosion modulus with flow velocity, shear stress, stream power, and unit stream power were 14.0~65.7%, 14.8~33.9%, 7.8~23.7%, and 9.7~29.5%, respectively. (4) At different polysaccharides rates, the relationships between sheet erosion modulus and hydrodynamic parameters were all in logarithmic functions. Moreover, flow velocity (R2 ≥ 0.920) and stream power (R2 ≥ 0.876) were better hydrodynamic parameters than shear stress (R2 ≥ 0.598) or unit stream power (R2 ≥ 0.537). Polysaccharides decreased the hydrodynamic parameters and the response rates of sheet erosion to hydrodynamics.


Assuntos
Hidrodinâmica , Chuva , Sedimentos Geológicos , Solo , Polissacarídeos
12.
PLoS One ; 17(4): e0267843, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35482778

RESUMO

BACKGROUND: Insomnia is the most common of the sleep disorders. Current pharmacotherapy treatment options are usually associated with adverse effects and withdrawal phenomena. Therapeutic alternatives with a more favorable safety profile for patients are needed. Mongolian medical warm acupuncture (MMWA) is an emerging therapeutic option for treating insomnia. However, the underlying mechanisms responsible for the anti-insomnia efficacy of the MMWA remain unclear. This study aims to investigate the effect of the MMWA on the alterations of the gut microbiota and serum metabolome in rats with insomnia. RESULTS: We found that the relative abundances of gut bacteria and the concentrations of several serum metabolites were obviously altered in PCPA-induced insomnia rats. The MMWA treatment exerted an anti-insomnia effect. In addition, the dysbiosis of the gut microbiota and the serum metabolites were ameliorated by the MMWA. Correlation analysis between the gut microbiota and metabolites suggested that the levels of Amide c18, Benzoyl chloride, Cytosine, and N, n-dimethylarginine were positively correlated with the relative abundance of Clostridium XlVa and Blautia, which characterized the insomnia rats. KEGG enrichment analysis identified the cAMP signaling pathway involving anti-insomnia effect of the MMWA. Moreover, the MMWA intervention significantly increased contents of butyrate in feces, while effectively inhibited the expression level of GAT-1 in brain tissues. CONCLUSION: This study reveals that the MMWA intervention might have a major impact on the modulation of host gut microbiota and metabolites, which in turn have a crucial role in the regulation of the host's signaling pathways associated with insomnia. The present study could provide useful ideas for the study of the intervention mechanisms of the MMWA in insomnia rat models.


Assuntos
Terapia por Acupuntura , Microbioma Gastrointestinal , Distúrbios do Início e da Manutenção do Sono , Animais , Disbiose/induzido quimicamente , Fezes/microbiologia , Gerbillinae , Humanos , Ratos , Distúrbios do Início e da Manutenção do Sono/terapia
13.
Iran J Immunol ; 18(4): 268-278, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34931613

RESUMO

BACKGROUND: It was reported that targeting the Toll-like receptor9 (TLR9) signaling pathway can be a promising therapeuticstrategy forinterventions in various inflammatory and infectiousdiseases. However,it was not known whether the human TLR9 isresponsive to Brucellacytidine-phosphate-guanosine (CpG) DNAsequences and activatesthehost's innate immune system. OBJECTIVE: The present study aimed to identify the novel humanTLR9agonists from Brucella CpG oligodeoxynucleotide(ODN) candidatesand verify their immune response regulatorymechanisms. METHODS: Molecular docking methods were used to discover potentagonists of the human TLR9. The potential molecules were furthervalidated by Western blot and enzyme-linked immunosorbentassay(ELISA). RESULTS: The experiment results showed a strong interactionandgood compatibility between the human TLR9 and BrucellaODN-1molecule. In addition, the induction of immune response byBrucella ODN-1 is a CpG-specific response. Moreover, the effectsof Brucella ODN-1 on cytokine response are dependent on theTLR9-mediated NF-κB pathway. CONCLUSION: These results indicated that the Brucella ODN-1 molecule canserve as a starting point to discover or designmore potent and specific TLR9 agonists that have the potential usein the treatment of infectious diseases.


Assuntos
Ilhas de CpG , Citocinas/imunologia , NF-kappa B , Receptor Toll-Like 9 , Brucella , Humanos , Leucócitos Mononucleares , Simulação de Acoplamento Molecular , Transdução de Sinais
14.
Biomed Res Int ; 2020: 8379358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32462021

RESUMO

MATERIALS AND METHODS: The petroleum ether (petrol), dichloromethane (CH2Cl2), ethyl acetate (EtOAc), and n-butyl alcohol (n-BuOH) fractions were isolated from alcohol extracts of D. moldavica L. Total phenolic and flavonoid contents and in vitro antioxidant activities of different fractions were evaluated. H9c2 cells were then treated with D. moldavica L. extracts before challenging with H2O2. Cell viability was determined by colorimetric assay, and ELISA was used to measure the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD). Apoptosis levels and mitochondrial membrane potential were measured by flow cytometry. The expressions of cell apoptosis regulatory proteins caspase-3, Bax, and Bcl-2 were determined by western blotting. RESULTS: Our results demonstrated that the EtOAc fraction from D. moldavica L. ethanol extract, which is rich in phenolic and flavonoid active constituents, had the strongest free radical scavenging activity. Additionally, this fraction increased H2O2-induced reduction in cell viability, SOD activity, and mitochondrial membrane potential. It also reduced H2O2-induced elevation in ROS production, contents of LDH and MDA, and H9c2 apoptosis. We further found that the EtOAc fraction increased Bcl-2 expression, while it decreased caspase-3 and Bax expressions induced by H2O2 in H9c2 cells. CONCLUSIONS: Our data revealed that the EtOAc fraction from D. moldavica L. ethanol extract ameliorates H2O2-induced cardiotoxicity via antiapoptotic and antioxidant mechanisms.


Assuntos
Apoptose/efeitos dos fármacos , Peróxido de Hidrogênio/efeitos adversos , Lamiaceae/química , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/farmacologia , Caspase 3 , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/farmacologia , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fenóis/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2 , Ratos , Superóxido Dismutase/metabolismo
15.
Front Immunol ; 11: 606045, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33613526

RESUMO

The inflammatory immune microenvironment plays an important role in the development of cardiac hypertrophy. Exosomes have emerged as the potent modulators of inflammatory responses. This study aimed to determine how exosomes derived from angiotensin II (Ang II)-induced hypertrophic cardiomyocytes (HCs) interfere with the inflammatory signal pathways in macrophages. Herein, we showed that increased exosome release was observed in HCs when compared to normal cardiomyocytes (NCs). Incubation of the murine macrophage cell line RAW264.7 in the presence of exosomes isolated from the culture media of HCs triggers the secretion of inflammatory cytokines interleukin (IL)-6 and IL-8. Cytokines release induced by HCs-derived exosomes was prevented by down-regulation of Argonaute2 (AGO2), suggesting that the non-coding RNAs were involved in exosome-induced inflammatory responses in RAW 264.7 macrophages. RNA sequencing assays further demonstrated that a total of seven microRNAs were differentially expressed between NCs-derived and HCs-derived exosomes. Importantly, miR-155 played a crucial role in the initiation of inflammation in macrophages. Further analyses demonstrated that HCs-derived exosomes induced the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 via miR-155. Our results support the concept that exosomal microRNAs have emerged as important inflammatory response modulators regulating cardiac hypertrophy.


Assuntos
Cardiomegalia/enzimologia , Exossomos/metabolismo , Inflamação/enzimologia , Macrófagos/enzimologia , MicroRNAs/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miócitos Cardíacos/metabolismo , Angiotensina II/toxicidade , Animais , Animais Recém-Nascidos , Cardiomegalia/genética , Cardiomegalia/patologia , Comunicação Celular , Microambiente Celular , Exossomos/efeitos dos fármacos , Exossomos/genética , Exossomos/patologia , Humanos , Inflamação/genética , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Macrófagos/patologia , Camundongos , MicroRNAs/genética , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Fosforilação , Células RAW 264.7 , Ratos Wistar , Transdução de Sinais
16.
Front Physiol ; 10: 1049, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31481897

RESUMO

Exosomes, which are membrane-enclosed nanovesicles released by almost all cell types, have been recognized to play important roles in mediating cell-cell communication. In recent years, the physiological and pathological effects of exosomes on cardiovascular disease have been extensively studied. Exosomes can transfer proteins, mRNAs, microRNAs, and other bioactive molecules to recipient cells to influence their biological properties. In recent years, accumulating evidence has suggested that cardiomyocyte-derived exosomes play an important role in the progression of cardiovascular disease. Here, we summarize the functional roles of cardiomyocyte-derived exosomes in cardiovascular physiology and pathology.

17.
Biomed Res Int ; 2019: 8250619, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31240226

RESUMO

BACKGROUND: The purpose of this study was to evaluate the alteration of the gut microbiota and its effect on adenosine monophosphate-activated protein kinase (AMPK)/nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) signaling pathway in two-kidney one-clip (2K1C) rats. METHODS: The 2K1C rat models were established. The rats were randomly divided into the following 2 groups: 2K1C group and sham group. Alterations of the gut microbiota were analyzed based on the high throughput sequencing method. Plasma concentrations of short chain fatty acids (SCFAs) were measured by chromatography. The protein expression of phosphorylated AMPK and acetyl-CoA carboxylase (ACC) was determined by western blotting. NADPH oxidase activity was measured by a luminometer. RESULTS: Microbial community analyses revealed that the structure and composition of the gut microbiota were significantly disrupted in 2K1C rats when compared to sham rats. This disruption was associated with the drastic increase in relative abundance of the genera Prevotella and the decrease in SCFA-producing bacterial population. We further confirm that SCFAs produced by the gut microbiota influence NADPH oxidase activity through AMPK. CONCLUSIONS: Our data implicated the important role of gut microbiota in the regulation of AMPK/NADPH oxidase signaling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Microbioma Gastrointestinal/fisiologia , Rim/metabolismo , NADPH Oxidases/metabolismo , Transdução de Sinais/fisiologia , Acetil-CoA Carboxilase/metabolismo , Animais , Bactérias/classificação , Bactérias/metabolismo , Ácidos Graxos Voláteis/sangue , Fezes/microbiologia , Humanos , Masculino , Metagenômica , Modelos Animais , Nitratos/sangue , Nitritos/sangue , Fosforilação , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
18.
Front Microbiol ; 10: 1249, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244794

RESUMO

Background: Dracocephalum moldavica L. is a popular traditional medicine used by many countries, which has a wide range of pharmacological effects. The aim of this work was to investigate the antimicrobial effects of D. moldavica L. extracts against clinical isolates of Staphylococcus aureus. Our results demonstrated that the minimal inhibitory concentration (MIC) for 50 and 90% of S. aureus isolates (MIC50 and MIC90) of the ethyl acetate (EtOAc) fraction from D. moldavica L. ethanol extract were 780 and 1,065 µg/ml, respectively. We further observed that the EtOAc fraction disrupted 24-h biofilm caused cell membrane damage and irregular cell shape. Additionally, the EtOAc fraction showed slight to moderate toxic effects on human epidermal keratinocyte (HaCaT) cells. Moreover, the results of the differential proteome revealed that 231 proteins were upregulated, while 61 proteins were downregulated in S. aureus after treatment with the EtOAc fraction. The differentially expressed proteins were functionally categorized by the Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. These proteins contribute to membrane damage, inhibition of biofilm formation, and changes in energy metabolism. Thus, the EtOAc fraction of D. moldavica L. ethanol extract, as a natural product, has the potential to be used as an antimicrobial agent to control the clinical isolates of S. aureus.

19.
BMC Res Notes ; 12(1): 27, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30646924

RESUMO

OBJECTIVE: This study investigated the distribution of acquired antibiotic resistance genes in Enterococcus species isolated from clinical patients in Baotou, China. RESULT: A total of 73 enterococca lisolates from clinical samples were collected from December 2016 to September 2017. Of the 73 enterococcal isolates, 36 (49.3%), 35 (47.9%), 1 (1.4%), and 1 (1.4%) were identified as E. faecium, E. faecalis, E. gallinarum, and E. raffinosus, respectively. The resistance rates of the enterococci to nitrofurantoin, tetracycline, gentamicin (high-level), ampicillin, ciprofloxacin and erythromycin were 24.7%, 49.3%, 50.7%, 54.8%, 74.0% and 89.0%, respectively. The most prevalent aminoglycoside resistance genes were aac(6')-Ie-aph(2″)-Ia (64.9%) and aph(3')IIIa (64.9%). The most common erythromycin ribosome methylation gene was erm(B) (67.7%), followed by erm(A) (4.6%) and erm(C) (1.5%). The tetracycline resistance gene tetM was found to be present in 100.0% of the tetracycline-resistant strains of enterococci. Thus, E. faecium and E. faecalis were identified as the species of greatest clinical importance associated with hospital-acquired enterococcal infections in Baotou, China. The antimicrobial resistance genes aac(6')-Ie-aph(2″)-Ia, aph(3')IIIa, tetM, and erm(B) were significantly more prevalent among the enterococcal isolates. Therefore, action should be taken to monitor drug resistance and antimicrobial resistance genes to manage multi-drug-resistant enterococcal infections.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana/genética , Enterococcus/genética , Enterococcus/isolamento & purificação , Genes Bacterianos/genética , Hospitais Universitários , China , Humanos
20.
Am J Cancer Res ; 8(1): 120-131, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29416925

RESUMO

Accumulating evidences have illuminated that an amount of microRNAs are involved in human diseases including hepatocellular carcinoma (HCC). In this study, we found that the expression of miR-382 in HCC tissues was down-regulated compared with the non-cancerous tissues. Over-expression of miR-382 could significantly inhibit the migration and invasion of HCC cells in vitro and in vivo. Bioinformatic algorithms and luciferase reporter assays suggested that Golgi Membrane Protein 1 (GOLM1) was a direct target of miR-382. Interestingly, we found the down-regulation of GOLM1 in HCC cells could rescue these cells from miR-382-mediated suppression of migration and invasion. Our findings might demonstrate that miR-382 inhibited the metastasis of HCC by targeting GOLM1. Furthermore, cox proportional hazards analyses suggested that low expression of miR-382 was an independent prognostic factor for the HCC patients. In conclusion, our results highlighted that miR-382, a novel prognostic factor, target GOLM1 to inhibit metastasis of hepatocellular carcinoma.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...