FASEB bioAdvances最新文献

{"title":"A combination of 5/6-nephrectomy and unilateral ureteral obstruction model accelerates progression of remote organ fibrosis in chronic kidney disease","authors":"Kyoka Homma,&nbsp;Yuki Enoki,&nbsp;Sato Uchida,&nbsp;Kazuaki Taguchi,&nbsp;Kazuaki Matsumoto","doi":"10.1096/fba.2023-00045","DOIUrl":"10.1096/fba.2023-00045","url":null,"abstract":"<p>Chronic kidney disease (CKD) involves progressive renal fibrosis, which gradually reduces kidney function and often causes various complications in extrarenal tissues. Therefore, we investigated fibrogenesis in extrarenal tissues (heart, liver, and lungs) in different experimental CKD models, such as the 5/6-nephrectomy (5/6 Nx), unilateral ureteral obstruction (UUO), and a combination (2/3 Nx + UUO). We evaluated the degree of fibrogenesis in kidneys and extrarenal tissues by histological analysis and quantification of fibrosis-related gene and protein expression. To elucidate the fibrosis mechanisms observed in 2/3 Nx + UUO mice, we evaluated the effect of indoxyl sulfate (IS), a typical uremic toxin accumulated in CKD, and transforming growth factor-β (TGF-β), a fibrosis-related factor, on fibrosis using human hepatoma (HepG2) and RAW264.7 cells. A significant decline in renal function was observed in the 5/6 Nx and 2/3 Nx + UUO models, whereas a significant increase in renal fibrosis was observed only in the obstructed kidneys. Notable amount of fibrosis was induced in the liver and heart in the 2/3 Nx + UUO model, with the induction of macrophage infiltration and increased tissue IS and TGF-β levels. In agreement with the results of in vivo experiments, co-stimulation with IS, TGF-β, and macrophage-conditioned medium increased the expression of fibrogenic genes in HepG2 cells. We demonstrated that the 2/3 Nx + UUO model induced both loss of renal function and renal fibrosis in the earlier stages, providing a novel CKD model that induces remote organ fibrosis in a shorter time.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 10","pages":"377-394"},"PeriodicalIF":2.7,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41144419","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}

{"title":"Discovery of phytochelatins in human urine: Evidence for function in selenium disposition and protection against cadmium","authors":"Zachery R. Jarrell,&nbsp;Ken H. Liu,&nbsp;Kristine K. Dennis,&nbsp;Xin Hu,&nbsp;Greg S. Martin,&nbsp;Dean P. Jones,&nbsp;Young-Mi Go","doi":"10.1096/fba.2023-00050","DOIUrl":"10.1096/fba.2023-00050","url":null,"abstract":"<p>This report identifies, for the first time, a phytochelatin compound, phytochelatin 2 [γ-E-C-γ-E-C-G], and related metabolites in human urine. Phytochelatins are metal-binding peptides produced by plants. They are present in nearly all human diets, due to their ubiquity in plants. The urinary concentration of phytochelatin 2 among 143 adults was in the low micromolar range, and phytochelatin 2 and its metabolites had differential correlations with urinary selenium and toxic metals. Activities of ingested phytochelatins are largely undescribed. Observed urinary metal interactions were investigated further in cell and animal models. Selenite reacted with phytochelatin to form a phytochelatin selenotrisulfide, and the preformed selenotrisulfide showed increased selenium uptake by renal proximal tubule cells. In vivo studies further showed that oral phytochelatin increased renal selenium content and decreased lung cadmium in mice. Presence of phytochelatin in human urine combined with its function in selenium and heavy metal distribution present a new route by which diet may influence metal disposition and bioavailability.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 9","pages":"367-375"},"PeriodicalIF":2.7,"publicationDate":"2023-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/c1/FBA2-5-367.PMC10478506.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10550705","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}

{"title":"Mitochondrial reactive oxygen species modify extracellular vesicles secretion rate","authors":"Mikkel Ø. Nørgård,&nbsp;Philip M. Lund,&nbsp;Nazmie Kalisi,&nbsp;Thomas L. Andresen,&nbsp;Jannik B. Larsen,&nbsp;Stefan Vogel,&nbsp;Per Svenningsen","doi":"10.1096/fba.2023-00053","DOIUrl":"10.1096/fba.2023-00053","url":null,"abstract":"<p>Extracellular vesicle (EV) secretion rate is stimulated by hypoxia that causes increased reactive oxygen species (ROS) production by the mitochondrial electron transport chain (ETC) and hypoxia-induced factor (HIF)-1 signaling; however, their contribution to the increased EV secretion rate is unknown. We found that the EV marker secretion rate in our EV reporter cell line CD9truc-EGFP was unaffected by the HIF-1α stabilizer roxadustat; yet, ETC stimulation by dichloroacetic acid (DCA) significantly increased EV secretion. The DCA-induced EV secretion was blocked by the antioxidant TEMPO and rotenone, an inhibitor of the ETC's Complex I. Under hypoxic conditions, the limited oxygen reduction impedes the ETC's Complex III. To mimic this, we inhibited Complex III with antimycin A, which increased ROS-dependent EV secretion. The electron transport between Complex I and III is accomplished by coenzyme Q created by the mevalonate pathway and tyrosine metabolites. Blocking an early step in the mevalonate pathway using pitavastatin augmented the DCA-induced EV secretion, and 4-nitrobenzoate—an inhibitor of the condensation of the mevalonate pathway with tyrosine metabolites—increased ROS-dependent EV secretion. Our findings indicate that hypoxia-mimetics targeting the ETC modify EV secretion and that ROS produced by the ETC is a potent stimulus for EV secretion.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 9","pages":"355-366"},"PeriodicalIF":2.7,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/25/FBA2-5-355.PMC10478507.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10550700","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}

{"title":"Two different isoforms of osteopontin modulate myelination and axonal integrity","authors":"Gisela Nilsson,&nbsp;Amin Mottahedin,&nbsp;Aura Zelco,&nbsp;Volker M. Lauschke,&nbsp;C. Joakim Ek,&nbsp;Juan Song,&nbsp;Maryam Ardalan,&nbsp;Sha Hua,&nbsp;Xiaoli Zhang,&nbsp;Carina Mallard,&nbsp;Henrik Hagberg,&nbsp;Jianmei W. Leavenworth,&nbsp;Xiaoyang Wang","doi":"10.1096/fba.2023-00030","DOIUrl":"10.1096/fba.2023-00030","url":null,"abstract":"<p>Abnormal myelination underlies the pathology of white matter diseases such as preterm white matter injury and multiple sclerosis. Osteopontin (OPN) has been suggested to play a role in myelination. Murine OPN mRNA is translated into a secreted isoform (sOPN) or an intracellular isoform (iOPN). Whether there is an isoform-specific involvement of OPN in myelination is unknown. Here we generated mouse models that either lacked both OPN isoforms in all cells (OPN-KO) or lacked sOPN systemically but expressed iOPN specifically in oligodendrocytes (OLs-iOPN-KI). Transcriptome analysis of isolated oligodendrocytes from the neonatal brain showed that genes and pathways related to increase of myelination and altered cell cycle control were enriched in the absence of the two OPN isoforms in OPN-KO mice compared to control mice. Accordingly, adult OPN-KO mice showed an increased axonal myelination, as revealed by transmission electron microscopy imaging, and increased expression of myelin-related proteins. In contrast, neonatal oligodendrocytes from OLs-iOPN-KI mice compared to control mice showed differential regulation of genes and pathways related to the increase of cell adhesion, motility, and vasculature development, and the decrease of axonal/neuronal development. OLs-iOPN-KI mice showed abnormal myelin formation in the early phase of myelination in young mice and signs of axonal degeneration in adulthood. These results suggest an OPN isoform-specific involvement, and a possible interplay between the isoforms, in myelination, and axonal integrity. Thus, the two isoforms of OPN need to be separately considered in therapeutic strategies targeting OPN in white matter injury and diseases.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 8","pages":"336-353"},"PeriodicalIF":2.7,"publicationDate":"2023-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fc/03/FBA2-5-336.PMC10405251.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9968171","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}

{"title":"An insight on the N-glycome of notochordal cell-rich porcine nucleus pulposus during maturation","authors":"Büşra Günay,&nbsp;Elizabeth Matthews,&nbsp;Jack Morgan,&nbsp;Marianna A. Tryfonidou,&nbsp;Radka Saldova,&nbsp;Abhay Pandit","doi":"10.1096/fba.2023-00011","DOIUrl":"https://doi.org/10.1096/fba.2023-00011","url":null,"abstract":"<p>Degeneration of the intervertebral disc is an age-related condition. It also accompanies the disappearance of the notochordal cells, which are remnants of the developmental stages of the nucleus pulposus (NP). Molecular changes such as extracellular matrix catabolism, cellular phenotype, and glycosaminoglycan loss in the NP have been extensively studied. However, as one of the most significant co- and posttranslational modifications, glycosylation has been overlooked in cells in degeneration. Here, we aim to characterize the <i>N</i>-glycome of young and mature NP and identify patterns related to aging. Accordingly, we isolated <i>N</i>-glycans from notochordal cell-rich NP from porcine discs, characterized them using a combined approach of exoglycosidase digestions and analysis with hydrophilic interaction ultra-performance liquid chromatography and mass spectrometry. We have assigned over 300 individual <i>N</i>-glycans for each age group. Moreover, we observed a notable abundance of antennary structures, galactosylation, fucosylation, and sialylation in both age groups. In addition, as indicated from our results, increasing outer arm fucosylation and decreasing α(2,3)-linked sialylation with aging suggest that these traits are age-dependent. Lastly, we have focused on an extensive characterization of the <i>N</i>-glycome of the notochordal cell-rich NP in aging without inferred degeneration, describing glycosylation changes specific for aging only. Our findings in combination with those of other studies, suggest that the degeneration of the NP does not involve identical processes as aging.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 8","pages":"321-335"},"PeriodicalIF":2.7,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2023-00011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50125125","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}

{"title":"Combinatorial islet protective therapeutic approaches in β-cell transplantation: Rationally designed solutions using a target product profile","authors":"Katie Lu,&nbsp;Timothy Brauns,&nbsp;Ann E. Sluder,&nbsp;Mark C. Poznansky,&nbsp;Fatma Dogan","doi":"10.1096/fba.2023-00029","DOIUrl":"10.1096/fba.2023-00029","url":null,"abstract":"<p>While progress has been made in the development of islet cell transplantation (ICT) as a viable alternative to the use of exogenous insulin therapy in the treatment of type 1 diabetes, it has not yet achieved its full potential in clinical studies. Ideally, ICT would enable lifelong maintenance of euglycemia without the need for exogenous insulin, blood glucose monitoring or systemic immune suppression. To achieve such an optimal result, therapeutic approaches should simultaneously promote long-term islet viability, functionality, and localized immune protection. In practice, however, these factors are typically tackled individually. Furthermore, while the requirements of optimal ICT are implicitly acknowledged across numerous publications, the literature contains few comprehensive articulations of the target product profile (TPP) for an optimal ICT product, including key characteristics of safety and efficacy. This review aims to provide a novel TPP for ICT and presents promising tried and untried combinatorial approaches that could be used to achieve the target product profile. We also highlight regulatory barriers to the development and adoption of ICT, particularly in the United States, where ICT is only approved for use in academic clinical trials and is not reimbursed by insurance carriers. Overall, this review argues that the clear definition of a TPP in addition to the use of combinatorial approaches could help to overcome the clinical barriers to the widespread adoption of ICT for the treatment of type 1 diabetes.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 7","pages":"287-304"},"PeriodicalIF":2.7,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/f4/FBA2-5-287.PMC10320848.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10664881","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}

{"title":"Comprehensive analysis of circRNAs for N7-methylguanosine methylation modification in human oral squamous cell carcinoma","authors":"Dongyuan Sun,&nbsp;Ning Song,&nbsp;Minmin Li,&nbsp;Xi Chen,&nbsp;Xinyue Zhang,&nbsp;Yang Yu,&nbsp;Jicheng Ying,&nbsp;Mengqi Xu,&nbsp;Wentian Zheng,&nbsp;Chengbing Han,&nbsp;Honghai Ji,&nbsp;Yingying Jiang","doi":"10.1096/fba.2023-00036","DOIUrl":"10.1096/fba.2023-00036","url":null,"abstract":"<p>N7-methylguanosine (m7G) modification is closely related to the occurrence of tumors. However, the m7G modification of circRNAs in oral squamous cell carcinoma (OSCC) remains to be investigated. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to measure the methylation levels of m7G and identify m7G sites in circRNAs in human OSCC and normal tissues. The host genes of differentially methylated and differentially expressed circRNAs were analyzed by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and circRNA–miRNA–mRNA networks were predicted using the miRanda and miRDB databases. The analysis identified 2348 m7G peaks in 624 circRNAs in OSCC tissues. In addition, the source of m7G-methylated circRNAs in OSCC was mainly the sense overlap region compared with normal tissues. The most conserved m7G motif in OSCC tissues was CCUGU, whereas the most conserved motif in normal tissues was RCCUG (R = G/A). Importantly, GO enrichment and KEGG pathway analysis showed that the host genes of differentially methylated and differentially expressed circRNAs were involved in many cellular biological functions. Furthermore, the significantly differentially expressed circRNAs were analyzed to predict the circRNA–miRNA–mRNA networks. This study revealed the whole profile of circRNAs of differential m7G methylation in OSCC and suggests that m7G-modified circRNAs may impact the development of OSCC.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 8","pages":"305-320"},"PeriodicalIF":2.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/65/3b/FBA2-5-305.PMC10405248.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10019444","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}

{"title":"Post-inflammatory administration of N-acetylcysteine reduces inflammation and alters receptor levels in a cellular model of Parkinson's disease","authors":"Zeynep Bengisu Kaya,&nbsp;Elif Karakoc,&nbsp;Pamela J. McLean,&nbsp;Esen Saka,&nbsp;Pergin Atilla","doi":"10.1096/fba.2022-00145","DOIUrl":"https://doi.org/10.1096/fba.2022-00145","url":null,"abstract":"<p>Parkinson's disease (PD) is a complex, multifactorial neurodegenerative disease with a prevalence of 1% over the age of 55. Neuropathological hallmarks of PD include the loss of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of Lewy bodies that contain a variety of proteins and lipids including alpha-synuclein (α-syn). Although the formation of α-syn occurs intracellularly, it can also be found in the extracellular space where it can be taken up by neighboring cells. Toll-like receptor 2 (TLR2) is an immune system receptor that has been shown to recognize extracellular α-syn and modulate its uptake by other cells. Lymphocyte-activation gene 3 (LAG3), an immune checkpoint receptor, has also been proposed to play a role in extracellular α-syn internalization; however, a recent study has disputed this role. Internalized α-syn can trigger expression and secretion of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-2, and IL-6 and induce neuroinflammation, apoptosis, and mitophagy that results in cellular death. In this study, we tested if <i>N</i>-acetylcysteine (NAC), an anti-inflammatory and anti-carcinogenic drug, can circumvent the detrimental effects of neuroinflammation and induce an anti-inflammatory response by modulating transcription and expression of TLR2 and LAG3 receptors. Cells overexpressing wild-type α-syn were treated with TNF-α to induce inflammation followed by NAC to inhibit the deleterious effects of TNF-α-induced inflammation and apoptosis. <i>SNCA</i> gene transcription and α-syn protein expression were validated by q-PCR and Western blot (WB), respectively. Cell viability was measured, and apoptosis was evaluated by WB and terminal deoxynucleotidyl transferase nick end labeling methods. Alterations in LAG3 and TLR2 receptor levels were evaluated by immunofluorescent labeling, WB, and q-PCR. TNF-α not only increased inflammation but also increased endogenous and overexpressed α-syn levels. NAC treatment decreased expression of TLR2 and increased transcription of LAG3 receptor and diminished inflammation-mediated toxicity and cell death. Here, we demonstrate that NAC can reduce neuroinflammation that occurs as a result of alpha-synuclein overexpression, via a TLR2-associated pathway, making it a promising candidate for therapeutic intervention. Further studies are needed to elucidate molecular mechanisms and pathways related to neuroinflammation in PD and to develop possible new therapeutic approaches to slow the clinical progression of PD.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 7","pages":"263-276"},"PeriodicalIF":2.7,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2022-00145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50135130","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}

{"title":"Bilateral transcranial direct-current stimulation promotes migration of subventricular zone-derived neuroblasts toward ischemic brain","authors":"Ruixue Lei,&nbsp;Shu Wang,&nbsp;Anchun Liu,&nbsp;Jing Cheng,&nbsp;Zhifeng Zhang,&nbsp;Jinyang Ren,&nbsp;Xujin Yao,&nbsp;Xiangyi Kong,&nbsp;Wenlong Ma,&nbsp;Fengyuan Che,&nbsp;Juan Chen,&nbsp;Qi Wan","doi":"10.1096/fba.2023-00017","DOIUrl":"10.1096/fba.2023-00017","url":null,"abstract":"<p>Ischemic insult stimulates proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) after stroke. However, only a fraction of NSC-derived neuroblasts from SVZ migrate toward poststroke brain region. We have previously reported that direct-current stimulation guides NSC migration toward the cathode in vitro. Accordingly, we set up a new method of transcranial direct-current stimulation (tDCS), in which the cathodal electrode is placed on the ischemic hemisphere and anodal electrode on the contralateral hemisphere of rats subjected to ischemia–reperfusion injury. We show that the application of this bilateral tDCS (BtDCS) promotes the migration of NSC-derived neuroblasts from SVZ toward the cathode direction into poststroke striatum. Reversing the position of the electrodes blocks the effect of BtDCS on the migration of neuroblasts from SVZ. BtDCS protects against neuronal death and improves the functional recovery of stroke animals. Thus, the migration of NSC-derived neuroblasts from SVZ toward poststroke brain region contributes to the effect of BtDCS against ischemia-induced neuronal death, supporting a potential development of noninvasive BtDCS as an endogenous neurogenesis-based stroke therapy.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 7","pages":"277-286"},"PeriodicalIF":2.7,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/0a/FBA2-5-277.PMC10320846.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796647","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}

{"title":"Anti-science conspiracies pose new threats to US biomedicine in 2023","authors":"Peter Hotez","doi":"10.1096/fba.2023-00032","DOIUrl":"10.1096/fba.2023-00032","url":null,"abstract":"&lt;p&gt;As America enters its fourth pandemic year, the full toll of COVID-19 on the public health of the country is coming into view. Even beyond our staggering 1.1 million deaths are the many millions of hospitalizations and the ensuing prolonged rehabilitations expected for long COVID cases. Newer data indicate that long COVID is more likely to occur after a severe bout of the infection.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The University of Washington Institute for Health Metrics employs a metric known as disability-adjusted life years or DALYs&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; which roughly refers to the years of life lost either from premature death or disability. On both fronts we will soon have numbers assigned to the DALYs lost from COVID-19, and they will be eye-wateringly high.&lt;/p&gt;&lt;p&gt;Tragically, many of these COVID-19 deaths and DALYs in America could have been averted with better acceptance of vaccines, especially during the deadly delta variant wave in the last half of 2021, and omicron BA.1 wave in the first quarter of 2022. In the months just prior to the onset of delta wave the Biden Administration had announced that any American who wanted a vaccine would have access to one.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; During delta, COVID-19 vaccinations exhibited over 90% protective immunity versus death,&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; and yet an estimated 40,000 Texans died because they declined to get immunized.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Nationally, that number of unnecessary deaths was approximately four to five-fold higher.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The analyses from &lt;i&gt;The New York Times&lt;/i&gt; and healthcare data specialist, Charles Gaba, reports that those deaths overwhelmingly occurred in conservative or Republican-majority states.&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt; Moreover, the “redder” the state in terms of voters, the lower the immunization rates, and the higher deaths climbed. This observation was so striking that David Leonhardt at &lt;i&gt;The New York Times&lt;/i&gt; invoked the term, “red Covid”.&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The phenomenon of red Covid was not a random occurrence but instead an expected outcome of predation linked to extremist politics.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; Some members of the House Freedom Caucus and even US senators sought to discredit the effectiveness and safety of COVID-19 vaccinations during the delta and omicron waves. They kicked this off at the July 2021 CPAC (Conservative Political Action) conference held in Dallas, Texas, claiming they will vaccinate you and then take away your guns and bibles,&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt; while highlighting prominent antivaccine activists.&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; This was preceded and followed by multiple public statements by both House and Senate members discrediting vaccines.&lt;span&gt;&lt;sup&gt;12-16&lt;/sup&gt;&lt;/span&gt; In parallel, both the watchdog Media Matters and a social science group based at ETH Zurich, the Swiss Federal Institute of Technology in Europe, documented how evening Fox News broadcasts disparaged va","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"5 6","pages":"228-232"},"PeriodicalIF":2.7,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/18/FBA2-5-228.PMC10242190.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9599235","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}