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1.
J Cell Biochem ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32048762

RESUMO

Perturbations in the balanced process of osteoblast-mediated bone formation and osteoclast-mediated bone resorption leading to excessive osteoclast formation and/or activity is the cause of many pathological bone conditions such as osteoporosis. The osteoclast is the only cell in the body capable of resorbing and degrading the mineralized bone matrix. Osteoclast formation from monocytic precursors is governed by the actions of two key cytokines macrophage-colony-stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL). Binding of RANKL binding to receptor RANK initiates a series of downstream signaling responses leading to monocytic cell differentiation and fusion, and subsequent mature osteoclast bone resorption and survival. The phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) signaling cascade is one such pathway activated in response to RANKL. The 3-phosphoinositide-dependent protein kinase 1 (PDK1), is considered the master upstream lipid kinase of the PI3K-Akt cascade. PDK1 functions to phosphorylate and partially activate Akt, triggering the activation of downstream effectors. However, the role of PDK1 in osteoclasts has yet to be clearly defined. In this study, we specifically deleted the PDK1 gene in osteoclasts using the cathepsin-K promoter driven Cre-LoxP system. We found that the specific genetic ablation of PDK1 in osteoclasts leads to an osteoclast-poor osteopetrotic phenotype in mice. In vitro cellular assays further confirmed the impairment of osteoclast formation in response to RANKL by PDK1-deficient bone marrow macrophage (BMM) precursor cells. PDK1-deficient BMMs exhibited reduced ability to reorganize actin cytoskeleton to form a podosomal actin belt as a result of diminished capacity to fuse into giant multinucleated osteoclasts. Notably, biochemical analyses showed that PDK1 deficiency attenuated the phosphorylation of Akt and downstream effector GSK3ß, and reduced induction of NFATc1. GSK3ß is a reported negative regulator of NFATc1. GSK3ß activity is inhibited by Akt-dependent phosphorylation. Thus, our data provide clear genetic and mechanistic insights into the important role for PDK1 in osteoclasts.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32033295

RESUMO

According to the requirements of the Healthy China Program, reasonable assessment of residents' health risks and economic loss caused by urban air pollution is of great significance for environmental health policy planning. Based on the data of PM2.5 concentration, population density, and urbanization level of 338 Chinese cities in the year of 2015, the epidemiological relative risk (RR) was adopted to estimate the negative health effects caused by exposure to PM2.5. Meanwhile, the Value of Statistical Life (VSL) and Cost of Illness (COI) methods were used to calculate economic loss. The results show that PM2.5 pollution remains serious in 2015, which brings about many people suffering from all kinds of fearful health problems especially premature death and related diseases. The mortality and morbidity increase dramatically, and the total direct economic loss related to PM2.5 pollution in 2015 was 1.846 trillion yuan, accounting for 2.73% of total annual GDP. In addition, there was a strong correlation between urbanization level and health risks as well as economic loss, which implies that people who live in highly urbanized cities may face more severe health and economic losses. Furthermore, 338 cities were divided into four categories based on urbanization level and economic loss, of which the key areas (type D) were the regions where an increase in monitoring and governance is most needed. In the process of urbanization, policy makers should pay more attention to health costs and regional differentiated management, as well as promote the construction of healthy cities more widely.

3.
Sci Total Environ ; 714: 136685, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32018954

RESUMO

Coastal communities and their wastewater treatment systems are vulnerable to the impacts of extreme events. Decision-making about transitioning critical infrastructure across scale - onsite, community, or centralized - to an improved treatment portfolio is complex as it couples financial, social, policy, technological, and environmental factors with impacts to public health and aquatic ecosystems. In this paper, we propose a system dynamics approach to consider important factors and dynamics that influence municipalities' decision-making process for wastewater infrastructure transitions in the Florida Keys, particularly considering some impacts of a changing climate. Our research utilizes social-technical transition theories to develop an adaptable and dynamic decision-making tool for transitioning to an improved portfolio of wastewater technologies and to determine strategies that improve the portfolio's performance measures (i.e. nutrient loading and reliability) under extreme weather scenarios. The initial simulation results demonstrate that it is important to incorporate the impacts from extreme events into the wastewater infrastructure decision-making process because they increased nutrient loading by >20% and decreased reliability by nearly 10%. With this climate-informed decision-making structure, strategies were developed to facilitate the transition to an improved wastewater treatment portfolio. The strategies include a new socio-economic decision-making approach, technology and economic policies, and socio-technical behavior change. The socio-technical strategy simulated widespread adoption of urine diversion technologies which made the greatest improvement to nutrient loading with an 81% decrease. Furthermore, the best approach to improve the reliability performance measure (from 81% to 83%) was the technology and economic policy which economically disincentivized investment in centralized wastewater systems and changed the community-level technology option.

4.
Bioresour Technol ; 303: 122937, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32062316

RESUMO

In this study, sequencing batch reactor (SBR) and aerobic upflow sludge bed reactor (AeUSB) were used to investigate the effects of sludge granulation on establishing partial nitrification (PN) process and explore the potential mechanism. The particle size was positively related to the NO2--N accumulating performance, satisfactory nitrite accumulation rate (NAR) of 96.4% and 77.3% were obtained with the appearance of micro-granules in SBR and AeUSB after day 105 and 83, respectively. To our knowledge, it is the first report describing the importance of extracellular polymeric substances (EPS) content and components, such as aromatic protein-like substances, by-product-like substances and special protein secondary structures (α-helices and 3-turn helices) for sludge granulation and even PN process. Quantitative microbial analysis suggested that ammonium oxidizing bacteria (AOB) predominated in nitrifying-bacterium in micro-granules system, guaranteeing a highly efficient PN process.

6.
Reprod Sci ; 27(1): 75-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32046374

RESUMO

Diminished ovarian reserve (DOR) is characterized by the depletion of the ovarian pool, which leads to reductions in oocyte quality and quantity. Studies have suggested that ovarian reserve or ovarian aging is tightly related to apoptosis. However, the cell death mechanism is not comprehensively understood. Parthanatos, a type of poly [ADP-ribose] polymerase 1(PARP1)-dependent and apoptosis-inducing factor (AIF)-mediated cell death, plays a crucial role in various disorders. In the present study, we aimed to investigate whether parthanatos is involved in the pathogenesis of DOR. We recruited 40 patients (20 DOR patients and 20 normal ovarian reserve (NOR) patients) and examined PAR expression and AIF translocation in their isolated cumulus GCs (granulosa cells) by fluorescence microscopy. Our results demonstrated that PAR expression and AIF nuclear translocation were significantly higher in cumulus GCs of DOR patients, suggesting that PARP1-dependent cell death may be associated with DOR pathophysiology. Moreover, we tested the protective function of melatonin on hydrogen peroxide (H2O2)-induced parthanatos in human ovarian cancer (IGROV1) cells. Our results demonstrated that H2O2 treatment of IGROV1 cells led to excessive protein PARylation and AIF translocation into the nuclei. Melatonin effectively inhibits PARylation, blocks translocation of AIF into the nucleus, and consequently decreases the risk of parthanatos in cumulus GCs.

7.
Environ Pollut ; 261: 113976, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32044612

RESUMO

Cadmium (Cd) is widely present in the environment as a heavy metal poison. Prenatal Cd exposure can damage the placental glucocorticoid barrier, leading to foetal growth restriction (FGR), but the molecular mechanism is unknown. We aimed to study the effects of prenatal Cd exposure on 11ß-HSD2 and its possible involvement in Cd induced damage in the placental glucocorticoid barrier. Pregnant rats were treated with CdCl2 (1.0 mg/kg/day) by gavage from gestational day (GD) 9-19. Maternal exposure to Cd increased the FGR rate of the offspring, and the levels of corticosterone in the placenta, maternal and foetal serum. Further in vitro experiments with placenta or JEG3 cells indicated that Cd was able to decrease 11ß-HSD2 and Sp1 expression in trophoblast cells but did not affect 11ß-HSD1. Additionally, decreased p300 and Sp1 enrichment at the 11ß-HSD2 promoter region was observed in the cells treated with Cd. Decreasing or increasing Sp1 expression accordingly inhibited or promoted the expression of 11ß-HSD2 and further decreased or increased p300 and Sp1 enrichment at the 11ß-HSD2 promoter region. In conclusion, Cd inhibits the expression of 11ß-HSD2 by affecting the binding of p300 to 11ß-HSD2 via a decrease in Sp1 expression, which damages the placental glucocorticoid barrier and exposes the foetus to excessive glucocorticoids, resulting in FGR. These findings reveal a possible underlying molecular mechanism by which Cd exposure leads to FGR.

8.
Water Res ; 171: 115443, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31945640

RESUMO

High-Solids Anaerobic co-Digestion (HS-AcD) of sewage sludge (biosolids) with the organic fraction of municipal solid waste is a promising waste management alternative due to high methane yields, lower reactor volume requirements, lower energy inputs, and less leachate production than liquid anaerobic digestion. This study evaluated the environmental and economic burdens and benefits of HS-AcD of biosolids, Food Waste (FW), and Yard Waste (YW) using Life Cycle Assessment (LCA) and Life Cycle Cost Analysis (LCCA) methods using Hillsborough County, Florida in the U.S. as a case study. Results for HS-AcD were compared with incineration, composting, and landfilling, with and without landfill gas use. The results showed that HS-AcD of a mixture of biosolids, FW, and YW had the lowest environmental impacts in all categories analyzed (global warming potential, acidification, eutrophication, and ecotoxicity). In terms of economics, HS-AcD had the lowest life cycle cost, with or without considering land acquisition. The results show that HS-AcD is the best choice to manage biosolids and the organic waste in Hillsborough County in terms of both environmental and economic sustainability.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , Anaerobiose , Florida , Alimentos , Metano , Esgotos , Resíduos Sólidos
9.
Food Chem ; 312: 125903, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31901700

RESUMO

Coloring is an important external quality of jujube fruit (Ziziphus jujuba Mill.), however during long-term storage, its commercial value degrades as the peel color and lustre significantly fade. Here, the gene expression and metabolite concentration were profiled in the fruit peel of jujube harvested at three ripening periods to elucidate the color formation mechanism. A strong accumulation of malvidin 3-O-glucoside and delphinidin 3-O-glucoside correlated with the reddening of jujube peel. At the onset of the fruit ripening, strong activities of the genes in the early steps of the flavonoid biosynthetic pathway were observed. During the last ripening periods, three UDP-glucose flavonoid 3-O-glucosyltransferase (UFGT) involved in the accumulation of anthocyanins were significantly increased and their proper manipulation could delay the peel reddening. This study sheds light on the metabolic pathways and candidate genes underlying the peel coloration in jujube and lays a foundation for the improvement of jujube fruit appeal during long-term storage.

10.
Cell Rep ; 30(4): 969-983.e4, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31956073

RESUMO

We perform a CRISPR-Cas9 genome-wide screen in glioblastoma stem cells and identify integrin αvß5 as an internalization factor for Zika virus (ZIKV). Expression of αvß5 is correlated with ZIKV susceptibility in various cells and tropism in developing human cerebral cortex. A blocking antibody against integrin αvß5, but not αvß3, efficiently inhibits ZIKV infection. ZIKV binds to cells but fails to internalize when treated with integrin αvß5-blocking antibody. αvß5 directly binds to ZIKV virions and activates focal adhesion kinase, which is required for ZIKV infection. Finally, αvß5 blocking antibody or two inhibitors, SB273005 and cilengitide, reduces ZIKV infection and alleviates ZIKV-induced pathology in human neural stem cells and in mouse brain. Altogether, our findings identify integrin αvß5 as an internalization factor for ZIKV, providing a promising therapeutic target, as well as two drug candidates for prophylactic use or treatments for ZIKV infections.

11.
Chem Commun (Camb) ; 56(12): 1859-1862, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31950954

RESUMO

We present the design and synthesis of water-soluble quinoline-indole-based derivatives (IM-1, IM-2, and IM-3) with three-photon absorption activity. IM-3 can specifically target DNA and RNA accompanied by an obvious three-photon fluorescence enhancement in the second near-infrared window (1000-1700 nm). The in vitro experiments demonstrate that IM-3 can simultaneously stain mitochondria and the nucleolus both in living and fixed cells. The organelle-specific targeting behaviour is successfully visualized under stimulated emission depletion (STED) nanoscopy.

12.
Bioresour Technol ; 297: 122459, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31784252

RESUMO

Stable sewage nitrogen removal with nitrogen removal efficiency of 87.5 ± 2.2% was achieved in a partial nitrification-anammox (PNA) biofilm system at low temperatures (12.8-16.3 °C). High-throughput sequencing analysis indicated that the microbial community structure in the sequencing batch biofilm reactor (SBBR) remained reasonably stable. Candidatus Brocadia was the only detected anammox genus and remained stable at 0.3-0.5%. Some psychrotolerant microorganisms that could secrete cryoprotective extracellular polymeric substances (EPS), including Flavobacterium and Thermomonas, were enriched at low temperatures. This could be conducive to the stable operation of the PNA-SBBR. Moreover, according to the EPS composition and characteristics analysis, the secretion of tightly-bound EPS that bound to the cell surface containing plentiful protein was stimulated at low temperatures, further improving the system stability. Overall, the reasonably stable microbial community structure, enrichment of psychrotolerant microorganisms, and increased secretion of EPS could play important roles for stable sewage nitrogen removal at low temperatures.


Assuntos
Microbiota , Nitrificação , Biofilmes , Reatores Biológicos , Desnitrificação , Matriz Extracelular de Substâncias Poliméricas , Nitrogênio , Oxirredução , Esgotos , Temperatura Ambiente
13.
Psychoneuroendocrinology ; 112: 104483, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757429

RESUMO

Infidelity is the major cause of breakups and individuals with a history of infidelity are more likely to repeat it, but may also present a greater opportunity for short-term sexual relationships. Here in a pre-registered, double-blind study involving 160 subjects we report that while both sexes valued faithful individuals most for short-term and long-term relationships, both single men and those in a relationship were more interested in having short-term relationships with previously unfaithful individuals than women. Oxytocin administration resulted in men rating the faces of unfaithful women as more attractive and likeable but in women rating those of unfaithful men as less attractive and also finding them less memorable. Oxytocin also increased single men's interest in having short-term relationships with previously unfaithful women whereas it increased single women's interest in having long-term relationships with faithful men. Thus, oxytocin release during courtship may first act to amplify sex-dependent priorities in attraction and mate choice before subsequently promoting romantic bonds.

14.
Water Res ; 170: 115363, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816567

RESUMO

For achieving energy-efficient wastewater treatment, a novel simultaneous nitrogen and phosphorus removal (SNPR) process, which integrated anammox, endogenous partial-denitrification and denitrifying dephosphatation in a sequencing batch reactor with granular sludge was developed to treat mainstream wastewater. After 200 days of operation, a simultaneous high-level nitrogen and phosphorus removal of 93.9% and 94.2%, respectively was achieved with an average influent C/N ratio of 2.9. Anammox pathway contributed 82.9% of the overall nitrogen removal because of the stable nitrite production from nitrate via endogenous partial-denitrification. In addition, phosphorus was mainly removed via denitrifying dephosphatation utilizing nitrate as the electron acceptor, resulting in a significant saving of carbon sources and oxygen demands. Further, adsorption/precipitation of phosphorus occurred in this novel SNPR process, which displaced the energy source to the metabolism of glycogen accumulating organisms (GAOs) for nitrite production and alleviated competition between phosphorus accumulating organisms (PAOs) and anammox for electron acceptor. Using 16S rRNA gene amplicon sequencing analysis, the study found that anammox bacteria (8.4%), GAOs (1.5%) and PAOs (1.1%) co-existed in this system, potentially resulting in simultaneous endogenous partial-denitrification, anammox and denitrifying dephosphatation. The above results demonstrated that the novel SNPR process is a promising technique for energy-efficient wastewater treatment.


Assuntos
Desnitrificação , Águas Residuárias , Reatores Biológicos , Nitrogênio , Fósforo , RNA Ribossômico 16S , Esgotos
15.
Cancer Biol Ther ; 21(2): 130-138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31690181

RESUMO

Programmed death ligand-1 (PD-L1) expression and the presence of tumor-infiltrating lymphocytes (TILs) in tumor microenvironment were common in chronic inflammatory tumor types and frequently responded to the PD-L1 pathway immune checkpoint blockade in the clinic. Animal models to optimize such immunotherapeutics comprise an important strategy but often fail to predict the efficacy of clinical approaches. To address this, we aimed to establish new mouse models. In this study, we found that the expression of PD-L1was present at the beginning stage but a gradual decline over time in the in vitro cell culture and also in the mouse model. Based upon this finding, we established the IFN-γ-(human peripheral blood mononuclear cell) PBMC-CDX (cell line-derived xenograft) and IFN-γ-PBMC-PDX (patient-derived xenograft) mouse models, which recapitulate human tumor and human immune system interactions. IFN-γ was injected peritumorally to maintain the positivity of PD-L1 in the tumor microenvironment. Under this circumstance, the PD-1 molecule on the human T lymphocyte surface is in contact with the PD-L1 molecule on the human tumor cells and, thus, the formatin of the PD-L1/PD-1 pathway in the tumor microenvironment.Treatment with anti-PD-1 monoclonal antibody (mAb) significantly inhibited the growth of both CDX and PDX tumors, but not non-human NCG models (without allogeneic human PBMCs and IFN-γ) . These experimental data provide an important and promising platform for the development of drugs and the evaluation of the drug efficacy of immunotherapies with anti-PD-1 mAb as well as the basis of preclinical mAb drug research.

16.
Genes Genomics ; 42(1): 77-85, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31736006

RESUMO

OBJECTIVE: Aim of this study was to detect the expression of miR-15a in rats following chronic constriction injury (CCI) and to investigate the regulatory functions of miR-15a during neuropathic pain (NP) development. METHODS: CCI was performed in adult Sprague-Dawley rats to set up the rat model of neuropathic pain. MiR-15a agomir and scrambled control were delivered into the implanted catheter of rats. The mechanical allodynia and thermal hyperalgesia were assessed in both CCI- and sham-operated groups. Rat lumbar spinal cord tissues were harvested for mRNA and protein analyses. The primary spinal microglia were isolated from adult Sprague-Dawley rats and transfected with miR-15a mimics, scramble miRNA, miR-15a inhibitor or its corresponding negative control. Cell lysates were collected for mRNA and protein analyses. RESULTS: Compared to sham-operated group, the expression of miR-15a in CCI rats was significantly reduced, whereas neuroinflammation in spinal cord tissues was increased. Intrathecal administration of miR-15a agomir significantly attenuated CCI-induced NP and the levels of proinflammatory cytokines, including IL-6, IL-1ß, and TNF-α. AKT3 was predicted and confirmed as a miR-15a-regulated gene. We further demonstrated that miR-15a overexpression downregulated the level of AKT3 in primary rat microglia and rat CCI model. Moreover, the upregulation of miR-15a induced the expressions of autophagy-associated proteins, suggesting that the regulation mechanism of miR-15a in NP development involves AKT3-mediated autophagy via inhibiting the expression of AKT3. CONCLUSION: Our findings indicated that miR-15a might serve as a promising therapeutic target for the management of NP through the stimulation of autophagic process.

17.
Nucleic Acids Res ; 48(D1): D226-D232, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31511885

RESUMO

Alternative polyadenylation (APA) is an important post-transcriptional regulation that recognizes different polyadenylation signals (PASs), resulting in transcripts with different 3' untranslated regions, thereby influencing a series of biological processes and functions. Recent studies have revealed that some single nucleotide polymorphisms (SNPs) could contribute to tumorigenesis and development through dysregulating APA. However, the associations between SNPs and APA in human cancers remain largely unknown. Here, using genotype and APA data of 9082 samples from The Cancer Genome Atlas (TCGA) and The Cancer 3'UTR Altas (TC3A), we systematically identified SNPs affecting APA events across 32 cancer types and defined them as APA quantitative trait loci (apaQTLs). As a result, a total of 467 942 cis-apaQTLs and 30 721 trans-apaQTLs were identified. By integrating apaQTLs with survival and genome-wide association studies (GWAS) data, we further identified 2154 apaQTLs associated with patient survival time and 151 342 apaQTLs located in GWAS loci. In addition, we designed an online tool to predict the effects of SNPs on PASs by utilizing PAS motif prediction tool. Finally, we developed SNP2APA, a user-friendly and intuitive database (http://gong_lab.hzau.edu.cn/SNP2APA/) for data browsing, searching, and downloading. SNP2APA will significantly improve our understanding of genetic variants and APA in human cancers.

18.
Neuroimage ; 206: 116315, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669409

RESUMO

Non-invasive quantitative imaging of cerebral oxygen metabolism (CMRO2) in small animal models is crucial to understand the role of oxidative metabolism in healthy and diseased brains. In this study, we developed a multimodal method combining near-infrared spectroscopy (NIRS) and MRI to non-invasively study oxygen delivery and consumption in the cortex of mouse and rat models. The term CASNIRS is proposed to the technique that measures CMRO2 with ASL and NIRS. To determine the reliability of this method, CMRO2 values were compared with reported values measured with other techniques. Also, the sensitivity of the CASNIRS technique to detect changes in CMRO2 in the cortex of the animals was assessed by applying a reduction in core temperature, which is known to reduce CMRO2. Cerebral blood flow (CBF) and CMRO2 were measured in five mice and five rats at a core temperature of 37 °C followed by another measurement at 33 °C. CMRO2 was 7.8 ±â€¯1.8 and 3.7 ±â€¯0.9 (ml/100 g/min, mean ±â€¯SD) in mice and rats respectively. These values are in good agreement with reported values measured by 15O PET, 17O NMR, and BOLD fMRI. In hypothermia, we detected a significant decrease of 37% and 32% in CMRO2 in the cortex of mice and rats, respectively. Q10 was calculated to be 3.2 in mice and 2.7 in rats. In this study we showed that it is possible to assess absolute values of metabolic correlates such as CMRO2, CBF and oxygen extraction fraction (OEF) noninvasively in living brain of mice and rats by combining NIRS with MRI. This will open new possibilities for studying brain metabolism in patients as well as the many mouse/rat models of brain disorders.

19.
Biochim Biophys Acta Mol Cell Res ; 1867(2): 118574, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31682865

RESUMO

During keratinocyte stratification and wound healing, keratinocytes undergo a switch between differentiation and motility. However, limited knowledge exists on the mechanisms of the switch. We have previously demonstrated that the expression of CD9 was changed in different wound stages and involved in the regulation of keratinocyte migration. In this study, we showed that CD9 expression was increased in both human and mouse keratinocytes undergoing differentiation. CD9 overexpression in keratinocytes stimulated terminal differentiation and reduced cell motility. CD9 silencing inhibited calcium-induced keratinocyte differentiation and increased cell motility. Furthermore, CD9 overexpression recruited E-cadherin to the plasma membrane and subsequently activated PI3K/Akt signaling, while CD9 knockdown inhibited the recruitment of E-cadherin to the plasma membrane and PI3K/Akt activation. Importantly, silencing E-cadherin expression or inhibiting PI3K/Akt signaling reversed CD9 overexpression-induced differentiation and -reduced motility. These results demonstrate that CD9 acts as an important node that regulates keratinocyte differentiation and motility. The recruitment of E-cadherin to the plasma membrane and activation of the PI3K/Akt signaling pathway mediated by CD9 play an important role in these processes.

20.
Biomed Pharmacother ; 123: 109722, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31865144

RESUMO

BACKGROUND AND PURPOSE: Recent studies have suggested that H2S may be involved in the pathophysiology of subarachnoid hemorrhage (SAH). Endogenous H2S is mainly formed by cystathionine ß-synthase (CBS), d-amino-acid oxidase (DAO), and 3-mercaptopyruvate sulfotransferase (3-MST) from the substrate cysteine in the central nervous system. In this study, we assessed the expression of CBS, 3-MST, and DAO in cerebrospinal fluid (CSF) from patients with SAH and rats and the expression in the rat brain. METHODS: CSF samples were collected within 48 h of aneurysm rupture in SAH patients. The CBS, DAO and 3-MST levels in CSF were measured using Western blot analyses, and correlations with the inflammatory parameter Interleukin-6 (IL-6) were assessed. Six months after SAH, the clinical outcomes were assessed. RESULTS: In human CSF samples, the CBS and DAO protein levels were detected and increased after SAH. However, 3-MST was not detected in the control group CSF but increased after SAH. Strong correlations were observed between the increasing levels of CBS, DAO, and 3-MST and IL-6 2 days after SAH. Furthermore, high CBS, 3-MST and DAO levels in the CSF samples were correlated with poor outcomes at 6 months after SAH onset. We also found that the expression of CBS, DAO and 3-MST in the rat CSF and brain (parietal cortex and hippocampus) increased following SAH. We detected strong correlations between the increases in CBS, 3-MST and IL-6 in the rat CSF and brain samples. CONCLUSIONS: These results indicate that the upregulated expression of CBS, DAO and 3-MST after SAH was closely associated with the inflammatory response and neurological deficits after SAH.

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