scholarly journals Clearing the Haze: How Does Nicotine Affect Hematopoiesis before and after Birth?

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 184
Author(s):  
Taylor Cool ◽  
Alessandra Rodriguez y Baena ◽  
E. Camilla Forsberg

Hematopoiesis is a tightly regulated process orchestrated by cell-intrinsic and cell-extrinsic cues. Over the past several decades, much effort has been focused on understanding how these cues regulate hematopoietic stem cell (HSC) function. Many endogenous key regulators of hematopoiesis have been identified and extensively characterized. Less is known about the mechanisms of long-term effects of environmental toxic compounds on hematopoietic stem and progenitor cells (HSPCs) and their mature immune cell progeny. Research over the past several decades has demonstrated that tobacco products are extremely toxic and pose huge risks to human health by causing diseases like cancer, respiratory illnesses, strokes, and more. Recently, electronic cigarettes have been promoted as a safer alternative to traditional tobacco products and have become increasingly popular among younger generations. Nicotine, the highly toxic compound found in many traditional tobacco products, is also found in most electronic cigarettes, calling into question their purported “safety”. Although it is known that nicotine is toxic, the pathophysiology of disease in exposed people remains under investigation. One plausible contributor to altered disease susceptibility is altered hematopoiesis and associated immune dysfunction. In this review, we focus on research that has addressed how HSCs and mature blood cells respond to nicotine, as well as identify remaining questions.

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2292 ◽  
Author(s):  
Gajalakshmi Ramanathan ◽  
Brianna Craver-Hoover ◽  
Rebecca J. Arechavala ◽  
David A. Herman ◽  
Jane H. Chen ◽  
...  

Electronic cigarettes (E-cigs) generate nicotine containing aerosols for inhalation and have emerged as a popular tobacco product among adolescents and young adults, yet little is known about their health effects due to their relatively recent introduction. Few studies have assessed the long-term effects of inhaling E-cigarette smoke or vapor. Here, we show that two months of E-cigarette exposure causes suppression of bone marrow hematopoietic stem and progenitor cells (HSPCs). Specifically, the common myeloid progenitors and granulocyte-macrophage progenitors were decreased in E-cig exposed animals compared to air exposed mice. Competitive reconstitution in bone marrow transplants was not affected by two months of E-cig exposure. When air and E-cig exposed mice were challenged with an inflammatory stimulus using lipopolysaccharide (LPS), competitive fitness between the two groups was not significantly different. However, mice transplanted with bone marrow from E-cigarette plus LPS exposed mice had elevated monocytes in their peripheral blood at five months post-transplant indicating a myeloid bias similar to responses of aged hematopoietic stem cells (HSC) to an acute inflammatory challenge. We also investigated whether E-cigarette exposure enhances the selective advantage of hematopoietic cells with myeloid malignancy associated mutations. E-cigarette exposure for one month slightly increased JAK2V617F mutant cells in peripheral blood but did not have an impact on TET2−/− cells. Altogether, our findings reveal that chronic E-cigarette exposure for two months alters the bone marrow HSPC populations but does not affect HSC reconstitution in primary transplants.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
K Pluta ◽  
Ł Balwicki

Abstract Research shows that over 80% of smokers start their habit under the age of 18. A few years ago young people undertook risky behaviors related to nicotine initiation mainly by smoking cigarettes. Today, next to traditional tobacco products, electronic cigarettes are becoming more and more popular. Due to the prevalence of new forms of nicotine addiction, modification of anti-tobacco prevention programs is required. The purpose of the research was exploration - learning the opinions and attitudes of young people towards e-cigarettes. The qualitative study was conducted using the FGI method (focus group interview). The meetings were modereted by specially trained psychologists. 48 students participated in the meetings of six focus groups, divided by gender and smoking status (smokers/non-smokers). The participants are young people aged 15-19, attending high schools in Warsaw, Kielce and Lublin. In conversations, young people emphasized the impact of e-cigarettes in smoking initiation - it usually occurs at the age of 12-14. E-cigarettes are perceived as cigarettes “for younger”, non-addictive, less serious, providing more entertainment. 'Cloud chasing' is particularly popular. They perform social functions - they are helpful in establishing relationships. Teenagers do not see the harmfulness of e-cigarettes. Participants mentioned their advantages over traditional tobacco products - they can be smoked everywhere and do not leave an unpleasant smell. Some of the respondents admit to the simultaneous use of electronic and traditional cigarettes. Moreover, many parents allow children to smoke electronic cigarettes. Vaping have become a natural way to relaxation and socialization for adolescents. E-cigarettes do not have such a negative connotation as traditional tobacco products. Young people do not see them as harmful, which is a challenge for effective preventive measures. Key messages Adolescents do not see e-cigarettes as harmful, which is a challenge for effective preventive measures. Vaping have become more and more popular - it's natural way to relaxation and socialization for young people.


2020 ◽  
pp. tobaccocontrol-2019-055417 ◽  
Author(s):  
Sara Schiff ◽  
Fei Liu ◽  
Tess Boley Cruz ◽  
Jennifer B Unger ◽  
Sam Cwalina ◽  
...  

BackgroundTobacco 21 (T21) laws, which raise the minimum legal age of sale of tobacco products to 21, have been proposed and implemented in states and cities across the USA. However, limited data are available on the effect of T21 laws on youth tobacco purchasing behaviours and access to tobacco products.MethodsParticipants in a population-based prospective cohort in southern California completed questionnaires before (n=1609, age=18–19 y) and after (n=1502, age=19–20 y) T21 was implemented in California (June 2016). We examined the prevalence of past 30-day cigarette and e-cigarette use, and among past 30-day users, purchase location of tobacco products before (pre-) versus after (post-) T21. We also examined whether, post-T21, participants were refused purchase of tobacco products due to their age, and the perceived relative ease of purchasing cigarettes and e-cigarettes (vs pre-T21).ResultsNegligible changes in cigarette and e-cigarette use were observed pre-T21 versus post-T21. At both time points, the majority of past 30-day users purchased cigarettes from gas stations and e-cigarettes from vape shops. Post-T21, the proportion of participants who reported purchasing cigarettes at gas stations decreased. Post-T21, most past 30-day cigarette or e-cigarette users were not refused purchase of cigarettes (65.4%) or e-cigarettes (82.0%) in the past 30 days, despite being under 21; half of the participants felt it was harder to purchase cigarettes (54.3%) and e-cigarettes (43.6%) post-T21.ConclusionPost-T21, few participants were refused purchase of any tobacco product, despite the illegality of such sales. Better enforcement of T21 is needed to improve the efficacy of T21 legislation.


2014 ◽  
Vol 307 (7) ◽  
pp. F783-F797 ◽  
Author(s):  
A. Zuk ◽  
M. Gershenovich ◽  
Y. Ivanova ◽  
R. T. MacFarland ◽  
S. P. Fricker ◽  
...  

We examined whether antagonism of the CXCR4 receptor ameliorates the loss of renal function following ischemia-reperfusion. CXCR4 is ubiquitously expressed on leukocytes, known mediators of renal injury, and on bone marrow hematopoietic stem cells (HSCs). Plerixafor (AMD3100, Mozobil) is a small-molecule CXCR4 antagonist that mobilizes HSCs into the peripheral blood and also modulates the immune response in in vivo rodent models of asthma and rheumatoid arthritis. Treatment with plerixafor before and after ischemic clamping ameliorated kidney injury in a rat model of bilateral renal ischemia-reperfusion. Serum creatinine and blood urea nitrogen were significantly reduced 24 h after reperfusion, as were tissue injury and cell death. Plerixafor prevented the renal increase in the proinflammatory chemokines CXCL1 and CXCL5 and the cytokine IL-6. Flow cytometry of kidney homogenates confirmed the presence of significantly fewer leukocytes with plerixafor treatment; additionally, myeloperoxidase activity was reduced. AMD3465, a monocyclam analog of plerixafor, was similarly renoprotective. Four weeks postreperfusion, long-term effects included diminished fibrosis, inflammation, and ongoing renal injury. The mechanism by which CXCR4 inhibition ameliorates AKI is due to modulation of leukocyte infiltration and expression of proinflammatory chemokines/cytokines, rather than a HSC-mediated effect. The data suggest that CXCR4 antagonism with plerixafor may be a potential option to prevent AKI.


Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5731-5741 ◽  
Author(s):  
Hal E. Broxmeyer ◽  
Kent Christopherson ◽  
Giao Hangoc ◽  
Scott Cooper ◽  
Charlie Mantel ◽  
...  

Abstract In the present study, surface CD1d, which is involved in immune cell interactions, was assessed for effects on hematopoiesis. Mouse BM hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) express CD1d. The numbers and cycling status of HPCs in the BM and spleen of different strains of cd1d−/− mice were enhanced significantly, suggesting that CD1d is a negative regulator of HPCs. In support of this, CD1d was required for the SCF and Flt3 ligand synergistic enhancement of CSF induction of HPC colony formation and for HPC response to myelosuppressive chemokines. Colony formation by immature subsets of HPCs was greatly enhanced when normal, but not cd1d−/−, BM cells were pretreated with CD1d Abs in vitro. These effects required the full CD1d cytoplasmic tail. In contrast, long-term, but not short-term, repopulating HSC engraftment was impaired significantly, an effect that was minimally influenced by the presence of a truncated CD1d cytoplasmic tail. Pretreatment of normal BM cells with CD1d Abs greatly enhanced their engraftment of HSCs. The results of the present study implicate CD1d in a previously unrecognized regulatory role of normal and stressed hematopoiesis.


Author(s):  
Junda Wang ◽  
Xupin Zhang ◽  
Jiebo Luo

While the long-term effects of COVID-19 are yet to be determined, its immediate impact on crowdfunding is nonetheless significant. This study takes a computational approach to more deeply comprehend this change. Using a unique data set of all the campaigns published over the past two years on GoFundMe, we explore the factors that have led to the successful funding of a crowdfunding project. In particular, we study a corpus of crowdfunded projects, analyzing cover images and other variables commonly present on crowdfunding sites. Furthermore, we construct a classifier and a regression model to assess the significance of features based on XGBoost. In addition, we employ counterfactual analysis to investigate the causality between features and the success of crowdfunding. More importantly, sentiment analysis and the paired sample t-test are performed to examine the differences in crowdfunding campaigns before and after the COVID-19 outbreak that started in March 2020. First, we note that there is significant racial disparity in crowdfunding success. Second, we find that sad emotion expressed through the campaign's description became significant after the COVID-19 outbreak. Considering all these factors, our findings shed light on the impact of COVID-19 on crowdfunding campaigns.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2916-2916
Author(s):  
Jimmy L. Zhao ◽  
Chao Ma ◽  
Ryan O'Connell ◽  
Arnav Mehta ◽  
Jun Wang ◽  
...  

Abstract Mammals respond to infection by rapid production of innate immune cells. Hematopoietic stem and progenitor cells (HSPCs) have the ability to respond to pathogens directly through toll-like receptors. However, how the pathogen sensing ability of HSPCs may contribute to immune cell output remains unknown. Using a novel single-cell proteomic platform and mouse genetic models, we have shown that in response to toll-like receptor stimulation, short-term HSCs and multipotent progenitor cells produce copious amounts of diverse cytokines through NF-κB signaling. Interestingly, the cytokine production ability of HSPCs trumps mature immune cells in both magnitude and breadth. Among cytokines produced by HSPCs, IL-6 is a particularly important regulator of myeloid differentiation and HSPC proliferation. This is especially important in mediating rapid early myeloid cell recovery during neutropenia after chemotherapy or HSC transplant. This study has uncovered an important property of HSPCs that enables them to convert danger signals into versatile cytokine signals for the regulation of stress-induced hematopoiesis. To translate these findings into human hematopoietic system, we have recently developed a human cytokine chip and our preliminary analysis suggests that purified human bone marrow HSCs also have the capacity to secrete cytokines. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 22 (5) ◽  
pp. 705-712 ◽  
Author(s):  
Hyun S Lee ◽  
Samara Wilson ◽  
Timea Partos ◽  
Ann McNeill ◽  
Leonie S Brose

Abstract Introduction In line with the European Union’s Tobacco Products Directive (TPD), new regulations for electronic cigarettes implemented in the United Kingdom between May 2016 and May 2017 included limiting refills to 10 mL, tank and cartridge sizes to 2 mL, and nicotine concentrations to 20 mg/mL. Aims To investigate the (1) awareness of new regulations, (2) product use before and after implementation, and (3) association between use of compliant products and subsequent smoking. Methods A UK online longitudinal survey of smokers, ex-smokers, and vapers was conducted between May and June 2016 (wave 4) and September 2017 (wave 5).The following methods were used: (1) to assess awareness of changes, proportions were calculated by smoking and vaping status (n = 1606). (2) Comparison of refill volume, tank and cartridge volumes, nicotine concentration at waves 4 and 5 (n = 199–388) was conducted. (3) Association was studied between number of TPD-compliant products used at wave 4 and smoking at wave 5, adjusted for wave 4 vaping status, age, gender, income, urges to smoke, and device type (n = 480). Results Awareness of regulations was highest for refill volume (10.1%; 37.4% among exclusive vapers) and nicotine concentration (9.5%; 27.3%). Higher proportions used TPD-compliant refill volumes (60.0%–73.7%, χ2(1) = 10.9, p = .001) and nicotine concentrations (89.2%–93.9%, χ2(1) = 7.41, p = .007) in wave 5 than wave 4, with little change for tank or cartridge volumes (77.1–75.5%, χ2(1) = 0.38, p = .540). The likelihood of smoking was similar for those using no or one TPD-compliant products as it was for those using two (OR = 1.10, 95% CI = 0.47–2.59) or three (OR = 1.56, 95% CI = 0.69–3.55). Conclusion Several months after full implementation, awareness of new regulations was low and most vapers used TPD-compliant products. Use of compliant products was not associated with subsequent smoking. Implications Using a longitudinal survey at the beginning and a few months after the end of the transition period for implementation of new regulation on electronic cigarettes, this is the first study to assess awareness of regulation and use of compliant products. After full implementation, awareness of changes was low overall (smokers, ex-smokers, and vapers combined) although higher among those who vaped. Nevertheless, most vapers (74%–94%) used products that were compliant with the new regulations and the use of products compliant with incoming regulations did not predict whether they were smoking cigarettes after implementation.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
I-Na Lu ◽  
Celia Dobersalske ◽  
Laurèl Rauschenbach ◽  
Sarah Teuber-Hanselmann ◽  
Anita Steinbach ◽  
...  

AbstractBrain tumors are typically immunosuppressive and refractory to immunotherapies for reasons that remain poorly understood. The unbiased profiling of immune cell types in the tumor microenvironment may reveal immunologic networks affecting therapy and course of disease. Here we identify and validate the presence of hematopoietic stem and progenitor cells (HSPCs) within glioblastoma tissues. Furthermore, we demonstrate a positive link of tumor-associated HSPCs with malignant and immunosuppressive phenotypes. Compared to the medullary hematopoietic compartment, tumor-associated HSPCs contain a higher fraction of immunophenotypically and transcriptomically immature, CD38- cells, such as hematopoietic stem cells and multipotent progenitors, express genes related to glioblastoma progression and display signatures of active cell cycle phases. When cultured ex vivo, tumor-associated HSPCs form myeloid colonies, suggesting potential in situ myelopoiesis. In experimental models, HSPCs promote tumor cell proliferation, expression of the immune checkpoint PD-L1 and secretion of tumor promoting cytokines such as IL-6, IL-8 and CCL2, indicating concomitant support of both malignancy and immunosuppression. In patients, the amount of tumor-associated HSPCs in tumor tissues is prognostic for patient survival and correlates with immunosuppressive phenotypes. These findings identify an important element in the complex landscape of glioblastoma that may serve as a target for brain tumor immunotherapies.


2017 ◽  
Vol 27 (e1) ◽  
pp. e70-e75 ◽  
Author(s):  
Joseph G L Lee ◽  
Elizabeth N Orlan ◽  
Kerry B Sewell ◽  
Kurt M Ribisl

ObjectiveRetailers that primarily or exclusively sell electronic cigarettes (e-cigarettes) or vaping products represent a new category of tobacco retailer. We sought to identify (a) how vape shops can be identified and (b) sales and marketing practices of vape shops.Data sourcesA medical librarian iteratively developed a search strategy and in February 2017 searched seven academic databases (ABI/INFORM Complete, ECONLit, Embase, Entrepreneurship, PsycINFO, PubMed/MEDLINE and Scopus). We hand searched Tobacco Regulatory Science and Tobacco Prevention & Cessation.Study selectionWe used dual, independent screening. Records were eligible if published in 2010 or later, were peer-reviewed journal articles and focused on vape shops.Data extractionWe used dual, independent data abstraction and assessed risk of bias. Of the 3605 records identified, 22 were included.Data synthesisWe conducted a narrative systematic review. Researchers relied heavily on Yelp to identify vape shops. Vape shop owners use innovative marketing strategies that sometimes diverge from those of traditional tobacco retailers. Vape shop staff believe strongly that their products are effective harm-reduction products. Vape shops were more common in areas with more White residents.ConclusionsVape shops represent a new type of retailer for tobacco products. Vape shops have potential to promote e-cigarettes for smoking cessation but also sometimes provide inaccurate information and mislabelled products. Given their spatial patterning, vape shops may perpetuate inequities in tobacco use. The growing literature on vape shops is complicated by researchers using different definitions of vape shops (eg, exclusively selling e-cigarettes vs also selling traditional tobacco products).


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