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Adipocytes in dermis are considered to be important participants in skin repair and regeneration, but the role of subcutaneous white adipose tissue (sWAT) in skin repair is poorly understood. Here, we revealed the dynamic changes of sWAT during wound healing process. Lineage-tracing mouse studies revealed that sWAT would enter into the large wound bed and participate in the formation of granulation tissue. Moreover, sWAT undergoes beiging after skin injury. Inhibition of sWAT beiging by genetically silencing PRDM16, a key regulator to beiging, hindered wound healing process. The transcriptomics results suggested that beige adipocytes in sWAT abundantly express neuregulin 4 (NRG4), which regulated macrophage polarization and the function of myofibroblasts. In diabetic wounds, the beiging of sWAT was significantly suppressed. Thus, adipocytes from sWAT regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes.
Sujet(s)
Tissu adipeux blanc , Peau , Cicatrisation de plaie , Animaux , Tissu adipeux blanc/métabolisme , Souris , Peau/métabolisme , Peau/anatomopathologie , Souris de lignée C57BL , Graisse sous-cutanée/métabolisme , Facteurs de transcription/métabolisme , Facteurs de transcription/génétique , Neurégulines/métabolisme , Neurégulines/génétique , Mâle , Protéines de liaison à l'ADN/métabolisme , Protéines de liaison à l'ADN/génétique , Tissu adipeux brun/métabolisme , Adipocytes beiges/métabolisme , Macrophages/métabolisme , Humains , Myofibroblastes/métabolismeRÉSUMÉ
The design and preparation of flexible aerogel materials with high deformability and versatility have become an emerging research topic in the aerogel fields, as the brittle nature of traditional aerogels severely affects their safety and reliability in use. Herein, we review the preparation methods and properties of flexible aerogels and summarize the various controlling and design methods of aerogels to overcome the fragility caused by high porosity and nanoporous network structure. The mechanical flexibility of aerogels can be revolutionarily improved by monomer regulation, nanofiber assembly, structural design and controlling, and constructing of aerogel composites, which can greatly broaden the multifunctionality and practical application prospects. The design and construction criterion of aerogel flexibility is summarized: constructing a flexible and deformable microstructure in an aerogel matrix. Besides, the derived multifunctional applications in the fields of flexible thermal insulation (flexible thermal protection at extreme temperatures), flexible wearable electronics (flexible sensors, flexible electrodes, electromagnetic shielding, and wave absorption), and environmental protection (oil/water separation and air filtration) are summarized. Furthermore, the future development prospects and challenges of flexible aerogel materials are also summarized. This review will provide a comprehensive research basis and guidance for the structural design, fabrication methods, and potential applications of flexible aerogels.
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The Tibetan Plateau is located in southwestern China. It has many important ecological functions, such as biodiversity protection, and is an important grassland agroecosystem in China. With the development of modern agriculture and animal husbandry, antibiotics are widely used to treat humans and livestock, and antibiotics cannot be fully metabolised by both. Antibiotics eventually find their way into the environment, affecting other parts of grassland agroecosystems. Triticale (Triticosecale wittmack) is an artificial hybrid forage that can be used for both grain and forage. This study revealed the diversity of seedborne bacteria in triticale on the Tibetan Plateau and the resistance of the bacteria to nine antibiotics. It identified 37 representative strains and successfully obtained the spliced sequences of 36 strains of the bacteria, which were clustered into 5 phyla and 16 genera. Among them, 18 strains showed resistance to at least one of the 9 antibiotics, and the colony-forming unit (CFU) abundance of antibiotic-resistant bacteria (ARB) accounted for 45.38% of the total samples. Finally, the bacterial motility and biofilm formation ability were measured, and their correlation with bacterial resistance was analysed. The results showed that the bacterial resistance did not have an absolute positive correlation with the motility or biofilm formation ability.
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Rich endophytic bacterial communities exist in fescue (Festuca ovina L.) and play an important role in fescue growth, cold tolerance, drought tolerance and antibiotic tolerance. To screen for probiotics carried by fescue seeds, seven varieties were collected from three different regions of China for isolation by the milled seed method and analyzed for diversity and motility, biofilm and antibiotic resistance. A total of 91 bacterial isolates were obtained, and based on morphological characteristics, 36 representative dominant strains were selected for 16S rDNA sequencing analysis. The results showed that the 36 bacterial strains belonged to four phyla and nine genera. The Firmicutes was the dominant phylum, and Bacillus, Paenibacillus and Pseudomonas were the dominant genera. Most of the strains had motility (80%) and were biofilm-forming (91.7%). In this study, 15 strains were capable of Indole-3-acetic acid (IAA) production, 24 strains were capable of nitrogen fixation, and some strains possessed amylase and protease activities, suggesting their potential for growth promotion. Determination of the minimum inhibitory concentration (MIC) against the bacteria showed that the strains were not resistant to tetracycline and oxytetracycline. Pantoea (QY6, LH4, MS2) and Curtobacterium (YY4) showed resistance to five antibiotics (ampicillin, kanamycin, erythromycin, sulfadiazine and rifampicin). Using Pearson correlation analysis, a significant correlation was found between motility and biofilm, and between biofilm and sulfadiazine. In this study, we screened two strains of Pantoea (QY6, LH4) with excellent growth-promoting ability as well as broad-spectrum antibiotic resistance. which provided new perspectives for subsequent studies on the strong ecological adaptations of fescue, and mycorrhizal resources for endophytic bacteria and plant interactions.
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As a high-quality plant resource for ecological restoration, Achnatherum splendens has strong adaptability and wide distribution. It is a constructive species of alkaline grassland in Northwest China. The close relationship between seed-borne bacteria and seeds causes a specific co-evolutionary effect which can enhance the tolerance of plants under various stresses. In this study, 272 bacterial isolates were isolated from the seeds of Achnatherum splendens in 6 different provinces of China. In total, 41 dominant strains were identified, and their motility, biofilm formation ability and antibiotic resistance were analyzed. The results showed that the bacteria of Achnatherum splendens belonged to 3 phyla and 14 genera, of which Firmicutes was the dominant phylum and Bacillus was the dominant genus. The motility and biofilm formation ability of the isolated strains were studied. It was found that there were six strains with a moving diameter greater than 8 cm. There were 16 strains with strong biofilm formation ability, among which Bacillus with biofilm formation ability was the most common, accounting for 37.5%. The analysis of antibiotic resistance showed that sulfonamides had stronger antibacterial ability to strains. Correlation analysis showed that the resistance of strains to aminoglycosides (kanamycin, amikacin, and gentamicin) was significantly positively correlated with their biofilm formation ability. This study provides fungal resources for improving the tolerance of plants under different stresses. In addition, this is the first report on the biological characteristics of bacteria in Achnatherum splendens.
RÉSUMÉ
In order to study the difference of cultivable seed-borne bacterial diversity between commercial varieties and wild species of Poa pratensis L., and their antibiotic resistance to sulfadiazine, tetracycline, oxytetracycline, ciprofloxacin, gentamicin, oxytetracycline and rifampin. In this study, 60 bacterium isolates were isolated by dilution-coated plate method. Through 16S rRNA sequence analysis, 40 representative isolates with different morphological characteristics were identified and phylogenetic tree was constructed. The results of diversity analysis showed that the seed-borne bacterial diversity of commercial varieties was richer than that of wild species. The antibiotic resistance of the isolated bacterial strains was studied by agar dilution method, and it was concluded that the antibiotic resistance of the seed-borne bacteria carried by commercial varieties was stronger than that of the wild species. Finally, the biofilm formation ability and swimming motility of the bacterial strain were measured, and the correlation between the two and the antibiotic resistance of the bacterial strain was analyzed. The analysis showed that the antibiotic resistance of bacterial strains in Poa pratensis L. was significantly correlated with their swimming motility. In addition, the swimming motility of the bacterial strains was significantly correlated with the biofilm formation ability. It is worth mentioning that this is the first time to study the drug-resistant bacteria distributed in the seed-borne bacteria of Poa pratensis L.
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Dermal white adipocytes are closely associated with skin homeostasis and wound healing. However, it has not been fully investigated whether adipose-derived products improve wound healing. Here, we obtained adipose acellular matrix (AAM) and adipose-derived growth factors (ADGFs) from human adipose tissue and fabricated an ADGF-loaded AAM via surface modification with heparin. The product, HEP-ADGF-AAM, contained an adipose-derived scaffold and released ADGFs in a controlled fashion. To test its efficacy in promoting wound healing, mice with full thickness wound received three different treatments: HEP-ADGF-AAM, AAM and ADM. Control mice received no further treatments. Among these treatments, HEP-ADGF-AAM best improved wound healing. It induced adipogenesis in situ after in vivo implantation and provided an adipogenic microenvironment for wounds by releasing ADGFs. HEP-ADGF-AAM not only induced adipocyte regeneration, but also enhanced fibroblast migration, promoted vessel formation, accelerated wound closure, and enhanced wound epithelialization. Moreover, there was a close interaction between HEP-ADGF-AAM and the wound bed, and collagen was turned over in HEP-ADGF-AAM. These results show that HEP-ADGF-AAM might substantially improve re-epithelialization, angiogenesis, and skin appendage regeneration, and is thus a promising therapeutic biomaterial for skin wound healing.
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Thermoplastic composite structures possess superior properties compared with thermosetting composites, including recyclability and high damage tolerance. However, the poor adhesion properties of thermoplastic composites make their joining process challenging. In this research, three bonding techniques, namely adhesive, mechanical joining, and hybrid bonding, are investigated using lap shear specimens to evaluate their mechanical properties and failure modes. The stress distributions at the joints of the three bonding techniques are analyzed by numerical simulation. The findings demonstrate that hybrid bonding enhances the strength of composite joints, albeit at the expense of some stiffness due to the presence of an open hole. This method is particularly suitable for applications that necessitate robust connections requiring high strength.
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The orbitofrontal cortex (OFC)-dorsal striatum (DS) is an important neural circuit that contributes to addictive behavior, including compulsive reinforcement, yet the specific types of neurons that play a major role still need to be further elucidated. Here, we used a place conditioning paradigm to measure the conditioned responses to methamphetamine (MA). The results demonstrated that MA increases the expression of c-Fos, synaptic plasticity in OFC and DS. Patch-clamp recording showed that MA activated projection neurons from the OFC to the DS, and chemogenetic manipulation of neuronal activity in OFC-DS projection neurons affects conditioned place preference (CPP) scores. And the combined patch-electrochemical technique was used to detect the DA release in OFC, the data indicated that the DA release was increased in MA group. Additionally, SCH23390, a D1R antagonist, was used to verify the function of D1R projection neurons, showing that SCH23390 reversed MA addiction-like behavior. Collectively, these findings provide evidence for the D1R neuron is sufficient to regulate MA addiction in the OFC-DS pathway, and the study provides new insight into the underlying mechanism of pathological changes in MA addiction.
Sujet(s)
Corps strié , Métamfétamine , Corps strié/métabolisme , Cortex préfrontal/métabolisme , Métamfétamine/pharmacologie , Neurones/métabolisme , Récepteur dopamine D1/métabolismeRÉSUMÉ
MYB98 is a key regulator of the genetic network behind pollen tube attraction toward the female gametophyte. MYB98 is specifically expressed in the synergid cells (SCs), a female gametophyte component cells specialized for pollen tube attraction. However, it had not been clear how exactly MYB98 achieves this specific expression pattern. In the current study, we have determined that a normal SC-specific expression of MYB98 is dependent on a 16-bp-long cis-regulatory element, CATTTACACATTAAAA, freshly named as the "S ynergid-specific A ctivation E lement of M YB98" (SaeM). An 84 bp fragment harboring SaeM in the middle was sufficient to drive exclusively SC-specific expression. The element was present in a significantly large proportion of SC-specific gene promoters and in the promoter of MYB98 homologous genes in the Brassicaceae (pMYB98s). Significance of such family-wide SaeM-like element conservation in exclusive SC-specific expression was confirmed by the Arabidopsis-like activation feature of Brassica oleracea-derived pMYB98 and absence of such feature of pMYB98 derived from a non-Brassicaceae member Prunus persica. Additionally, the yeast-one-hybrid assay showed that the SaeM can be recognized by ANTHOCYANINLESS2 (ANL2) and DAP-seq data further suggested for additional three ANL2 homologs targeting the similar cis-element. Overall, our study has concluded that SaeM plays a crucial role in driving exclusively SC-specific expression of MYB98 and strongly suggests for the involvement of ANL2 and its homologs in its dynamic regulation in planta. Future study on the transcription factors is expected to shed more light on the mechanism behind the process.
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[This corrects the article DOI: 10.3389/fcell.2022.845158.].
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Recently, the role of the gut microbiota in the context of drug addiction has attracted the attention of researchers; however, the specific effects and underlying mechanisms require further exploration. To accomplish this, C57BL/6 mice were firstly treated with methamphetamine (MA). Conditioned place preference (CPP) behavior changes, gut permeability and function, microglial activation, and inflammatory cytokine expression were systematically analyzed in antibiotics-treated mice with microbiota depletion and in fecal microbiota transplantation mice with microbiota reconstitution. MA treatment altered microbiota composition and caused gut dysbiosis. Depletion of gut microbiota with antibiotics inhibited MA-induced CPP formation, and fecal microbiota transplantation reversed this inhibition. Mechanistic analyses indicated that antibiotic treatment decreased gut permeability and neuroinflammation, while fecal microbiota transplantation offset the impact of antibiotic treatment. Additionally, MA-induced microglial activation was suppressed by antibiotics but restored by microbiota transplantation, and this correlated well with the CPP score. Compared to antibiotic treatment, microbiota transplantation significantly increased 5-HT4 receptor expression in both the nucleus accumbens and the hippocampus. Furthermore, when fecal microbiota from healthy mice was transplanted into MA-treated mice, the CPP scores decreased. Our results provide a novel avenue for understanding MA addiction and suggest a potential future intervention strategy.
Sujet(s)
Microbiome gastro-intestinal , Métamfétamine , Souris , Animaux , Transplantation de microbiote fécal/méthodes , Microbiome gastro-intestinal/physiologie , Souris de lignée C57BL , Métamfétamine/pharmacologie , Antibactériens/pharmacologieRÉSUMÉ
[This corrects the article DOI: 10.3389/fcell.2022.845158.].
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BACKGROUND: Parkinson's disease (PD) is a neurological disorder. Recently, celastrol (Cel) has been reported to have neuroprotective properties. We investigated the protective effects of Cel on PD in a cell model with 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells and further addressed the underlying protective mechanisms of Cel. METHODS: PC12 cells were treated with 6-OHDA, and Cel was added to the medium at various concentrations. The CCK-8 assay, Hoechst/PI staining, and flow cytometry analysis were performed to detect cellular viability and apoptosis. Mitochondrial membrane potential (MMP) was examined by JC-1 staining. ROS level was quantified by ROS staining. The effects of Cel on the expression of miR-146a and PI3K/Akt/mTOR pathway were then clarified using real-time PCR and Western blotting. Moreover, a miR-146a mimic was synthesized and transfected into PC12 cells to further determine the mechanisms of Cel's neuronal protection against 6-OHDA-induced neurotoxicity. RESULTS: Cel greatly improved cell viability and lessened apoptosis. Flow cytometry showed that Cel especially inhibited early apoptosis. Cel also obviously restored the MMP and decreased ROS level destroyed by 6-OHDA. Moreover, 6-OHDA increased the expression of miR-146a and decreased pAkt/mTOR protein levels, whereas Cel reversed these changes. In particular, miR-146a targeted and inhibited the expression of PI3K, an upstream molecule of Akt/mTOR. Transfection of 6-OHDA-treated neurons with miR-146a mimic notably attenuated Cel's protective effects. LIMITATIONS: There were no animal experiments in our study. CONCLUSIONS: Cel exerts neuroprotective activity against 6-OHDA-caused neurotoxicity by regulating miR-146a/PI3K/Akt/mTOR pathway, which provides a potential application of Cel for treating neurodegenerative diseases.
Sujet(s)
Tumeurs de la surrénale , microARN , Neuroprotecteurs , Maladie de Parkinson , Phéochromocytome , Animaux , Apoptose , microARN/génétique , microARN/métabolisme , Neuroprotecteurs/pharmacologie , Oxidopamine/toxicité , Triterpènes pentacycliques , Phosphatidylinositol 3-kinases/métabolisme , Protéines proto-oncogènes c-akt/métabolisme , Rats , Espèces réactives de l'oxygène , Transduction du signal/physiologie , Sérine-thréonine kinases TOR/métabolismeRÉSUMÉ
Background: Fat grafting is a frequently used technique; however, its survival/ regeneration mechanism is not fully understood. The browning of white adipocytes, a process initiated in response to external stimuli, is the conversion of white to beige adipocytes. The physiologic significance of the browning of adipocytes following transplantation is unclear. Methods: C57BL/6 mice received 150 mg grafts of inguinal adipose tissue, and then the transplanted fat was harvested and analyzed at different time points to assess the browning process. To verify the role of browning of adipocytes in fat grafting, the recipient mice were allocated to three groups, which were administered CL316243 or SR59230A to stimulate or suppress browning, respectively, or a control group after transplantation. Results: Browning of the grafts was present in the center of each as early as 7 days post-transplantation. The number of beige cells peaked at day 14 and then decreased gradually until they were almost absent at day 90. The activation of browning resulted in superior angiogenesis, higher expression of the pro-angiogenic molecules vascular endothelial growth factor A (VEGF-A) and fibroblast growth factor 21 (FGF21), fewer macrophages, and ultimately better graft survival (Upregulation, 59.17% ± 6.64% vs. Control, 40.33% ± 4.03%, *p < 0.05), whereas the inhibition of browning led to poor angiogenesis, lower expression of VEGF-A, increased inflammatory macrophages, and poor transplant retention at week 10 (Downregulation, 20.67% ± 3.69% vs. Control, 40.33% ± 4.03%, *p < 0.05). Conclusion: The browning of WAT following transplantation improves the survival of fat grafts by the promotion of angiogenesis and reducing macrophage.
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Brown adipose tissue (BAT) transplantation is a promising means of increasing whole-body energy metabolism to ameliorate obesity. However, the changes in BAT following transplantation and the effects of the microenvironment of the recipient site on graft function have yet to be fully characterized. Therefore, we aimed to determine the effects of transplanting BAT from C57BL/6 mice into the dorsal subcutaneous region or deep to the quadriceps femoris muscle of leptin-deficient ob/ob mice. Subcutaneously transplanted BAT lost features of BAT and demonstrated greater inflammatory cell infiltration and more oil cysts 16 weeks following transplantation. By contrast, the sub-muscularly transplanted BAT maintained features of BAT and was more highly vascularized. Interestingly, sub-muscular BAT transplantation led to a significant increase in oxygen consumption and less inflammation in subcutaneous fat, which was associated with long-term reductions in insulin resistance and body mass gain, whereas the subcutaneous transplants failed after 16 weeks. These results demonstrate that the beneficial effects of BAT transplantation depend upon the microenvironment of the recipient site. Skeletal muscle may provide a microenvironment that maintains the inherent features of BAT grafts over a long period of time, which facilitates a reduction in obesity and improvements in glucose homeostasis.
Sujet(s)
Tissu adipeux brun , Microenvironnement cellulaire , Insulinorésistance , Muscles squelettiques/métabolisme , Obésité/métabolisme , Graisse sous-cutanée/métabolisme , Tissu adipeux brun/métabolisme , Tissu adipeux brun/transplantation , Animaux , Mâle , Souris , Souris obèse , Obésité/anatomopathologie , Obésité/thérapieRÉSUMÉ
Carbohydrates (sugars) are an essential energy-source for all life forms. They take a significant share of our daily consumption and are used for biofuel production as well. However, sugarcane and sugar beet are the only two crop plants which are used to produce sugar in significant amounts. Here, we have discovered and fine-tuned a phenomenon in rice which leads them to produce sugary-grain. We knocked-out GCS1 genes in rice by using CRISPR technology, which led to fertilization failure and pollen tube-dependent ovule enlargement morphology (POEM) phenomenon. Apparently, the POEMed-like rice ovule ('endosperm-focused') can grow near-normal seed-size unlike earlier observations in Arabidopsis in which gcs1 ovules ('embryo-focused') were aborted quite early. The POEMed-like rice ovules contained 10-20% sugar, with extremely high sucrose content (98%). Trancriptomic analysis revealed that the osgcs1 ovules had downregulation of starch biosynthetic genes, which would otherwise have converted sucrose to starch. Overall, this study shows that pollen tube content release is sufficient to trigger sucrose unloading at rice ovules. However, successful fertilization is indispensable to trigger sucrose-starch conversion. These findings are expected to pave the way for developing novel sugar producing crops suited for diverse climatic regions.
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Régulation de l'expression des gènes végétaux/physiologie , Oryza/génétique , Oryza/métabolisme , Protéines végétales/métabolisme , Saccharose/métabolisme , Clustered regularly interspaced short palindromic repeats , Mutation , Protéines végétales/génétique , Tube pollinique/physiologie , TranscriptomeRÉSUMÉ
Toosendanin (TSN) is a tetracyclic triterpenoid extracted from Melia toosendan Sieb, et Zucc, which primarily grows in specific areas of China. Although toosendanin (TSN) exerts antitumoral effects on various human cancer cells, its influence on gastric cancer (GC) is remains to be elucidated. MicroRNAs (miRNAs/miRs) serve crucial roles in apoptosis and proliferation of cancer cells. miR23a3p has been shown to be associated with human GC; however, the specific function of miR23a3p in GC remains unclear. Therefore, the present study aimed to elucidate the role of miR23a3p in the regulation of GC cell proliferation and apoptosis induced in vitro by TSN treatment. Subsequently, apoptosisrelated genes expression levels were quantified by reverse transcriptionquantitative PCR and western blot analysis, respectively, and the target relationship between miR23a3p and BCL2 was determined by luciferase reporter gene analysis. Additionally, cell proliferation and apoptosis experiments were carried out. The results indicated that TSN inhibited proliferation and induced apoptosis in MKN45 cells. Moreover, it upregulated the expression of miR23a3p. Bcell lymphoma2 (BCL2) was identified as a potential target gene of miR23a3p, which was demonstrated to bind to the 3'untranslated region of BCL2 mRNA, as detected by the luciferase reporter assay. Further studies revealed that BCL2 expression was downregulated following overexpression of miR23a3p. In addition, the overexpression of the miR23a3p inhibited proliferation, induced G1 arrest and increased apoptosis in MKN45 cells. The results of the present study demonstrated that miR23a3p inhibited proliferation and induced apoptosis of GC cells, which may be attributable to its direct targeting of BCL2. These results may provide a novel insight into the apoptosis of GC cells, and may lead to investigations into the mechanisms of the effects of TSN.
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Antinéoplasiques d'origine végétale/pharmacologie , Médicaments issus de plantes chinoises/pharmacologie , microARN/génétique , Protéines proto-oncogènes c-bcl-2/génétique , Tumeurs de l'estomac/génétique , Points de contrôle du cycle cellulaire , Lignée cellulaire tumorale , Prolifération cellulaire/effets des médicaments et des substances chimiques , Survie cellulaire/effets des médicaments et des substances chimiques , Régulation négative , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques , Humains , Tumeurs de l'estomac/traitement médicamenteuxRÉSUMÉ
Melatonin (MLT) is widely used to treat sleep disorders although the underlying mechanism is still elusive. In mice, using wheel-running detection, we found that exogenous MLT could completely recover the period length prolonged by N-methyl-D-aspartate receptor (NMDAR) impairment due to the injection of the NMDAR antagonist MK-801, a preclinical model of psychosis. The analysis of the possible underlying mechanisms indicated that MLT could regulate the homeostatic state in the ventrolateral preoptic nucleus (VLPO) instead of the circadian process in the suprachiasmatic nucleus (SCN). In addition, our data showed that MK-801 decreased Ca2+ -related CaMKII expression and CREB phosphorylation levels in the VLPO, and MLT could rescue these intracellular impairments but not NMDAR expression levels. Accordingly, Gcamp6 AAV virus was injected in-vivo to further monitor intracellular Ca2+ levels in the VLPO, and MLT demonstrated a unique ability to increase Ca2+ fluorescence compared with MK-801-injected mice. Additionally, using the selective melatonin MT2 receptor antagonist 4-phenyl-2-propionamidotetralin (4P-PDOT), we discovered that the pharmacological effects of MLT upon NMDAR impairments were mediated by melatonin MT2 receptors. Using electroencephalography/electromyography (EEG/EMG) recordings, we observed that the latency to the first nonrapid eye movement (NREM) sleep episode was delayed by MK-801, and MLT was able to recover this delay. In conclusion, exogenous MLT by acting upon melatonin MT2 receptors rescues sleep phase delayed by NMDAR impairment via increasing intracellular Ca2+ signaling in the VLPO, suggesting a regulatory role of the neurohormone on the homeostatic system.
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Signalisation calcique/effets des médicaments et des substances chimiques , Calcium-Calmodulin-Dependent Protein Kinase Type 2/métabolisme , Protéine de liaison à l'élément de réponse à l'AMP cyclique/métabolisme , Maléate de dizocilpine/pharmacologie , Mélatonine/pharmacologie , Aire préoptique/métabolisme , Récepteur de la mélatonine de type MT2/métabolisme , Phases du sommeil/effets des médicaments et des substances chimiques , Animaux , Électroencéphalographie , Électromyographie , Mâle , Mélatonine/métabolisme , SourisRÉSUMÉ
Secreted protein acidic and rich in cysteine (SPARC) has a close association with inflammatory response and oxidative stress in tissues and is widely expressed in intracranial aneurysms (IAs), especially in smooth muscle cells. Therefore, it is inferred that SPARC might be involved in the formation and development of IAs through the inflammatory response pathway or oxidative stress pathway. The aim of this study is to investigate the pathological mechanism of SPARC in oxidative stress, inflammation, and apoptosis during the formation of IAs, as well as the involvement of TGF-ß1 and NOX4 molecules. Human brain vascular smooth muscle cells (HBVSMCs) were selected as experimental objects. After the cells were stimulated by recombinant human SPARC protein in vitro, the ROS level in the cells was measured using an ID/ROS fluorescence analysis kit combined with fluorescence microscope and flow cytometry. The related protein expression in HBVSMCs was measured using western blotting. The mitochondrial membrane potential change was detected using a mitochondrial membrane potential kit and laser confocal microscope. The mechanism was explored by intervention with reactive oxygen scavengers N-acetylcysteine (NAC), TGF-ß1 inhibitor (SD-208), and siRNA knockout. The results showed that SPARC upregulated the expression of NOX4 through the TGF-ß1-dependent signaling pathway, leading to oxidative stress and pro-inflammatory matrix behavior and apoptosis in HBVSMCs. These findings demonstrated that SPARC may promote the progression of IAs.