Increased risk of developing cerebro-cardiovascular diseases in police officers: a nationwide retrospective cohort study.

BACKGROUND: Police officers face an increased risk of developing cerebro-cardiovascular diseases (CVD). However, current literature lacks population-based cohort studies specifically focusing on this association. This study aimed to investigate the association between police officers and the risk of developing CVD compared with education officers, while accounting for socioeconomic and demographic factors. METHODS: We used the Korean National Health Insurance Service data spanning from 2009 to 2020. In this population-based retrospective matched cohort study, we identified age, sex, and calendar years of job-enrollment-matched education officers for each police officer. This study evaluated the CVD occurrence, including acute myocardial infarction, ischemic stroke, and hemorrhagic stroke. Using multivariable Cox regression analysis, we determined the risk of developing CVD, expressed as a hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Among 104,134 police officers and 104,134 education officers, 4,391(42.2%) cases and 3,631(34.9%) cases of CVD occurred, respectively. The mean ± standard deviation age was 38.4 ± 9.4 years in police officers and 38.6 ± 9.5 years in education officers. The proportion of men was 84.8 % in both groups. Police officers were significantly associated with a higher risk of developing CVD compared with education officers, with an adjusted HR of 1.15 (95% CI, 1.09-1.22). In addition, police officers had significantly higher risks for acute myocardial infarction (adjusted HR, 1.16; 95% CI, 1.06-1.26) and ischemic stroke (adjusted HR, 1.17; 95% CI, 1.09-1.25). CONCLUSIONS: The findings of our study highlight a significant increase in the risk of developing CVD among police officers, particularly among those aged 45 years and older and those with uncontrolled blood pressure compared to their education officer counterparts. Future cohort studies are required to confirm this association.

Hexane Fraction of Adenophora triphylla var. japonica Root Extract Inhibits Angiogenesis and Endothelial Cell-Induced Erlotinib Resistance in Lung Cancer Cells.

The aim of this study was to investigate the anti-angiogenic effects of the hexane fraction of Adenophora triphylla var. japonica root extract (HAT) and its influence on the development of erlotinib resistance in human lung cancer cells. HAT significantly reduced the migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). The phosphorylation levels of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream molecules were decreased via HAT, indicating its anti-angiogenic potential in endothelial cells (ECs). A docking analysis demonstrated that ß-sitosterol and lupeol, representative components of HAT, exhibit a high affinity for binding to VEGFR2. In addition, conditioned media from HAT-pretreated H1299 human lung cancer cells attenuated cancer-cell-induced chemotaxis of HUVECs, which was attributed to the decreased expression of angiogenic and chemotactic factors in H1299 cells. Interestingly, co-culture of erlotinib-sensitive PC9 human lung cancer cells with HUVECs induced erlotinib resistance in PC9 cells. However, co-culture with HAT-pretreated HUVECs partially restored the sensitivity of PC9 cells to erlotinib. HAT inhibited the development of erlotinib resistance by attenuating hepatocyte growth factor (HGF) production by ECs. Taken together, our results demonstrate that HAT exerts its anticancer effects by regulating the crosstalk between ECs and lung cancer cells.

The Ethanolic Extract of Dictyopteris Divaricata Induces Apoptosis in Non-Small Cell Lung Cancer Cells by Inhibiting STAT3 Activity.

Dictyopteris divaricata (DD) has been reported to exert diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. In this study, we aimed to investigate the anticancer potential of the ethanolic extract of DD (EDD) in non-small cell lung cancer (NSCLC) cells and to explore the underlying mechanism. EDD significantly suppressed cell proliferation in H1299, PC9, and H1975 NSCLC cells. EDD treatment increased the proportion of Annexin V-positive cells and cells in sub-G1 phase, indicating the induction of apoptosis. This observation was further supported by the presence of fragmented nuclei and increased expression of cleaved PARP and cleaved caspase-3 in NSCLC cells following EDD treatment. Mechanistically, EDD decreased the phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) and Src. Transfection of constitutively activated STAT3 into H1975 cells partially attenuated EDD-induced apoptosis, highlighting the contribution of STAT3 inhibition to the anticancer activity of EDD. In addition, we identified fucosterol as a major constituent of EDD that exhibited similar anticancer potential in NSCLC cells. Taken together, our results demonstrate that EDD induces apoptosis in NSCLC cells by inhibiting STAT3 activity. We propose EDD as a potential candidate for the development of therapies targeting NSCLC.

The Effect of Parent Cell Type on Small Extracellular Vesicle-Derived Vehicle Functionality.

Cell therapies involving c-kit+ progenitor cells (CPCs) and mesenchymal stem cells (MSCs) have been actively studied for cardiac repair. The benefits of such therapies have more recently been attributed to the release of small extracellular vesicles (sEVs) from the parent cells. These sEVs are 30-180 nm vesicles containing protein/nucleic acid cargo encapsulated within an amphiphilic bilayer membrane. Despite their pro-reparative effects, sEV composition and cargo loading is highly variable, making it challenging to develop robust therapies with sEVs. Synthetic alternatives have been developed to allow cargo modulation, including prior work from the laboratory, to design sEV-like vehicles (ELVs). ELVs are synthesized from the sEV membrane but allow controlled cargo loading. It is previously shown that loading pro-angiogenic miR-126 into CPC-derived ELVs significantly increases endothelial cell angiogenesis compared to CPC-sEVs alone. Here, they expand on this work to design MSC-derived ELVs  and study the role of the parent cell type on ELV composition and function. It is found that ELV origin does affect the ELV potency and that ELV membrane composition can affect outcomes. This study showcases the versatility of ELVs to be synthesized from different parent cells and highlights the importance of selecting ELV source cells based on the desired functional outcomes.

Statistical modeling of extracellular vesicle cargo to predict clinical trial outcomes for hypoplastic left heart syndrome.

Cardiac-derived c-kit+ progenitor cells (CPCs) are under investigation in the CHILD phase I clinical trial (NCT03406884) for the treatment of hypoplastic left heart syndrome (HLHS). The therapeutic efficacy of CPCs can be attributed to the release of extracellular vesicles (EVs). To understand sources of cell therapy variability we took a machine learning approach: combining bulk CPC-derived EV (CPC-EV) RNA sequencing and cardiac-relevant in vitro experiments to build a predictive model. We isolated CPCs from cardiac biopsies of patients with congenital heart disease (n = 29) and the lead-in patients with HLHS in the CHILD trial (n = 5). We sequenced CPC-EVs, and measured EV inflammatory, fibrotic, angiogeneic, and migratory responses. Overall, CPC-EV RNAs involved in pro-reparative outcomes had a significant fit to cardiac development and signaling pathways. Using a model trained on previously collected CPC-EVs, we predicted in vitro outcomes for the CHILD clinical samples. Finally, CPC-EV angiogenic performance correlated to clinical improvements in right ventricle performance.

Root Extract of Trichosanthes kirilowii Suppresses Metastatic Activity of EGFR TKI-Resistant Human Lung Cancer Cells by Inhibiting Src-Mediated EMT.

The roots of Trichosanthes kirilowii (TK) have been used in traditional oriental medicine for the treatment of respiratory diseases. In this study, we investigated whether an ethanolic root extract of TK (ETK) can regulate the metastatic potency of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant human lung cancer cells. The relative migration and invasion abilities of erlotinib-resistant PC9 (PC9/ER) and gefitinib-resistant PC9 (PC9/GR) cells were higher than those of parental PC9 cells. Mesenchymal markers were overexpressed, whereas epithelial markers were downregulated in resistant cells, suggesting that resistant cells acquired the EMT phenotype. ETK reduced migration and invasion of resistant cells. The expression levels of N-cadherin and Twist were downregulated, whereas Claudin-1 was upregulated by ETK, demonstrating that ETK suppresses EMT. As a molecular mechanism, Src was dephosphorylated by ETK. The anti-metastatic effect of ETK was reduced by transfecting PC9/ER cells with a constitutively active form of c-Src. Dasatinib downregulated N-cadherin, Twist, and vimentin, suggesting that Src regulates EMT in resistant cells. Notably, CuB played a key role in mediating the anti-metastatic activity of ETK. Collectively, our results demonstrate that ETK can attenuate the metastatic ability of EGFR-TKI-resistant lung cancer cells by inhibiting Src-mediated EMT.

Customized Loading of microRNA-126 to Small Extracellular Vesicle-Derived Vehicles Improves Cardiac Function after Myocardial Infarction.

Small extracellular vesicles (sEVs) are promising for cell-based cardiac repair after myocardial infarction. These sEVs encapsulate potent cargo, including microRNAs (miRs), within a bilayer membrane that aids sEV uptake when administered to cells. However, despite their efficacy, sEV therapies are limited by inconsistencies in the sEV release from parent cells and variability in cargo encapsulation. Synthetic sEV mimics with artificial bilayer membranes allow for cargo control but suffer poor stability and rapid clearance when administered in vivo. Here, we developed an sEV-like vehicle (ELV) using an electroporation technique, building upon our previously published work, and investigated the potency of delivering electroporated ELVs with pro-angiogenic miR-126 both in vitro and in vivo to a rat model of ischemia-reperfusion. We show that electroporated miR-126+ ELVs improve tube formation parameters when administered to 2D cultures of cardiac endothelial cells and improve both echocardiographic and histological parameters when delivered to a rat left ventricle after ischemia reperfusion injury. This work emphasizes the value of using electroporated ELVs as vehicles for delivery of select miR cargo for cardiac repair.

A novel and cost-effective method for high-throughput 3D culturing and rhythmic assessment of hiPSC-derived cardiomyocytes using retroreflective Janus microparticles.

BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) gain attention as a potent cell source in regenerative medicine and drug discovery. With the necessity of the demands for experimental models to create a more physiologically relevant model of the heart in vitro we herein investigate a 3D culturing platform and a method for assessing rhythm in hiPSC-CMs. METHODS: The 3D cell culture PAMCELL™ plate is designed to enable cells to attach exclusively to adhesive patterned areas. These cell adhesive zones, named as micro-patterned pads, feature micron silica beads that are surface-modified with the well-known arginyl-glycyl-aspartic acid (RGD) peptide. RGD binding to the surface of hiPSC-CMs facilitates cell-cell attachment and the formation of uniform-size spheroids, which is controlled by the diameter of the micro-patterned pads. The assessment and evaluation of 3D hiPSC-CMs beating pattern are carried out using reflective properties of retroreflective Janus micro-particle (RJP). These RJPs are modified with an antibody targeting the gap junction protein found on the surface of hiPSC-CM spheroids. The signal assessment system comprises a camera attached to an optical microscope and a white light source. RESULTS: The 3D PAMCELL™ R100 culture plate efficiently generate approximately 350 uniform-sized hiPSC-CM spheroids in each well of a 96-well plate and supported a 20-day culture. Analysis of genes and protein expression levels reveal that iPSC-CM spheroids grown on PAMCELL™ R100 retain cardiac stem cell characteristics and functions, outperforming traditional 2D culture platform. Additionally, the RJPs enable monitoring and evaluation of in vitro beating properties of cardiomyocytes without using complex monitoring setup. The system demonstrates its capability to identify alteration in the rhythmic activity of cardiac cells when exposed to ion channel blockers, nifedipine and E4031. CONCLUSIONS: The integration of the 3D culture method and RJPs in this study establishes a platform for evaluating the rhythmic properties of 3D hiPSC-CMs. This approach holds significant potential for identifying arrhythmias or other cardiac abnormalities, ultimately contributing to the development of more effective therapies for heart diseases.

Scarring the early-life microbiome: its potential life-long effects on human health and diseases.

The gut microbiome is widely recognized as a dynamic organ with a profound influence on human physiology and pathology. Extensive epidemiological and longitudinal cohort studies have provided compelling evidence that disruptions in the early-life microbiome can have long-lasting health implications. Various factors before, during, and after birth contribute to shaping the composition and function of the neonatal and infant microbiome. While these alterations can be partially restored over time, metabolic phenotypes may persist, necessitating research to identify the critical period for early intervention to achieve phenotypic recovery beyond microbiome composition. In this review, we provide current understanding of changes in the gut microbiota throughout life and the various factors affecting these changes. Specifically, we highlight the profound impact of early-life gut microbiota disruption on the development of diseases later in life and discuss perspectives on efforts to recover from such disruptions. [BMB Reports 2023; 56(9): 469-481].

Delocalized Lithium Ion Flux by Solid-State Electrolyte Composites Coupled with 3D Porous Nanostructures for Highly Stable Lithium Metal Batteries.

This work investigates the root cause of failure with the ultimate anode, Li metal, when employing conventional/composite separators and/or porous anodes. Then a feasible route of utilizing Li metal is presented. Our operando and microscopy studies have unveiled that Li+ flux passing through the conventional separator is not uniform, resulting in preferential Li plating/stripping. Porous anodes alone are subject to clogging with moderate- or high-loading cathodes. Here we discovered it is necessary to seek synergy from our separator and anode pair to deliver delocalized Li+ to the anode and then uniformly plate Li metal over the large surface areas of the porous anode. Our polymer composite separator containing a solid-state electrolyte (SE) can provide numerous Li+ passages through the percolated SE and pore networks. Our finite element analysis and comparative tests disclosed the synergy between the homogeneous Li+ flux and current density reduction on the anode. Our composite separators have induced compact and uniform Li plating with robust inorganic-rich solid electrolyte interphase layers. The porous anode decreased the nucleation overpotential and interfacial contact impedance during Li plating. Full cell tests with LiFePO4 and Li[Ni0.8Mn0.1Co0.1]O2 (NMC811) exhibited remarkable cycling behaviors: ∼80% capacity retention at the 750th and 235th cycle, respectively. A high-loading NMC811 (4 mAh cm-2) full cell displayed maximum cell-level energy densities of 334 Wh kg-1 and 783 Wh L-1. This work proposes a solution for raising energy density by adopting Li metal, which could be a viable option considering only incremental advancement in conventional cathodes lately.

An Ethanol Extract of Perilla frutescens Leaves Suppresses Adrenergic Agonist-Induced Metastatic Ability of Cancer Cells by Inhibiting Src-Mediated EMT.

Previous studies have indicated that the adrenergic receptor signaling pathway plays a fundamental role in chronic stress-induced cancer metastasis. In this study, we investigated whether an ethanol extract of Perilla frutescens leaves (EPF) traditionally used to treat stress-related symptoms by moving Qi could regulate the adrenergic agonist-induced metastatic ability of cancer cells. Our results show that adrenergic agonists including norepinephrine (NE), epinephrine (E), and isoproterenol (ISO) increased migration and invasion of MDA-MB-231 human breast cancer cells and Hep3B human hepatocellular carcinoma cells. However, such increases were completely abrogated by EPF treatment. E/NE induced downregulation of E-cadherin and upregulation of N-cadherin, Snail, and Slug. Such effects were clearly reversed by pretreatment with EPF, suggesting that the antimetastatic activity of EPF could be related to epithelial-mesenchymal transition (EMT) regulation. EPF suppressed E/NE-stimulated Src phosphorylation. Inhibition of Src kinase activity with dasatinib completely suppressed the E/NE-induced EMT process. Transfecting MDA-MB-231 cells with constitutively activated Src (SrcY527F) diminished the antimigration effect of EPF. Taken together, our results demonstrate that EPF can suppress the adrenergic agonist-promoted metastatic ability of cancer cells by inhibiting Src-mediated EMT. This study provides basic evidence supporting the probable use of EPF to prevent metastasis in cancer patients, especially those under chronic stress.

Knockdown of deleterious miRNA in progenitor cell-derived small extracellular vesicles enhances tissue repair in myocardial infarction.

Small extracellular vesicles (sEVs) play a critical role in cardiac cell therapy by delivering molecular cargo and mediating cellular signaling. Among sEV cargo molecule types, microRNA (miRNA) is particularly potent and highly heterogeneous. However, not all miRNAs in sEV are beneficial. Two previous studies using computational modeling identified miR-192-5p and miR-432-5p as potentially deleterious in cardiac function and repair. Here, we show that knocking down miR-192-5p and miR-432-5p in cardiac c-kit+ cell (CPC)-derived sEVs enhances the therapeutic capabilities of sEVs in vitro and in a rat in vivo model of cardiac ischemia reperfusion. miR-192-5p- and miR-432-5p-depleted CPC-sEVs enhance cardiac function by reducing fibrosis and necrotic inflammatory responses. miR-192-5p-depleted CPC-sEVs also enhance mesenchymal stromal cell-like cell mobilization. Knocking down deleterious miRNAs from sEV could be a promising therapeutic strategy for treatment of chronic myocardial infarction.

Alzheimer's disease-like cortical atrophy mediates the effect of air pollution on global cognitive function.

Little is known about the effect of air pollution on Alzheimer's disease (AD)-specific brain structural pathologies. There is also a lack of evidence on whether this effect leads to poorer cognitive function. We investigated whether, and the extent to which, AD-like cortical atrophy mediated the association between air pollution exposures and cognitive function in dementia-free adults. We used cross-sectional data from 640 participants who underwent brain magnetic resonance imaging and the Montreal Cognitive Assessment (MoCA). Mean cortical thickness (as the measure of global cortical atrophy) and machine learning-based AD-like cortical atrophy score were estimated from brain images. Concentrations of particulate matter with diameters ≤ 10 µm (PM10) and ≤ 2.5 µm (PM2.5) and nitrogen dioxide (NO2) were estimated based on each participant's residential address. Following the product method, a mediation effect was tested by conducting a series of three regression analyses (exposure to outcome; exposure to mediator; and exposure and mediator to outcome). A 10 µg/m3 increase in PM10 (ß = -1.13; 95 % CI, -1.73 to -0.53) and a 10 ppb increase in NO2 (ß = -1.09; 95 % CI, -1.40 to -0.78) were significantly associated with a lower MoCA score. PM10 (ß = 0.27; 95 % CI, 0.06 to 0.48) and NO2 (ß = 0.35; 95 % CI, 0.25 to 0.45) were significantly associated with an increased AD-like cortical atrophy score. Effects of PM10 and NO2 on MoCA scores were significantly mediated by mean cortical thickness (proportions mediated: 25 %-28 %) and AD-like cortical atrophy scores (13 %-16 %). The findings suggest that air pollution exposures may induce AD-like cortical atrophy, and that this effect may lead to poorer cognitive function in dementia-free adults.

Hexane fraction of Adenophora triphylla var. japonica root extract induces apoptosis of human lung cancer cells by inactivating Src/STAT3 pathway.

The aim of this study was to investigate the anticancer effect of Adenophora triphylla var. japonica (AT) root extract on human non-small cell lung cancer (NSCLC) cells and the mechanism involved in such effect. Among three fractions of AT root extract, hexane fraction (HAT) significantly decreased the proliferation of NSCLC cells. Besides, HAT treatment dose-dependently inhibited colony formation of NSCLC cells. These effects were associated with apoptosis induction evidenced by increased chromatin condensation, accumulation of sub-G1 DNA content and annexin V-positive cells, and enhanced expression of apoptotic proteins, including cleaved-caspases and cleaved-poly (ADP-ribose) polymerase (PARP). Notably, phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) and Src were decreased by HAT. Transfection with STAT3 or Src for constitutive activation reversed the anti-proliferative effect of HAT on H1299 cells. Taken together, our findings suggest that HAT-induced apoptosis in NSCLC cells is mediated by inhibition of Src/STAT3 pathway.

The Ethanolic Extract of Trichosanthes Kirilowii Root Exerts anti-Cancer Effects in Human Non-Small Cell Lung Cancer Cells Resistant to EGFR TKI.

The aim of this study was to investigate whether the ethanol extract of the Trichosanthes kirilowii root (ETK), traditionally used to treat lung diseases, exhibits anticancer activity in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant non-small cell lung cancer (NSCLC) cells. ETK treatment suppressed the growth of EGFR TKI-resistant NSCLC cells, including H1299, H1975, PC9/ER (erlotinib-resistant PC9) and PC9/GR (gefitinib-resistant PC9) cells, in a concentration- and time-dependent manner. Dose-dependent decline in anchorage-dependent and -independent colony formation was also detected following ETK treatment. We demonstrate that the growth-inhibitory effect of ETK was related to apoptosis induction, based on flow cytometry results showing ETK-induced increase in the percentage of cells with sub-G1 DNA and the population of annexin V-positive cells. Consistently, ETK induced chromatin condensation and cleavage of poly(ADP-ribose) polymerase (PARP). As a molecular mechanism, the phosphorylation level of signal transducer and activator of transcription 3 (STAT3) and Src was decreased by ETK. ETK-induced apoptosis was partially reversed by transfection of constitutively activated STAT3, indicating that STAT3 inactivation mediated ETK-induced apoptosis in EGFR TKI-resistant NSCLC cells. Our results provide basic evidence supporting the role of ETK as a novel therapeutic in EGFR TKI-resistant NSCLC.

Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure.

Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.

ß2-Adrenergic Receptor Signaling Pathway Stimulates the Migration and Invasion of Cancer Cells via Src Activation.

Chronic stress has been reported to stimulate the release of catecholamines, including norepinephrine (NE) and epinephrine (E), which promote cancer progression by activating the adrenergic receptor (AR). Although previous studies showed that ß2-AR mediated chronic stress-induced tumor growth and metastasis, the underlying mechanism has not been fully explored. In this study, we aimed to investigate the molecular mechanism by which ß2-AR exerts a pro-metastatic function in hepatocarcinoma (HCC) cells and breast cancer (BC) cells. Our results showed that Hep3B human HCC cells and MDA-MB-231 human BC cells exhibited the highest ADRB2 expression among diverse HCC and BC cell lines. NE, E, and isoprenaline (ISO), adrenergic agonists commonly increased the migration and invasion of Hep3B cells and MDA-MB-231 cells. The phosphorylation level of Src was significantly increased by E/NE. Dasatinib, a Src kinase inhibitor, blocked E/NE-induced migration and invasion, indicating that AR agonists enhanced the mobility of cancer cells by activating Src. ADRB2 knockdown attenuated E/NE-induced Src phosphorylation, as well as the metastatic ability of cancer cells, suggesting the essential role of ß2-AR. Taken together, our results demonstrate that chronic stress-released catecholamines promoted the migration and invasion of HCC cells and BC cells via ß2-AR-mediated Src activation.

Factors Affecting Human Papillomavirus Vaccination in Men: Systematic Review.

BACKGROUND: Despite the high risks associated with human papillomavirus (HPV), the HPV vaccination rate of men is far lower than women. Most previous review studies have focused on female vaccination and related affecting factors. However, previous studies have reported that the factors affecting HPV vaccination differ by gender. OBJECTIVE: The aim of this review was to identify the factors affecting HPV vaccine initiation in men through a systematic review approach. METHODS: A literature review was conducted across 3 central electronic databases for relevant articles. A total of 30 articles published between 2013 and 2019 met the inclusion criteria and were reviewed in this study. RESULTS: In total, 50 factors affecting HPV vaccination in men were identified, including 13 sociodemographic factors and social structure factors, 12 belief-related variables, 4 family factors, 4 community factors, 14 variables related to needs, and 3 environmental factors. CONCLUSIONS: To increase HPV vaccination rates in men, strategies targeting young males and their families should consider frequent visits to or contact with health care providers so that health care professionals can provide recommendations for HPV vaccination.

The Root Extract of Peucedanum praeruptorum Dunn Exerts Anticancer Effects in Human Non-Small-Cell Lung Cancer Cells with Different EGFR Mutation Statuses by Suppressing MET Activity.

The aim of this study was to investigate the anticancer effects of the root extract of Peucedanum praeruptorum Dunn (EPP) in human non-small-cell lung cancer (NSCLC) cells and explore the mechanisms of action. We used four types of human lung cancer cell lines, including H1299 (epidermal growth factor receptor (EGFR) wild-type), PC9 (EGFR Glu746-Ala750 deletion mutation in exon 19; EGFR tyrosine kinase inhibitor (TKI)-sensitive), H1975 (EGFR L858R/T790M double-mutant; EGFR TKI-resistant), and PC9/ER (erlotinib-resistant) cells. EPP suppressed cell growth and the colony formation of NSCLC cells in a concentration-dependent manner. EPP stimulated chromatin condensation, increased the percentage of sub-G1 phase cells, and enhanced the proportion of annexin V-positive cells, demonstrating that EPP triggered apoptosis in NSCLC cells regardless of the EGFR mutation and EGFR TKI resistance status. The phosphorylation level of the signal transducer and activator of transcription 3 (STAT3) and AKT was decreased by EPP. The expression of STAT3 target genes was also downregulated by EPP. EPP reversed hepatocyte growth factor (HGF)-induced MET phosphorylation and gefitinib resistance. Taken together, our results demonstrate that EPP exerted anticancer effects not only in EGFR TKI-sensitive NSCLC cells, but also in EGFR TKI-resistant NSCLC cells, by suppressing MET activity.

Comparative computational RNA analysis of cardiac-derived progenitor cells and their extracellular vesicles.

Stem/progenitor cells, including cardiac-derived c-kit+ progenitor cells (CPCs), are under clinical evaluation for treatment of cardiac disease. Therapeutic efficacy of cardiac cell therapy can be attributed to paracrine signaling and the release of extracellular vesicles (EVs) carrying diverse cargo molecules. Despite some successes and demonstrated safety, large variation in cell populations and preclinical/clinical outcomes remains a problem. Here, we investigated this variability by sequencing coding and non-coding RNAs of CPCs and CPC-EVs from 30 congenital heart disease patients and used machine learning methods to determine potential mechanistic insights. CPCs retained RNAs related to extracellular matrix organization and exported RNAs related to various signaling pathways to CPC-EVs. CPC-EVs are enriched in miRNA clusters related to cell proliferation and angiogenesis. With network analyses, we identified differences in non-coding RNAs which give insight into age-dependent functionality of CPCs. By taking a quantitative computational approach, we aimed to uncover sources of CPC cell therapy variability.