Treatment Of Respiratory Diseases Research Articles

Mannose targeting of poly(lactic-co-glycolic acid): a promising approach for improving sublingual allergen-specific immunotherapy

Objective One of the most effective treatments for allergic respiratory diseases is allergen-specific sublingual immunotherapy (SLIT). While, mannose targeting has been applied in various immunostimulatory approaches, but it has not been investigated in sublingual allergen-specific immunosuppressive treatment. This study assesses mannose targeting for the ovalbumin (Ova) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles(NPs). Methods The emulsion-solvent evaporation method was employed for the synthesis of PLGA NPs containing Ova, and subsequently they attached to D-mannose. Ova-sensitized mice underwent treatment in different ways: subcutaneous administration of 10 µg Ova, sublingual administration of 5 and 10 µg Ova loaded in PLGA NPs, 5 and 10 µg Ova loaded in mannose-targeted PLGA NPs, 10 µg Ova, and 10 µg Ova loaded in dendritic cell-specific aptamer-attached PLGA NPs. Serum Ova-specific IgE and IgG2a levels, as well as IFN-γ, IL-4, IL-10, and IL-17a levels in the supernatant of Ova-stimulated splenocytes were measured. Splenocyte proliferation was assessed using an MTT assay, and also lung histological examinations, and nasal lavage fluid cell counting were performed. Results Ova-specific IgE, IL-4, IL-17a levels, eosinophil cell count, and splenocyte proliferation were remarkably reduced in the mice treated with mannose or aptamer targeted NPs compared to other groups. Also, IL-10 and IFN-γ levels were remarkably increased in the targeted NPs groups. Conclusion Our findings indicated that mannose targeting of PLGA NPs could decrease allergen dose and improve immunomodulatory effects of SLIT. However, this approach suggests an effective formulation for SLIT in the mice model, further studies with common allergens are needed for application in humans.

A Comparative Study of Metaheuristic Feature Selection Algorithms for Respiratory Disease Classification

The correct diagnosis and early treatment of respiratory diseases can significantly improve the health status of patients, reduce healthcare expenses, and enhance quality of life. Therefore, there has been extensive interest in developing automatic respiratory disease detection systems. Most recent methods for detecting respiratory disease use machine and deep learning algorithms. The success of these machine learning methods depends heavily on the selection of proper features to be used in the classifier. Although metaheuristic-based feature selection methods have been successful in addressing difficulties presented by high-dimensional medical data in various biomedical classification tasks, there is not much research on the utilization of metaheuristic methods in respiratory disease classification. This paper aims to conduct a detailed and comparative analysis of six widely used metaheuristic optimization methods using eight different transfer functions in respiratory disease classification. For this purpose, two different classification cases were examined: binary and multi-class. The findings demonstrate that metaheuristic algorithms using correct transfer functions could effectively reduce data dimensionality while enhancing classification accuracy.

Harnessing spectrophotometry resolution power for determining ternary mixture for respiratory disorders treatment in their pharmaceutical formulation.

A ternary mixture incorporating Hydroxyzine hydrochloride (HYX), Ephedrine hydrochloride (EPH) and Theophylline (THP) frequently prescribed for the treatment of respiratory diseases. Herein, two spectrophotometric methods are designated and applied to resolve these three components in their mixture. Method A is ratio-subtraction combined with derivative spectrophotometry, where THP can be determined directly at its λmax 271 nm (neither HYX or EPH interfere), then for determination of HYX and EPH, the ternary mixture was divided by 22 μg/mL of THP and after subtraction of the plateau region, HYX can be determined directly at its λmax 234.2 nm (absence of EPH intervention). Finally, the third derivative (3D) spectrophotometric approach was utilized to estimate EPH by detecting the peak amplitude at 222 nm with Δλ = 4 and a scaling factor 100. Principal Component Regression (PCR) and Partial Least Squares (PLS), two multivariate calibration approaches, were applied effectively in Method B. This method effectively quantified the mixture under investigation by using the absorption spectra obtained from suitable solutions of the three components in the 210-230 nm region. The calibration models were evaluated using cross-validation with PCR and PLS, producing statistical characteristics that demonstrate the effectiveness of the calibration models. Synthetic and pharmaceutical preparations were also used to conduct external validation. In pharmaceutical formulation, these methods were successfully applied to analyze HYX, EPH, and THP without overlap from formulation's excipients. Moreover, the study's findings were statistically contrasted with those of earlier reported HPLC method. Appraisal approaches were used to determine whether the new spectrophotometric methods had an adverse environmental impact involving the Green Analytical Procedure Index (GAPI) and the AGREE (Analytical Greenness). These evaluations delivered information about the methods' eco-friendliness and sustainability, proving that they are in line with ecologically attributed practices. Furthermore, the Blue Applicability Grade Index (BAGI) was utilized to identify and verify the feasibility and practicality of the suggested approaches.

Intratracheal delivery of macrophage targeted Celastrol-loaded PLGA nanoparticles for enhanced anti-inflammatory efficacy in acute lung injury mice

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common causes of respiratory failure in critically ill patients. There is still a lack of definitive and effective treatment options, and the mortality rate remains as high as 30% to 40%. Effective therapeutics for ALI/ARDS are greatly hindered by the side effects resulting from inefficient delivery to the disease lesions and off-targeting biodistribution of drugs. Macrophages play an integral role in maintaining the steady state of the immune system and are involved in inflammation processes. Thus, nanodrug to accurately target macrophages have the potential to transform disease treatment. Here, we developed an mannosylated drug delivery system to target and deliver celastrol (Cel) to the alveolar macrophages for enhanced alleviating the cytokines in LPS-induce ALI mice. In vitro data demonstrated that the as-synthesized Man@Cel-NPs significantly improved the targeting of Cel into the inflammatory macrophages via mannose receptor-mediated phagocytosis. In vivo experiments further showed that intratracheal delivery of Man@Cel-NPs can improve the dysregulation of inflammatory response in LPS-induced mice by inhibiting the release of inflammatory cytokines and increasing autophagy and decreasing apoptosis in lungs. This work provides a potential NP platform for the locally tracheal delivery of herbal ingredients and exhibits promising clinical potential in the treatment of numerous respiratory diseases, including ALI/ARDS.

Lilium brownii/Baihe as Nutraceuticals: Insights into Its Composition and Therapeutic Properties.

Nutraceuticals are compounds or components in food that offer health benefits. They can be incorporated into food to make it functional or used as supplements or medicine. Lilium brownii/Baihe is one of the classic nutraceuticals. The chemical composition of Lilium is complex and has a variety of pharmacological effects. Moreover, the compound preparation based on Lilium has been used in the treatment of respiratory diseases in traditional Chinese medicine. In addition, Lanzhou lily has become food on the dinner table. Therefore, Lilium brownii/Baihe is a nutraceutical with a long history. Based on the current understanding of Lilium, this review provides an in-depth discussion of the bioactive components and pharmacological effects of Lilium. This is important to provide theoretical reference for the in-depth study of Lilium as well as its development and application in medicine, food, and other industries.

Economic impact of mortality prediction by predictive model at first and second treatment for bovine respiratory disease.

To evaluate a predictive model's ability to determine cattle mortality following first and second treatment for bovine respiratory disease and to understand the differences in net returns comparing predictive models to the status quo. 2 boosted decision tree models were constructed, 1 using data known at first treatment and 1 with data known at second treatment. Then, the economic impact of each outcome (true positive, true negative, false positive, and false negative) was estimated using various market values to determine the net return per head of using the predictive model to determine which animals should be culled at treatment. This was compared to the status quo to determine the difference in net return. The models constructed for the prediction of mortality performed with moderate accuracy (areas under the curve > 0.7). The economic analysis found that the models at a high specificity (> 90%) could generate a positive net return in comparison to status quo. This study showed that predictive models may be a useful tool to make culling decisions and could result in positive net returns. Bovine respiratory disease is the costliest health condition experienced by cattle on feed. Feedyard record-keeping systems generate vast amounts of data that could be used in predictive models to make management decisions. It is essential to understand the accuracy of predictions made via machine learning. However, the economic impact of implementing predictive models in a feedyard will influence adoption.

The role of respiratory infections in the formation of airway hyperresponsiveness in children

Airway hyperresponsiveness (AHR) is a heterogeneous and complex disorder characterized by excessive narrowing of the airways in response to various exogenous and endogenous stimuli. This article presents information from the last five years, including 50 publications from PubMed and Google Scholar, on the most common viruses that provoke the development of airway hyperresponsiveness in children, including respiratory syncytial virus, rhinovirus, metapneumovirus, influenza and parainfluenza viruses, SARS-CoV-2 coronavirus, adenovirus, and bocavirus. It describes a number of pathophysiological mechanisms by which viruses damage the respiratory epithelium and lead to the formation of infectious and post-infectious bronchial hypersensitivity. The role of hyperexpression of cytokines and inflammatory mediators in the development of AHR, especially in early childhood, is emphasized. It is shown that the inflammatory process and a balanced immune response are crucial for mitigating the severity of the disease caused by viruses. Understanding the molecular mechanisms of inflammatory reactions and the immune response to acute respiratory viral infections can help develop more effective methods for the prevention and treatment of respiratory diseases in children.

Quantifying trade-offs between therapeutic efficacy and resistance dissemination for enrofloxacin dose regimens in cattle

The use of antimicrobial drugs in food-producing animals contributes to the selection pressure on pathogenic and commensal bacteria to become resistant. This study aims to evaluate the existence of trade-offs between treatment effectiveness, cost, and the dynamics of resistance in gut commensal bacteria. We developed a within-host ordinary differential equation model to track the dynamics of antimicrobial drug concentrations and bacterial populations in the site of infection (lung) and the gut. The model was parameterized to represent enrofloxacin treatment for bovine respiratory disease (BRD) caused by Pastereulla multocida in cattle. Three approved enrofloxacin dosing regimens were compared for their effects on resistance on P. multocida and commensal E. coli: 12.5 mg/kg and 7.5 mg/kg as a single dose, and 5 mg/kg as three doses. Additionally, we explored non-FDA-approved regimes. Our results indicated that both 12.5 mg/kg and 7.5 mg/kg as a single dose scenario increased the most the treatment costs and prevalence of P. multocida resistance in the lungs, while 5 mg/kg as three doses increased resistance in commensal E. coli bacteria in the gut the most out of the approved scenarios. A proposed non-FDA-approved scenario (7.5 mg/kg, two doses 24 h apart) showed low economic costs, minimal P. multocida, and moderate effects on resistant E. coli. Overall, the scenarios that decrease P. multocida, including resistant P. multocida did not coincide with those that decrease resistant E. coli the most, suggesting a trade-off between both outcomes. The sensitivity analysis suggests that bacterial populations were the most sensitive to drug conversion factors into plasma (β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\beta}$$\\end{document}), elimination of the drug from the colon (ϑ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\vartheta$$\\end{document}), fifty percent sensitive bacteria (P. multocida) killing effect (Ls50\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{L}}_{\ ext{s50}}$$\\end{document}), fifty percent of bacteria (E. coli) above ECOFF killing effect (Cr50\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{C}}_{\ ext{r50}}$$\\end{document}), and net drug transfer rate in the lung (γ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\gamma$$\\end{document}) parameters.

Bioinspired Hyaluronic Acid‐Based Hydrogel Fuels Bi‐Directional Lung Organoid Maturation via PIEZO1 and ITGB1 Mediated Mechanosensation

AbstractLung diseases are one of the leading causes of global mortality. Advances in induced pluripotent stem cell (iPSC) differentiation have enabled the creation of bronchiolar and alveolar lung organoids, advancing research on lung conditions. Traditional Matrigel encapsulation, reliant on the spontaneous assembly and propagation of cells with limited external intervention, often results in variability and low reproducibility. The absence of hyaluronic acid (HA) in Matrigel, a key lung extracellular matrix component, limits bronchiolar and alveolar cell differentiation, reducing the efficacy and reproducibility of iPSC‐derived organoid generation. To address this, a novel hybrid hydrogel combining HA and 23% Matrigel, inspired by the natural lung environment, is developed. This hydrogel offers improved biochemical support and viscoelastic properties, significantly accelerating organoid development. Within eight days, the hydrogel produces uniformly sized organoids containing both bronchiolar and alveolar epithelial cells. Increased levels of active mechanosensors and transducers, including PIEZO1, Integrin, and Myosin, suggest that the hydrogel's altered viscoelasticity triggers a mechanotransduction cascade. This bioinspired hydrogel provides a robust, fast model for biomedical research, facilitating rapid drug screening, respiratory disease treatment studies, and surfactant trafficking investigations. Furthermore, it enables the exploration of underlying biomechanical mechanisms to enhance the controllability of organoid generation and maturation.

Whole Blood Theophylline Measurements Using an Electrochemical DNA Aptamer-based Biosensor

Theophylline, a bronchodilator used in the treatment of respiratory diseases, displays a narrow therapeutic range requiring therapeutic drug monitoring to maximize its effectiveness and safety. Current measurements of theophylline concentrations are, however, achieved using chromatography or immunoassays, which, in spite of their high accuracy and sensitivity, rely on expensive laboratory-based instruments operated by trained personnel or provide only semi-quantitative results, respectively. In response, we developed an electrochemical DNA aptamer-based (E-AB) sensor for theophylline on screen-printed electrodes. Our sensors enable rapid (<30 s) and selective measurements against theophylline structural analogs in clinically relevant range (55–110 μM) in finger-pricked-sized volumes of undiluted blood samples (<100 μL). Given these attributes, we envision that our results contribute to the development of a low-cost and convenient sensing device for molecular monitoring at the point-of-care.

Evaluation of 4-fluoro-7-nitrobenzofurazan as a dual-function chromogenic and fluorogenic probe for tulathromycin and its innovative utility for development of two eco-friendly and high-through microwell assays for analysis of pharmaceutical formulations

Tulathromycin is a triamilide antibacterial drug which has been approved for use in the European Union and the United States for the treatment and prevention of bovine respiratory diseases. The aim of this study was the development of two innovative microwell spectrometric (photometric and fluorometric) assays for determination of tulathromycin in its pharmaceutical formulations. To achieve this goal, 4-fluoro-7-nitrobenzofurazan was investigated as a dual-function chromogenic and fluorogenic probe for tulathromycin. The reaction between tulathromycin and 4-fluoro-7-nitrobenzofurazan proceeded smoothly in an alkaline medium, resulting in the formation of a colored and fluorescent product. The product displayed a maximum light absorption at 475 nm and emitted fluorescence at 545 nm when excited at 475 nm. Extensive investigations were conducted to optimize the factors affecting the tulathromycin /4-fluoro-7-nitrobenzofurazan reaction, and the optimal conditions were established. Using these optimized conditions, both microwell-based photometric and fluorometric assays were developed. The calibration curves relating the absorbance and fluorescence intensities of the reaction product with the corresponding tulathromycin concentrations were generated. The absorbance-concentration relationship was found to be linear within a tulathromycin concentration range of 10–400 µg mL−1, with a limit of quantitation of 6.2 µg mL−1. On the other hand, the fluorescence-concentration relationship was linear within a concentration range of 0.04–1.2 µg mL−1, with a limit of quantitation of 0.06 µg mL−1. Rigorous validations of both assays’ procedures were performed, and both assays were successfully employed for the analysis of tulathromycin–containing pharmaceutical formulations (injections) with satisfactory accuracy and precision. The ecologically friendly assessment of both assays demonstrated their compliance with the principles of green analytical chemistry approaches. Moreover, the proposed microwell-based assays enabled the simultaneous analysis of multiple samples using small volumes, enabling high-throughput analysis. In conclusion, this study represents the first evaluation of 4-fluoro-7-nitrobenzofurazan as a probe with dual functionality for the microwell-based photometric and fluorometric analysis of tulathromycin. The developed assays serve as valuable analytical tools for ensuring the quality of tulathromycin ’s pharmaceutical formulations.

The effects of all-trans retinoic acid on prednisolone-induced osteoporosis in zebrafish larvae

Glucocorticoids (GCs) are extensively used as anti-inflammatory and immunosuppressive medications in the long-term treatment of rheumatic disorders, respiratory diseases, renal diseases, and organ transplantation. Prolonged use of GCs can reduce bone mineral density, leading to osteoporosis (Glucocorticoid Induced Osteoporosis, GIOP) and fracture. All-trans retinoic acid (ATRA) is an active vitamin A metabolite that regulates embryonic development and adult organ function. ATRA has been found in studies to enhance osteogenesis. To examine the interventional effects of ATRA on GIOP and the mechanisms of ATRA activities, we first performed bioinformatic analysis to identify potential gene targets of ATRA. Zebrafish larvae were recruited as experimental animals, and the frequently used GC, prednisolone, was administered to larvae to construct a GIOP model. We evaluated the influence of exogenous ATRA on the activities of bone metabolic enzymes, the expression of genes linked to osteoblasts and osteoclasts, and the restoration of bone mineral density and bone mass in GIOP zebrafish larvae. Furthermore, we studied the influence of RBM14, a transcriptional coactivator and negative reciprocal factor of ATRA, on the regulation of osteoblastic gene expression during the anti-GIOP process of ATRA using the morpholino knockdown approach. The findings of bone metabolic enzyme activity (alkaline phosphatase, ALP and tartrate-resistant acid phosphatase, TRAP) and expression assays of osteoblastic marker genes (Runx2a, Runx2b, SP7, Csf1a, RANKL, and CTSK) indicated that ATRA had bidirectional effects on osteogenesis. However, in the GIOP model, ATRA reversed the GIOP-induced osteoporosis phenotype by inhibiting the GIOP-induced suppression of osteoblastic metabolic enzyme (ALP) activities and osteoblastic marker gene expression (Runx2a, Runx2b, and SP7), and this antagonism was concentration-dependent. We also observed that ATRA inhibited RBM14 expression in zebrafish larvae, while ATRA alone and RBM14 knockdown showed a consistent induction of osteoblast marker gene expression, implying that ATRA's inhibitory effect on RBM14 expression may underlie ATRA's osteogenic effects. Based on these data, we postulated that ATRA may ameliorate GIOP by decreasing RBM14 expression, thereby enhancing osteoblastic marker gene expression.

Italian survey on the effectiveness of halotherapy administered via the Aerosal® system.

Over the years, halotherapy (HT) has shown promise in the treatment of respiratory and dermatological diseases. However, its widespread acceptance remains limited due to the absence of official guidelines and awareness among doctors and patients. Among the patented systems of administration of HT, Aerosal® is the only one consisting of 3 certified elements, all classified as Medical Devices Class 2A: a dry saline dispenser called Aerosalmed®, a 30 g salt dose named AeroNaCL®, and a confined environment in marine multilayered construction with walls coated in salt called Aerosal®. We conducted an online survey of subjects undergoing Aerosal® HT across 80 Italian centers. Participants provided demographic data, reasons for choosing HT, and perceptions of its effectiveness. Following 10 treatment sessions, they rated improvements in various aspects, such as skin condition, sleep quality, relaxation, and respiratory benefits. Most participants learned about HT through word of mouth rather than medical advice, suggesting a discrepancy between patient satisfaction and medical endorsement. Over 92% reported resolution of their health issues post-treatment, with significant improvements in sleep quality and relaxation, particularly in adults. The therapy showed promise in various conditions, including respiratory and skin disorders, possibly attributed to stress reduction and intrinsic therapeutic effects. Despite skepticism, HT administered through the Aerosal® system has shown therapeutic potential. The psycho-physical benefits observed in patients advocate for greater consideration of this therapy by clinicians, emphasizing its safety, tolerability, and absence of notable side effects. In this context, standardized systems like Aerosal® are crucial for ensuring treatment safety and efficacy.

Ensifentrine: First Approval.

Ensifentrine, an inhaled, selective phosphodiesterase (PDE) 3 and PDE4 inhibitor, is being developed by Verona Pharma plc for the treatment of respiratory diseases, including chronic obstructive pulmonary disease (COPD). In June 2024, ensifentrine (OHTUVAYRE™) inhalation suspension was approved for the maintenance treatment of COPD in adult patients in the USA. This article summarizes the milestones in the development of ensifentrine leading to this first approval for the maintenance treatment of COPD.

3D Bioprinitng technologies for the enhancement and application of functional lung organoid models

Respiratory diseases, ranging from minor infections to serious chronic diseases and malignancies, negatively affect the respiratory system and are influenced by various environmental factors such as air pollution, occupational hazards, and tobacco smoke, as well as lifestyle, genetic causes, and infectious agents. The prevalence and severity of respiratory diseases requires the development of advanced models to better understand their pathophysiology and develop effective treatments. In this context, 3D bioprinting technology is emerging as an innovative tool to create functional lung organoid models. The use of induced pluripotent stem cells (iPSCs) and extracellular matrix (ECM) in bioprinting enables the development of organoids that closely mimic human lung tissue. Bioprinting-based organoids can better replicate the dynamic environment of the human lung, facilitating more accurate disease modeling and drug testing. In this review, we highlight the potential of bioprinted lung organoids in understanding the mechanisms of chronic respiratory diseases, testing the efficacy and safety of new drugs, and exploring regenerative medicine approaches. The integration of advanced bioprinting and organoid technologies is a promising field in respiratory disease research and treatment, offering new hope for patients suffering from lung diseases.

Advances in the application of robotic-assisted bronchoscopy

In recent years, advances in interventional bronchoscopy have led to safer and more effective solutions for the diagnosis and treatment of respiratory diseases. However, the techniques currently used to diagnose and treat peripheral pulmonary lesions (PPL) have certain limitations. Robotic-assisted bronchoscopy (RAB) offers a new solution to these limitations. Currently, three RABs have been approved by the US Food and Drug Administration (FDA) and are successfully marketed, while two domestic RABs are in the research and development stage. This article provided an overview of the advantages and disadvantages of various techniques and introduced five RABs in detail. It also discussed the advantages and disadvantages of RAB technology and future trends in its development.

Nanoparticle-Based Drug Delivery Systems in Inhaled Therapy: Improving Respiratory Medicine.

Inhaled nanoparticle (NP) therapy poses intricate challenges in clinical and pharmacodynamic realms. Recent strides have revolutionized NP technology by enabling the incorporation of diverse molecules, thus circumventing systemic clearance mechanisms and enhancing drug effectiveness while mitigating systemic side effects. Despite the established success of systemic NP delivery in oncology and other disciplines, the exploration of inhaled NP therapies remains relatively nascent. NPs loaded with bronchodilators or anti-inflammatory agents exhibit promising potential for precise distribution throughout the bronchial tree, offering targeted treatment for respiratory diseases. This article conducts a comprehensive review of NP applications in respiratory medicine, highlighting their merits, ranging from heightened stability to exacting lung-specific delivery. It also explores cutting-edge technologies optimizing NP-loaded aerosol systems, complemented by insights gleaned from clinical trials. Furthermore, the review examines the current challenges and future prospects in NP-based therapies. By synthesizing current data and perspectives, the article underscores the transformative promise of NP-mediated drug delivery in addressing chronic conditions such as chronic obstructive pulmonary disease, a pressing global health concern ranked third in mortality rates. This overview illuminates the evolving landscape of NP inhalation therapies, presenting optimistic avenues for advancing respiratory medicine and improving patient outcomes.

Pharmacological mechanisms of Ma Xing Shi Gan Decoction in treating influenza virus-induced pneumonia: intestinal microbiota and pulmonary glycolysis.

Influenza virus is one of the most common pathogens that cause viral pneumonia. During pneumonia, host immune inflammation regulation involves microbiota in the intestine and glycolysis in the lung tissues. In the clinical guidelines for pneumonia treatment in China, Ma Xing Shi Gan Decoction (MXSG) is a commonly prescribed traditional Chinese medicine formulation with significant efficacy, however, it remains unclear whether its specific mechanism of action is related to the regulation of intestinal microbiota structure and lung tissue glycolysis. This study aimed to investigate the mechanism of action of MXSG in an animal model of influenza virus-induced pneumonia. Specifically, we aimed to elucidate how MXSG modulates intestinal microbiota structure and lung tissue glycolysis to exert its therapeutic effects on pneumonia. We established a mouse model of influenza virus-induced pneumoni, and treated with MXSG. We observed changes in inflammatory cytokine levels and conducted 16S rRNA gene sequencing to assess the intestinal microbiota structure and function. Additionally, targeted metabolomics was performed to analyze lung tissue glycolytic metabolites, and Western blot and enzyme-linked immunosorbent assays were performed to assess glycolysis-related enzymes, lipopolysaccharides (LPSs), HIF-1a, and macrophage surface markers. Correlation analysis was conducted between the LPS and omics results to elucidate the relationship between intestinal microbiota and lung tissue glycolysis in pneumonia animals under the intervention of Ma Xing Shi Gan Decoction. MXSG reduced the abundance of Gram-negative bacteria in the intestines, such as Proteobacteria and Helicobacter, leading to reduced LPS content in the serum and lungs. This intervention also suppressed HIF-1a activity and lung tissue glycolysis metabolism, decreased the number of M1-type macrophages, and increased the number of M2-type macrophages, effectively alleviating lung damage caused by influenza virus-induced pneumonia. MXSG can alleviate glycolysis in lung tissue, suppress M1-type macrophage activation, promote M2-type macrophage activation, and mitigate inflammation in lung tissue. This therapeutic effect appears to be mediated by modulating gut microbiota and reducing endogenous LPS production in the intestines. This study demonstrates the therapeutic effects of MXSG on pneumonia and explores its potential mechanism, thus providing data support for the use of traditional Chinese medicine in the treatment of respiratory infectious diseases.

Trait development and genetic parameters of resilience indicators based on variability in milk consumption recorded by automated milk feeders in North American Holstein calves

The implementation of automated milk feeders (AMF) on precision dairy farms has enabled efficient management of large numbers of group-housed replacement calves with reduced labor requirements and improved calf welfare. In this study, we investigated the feasibility of deriving calf resilience indicators based on variability in milk consumption using data from 10,076 North American Holstein calves collected between 2015 and 2021. We modeled and evaluated deviations in observed and predicted daily milk consumption trajectories as indicators of resilience to environmental perturbations. We also analyzed average milk intake and the number of treatments for bovine respiratory disease (BRD) and their genetic correlations with the derived resilience parameters. Milk consumption was recorded using the Förster-Technik AMF. Deviations in cumulative milk intake were modeled using various methods, including quantile regression and the Gompertz function. Ten resilience indicators were derived to quantify the degree and duration of perturbations, including amplitude, perturbation time, recovery time, and deviation velocities. After data editing, genomic data from 9,273 calves and pedigree information from 10,076 calves with 321,388 phenotypic records were used to estimate genetic parameters for 12 traits, including 10 calf resilience indicators as well as average milk intake and treatments for bovine respiratory disease. Substantial phenotypic variability was observed for all calf resilience indicators derived and genetic parameters related to these novel resilience indicators were estimated. The heritability estimates for the resilience traits are as follows: amplitude of the deviation (in L) 0.047 (0.032, 0.064) (HPD interval), perturbation time of deviation (in d) 0.011 (0.0056, 0.016), recovery time of the deviation (in d) 0.025 (0.016, 0.035), maximum velocity of perturbation (L/d) 0.039 (0.024, 0.053), average velocity of perturbation (L/d) 0.038 (0.022, 0.050), area between the curves (L x d) 0.039 (0.027, 0.054), recovery ratio 0.053 (0.036, 0.072), deviation variance 0.049 (0.32, 0.068), log-deviation variance 0.027 (0.016, 0.044), deviation auto-correlation 0.010 (0.0042, 0.017) and number of deviation occurrences 0.023 (0.0094, 0.036). Some of the highlighted genetic correlations observed with average milk consumption include amplitude: 0.569 (0.474, 0.666), perturbation time: -0.534 (-0.73, -0.342), and average velocity: 0.554 (0.432, 0.672). Similarly, the genetic correlations between the number of times treated for BRD with perturbation time was 0.494 (0.251, 0.723), -0.294 (-0.52, -0.095) with number of deviations, and 0.348 (0.131, 0.578) with deviation autocorrelation. This study highlights the genetic influence on various resilience traits in calves, including amplitude, perturbation time, recovery time, and velocity measures of the perturbation. Our findings suggest the need for prioritizing genetic selection based on traits like recovery time, which exhibits higher heritability and a moderate genetic correlation with the number of times a calf is treated for BRD. The combination of AMF data, mathematical modeling, and genomic evaluation provides a comprehensive framework for assessing and breeding more resilient dairy calves in the face of environmental and health challenges.

SARS-CoV-2-Infection in People Addicted to Illegal Drugs - Is There a Protective Effect of Opioid Maintenance Treatment?

People addicted to illegal drugs were discussed as a risk group for SARS-CoV-2 infections, with increased susceptibility and a severe course of infection. In this study, the frequency of SARS-CoV-2 infections of drug-dependent persons admitted to inpatient detoxification treatment in five psychiatric hospitals was determined by implementing routine polymerase chain reaction (PCR)-testing at admission (9/2020) up to one year. Main substance-related diagnosis, comorbid respiratory disease, housing situation, and current opioid maintenance treatment (OMT) were documented. An age-matched control group of psychiatric inpatients without dependence from illegal drugs was established. Data from 1675 patients (male 79.5%; mean age 39.5 years; opioid dependence 81.5% homelessness; 2.4%; chronic respiratory disease 6.3%) were included. Out of 1365 patients dependent on opioids, 50.2% were currently in OMT. Six (3 female; mean age 40.3 years) patients tested positive for SARS-CoV-2 by PCR (0.36%), and none showed symptoms of COVID-19. All six were opioid dependent, 5 currently not in OMT. In the control group, 11 out of 1811 inpatients tested positive (0.61%). The rate of SARS-CoV-2-infections in persons with dependence on illegal drugs was not increased compared to a control group of psychiatric patients. OMT is presumably a protective factor, e. g. in the participating cities, OMT facilities offered an easy access to vaccination programs. In contrast, drug addicts in the USA were severely affected by the pandemic. Differences between countries might partially be explained by social factors such as the higher availability of OMT in Germany and a much lower frequency of homelessness.