ABSTRACT
OBJECTIVE: Obstructive Sleep Apnea (OSA) during pregnancy is characterized by intermittent hypoxia (IH) during sleep and will lead to the rise of oxidative stress in the fetal body. Pyroptosis, a type of inflammatory and programmable cell death mediated by Gasdermin D (GSDMD), plays a substantial role in oxygen deprivation's contribution to neural system damage. Existing research shows that Nicotinamide Adenine Dinucleotide Phosphate (NADPH) plays a protective role in alleviating brain tissue pyroptosis. We speculate that exogenous NADPH may play a protective role in OSA during pregnancy. METHODS: A model of GIH group was established to simulate the pathophysiological mechanisms of OSA during pregnant and AIR group was established by giving the same frequency. Sham group was established by injecting NS and the NADPH group was established and given exogenous NADPH. We utilized the Morris Water Maze to assess cognitive function impairment, Luxol Fast Blue (LBF) staining to confirm myelin sheath formation, TUNEL staining to examine cell death in fetal mice brain tissue, and Western blotting to detect pertinent protein expressions. RESULTS: The GIH group offspring exhibited decreases in spatial learning and memory abilities, reduced numbers of oligodendrocytes and formed myelin, as well as increased expression of pyroptosis-related proteins. The NADPH group offspring showed restoration in spatial learning and memory abilities increased counts of oligodendrocytes and formed myelin sheaths, in addition to decreased expression of pyroptosis-related. CONCLUSIONS: This study demonstrates that early injection of exogenous NADPH can alleviate the damage to fetal brain development caused by gestational intermittent hypoxia (GIH).
Subject(s)
NADP , Pyroptosis , Animals , Pregnancy , Female , Mice , NADP/metabolism , Brain Injuries/pathology , Brain Injuries/metabolism , Hypoxia/metabolism , Brain/pathology , Brain/metabolism , Disease Models, Animal , Male , Mice, Inbred C57BL , Prenatal Exposure Delayed EffectsABSTRACT
OBJECTIVES: The study aimed to explore the underlying mechanisms of OSA-related cognitive impairment by investigating the altered topology of brain white matter networks in children with OSA. METHODS: Graph theory was used to examine white matter networks' network topological properties in 46 OSA and 31 non-OSA children. All participants underwent MRI, polysomnography, and cognitive testing. The effects of the obstructive apnea-hypopnea index (OAHI) on topological properties of white matter networks and network properties on cognition were studied using hierarchical linear regression. Mediation analyses were used to explore whether white matter network properties mediated the effects of OAHI on cognition. RESULTS: Children with OSA had significantly higher assortativity than non-OSA children. Furthermore, OAHI was associated with the nodal properties of several brain regions, primarily in the frontal and temporal lobes. The relationship between OAHI and verbal comprehension index was mediated through clustering coefficients in the right temporal pole of the superior temporal gyrus. CONCLUSIONS: OSA affects the development of white matter networks in children's brains. Besides, the mediating role of white matter network properties between the OAHI and the verbal comprehension index provided neuroimaging evidence of impaired cognitive function in children with OSA.
Subject(s)
Magnetic Resonance Imaging , Polysomnography , Sleep Apnea, Obstructive , White Matter , Humans , Male , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/complications , White Matter/diagnostic imaging , White Matter/pathology , Female , Child , Cognition/physiology , Brain/diagnostic imaging , Brain/pathology , Neuropsychological Tests/statistics & numerical data , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/etiologyABSTRACT
One-step separation of C2 H4 from ternary C2 mixtures by physisorbents remains a challenge to combine excellent separation performance with high stability, low cost, and easy scalability for industrial applications. Herein, we report a strategy of constructing negative electrostatic pore environments in a stable, low-cost, and easily scaled-up aluminum MOF (MOF-303) for efficient one-step C2 H2 /C2 H6 /C2 H4 separation. This material exhibits not only record high C2 H2 and C2 H6 uptakes, but also top-tier C2 H2 /C2 H4 and C2 H6 /C2 H4 selectivities at ambient conditions. Theoretical calculations combined with in situ infrared spectroscopy indicate that multiple N/O sites on pore channels can build a negative electro-environment to provide stronger interactions with C2 H2 and C2 H6 over C2 H4 . Breakthrough experiments confirm its exceptional separation performance for ternary mixtures, affording one of the highest C2 H4 productivity of 1.35â mmol g-1 . This material is highly stable and can be easily synthesized at kilogram-scale from cheap raw materials using a water-based green synthesis. The benchmark combination of excellent separation properties with high stability and low cost in scalable MOF-303 has unlocked its great potential in this challenging industrial separation.
ABSTRACT
Objective: Obstructive sleep apnea (OSA) seriously affects the children's cognitive functions, but the neuroimaging mechanism of cognitive impairment is still unclear. The purpose of our study was to explore the difference in brain local gray matter volume (GMV) between children with OSA and non-OSA, and the correlation between the difference regions of brain gray matter volume and cognitive, the severity of OSA. Method: Eighty-three children aged 8-13 years were recruited in our study, 52 children were diagnosed as OSA by polysomnography, and 31 as the non-OSA. All the subjects were underwent high-resolution 3-dimensional T1-weighted magnetic resonance images. The voxel-based morphometry (VBM) was be used to analyse the local GMV. The Das-Naglieri cognitive assessment system (DN: CAS) was used to assess the subjects' cognitive. The difference of local GMV between the two groups was analyzed by two-sample T-test. The PSG variables and the scores of DN: CAS between the OSA group and non-OSA group were compared by independent samples t-tests. Pearson correlation was used to calculate the association between the difference areas of gray matter volumes in brain and DN: CAS scores, obstructive apnea/hypopnea index (OAHI, an index of the severity of OSA). Results: The gray matter volume of the right Middle Frontal Gyrus (MFG_R) in OSA children were larger than the non-OSA children, and the OSA children had lower scores of the Word Series in DN: CAS. There was negative correlation between the scores of Expressive Attention in DN: CAS and the gray matter volume of the right middle frontal gyrus, and it was no significantly correlation between OAHI and the gray matter volume of the right middle frontal gyrus. Conclusion: Our results suggest that the development of gray matter volume in frontal cortex, which associated with attention, were sensitive to the effects of OSA, provides neuroimaging evidence for cognitive impairment in children with OSA.
ABSTRACT
OBJECTIVE: Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) is a sleep respiratory disease associated with cognitive impairment, The nuclear factor erythroid 2 related factor 2 (Nrf2) plays a neuroprotective role. This study was designed to investigate the mechanism of Nrf2 protecting neural cells from endoplasmic reticulum stress (ERS), induced by chronic intermittent hypoxia (CIH) and sleep fragmentation (SF) which caused cognitive impairment in mice. METHODS: Establishment of CIH and SF mice to simulate OSAHS mouse model. An eight-arm maze behavior test measured the cognitive function of mice, and Nissl staining and TUNEL staining were used to detect pathological changes in hippocampal neurons. The expression of ERS and Nrf2 and its downstream related mRNAs and proteins were detected by qRT-PCR and Western blotting. RESULTS: CIH and SF lead to cognitive impairment in mice, and Sulforaphane (SFN, Nrf2 agonist) plays a protective role, while Nrf2-KO aggravates the cognitive impairment. CIH and SF reduced the number of Nissl bodies in neurons and induced apoptosis. The mRNA levels of BiP, CHOP, Nrf2, GCLC and Prdx1 in CIH, SF and CIH + SF groups were increased (p = 0.001), whereas the mRNA levels of BiP and CHOP in the CIH + SF + SFN group were decreased (p = 0.02) while those of Nrf2 and Prdx1 were increased (p = 0.005). The CIH + SF + Nrf2-KO group, the mRNA levels of CHOP were increased (p = 0.001) while Nrf2, GCLC and Prdx1 were decreased (p = 0.001). The protein levels of CHOP and active Caspase-12 in CIH, SF, CIH + SF and CIH + SF + Nrf2-KO groups were increased (p = 0.03), while those of Prdx1 and Nrf2 were increased (p = 0.03) in the CIH + SF + SFN group, while decreased (p = 0.02) in the Nrf2-KO group. CONCLUSIONS: Chronic intermittent hypoxia(CIH) and sleep fragmentation(SF) could aggravate the inflammatory response of nerve cells through endoplasmic reticulum stress, leading to apoptosis of nerve cells, and causing cognitive impairment in mice.Nrf2 alleviates cognitive impairment induced by chronic intermittent hypoxia and sleep fragmentation by modulating endoplasmic reticulum stress. Activation of Nrf2 protects cognitive impairment through the Nrf2-Prdx1 signaling pathway.
Subject(s)
Cognitive Dysfunction , NF-E2-Related Factor 2 , Sleep Apnea, Obstructive , Animals , Mice , Disease Models, Animal , Hypoxia/complications , NF-E2-Related Factor 2/genetics , Sleep Apnea, Obstructive/complications , Sleep Deprivation/complicationsABSTRACT
Funiu Mountains are located in a transition region between warm temperate zone and northern subtropical region, where a variety of plant species are distributed with sensitive response to climate change. Their response characteristics to climate change are still unclear. We developed the basal area increment (BAI) index chronologies of Pinus tabuliformis, P. armandii, and P. massoniana in the Funiu Mountains to examine their growth trend and their sensitivity to climatic change. The results showed that the BAI chronologies gave a clue that the three conife-rous species had similar radial growth rate. The large Gleichlufigkeit (GLK) indices among the three BAI chronologies also indicated that the three species had a similar growth trend. Results of correlation analysis showed that the three species also had similar response to climatic change to a certain extent. Radial growth of all the three species was significantly positively correlated with the total monthly precipitation in December of previous year and June of the current year, but negatively correlated with the precipitation in September and the mean monthly temperature in June of the current year. There were some differences in the responses of the three coniferous to climate change. P. massoniana had a significant negative correlation with the mean temperature in March, and a significant positive correlation with the precipitation in March, while P. armandii and P. massoniana were affected negatively by the maximum temperature in August. Results of the moving correlation analysis showed that the three coniferous species had some similar sensitivity to climate change. Their positive responses to precipitation in previous December consistently increased, as well as the negative correlation with precipitation in current September. As to P. masso-niana, they had a relatively stronger climatic sensitivity and higher stability than the other two species. It would be more suitable for P. massoniana trees on the southern slope of the Funiu Mountains under global warming.
Subject(s)
Pinus , Tracheophyta , Climate Change , Trees , China , Global WarmingABSTRACT
We propose a hetero-nano-fin structure to further improve the efficiency of Pancharatnam-Berry phase metasurfaces. Two hetero-nano-fin types, MgF2/GaN and MgF2/Nb2O5, were investigated. The overall polarization conversion efficiency (PCE) improved from 52.7 to 54% for the MgF2/GaN nano-fin compared with the bare GaN nano-fin. The overall PCE of the Nb2O5 nano-fin was 1.7 times higher than that of the GaN nano-fin. The overall PCE improved from 92.4% up to 96% after the application of MgF2 antireflection. Moreover, the antireflection improves efficiency by an average of 4.3% in wavelengths from 450 to 700 nm. Although the increment of energy seems minimal, antireflection is crucial for a metasurface, not only enhancing efficiency but also reducing background signal of a meta-device.
ABSTRACT
Gastric cancer is one of the cancers with the highest morbidity and mortality. Although several therapeutic approaches have been developed to treat this disease, the overall survival rate is still very low due to metastasis, drug resistance, and so forth. Therefore, it is necessary to discover new regulatory molecules and signaling pathways that modulate the metastasis of gastric cancer cells. A Disintegrin And Metalloprotease 12 (ADAM12) was highly expressed in gastric cancer tissues and presented in the patient urine. However, it is unclear whether and how ADAM12 regulates the migration of gastric cancer cells. In this work, we used the secretome protein enrichment with click sugars (SPECS) method to purify the secreted glycosylated proteins and performed quantitative proteomics to identify the secreted proteins that were differentially regulated by ADAM12S, the short and secreted form of ADAM12. Our proteomic and biochemical analyses revealed that ADAM12S upregulated the cell surface glycoprotein CD146, a cell adhesion molecule and melanoma marker, which was dependent on the catalytic residue of ADAM12S. Furthermore, we discovered that the ADAM12S-enhanced migration of gastric cancer cells was, at least partially, mediated by CD146. This work may help to evaluate whether ADAM12 could be a potential therapeutic target for the treatment of gastric cancer patients.
Subject(s)
Proteomics , Stomach Neoplasms , ADAM Proteins/genetics , ADAM Proteins/metabolism , ADAM12 Protein/genetics , CD146 Antigen , Humans , Membrane Proteins/metabolism , Proteomics/methods , Stomach Neoplasms/geneticsABSTRACT
Certain animals harbor a high proportion of pathogens, particular the zoonotic pathogens, in their gut microbiome but are usually asymptomic; however, their carried pathogens may seriously threaten the public health. By understanding how the microbiome overcomes the negative effects of pathogens to maintain host health, we can develop novel solutions to control animal-mediated pathogen transmission including identification and application of beneficial microbes. Here, we analyzed the gut microbiota of 10 asymptomic captive sika deer individuals by full-length 16S rDNA sequencing. Twenty-nine known pathogens capable of infecting humans were identified, and the accumulated proportions of the identified pathogens were highly variable among individuals (2.33 to 39.94%). The relative abundances of several beneficial bacteria, including Lactobacillus and Bifidobacterium, were found to be positively correlated with the relative abundances of accumulated pathogens. Whole-genome metagenomic analysis revealed that the beneficial- and pathogenic-associated functions, such as genes involved in the synthesis of short chain fatty acids and virulence factors, were also positively correlated in the microbiome, indicating that the beneficial and pathogenic functions were maintained at a relatively balanced ratio. Furthermore, the bacteriophages that target the identified pathogens were found to be positively correlated with the pathogenic content in the microbiome. Several high-quality genomes of beneficial bacteria affiliated with Lactobacillus and Bifidobacterium and bacteriophages were recovered from the metagenomic data. Overall, this study provides novel insights into the interplay between beneficial and pathogenic content to ensure maintenance of a healthy gut microbiome, and also contributes to discovery of novel beneficial microbes and functions that control pathogens. KEY POINTS: ⢠Certain asymptomic captive sika deer individuals harbor relatively high amounts of zoonotic pathogens. ⢠The beneficial microbes and the beneficial functions are balanced with the pathogenic contents in the gut microbiome. ⢠Several high-quality genomes of beneficial bacteria and bacteriophages are recovered by metagenomics.
Subject(s)
Deer , Gastrointestinal Microbiome , Microbiota , Animals , Bacteria , Bifidobacterium , Humans , Lactobacillus , MetagenomicsABSTRACT
Caffeine has been used as a first-line drug for treatment of apnea neonatorum for decades due to its high safety and effectiveness. Studies report that caffeine mainly acts as a blocker of Adenosine Receptors (ARs). However, the mechanism of caffeine in reducing apnea neonatorum in the central nervous system has not been fully explored. Medial parabrachial nucleus (MPB) is part of the respiratory center of the pons that may be related to the activity of caffeine. Previous studies have not explored the effect and mechanism of caffeine on MPB neurons. To elucidate this, the current study used antagonists of A1 and A2a receptors to mimic the effect of caffeine in MPB of mice in vitro using the patch-clamp technique. The firing rates and spontaneous post-synaptic currents were recorded. The findings of the study showed that caffeine excited MPB neurons. Notably, the adenosine A1R antagonist 8-cyclopentyl-1,3-dimethyl-xanthine (CPT) but not the adenosine A2aR antagonist Istradefylline (KW6002) mimicked the exciting effect of caffeine, implying that caffeine excited MPB neurons in mice by blocking A1Rs. Further, the results indicated that caffeine could increase efficiency of synaptic transmission to excite MPB neurons. These findings suggest that A1Rs in MPB may be potential targets for caffeine in reducing apnea neonatorum.
Subject(s)
Parabrachial Nucleus , Receptor, Adenosine A1 , Adenosine/pharmacology , Animals , Apnea , Caffeine/pharmacology , Mice , Neurons/metabolism , Parabrachial Nucleus/metabolism , Receptor, Adenosine A1/metabolism , Receptor, Adenosine A2AABSTRACT
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is widely known for its multiple systems damage, especially neurocognitive deficits in children. Since their discovery, adenosine A2A receptors (A2ARs) have been considered as key elements in signaling pathways mediating neurodegenerative diseases such as Huntington's and Alzheimer's, as well as cognitive function regulation. Herein, we investigated A2AR role in cognitive impairment induced by chronic intermittent hypoxia (CIH). Mice were exposed to CIH 7 h every day for 4 weeks, and intraperitoneally injected with A2AR agonist CGS21680 or A2AR antagonist SCH58261 half an hour before IH exposure daily. The 8-arm radial arm maze was utilized to assess spatial memory after CIH exposures.To validate findings using pharmacology, the impact of intermittent hypoxia was investigated in A2AR knockout mice. CIH-induced memory dysfunction was manifested by increased error rates in the radial arm maze test. The behavioral changes were associated with hippocampal pathology, neuronal apoptosis, and synaptic plasticity impairment. The stimulation of adenosine A2AR exacerbated memory impairment with more serious neuropathological damage, attenuated long-term potentiation (LTP), syntaxin down-regulation, and increased BDNF protein. Moreover, apoptosis-promoting protein cleaved caspase-3 was upregulated while anti-apoptotic protein Bcl-2 was downregulated. Consistent with these findings, A2AR inhibition with SCH58261 and A2AR deletion exhibited the opposite result. Overall, these findings suggest that A2AR plays a critical role in CIH-induced impairment of learning and memory by accelerating hippocampal neuronal apoptosis and reducing synaptic plasticity. Blockade of adenosine A2A receptor alleviates cognitive dysfunction after chronic exposure to intermittent hypoxia in mice.
Subject(s)
Adenosine A2 Receptor Antagonists/therapeutic use , Cognition Disorders/prevention & control , Hypoxia, Brain/drug therapy , Hypoxia, Brain/psychology , Receptor, Adenosine A2A/drug effects , Animals , Brain-Derived Neurotrophic Factor/metabolism , Caspase 3/metabolism , Chronic Disease , Cognition Disorders/chemically induced , Cognitive Dysfunction , Hippocampus/pathology , Long-Term Potentiation/drug effects , Male , Maze Learning/drug effects , Mice , Mice, Inbred C57BL , Mice, Knockout , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Psychomotor Performance/drug effects , Pyrimidines/therapeutic use , Receptor, Adenosine A2A/genetics , Triazoles/therapeutic useABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the important antibiotic resistant pathogens causing infections in humans and animals. The increasing observation of MRSA in wildlife species has raised the concern of its impact on animal health and the potential of zoonotic transmission. This study investigated the prevalence of S. aureus in fecal samples from non-human primates in a zoo located in Jiangsu, China, in which 6 out of 31 (19.4%) fecal samples, and 2 out of 14 (14.3%) indoor room floor swab samples were S. aureus-positive. The antibiotic susceptibility tests of the eight isolates showed that the two isolates were resistant to both penicillin and cefoxitin, the three isolates were resistant only to penicillin, while three isolates were susceptible to all detected antibiotics. The two isolates resistant to cefoxitin were further identified as MRSA by the presence of mecA. Five different spa types were identified including t034 of two MRSA isolates from Trachypithecus francoisi, t189 of two methicillin-susceptible S. aureus (MSSA) isolates from Rhinopithecus roxellana, t377 of two MSSA isolates from Colobus guereza, and two novel spa types t19488 and t19499 from Papio anubis. Whole genome sequencing analysis showed that MRSA t034 isolates belonged to ST398 clustered in clonal complex 398 (CC398) and carried the type B ΦSa3 prophage. The phylogenetic analysis showed that the two MRSA t034/ST398 isolates were closely related to the human-associated MSSA in China. Moreover, two MRSA isolates contained the virulence genes relating to the cell adherence, biofilm formation, toxins, and the human-associated immune evasion cluster, which indicated the potential of bidirectional transfer of MRSA between monkeys and humans. This study is the first to report MRSA CC398 from monkey feces in China, indicating that MRSA CC398 could colonize in monkey and have the risk of transmission between humans and monkeys.
ABSTRACT
In this study, the phase modulation ability of a dielectric Pancharatnam-Berry (PB) phase metasurface, consisting of nanofins, is theoretically analyzed. It is generally considered that the optical thickness of the unit cell of a PB-phase metasurface is λ/2, i.e., a half-waveplate for polarization conversion. It is found that the λ/2 is not essential for achieving a full 2π modulation. Nevertheless, a λ/2 thickness is still needed for a high polarization conversion efficiency. Moreover, a gradient phase metasurface is designed. With the help of the particle swarm optimization (PSO) method, the wavefront errors of the gradient phase metasurface are reduced by fine-tuning the rotation angle of the nanofins. The diffraction efficiency of the gradient phase metasurface is thus improved from 73.4% to 87.3%. This design rule can be utilized to optimize the efficiency of phase-type meta-devices, such as meta-deflectors and metalenses.
ABSTRACT
In this study, the optical properties of a meta-GMR consisting of a metasurface stacked on a planar dielectric slab waveguide were theoretically investigated. Two different metasurfaces, namely chiral split-ring resonator dimer arrays with/without a rod-shaped antenna, were investigated and compared. Conventional GMR filters utilize gratings to couple the free-space electromagnetic field to the waveguide. The highly dispersive nature of grating leads to low angular tolerance. Here, the grating is replaced by metasurfaces. The metasurface unit cell can be regarded as a polarizable dipole that couples the free-space electromagnetic field to the waveguide and decouples the waveguide mode to the radiation modes. Based on the localized nature of the resonant metasurfaces, the metasurface/GMR hybrid mode exhibits a superior angular tolerance as compared with a conventional GMR filter. This study can open a new avenue to tailor the optical properties of GMR-based devices.
ABSTRACT
Luminogens with aggregation-induced emission (AIE) have been used to develop a new type of molecular probes based on analyte-triggered aggregation, but it still remains a challenge to design water-soluble AIE-active probe for specific detection of metal ions. Herein, we designed and synthesized a water-soluble molecular probe with AIE property for discriminative detection of aluminum ion and lead ion. Four carboxylic acid groups were incorporated into a tetraphenylethylene unit to enhance the coordination affinity and increase water-solubility in aqueous solution. The designed probe can be selectively lighted up by aluminum ion and lead ion via coordination-triggered AIE process. Discrimination of aluminum ion and lead ions based on the probe can be achieved in quantitative manner with the assistance of suitable masking reagents. This probe was further used to image aluminum ions in living cells of seedling roots of Arabidopsis, and the results showed that this probe is capable of imaging aluminum ions in living cells avoiding the interference of lead ions, and is suited for long-term imaging due to its excellent photostability. This work expands the application scope of AIE-active probes in discriminative detection of metal ions, and provides a design direction for water-soluble AIE probes to avoid the false signals from self-precipitation under physiological conditions.
Subject(s)
Aluminum/analysis , Arabidopsis/chemistry , Lead/analysis , Molecular Imaging , Molecular Probes/chemistry , Plant Roots/chemistry , Seedlings/chemistry , Water/chemistry , Cell Survival , Ions , Molecular Probes/chemical synthesis , Solubility , Spectrometry, Fluorescence , Stilbenes/chemistryABSTRACT
Therapeutic strategies are urgently needed for patients with acute myeloid leukemia (AML). Leukocyte immunoglobulin-like receptor B4 (LILRB4), which suppresses T-cell activation and supports tissue infiltration of AML cells, represents an attractive drug target for anti-AML therapeutics. Here, we report the identification and development of an LILRB4-specific humanized mAb that blocks LILRB4 activation. This mAb, h128-3, showed potent activity in blocking the development of monocytic AML in various models including patient-derived xenograft mice and syngeneic immunocompetent AML mice. MAb h128-3 enhanced the anti-AML efficacy of chemotherapy treatment by stimulating mobilization of leukemia cells. Mechanistic studies revealed four concordant modes of action for the anti-AML activity of h128-3: (i) reversal of T-cell suppression, (ii) inhibition of monocytic AML cell tissue infiltration, (iii) antibody-dependent cellular cytotoxicity, and (iv) antibody-dependent cellular phagocytosis. Therefore, targeting LILRB4 with antibody represents an effective therapeutic strategy for treating monocytic AML.
Subject(s)
Antineoplastic Agents, Immunological/pharmacology , Apolipoproteins E/metabolism , Cell Transformation, Neoplastic/immunology , Cell Transformation, Neoplastic/metabolism , Leukemia, Myeloid, Acute/etiology , Leukemia, Myeloid, Acute/metabolism , Membrane Glycoproteins/metabolism , Receptors, Immunologic/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Animals , Antibodies, Blocking , Antibodies, Monoclonal , Antibody-Dependent Cell Cytotoxicity , Antineoplastic Agents, Immunological/therapeutic use , Apolipoproteins E/chemistry , Apoptosis , Cell Line , Cell Transformation, Neoplastic/drug effects , Coculture Techniques , Disease Models, Animal , Humans , Leukemia, Myeloid, Acute/pathology , Membrane Glycoproteins/antagonists & inhibitors , Membrane Glycoproteins/chemistry , Mice , Mice, Knockout , Models, Biological , Models, Molecular , Protein Binding/drug effects , Rabbits , Receptors, Immunologic/antagonists & inhibitors , Receptors, Immunologic/chemistry , Structure-Activity Relationship , T-Lymphocytes/drug effects , Xenograft Model Antitumor AssaysABSTRACT
Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with multiple system diseases. Neurocognitive dysfunction resulting from central nervous system complications has been reported, especially in children with OSAHS. Chronic intermittent hypoxia is accepted to be the major pathophysiological mechanism of OSAHS. Adenosine plays an important role in cellular function via interactions with its receptors. A2a receptor has been recognized as a factor involved in neuroprotection. However, the role of adenosine A2a receptor in intermittent hypoxia induced cellular injury is not completely understood. In this study, we aim to investigate the underlying mechanisms of A2a receptor mediated cellular damage caused by intermittent hypoxia in PC12 cells. We found that activated A2a receptor by CGS21680 decreased cellular viability, increased PKC as well as ATP-sensitive potassium channel (KATP) subunits expression Kir6.2 and SUR1. Inhibition of A2a receptor by SCH58261 increased cellular viability, suppressed PKC and SUR1 expression level, ultimately showing a protective role in PC12 cells. Moreover, we observed that CHE, which is an antagonist of PKC, downregulated Kir6.2 and SUR1 expression and increased cellular viability. Additionally, we found that A2a receptor activation induced cell injury was associated with increased Cleaved-Caspase 3 expression, which can be decreased by inhibition of A2a receptor or PKC. In conclusion, our findings indicate that A2a receptor induced KATP expression by PKC activation and plays a role in accelerating PC12 cells injury induced by intermittent hypoxia exposure via A2a-PKC-KATP signal pathway mediated apoptosis.
Subject(s)
Adenosine A2 Receptor Antagonists/pharmacology , Cell Hypoxia/physiology , KATP Channels/metabolism , Protein Kinase C/metabolism , Receptor, Adenosine A2A/metabolism , Adenosine/analogs & derivatives , Adenosine/pharmacology , Adenosine A2 Receptor Agonists/pharmacology , Adenosine Triphosphate/metabolism , Animals , Cell Hypoxia/drug effects , PC12 Cells , Phenethylamines/pharmacology , Potassium Channels/metabolism , Pyrimidines/pharmacology , Random Allocation , Rats , Signal Transduction , Sulfonylurea Receptors/metabolism , Triazoles/pharmacologyABSTRACT
Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia1. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/pathology , Receptors, Cell Surface/metabolism , Signal Transduction , Tumor Escape/immunology , Animals , Apolipoproteins E/metabolism , Arginase/metabolism , CD4-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/cytology , Cell Movement , Cell Proliferation , Female , Humans , Immune Tolerance/immunology , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Male , Membrane Glycoproteins , Mice , Mice, Inbred C57BL , Mice, Inbred NOD , Mice, SCID , Protein Binding , Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism , Receptors, Cell Surface/deficiency , Receptors, Cell Surface/genetics , Receptors, Immunologic , Receptors, Urokinase Plasminogen Activator/metabolism , Tumor Escape/drug effects , Xenograft Model Antitumor AssaysABSTRACT
The present study was conducted to answer a single question: What is the role of picture-posting activities on social networking sites in emotion regulation? Across three studies, we find evidence suggesting that posting "psychologically distant" pictures is related to online negative emotional disclosure and could be a strategy for reducing negative affect by promoting cognitive reappraisal. We discuss important theoretical and practical implications of our study.
Subject(s)
Disclosure , Emotions/physiology , Social Media , Humans , PhotographyABSTRACT
BACKGROUND: Xianyu decoction (XD), a Chinese experience recipe, shows inhibitory effects on lung cancer. However, the potential functions of XD on pneumonia were unknown. This study aimed to investigate the effect of XD on inflammatory response of childhood pneumonia. METHODS: Human lung bronchial epithelial cell line BEAS-2B was cultured in different doses of LPS with or without XD treatment. The expression of miR-15a and IKBKB were altered by transfection assay. RT-PCR and western blot were used to evaluate the effects of XD and miR-15a mimic/inhibitor on the expression levels of miR-15a, IKBKB, p65 and IκBα. ELISA was used to determine the levels of CRP, IL-6 and IL-8. RESULTS: High expression of miR-15a was observed in serum and cell model of pneumonia. miR-15a promoted the expression of inflammatory cytokines IL-6, IL-8, CRP and IKBKB in vitro. XD treatment downregulated the level of miR-15a in pneumonia children. In addition, XD reduced the expression of inflammatory cytokines and the phosphorylation levels of p65 and IκBα by inhibition of miR-15a and IKBKB expression in LPS-stimulated BEAS-2B cells. CONCLUSION: XD downregulated the level of miR-15a in serum of pneumonia children. Additionally, XD inhibited inflammatory response in LPS-stimulated BEAS-2B cells possibly by blocking IKBKB/NF-κB signal pathway which was regulated by miR-15a.