Cannabis Vape Product Sales in California Following CDC's Initial Advisory About Lung Injuries.

Introduction: The 2019 outbreak of e-cigarette or vaping product use-associated lung injury (EVALI) is believed to have been caused by vitamin E acetate, an additive used in some cannabis vaporizer products. Previous studies have primarily focused on changes in sales of electronic nicotine delivery systems following the initial advisory issued by the Centers for Disease Control (CDC) on August 17, 2019. The present study is intended to examine variation by age groups in sales of regulated cannabis vape products in the state of California before, during, and after the outbreak. Methods: Weekly sales revenue of cannabis vape products (from January 1, 2018, to December 31, 2020) was obtained from a sample of recreational cannabis retailers licensed in California. An interrupted time series analysis, using AutoRegressive, Integrated, Moving Average methods, was employed to estimate changes in the sales and market share of cannabis vape products in the weeks following the CDC advisory. Results: The total volume of regulated cannabis vape product sales increased substantially over the 3-year study period (2018-2020). Sales and market share of cannabis vape products, however, declined in both young and older adults immediately following the advisory, rebounding to pre-EVALI levels only for the young adults. For sales, the potential EVALI effect following the CDC's advisory equates to an 8.0% and 2.2% decline below expected levels in the older and young adults, respectively. Conclusions: The differential age effect on sales may reflect concerns regarding health effects of cannabis vaping products and greater awareness of the outbreak among older adults. Findings highlight the importance of informing consumers about health risks associated with using cannabis vape products acquired from regulated versus illicit sources.

Continuous chest compressions are associated with higher peak inspiratory pressures when compared to 30:2 in an experimental cardiac arrest model.

BACKGROUND: Ventilation during cardiopulmonary resuscitation (CPR) has long been a part of the standard treatment during cardiac arrests. Ventilation is usually given either during continuous chest compressions (CCC) or during a short pause after every 30 chest compressions (30:2). There is limited knowledge of how ventilation is delivered if it effects the hemodynamics and if it plays a role in the occurrence of lung injuries. The aim of this study was to compare ventilation parameters, hemodynamics, blood gases and lung injuries during experimental CPR given with CCC and 30:2 in a porcine model. METHODS: Sixteen pigs weighing approximately 33 kg were randomized to either receive CPR with CCC or 30:2. Ventricular fibrillation was induced by passing an electrical current through the heart. CPR was started after 3 min and given for 20 min. Chest compressions were provided mechanically with a chest compression device and ventilations were delivered manually with a self-inflating bag and 12 l/min of oxygen. During the experiment, ventilation parameters and hemodynamics were sampled continuously, and arterial blood gases were taken every five minutes. After euthanasia and cessation of CPR, the lungs and heart were removed in block and visually examined followed by sampling of lung tissue which were examined using microscopy. RESULTS: In the CCC group and the 30:2 group, peak inspiratory pressure (PIP) was 58.6 and 35.1 cmH2O (p < 0.001), minute volume (MV) 2189.6 and 1267.1 ml (p < 0.001), peak expired carbon dioxide (PECO2) 28.6 and 39.4 mmHg (p = 0.020), partial pressure of carbon dioxide (PaCO2) 50.2 and 61.1 mmHg (p = 0.013) and pH 7.3 and 7.2 (p = 0.029), respectively. Central venous pressure (CVP) decreased more over time in the 30:2 group (p = 0.023). All lungs were injured, but there were no differences between the groups. CONCLUSIONS: Ventilation during CCC resulted in a higher PIP, MV and pH and lower PECO2 and PaCO2, showing that ventilation mode during CPR can affect ventilation parameters and blood gases.

Exosomes: Potential Next-Generation Nanocarriers for the Therapy of Inflammatory Diseases.

Inflammatory diseases are common pathological processes caused by various acute and chronic factors, and some of them are autoimmune diseases. Exosomes are fundamental extracellular vesicles secreted by almost all cells, which contain a series of constituents, i.e., cytoskeletal and cytosolic proteins (actin, tubulin, and histones), nucleic acids (mRNA, miRNA, and DNA), lipids (diacylglycerophosphates, cholesterol, sphingomyelin, and ceramide), and other bioactive components (cytokines, signal transduction proteins, enzymes, antigen presentation and membrane transport/fusion molecules, and adhesion molecules). This review will be a synopsis of the knowledge on the contribution of exosomes from different cell sources as possible therapeutic agents against inflammation, focusing on several inflammatory diseases, neurological diseases, rheumatoid arthritis and osteoarthritis, intestinal bowel disease, asthma, and liver and kidney injuries. Current knowledge indicates that the role of exosomes in the therapy of inflammation and in inflammatory diseases could be distinctive. The main limitations to their clinical translation are still production, isolation, and storage. Additionally, there is an urgent need to personalize the treatments in terms of the selection of exosomes; their dosages and routes of administration; and a deeper knowledge about their biodistribution, type and incidence of adverse events, and long-term effects of exosomes. In conclusion, exosomes can be a very promising next-generation therapeutic option, superior to synthetic nanocarriers and cell therapy, and can represent a new strategy of effective, safe, versatile, and selective delivery systems in the future.

[Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy].

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

Therapeutic Effectiveness of Interferon-α2b against COVID-19 with Community-Acquired Pneumonia: The Ukrainian Experience.

Despite several targeted antiviral drugs against SARS-CoV-2 currently being available, the application of type I interferons (IFNs) still deserves attention as an alternative antiviral strategy. This study aimed to assess the therapeutic effectiveness of IFN-α in hospitalized patients with COVID-19-associated pneumonia. The prospective cohort study included 130 adult patients with coronavirus disease (COVID-19). A dose of 80,000 IU of IFN-α2b was administered daily intranasally for 10 days. Adding IFN-α2b to standard therapy reduces the length of the hospital stay by 3 days (p < 0.001). The level of CT-diagnosed lung injuries was reduced from 35% to 15% (p = 0.011) and CT injuries decreased from 50% to 15% (p = 0.017) by discharge. In the group of patients receiving IFN-α2b, the SpO2 index before and after treatment increased from 94 (92-96, Q1-Q3) to 96 (96-98, Q1-Q3) (p < 0.001), while the percentage of patients with normal saturation increased (from 33.9% to 74.6%, p < 0.05), but the level of SpO2 decreased in the low (from 52.5% to 16.9%) and very low (from 13.6% to 8.5%) categories. The addition of IFN-α2b to standard therapy has a positive effect on the course of severe COVID-19.

Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy / 中华肿瘤杂志

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

Maternal NO2 exposure disturbs the long noncoding RNA expression profile in the lungs of offspring in time-series patterns.

Gestation is a sensitive window to nitrogen dioxide (NO2) exposure, which may disturb fetal lung development and lung function later in life. Animal and epidemiological studies indicated that long noncoding RNAs (lncRNAs) participate in abnormal lung development induced by environmental pollutant exposure. In the present study, pregnant C57BL/6J mice were exposed to 2.5 ppm NO2 (mimicking indoor occupational exposure) or clean air, and lncRNAs expression profiles in the lungs of offspring mice were determined by lncRNA-seq on embryonic day 13.5 (E13.5), E18.5, postnatal day 1 (P1), and P14. The lung histopathology examination of offspring was performed, followed by weighted gene coexpression network analysis (WGCNA), prediction of lncRNAs-target genes, and the biological processes enrichment analysis of lncRNAs. Our results indicated that maternal NO2 exposure induced hypoalveolarization on P14 and differentially expressed lncRNAs showed a time-series pattern. Following WGCNA and enrichment analysis, 2 modules participated in development-related pathways. Importantly, the expressions of related genes were altered, some of which were confirmed to be related to abnormal vascular development and even lung diseases. The research points out that the maternal NO2 exposure leads to abnormal lung development in offspring that might be related to altered lncRNAs expression profiles with time-series-pattern.

Imaging the acute respiratory distress syndrome: past, present and future.

In patients with the acute respiratory distress syndrome (ARDS), lung imaging is a fundamental tool in the study of the morphological and mechanistic features of the lungs. Chest computed tomography studies led to major advances in the understanding of ARDS physiology. They allowed the in vivo study of the syndrome's lung features in relation with its impact on respiratory physiology and physiology, but also explored the lungs' response to mechanical ventilation, be it alveolar recruitment or ventilator-induced lung injuries. Coupled with positron emission tomography, morphological findings were put in relation with ventilation, perfusion or acute lung inflammation. Lung imaging has always been central in the care of patients with ARDS, with modern point-of-care tools such as electrical impedance tomography or lung ultrasounds guiding clinical reasoning beyond macro-respiratory mechanics. Finally, artificial intelligence and machine learning now assist imaging post-processing software, which allows real-time analysis of quantitative parameters that describe the syndrome's complexity. This narrative review aims to draw a didactic and comprehensive picture of how modern imaging techniques improved our understanding of the syndrome, and have the potential to help the clinician guide ventilatory treatment and refine patient prognostication.

The Protective Effects and Mechanism of Doxepin on Radiation-Induced Lung Injury in Rats.

Radiation-induced lung injuries (RILI) is one of the serious complications of radiotherapy posed by the damage of alveolar cells and inflammation over-reaction. We aimed to investigate the potential protective effects of doxepin on RILI (20 Gy total dose at 3 Gy/min of X-ray irradiation), as well as its underlying mechanism. For animal experiments, such parameters as Immunohistochemistry and hematoxylin and eosin (H&E) staining, WBC (white blood cell), CRP (C-reactive protein), Western blot, and q-PCR were detected. The results indicated that both survival status and weight increase of irradiated rats treated by doxepin (3 mg/kg/day, rat) were higher than those of treated with irradiation alone (Dosing started the day before irradiation). Further, histological examinations showed doxepin could tenuate the radiation injury, as indicated as alveolar inflammatory exudation and there was only mild interstitial inflammation infiltration. Western blotting and q-PCR showed that expression of NF-κß in X group were higher than that in XMD group. For the first time, we reported doxepin functioned as a radioprotectant candidate, which provide a promising application of doxepin for protecting radiotherapy injuries.

Single-cell transcriptomics reveals immune dysregulation mediated by IL-17A in initiation of chronic lung injuries upon real-ambient particulate matter exposure.

BACKGROUND: Long-term exposure to fine particulate matter (PM2.5) increases susceptibility to chronic respiratory diseases, including inflammation and interstitial fibrosis. However, the regulatory mechanisms by which the immune response mediates the initiation of pulmonary fibrosis has yet to be fully characterized. This study aimed to illustrate the interplay between different cell clusters and key pathways in triggering chronic lung injuries in mice following PM exposure. RESULTS: Six-week-old C57BL/6J male mice were exposed to PM or filtered air for 16 weeks in a real-ambient PM exposure system in Shijiazhuang, China. The transcriptional profiles of whole lung cells following sub-chronic PM exposure were characterized by analysis of single-cell transcriptomics. The IL-17A knockout (IL-17A-/-) mouse model was utilized to determine whether the IL-17 signaling pathway mediated immune dysregulation in PM-induced chronic lung injuries. After 16-week PM exposure, chronic lung injuries with excessive collagen deposition and increased fibroblasts, neutrophils, and monocytes were noted concurrent with a decreased number of major classes of immune cells. Single-cell analysis showed that activation of the IL-17 signaling pathway was involved in the progression of pulmonary fibrosis upon sub-chronic PM exposure. Depletion of IL-17A led to significant decline in chronic lung injuries, which was mainly triggered by reduced recruitment of myeloid-derived suppressor cells (MDSCs) and downregulation of TGF-ß. CONCLUSION: These novel findings demonstrate that immunosuppression via the IL-17A pathway plays a critical role in the initiation of chronic lung injuries upon sub-chronic PM exposure.

State marijuana policies and vaping associated lung injuries in the US.

BACKGROUND: The United States' 2019 outbreak of e-cigarette or vaping-associated lung injuries (EVALI) was linked to an additive most common in informally-sourced vaporizable marijuana concentrates. This study estimates how states' recreational and medical marijuana policies related to their 2019 EVALI incidence and residents' likelihood of vaping as their primary mode of marijuana use. METHODS: Multivariable negative binomial regressions estimated associations between states' total 2019 EVALI cases and marijuana policies: recreational legalization, medical legalization only, and whether medical-only policies allowed home cultivation, prohibited combustible use, or had operational dispensaries. Logistic regressions used survey data from the Behavioral Risk Factor Surveillance System's 2016-2019 marijuana supplements to assess how these policies related to past-30-day marijuana users' selection of vaping as their primary mode of use. RESULTS: EVALI incidence was 42% lower in recreational marijuana states (95%CI=0.339,0.993), versus a positive but statistically insignificant association with medical legalization alone. Adjusting for policy attributes revealed heterogeneity: among medical-marijuana-only states, EVALI incidences were > 60% lower where laws allowed home cultivation (aIRR=0.374; 95%CI=0.196, 0.715). Similarly, among past-30-day marijuana users, odds of vaping as one's primary mode of use were > 40% lower in medical-only states where home cultivation was allowed versus prohibited (aOR=0.588; 95%CI=0.365,0.946). CONCLUSIONS: Marijuana policy attributes linked to lower EVALI incidences were also associated with reduced likelihoods of vaping as one's primary mode of use. As additives in informally-sourced vaping concentrates could drive future EVALI cases, marijuana policy design should account for effects on mode of use in licit and illicit markets, to limit the scope of future outbreaks.

The effect of miR-21-5p on the MAP2K3 expressions and cellular apoptosis in the lung tissues of neonatal rats with hyperoxia-induced lung injuries.

OBJECTIVE: To explore the effect of miR-21-5p on the MAP2K3 expressions and cellular apoptosis in the lung tissues of neonatal rats with hyperoxia-induced lung injuries (HILI). METHODS: Twenty Sprague-Dawley neonatal rats were assigned to the normal group, and 120 rats were used to create a HILI model and were divided into the following six groups of 20 rats each: the model group, the miR-21-5p NC group, the miR-21-5p agomir group, the oe-NC group (MAP2K3 overexpression NC), the oe-MAP2K3 group, and the miR-21-5p agomir+oe-MAP2K3 group. RESULTS: miR-21-5p can target MAP2K3. Compared with the normal rats, the rats with HILI had lower miR-21-5p expression levels and higher MAP2K3 expression levels in the lung tissues (both P<0.05). Unlike the normal group, the other groups all presented different degrees of lung injuries, lower Bcl-2 expression levels, higher cellular apoptosis rates, and higher expression levels of cleaved caspase-3, Bax, IL-6, and TNF-α (all P<0.05). Compared with the model and the miR-21-5p NC groups, the miR-21-5p agomir group had better results in terms of the aforementioned markers; compared with the oe-NC group, the oe-MAP2K3 group had worse results in terms of these markers (all P<0.05). Moreover, we found that the protective effects of miR-21-5p overexpression on the lung tissues of HILI rats can be partially blocked by MAP2K3 overexpression. CONCLUSION: miR-21-5p can inhibit MAP2K3 expression and reduce cellular apoptosis in HILI, thereby exerting protective effects on neonatal rats with HILI.

Maternal smoking-induced lung injuries in dams and offspring via inflammatory cytokines.

Maternal smoking during pregnancy can induce permanent changes in neonatal inflammation, which will result in lifelong implications. An original study of data from GSE96978, composed of 2 subseries (GSE96976 and GSE96977), investigated genome-wide changes in ELT cells, the lungs of mouse dams and their juvenile offspring and focused on finding an in vitro alternative as a human tissue-based replacement for the use of animals. Therefore, the study only analyzed the similarities of GO terms between ELT cells and dams. However, the relationship between differentially expressed genes (DEGs) in dams and offspring was not investigated. The present study aimed to identify the key molecules involved in maternal smoking-induced dam and offspring lung injuries. Data from GSE96977 were downloaded from Gene Expression Omnibus (GEO) data sets. In our study, differentially expressed genes (DEGs) in dams and offspring were reanalyzed using the limma package. The results of Gene Set Enrichment Analysis (GSEA) showed that the DEGs in the lungs of dams were significantly enriched in immune-related functions and those in the lungs of offspring were enriched in cell growth. Furthermore, a total of 90 DEGs shared in the dam and offspring datasets were screened out. In addition, most of these DEGs were enriched in cytokine and cytokine receptor interaction KEGG pathways. Furthermore, protein-protein interaction (PPI) network analysis screened out 4 core genes in cluster 1. In addition, the miRNAs related to these core genes were predicted, and mmu-miR-1903 was screened out. Taken together, our data indicate that inflammatory responses may play an important role in maternal smoking induced lung injuries in dams and offspring. Furthermore, mmu-miR-1903 is a potential epigenetic biomarker of lung inflammation in the offspring of dams who smoked during pregnancy. In conclusion, by screening shared differential genes, we only need to detect maternal genes to predict maternal smoking-induced lung injuries in offspring.

Cytoprotective effects of erythropoietin: What about the lung?

Erythropoietin (Epo) is a pleiotropic cytokine, essential for erythropoiesis. Epo and its receptor (Epo-R) are produced by several tissues and it is now admitted that Epo displays other physiological functions than red blood cell synthesis. Indeed, Epo provides cytoprotective effects, which consist in prevention or fight against pathological processes. This perspective article reviews the various protective effects of Epo in several organs and tries to give a proof of concept about its effects in the lung. The tissue-protective effects of Epo could be a promising approach to limit the symptoms of acute and chronic lung diseases.

Calidad de vida y lesiones radiológicas en pacientes con tuberculosis sensible en el cono norte de Lima, Perú / Quality of life and radiological injuries in patients with sensitive tuberculosis in Cono Norte, Lima, Perú

RESUMEN Objetivo Determinar la correlación entre calidad de vida y lesiones pulmonares por radiografía en pacientes con tuberculosis en Lima Norte (Lima, Perú), durante el periodo 2018. Métodos Se realizó un estudio descriptivo de correlación para evaluar la calidad de vida y lesiones pulmonares por radiografía de los pacientes en tratamiento con esquema sensible de la jurisdicción del Hospital Nacional Sergio Bernales. La muestra correspondió a 102 pacientes pertenecientes al programa de tuberculosis, para la cual se utilizó el cuestionario respiratorio de Saint George, que mide la calidad de vida, constituida por tres dimensiones: síntomas, actividad social o impacto. Las lesiones radiológicas se cuantificaron mediante la clasificación de Willcox. Para el análisis de los datos se utilizó el programa SPSS, versión 23. Se estimó Chi-cuadrado y el coeficiente de correlación para determinar asociación de las variables. Resultados La correlación de Spearman es 0,622, lo que indica una relación positiva alta entre calidad de vida y lesiones pulmonares en pacientes con tuberculosis (p<0,05). Se determinó asociación entre calidad de vida y tiempo de tratamiento, con cambios en el tercer mes. Conclusión Existe una asociación entre calidad de vida y lesiones pulmonares por radiografía de pacientes con tuberculosis.

ABSTRACT Objective To determine the correlation between quality of life and lung lesions by radiography of patients with tuberculosis in Lima Norte (Lima, Peru) during the 2018 period. Methods A descriptive correlation study was carried out to evaluate the quality of life and lung lesions by radiography of patients in sensitive scheme treatment of the jurisdiction of the Sergio Bernales National Hospital. The sample corresponded to 102 patients belonging to the tuberculosis program and the Saint George respiratory questionnaire was used, which measures the quality of life, which consists of three dimensions: symptoms, activity, social, or impact. Radiological lesions were quantified by Willcox classification. For the data analysis, the SPSS version 23 program was used. Chi square and the correlation coefficient were estimated to determine the association of the variables. Results Spearman's correlation is 0.622, which indicates a high positive relationship between quality of life and lung lesions in patients with tuberculosis (p<0.05). An association between quality of life and treatment time was determined, with changes in the third month. Conclusion There is an association between quality of life and lung lesions by radiography of patients with tuberculosis.

Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients.

MicroRNAs (miRNAs) are critical modulators of endothelial homeostasis, which highlights their involvement in vascular diseases, including those caused by virus infections. Our main objective was to identify miRNAs involved in the endothelial function and determine their expression in post-mortem lung biopsies of COVID-19 patients with severe respiratory injuries and thrombotic events. Based on functional enrichment analysis, miR-26a-5p, miR-29b-3p, and miR-34a-5p were identified as regulators of mRNA targets involved in endothelial and inflammatory signaling pathways, as well as viral diseases. A miRNA/mRNA network, constructed based on protein-protein interactions of the miRNA targets and the inflammatory biomarkers characterized in the patients, revealed a close interconnection of these miRNAs in association to the endothelial activation/dysfunction. Reduced expression levels of selected miRNAs were observed in the lung biopsies of COVID-19 patients (n = 9) compared to the Controls (n = 10) (P < 0.01-0.0001). MiR-26a-5p and miR-29b-3p presented the best power to discriminate these groups (area under the curve (AUC) = 0.8286, and AUC = 0.8125, respectively). The correlation analysis of the miRNAs with inflammatory biomarkers in the COVID-19 patients was significant for miR-26a-5p [IL-6 (r2 = 0.5414), and ICAM-1 (r2 = 0.5624)], and miR-29b-3p [IL-4 (r2 = 0.8332) and IL-8 (r2 = 0.2654)]. Altogether, these findings demonstrate the relevance and the non-random involvement of miR-26a-5p, miR-29b-3p, and miR-34a-5p in endothelial dysfunction and inflammatory response in patients with SARS-CoV-2 infection and the occurrence of severe lung injury and immunothrombosis.

Addressing the Importance of Stem Cell-Based Therapy: A Perspective in the Treatment of COVID-19.

Severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) is an extremely pathogenic virus belonging to the family of Coronaviridae. First identified in Wuhan, China in December 2019 after an epidemiological investigation of an emerging cluster of pneumonia of unknown etiology, SARS-CoV-2 was declared the cause of a pandemic on March 11 by the World Health Organization (WHO), pointing to the over 118000 cases of Coronavirus disease 2019 (COVID-19) in over 110 countries. Despite the promising results of drug repositioning studies in the treatment of COVID-19, the evidence of their safety and efficacy remains inconclusive. Cell based therapy has been proven safe and possibly effective in treating multiple lung injuries and diseases, but its potential use in the treatment of COVID-19 has not been yet elucidated. Our aim in this review is to provide an overview of the immunomodulatory effect and the regenerative capacity of stem cells and their secretome in the treatment of many diseases including lung injuries. Those findings may contribute to a better understanding of the potential of stem cell therapy in SARS-CoV-2 infection and its potential use in order to find a solution for this healthcare crisis.

Association of vaping-related lung injuries with rates of e-cigarette and cannabis use across US states.

BACKGROUND AND AIMS: Responses to the 2019 US outbreak of 'e-cigarette or vaping product use-associated lung injury' (EVALI) ranged from temporary restrictions on nicotine e-cigarette sales to critiques of state cannabis policies. However, if either mass-marketed nicotine e-cigarettes or cannabis use per se drove this outbreak, as opposed to an additive in regionally available black-market e-liquids, states' rates of vaping and/or cannabis use should predict their EVALI prevalence. This study tests that relationship. DESIGN: Observational study of EVALI data from US states' health departments SETTING: United States. PARTICIPANTS: All US states (n = 50). MEASUREMENTS: The outcome of interest was each state's total EVALI cases per 12-64-year-old resident-an age group covering most EVALI patients-as reported in the second week of January 2020. Predictors are 2017-18 rates of adult e-cigarette use and past-month cannabis use by state. FINDINGS: The average state EVALI prevalence was 1.4 cases per 100 000 12-64-year-olds. Maps suggest a high-prevalence cluster comprising seven contiguous states in the northern Midwest. EVALI cases per capita were negatively associated with rates of vaping and past-month cannabis use, with the preferred specification's coefficients at -0.239 [95% confidence interval (CI) = -0.441, -0.037; P = 0.02] and -0.086 (95% CI = -0.141, -0.031; P = 0.003), respectively. Robustness checks supported this finding. CONCLUSIONS: In the United States, states with higher rates of e-cigarette and cannabis use prior to the 2019 'e-cigarette or vaping product use-associated lung injury' (EVALI) outbreak had lower EVALI prevalence. These results suggest that EVALI cases did not arise from e-cigarette or cannabis use per se, but rather from locally distributed e-liquids or additives most prevalent in the affected areas.

Angiotensin-Converting Enzyme 2 (ACE2) in the Pathogenesis of ARDS in COVID-19.

Seventeen years after the epidemic of SARS coronavirus, a novel coronavirus SARS-CoV-2-emerged resulting in an unprecedented pandemic. Angiotensin-converting enzyme 2 (ACE2) is an essential receptor for cell entry of SARS-CoV-2 as well as the SARS coronavirus. Despite many similarities to SARS coronavirus, SARS-CoV-2 exhibits a higher affinity to ACE2 and shows higher infectivity and transmissibility, resulting in explosive increase of infected people and COVID-19 patients. Emergence of the variants harboring mutations in the receptor-binding domain of the Spike protein has drawn critical attention to the interaction between ACE2 and Spike and the efficacies of vaccines and neutralizing antibodies. ACE2 is a carboxypeptidase which degrades angiotensin II, B1-bradykinin, or apelin, and thereby is a critical regulator of cardiovascular physiology and pathology. In addition, the enzymatic activity of ACE2 is protective against acute respiratory distress syndrome (ARDS) caused by viral and non-viral pneumonias, aspiration, or sepsis. Upon infection, both SARS-CoV-2 and SARS coronaviruses downregulates ACE2 expression, likely associated with the pathogenesis of ARDS. Thus, ACE2 is not only the SARS-CoV-2 receptor but might also play an important role in multiple aspects of COVID-19 pathogenesis and possibly post-COVID-19 syndromes. Soluble forms of recombinant ACE2 are currently utilized as a pan-variant decoy to neutralize SARS-CoV-2 and a supplementation of ACE2 carboxypeptidase activity. Here, we review the role of ACE2 in the pathology of ARDS in COVID-19 and the potential application of recombinant ACE2 protein for treating COVID-19.