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1.
J Neurovirol ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36070137

RESUMO

Fatty acid-binding proteins (FABPs) are relevant to multiple neurodegenerative diseases. However, the roles and mechanisms of FABPs in HIV-associated neurocognitive disorder (HAND) remain yet unclear. In this study, cultured BV-2 microglial cells and HT-22 neuronal cells were used for in vitro experiments and HAND mouse models were constructed through intracerebroventricular injection of lentiviral vectors for in vivo experiments. FABP expression was determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. The interrelationship between Fabp4 and NF-κB signaling was investigated using chromatin immunoprecipitation, qRT-PCR, and Western blot. The role of Fabp4 in regulating inflammatory response was determined using qRT-PCR, enzyme-linked immunosorbent assay, Western blot, and immunofluorescence staining. Cell viability and apoptosis were analyzed using cell counting kit-8 assay and flow cytometry assay, respectively. Our results suggested an upregulation of Fabp4 expression in the presence of Tat. Tat-induced Fabp4 expression was directly regulated by NF-κB p65, followed by, Fabp4 facilitating Tat-activated NF-κB signaling pathway. We also observed that Fabp4 knockdown in microglial cells significantly suppressed inflammatory response and neuronal apoptosis both in vitro and in vivo. In conclusion, the presence of Tat in microglial cells results in Fabp4 and NF-κB to form a positive feedback loop leading to exacerbate inflammatory response and neuronal apoptosis.

2.
Am J Physiol Renal Physiol ; 323(4): F411-F424, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35979968

RESUMO

While angiotensin-converting enzyme (ACE) regulates blood pressure by producing angiotensin II as part of the renin-angiotensin system, we recently reported that elevated ACE in neutrophils promotes an effective immune response and increases resistance to infection. Here, we investigate if such neutrophils protect against renal injury in immune complex (IC)-mediated crescentic glomerulonephritis (GN) through complement. Nephrotoxic serum nephritis (NTN) was induced in wild-type and NeuACE mice that overexpress ACE in neutrophils. Glomerular injury of NTN in NeuACE mice was attenuated with much less proteinuria, milder histological injury, and reduced IC deposits, but presented with more glomerular neutrophils in the early stage of the disease. There were no significant defects in T and B cell functions in NeuACE mice. NeuACE neutrophils exhibited enhanced IC uptake with elevated surface expression of FcγRII/III and complement receptor CR1/2. IC uptake in neutrophils was enhanced by NeuACE serum containing elevated complement C3b. Given no significant complement activation by ACE, this suggests that neutrophil ACE indirectly preactivates C3 and that the C3b-CR1/2 axis and elevated FcγRII/III play a central role in IC elimination by neutrophils, resulting in reduced glomerular injury. The present study identified a novel renoprotective role of ACE in glomerulonephritis; elevated neutrophilic ACE promotes elimination of locally formed ICs in glomeruli via C3b-CR1/2 and FcγRII/III, ameliorating glomerular injury.NEW & NOTEWORTHY We studied immune complex (IC)-mediated crescentic glomerulonephritis in NeuACE mice that overexpress ACE only in neutrophils. Such mice show no significant defects in humoral immunity but strongly resist nephrotoxic serum nephritis (less proteinuria, milder histological damage, reduced IC deposits, and more glomerular neutrophils). NeuACE neutrophils enhanced IC uptake via increased surface expression of CR1/2 and FcgRII/III, as well as elevated serum complement C3b. These results suggest neutrophil ACE as a novel approach to reducing glomerulonephritis.


Assuntos
Glomerulonefrite , Nefrite , Angiotensina II/metabolismo , Animais , Complexo Antígeno-Anticorpo/metabolismo , Complemento C3b/metabolismo , Glomerulonefrite/metabolismo , Camundongos , Nefrite/metabolismo , Neutrófilos/metabolismo , Proteinúria/metabolismo
3.
Front Immunol ; 12: 744300, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777356

RESUMO

As first responder cells in host defense, neutrophils must be carefully regulated to prevent collateral tissue injury. However, the intracellular events that titrate the neutrophil's response to inflammatory stimuli remain poorly understood. As a molecular switch, Ras activity is tightly regulated by Ras GTPase activating proteins (RasGAP) to maintain cellular active-inactive states. Here, we show that RASAL3, a RasGAP, is highly expressed in neutrophils and that its expression is upregulated by exogenous stimuli in neutrophils. RASAL3 deficiency triggers augmented neutrophil responses and enhanced immune activation in acute inflammatory conditions. Consequently, mice lacking RASAL3 (RASAL3-KO) demonstrate accelerated mortality in a septic shock model via induction of severe organ damage and hyperinflammatory response. The excessive neutrophilic hyperinflammation and increased mortality were recapitulated in a mouse model of sickle cell disease, which we found to have low neutrophil RASAL3 expression upon LPS activation. Thus, RASAL3 functions as a RasGAP that negatively regulates the cellular activity of neutrophils to modulate the inflammatory response. These results demonstrate that RASAL3 could serve as a therapeutic target to regulate excessive inflammation in sepsis and many inflammatory disease states.


Assuntos
Inflamação/imunologia , Neutrófilos/imunologia , Proteínas Ativadoras de ras GTPase/imunologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
4.
Appl Opt ; 60(22): 6520-6525, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34612889

RESUMO

Based on asymmetric graphene ellipses, the tunable propagation characteristics of metamaterial absorber (MMA) have been investigated in the THz region. Two distinct absorption peaks of 84% and 90% are observed at 1.06 THz and 1.67 THz, respectively. Besides a high Q factor exceeding 20, the Fano resonance can also be modulated in a wide range (e.g., the frequency modulation depth reaches more than 43.8% if the Fermi energy level changes in the range of 0.2-1.0 eV). Additionally, a bidirectional THz MMA is achieved by replacing the metal substrate with a uniform graphene layer. If the terahertz wave is incident in the forward direction, the proposed graphene double stripe microstructure shows a typical MMA with its absorption reaching 88%. On the other hand, if the terahertz wave is incident in the reverse direction, the graphene double stripe microstructure behaves as a reflective modulator, and its amplitude and frequency MD will reach 60% and 85%. These results contribute to the design of tunable THz devices, such as filters, absorbers, and modulators.

5.
Front Pharmacol ; 12: 707696, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526897

RESUMO

Neuroinflammatory response is the immune response mechanism of the innate immune system of the central nervous system. Both primary and secondary injury can activate neuroinflammatory response. Among them, the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a key role in the inflammatory response of the central system. Inflammasome is a type of pattern recognition receptor, a cytoplasmic polyprotein complex composed of members of the Nod-like receptor (NLR) family and members of the pyrin and HIN domain (PYHIN) family, which can be affected by a variety of pathogen-related molecular patterns or damage-related molecular patterns are activated. As one of the research hotspots in the field of medical research in recent years, there are increasing researches on immune function abnormalities in the onset of neurological diseases such as depression, AD, ischemic brain injury and cerebral infarction, the NLRP3 inflammasome causes the activated caspase-1 to cleave pre-interleukin-1ß and pre-interleukin-18 into mature interleukin-1ß and interleukin-18, in turn, a large number of inflammatory factors are produced, which participate in the occurrence and development of the above-mentioned diseases. Targeted inhibition of the activation of inflammasomes can reduce the inflammatory response, promote the survival of nerve cells, and achieve neuroprotective effects. This article reviews NLRP3 inflammasome's role in neurological diseases and related regulatory mechanisms, which providing references for future research in this field.

6.
Fitoterapia ; 155: 104970, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34419561

RESUMO

The natural product Huperzine A isolated from Huperzia serrata is a targeted inhibitor of acetylcholinesterase that has been approved for clinical use in the treatment of Alzheimer's disease. Given the large demand for natural sources of Huperzine A  (Hup. A), efforts have been made to explore whether it is also produced by endophytic fungi from H. serrata and, if so, identify its biosynthetic pathway. These studies have indicated that endophytic fungi from H. serrata represent a huge and largely untapped resource for natural products (including Hup. A) with chemical structures that have been optimized by evolution for biological and ecological relevance. To date, more than three hundred endophytic fungi have been isolated from H. serrata, of which 9 strains can produce Hup. A, whilst more than 20 strains produce other important metabolites, such as polyketones, xanthones, alkaloids, steroids, triterpenoids, furanone derivatives, tremulane sesquitepenes and diterpenoids. In total, 200 secondary metabolites have been characterized in endophytic fungi from H. serrata to date. Functionally, some have cholinesterase-inhibitory or antibacterial activity. This review also considers the different classes of secondary metabolites produced by endophytic fungi, along with their possible applications. We systematically describe the taxonomy, biology, and chemistry of these secondary metabolites. It also summarizes the biosynthetic synthesis of metabolites, including that of Hup. A. The review will aid researchers in obtaining a clearer understanding of this plant-endophyte relationship to better exploit the excellent resources it offers that may be utilized by pharmaceutical industries.


Assuntos
Produtos Biológicos/isolamento & purificação , Fungos/química , Huperzia/microbiologia , Produtos Biológicos/farmacologia , Endófitos/química , Endófitos/isolamento & purificação , Fungos/isolamento & purificação , Estrutura Molecular , Metabolismo Secundário
7.
Sci Transl Med ; 13(604)2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321319

RESUMO

Angiotensin-converting enzyme inhibitors (ACEIs) are used by millions of patients to treat hypertension, diabetic kidney disease, and heart failure. However, these patients are often at increased risk of infection. To evaluate the impact of ACEIs on immune responses to infection, we compared the effect of an ACEI versus an angiotensin receptor blocker (ARB) on neutrophil antibacterial activity. ACEI exposure reduced the ability of murine neutrophils to kill methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Klebsiella pneumoniae in vitro. In vivo, ACEI-treated mice infected with MRSA had increased bacteremia and tissue bacteria counts compared to mice treated with an ARB or with no drug. Similarly, ACEIs, but not ARBs, increased the incidence of MRSA-induced infective endocarditis in mice with aortic valve injury. Neutrophils from ACE knockout (KO) mice or mice treated with an ACEI produced less leukotriene B4 (LTB4) upon stimulation with MRSA or lipopolysaccharide, whereas neutrophils overexpressing ACE produced more LTB4 compared to wild-type neutrophils. As a result of reduced LTB4 production, ACE KO neutrophils showed decreased survival signaling and increased apoptosis. In contrast, neutrophils overexpressing ACE had an enhanced survival phenotype. Last, in a cohort of human volunteers receiving the ACEI ramipril for 1 week, ACEI administration reduced neutrophil superoxide and reactive oxygen species production and neutrophils isolated from volunteers during ramipril treatment had reduced bactericidal activity. Together, these data demonstrate that ACEI treatment, but not ARB treatment, can reduce the bacterial killing ability of neutrophils.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Staphylococcus aureus Resistente à Meticilina , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Humanos , Camundongos , Camundongos Knockout , Neutrófilos
8.
Nanotechnology ; 32(41)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34237709

RESUMO

Polyacrylonitrile/Ti3C2TxMXene/silver nanoparticles fiber membranes with different silver nanoparticles contents and thickness of porous structure have been successfully prepared by electrospinning. Through the measurement of terahertz time domain spectrum, the shielding effect of the fiber membrane with 1% silver nanoparticles content can reach up to 12 dB. Moreover, the thickness of the spinning fiber membranes is controlled by adjusting the spinning time, so as to better analyze the influence of the thickness of the shielding performance in terahertz band. We attribute this excellent phenomenon to porous structure of the spun fiber membrane and combination of Ti3C2TxMXene with few-layers and silver nanoparticles to increase the absorption and conductivity of the fiber membrane, thereby enhancing the shielding effect in terahertz range. Meanwhile, the prepared polyacrylonitrile/Ti3C2TxMXene/silver nanoparticles fiber membranes show good stability and little change in terahertz shielding effect after high temperature annealing. This may provide potential ideas about the development of high-performance terahertz shielding materials, which are of great significance of terahertz electromagnetic shielding.

9.
Opt Lett ; 46(10): 2252-2255, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33988557

RESUMO

Metasurfaces consisting of different shapes of resonant units are used to manipulate light beams at subwavelength scales. In many cases, interactions among the resonant units are suppressed or avoided because of mode splitting in metasurfaces. Here we theoretically and numerically investigate metasurfaces composed of multiple antennas with anti-Hermitian coupling in a single layer. By utilizing the anti-Hermitian coupling, the results show that antennas with similar resonance frequencies at a subwavelength distance can individually absorb their corresponding frequency photons. The antennas whose reflection phase can be tailored by changing the number of antennas have the same resonance frequencies. This Letter paves the way for various potential applications in broadband absorption, photon sorting, image sensors, and phase modulation.

10.
Oncoimmunology ; 10(1): 1870811, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33537175

RESUMO

Granulocytes are key players in cancer metastasis. While tumor-induced de novo expansion of immunosuppressive myeloid-derived suppressor cells (MDSCs) is well-described, the fate and contribution of terminally differentiated mature neutrophils to the metastatic process remain poorly understood. Here, we show that in experimental metastatic cancer models, CXCR4hiCD62Llo aged neutrophils accumulate via disruption of neutrophil circadian homeostasis and direct stimulation of neutrophil aging mediated by angiotensin II. Compared to CXCR4loCD62Lhi naive neutrophils, aged neutrophils more robustly promote tumor migration and support metastasis through the increased release of several metastasis-promoting factors, including neutrophil extracellular traps (NETs), reactive oxygen species, vascular endothelial growth factors, and metalloproteinases (MMP-9). Adoptive transfer of aged neutrophils significantly enhanced metastasis of breast (4T1) and melanoma (B16LS9) cancer cells to the liver, and these effects were predominantly mediated by NETs. Our results highlight that in addition to modulating MDSC production, targeting aged neutrophil clearance and homeostasis may be effective in reducing cancer metastasis.


Assuntos
Armadilhas Extracelulares , Melanoma , Células Supressoras Mieloides , Idoso , Granulócitos , Humanos , Selectina L , Neutrófilos , Receptores CXCR4
11.
Pathogens ; 9(10)2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33050033

RESUMO

Toll-like receptor (TLR) signaling is an indispensable factor in immune cells activation. Many TLR ligands have been identified, and were characterized the immunological functions such as inflammatory cytokine production in immune cells. However, the anti-inflammatory response in TLR ligand-mediated manner is poorly understood. In this report, we show that bacterial lipoteichoic acid (LTA), which is a TLR2 ligand from gram-positive bacteria including Staphylococcus aureus (S. aureus), suppresses TLR-mediated inflammatory response in dendritic cells (DCs). The TLR ligand-induced Tumor Necrosis Factor-alpha (TNF-α) production was suppressed in the bone marrow derived dendritic cells (BMDCs) by co-treatment of LTA. The cellular activation, which was characterized as upregulations of CD80, CD86 and major histocompatibility complex II (MHC II) expression, was also suppressed in the TLR ligand stimulated BMDCs in the presence of LTA. While LTA itself didn't induced both TNF-α production and upregulation of cell surface markers. The LTA mediated immunosuppressive function was abolished by TLR2 blocking in lipopolysaccharide (LPS)-stimulated BMDCs. Furthermore, LTA also showed the immunosuppressive function in the generation of IFN-γ+CD4+ T (Th1) cells by attenuation of antigen presenting activity in the BMDCs. In the imiquimod (IMQ)-induced acute skin inflammation, LTA suppressed the inflammation by downregulation of the activation in skin accumulated DCs. Thus, LTA is a TLR2 dependent immunological suppressor against inflammatory response induced by other TLR ligands in the DCs.

12.
Cell Mol Biol Lett ; 25: 31, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32508938

RESUMO

Angiotensin-converting enzyme (ACE), a dicarboxypeptidase, plays a major role in the regulation of blood pressure by cleaving angiotensin I into angiotensin II (Ang II), a potent vasoconstrictor. Because of its wide substrate specificity and tissue distribution, ACE affects many diverse biological processes. In inflammatory diseases, including granuloma, atherosclerosis, chronic kidney disease and bacterial infection, ACE expression gets upregulated in immune cells, especially in myeloid cells. With increasing evidences connecting ACE functions to the pathogenesis of these acquired diseases, it is suggested that ACE plays a vital role in immune functions. Recent studies with mouse models of bacterial infection and tumor suggest that ACE plays an important role in the immune responses of myeloid cells. Inhibition of ACE suppresses neutrophil immune response to bacterial infection. In contrast, ACE overexpression in myeloid cells strongly induced bacterial and tumor resistance in mice. A detailed biochemical understanding of how ACE activates myeloid cells and which ACE peptide(s) (substrate or product) mediate these effects could lead to the development of novel therapies for boosting immunity against a variety of stimuli, including bacterial infection and tumor.


Assuntos
Hematopoese/imunologia , Inflamação/imunologia , Células Mieloides/imunologia , Peptidil Dipeptidase A/fisiologia , Imunidade Adaptativa , Animais , Infecções Bacterianas/imunologia , Humanos , Camundongos , Neoplasias/imunologia , Peptidil Dipeptidase A/imunologia
13.
Pathogens ; 9(2)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093163

RESUMO

Staphylococcus aureus (S. aureus) is a commensal bacterium in the human body; however, the bacterium frequently generates serious inflammation and infectious diseases. Some strains of S. aureus, such as methicillin-resistant Staphylococcus aureus (MRSA), are still a serious problem in public health facilities. Thus, an effective protection strategy is eagerly expected for the prevention and cure of MRSA infection. Here, we report that a specific fraction of an S. aureus lipoprotein (SA-LP) established a protective response against MRSA infection. The fractionated S. aureus lipoprotein SA-LP-F2, which is contained in 30-50 kDa of crude S. aureus lipoprotein (SA-LP-C), effectively activated dendritic cells (DCs) and the SA-LP-F2-pulsed DCs generated IFN-γ+CD4+ T (Th1) and IL-17A+CD4+ T (Th17) cells by in vitro antigen presentation. The SA-LP-F2 immunization upregulated the Th1 and Th17 populations so that MRSA colonization on the skin was suppressed during the challenge phase with MRSA. By following the effector T cell upregulation, the neutrophil function, which was a substantial effector cell against MRSA, was also enhanced in the SA-LP-F2-immunized mice. Finally, we found that the protective effect of SA-LP-F2 immunization was maintained for at least 90 days because the immunized mice continued to show a protective response during the MRSA challenge period. In the MRSA challenge, reactivated Th1 and Th17 populations were maintained in the SA-LP-F2-immunized mice as compared to naive mice. In addition, the neutrophil population was also upregulated in the mice. The memory CD4+ T cell (central memory T; TCM and effector memory T; TEM) population was established by SA-LP-F2 immunization and was maintained at higher levels than usual. Taken together, our findings may provide a breakthrough in the establishment of an immunization strategy against MRSA infection.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31918307

RESUMO

The aim of this work is to develop an efficient and economical method for the enrichment of total flavonoids from Pteris ensiformis Burm. extracts. Resin screening, adsorption kinetics, adsorption isotherms and thermodynamics were successively researched prior to the dynamic adsorption and desorption tests. NKA-II resin was chosen as the best adsorbent, and the adsorption data were best described by the pseudo-second-order kinetics model and Langmuir isotherm model. The optimum enrichment conditions were as follows: for adsorption the total flavonoids concentration, flow rate and volume of sample were 1.84 mg/mL, 2 BV/h and 5 BV, respectively, and for desorption the flavonoids-loaded NKA-II resin column was desorbed by 7 BV of 50% ethanol at a rate of 2 BV/h. The product had a 6.63-fold higher total flavonoids content than crude extracts, and the recovery yield of total flavonoids was 80.65%. Furthermore, flavonoids-enriched extracts exhibited higher in vitro scavenging activity against superoxide anion radical and hydroxyl radical than crude extracts. In addition, higher antiproliferative activity of flavonoids-enriched extracts against MCF-7 and HepG-2 cell lines was also found as compared to the crude extracts. The developed method is appropriate for large-scale enrichment of total flavonoids from Pteris ensiformis Burm. extracts in the food and pharmaceutical industries.


Assuntos
Antioxidantes , Proliferação de Células/efeitos dos fármacos , Flavonoides , Pteris/química , Adsorção , Antineoplásicos/análise , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antioxidantes/análise , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Flavonoides/análise , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Células Hep G2 , Humanos , Células MCF-7 , Extratos Vegetais/química , Resinas Sintéticas/química
15.
J Biol Chem ; 295(5): 1369-1384, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-31871049

RESUMO

Angiotensin-converting enzyme (ACE) affects blood pressure. In addition, ACE overexpression in myeloid cells increases their immune function. Using MS and chemical analysis, we identified marked changes of intermediate metabolites in ACE-overexpressing macrophages and neutrophils, with increased cellular ATP (1.7-3.0-fold) and Krebs cycle intermediates, including citrate, isocitrate, succinate, and malate (1.4-3.9-fold). Increased ATP is due to ACE C-domain catalytic activity; it is reversed by an ACE inhibitor but not by an angiotensin II AT1 receptor antagonist. In contrast, macrophages from ACE knockout (null) mice averaged only 28% of the ATP levels found in WT mice. ACE overexpression does not change cell or mitochondrial size or number. However, expression levels of the electron transport chain proteins NDUFB8 (complex I), ATP5A, and ATP5ß (complex V) are significantly increased in macrophages and neutrophils, and COX1 and COX2 (complex IV) are increased in macrophages overexpressing ACE. Macrophages overexpressing ACE have increased mitochondrial membrane potential (24% higher), ATP production rates (29% higher), and maximal respiratory rates (37% higher) compared with WT cells. Increased cellular ATP underpins increased myeloid cell superoxide production and phagocytosis associated with increased ACE expression. Myeloid cells overexpressing ACE indicate the existence of a novel pathway in which myeloid cell function can be enhanced, with a key feature being increased cellular ATP.


Assuntos
Trifosfato de Adenosina/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Células Mieloides/metabolismo , Peptidil Dipeptidase A/metabolismo , Animais , Ciclo do Ácido Cítrico , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Neutrófilos/metabolismo , Oxirredução , Estresse Oxidativo , Peptidil Dipeptidase A/genética , Regulação para Cima
16.
Biochem Biophys Res Commun ; 520(3): 573-579, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31615657

RESUMO

BACKGROUND: Macrophages are ubiquitous in all stages of atherosclerosis, exerting tremendous impact on lesion progression and plaque stability. Because macrophages in atherosclerotic plaques express angiotensin-converting enzyme (ACE), current dogma posits that local myeloid-mediated effects worsen the disease. In contrast, we previously reported that myeloid ACE overexpression augments macrophage resistance to various immune challenges, including tumors, bacterial infection and Alzheimer's plaque deposition. Here, we sought to assess the impact of myeloid ACE on atherosclerosis. METHODS: A mouse model in which ACE is overexpressed in myelomonocytic lineage cells, called ACE10, was generated and sequentially crossed with ApoE-deficient mice to create ACE10/10ApoE-/- (ACE10/ApoE). Control mice were ACEWT/WTApoE-/- (WT/ApoE). Atherosclerosis was induced using an atherogenic diet alone, or in combination with unilateral nephrectomy plus deoxycorticosterone acetate (DOCA) salt for eight weeks. RESULTS: With an atherogenic diet alone or in combination with DOCA, the ACE10/ApoE mice showed significantly less atherosclerotic plaques compared to their WT/ApoE counterparts (p < 0.01). When recipient ApoE-/- mice were reconstituted with ACE10/10 bone marrow, these mice showed significantly reduced lesion areas compared to recipients reconstituted with wild type bone marrow. Furthermore, transfer of ACE-deficient bone marrow had no impact on lesion area. CONCLUSION: Our data indicate that while myeloid ACE may not be required for atherosclerosis, enhanced ACE expression paradoxically reduced disease progression.


Assuntos
Aterosclerose/enzimologia , Aterosclerose/prevenção & controle , Células Mieloides/enzimologia , Peptidil Dipeptidase A/metabolismo , Animais , Aterosclerose/genética , Pressão Sanguínea , Transplante de Medula Óssea , Linhagem da Célula/genética , Colesterol/sangue , Dieta Aterogênica , Modelos Animais de Doenças , Progressão da Doença , Humanos , Macrófagos/enzimologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Células Mieloides/patologia , Peptidil Dipeptidase A/genética , Regulação para Cima
17.
Antioxidants (Basel) ; 8(10)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554157

RESUMO

In the present work, the ultrasonic-assisted extraction (UAE) of total flavonoids (TF) from Pteris cretica L. was optimized by response surface methodology (RSM) on the basis of a single-factor experiment. The optimized UAE parameters were as follows: Ethanol concentration 56.74%, extraction time 45.94 min, extraction temperature 74.27 °C, and liquid/solid ratio 33.69 mL/g. Under the optimized conditions, the total flavonoids yield (TFY) was 4.71 ± 0.04%, which was higher than that obtained by heat reflux extraction (HRE). The extracts were further analyzed by HPLC, and five major flavonoids, including rutin, quercitrin, luteolin, apigenin, and luteolin-7-O-glucoside, were identified and quantified. Furthermore, the results of the antioxidant test showed that the TF extract obtained under optimized UAE conditions exhibited good 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS+•), nitric oxide radical (NO•) scavenging activities, and ferrous ion (Fe2+) chelating capacity, with IC50 values of 74.49, 82.92, 89.12, and 713.41 µg/mL, respectively. Results indicated that the UAE technique developed in this work was an efficient, rapid, and simple approach for the extraction of flavonoids with antioxidant activity from P. cretica.

18.
Molecules ; 24(17)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484401

RESUMO

For the full development and utilization of Sophora tonkinensis Gagnep., this study was primarily intended to established a simple and efficient approach for the preparative purification of total flavonoids from S. tonkinensis by macroporous resin column chromatography (MRCC). The adsorption and desorption characteristics of the total flavonoids on ten macroporous resins were first studied, and AB-8 resin was chosen as the most suitable, and the adsorption data were best fitted to the pseudo-second-order kinetics model and Langmuir isotherm model. Furthermore, the technological parameters for the purification of the total flavonoids were optimized using column chromatography. After a sample one-step purification procedure, the content of the total flavonoids increased by about 4.76-fold from 12.14% to 57.82%, with a recovery yield of 84.93%. In addition, the comparative analysis of the flavonoid extracts before and after purification was performed by high-performance liquid chromatography coupled with photodiode-array detection (HPLC-PAD). The results showed that the contents of six major flavonoids in the purified product were all higher than before the purification. Therefore, the AB-8 MRCC established in this work was a promising method for the industrial-scale purification of the total flavonoids from S. tonkinensis.


Assuntos
Flavonoides/química , Extratos Vegetais/química , Resinas Vegetais/química , Sophora/química , Cromatografia Líquida de Alta Pressão
19.
Chin J Nat Med ; 17(7): 545-550, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31514986

RESUMO

Two new flavonoid glycosides, named viscumneoside XII (1), and viscumneoside XIII (2); a new dihydrogen flavonoid glycoside product named viscumneoside XIV (3), were isolated from the aerial part of Viscum album, along with seven known compounds (4-10). Their structures were identified by analysis of spectroscopic data. In addition, cytotoxicity assay showed that 1, 2 and 3 possessed significant inhibitory activities against C6, A549 and MDA-MB-231 (the inhibition rate arrived about 50%, 70% and 74% respectively with IC50 ≤ 60.00 µmol·L-1), while the inhibition of TF-1 and Hela was not significant.


Assuntos
Antineoplásicos/química , Flavonoides/química , Glicosídeos/química , Viscum album/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/farmacologia , Glicosídeos/farmacologia , Humanos , Estrutura Molecular , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia
20.
Front Plant Sci ; 10: 890, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354764

RESUMO

The NAC proteins form one of the largest families of plant-specific transcription factors (TFs) and play essential roles in developmental processes and stress responses. In this study, we characterized a NAC domain transcription factor, OoNAC72, from a legume Oxytropis ochrocephala. OoNAC72 was proved to be localized in the nuclei in tobacco lower epidermal cells and had transcriptional activation activity in yeast, confirming its transcription activity. OoNAC72 expression could be induced by drought, salinity and exogenous abscisic acid (ABA) in O. ochrocephala seedlings. Furthermore, over-expression of OoNAC72 driven by CaMV35S promoter in Arabidopsis resulted in ABA hypersensitivity and enhanced tolerance to drought and salt stresses during seed germination and post-germinative growth periods. In addition, over-expression of OoNAC72 enhanced the expression of stress-responsive genes such as RD29A, RD29B, RD26, LEA14, ANACOR19, ZAT10, PP2CA, and NCED3. These results highlight the important regulatory role of OoNAC72 in multiple abiotic stress tolerance, and may provide an underlying reason for the spread of O. ochrocephala.

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