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1.
Clin Infect Dis ; 77(Suppl 7): S507-S518, 2023 12 20.
Article in English | MEDLINE | ID: mdl-38118007

ABSTRACT

Antimicrobial resistance (AMR) is a multifaceted global health problem disproportionately affecting low- and middle-income countries (LMICs). The Capturing data on Antimicrobial resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project was tasked to expand the volume of AMR and antimicrobial use data in Asia. The CAPTURA project used 2 data-collection streams: facility data and project metadata. Project metadata constituted information collected to map out data sources and assess data quality, while facility data referred to the retrospective data collected from healthcare facilities. A down-selection process, labelled "the funnel approach" by the project, was adopted to use the project metadata in prioritizing and selecting laboratories for retrospective AMR data collection. Moreover, the metadata served as a guide for understanding the AMR data once they were collected. The findings from CAPTURA's metadata add to the current discourse on the limitation of AMR data in LMICs. There is generally a low volume of AMR data generated as there is a lack of microbiology laboratories with sufficient antimicrobial susceptibility testing capacity. Many laboratories in Asia are still capturing data on paper, resulting in scattered or unused data not readily accessible or shareable for analyses. There is also a lack of clinical and epidemiological data captured, impeding interpretation and in-depth understanding of the AMR data. CAPTURA's experience in Asia suggests that there is a wide spectrum of capacity and capability of microbiology laboratories within a country and region. As local AMR surveillance is a crucial instrument to inform context-specific measures to combat AMR, it is important to understand and assess current capacity-building needs while implementing activities to enhance surveillance systems.


Subject(s)
Anti-Bacterial Agents , Developing Countries , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Retrospective Studies , Drug Resistance, Bacterial , Asia/epidemiology
2.
Clin Infect Dis ; 77(Suppl 7): S581-S587, 2023 12 20.
Article in English | MEDLINE | ID: mdl-38118016

ABSTRACT

Antimicrobial resistance (AMR) is a growing global public health challenge associated with 4.95 million deaths in 2019 and an estimated 10 million deaths per year by 2050 in the absence of coordinated action. A robust AMR surveillance system is therefore required to avert such a scenario. Based on an analysis of country-level AMR data in 8 Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) countries, we present a list of key recommendations to strengthen AMR surveillance. We propose 10 primary considerations under 3 broad categories, including recommendations on (1) laboratory and testing practices, (2) data management and analysis, and (3) data use.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Bacterial , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Asia , Public Health , Laboratories
3.
Plast Reconstr Surg Glob Open ; 11(10): e5347, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37859638

ABSTRACT

Venomous snakebites can cause severe injury. The loss of tendon and skin of the hand is incredibly challenging for the surgeon. A single-staged reconstruction with the free composite anterolateral thigh flap is an acceptable option for a complex thumb injury. In this case, reconstruction for a 23-year-old patient with a complex cobra-induced thumb injury had failed to cover the defect with a skin graft. There was a limitation in choice, and the patient was treated with the free composite anterolateral thigh (ALT) flap and fascia lata flap in one stage to reconstruct both the extensor tendon and the soft tissue coverage. The flap was well-vascularized, and no complications were reported. A single-stage reconstruction with a composite ALT flap with vascularized fascia was chosen as a suitable alternative. The result is satisfying both aesthetically and functionally. This technique can help shorten treatment time and restore function quickly, allowing patients to return to work in less time. The disadvantages of this technique are flap thickness, which can affect finger movement and aesthetics. The composite ALT flap with vascularized fascia lata shows that it is a reliable procedure for single-staged reconstruction, especially combined with the tendon preparation in the hand.

4.
Sci Transl Med ; 15(683): eade6023, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36791210

ABSTRACT

The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2-related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.


Subject(s)
Antibody Formation , COVID-19 , Humans , Aged , BNT162 Vaccine , SARS-CoV-2 , Immunoglobulin G , Antibodies, Viral
5.
Cell Rep Med ; 4(2): 100943, 2023 02 21.
Article in English | MEDLINE | ID: mdl-36791724

ABSTRACT

The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, we track the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, providing an opportunity for the emergence of genetically divergent variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Persistent Infection , Genome, Viral , Genotype
6.
Sci Rep ; 13(1): 3137, 2023 02 23.
Article in English | MEDLINE | ID: mdl-36823427

ABSTRACT

Following the rising concern on environmental issues caused by conventional fossil-based plastics and depleting crude oil resources, polyhydroxyalkanoates (PHAs) are of great interest by scientists and biodegradable polymer market due to their outstanding properties which include high biodegradability in various conditions and processing flexibility. Many polyhydroxyalkanoate-synthesizing microorganisms, including normal and halophilic bacteria, as well as algae, have been investigated for their performance in polyhydroxyalkanoate production. However, to the best of our knowledge, there is still limited studies on PHAs-producing marine yeast. In the present study, a halophilic yeast strain isolated from Spratly Island in Vietnam were investigated for its potential in polyhydroxyalkanoate biosynthesis by growing the yeast in Zobell marine agar medium (ZMA) containing Nile red dye. The strain was identified by 26S rDNA analysis as Pichia kudriavzevii TSLS24 and registered at Genbank database under code OL757724. The amount of polyhydroxyalkanoates synthesized was quantified by measuring the intracellular materials (predicted as poly(3-hydroxybutyrate) -PHB) by gravimetric method and subsequently confirmed by Fourier transform infrared (FTIR) spectroscopic and nuclear magnetic resonance (NMR) spectroscopic analyses. Under optimal growth conditions of 35 °C and pH 7 with supplementation of glucose and yeast extract at 20 and 10 gL-1, the isolated strain achieved poly(3-hydroxybutyrate) content and concentration of 43.4% and 1.8 gL-1 after 7 days of cultivation. The poly(3-hydroxybutyrate) produced demonstrated excellent biodegradability with degradation rate of 28% after 28 days of incubation in sea water.


Subject(s)
Polyhydroxyalkanoates , Polyhydroxyalkanoates/chemistry , Pichia/metabolism , Vietnam , Magnetic Resonance Spectroscopy
7.
Microbiol Resour Announc ; 12(1): e0111322, 2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36448812

ABSTRACT

Here, we report a recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage XAM (Omicron BA.1.1/BA.2.9) strain that was collected in Santo Domingo, Dominican Republic. This demonstrates how SARS-CoV-2 variants can vary greatly between regions and thus underlines the great importance of regional genomic surveillance efforts.

8.
Curr Opin Biotechnol ; 78: 102844, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36410153

ABSTRACT

Starch and sugars account for most of the dry weight of horticultural crops and in many species, are known determinants of quality. However, we posit that these carbohydrates often have less-obvious roles in plant tissues with direct implications for the postharvest quality and produce shelf life. The latter has not been given as much attention, but with the recent interest in reducing the scale of postharvest waste and loss, we highlight how dynamic changes in the spatial-temporal accumulation of carbohydrates, can influence myriads of biological processes affecting postharvest attributes. Versatile roles, some surprising, that carbohydrates play in determining produce of high value to consumers, are highlighted, and gene targets for biotechnological improvement are specified.


Subject(s)
Starch , Sugars , Carbohydrates
9.
J Clin Transl Pathol ; 2(2): 31-36, 2022.
Article in English | MEDLINE | ID: mdl-36275841

ABSTRACT

Oropharyngeal squamous cell carcinomas (OPSCCs) have shown an alarming rate of increase in incidence over the past several decades, markedly in men. In the United States, transcriptionally-active human papillomavirus (HPV), particularly HPV 16, has become the highest contributive agent of OPSCCs, affecting approximately 16,000 people a year. Compared to patients with HPV-negative OPSCCs, patients with HPV-positive OPSCCs exhibit better health responses to chemoradiotherapy and an overall increase in long-term survival. Despite promising treatment options, many OPSCCs are discovered at an advanced stage, and ~20% of cases will recur after definitive treatment. Therefore, extensive research is ongoing to identify new targets for precision treatment and to stratify tumor prognosis. The aim of this review is to capture the most updated research on HPV-positive OPSCCs, emphasizing their relevance as potential new targets for precision medicine and survival prognosis.

10.
Heliyon ; 8(9): e10680, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36185146

ABSTRACT

Globalization of the world needs the modernization of laws, theory, and philosophy, especially since World War II. This could increase researchers' attention towards the modernization of philosophy. The goals also include examining the mediating impact of modern societies among the links of globalization, modernization of laws and theories, and modernization of philosophy in Vietnam. This study has taken the quantitative method and received the data from researchers in philosophy, politics and sociology (university lecturers, researchers and activists in the field of philosophy, politics and sociology) of Vietnam using questionnaires. The smart-PLS was executed to test the relationships between the understudy constructs. The results indicated that globalization, modernization of laws, and theories positively and significantly associated with the modernization of philosophy in Vietnam. The outcomes also revealed that modern societies significantly mediate the links among globalization, modernization of laws and theories, and modernization of philosophy in Vietnam. These results motivate the regulators to focus on the modernization of philosophies in terms of globalization and modernization of laws, theories, and societies.

11.
Am J Cancer Res ; 12(8): 3679-3692, 2022.
Article in English | MEDLINE | ID: mdl-36119846

ABSTRACT

Epigenomic-wide DNA methylation profiling holds the potential to reflect both electronic cigarette exposure-associated risks and individual poor health outcomes. However, a systemic study in animals or humans is still lacking. Using the Infinium Mouse Methylation BeadChip, we examined the DNA methylation status of white blood cells in male ApoE-/- mice after 14 weeks of electronic cigarette exposure with the InExpose system (2 hr/day, 5 days/week, 50% PG and 50% VG) with low (6 mg/ml) and high (36 mg/ml) nicotine concentrations. Our results indicate that electronic cigarette aerosol inhalation induces significant alteration of 8,985 CpGs in a dose-dependent manner (FDR<0.05); 7,389 (82.2%) of the CpG sites are annotated with known genes. Among the top 6 significant CpG sites (P-value<1e-8), 4 CpG sites are located in the known genes, and most (3/5) of these genes have been related to cigarette smoking. The other two CpGs are close to/associated with the Phc2 gene that was recently linked to smoking in a transcriptome-wide associations study. Furthermore, the gene set enrichment analysis highlights the activation of MAPK and 4 cardiomyocyte/cardiomyopathy-related signaling pathways (including adrenergic signaling in cardiomyocytes and arrhythmogenic right ventricular cardiomyopathy) following repeated electronic cigarette use. The MAPK pathway activation correlates well with our finding of increased cytokine mRNA expression after electronic cigarette exposure in the same batch of mice. Interestingly, two pathways related to mitochondrial activities, namely mitochondrial gene expression and mitochondrial translation, are also activated after electronic cigarette exposure. Elucidating the relationship between these pathways and the increased circulating mitochondrial DNA observed here will provide further insight into the cell-damaging effects of prolonged inhalation of e-cigarette aerosols.

12.
medRxiv ; 2022 Jul 02.
Article in English | MEDLINE | ID: mdl-35794895

ABSTRACT

The chronic infection hypothesis for novel SARS-CoV-2 variant emergence is increasingly gaining credence following the appearance of Omicron. Here we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral loads. During the infection, we found an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately two-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution led to the emergence and persistence of at least three genetically distinct genotypes suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, using unique molecular indexes for accurate intrahost viral sequencing, we tracked the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, ultimately providing opportunity for the emergence of genetically divergent and potentially highly transmissible variants as seen with Delta and Omicron.

13.
Med ; 3(5): 325-334.e4, 2022 05 13.
Article in English | MEDLINE | ID: mdl-35399324

ABSTRACT

Background: The SARS-CoV-2 Omicron variant became a global concern due to its rapid spread and displacement of the dominant Delta variant. We hypothesized that part of Omicron's rapid rise was based on its increased ability to cause infections in persons that are vaccinated compared to Delta. Methods: We analyzed nasal swab PCR tests for samples collected between December 12 and 16, 2021, in Connecticut when the proportion of Delta and Omicron variants was relatively equal. We used the spike gene target failure (SGTF) to classify probable Delta and Omicron infections. We fitted an exponential curve to the estimated infections to determine the doubling times for each variant. We compared the test positivity rates for each variant by vaccination status, number of doses, and vaccine manufacturer. Generalized linear models were used to assess factors associated with odds of infection with each variant among persons testing positive for SARS-CoV-2. Findings: For infections with high virus copies (Ct < 30) among vaccinated persons, we found higher odds that they were infected with Omicron compared to Delta, and that the odds increased with increased number of vaccine doses. Compared to unvaccinated persons, we found significant reduction in Delta positivity rates after two (43.4%-49.1%) and three vaccine doses (81.1%), while we only found a significant reduction in Omicron positivity rates after three doses (62.3%). Conclusion: The rapid rise in Omicron infections was likely driven by Omicron's escape from vaccine-induced immunity. Funding: This work was supported by the Centers for Disease Control and Prevention (CDC).


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19 Vaccines , Hospitalization , Humans , SARS-CoV-2/genetics
14.
Sci Rep ; 12(1): 5729, 2022 04 06.
Article in English | MEDLINE | ID: mdl-35388102

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic-caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- has posed a global threat and presented with it a multitude of economic and public-health challenges. Establishing a reliable means of readily available, rapid diagnostic testing is of paramount importance in halting the spread of COVID-19, as governments continue to ease lockdown restrictions. The current standard for laboratory testing utilizes reverse transcription quantitative polymerase chain reaction (RT-qPCR); however, this method presents clear limitations in requiring a longer run-time as well as reduced on-site testing capability. Therefore, we investigated the feasibility of a reverse transcription looped-mediated isothermal amplification (RT-LAMP)-based model of rapid COVID-19 diagnostic testing which allows for less invasive sample collection, named SaliVISION. This novel, two-step, RT-LAMP assay utilizes a customized multiplex primer set specifically targeting SARS-CoV-2 and a visual report system that is ready to interpret within 40 min from the start of sample processing and does not require a BSL-2 level testing environment or special laboratory equipment. When compared to the SalivaDirect and Thermo Fisher Scientific TaqPath RT-qPCR testing platforms, the respective sensitivities of the SaliVISION assay are 94.29% and 98.28% while assay specificity was 100% when compared to either testing platform. Our data illustrate a robust, rapid diagnostic assay in our novel RT-LAMP test design, with potential for greater testing throughput than is currently available through laboratory testing and increased on-site testing capability.


Subject(s)
COVID-19 , COVID-19/diagnosis , COVID-19 Testing , Communicable Disease Control , Diagnostic Tests, Routine , Humans , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2/genetics , Saliva/chemistry , Sensitivity and Specificity
15.
Hepatology ; 75(4): 983-996, 2022 04.
Article in English | MEDLINE | ID: mdl-34387871

ABSTRACT

BACKGROUND AND AIMS: Chronic HCV infection is a leading etiologic driver of cirrhosis and ultimately HCC. Of the approximately 71 million individuals chronically infected with HCV, 10%-20% are expected to develop severe liver complications in their lifetime. Epigenetic mechanisms including DNA methylation and histone modifications become profoundly disrupted in disease processes including liver disease. APPROACH AND RESULTS: To understand how HCV infection influences the epigenome and whether these events remain as "scars" following cure of chronic HCV infection, we mapped genome-wide DNA methylation, four key regulatory histone modifications (H3K4me3, H3K4me1, H3K27ac, and H3K27me3), and open chromatin in parental and HCV-infected immortalized hepatocytes and the Huh7.5 HCC cell line, along with DNA methylation and gene-expression analyses following elimination of HCV in these models through treatment with interferon-α (IFN-α) or a direct-acting antiviral (DAA). Our data demonstrate that HCV infection profoundly affects the epigenome (particularly enhancers); HCV shares epigenetic targets with interferon-α targets; and an overwhelming majority of epigenetic changes induced by HCV remain as "scars" on the epigenome following viral cure. Similar findings are observed in primary human patient samples cured of chronic HCV infection. Supplementation of IFN-α/DAA antiviral regimens with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine synergizes in reverting aberrant DNA methylation induced by HCV. Finally, both HCV-infected and cured cells displayed a blunted immune response, demonstrating a functional effect of epigenetic scarring. CONCLUSIONS: Integration of epigenetic and transcriptional data elucidate key gene deregulation events driven by HCV infection and how this may underpin the long-term elevated risk for HCC in patients cured of HCV due to epigenome scarring.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis C, Chronic , Hepatitis C , Liver Neoplasms , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Epigenome , Hepacivirus/genetics , Hepatitis C/complications , Hepatitis C/drug therapy , Hepatitis C/genetics , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/genetics , Humans , Interferon-alpha/pharmacology , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics
16.
Appl Microbiol Biotechnol ; 105(10): 4005-4015, 2021 May.
Article in English | MEDLINE | ID: mdl-33950278

ABSTRACT

The coronavirus disease (COVID-19) caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide. Given that this contagious viral outbreak is still unfolding, it is urgent to understand the pathogenesis of SARS-CoV-2 infection and explore effective treatments to protect patients from developing a severe illness related to COVID-19. Recently, IFN-α has been considered a potential therapeutic strategy to treat COVID-19 disease, mainly because the innate immune system rapidly produces IFN-α as the first line of defense to combat viral infections. However, IFN-α can also play a role in immunoregulatory effects, causing pathogenic damage and uncontrolled inflammatory responses. There are 13 human IFN-α subtypes that bind to the same receptor and induce different interferon-stimulated gene (ISG) expression, regulating various antiviral and immunoregulatory effects. The varying degrees of inflammatory regulations may raise concerns about the possible side effects to enlarge the inflammatory responses, exacerbating the severity of infection. Thus, the analysis of various IFN-α subtype induction during SARS-CoV-2 infection is necessary in exploring the mechanism of COVID-19 pathogenesis. This review summarizes the current understanding of IFN-α in the pathogenesis of respiratory virus diseases and IFN-α based clinical intervention used in SARS-CoV-2 infection and other respiratory virus diseases. Besides, new ideas in selecting suitable IFN-α subtypes or combinations as drug candidates for viral infection treatment will also be discussed.Key Points• IFN-α plays an important role in anti-viral and immunoregulatory effects in COVID-19 patients caused by SARS-CoV-2.• The uncontrolled inflammation and disease severity correlated to the diversity of IFN-α subtype induction.• Selecting suitable IFN-α subtypes or combinations as drug candidates will be beneficial for the treatment of patients with COVID-19.


Subject(s)
COVID-19 , Antiviral Agents/therapeutic use , Humans , Interferon-alpha/therapeutic use , SARS-CoV-2
17.
RSC Adv ; 11(51): 32435-32445, 2021 Sep 27.
Article in English | MEDLINE | ID: mdl-35495543

ABSTRACT

Based on molecular dynamics (MD) simulations, we investigate the liquid-amorphous phase transition, slow dynamic and dynamical heterogeneity (DH) for bulk iron in temperatures ranging 300-2300 K. The structure of obtained models is explored through the pair radial distribution function (PRDF) and simplex statistics. It was shown that the splitting of a PRDF second peak appears when the liquid transforms to an amorphous solid. This feature is originated from the transformation of simplexes from strongly-to weakly-distorted tetrahedron type. Further, we reveal that the diffusivity in the liquid is realized through the local density fluctuations (LDF) which are strongly correlated with each other. The diffusion coefficient is found to be a product of the rate of LDF act and mean square displacement of particles per LDF act. The later quantity mainly contributes to the slow dynamics and DH in the liquid. We found that the mobile atom clusters move during relaxation time, but mobile atoms do not tend to leave their cluster. Our work is expected to contribute a pathway to determine the liquid-amorphous phase transition and DH heterogeneity of bulk metal.

18.
Explor Res Hypothesis Med ; 6(2): 60-66, 2021 Jun.
Article in English | MEDLINE | ID: mdl-35419501

ABSTRACT

Recurrence and metastasis are the foremost causes of morbidity and mortality for breast cancer (BC). Recent studies have highlighted the critical role of the tumor microenvironment, in particular, because it is related to tumor-associated macrophages (TAMs), in metastasis of BC. TAMs are mainly derived from macrophages that are recruited by C-C motif chemokine ligand 5, which are secreted by cancer cells and cancer-related stromal cells. Although E-cigarettes (E-cigs) were originally proposed as a healthy substitute for conventional cigarette smoking, clinical and experimental evidence has highlighted the potentially lethal effects of this alternative. Several studies have illustrated the immune or macrophage activation and DNA damaging effects of E-cigs. However, the potentially pivotal role of TAM-BC crosstalk during BC progression and metastasis for E-cig vaping has not been explored. This review discussed the significant effect that E-cig use had on the BC tumor microenvironment, which ultimately led to enhanced tumor malignancy and metastasis, with an emphasis on the extent that E-cig uses had on the crosstalk between cancer and immune cells, as well as the potential underlying mechanisms that drive this aggressive phenotype of BC. This review advances our understanding of this matter and provides scientific evidence that could highlight risks associated with vaping and suggest a potential intervention for the treatment of aggressive BCs that present an increased risk of metastasis.

19.
Arterioscler Thromb Vasc Biol ; 41(2): 839-853, 2021 02.
Article in English | MEDLINE | ID: mdl-33380174

ABSTRACT

OBJECTIVE: Electronic cigarette (e-cig) use has recently been implicated in promoting atherosclerosis. In this study, we aimed to investigate the mechanism of e-cig exposure accelerated atherosclerotic lesion development. Approach and Results: Eight-week-old ApoE-/- mice fed normal laboratory diet were exposed to e-cig vapor (ECV) for 2 hours/day, 5 days/week for 16 weeks. We found that ECV exposure significantly induced atherosclerotic lesions as examined by Oil Red O staining and greatly upregulated TLR9 (toll-like receptor 9) expression in classical monocytes and in the atherosclerotic plaques, which the latter was corroborated by enhanced TLR9 expression in human femoral artery atherosclerotic plaques from e-cig smokers. Intriguingly, we found a significant increase of oxidative mitochondria DNA lesion in the plasma of ECV-exposed mice. Administration of TLR9 antagonist before ECV exposure not only alleviated atherosclerosis and the upregulation of TLR9 in plaques but also attenuated the increase of plasma levels of inflammatory cytokines, reduced the plaque accumulation of lipid and macrophages, and decreased the frequency of blood CCR2+ (C-C chemokine receptor type 2) classical monocytes. Surprisingly, we found that cytoplasmic mitochondrial DNA isolated from ECV extract-treated macrophages can enhance TLR9 activation in reporter cells and the induction of inflammatory cytokine could be suppressed by TLR9 inhibitor in macrophages. CONCLUSIONS: E-cig increases level of damaged mitochondrial DNA in circulating blood and induces the expression of TLR9, which elevate the expression of proinflammatory cytokines in monocyte/macrophage and consequently lead to atherosclerosis. Our results raise the possibility that intervention of TLR9 activation is a potential pharmacological target of ECV-related inflammation and cardiovascular diseases.


Subject(s)
Aorta/metabolism , Atherosclerosis/etiology , DNA Damage , DNA, Mitochondrial/metabolism , E-Cigarette Vapor/adverse effects , Inflammation/etiology , Macrophages/metabolism , Mitochondria/metabolism , Toll-Like Receptor 9/metabolism , Animals , Aorta/pathology , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , DNA, Mitochondrial/genetics , Disease Models, Animal , Female , Humans , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Inflammation Mediators/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout, ApoE , Middle Aged , Mitochondria/genetics , Mitochondria/pathology , RAW 264.7 Cells , Signal Transduction , Smokers , Vaping
20.
Int J Clin Exp Pathol ; 13(8): 2075-2081, 2020.
Article in English | MEDLINE | ID: mdl-32922603

ABSTRACT

Electronic cigarettes (E-cigs) smoking or vaping is an emerging problem to public health due to its popularity. While its multi-faceted detrimental effects on human health are being reported, no current study addresses the effect of E-cigs on tumor metastasis, the main cause of tumor mortality. Using a well-established human breast cancer cell line MDA MB-231, we first showed that E-cig vapor extract (nicotine 24 mg/ml, propylene glycol 50%, vegetable glycerin 50%, no flavorings) significantly enhanced tumor cell migration (P<0.0001), but showed no significant effect on tumor cell proliferation (P>0.05). To evaluate the metastasis-promoting effect of E-cigs in vivo, we used NOD-SCID-Gamma mice and introduced tumor cells to the mice by tail vein injection. Among these mice, 4-week E-cigs exposure (nicotine 24 mg/ml, propylene glycol 50%, vegetable glycerin 50%, no flavorings, 2 h/day, 5 days/week) almost doubled the tumor load in the exposed lungs compared to controls (P=0.0036). While E-cig exposure did not alter the proliferative index of tumor cells colonized in the lungs (P=0.7953), tumor cell apoptosis was significantly reduced (P<0.001). Taken together, our data for the first time, demonstrated the lung colonization-promoting effects of E-cigs on human breast cancer cells. These findings show the risks of E-cigs on the lung metastasis of various cancers, and warrant more studies on the underlying mechanisms.

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