ABSTRACT
This study aimed to valorize pawpaw (Carica papaya L.) leaves as a rich source of polyphenols through the application of ionic liquid-based microwave-assisted extraction (ILMAE). Initially, the ILMAE process was optimized using response surface methodology (RSM), resulting in a total polyphenols yield of 27.84 ± 0.33 mg GAE/g DW under the optimal conditions: [BMIM]Br concentration of 0.57 mol/L, extraction time of 14 min, microwave power of 460 W, extraction temperature of 77 °C, solvent-to-material ratio of 30 mL/g, and three extraction cycles. Compared to conventional methods such as maceration extraction (ME), heat reflux extraction (HRE), and microwave-assisted extraction (MAE), the ILMAE method exhibited a significantly higher PLTP yield. Furthermore, the PLTP extracts demonstrated strong antioxidant activity against DPPH⢠and ABTS+⢠radicals, as well as a significant inhibitory effect on α-glucosidase activity. This work demonstrates that ILMAE is a green and efficient strategy for the valorization of pawpaw leaves.
ABSTRACT
Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types and known for its suppressive effect on T cells through its interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophils has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. The administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function, suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by their increased plasma alanine transaminase (ALT) levels and frequencies of inflammatory leukocytes in the liver, implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for the enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities, assisting in a smooth transition into the resolution phase in MRSA infection.
ABSTRACT
Lactococcus lactis subsp. cremoris C60 is a probiotic strain of lactic acid bacteria (LAB) which induces various immune modifications in myeloid lineage cells. These modifications subsequently regulate T cell function, resulting in enhanced immunity both locally and systemically. Here, we report that C60 suppresses tumor growth by enhancing macrophage function via metabolic alterations, thereby increasing adenosine triphosphate (ATP) production in a murine melanoma model. Intragastric (i.g.) administration of C60 significantly reduced tumor volume compared to saline administration in mice. The anti-tumor function of intratumor (IT) macrophage was upregulated in mice administered with C60, as evidenced by an increased inflammatory phenotype (M1) rather than an anti-inflammatory/reparative (M2) phenotype, along with enhanced antigen-presenting ability, resulting in increased tumor antigen-specific CD8+ T cells. Through this functional modification, we identified that C60 establishes a glycolysis-dominant metabolism, rather than fatty acid oxidation (FAO), in IT macrophages, leading to increased intracellular ATP levels. To address the question of why orally supplemented C60 exhibits functions in distal places, we found a possibility that bacterial cell wall components, which could be distributed throughout the body from the gut, may induce stimulatory signals in peripheral macrophages via Toll-like receptors (TLRs) signaling activation. Thus, C60 strengthens macrophage anti-tumor immunity by promoting a predominant metabolic shift towards glycolysis upon TLR-mediated stimulation, thereby increasing substantial energy production.
ABSTRACT
Lactic acid bacteria (LAB) possess the ability to argument T cell activity through functional modification of antigen presenting cells (APCs), such as dendritic cells (DCs) and macrophages. Nevertheless, the precise mechanism underlying LAB-induced enhancement of antigen presentation in APCs remains incompletely understood. To address this question, we investigated the detailed mechanism underlying the enhancement of major histocompatibility complex (MHC) class I-restricted antigen presentation in DCs using a probiotic strain known as Lactococcus lactis subsp. Cremoris C60. We found that Heat-killed-C60 (HK-C60) facilitated the processing and presentation of ovalbumin (OVA) peptide antigen OVA257-264 (SIINFEKL) via H-2Kb in bone marrow-derived dendritic cells (BMDCs), leading to increased generation of effector CD8+ T cells both in vitro and in vivo. We also revealed that HK-C60 stimulation augmented the activity of 20S immunoproteasome (20SI) in BMDCs, thereby enhancing the MHC class I-restricted antigen presentation machinery. Furthermore, we assessed the impact of HK-C60 on CD8+ T cell activation in an OVA-expressing B16-F10 murine melanoma model. Oral administration of HK-C60 significantly attenuated tumor growth compared to control treatment. Enhanced Ag processing and presentation machineries in DCs from both Peyer's Patches (PPs) and lymph nodes (LNs) resulted in an increased tumor antigen specific CD8+ T cells. These findings shed new light on the role of LAB in MHC class-I restricted antigen presentation and activation of CD8+ T cells through functional modification of DCs.
Subject(s)
Antigen Presentation , Dendritic Cells , Animals , Mice , Histocompatibility Antigens Class I , CD8-Positive T-Lymphocytes , Antigens , Ovalbumin , Major Histocompatibility ComplexABSTRACT
Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with poor prognosis, which is mainly due to drug resistance. The biology determining the response to chemo-radiotherapy in HNSCC is poorly understood. Using clinical samples, we found that miR124-3p and miR766-3p are overexpressed in chemo-radiotherapy-resistant (non-responder) HNSCC, as compared to responder tumors. Our study shows that inhibition of miR124-3p and miR766-3p enhances the sensitivity of HNSCC cell lines, CAL27 and FaDu, to 5-fluorouracil and cisplatin (FP) chemotherapy and radiotherapy. In contrast, overexpression of miR766-3p and miR124-3p confers a resistance phenotype in HNSCC cells. The upregulation of miR124-3p and miR766-3p is associated with increased HNSCC cell invasion and migration. In a xenograft mouse model, inhibition of miR124-3p and miR766-3p enhanced the efficacy of chemo-radiotherapy with reduced growth of resistant HNSCC. For the first time, we identified that miR124-3p and miR766-3p attenuate expression of CREBRF and NR3C2, respectively, in HNSCC, which promotes aggressive tumor behavior by inducing the signaling axes CREB3/ATG5 and ß-catenin/c-Myc. Since miR124-3p and miR766-3p affect complementary pathways, combined inhibition of these two miRNAs shows an additive effect on sensitizing cancer cells to chemo-radiotherapy. In conclusion, our study demonstrated a novel miR124-3p- and miR766-3p-based biological mechanism governing treatment-resistant HNSCC, which can be targeted to improve clinical outcomes in HNSCC.
ABSTRACT
Creatine is an organic compound which is utilized in biological activities, especially for adenosine triphosphate (ATP) production in the phosphocreatine system. This is a well-known biochemical reaction that is generally recognized as being mainly driven in specific parts of the body, such as the skeletal muscle and brain. However, our report shows a novel aspect of creatine utilization and ATP synthesis in innate immune cells. Creatine supplementation enhanced immune responses in neutrophils, such as cytokine production, reactive oxygen species (ROS) production, phagocytosis, and NETosis, which were characterized as antibacterial activities. This creatine-induced functional upregulation of neutrophils provided a protective effect in a murine bacterial sepsis model. The mortality rate in mice challenged with Escherichia coli K-12 was decreased by creatine supplementation compared with the control treatment. Corresponding to this decrease in mortality, we found that creatine supplementation decreased blood pro-inflammatory cytokine levels and bacterial colonization in organs. Creatine supplementation significantly increased the cellular ATP level in neutrophils compared with the control treatment. This ATP increase was due to the phosphocreatine system in the creatine-treated neutrophils. In addition, extracellular creatine was used in this ATP synthesis, as inhibition of creatine uptake abolished the increase in ATP in the creatine-treated neutrophils. Thus, creatine is an effective nutrient for modifying the immunological function of neutrophils, which contributes to enhancement of antibacterial immunity.
ABSTRACT
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.
Subject(s)
HIV-1 , NF-kappa B , Mice , Animals , NF-kappa B/genetics , NF-kappa B/metabolism , Microglia/metabolism , HIV-1/metabolism , Feedback , Apoptosis , Fatty Acid-Binding Proteins/metabolismABSTRACT
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.
Subject(s)
Glomerulonephritis , Nephritis , Angiotensin II/metabolism , Animals , Antigen-Antibody Complex/metabolism , Complement C3b/metabolism , Glomerulonephritis/metabolism , Mice , Nephritis/metabolism , Neutrophils/metabolism , Proteinuria/metabolismABSTRACT
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.
Subject(s)
Inflammation/immunology , Neutrophils/immunology , ras GTPase-Activating Proteins/immunology , Animals , Mice , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Biological Products/isolation & purification , Fungi/chemistry , Huperzia/microbiology , Biological Products/pharmacology , Endophytes/chemistry , Endophytes/isolation & purification , Fungi/isolation & purification , Molecular Structure , Secondary MetabolismABSTRACT
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.
ABSTRACT
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.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Methicillin-Resistant Staphylococcus aureus , Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Humans , Mice , Mice, Knockout , NeutrophilsABSTRACT
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.
ABSTRACT
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.
Subject(s)
Extracellular Traps , Melanoma , Myeloid-Derived Suppressor Cells , Aged , Granulocytes , Humans , L-Selectin , Neutrophils , Receptors, CXCR4ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Hematopoiesis/immunology , Inflammation/immunology , Myeloid Cells/immunology , Peptidyl-Dipeptidase A/physiology , Adaptive Immunity , Animals , Bacterial Infections/immunology , Humans , Mice , Neoplasms/immunology , Peptidyl-Dipeptidase A/immunologyABSTRACT
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.
ABSTRACT
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.