Effects of nasal allergens and environmental particulate matter on brainstem metabolites and the consequence of brain-spleen axis in allergic rhinitis.

BACKGROUND: The growing consensus links exposure to fine particulate matter (PM2.5) with an increased risk of respiratory diseases. However, little is known about the additional effects of particulate matter on brainstem function in allergic rhinitis (AR). Furthermore, it is unknown to what extent the PM2.5-induced effects in the brainstem affect the inflammatory response in AR. This study aimed to determine the effects, mechanisms and consequences of brainstem neural activity altered by allergenic stimulation and PM2.5 exposure. METHODS: Using an AR model of ovalbumin (OVA) elicitation and whole-body PM2.5 exposure, the metabolic profile of the brainstem post-allergen stimulation was characterized through in vivo proton magnetic resonance imaging (1H-MRS). Then, the transient receptor potential vanilloid-1 (TRPV1) neuronal expression and sensitivity in the trigeminal nerve in AR were investigated. The link between TRPV1 expression and brainstem differential metabolites was also determined. Finally, we evaluated the mediating effects of brainstem metabolites and the consequences in the brain-spleen axis in the inflammatory response of AR. RESULTS: Exposure to allergens and PM2.5 led to changes in the metabolic profiles of the brainstem, particularly affecting levels of glutamine (Gln) and glutamate (Glu). This exposure also increased the expression and sensitivity of TRPV1+ neurons in the trigeminal nerve, with the levels of TRPV1 expression closely linked to the brainstem metabolism of Glu and Gln. Moreover, allergens increased the activity of p38, while PM2.5 led to the phosphorylation of p38 and ERK, resulting in the upregulation of TRPV1 expression. The brainstem metabolites Glu and Gln were found to partially mediate the impact of TRPV1 on AR inflammation, which was supported by the presence of pro-inflammatory changes in the brain-spleen axis. CONCLUSION: Brainstem metabolites are altered under allergen stimulation and additional PM2.5 exposure in AR via sensitization of the trigeminal nerve, which exacerbates the inflammatory response via the brain-splenic axis.

Exercise ameliorates fine particulate matter-induced metabolic damage through the SIRT1/AMPKα/PGC1-α/NRF1 signaling pathway.

Air pollution, particularly fine particulate matter (PM2.5), poses a major threat to human health. Exercise has long been recognized as a beneficial way to maintain physical health. However, there is limited research on whether exercise can mitigate the damage caused by PM2.5 exposure. In this study, the mice were exercised on the IITC treadmill for 1 h per day, then exposed to concentrated PM2.5 for 8 h. After 2, 4 and 6-month exercise and PM2.5 exposure, the glucose tolerance and insulin tolerance were determined. Meanwhile, the corresponding indicators in epididymal white adipose tissue (eWAT), brown adipose tissue (BAT) and skeletal muscle were detected. The results indicated that PM2.5 exposure significantly increased insulin resistance (IR), while exercise effectively attenuated this response. The observations of muscle, BAT and eWAT by transmission electron microscopy (TEM) showed that PM2.5 significantly reduced the number of mitochondria in all of the three tissues mentioned above, and decreased the mitochondrial area in skeletal muscle and BAT. Exercise reversed the changes in mitochondrial area in all of the three tissues, but had no effect on the reduction of mitochondrial number in skeletal muscle. At 2 months, the expressions of Mfn2, Mfn1, OPA1, Drp1 and Fis1 in eWAT of the PM mice showed no significant changes when compared with the corresponding FA mice. However, at 4 months and 6 months, the expression levels of these genes in PM mice were higher than those in the FA mice in skeletal muscle. Exercise intervention significantly reduced the upregulation of these genes induced by PM exposure. The study indicated that PM2.5 may impact mitochondrial biogenesis and dynamics by inhibiting the SIRT1/AMPKα/PGC1-α/NRF1 pathway, which further lead to IR, glucose and lipid disorders. However, exercise might alleviate the damages caused by PM2.5 exposure.

Comprehensive performance evaluation of six bioaerosol samplers based on an aerosol wind tunnel.

Choosing a suitable bioaerosol sampler for atmospheric microbial monitoring has been a challenge to researchers interested in environmental microbiology, especially during a pandemic. However, a comprehensive and integrated evaluation method to fully assess bioaerosol sampler performance is still lacking. Herein, we constructed a customized wind tunnel operated at 2-20 km/h wind speed to systematically and efficiently evaluate the performance of six frequently used samplers, where various aerosols, including Arizona test dust, bacterial spores, gram-positive and gram-negative bacteria, phages, and viruses, were generated. After 10 or 60 min of sampling, the physical and biological sampling efficiency and short or long-term sampling capabilities were determined by performing aerodynamic particle size analysis, live microbial culturing, and a qPCR assay. The results showed that AGI-30 and BioSampler impingers have good physical and biological sampling efficiencies for short-term sampling. However, their ability to capture aerosols at low concentrations is restricted. SASS 2300 and BSA-350 wet-wall cyclones had excellent enrichment ratios and high microbial cultivability in both short-term and long-term sampling; however, they were not suitable for quantitative studies of aerosols. Polycarbonate filter samplers showed outstanding performance in physical and long-term sampling but lacked the ability to maintain microbial activity, which can be improved by gelatin filter samplers. However, limitations remain for some fragile microorganisms, such as E. coli phage PhiX174 and coronavirus GX_P2V. In addition, the effects of wind speed and direction should be considered when sampling particles larger than 4 µm. This study provides an improved strategy and guidance for the characterization and selection of a bioaerosol sampler for better measurement and interpretation of collected ambient bioaerosols.

A systematic review and meta­analysis of Arbidol therapy for acute respiratory viral infections: A potential treatment for COVID­19.

Arbidol (ARB) is efficacious for the treatment of influenza, and has been recommended for COVID-19. The present systematic review was performed to assess the existing knowledge on ARB therapy for acute respiratory viral infections, especially COVID-19. Subsequently, six databases were searched for publications reporting clinical outcomes of ARB therapy, and registered clinical trials up to May 6, 2022. The available literature was rigorously appraised. Based on the inclusion and exclusion criteria, 20 articles were identified for the final review. The result of meta-analysis showed that there was no significant difference in the negative rate of PCR day 7 [risk ratio (RR), 1.1; 95% CI, 0.87-1.40], negative rate of PCR day 14 (RR, 1.24; 95% CI, 0.92-1.67), PCR negative conversion time [mean difference (MD), -0.26; 95% CI, -1.41-0.90], time of clinical improvement (MD, 1.11; 95% CI, 0.01-2.22), hospital stay (MD, 0.16; 95% CI, -1.62-1.93), rate of improvement on chest computed tomography (CT) (RR, 1.19; 95% CI, 0.74-1.91), duration of CT absorption (MD, -1.43; 95% CI, -10.28-7.42), disease progression (RR, 1.05; 95% CI, 0.64-1.71) and mortality (RR, 0.68; 95% CI, 0.42-1.11). ARB demonstrated significant difference in the rate of clinical improvement (RR, 0.81; 95% CI, 0.67-0.97), duration of fever (MD, -0.38; 95% CI, -0.74- -0.02) and adverse events (RR, 0.65; 95% CI, 0.45-0.94). Although past clinical studies indicates notable results of ARB on influenza, there is no consensus on the drug for therapeutic and prophylaxis of COVID-19. The safety of ARB should be carefully monitored. High quality randomized controlled studies are urgently needed to thoroughly evaluate the efficacy and safety of ARB in patients with acute respiratory viral infections, especially COVID-19.

Time-Course Transcriptome Analysis of Lungs From Mice Infected With Hypervirulent Klebsiella pneumoniae via Aerosolized Intratracheal Inoculation.

Hypervirulent Klebsiella pneumoniae (hvKp) can cause life-threatening community-acquired infections among healthy young individuals and is thus of concern for global dissemination. In this study, a mouse model of acute primary hvKp pneumonia was established via aerosolized intratracheal (i.t.) inoculation, laying the foundation for conducting extensive studies related to hvKp. Subsequently, a time-course transcriptional profile was created of the lungs from the mouse model at 0, 12, 24, 48 and 60 hours post-infection (hpi) using RNA Sequencing (RNA-Seq). RNA-Seq data were analyzed with the use of Mfuzz time clustering, weighted gene co-expression network analysis (WGCNA) and Immune Cell Abundance Identifier for mouse (ImmuCellAI-mouse). A gradual change in the transcriptional profile of the lungs was observed that reflected expected disease progression. At 12 hpi, genes related to acute phase inflammatory response increased in expression and lipid metabolism appeared to have a pro-inflammatory effect. At 24 hpi, exacerbation of inflammation was observed and active IFN-γ suggested that signaling promoted activation and recruitment of macrophages occurred. Genes related to maintaining the structural integrity of lung tissues showed a sustained decrease in expression after infection and the decrease was especially marked at 48 hpi. TNF, IL-17, MAPK and NF-kB signaling pathways may play key roles in the immunopathogenesis mechanism at all stages of infection. Natural killer (NK) cells consistently decreased in abundance after infection, which has rarely been reported in hvKp infection and could provide a new target for treatment. Genes Saa1 and Slpi were significantly upregulated during infection. Both Saa1, which is associated with lipopolysaccharide (LPS) that elicits host inflammatory response, and Slpi, which encodes an antimicrobial protein, have not previously been reported in hvKp infections and could be important targets for subsequent studies. To t our knowledge, this paper represents the first study to investigate the pulmonary transcriptional response to hvKp infection. The results provide new insights into the molecular mechanisms underlying the pathogenesis of hvKp pulmonary infection that can contribute to the development of therapies to reduce hvKp pneumonia.

Dual-wavelength-excitation aerosol fluorescence spectra detection using combined spectrometer with Czerny-Turner design.

We developed a dual-wavelength-excitation aerosol fluorescence spectra detection device prototype. In our system, the 263 nm and 355 nm lasers are used to sequentially excite the fluorescence of aerosol stream, which is located spatially and temporally by two crossed infrared lasers; a bifurcated fiber bundle is applied to receive the fluorescence spectra of 274-463 nm and 374-565 nm. Besides, with a 32-channel photomultiplier tube as detector, a self-developed combined spectrometer with Czerny-Turner design is employed to detect the two band spectra in a preset timing sequence. Experiments show that the system can detect the fluorescence spectra, after dual-wavelength-excitation, of three intrinsic fluorophore samples and three bioaerosol samples.

An experimental method for efficiently evaluating the size-resolved sampling efficiency of liquid-absorption aerosol samplers.

Aerosol samplers are critical tools for studying indoor and outdoor aerosols. Development and evaluation of samplers is often labor-intensive and time-consuming due to the need to use monodisperse aerosols spanning a range of sizes. This study develops a rapid experimental methodology using polydisperse solid aerosols to evaluate size-resolved aerosol-to-aerosol (AtoA) and aerosol-to-hydrosol (AtoH) sampling efficiencies. Arizona Test Dust (diameter 0.5-20 µm) was generated and dispersed into an aerosol test chamber and two candidate samplers were tested. For the AtoA test, aerosols upstream and downstream of a sampler were measured using an online aerodynamic particle sizer. For the AtoH test, aerosols collected in sampling medium were mixed with a reference sample and then measured by the laser diffraction method. The experimental methodology were validated as an impressive time-saving procedure, with reasonable spatial uniformity and time stability of aerosols in the test chamber and an acceptable accuracy of absolute mass quantification of collected particles. Evaluation results showed that the AGI-30 and the BioSampler sampler had similar size-resolved sampling efficiencies and that efficiencies decreased with decreasing sampling flow rate. The combined evaluation of AtoA and AtoH efficiency provided more comprehensive performance indicators than either test alone. The experimental methodology presented here can facilitate the design and choice of aerosol sampler.

Complete Protection Against Yersinia pestis in BALB/c Mouse Model Elicited by Immunization With Inhalable Formulations of rF1-V10 Fusion Protein via Aerosolized Intratracheal Inoculation.

Pneumonic plague, caused by Yersinia pestis, is an infectious disease with high mortality rates unless treated early with antibiotics. Currently, no FDA-approved vaccine against plague is available for human use. The capsular antigen F1, the low-calcium-response V antigen (LcrV), and the recombinant fusion protein (rF1-LcrV) of Y. pestis are leading subunit vaccine candidates under intense investigation; however, the inability of recombinant antigens to provide complete protection against pneumonic plague in animal models remains a significant concern. In this study, we compared immunoprotection against pneumonic plague provided by rF1, rV10 (a truncation of LcrV), and rF1-V10, and vaccinations delivered via aerosolized intratracheal (i.t.) inoculation or subcutaneous (s.c.) injection. We further considered three vaccine formulations: conventional liquid, dry powder produced by spray freeze drying, or dry powder reconstituted in PBS. The main findings are: (i) rF1-V10 immunization with any formulation via i.t. or s.c. routes conferred 100% protection against Y. pestis i.t. infection; (ii) rF1 or rV10 immunization using i.t. delivery provided significantly stronger protection than rF1 or rV10 immunization via s.c. delivery; and (iii) powder formulations of subunit vaccines induced immune responses and provided protection equivalent to those elicited by unprocessed liquid formulations of vaccines. Our data indicate that immunization with a powder formulation of rF1-V10 vaccines via an i.t. route may be a promising vaccination strategy for providing protective immunity against pneumonic plague.

Aerosolized Intratracheal Inoculation of Recombinant Protective Antigen (rPA) Vaccine Provides Protection Against Inhalational Anthrax in B10.D2-Hc0 Mice.

Anthrax caused by Bacillus anthracis is a fatal zoonotic disease with a high lethality and poor prognosis. Inhalational anthrax is the most severe of the three forms of anthrax. The currently licensed commercial human anthrax vaccines require a complex immunization procedure for efficacy and have side effects that limit its use in emergent situations. Thus, development of a better anthrax vaccine is necessary. In this study, we evaluate the potency and efficacy of aerosolized intratracheal (i.t.) inoculation with recombinant protective antigen (rPA) subunit vaccines against aerosolized B. anthracis Pasteur II spores (an attenuated strain) challenge in a B10.D2-Hc0 mouse (deficient in complement component C5) model. Immunization of rPA in liquid, powder or powder reconstituted formulations via i.t. route conferred 100% protection against a 20× LD50 aerosolized Pasteur II spore challenge in mice, compared with only 50% of subcutaneous (s.c.) injection with liquid rPA. Consistently, i.t. inoculation of rPA vaccines induced a higher lethal toxin (LeTx) neutralizing antibody titer, a stronger lung mucosal immune response and a greater cellular immune response than s.c. injection. Our results demonstrate that immunization with rPA dry powder vaccine via i.t. route may provide a stable and effective strategy to improve currently available anthrax vaccines and B10.D2-Hc0 mice challenged with B. anthracis attenuated strains might be an alternative model for anthrax vaccine candidate screening.

The association study of Apolipoprotein E polymorphisms and chronic obstructive pulmonary disease in the Chinese population: A case-control study.

Chronic obstructive pulmonary disease (COPD) patients have increased cardiovascular morbidity and mortality. Apolipoprotein E (ApoE) is involved in chronic inflammation which is the common characteristic of emphysema and cardiovascular disease. ApoE polymorphisms are associated with cardiovascular disorders and atherosclerosis. There is no report about the association between ApoE polymorphism and COPD.A total of 480 COPD patients and 322 controls who were unrelated Chinese Han individuals were enrolled. Rs429358 and rs7412 were genotyped and the associations between ApoE polymorphisms and COPD risk were analyzed by logistic regression analysis. Online software SHEsis were applied to perform linkage disequilibrium (LD) and haplotypes analysis. The interactions of ApoE and environmental factor on COPD susceptibility was analyzed by software MDR3.0.2.No significant association was found between rs429358, rs7412 and COPD under different genetic models. Rs429358 and smoking formed the best model in the MDR analysis. The frequency of E2/E2 phenotype was the lowest in 2 groups. E3/E3 was the most common phenotype, accounting for 69.8% of COPD patients and 68.9% of controls. No statistically difference was identified between the cases and controls under different phenotypes.This was the first genetic association study between ApoE and COPD. No positive association was found in the Chinese Han population. Rs429358 and smoking status existed significant interaction, indicating that both of ApoE and smoking may be involved in the development of COPD disease.

Peroxiredoxin 6 overexpression regulates adriamycin-induced myocardial injury, oxidative stress and immune response in rats.

BACKGROUND: Adriamycin is an anthracycline drug used to treat a variety of tumors. Adriamycin has a much stronger affinity for myocardial tissue than other body tissues. Cancer patients treated with adriamycin are prone to toxic damage to heart tissue. Peroxiredoxin 6 (PRDX6) is a novel antioxidant enzyme in metabolic diseases, the aim of this study was to investigate the role of PRDX6 in myocardial injury. METHODS: Sixty male specific-pathogen-free Wistar rats were enrolled and divided equally into the control group (control), the Adriamycin group, the Adriamycin + empty vector lentivirus (Adriamycin + LV) group, and the Adriamycin + Peroxiredoxin 6 overexpression (Adriamycin + PRDX6) group. Western blot, reverse transcription-polymerase chain reaction (PCR), enzyme-linked immunosorbent assay, hematoxylin and eosin staining (HE) and immunohistochemistry were used in this research. RESULTS: The myocardial tissues of the Adriamycin group had significantly lower expression levels of PRDX6 and PRDX6 mRNA than those of the control group, and the myocardial tissues of the Adriamycin + PRDX6 rats had significantly higher expression levels of PRDX6 and PRDX6 mRNA than those of the Adriamycin + LV group. Serum creatine kinase isoenzyme (CK-MB), myoglobin (Mb), cardiac troponin I (cTnI), myocardial injury, positive rate of caspase-3, B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) levels, malondialdehyde (MDA), lactate dehydrogenase (LDH), IL-1ß, IL-6, inducible nitric oxide synthase (iNOS), and IL-4 proteins in the adriamycin-induced rats were significantly higher than those in the control group, while superoxide dismutase (SOD) activity was significantly lower than that in the control group. PRDX6 overexpression reversed the above results. CONCLUSIONS: PRDX6 overexpression can alleviate adriamycin-induced myocardial injury in rats, which may be related to oxidative stress regulation and the levels of inflammatory factors.

LNCRNA Gas5 suppression protected Hl-1 cells against hypoxia injury by sponging Mir-222-3p.

Hypoxia may cause diseases in human beings. The up- or down- regulation of lncRNAs were identified to possess the ability to protect the myocardial cells from hypoxia injury. This study explored the role of lncRNA GAS5 in sodium Hydrosulfite Induced Hl-1 Cells in vitro. RT-qPCR was applied to measure the expressions of RNAs whereas the cell viability was detected with CCK-8. Luciferase report assay was performed to validate the binding between lncRNA GAS5 and miR-222-3p. The proteins regarding PI3K/AKT signaling were evaluated through western blot analysis. The results showed that the hypoxia could reduce cell viabilities and enhance the apoptosis. Meanwhile, the PI3K/AKT signaling pathway was suppressed as well. lncRNA GAS5 got expressed higher in hypoxic cells whereas the suppressed GAS5 was able to increase cell viabilities while inhibiting apoptosis. MiR-222-3p was the target gene of lncRNA as determined by the luciferase report assay and its expressions were low in hypoxic cells. The overexpressed miR-222-3p could promote proliferation and inhibit apoptosis. Then, the correlation of GAS5 and miR-222-3p was measured which showed that miR-222-3p could resume the functions of GAS5 in cell viabilities and apoptosis through protein regulation in PI3K and AKT signaling pathways.