Although many high-risk mucosal and cutaneous human papillomaviruses (HPVs) theoretically have the potential to synthesize L1 isoforms differing in length, previous seroepidemiological studies only focused on the short L1 variants, co-assembling with L2 to infectious virions. Using the multimammate mouse Mastomys coucha as preclinical model, this is the first study demonstrating seroconversion against different L1 isoforms during the natural course of papillomavirus infection. Intriguingly, positivity with the cutaneous MnPV was accompanied by a strong seroresponse against a longer L1 isoform, but to our surprise, the raised antibodies were non-neutralizing. Only after a delay of around 4 months, protecting antibodies against the short L1 appeared, enabling the virus to successfully establish an infection. This argues for a novel humoral immune escape mechanism that may also have important implications on the interpretation of epidemiological data in terms of seropositivity and protection of PV infections in general.
Objective To develop a bioluminescence-labelled bacterial infection model to monitor the colonization and clearance process of Escherichia coli O157:H7 in the lungs of mice following influenza A virus/Puerto Rico/8/34 (H1N1) strain (IAV/PR8) infection. Methods BALB/c mice were administered IAV/PR8 or 0.01 M phosphate-buffered saline (PBS; pH 7.4) intranasally 4 days prior to intranasal administration of 1 × 107 colony-forming units (CFU) of E. coli O157:H7-lux. Whole-body bioluminescent signals were monitored at 10 min, 4 h, 8 h, 12 h, 16 h and 24 h post-bacterial infection. Lung bioluminescent signals and bacterial load (CFU/g) were monitored at 4 h, 8 h, 12 h, 16 h and 24 h post-bacterial infection. Results Prior IAV/PR8 infection of mice resulted in a higher level of bacterial colonization and a lower rate of bacterial clearance from the lungs compared with mice treated with PBS. There were also consistent findings between the bioluminescence imaging and the CFU measurements in terms of identifying bacterial colonization and monitoring the clearance dynamics of E. coli O157:H7-lux in mouse lungs. Conclusion This novel bioluminescence-labelled bacterial infection model rapidly detected bacterial colonization of the lungs and monitored the clearance dynamics of E. coli O157:H7-lux following IAV/PR8 infection.
Particulate matter (PM), a major air pollutant in Beijing in recent years, poses a formidable public health threat. Even through many studies have documented the chemical and biological characteristics of PM, less is known about these characteristics on hazardous haze days (Air Quality Index, AQI 301-500) and the difference with sunny or unhealthy haze day (AQI 151-200) characteristics. Herein, studies were performed during a red alert air pollution event (continuous hazardous haze days) and the first few days following the event (sunny days first and then unhealthy haze days) in Beijing from December 19 to 25, 2016. A laser particle counter and an ANDERSEM-6 sampler were used to study the concentration and size distributions dynamics of the PM and the culturable airborne bacteria and fungi, respectively. PM2.5 was sampled by a high-volume air sampler and the chemical compositions, bacterial and fungal community structures, and endotoxin levels were analyzed. The results showed that the PM concentrations on the hazardous haze days and unhealthy haze days were 10.7 and 8.0 times higher, respectively, than those on the sunny days. The chemical composition of PM2.5 was highly correlated with the AQI. The concentration and percentage of water-soluble inorganic ions (WSII), which dominated the PM2.5 constituents, as well as the levels of endotoxin were higher on hazardous haze days than on unhealthy haze days and sunny days. Interestingly, the abundances of bacteria and fungi demonstrated the following order: unhealthy haze days> sunny days> hazardous haze days. Most culturable bacteria and fungi were distributed in particles with aerodynamic diameters of 2.1-4.7 μm. Redundancy analysis found total organic carbon explained 30.0% and 27.1% of total variations in bacterial composition and fungal composition at the genera level, respectively. Our results facilitate a better understanding of the biological and chemical composition dynamics of PM in Beijing.
Since December 2019, coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a great challenge to the world's public health system. Nosocomial infections have occurred frequently in medical institutions worldwide during this pandemic. Thus, there is an urgent need to construct an effective surveillance and early warning system for pathogen exposure and infection to prevent nosocomial infections in negative-pressure wards. In this study, visualization and construction of an infection risk assessment of SARS-CoV-2 through aerosol and surface transmission in a negative-pressure ward were performed to describe the distribution regularity and infection risk of SARS-CoV-2, the critical factors of infection, the air changes per hour (ACHs) and the viral variation that affect infection risk. The SARS-CoV-2 distribution data from this model were verified by field test data from the Wuhan Huoshenshan Hospital ICU ward. ACHs have a great impact on the infection risk from airborne exposure, while they have little effect on the infection risk from surface exposure. The variant strains demonstrated significantly increased viral loads and risks of infection. The level of protection for nurses and surgeons should be increased when treating patients infected with variant strains, and new disinfection methods, electrostatic adsorption and other air purification methods should be used in all human environments. The results of this study may provide a theoretical reference and technical support for reducing the occurrence of nosocomial infections.
Abstract Recombinant adeno-associated viruses (AAVs) play a pivotal role in gene therapy, a promising approach aimed at treating various genetic disorders by introducing modified genetic material into cells or tissues. These AAV capsids are utilized as a vector in transferring genetic material into host cells. In discovery research, many AAV serotypes are developed in parallel to identify the optimal subtype for subsequent preclinical and clinical use. However, gene therapies have found limited success in clinical translation, in part, due to variable transgene delivery efficacy between traditional in vitro and in vivo models and human models. This study presents an organoid-based approach that mimics human physiology, as well as organ-specific features and cell diversity within an organ. Organoids are 3D structures derived from stem cells that resemble the cellular architecture and functionality of a specific organ. Compared to conventional 2D cell cultures, organoids provide a more comprehensive modeling of complex cell signaling, cell-cell and cell-extracellular matrix interactions, simulating the complex interplay between various cell types and functions. Within this study, several human-based organoid models were built, cerebral and cardiac, and verified by identifying the expression level of known marker genes through RNA sequencing. Five different AAV serotypes were utilized to evaluate transgene efficacy using each type of organoid model. Expression of delivered GFP transgene within each organoid was then compared to evaluate transduction and select the optimal AAV serotype in comparison to commercial wild-type AAVs. We outline the use of human organoid as an improved preclinical model for selecting AAV serotypes and evaluating transgene delivery efficacy to help provide better guidance for gene therapy development when moving into clinical research. Citation Format: Yingying Fu, Zhen Qi, Zhanguan Zuo, Spencer Chiang, An Ouyang, Glory Gao, Shuge Guan, Jin-Qiu (Jessie) Chen, Rosanna Zhang, Cheng Wang. Selection of AAV capsids by evaluating transgene delivery using human organoid models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4245.
Abstract The neuregulin-1 (NRG1)/ERBB4 signaling pathway has emerged as a cardioprotective pathway and is a promising target for the treatment of chronic heart failure. Activation of ERBB4 signaling is known to decrease cardiomyocyte cell death and hypertrophy, and fibroblast collagen synthesis. Recombinant NRG1 (rNRG1) is currently tested in phase III clinical trials for heart failure, but its need for intravenous administration is a disadvantage. In an attempt to circumvent this, we hypothesized that small-molecule-induced activation of ERBB4 is feasible and would recapitulate the effects of its natural ligand on myocytes and fibroblasts. To this end, we screened 10,240 compounds for their ability to induce homodimerization of ERBB4. We identified a series of 8 similar compounds (named EF-1 – EF-8) that concentration-dependently induced ERBB4 dimerization, with EF-1 being the most potent and effective compound (n = 4-5 independent repeats in each group; Emax = 27.9 ± 4.8% relative to NRG1, EC50 = 10.5 ± 4.5 x 10-6). EF-1 showed neither cytotoxicity nor increased cell proliferation of tumor cell lines. In vitro, EF-1 significantly decreased in a concentration-dependent manner hydrogen peroxide–induced cardiomyocyte cell death (n = 4 independent repeats in each group; P<0.0001 compared to siERBB4, Fig. 1A), angiotensin-II (AngII)-induced cardiomyocyte hypertrophy (n = 20 individual cardiomyocytes in each group; P<0.0001 compared to AngII/vehicle, Fig. 1B), and collagen expression in cultured human fibroblasts (n = 3 independent repeats in each group; P=0.03 compared to siERBB4, Fig. 1C). The observed effects in cultured cardiomyocytes and fibroblasts could be abrogated by siRNA targeting ERBB4, indicating that they were mediated by ERBB4. Moreover, when used in vivo, EF-1 (2 mg/kg/day) significantly decreased AngII-induced left ventricular Col1a1 and Col3a1 mRNA expression (n = 4-5 mice in each group; P=0.02 and P=0.004 compared to AngII/vehicle, respectively) and inhibited AngII-induced myocardial total and interstitial fibrosis in wild-type mice (n = 4-5 mice in each group, Fig. 2), but not in Erbb4-null mice. Moreover, EF-1 decreased acute cardiotoxicity (assessed by troponin release) in wild-type mice treated with doxorubicin (DOX; n = 8-9 mice in each group; P<0.0001 compared to DOX/vehicle), but not in Erbb4-null mice. In conclusion, we show that small-molecule-induced ERBB4 dimerization and activation is feasible, and recapitulates anti-fibrotic and cardiomyocyte protective effects in the heart in an ERBB4-dependent manner, both in vitro and in vivo. This could be the start for the further development of small-molecule ERBB4 agonists as a novel class of drugs to treat heart failure. Cardiomyocyte-protective effect in vitroAnti-fibrotic effect in vivo
Objective:To establish a method to determinate the quantity of baicalin and chlorogenic acid in Yinhuang capsules simultaneously.Methods:The isoabsorptive point of baicalin and chlorogenic acid,the solvent agent and the ex-tracting time were detected by UV,the constitution and rate of mobile phase were determined by HPLC.Results:The quantity of baicalin and chlorogenic acid in Yinhuang capsules was determined simultaneously by HPLC and the method was confirmed methodologically.Conclusion:The method has the advantage of easiness and efficiency,and lays firm foundation for studies on the quantity determination of Yinhuang capsules.
[Objective] To evaluate the possible effects of power frequency electromagnetic fields(EMF)(50 Hz)on the health condition and neurobehavioral function of workers in transformer stations.[ Methods] Intensity of EMF at transformer stations of 18 factories was measured with HI-3604 EMF radiation meter. Neurobehavioral function of 105 electricians and 110 controls were examined with Neurobehavior Core Test Battery(NCTB)recommended by World Health Organization(WHO). Some neural discomfort symptoms of the two groups were recorded by questionnaires. Hematological indices of the two groups were determined including IgG, IgM, IgA, leukocyte formulae(neutrophil, lymphocyte, monocyte, eosinophil, basophil), erythrocyte indices(hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration)and platelet. [Results] Electric field intensity of 220 kV transformer stations was significantly higher than that of 35 kV transformer stations(P 0.01), but the magnetic field intensity in the two kinds of workplaces were not significantly different(P 0.05). It showed that in the exposure group the emotional state of tension, depress, anger, fatigue and confusion appeared more obviously than those in the control group(P 0.05), but the score of vigour was lower(P 0.05). The average scores of Benton visual retention, correct tapping dots and sum tapping dots of electricians were all lower than those of controls(P 0.05). The prevalence of headache, dizzy, insomnia, dreamful and hypomnesia in electricians were higher than those in the control group(P 0.01). Average lymphocyte count of electricians was higher than that of controls(P 0.05), but mean corpuscular hemoglobin concentration level of electricians was lower than that of controls(P 0.05). There was no significant difference of IgG, IgM and IgA between the two groups.[Conclusion] Neurobehavioral function of electricians working under power frequency electric fields may be impaired to a certain extend. Long term exposure to power frequency electric field may induce neural symptoms and slight alterations in some hematological indices, but it is not concluded that occupational exposure to 50 Hz EMF can influence their immune system.
The intestinal bacteria are the enormous bacteria organism which colonize the intestinal tract. It has been found recently that the intestinal bacteria participate in modulating the multi-system physiology activity, including the cardiovascular system, the endocrine and metabolic system and so on. Thyroid gland is one of the most important organs in the endocrine system. Iodine plays an essential role in the chemical structure of thyroid hormone. Further more, trace mineral selenium is rather important in the conversion of T4 to T3. Once the component of the intestinal bacteria changes, it will not only be associated with the autoimmune thyroid diseases, but also affect the absortion and metabolism of the thyroid hormones and other agents, such as exogenous thyroxine, iodine and selenium. However, current researches focusing on the association between intestinal bacteria and thyroid homeostasis are far from clear enough, and more iceberg unseen may be in the sea.
Key words:
Intestinal bacteria; Thyroid; Autoimmune; Thyroxine; Iodine; Selenium
Purpose To explore the effect of the group intervention on smoking cessation based on social cognitive theory. Methods Totally 225 recruited smokers were randomly divided into intervention group and control group.The intervention group attended an intervention training program.Evaluation of the effect on smoking cessation was carried out six months after the intervention. Results Smoking quitting rate in the intervention group was 40.5%,statistically significantly higher than that of control group(5.2%). The numbers of daily cigarette consumption in the intervention group decreased by 11.5 cigarettes,while that in the control group by 1.7 cigarettes only.Their quitting intention advanced forward based on transtheoretical model and emotional self-efficacy and social self-efficacy score were improved significantly too.The intervention group were satisfied with the intervention training program.Age,attending the intervention and anticipation of successful cessation in the basal investigation were the factors that influenced quitting behavior. Conclusions The group intervention on smoking cessation based on social cognitive theory can significantly improve the quitting rate and can be accepted by smokers.As a feasible method,it is worth popularizing.
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