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1.
Nature ; 621(7980): 830-839, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37674079

RESUMO

The immune-suppressive tumour microenvironment represents a major obstacle to effective immunotherapy1,2. Pathologically activated neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a critical component of the tumour microenvironment and have crucial roles in tumour progression and therapy resistance2-4. Identification of the key molecules on PMN-MDSCs is required to selectively target these cells for tumour treatment. Here, we performed an in vivo CRISPR-Cas9 screen in a tumour mouse model and identified CD300ld as a top candidate of tumour-favouring receptors. CD300ld is specifically expressed in normal neutrophils and is upregulated in PMN-MDSCs upon tumour-bearing. CD300ld knockout inhibits the development of multiple tumour types in a PMN-MDSC-dependent manner. CD300ld is required for the recruitment of PMN-MDSCs into tumours and their function to suppress T cell activation. CD300ld acts via the STAT3-S100A8/A9 axis, and knockout of Cd300ld reverses the tumour immune-suppressive microenvironment. CD300ld is upregulated in human cancers and shows an unfavourable correlation with patient survival. Blocking CD300ld activity inhibits tumour development and has synergistic effects with anti-PD1. Our study identifies CD300ld as a critical immune suppressor present on PMN-MDSCs, being required for tumour immune resistance and providing a potential target for cancer immunotherapy.


Assuntos
Células Supressoras Mieloides , Neoplasias , Neutrófilos , Receptores Imunológicos , Animais , Humanos , Camundongos , Sistemas CRISPR-Cas , Progressão da Doença , Edição de Genes , Imunoterapia , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/patologia , Neoplasias/imunologia , Neoplasias/patologia , Neutrófilos/imunologia , Neutrófilos/patologia , Receptores Imunológicos/imunologia , Análise de Sobrevida , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/patologia , Microambiente Tumoral , Ativação Linfocitária
2.
BMC Psychiatry ; 24(1): 335, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702695

RESUMO

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a complex condition associated with alcohol use disorder (AUD), characterized by significant variations in symptom severity among patients. The psychological and emotional symptoms accompanying AWS significantly contribute to withdrawal distress and relapse risk. Despite the importance of neural adaptation processes in AWS, limited genetic investigations have been conducted. This study primarily focuses on exploring the single and interaction effects of single-nucleotide polymorphisms in the ANK3 and ZNF804A genes on anxiety and aggression severity manifested in AWS. By examining genetic associations with withdrawal-related psychopathology, we ultimately aim to advance understanding the genetic underpinnings that modulate AWS severity. METHODS: The study involved 449 male patients diagnosed with alcohol use disorder. The Self-Rating Anxiety Scale (SAS) and Buss-Perry Aggression Questionnaire (BPAQ) were used to assess emotional and behavioral symptoms related to AWS. Genomic DNA was extracted from peripheral blood, and genotyping was performed using PCR. RESULTS: Single-gene analysis revealed that naturally occurring allelic variants in ANK3 rs10994336 (CC homozygous vs. T allele carriers) were associated with mood and behavioral symptoms related to AWS. Furthermore, the interaction between ANK3 and ZNF804A was significantly associated with the severity of psychiatric symptoms related to AWS, as indicated by MANOVA. Two-way ANOVA further demonstrated a significant interaction effect between ANK3 rs10994336 and ZNF804A rs7597593 on anxiety, physical aggression, verbal aggression, anger, and hostility. Hierarchical regression analyses confirmed these findings. Additionally, simple effects analysis and multiple comparisons revealed that carriers of the ANK3 rs10994336 T allele experienced more severe AWS, while the ZNF804A rs7597593 T allele appeared to provide protection against the risk associated with the ANK3 rs10994336 mutation. CONCLUSION: This study highlights the gene-gene interaction between ANK3 and ZNF804A, which plays a crucial role in modulating emotional and behavioral symptoms related to AWS. The ANK3 rs10994336 T allele is identified as a risk allele, while the ZNF804A rs7597593 T allele offers protection against the risk associated with the ANK3 rs10994336 mutation. These findings provide initial support for gene-gene interactions as an explanation for psychiatric risk, offering valuable insights into the pathophysiological mechanisms involved in AWS.


Assuntos
Anquirinas , Fatores de Transcrição Kruppel-Like , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Anquirinas/genética , Adulto , Fatores de Transcrição Kruppel-Like/genética , Pessoa de Meia-Idade , Síndrome de Abstinência a Substâncias/genética , Síndrome de Abstinência a Substâncias/psicologia , Alcoolismo/genética , Alcoolismo/psicologia , Agressão/psicologia , Agressão/fisiologia , Ansiedade/genética , Ansiedade/psicologia , Epistasia Genética , Sintomas Comportamentais/genética , Predisposição Genética para Doença/genética , Alelos
3.
Crit Rev Food Sci Nutr ; : 1-23, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36756885

RESUMO

Pectin is a complex polysaccharide found in plant cell walls and interlayers. As a food component, pectin is benefit for regulating intestinal flora. Metabolites of intestinal flora, including short-chain fatty acids (SCFAs), bile acids (BAs) and lipopolysaccharides (LPS), are involved in blood glucose regulation. SCFAs promote insulin synthesis through the intestine-GPCRs-derived pathway and hepatic adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway to promote hepatic glycogen synthesis. On the one hand, BAs stimulate intestinal L cells and pancreatic α cells to secrete Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) through receptors G protein-coupled receptor (TGR5) and farnesoid X receptor (FXR). On the other hand, BAs promote hepatic glycogen synthesis through AMPK pathway. LPS inhibits the release of inflammatory cytokines through Toll-like receptors (TLRs)-myeloid differentiation factor 88 (MYD88) pathway and mitogen-activated protein kinase (MAPK) pathway, thereby alleviating insulin resistance (IR). In brief, both SCFAs and BAs promote GLP-1 secretion through different pathways, employing strategies of increasing glucose consumption and decreasing glucose production to maintain normal glucose levels. Notably, pectin can also directly inhibit the release of inflammatory cytokines through the -TLRs-MYD88 pathway. These data provide valuable information for further elucidating the relationship between pectin-intestinal flora-glucose metabolism.

4.
BMC Public Health ; 23(1): 139, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36658507

RESUMO

BACKGROUND: Migration can be linked to the transmission of COVID-19. COVID-19 vaccine uptake and hesitancy among rural-to-urban migrant workers in China, the largest group of internal migrants in the world, has not been characterized. OBJECTIVE: To investigate COVID-19 vaccine uptake and identify vaccine hesitancy-associated factors among rural-to-urban migrant workers in the first round of COVID-19 vaccination in China. METHODS: A cross-sectional questionnaire-based survey was conducted, including 14,917 participants. Socio-demographics, COVID-19 vaccine uptake, vaccine hesitancy and its associated factors based on Vaccine Hesitancy Determinants Matrix (VHDM) were applied for the survey. Data were principally analyzed by logistic regression analysis. RESULTS: The COVID-19 vaccine uptake and vaccine hesitancy rates were 7.1% and 57.7%, respectively. Vaccine hesitancy was strongly associated with VHDM, including individual factors (female, higher annual income and fewer medical knowledge), group factors (less family support, friend support and public opinion support), COVID-19 epidemic factors (lower fatality, infection and emotional distress) and vaccine factors (less vaccine necessity, vaccine safety, vaccine efficacy, vaccine importance and vaccine reliability). CONCLUSION: The VHDM model has the potential utility in efforts to reduce COVID-19 vaccine hesitancy. Greater efforts should be put into addressing positive predictors associated with vaccine hesitancy.


Assuntos
COVID-19 , Migrantes , Feminino , Humanos , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Reprodutibilidade dos Testes , Hesitação Vacinal , Vacinação , China/epidemiologia
5.
J Clin Lab Anal ; 37(11-12): e24933, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37387262

RESUMO

BACKGROUND: Previous studies suggest that alcohol dependence is associated with increased risk of depression. The occurrence of depressive symptoms is related to polymorphisms in various genetic regions. This study aimed to investigate the interaction of RETN gene polymorphisms (rs1477341, rs3745368) with alcohol dependence on depressive symptoms in adult male during acute alcohol withdrawal. METHODS: A total of 429 male adults were recruited in this study. Alcohol dependence was assessed using the Michigan alcoholism screening test (MAST). Depression was assessed using the 20-item self-rating depression scale (SDS). Hierarchical regression analysis was used to evaluate the interaction between genes and alcohol dependence on depression. Region of significance (ROS) test was used to explain the interaction effect. The strong and weak forms of the differential susceptibility and diathesis models were used to determine which fits the data better. RESULTS: Our results showed that MAST scores were significantly positively associated with SDS scores (r = 0.23, p < 0.01) in alcohol-dependent patients during alcohol withdrawal. The interaction between genotype and alcohol dependence was significant (ß = -0.14, p < 0.05) in a strong diathesis-stress model. Susceptibility for depression symptoms was associated with alcohol dependence in RETN rs1477341 A carriers. Specifically, those that showed more alcohol dependence and the A allele of RETN rs1477341 exhibited more depression symptoms. However, RETN rs3745368 had no significant interaction with alcohol dependence. CONCLUSIONS: The A allele of RETN rs1477341 may correlate with susceptibility to depression symptoms in alcohol-dependent individuals during acute alcohol withdrawal.


Assuntos
Alcoolismo , Síndrome de Abstinência a Substâncias , Adulto , Humanos , Masculino , Alcoolismo/complicações , Alcoolismo/genética , Depressão/epidemiologia , Depressão/genética , Suscetibilidade a Doenças , Polimorfismo Genético , Genótipo , Polimorfismo de Nucleotídeo Único/genética , Resistina/genética
6.
Plant Dis ; 107(4): 1060-1066, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36122196

RESUMO

The present study was performed to evaluate the effect of crop rotation on Fusarium mycotoxins and species in cereals in Sichuan Province. A total of 311 cereal samples were randomly collected and analyzed from 2018 to 2019 in Sichuan Province. The results of mycotoxin analysis showed that the major trichothecene mycotoxins in Sichuan Province were nivalenol (NIV) and deoxynivalenol (DON), and the mean concentration of total trichothecenes (including NIV, fusarenone X [4ANIV], DON, 3-acetyldeoxynivalenol [3ADON], and 15-acetyldeoxynivalenol [15ADON]) in wheat was significantly higher than that in maize and rice. The concentration of total trichothecenes in the succeeding crops was significantly higher than that in the previous crops. In addition, wheat grown after maize had reduced incidence and concentration of trichothecene mycotoxins compared with that grown after rice, and ratooning rice grown after rice had increased incidence and concentration of trichothecene mycotoxins. Our data indicated that Fusarium asiaticum with the NIV chemotype was predominant in wheat and rice samples, while the number of the NIV chemotypes of F. asiaticum and Fusarium meridionale and the 15ADON chemotype of Fusarium graminearum in maize were almost the same. Although the composition of Fusarium species was affected by crop rotations, there were no differences when comparing the same crop rotation except for the maize-wheat rotation. Moreover, the same species and chemotype of Fusarium strains originated from different crops in various rotations, but there were no significant differences in pathogenicity in wheat and rice. These results contribute to the knowledge of the effect of crop rotation on Fusarium mycotoxins and species affecting cereals in Sichuan Province, which may lead to improved strategies for control of Fusarium mycotoxins and fungal disease in China.


Assuntos
Fusarium , Micotoxinas , Oryza , Tricotecenos , Grão Comestível/microbiologia , Produtos Agrícolas , China , Triticum/microbiologia , Oryza/microbiologia , Produção Agrícola
7.
Int J Mol Sci ; 24(4)2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36834566

RESUMO

Hydroxyl-α-sanshool is the main alkylamide produced by Zanthoxylum armatum DC., and it is responsible for numbness after consuming Z. armatum-flavored dishes or food products. The present study deals with the isolation, enrichment, and purification of hydroxyl-α-sanshool. The results indicated that the powder of Z. armatum was extracted with 70% ethanol and then filtrated; the supernatant was concentrated to get pasty residue. Petroleum ether (60-90 °C) and ethyl acetate at a 3:2 ratio, with an Rf value of 0.23, were chosen as the eluent. Petroleum ether extract (PEE) and ethyl acetate-petroleum ether extract (E-PEE) were used as the suitable enriched method. Afterward, the PEE and E-PEE were loaded onto silica gel for silica gel column chromatography. Preliminary identification was carried out by TLC and UV. The fractions containing mainly hydroxyl-α-sanshool were pooled and dried by rotary evaporation. Lastly, all of the samples were determined by HPLC. The yield and recovery rates of hydroxyl-α-sanshool in the p-E-PEE were 12.42% and 121.65%, respectively, and the purity was 98.34%. Additionally, compared with E-PEE, the purity of hydroxyl-α-sanshool in the purification of E-PEE (p-E-PEE) increased by 88.30%. In summary, this study provides a simple, rapid, economical, and effective approach to the separation of high-purity hydroxyl-α-sanshool.


Assuntos
Zanthoxylum , Zanthoxylum/química , Sílica Gel , Extratos Vegetais/química , Cromatografia
8.
Int J Mol Sci ; 24(13)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37446158

RESUMO

Pellicle biofilm-forming bacteria Bacillus amyloliquefaciens are the major spoilage microorganisms of soy products. Due to their inherent resistance to antibiotics and disinfectants, pellicle biofilms formed are difficult to eliminate and represent a threat to food safety. Here, we assessed linalool's ability to prevent the pellicle of two spoilage B. amyloliquefaciens strains. The minimum biofilm inhibitory concentration (MBIC) of linalool against B. amyloliquefaciens DY1a and DY1b was 4 µL/mL and 8 µL/mL, respectively. The MBIC of linalool had a considerable eradication rate of 77.15% and 83.21% on the biofilm of the two strains, respectively. Scanning electron microscopy observations revealed that less wrinkly and thinner pellicle biofilms formed on a medium supplemented with 1/2 MBIC and 1/4 MBIC linalool. Also, linalool inhibited cell motility and the production of extracellular polysaccharides and proteins of the biofilm matrix. Furthermore, linalool exposure reduced the cell surface hydrophobicity, zeta potential, and cell auto-aggregation of B. amyloliquefaciens. Molecular docking analysis demonstrated that linalool interacted strongly with quorum-sensing ComP receptor and biofilm matrix assembly TasA through intermolecular hydrogen bonds, hydrophobic contacts, and van der Waals forces interacting with site residues. Overall, our findings suggest that linalool may be employed as a potential antibiofilm agent to control food spoilage B. amyloliquefaciens.


Assuntos
Bacillus amyloliquefaciens , Simulação de Acoplamento Molecular , Biofilmes
9.
Biochem Biophys Res Commun ; 617(Pt 1): 42-47, 2022 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-35675737

RESUMO

Hematopoietic stem cell (HSC) transplantation represents an important curative therapy for numerous hematological and immune diseases. Many efforts have been applied to achieve attainable ex vivo HSC expansion. We previously showed that angiopoietin-like proteins 2 (Angptl2) binds and activates the immune inhibitory receptor human leukocyte immunoglobulin (Ig)-like receptor B2 (LILRB2) to support the expansion of HSC. However, soluble Angptl2 is unstable and the downstream signaling would be attenuated by ligand-binding triggered receptor endocytosis, compromising the potential of Angptl2 to expand HSCs. We proposed that membrane anchored Angptl2 will overcome these limitations. In this study, we constructed the C-terminal and N-terminal anchored membrane Angptl2 (Cm-Angptl2 and Nm-Angptl2) by adding a transmembrane domain at the C-terminal or an anchor sequence at the N-terminal respectively. Both forms of Angptl2 showed efficient expression on the surface of feeder cells. Nm-Angptl2, but not Cm-Angptl2, induces a potent activation of LILRB2 reporter, indicating the fibronectin (FBN) domain at the C-terminus of Angptl2 is essential to stimulate LILRB2 signaling. Compared to soluble Angptl2, Nm-Angptl2 displays higher activities to activate LILRB2 reporter, and to promote the expansion of mouse HSCs as determined by transplantation and limiting dilution assay. Our study revealed the importance of FBN domain for Angptl2 to activate LILRB2 and demonstrated that Nm-Angptl2 have enhanced activities than the soluble protein in LILRB2 activation and HSC expansion, providing a strategy to explore the mode of ligand induced receptor signaling, and an optimized approach to expand HSCs ex vivo.


Assuntos
Proteína 2 Semelhante a Angiopoietina , Transplante de Células-Tronco Hematopoéticas , Proteínas Semelhantes a Angiopoietina/metabolismo , Angiopoietinas/metabolismo , Animais , Células-Tronco Hematopoéticas/metabolismo , Ligantes , Camundongos , Receptores Imunológicos/metabolismo
10.
J Nanobiotechnology ; 20(1): 88, 2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35183183

RESUMO

Atherosclerosis (AS) is a leading cause of vascular diseases that severely threats the human health due to the lack of efficient therapeutic methods. During the development and progress of AS, macrophages play critical roles, which are polarized into pro-inflammatory M1 phenotype to excrete abundant cytokines and overproduce reactive oxygen species (ROS), and take up excess amount of lipid to form foam cells. In this work, we developed a MnO2-based nanomedicine to re-educate macrophages for targeting AS therapy. The MnO2 was one-pot synthesized under mild condition, showing intrinsic catalase-mimic activity for self-oxygenation by using endogenous H2O2 as substrate. Moreover, the mesoporous structure as well as the abundant metal coordination sites in MnO2 structure facilitated the loading of an anti-AS drug of curcumin (Cur), achieving extraordinarily high drug loading capacity of 54%. Cur displayed a broad spectrum of anti-oxidant and anti-inflammatory capabilities to repolarize M1 macrophages into M2 phenotype, and the catalytic MnO2 recovered the function of lipid efflux transporter to remove lipid from cells by suppressing HIF-1α. Collectively, the nanocarrier and the payload drug functioned as an all-active nanoplatform to synergistically alleviate the syndromes of AS. In ApoE-/- mice model, the nanosystem could significantly prolong the circulation half-life of Cur by sixfold, and enhance drug accumulation in atherosclerotic lesion by 3.5-fold after intravenous injection by virtue of surface hyaluronic acid (HA) modification. As a result, a robust anti-AS efficacy was achieved as evidenced by the decrease of atherosclerotic lesion, plaque area, lipid level.


Assuntos
Aterosclerose , Nanopartículas , Animais , Aterosclerose/tratamento farmacológico , Peróxido de Hidrogênio , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Camundongos , Nanopartículas/química , Óxidos/química
11.
BMC Pregnancy Childbirth ; 22(1): 19, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996368

RESUMO

BACKGROUND: Subacute thyroiditis (SAT) is rarely diagnosed in pregnant women, and only 7 cases have been reported to date. Thyroid dysfunction, especially hyperthyroidism, during pregnancy has been associated with both maternal and neonatal complications. Thus, the early diagnosis and treatment of SAT during pregnancy may be beneficial. We present a case report and literature review to complement the diagnostic evaluation and management of SAT during pregnancy. CASE PRESENTATION: A 27-year-old woman presented in gestational week 17 of her first pregnancy and had a negative prior medical history. She presented to the Endocrinology Department complaining of neck pain for one month that had intensified in the last five days. Physical examination revealed a diffusely enlarged thyroid gland that was firm and tender on palpation. The patient also had an elevated temperature and heart rate. The increasing and long-lasting pain coupled with a decreased level of thyroid-stimulating hormone indicated hyperthyroidism. Ultrasound findings were indicative of SAT. Importantly, the pain was so severe that 10 mg of oral prednisone per day was administered in gestational week 18, which was increased to 15 mg/d after 10 days that was discontinued in week 28. Levothyroxine was started in gestational week 24 and administered throughout the pregnancy. The patient responded well to the treatments, and her neck pain disappeared in gestational week 21. She gave birth to a healthy male in gestational week 41. CONCLUSION: SAT can be diagnosed and effectively managed during pregnancy, thus benefiting mothers and infants.


Assuntos
Complicações na Gravidez/diagnóstico , Tireoidite Subaguda/diagnóstico , Adulto , Feminino , Glucocorticoides/uso terapêutico , Humanos , Nascido Vivo , Cervicalgia/etiologia , Prednisona/uso terapêutico , Gravidez , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Testes de Função Tireóidea , Tireoidite Subaguda/tratamento farmacológico , Tiroxina/uso terapêutico , Resultado do Tratamento
12.
Int J Mol Sci ; 23(14)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35887160

RESUMO

Our previous study extracted and identified an antibacterial peptide that was named NP-6. Herein, we investigated the physicochemical properties of NP-6, and elucidated the mechanisms underlying its antimicrobial activity against Staphylococcus aureus. The results showed that the hemolysis activity of NP-6 was 2.39 ± 0.13%, lower than Nisin A (3.91 ± 0.43%) at the same concentration (512 µg/mL). Negligible cytotoxicity towards RAW264.7 cells was found when the concentration of NP-6 was lower than 512 µg/mL. In addition, it could keep most of its activity in fetal bovine serum. Moreover, transmission electron microscopy, confocal laser scanning microscopy, and flow cytometry results showed that NP-6 can destroy the integrity of the bacterial cell membrane and increase the membrane permeability. Meanwhile, NP-6 had binding activity with bacterial DNA and RNA in vitro and strongly inhibited the intracellular ß-galactosidase activity of S. aureus. Our findings suggest that NP-6 could be a promising candidate against S. aureus.


Assuntos
Antibacterianos , Staphylococcus aureus , Antibacterianos/farmacologia , Bactérias , Membrana Celular , Testes de Sensibilidade Microbiana , Peptídeos/farmacologia
13.
Eur J Vasc Endovasc Surg ; 59(1): 98-107, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31744785

RESUMO

OBJECTIVE: This study aimed to investigate the effect of long non-coding RNA (lncRNA) DLGAP1 antisense RNA 1 (DLGAP1-AS1) on vascular endothelial cell (VEC) injury via the phosphoinositide 3-kinase (PI3K)/Akt pathway in rat models of acute lower limb ischaemia-reperfusion (I/R). METHODS: Differentially expressed lncRNAs related to I/R were screened using the gene expression omnibus database. Acute lower limb I/R models were induced in male Wistar rats, in which the regulatory mechanisms of DLGAP1-AS1 silencing were analysed after the treatment of small interfering RNA (siRNA) against DLGAP1-AS1 or an inhibitor of the PI3K/Akt pathway. The relationship between DLGAP1-AS1 and the PI3K/Akt pathway was analysed. The levels of tumour necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1), as well as malondialdehyde (MDA) concentration and creatine kinase (CK) activity, were measured. The number of circulating endothelial cells (CECs) and apoptosis of VECs were identified. RESULTS: Microarray based analysis indicated that DLGAP1-AS1 was highly expressed in I/R, which was further confirmed by detection of expression in rat models of acute lower limb I/R. Notably, the treatment of siRNA against DLGAP1-AS1 led to the activation of the PI3K/Akt pathway. In response to siRNA against DLGAP1-AS1, the levels of TNF-α and VCAM-1 were decreased, and MDA concentration and CK activity was downregulated. Reduced CEC numbers and suppressed VEC apoptosis were also observed. CONCLUSION: DLGAP1-AS1 silencing could further suppress the oxidative stress, exert an anti-apoptosis effect, and reduce inflammatory reaction, whereby VEC injury is alleviated by activation of the PI3K/Akt pathway in rats with acute lower limb I/R.


Assuntos
Apoptose/genética , Células Endoteliais/patologia , RNA Longo não Codificante/metabolismo , Traumatismo por Reperfusão/genética , Transdução de Sinais/genética , Animais , Proliferação de Células/genética , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Masculino , Estresse Oxidativo/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia
14.
J Asian Nat Prod Res ; 22(2): 167-178, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30507305

RESUMO

In this study, we developed a novel liquid fermentation medium of Cordyceps militaris using pupa powder and wheat bran as nitrogen resources instead of the traditionally used peptone. This process not only reduced the cost by approximately 50%, but increased production by over 30%. Then, we explored a method to extract and purify cordycepin by combining hydrothermal reflux extraction with macroporous resin adsorption, which is inexpensive and suitable for the industrial production. The optimum conditions for hydrothermal reflux were extracting three times at 95 °C with 1:10 sample-to-water ratio, and the cordycepin purity with macroporous resin HPD-100 reached 95.23%.[Formula: see text].


Assuntos
Cordyceps , Desoxiadenosinas , Fermentação , Estrutura Molecular
15.
Appl Microbiol Biotechnol ; 103(5): 2217-2228, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30623204

RESUMO

Antimicrobial peptides (AMPs) have generated growing attention because of the increasing bacterial resistance. However, the discovery and identification of AMPs have proven to be challenging due to the complex purification procedure associated with conventional methods. For the reasons given above, it is necessary to explore more efficient ways to obtain AMPs. We established a new method for discovery and identification of novel AMPs by proteomics and bioinformatics from Zanthoxylum bungeanum Maxim seeds protein hydrolysate directly. This process was initially achieved by employing ultra-performance liquid chromatography-electrospray ionization-mass spectrometry/mass (UPLC-ESI-MS/MS) spectrometry to identify peptides derived from Z. bungeanum Maxim seed protein hydrolysates. Three online servers were introduced to predict potential AMPs. Sixteen potential AMPs ranging from 1.5 to 2.7 kDa were predicted and chemically synthesized, one of which, designated NP-6, inhibited activity against all the tested strains according to antimicrobial assay. Time-killing assay indicated that NP-6 could quickly kill almost all the Escherichia coli within 180 min and Staphylococcus aureus at 360 min. Moreover, the simulation 3D structure of NP-6 was consisted of α-helix and random coil, and this was verified by circular dichroism (CD) spectra. At last, the scanning electron microscope (SEM) images of E. coli and S. aureus treated by NP-6 demonstrated that NP-6 had a significant effect on bacteria cell morphology. Our findings provide an efficient approach for discovery of AMPs, and Z. bungeanum Maxim seeds may be a nature resource to extract antimicrobial agents.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Escherichia coli/efeitos dos fármacos , Sementes/química , Staphylococcus aureus/efeitos dos fármacos , Zanthoxylum/química , Cromatografia Líquida de Alta Pressão , Biologia Computacional/métodos , Descoberta de Drogas/métodos , Testes de Sensibilidade Microbiana , Hidrolisados de Proteína/análise , Hidrolisados de Proteína/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
16.
Appl Microbiol Biotechnol ; 103(16): 6593-6604, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31286166

RESUMO

A novel antimicrobial peptide named NP-6 was identified in our previous work. Here, the mechanisms of the peptide against Escherichia coli (E. coli) were further investigated, as well as the peptide's resistance to temperature, pH, salinity, and enzymes. The transmission electron microscopy (TEM), confocal laser scanning microcopy (CLSM), and flow cytometric (FCM) analysis, combined with measurement of released K+, were performed to evaluate the effect of NP-6 E. coli cell membrane. The influence of NP-6 on bacterial DNA/RNA and enzyme was also investigated. The leakage of K+ demonstrated that NP-6 could increase the permeability of E. coli cell membrane. The ATP leakage, FCM, and CLSM assays suggested that NP-6 caused the disintegration of bacterial cell membrane. The TEM observation indicated that NP-6 could cause the formation of empty cells and debris. Besides, the DNA-binding assay indicated that NP-6 could bind with bacterial genomic DNA in a way that ethidium bromide (EB) did, and suppress the migration of DNA/RNA in gel retardation. Additionally, NP-6 could also affect the activity of ß-galactosidase. Finally, the effect of different surroundings such as heating, pH, ions, and protease on the antimicrobial activity of NP-6 against E. coli was also investigated. Results showed that the peptide was heat stable in the range of 60~100 °C and performed well at pH 6.0~8.0. However, the antimicrobial activity of NP-6 decreased significantly in the presence of Mg2+/Ca2+, and after incubation with trypsin/proteinase K. The results will provide a theoretical support in the further application of NP-6.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Membrana Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Membrana Celular/ultraestrutura , DNA Bacteriano/metabolismo , Estabilidade de Medicamentos , Escherichia coli/ultraestrutura , Concentração de Íons de Hidrogênio , Viabilidade Microbiana/efeitos dos fármacos , Ligação Proteica , Salinidade , Sementes/química , Temperatura , Zanthoxylum/química , beta-Galactosidase/antagonistas & inibidores
17.
Molecules ; 23(11)2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30453539

RESUMO

We investigated the permselectivity and interfacial electron transfers of an amphiphilic branch-tailed fluorosurfactant self-assembled monolayer (FS-SAM) on a gold electrode by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The FS-SAM was prepared by a self-assembly technique and a "click" reaction. The barrier property and interfacial electron transfers of the FS-SAM were also evaluated using various probes with different features. The FS-SAM allowed a higher degree of permeation by small hydrophilic (Cl- and F-) electrolyte ions than large hydrophobic (ClO4- and PF6-) ones. Meanwhile, the redox reaction of the Fe(CN)63- couple was nearly completely blocked by the FS-SAM, whereas the electron transfer of Ru(NH3)63+ was easier than that of Fe(CN)63-, which may be due to the underlying tunneling mechanism. For hydrophobic dopamine, the hydrophobic bonding between the FS-SAM exterior fluoroalkyl moieties and the hydrophobic probes, as well as the hydration resistance from the interior hydration shell around the oligo (ethylene glycol) moieties, hindered the transport of hydrophobic probes into the FS-SAM. These results may have profound implications for understanding the permselectivity and electron transfers of amphiphilic surfaces consisting of molecules containing aromatic groups and branch-tailed fluorosurfactants in their structures.


Assuntos
Eletroquímica/métodos , Eletrodos , Elétrons , Fluorescência , Ouro/química , Tensoativos/química , Transporte de Elétrons , Cinética , Oxirredução
18.
J Food Sci Technol ; 55(7): 2786-2794, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30042595

RESUMO

Volatile oil in Chrysanthemum morifolium Ramat (C. morifolium) was extracted by the method of water vapor distillation and its chemical components was identified by gas-chromatography coupled with mass spectrometry (GC-MS). The volatile oil are evaluated for antibacterial activity against Escherichia coli, Staphylococcus aureus, Salmonella enteritids, Pseudomonas aeruginosa and Bacillus subtilis. Effects of surfactant, temperature, pH and ultraviolet light on antibacterial activity stability of volatile oil were analyzed too. Total 56 compounds were identified in C. morifolium volatile oil. The main constituents in C. morifolium volatile oil were monoterpenes and sesquiterpenes compounds, including hydrocarbons, esters, aldehydes, ketones, phenols and organic acids. α-curcumene was the most abundant volatile component (12.55%). The volatile oil showed promising antibacterial activity against 5 selected strains. The inhibitory effect on P. aeruginosa exhibited maximum inhibition zone diameter 20.43 mm, and E. coli showed 12.29 mm. The volatile oil treated with surfactant Tween 20 showed the strongest antibacterial activity, followed by Tween 80 and the SDS lowest, which showed the lowest. pH also had different effect on antibacterial activity stability of the C. morifolium volatile oil. No significant difference effect on antibacterial activity stability of volatile oil was observed with temperature and UV treatment.

20.
J Virol ; 88(20): 12163-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25078699

RESUMO

The interferon (IFN)-inducible viperin protein restricts a broad range of viruses. However, whether viperin plays a role during herpes simplex virus 1 (HSV-1) infection is poorly understood. In the present study, it was shown for the first time that wild-type (WT) HSV-1 infection couldn't induce viperin production, and ectopically expressed viperin inhibited the replication of UL41-null HSV-1 but not WT viruses. The underlying molecular mechanism is that UL41 counteracts viperin's antiviral activity by reducing its mRNA accumulation.


Assuntos
Herpesvirus Humano 1/fisiologia , Proteínas/antagonistas & inibidores , Proteínas Virais/fisiologia , Células HEK293 , Humanos , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Proteínas/fisiologia , Replicação Viral/fisiologia
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