NeuroImmune pharmacology and therapeutics最新文献_第5页

The link between chronic cocaine use, B cell perturbations, and blunted immune recovery in HIV-infected individuals on suppressive ART. 慢性可卡因使用、B细胞紊乱和艾滋病病毒感染者接受抑制性抗逆转录病毒治疗后免疫恢复迟钝之间的联系

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-25 Epub Date: 2023-03-27 DOI: 10.1515/nipt-2022-0019

Da Cheng, Zhenwu Luo, Sylvia Fitting, William Stoops, Sonya L Heath, Lishomwa C Ndhlovu, Wei Jiang

{"title":"The link between chronic cocaine use, B cell perturbations, and blunted immune recovery in HIV-infected individuals on suppressive ART.","authors":"Da Cheng, Zhenwu Luo, Sylvia Fitting, William Stoops, Sonya L Heath, Lishomwa C Ndhlovu, Wei Jiang","doi":"10.1515/nipt-2022-0019","DOIUrl":"10.1515/nipt-2022-0019","url":null,"abstract":"Background: We recently reveal that anti-CD4 autoantibodies contribute to blunted CD4+ T cell reconstitution in HIV+ individuals on antiretroviral therapy (ART). Cocaine use is common among HIV+ individuals and is associated with accelerated disease progression. However, the mechanisms underlying cocaine-induced immune perturbations remain obscure.Methods: We evaluated plasma levels of anti-CD4 IgG and markers of microbial translocation, as well as B-cell gene expression profiles and activation in HIV+ chronic cocaine users and non-users on suppressive ART, as well as uninfected controls. Plasma purified anti-CD4 IgGs were assessed for antibody-dependent cytotoxicity (ADCC).Results: HIV+ cocaine users had increased plasma levels of anti-CD4 IgGs, lipopolysaccharide (LPS), and soluble CD14 (sCD14) versus non-users. An inverse correlation was observed in cocaine users, but not non-drug users. Anti-CD4 IgGs from HIV+ cocaine users mediated CD4+ T cell death through ADCC in vitro. B cells from HIV+ cocaine users exhibited activation signaling pathways and activation (cycling and TLR4 expression) related to microbial translocation versus non-users.Conclusions: This study improves our understanding of cocaine associated B cell perturbations and immune failure and the new appreciation for autoreactive B cells as novel therapeutic targets.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"71-79"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9563743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abnormal brain diffusivity in participants with persistent neuropsychiatric symptoms after COVID-19. COVID-19 后出现持续神经精神症状的参与者大脑弥散异常。

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-25 Epub Date: 2023-01-05 DOI: 10.1515/nipt-2022-0016

Huajun Liang, Thomas Ernst, Kenichi Oishi, Meghann C Ryan, Edward Herskovits, Eric Cunningham, Eleanor Wilson, Shyamasundaran Kottilil, Linda Chang

{"title":"Abnormal brain diffusivity in participants with persistent neuropsychiatric symptoms after COVID-19.","authors":"Huajun Liang, Thomas Ernst, Kenichi Oishi, Meghann C Ryan, Edward Herskovits, Eric Cunningham, Eleanor Wilson, Shyamasundaran Kottilil, Linda Chang","doi":"10.1515/nipt-2022-0016","DOIUrl":"10.1515/nipt-2022-0016","url":null,"abstract":"Objectives: We aimed to compare brain white matter integrity in participants with post-COVID-19 conditions (PCC) and healthy controls.Methods: We compared cognitive performance (NIH Toolbox®), psychiatric symptoms and diffusion tensor imaging (DTI) metrics between 23 PCC participants and 24 controls. Fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities were measured in 9 white matter tracts and 6 subcortical regions using MRICloud.Results: Compared to controls, PCC had similar cognitive performance, but greater psychiatric symptoms and perceived stress, as well as higher FA and lower diffusivities in multiple white matter tracts (ANCOVA-p-values≤0.001-0.048). Amongst women, PCC had higher left amygdala-MD than controls (sex-by-PCC p=0.006). Regardless of COVID-19 history, higher sagittal strata-FA predicted greater fatigue (r=0.48-0.52, p<0.001) in all participants, and higher left amygdala-MD predicted greater fatigue (r=0.61, p<0.001) and anxiety (r=0.69, p<0.001) in women, and higher perceived stress (r=0.45, p=0.002) for all participants.Conclusions: Microstructural abnormalities are evident in PCC participants averaged six months after COVID-19. The restricted diffusivity (with reduced MD) and higher FA suggest enhanced myelination or increased magnetic susceptibility from iron deposition, as seen in stress conditions. The higher amygdala-MD in female PCC suggests persistent neuroinflammation, which might contribute to their fatigue, anxiety, and perceived stress.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"37-48"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9318993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual-Peak Lorentzian CEST MRI for antiretroviral drug brain distribution. 抗逆转录病毒药物脑分布的双峰洛伦兹CEST磁共振成像。

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-25 Epub Date: 2022-09-13 DOI: 10.1515/nipt-2022-0012

Yutong Liu, Gabriel C Gauthier, Howard E Gendelman, Aditya N Bade

{"title":"Dual-Peak Lorentzian CEST MRI for antiretroviral drug brain distribution.","authors":"Yutong Liu, Gabriel C Gauthier, Howard E Gendelman, Aditya N Bade","doi":"10.1515/nipt-2022-0012","DOIUrl":"10.1515/nipt-2022-0012","url":null,"abstract":"Objectives: Spatial-temporal biodistribution of antiretroviral drugs (ARVs) can now be achieved using MRI by utilizing chemical exchange saturation transfer (CEST) contrasts. However, the presence of biomolecules in tissue limits the specificity of current CEST methods. To overcome this limitation, a Lorentzian line-shape fitting algorithm was developed that simultaneously fits CEST peaks of ARV protons on its Z-spectrum.Case presentation: This algorithm was tested on the common first line ARV, lamivudine (3TC), that has two peaks resulting from amino (-NH2) and hydroxyl (-OH) protons in 3TC. The developed dual-peak Lorentzian function fitted these two peaks simultaneously, and used the ratio of -NH2 and -OH CEST contrasts as a constraint parameter to measure 3TC presence in brains of drug-treated mice. 3TC biodistribution calculated using the new algorithm was compared against actual drug levels measured using UPLC-MS/MS. In comparison to the method that employs the -NH2 CEST peak only, the dual-peak Lorentzian fitting algorithm showed stronger correlation with brain tissue 3TC levels, signifying estimation of actual drug levels.Conclusions: We concluded that 3TC levels can be extracted from confounding CEST effects of tissue biomolecules resulting in improved specificity for drug mapping. This algorithm can be expanded to measure a variety of ARVs using CEST MRI.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"63-69"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9270378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of cannabinoids on inflammasome signaling in HIV-1 infection. 大麻素对 HIV-1 感染中炎性信号转导的影响。

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-25 Epub Date: 2023-02-23 DOI: 10.1515/nipt-2023-0002

Alice K Min, Aislinn M Keane, Matthew Paltiel Weinstein, Talia H Swartz

{"title":"The impact of cannabinoids on inflammasome signaling in HIV-1 infection.","authors":"Alice K Min, Aislinn M Keane, Matthew Paltiel Weinstein, Talia H Swartz","doi":"10.1515/nipt-2023-0002","DOIUrl":"10.1515/nipt-2023-0002","url":null,"abstract":"Human immunodeficiency virus type 1 (HIV-1) is a chronic disease that afflicts over 38 million people worldwide without a known cure. The advent of effective antiretroviral therapies (ART) has significantly decreased the morbidity and mortality associated with HIV-1 infection in people living with HIV-1 (PWH), thanks to durable virologic suppression. Despite this, people with HIV-1 experience chronic inflammation associated with co-morbidities. While no single known mechanism accounts for chronic inflammation, there is significant evidence to support the role of the NLRP3 inflammasome as a key driver. Numerous studies have demonstrated therapeutic impact of cannabinoids, including exerting modulatory effects on the NLRP3 inflammasome. Given the high rates of cannabinoid use in PWH, it is of great interest to understand the intersecting biology of the role of cannabinoids in HIV-1-associated inflammasome signaling. Here we describe the literature of chronic inflammation in people with HIV, the therapeutic impact of cannabinoids in PWH, endocannabinoids in inflammation, and HIV-1-associated inflammation. We describe a key interaction between cannabinoids, the NLRP3 inflammasome, and HIV-1 viral infection, which supports further investigation of the critical role of cannabinoids in HIV-1 infection and inflammasome signaling.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"79-88"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9264692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mu opioid receptor-mediated release of endolysosome iron increases levels of mitochondrial iron, reactive oxygen species, and cell death. 缪阿片受体介导的溶酶体内铁释放会增加线粒体铁、活性氧和细胞死亡水平。

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-25 Epub Date: 2022-09-14 DOI: 10.1515/nipt-2022-0013

Peter W Halcrow, Nirmal Kumar, Emily Hao, Nabab Khan, Olimpia Meucci, Jonathan D Geiger

{"title":"Mu opioid receptor-mediated release of endolysosome iron increases levels of mitochondrial iron, reactive oxygen species, and cell death.","authors":"Peter W Halcrow, Nirmal Kumar, Emily Hao, Nabab Khan, Olimpia Meucci, Jonathan D Geiger","doi":"10.1515/nipt-2022-0013","DOIUrl":"10.1515/nipt-2022-0013","url":null,"abstract":"Objectives: Opioids including morphine and DAMGO activate mu-opioid receptors (MOR), increase intracellular reactive oxygen species (ROS) levels, and induce cell death. Ferrous iron (Fe2+) through Fenton-like chemistry increases ROS levels and endolysosomes are \"master regulators of iron metabolism\" and contain readily-releasable Fe2+ stores. However, mechanisms underlying opioid-induced changes in endolysosome iron homeostasis and downstream-signaling events remain unclear.Methods: We used SH-SY5Y neuroblastoma cells, flow cytometry, and confocal microscopy to measure Fe2+ and ROS levels and cell death.Results: Morphine and DAMGO de-acidified endolysosomes, decreased endolysosome Fe2+ levels, increased cytosol and mitochondria Fe2+ and ROS levels, depolarized mitochondrial membrane potential, and induced cell death; effects blocked by the nonselective MOR antagonist naloxone and the selective MOR antagonist β-funaltrexamine (β-FNA). Deferoxamine, an endolysosome-iron chelator, inhibited opioid agonist-induced increases in cytosolic and mitochondrial Fe2+ and ROS. Opioid-induced efflux of endolysosome Fe2+ and subsequent Fe2+ accumulation in mitochondria were blocked by the endolysosome-resident two-pore channel inhibitor NED-19 and the mitochondrial permeability transition pore inhibitor TRO.Conclusions: Opioid agonist-induced increases in cytosolic and mitochondrial Fe2+ and ROS as well as cell death appear downstream of endolysosome de-acidification and Fe2+ efflux from the endolysosome iron pool that is sufficient to affect other organelles.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"19-35"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9684727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Apigenin improves cytotoxicity of antiretroviral drugs against HTLV-1 infected cells through the modulation of AhR signaling. 芹菜素通过调节 AhR 信号转导提高抗逆转录病毒药物对 HTLV-1 感染细胞的细胞毒性。

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-25 Epub Date: 2023-02-17 DOI: 10.1515/nipt-2022-0017

Dominic Sales, Edward Lin, Victoria Stoffel, Shallyn Dickson, Zafar K Khan, Joris Beld, Pooja Jain

{"title":"Apigenin improves cytotoxicity of antiretroviral drugs against HTLV-1 infected cells through the modulation of AhR signaling.","authors":"Dominic Sales, Edward Lin, Victoria Stoffel, Shallyn Dickson, Zafar K Khan, Joris Beld, Pooja Jain","doi":"10.1515/nipt-2022-0017","DOIUrl":"10.1515/nipt-2022-0017","url":null,"abstract":"Objectives: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neuroinflammatory autoimmune disease characterized by high levels of infected immortalized T cells in circulation, which makes it difficult for antiretroviral (ART) drugs to work effectively. In previous studies, we established that Apigenin, a flavonoid, can exert immunomodulatory effects to reduce neuroinflammation. Flavonoids are natural ligands for the aryl hydrocarbon receptor (AhR), which is a ligand activated endogenous receptor involved in the xenobiotic response. Consequently, we tested Apigenin's synergy in combination with ART against the survival of HTLV-1-infected cells.Methods: First, we established a direct protein-protein interaction between Apigenin and AhR. We then demonstrated that Apigenin and its derivative VY-3-68 enter activated T cells, drive nuclear shuttling of AhR, and modulate its signaling both at RNA and protein level.Results: In HTLV-1 producing cells with high AhR expression, Apigenin cooperates with ARTs such as Lopinavir (LPN) and Zidovudine (AZT), to impart cytotoxicity by exhibiting a major shift in IC50 that was reversed upon AhR knockdown. Mechanistically, Apigenin treatment led to an overall downregulation of NF-κB and several other pro-cancer genes involved in survival.Conclusions: This study suggest the potential combinatorial use of Apigenin with current first-line antiretrovirals for the benefit of patients affected by HTLV-1 associated pathologies.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"49-62"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9270379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanisms of Zika astrocyte infection and neuronal toxicity. 寨卡病毒感染星形胶质细胞和神经元毒性的机制。

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-25 Epub Date: 2022-10-21 DOI: 10.1515/nipt-2022-0014

Courtney Veilleux, Eliseo A Eugenin

{"title":"Mechanisms of Zika astrocyte infection and neuronal toxicity.","authors":"Courtney Veilleux, Eliseo A Eugenin","doi":"10.1515/nipt-2022-0014","DOIUrl":"10.1515/nipt-2022-0014","url":null,"abstract":"Objectives: Zika virus (ZIKV) has become an epidemic in several countries and was declared a major public health issue by the WHO. Although ZIKV infection is asymptomatic or shows mild fever-related symptoms in most people, the virus can be transmitted from a pregnant mother to the fetus, resulting in severe brain developmental abnormalities, including microcephaly. Multiple groups have identified developmental neuronal and neuronal progenitor compromise during ZIKV infection within the fetal brain, but little is known about whether ZIKV could infect human astrocytes and its effect on the developing brain. Thus, our objective was to determine astrocyte ZiKV infection in a developmental-dependent manner.Methods: We analyze infection of pure cultures of astrocytes and mixed cultures of neurons and astrocytes in response to ZIKV using plaque assays, confocal, and electron microscopy to identify infectivity, ZIKV accumulation and intracellular distribution as well as apoptosis and interorganelle dysfunction.Results: Here, we demonstrated that ZIKV enters, infects, replicates, and accumulates in large quantities in human fetal astrocytes in a developmental-dependent manner. Astrocyte infection and intracellular viral accumulation resulted in neuronal apoptosis, and we propose astrocytes are a ZIKV reservoir during brain development.Conclusions: Our data identify astrocytes in different stages of development as major contributors to the devastating effects of ZIKV in the developing brain.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"5-18"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9270376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PurA sensitizes cells to toxicity induced by oxidative stress PurA使细胞对氧化应激引起的毒性敏感

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-23 DOI: 10.1515/nipt-2022-0020

Hawra Albukhaytan, B. Torkzaban, I. Sariyer, S. Amini

{"title":"PurA sensitizes cells to toxicity induced by oxidative stress","authors":"Hawra Albukhaytan, B. Torkzaban, I. Sariyer, S. Amini","doi":"10.1515/nipt-2022-0020","DOIUrl":"https://doi.org/10.1515/nipt-2022-0020","url":null,"abstract":"Abstract Objectives PurA is an evolutionary conserved protein that is known to bind to single stranded DNA or RNA and regulate both transcription and translation. PurA has been implicated in many neurological and neurodevelopmental deficits, but its role in response to cellular stress has not yet been clarified. In this study, we have studied the cells’ stress response in the presence and absence of PurA expression. Methods Oxidative stress was induced in MEF cells obtained from PURA WT and K/O mice by paraquat treatments. The cellular response to stress was determined and compared by viability assays, immunocytochemistry and biochemical analyses. Results Interestingly, paraquat treated PurA expressing MEF cells showed higher sensitivity and less cellular viability than those with no PurA expression. Moreover, western blot analysis revealed increase in the expression of the apoptotic marker cleaved caspase 3 and autophagy marker LC3-II in PurA WT MEF cells compared to the PurA K/O MEF cells under oxidative stress induction. Conclusions Our observations indicate that PurA may play a key role in regulating cellular toxicity induced by oxidative stress and emphasize its importance for cell-fate determination under cytotoxic stress conditions.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"119 - 125"},"PeriodicalIF":0.0,"publicationDate":"2023-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47831064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Network meta-analysis on alcohol-mediated modulation of Alzheimer’s disease in the diseases of inflammation including COVID-19 酒精介导的阿尔茨海默病在包括新冠肺炎在内的炎症疾病中的调节作用的网络荟萃分析

NeuroImmune pharmacology and therapeutics Pub Date : 2023-02-21 DOI: 10.1515/nipt-2022-0018

Muhammed Bishir, Tatiana Rengifo, Wenfei Huang, Ryan J. Kim, S. Chidambaram, Sulie L. Chang

{"title":"Network meta-analysis on alcohol-mediated modulation of Alzheimer’s disease in the diseases of inflammation including COVID-19","authors":"Muhammed Bishir, Tatiana Rengifo, Wenfei Huang, Ryan J. Kim, S. Chidambaram, Sulie L. Chang","doi":"10.1515/nipt-2022-0018","DOIUrl":"https://doi.org/10.1515/nipt-2022-0018","url":null,"abstract":"Abstract Objectives Cross sectional surveys have reported that alcohol consumption has skyrocketed during the COVID-19 pandemic. Chronic alcohol use triggers systemic inflammation which leads to neuroinflammation and neurodegeneration. In the present study, we hypothesize that alcohol consumption and cytokine elevation during inflammatory conditions synergistically increase amyloid-beta precursor protein (APP) expression and worsens Alzheimer’s disease (AD) pathology. Methods QIAGEN Ingenuity Pathway Analysis (IPA) was employed to conduct network meta-analysis on the molecular mechanisms underlying ethanol (EtOH) influence on APP expression and AD in inflammatory conditions including COVID-19, inflammation of respiratory system, organ, absolute anatomical region, body cavity, joint, respiratory system component, gastrointestinal tract, large intestine, liver, central nerve system, and lung. IPA tools were utilized to identify the molecules associated with EtOH, inflammatory conditions and the common molecules between them. Results Simulation activity of EtOH, mimicking exposure to alcohol, upregulated the APP expression and augmented AD pathology in all inflammatory conditions including COVID-19. Our studies identified six molecules including ADORA2A, Cytokine, IFN-gamma, IL1-beta, Immunoglobulin and TNF, which concurrently contribute to increased APP expression and AD progression upon EtOH simulation in all diseases studied. Conclusions The present study has revealed molecular mechanisms underlying alcohol augmentation of AD in COVID-19 and other diseases of inflammation.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45526010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Challenges in ultralong-acting formulation development: eyes on buprenorphine 长效制剂开发面临的挑战：丁丙诺啡

NeuroImmune pharmacology and therapeutics Pub Date : 2023-01-24 DOI: 10.1515/nipt-2023-0001

S. Deodhar, Benson J. Edagwa, Brady Sillman

引用次数: 0