Nanocurcumin supplementation improves pulmonary function in severe COPD patients: A randomized, double blind, and placebo-controlled clinical trial.

Considering the anti-inflammatory properties of curcumin, the present study was designed to investigate the effect of nano-curcumin on respiratory indices and interleukin-6 (IL-6) levels in severe chronic obstructive pulmonary disease (COPD) patients as a common pulmonary disease causing restricted airflow and breathing problems. In the current double-blind placebo-controlled randomized clinical trial study, 60 patients with stages 3 and 4 COPD were randomly assigned into 80 mg nano-curcumin (n = 30) and placebo groups (n = 30) for 3 months. The effect of nano-curcumin on pulmonary function was evaluated by the first second of forced expiration (FEV1) to the full, forced vital capacity (FVC) ratio. IL-6 serum level, blood pressure, and anthropometric indices were also measured. Nano-curcumin supplementation led to a significant decrease in IL-6 level (p < 0.001) and an increase in FEV1 (p < 0.001), FVC (p = 0.003), and FEV1/FVC (p < 0.001) compared to placebo at the endpoint. Nano-curcumin had a significantly increasing effect on weight and body mass index compared to the placebo group (PANCOVA adjusted for baseline values = 0.042). There was a meaningful improvement in systolic blood pressure in the nano-curcumin group compared to the placebo group (PANCOVA adjusted for baseline values = 0.026). There was no significant difference between the two groups in terms of waist circumference, waist-to-hip ratio, and diastolic blood pressure (PANCOVA adjusted for baseline values >0.05). Nano-curcumin supplement seems to have favorable effects on inflammation status and respiratory indices of patients with severe COPD.

IgG4-related Lung Disease: A Case Report and Review of the Literature.

IgG4-related disease (IgG4-RD) is a systemic autoimmune disease characterized by the infiltration of a large number of IgG4+ plasma cells, neoplastic lesions in the affected tissues, and a sharp increase in the concentration of serum IgG4. IgG4-RD is a rare and novel disease involving multiple organs with various clinical manifestations. Understanding and studying the pulmonary manifestations of IgG4-RD is critical for improving diagnosis, treatment, and prognosis. However, lung involvement alone is less common. Here we present a rare case of IgG4-related lung disease (IgG4-RLD) to show the variable manifestations of this disease in the lungs and review the relevant literature.

Compound 511 ameliorates MRSA-induced lung injury by attenuating morphine-induced immunosuppression in mice via PI3K/AKT/mTOR pathway.

BACKGROUND: Opioids are widely used in clinical practice. However, their long-term administration causes respiratory depression, addiction, tolerance, and severe immunosuppression. Traditional Chinese medicine (TCM) can alleviate opioid-induced adverse effects. Compound 511 is particularly developed for treating opioid addiction, based on Jiumi Liangfang, an ancient Chinese drug treatment and rehabilitation monograph completed in 1833 A.D. It is an herbal formula containing eight plants, each of them contributing to the overall pharmacological effect of the product: Panax ginseng C. A. Meyer (8.8%), Astragalus membranaceus (Fisch.) (18.2%), Datura metel Linn. (10.95%), Corydalis yanhusuo W. T. Wang (14.6%), Acanthopanar gracilistµlus W. W. Smith (10.95%), Ophiopogon japonicus (Linn. f.) Ker-Gawl. (10.95%), Gynostemma pentaphyllum (Thunb.) Makino (10.95%), Polygala arvensis Willd. (14.6%). This formula effectively ameliorates opioid-induced immunosuppression. However, the underlying mechanism remains unclear. PURPOSE: To reveal the effects of Compound 511 on the immune response of morphine-induced immunosuppressive mice and their potential underlying molecular mechanism. This study provides information for a better clinical approach and scientific use of opioids. METHODS: Immunosuppression was induced in mice by repeated morphine administration. Th1/Th2/Th17/Treg cell levels were measured using flow cytometry. Splenic transcription factors of Th1/Th2/Th17/Treg and outputs of the regulatory PI3K/AKT/mTOR signaling pathway were determined. Subsequently, methicillin-resistant Staphylococcus aureus (MRSA) was administered intranasally to morphine-induced immunosuppressive mice pretreated with Compound 511. Their lung inflammatory status was assessed using micro-computer tomography (CT), hematoxylin and eosin (H&E) staining, and enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to morphine, Compound 511 significantly decreased the immune organ indexes of mice, corrected the Th1/Th2 and Treg/Th17 imbalance in the immune organs and peripheral blood, reduced the mRNA levels of FOXP3 and GATA3, and increased those of STAT3 and T-bet in the spleen. It improved immune function and reduced MRSA-induced lung inflammation. CONCLUSION: Compound 511 ameliorates opioid-induced immunosuppression by regulating the balance of Th1/Th2 and Th17/Treg via PI3K/AKT/mTOR signaling pathway. Thus, it effectively reduces susceptibility of morphine-induced immunosuppressive mice to MRSA infection.

Circadian clock-based therapeutics in chronic pulmonary diseases.

The circadian clock is the biochemical oscillator that orchestrates the observable circadian rhythms in physiology and behavior. Disruption of the circadian clock in the lungs during chronic pulmonary diseases is considered one of the key etiological risk factors that drive pathobiology. Preclinical studies support that pharmacological manipulation of the circadian clock is a conceivable approach for the development of novel clock-based therapeutics. Despite recent advances, no effort has been undertaken to integrate novel findings for the treatment and management of chronic lung diseases. We, therefore, recognize the need to discuss the candidate clock genes that can be potentially targeted for therapeutic intervention. Here, we aim to create the first roadmap that will advance the development of circadian- clock-based therapeutics that may provide better outcomes in treating chronic pulmonary diseases.

Correlation Analysis and Application of Respiratory and Lung Diseases in Pediatrics of Traditional Chinese Medicine Based on Factor Analysis Method.

Many scholars have studied the influencing factors of children's lung infection, whether it is the region or the environment, or the living air quality of the mother during pregnancy. Western medicine is the most frequently used medicine, but Chinese medicine has more remarkable characteristics in treating children's lung diseases. For viral invasive diseases, people often use antibiotics to treat them. Children's lung conditions are too fragile, and taking antibiotics will lead to the damage of Staphylococcus in the lungs, resulting in pulmonary respiratory insufficiency. Although the conditioning time of traditional Chinese medicine is longer than that of western medicine, traditional Chinese medicine will not cause secondary damage to the lungs. In this paper, we introduce factor analysis and principal component analysis and compare the performance of the three analysis methods by using data such as cure rate, improvement rate, mortality rate, and drug taking frequency as evaluation indexes. In the model comparison, the accuracy rate of factor analysis method is over 97%, while the error rate is below 5%. Compared with the other two analysis methods, this method has a better application effect. Finally, we compare the comprehensive scores of eigenvalues of the three analysis methods. From 2016 to 2021, the comprehensive scores of factor analysis gradually increased.

Celiac disease and idiopathic pulmonary hemosiderosis: a literature review of the Lane-Hamilton syndrome.

Lane-Hamilton syndrome (LHS) presents a medical emergency, with 14% mortality due to Idiopathic Pulmonary Hemosiderosis (IPH) in acute phase. Despite the clinical severity of this entity, there has been no published review in the international literature, resulting in lack of awareness and delayed diagnosis.A rigorous search of international databases yielded a total of 80 LHS cases from January 1971 to August 2020. We analyzed 44 children (8.56 ± 4.72 years, 21 boys) and 36 adults (33.61 ± 13.41 years, 12 men) to present the clinical manifestations, radiological and immunological pattern, therapeutic approaches and outcome of LHS. We also elaborated on clinical and laboratory findings' associations to propose diagnostic indexes and clarified differences based on age distribution.Celiac disease (CD) and IPH diagnosis was made concurrently in 46 patients, whereas in 21 patients, the diagnosis of LHS was delayed for 2.5y (3 months-11 years). Hemoptysis (n = 56, 70%), dyspnea (n = 47, 58.8%), anemia (n = 72, 90%), and iron deficiency (n = 54, 67.5%) were most commonly observed. Medical history revealed recurrent episodes of hemoptysis (n = 38) and persistent iron deficiency anemia (n = 25) in need of multiple blood transfusions or iron supplementation. Patchy infiltrate opacities to consolidation predominated in children, whereas bilateral diffuse ground-glass opacities in adults. Duodenal biopsy was performed in 66 cases (diagnostic 87.8%), BAL in 51 (diagnostic 74.5%), and surgical lung biopsy in 20. Anti-tTG titer was positive in all 24 (54.6%) children and 19 (52.8%) adults that documented this assay. Prednisone or methylprednisolone pulse therapy and GFD were initiated in the acute phase, whereas chronic therapy included GFD, along with long-term prednisone in refractory cases. Three cases with severe respiratory failure or hemodynamic instability were intubated and a further three succumbed.A thorough understanding of LHS may reveal further diagnostic indexes and a consensus on therapy guidelines. Screening for CD is essential in all IPH cases for timely recognition and favorable outcome.

Natural therapeutics and nutraceuticals for lung diseases: Traditional significance, phytochemistry, and pharmacology.

BACKGROUND: Lung diseases including chronic obstructive pulmonary disease (COPD), infections like influenza, acute respiratory distress syndrome (ARDS), asthma and pneumonia lung cancer (LC) are common causes of sickness and death worldwide due to their remoteness, cold and harsh climatic conditions, and inaccessible health care facilities. PURPOSE: Many drugs have already been proposed for the treatment of lung diseases. Few of them are in clinical trials and have the potential to cure infectious diseases. Plant extracts or herbal products have been extensively used as Traditional Chinese Medicine (TCM) and Indian Ayurveda. Moreover, it has been involved in the inhibition of certain genes/protiens effects to promote regulation of signaling pathways. Natural remedies have been scientifically proven with remarkable bioactivities and are considered a cheap and safe source for lung disease. METHODS: This comprehensive review highlighted the literature about traditional plants and their metabolites with their applications for the treatment of lung diseases through experimental models in humans. Natural drugs information and mode of mechanism have been studied through the literature retrieved by Google Scholar, ScienceDirect, SciFinder, Scopus and Medline PubMed resources against lung diseases. RESULTS: In vitro, in vivo and computational studies have been explained for natural metabolites derived from plants (like flavonoids, alkaloids, and terpenoids) against different types of lung diseases. Probiotics have also been biologically active therapeutics against cancer, anti-inflammation, antiplatelet, antiviral, and antioxidants associated with lung diseases. CONCLUSION: The results of the mentioned natural metabolites repurposed for different lung diseases especially for SARS-CoV-2 should be evaluated more by advance computational applications, experimental models in the biological system, also need to be validated by clinical trials so that we may be able to retrieve potential drugs for most challenging lung diseases especially SARS-CoV-2.

Açaí (Euterpe Oleraceae Mart.) Seeds Regulate NF-κB and Nrf2/ARE Pathways Protecting Lung against Acute and Chronic Inflammation.

BACKGROUND/AIMS: Respiratory diseases are the world's biggest cause of mortality and disability. Specific nutrients have been proposed to positively affect disease progression as novel therapy alternatives to glucocorticosteroids. There has been a lot of attention in the possible health advantages of dietary assumption of Açai Seeds, popular native fruit found in the Amazon region which is rich in bioactive compounds. Until today nobody investigated the beneficial property of Açai Seeds administration in lung disease. METHODS: In our study we use two model of lung disease: for acute lung disease we use an intrapleural injection of Carrageenan; for chronic disease we used an intratracheal instillation of bleomycin. Açai Seeds was administered orally dissolved in saline. RESULTS: We found that Açai Seeds was able to reduce histological alteration, cells infiltration, pro inflammatory cytokine release, inflammation, and oxidative stress in both acute and chronic model of lung disease. CONCLUSION: Our data clearly demonstrate for the first time that Açai Seeds administration was useful against lung disease by the reduction of NF-κB nuclear translocation and by the stimulation of Nrf2/ARE pathways promoting the physiological antioxidant defense.

An overview of drugs for the treatment of Mycobacterium kansasii pulmonary disease.

OBJECTIVES: The aim of this study was to determine and compare the efficacy of drugs to treat Mycobacterium kansasii (Mkn) pulmonary disease by performing minimum inhibitory concentration (MIC) determination and time-kill studies. METHODS: We determined the MICs to 13 drugs against the Mkn standard laboratory strain ATCC 12478 and 20 clinical isolates and performed time-kill studies with 18 drugs from different classes using the standard laboratory strain of Mkn. The ß-lactam antibiotics were tested with or without the combination of the ß-lactamase inhibitor avibactam. An inhibitory sigmoid Emax model was used to describe the relationship between drug concentrations and bacterial burden. RESULTS: Among the 13 tested drugs in the MIC experiments, the lowest MIC was recorded for bedaquiline. Among the 18 drugs used in the time-kill studies, maximum kill with cefdinir, tebipenem, clarithromycin, azithromycin, moxifloxacin, levofloxacin, tedizolid, bedaquiline, pretomanid and telacebac was greater than that for some of the drugs (isoniazid, rifampicin and ethambutol) used in standard combination therapy. CONCLUSION: We report preclinical data on the efficacy and potency of drugs that can potentially be repurposed to create a safe, effective and likely shorter-duration regimen for the treatment of Mkn pulmonary disease.

The ethanol extract of flower buds of Tussilago farfara L. attenuates cigarette smoke-induced lung inflammation through regulating NLRP3 inflammasome, Nrf2, and NF-κB.

ETHNOPHARMACOLOGICAL RELEVANCE: The flower buds of Tussilago farfara L. (Abbreviated as FTF) were widely used in traditional Chinese medicine (TCM) to treat respiratory diseases, including asthma, dry throat, great thirst, turbid saliva, stinky pus, and coughs caused by various causes. AIM OF STUDY: The aim of study is to explore the efficiency of FTF in vitro and in vivo for the treatment of lung inflammation, and to illustrate the possible mechanisms of FTF in treating inflammation-related respiratory diseases targeting NOD-like receptor 3 (NLRP3) inflammasome, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear transcription factor-κB (NF-κB). METHODS: Lung inflammation model in vivo was induced by exposure of mice to cigarette smoke (CS) for two weeks. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory factors, and histology in lung tissues were investigated in presence or absence of ethanol extract of the flower buds of T. farfara L. (FTF-EtOH). In the cell-based models, nitric oxide (NO) assay, flow cytometry assay, enzyme-linked immunosorbent assay (Elisa), and glutathione (GSH) assay were used to explore the anti-inflammatory and anti-oxidant effects of FTF-EtOH. Possible anti-inflammatory mechanisms of FTF targeting NLRP3 inflammasome, Nrf2, and NF-κB have been determined using western blot, quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), immunofluorescence assay, nuclear and cytoplasmic extraction, and ubiqutination assay. RESULTS: FTF-EtOH suppressed CS-induced overproduction of inflammatory factors [e.g., tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß)], and upregulation of the content of intracellular MDA in the lung homogenate of mice. In cell-based models, FTF-EtOH reduced the lipopolysaccharide (LPS)-induced overproduction of inflammatory factors, and attenuated the CS extract-induced overgeneration of reactive oxygen species (ROS). Furthermore, FTF-EtOH up-regulated Nrf2 and its downstream genes through enhancing the stability of Nrf2 protein, and inhibited the activation of NF-κB and NLRP3 inflammasome, which have been confirmed by detecting the protein levels in the mouse model. CONCLUSIONS: FTF-EtOH effectively attenuated lung inflammation in vitro and in vivo. The protection of FTF-EtOH against inflammation was produced by activation of Nrf2 and inhibitions of NF-κB and NLRP3 inflammasome. These datas definitely support the ethnopharmacological use of FTF as an anti-inflammatory drug for treating respiratory diseases in TCM.

Biolabel-led research pattern positions the effects and mechanisms of Sophorae Tonkinensis radix et rhizome on lung diseases: A novel strategy for computer-aided herbal medicine research based on omics and bioinformatics.

Previous studies have shown that Sophorae Tonkinensis radix et rhizome (ST) can be used to treat some lung diseases. However, the therapeutic potentials, therapeutic advantages, mechanism of action, and material basis of ST treatment of lung diseases remain unclear. Thus, the aim of this study was to carry out an integrated analysis based on the biolabel-led research pattern. Proteomics and metabonomics were applied to explore the biolabels responsible for the effect of ST on lung tissue. Based on the biolabels, a bioinformatics database was used to topologically analyze the therapeutic potentials, therapeutic advantages, mechanism of action, and material basis of ST in treating lung diseases. Four human lung-cancer cell models were used to validate the results of the biolabel analysis. In total, 45 proteins and 3 metabolites were significantly enriched in 13 pathways and were considered as biolabels. Bioinformatics revealed that the therapeutic potentials of ST involved a variety of lung diseases, especially lung neoplasms. Under the mediation of 40 biolabels, 29 compounds may be the material basis of ST in treating lung diseases. In a verification experiment, ST had a significant inhibitory effect on the H226 cell line (lung squamous cell carcinoma), which ranks first in morbidity and mortality among lung cancers in China. Additionally, five biolabels (CPS1, CKM, CPT1B, COX5B, and COX4I1) were involved in the anti-lung cancer mechanism of ST and 3 compounds (gallic acid, betulinic acid, and caffeic acid). These findings indicate that the biolabel-led research pattern was helpful in achieving the objectives of this study.

Therapeutic potential of indole alkaloids in respiratory diseases: A comprehensive review.

BACKGROUND: Indole alkaloids are very promising for potential therapeutic purposes and appear to be particularly effective against respiratory diseases. Several experimental studies have been performed, both in vivo and in vitro, to evaluate the effectiveness of indole alkaloids for the management of respiratory disorders, including asthma, emphysema, tuberculosis, cancer, and pulmonary fibrosis. PURPOSE: The fundamental objective of this review was to summarize the in-depth therapeutic potential of indole alkaloids against various respiratory disorders. STUDY DESIGN: In addition to describing the therapeutic potential, this review also evaluates the toxicity of these alkaloids, which have been utilized for therapeutic benefits but have demonstrated toxic consequences. Some indole alkaloids, including scholaricine, 19-epischolaricine, vallesamine, and picrinine, which are derived from the plant Alstonia scholaris, have shown toxic effects in non-rodent models. METHODS: This review also discusses clinical studies exploring the therapeutic efficacy of indole alkaloids, which have confirmed the promising benefits observed in vivo and in vitro. RESULTS: The indole alkaloidal compounds have shown efficacy in subjects with respiratory diseases. CONCLUSION: The available data established both preclinical and clinical studies confirm the potential of indole alkaloids to treat the respiratory disorders.

Development and validation of a rapid high-performance thin-layer chromatographic method for quantification of gallic acid, cinnamic acid, piperine, eugenol, and glycyrrhizin in Divya-Swasari-Vati, an ayurvedic medicine for respiratory ailments.

Divya-Swasari-Vati is a calcium containing polyherbal ayurvedic medicine prescribed for the lung-related ailments observed in the current pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 infections. The formulation is a unique quintessential blend of nine herbs cited in Ayurvedic texts for chronic cough and lung infection. Analytical standardization of herbal medicines is the pressing need of the hour to ascertain the quality compliance. This persuaded us to develop a simple, rapid, and selective high-performance thin-layer chromatographic method for Divya-Swasari-Vati quality standardization. The developed method was validated for the quantification of marker components, gallic acid, cinnamic acid, piperine, eugenol and glycyrrhizin, against reference standards in five different batches of Divya-Swasari-Vati. The analytes were identified by visualization at 254 nm, and by matching their retention factor with authentic standards. The developed method was validated as per the guidelines recommended by the International Council for Harmonization for parameters like, linearity, limit of detection, limit of quantification, accuracy, and precision. Therefore, the developed novel high-performance thin-layer chromatographic process could be employed for rapid standardization of Divya-Swasari-Vati and other related herbal formulation, which would aid in quality manufacturing and product development.

Hemosiderosis pulmonar idiopática: seguimiento de pacientes durante 25 años (1995-2019) / Idiopathic pulmonary hemosiderosis: follow-up of patients for 25 years (1995-2019)

La hemosiderosis pulmonar idiopática (HPI) es una causa de hemorragia alveolar difusa. OBJETIVO: describir la evolución de niños con HPI en nuestra institución. Se realizó una revisión retrospectiva con protocolo de seguimiento. Se reclutaron 13 pacientes, 7 hombres. Procedentes de una zona agrícola (6/13). No todos presentaron la tríada diagnóstica completa: infiltrados algodonosos (9/13), anemia (11/13), hemoptisis (9/13). Todos evidenciaron un recuento de hemosiderófagos sobre 30% en el lavado broncoalveolar. Tomografía computada de tórax: normal (5/13), patrón intersticial (5/13), vidrio esmerilado (2/13) y fibrosis (1/13). Espirometría: normal (7/13), restrictiva (4/13), obstructiva (1/13) y no efectuada (1/13). Tratamiento durante la fase aguda: bolos de metilprednisolona (7/13) o prednisona (6/13) o hidrocortisona (1/13). En la fase de mantención se administró: prednisona (13/13) más un inmunosupresor, azathioprina (12/13), hidroxicloroquina (1/13), micofenolato (1/13), más budesonida MDI (13/13). Ocho pacientes detuvieron los sangrados. Dos pacientes fallecieron y hubo cinco embarazos de curso fisiológico en 3 adolescentes. Se observó: a) diferentes modalidades de presentación que retrasaron el diagnóstico; b) gran exposición a pesticidas; c) mejor pronóstico si el diagnóstico y el tratamiento eran precoces, también en niñas adolescentes; d) la mayoría detuvo los episodios de sangrado.

Idiopathic pulmonary hemosiderosis (IPH) is a cause of diffuse alveolar hemorrhage. OBJECTIVE: to describe the evolution of children with IPH in our institution. Retrospective monitoring with a follow-up protocol was carried out. 13 patients, seven males, were recruited. From an agricultural area (6/13). Not all of patients had the complete diagnostic triad: cotton infiltrates (9/13), anemia (11/13), hemoptysis (9/13). Hemosiderin-laden macrophages counting in the bronchoalveolar lavage fluid was over 30% in all the patients. Computed chest tomography was informed as normal (5/13), interstitial pattern (5/13), ground glass (2/13) and fibrosis (1/13). Spirometry: normal (7/13), restrictive (4/13), obstructive (1/13) and not performed (1/13). Treatment during the acute phase: bolus of methylprednisolone (7/13) or prednisone (6/13) or hydrocortisone (1/13). In the maintenance phase: prednisone (13/13) plus an immunosuppressant, azathioprine (12/13), hydroxychloroquine (1/13), mycophenolate (1/13), plus budesonide MDI (13/13). Eight patients stopped the bleeding episodes. Two patients died and there were five physiological pregnancies in 3 adolescents. It was observed:(a) different modes of IPH presentation that delayed its diagnosis; (b) large exposure to pesticides; (c) prognosis improved if diagnosis and treatment were early, also in adolescent girls; (d) most of the patients stopped the bleeding episodes.

Therapeutic properties of Punica granatum L (pomegranate) and its applications in lung-based diseases: A detailed review.

Respiratory diseases are the prime cause of death and disability worldwide. The majority of lung-based diseases are resistant to treatment. Hence, research on unique drugs/compounds with a more efficient and minimum side effect for treating lung diseases is urgent. Punica granatum L (pomegranate) fruit has been used in the prevention and treatment of various respiratory disorders in recent times. In vivo and in vitro studies have demonstrated that pomegranate fruit, as well as its juice, extract, peel powder, and oil, exert anti-proliferative, anti-oxidant, anti-microbial, anti-inflammatory, anti-cancer, and anti-tumorigenic properties by attenuating various respiratory conditions such as asthma, lung fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), and alveolar inflammation via modulating various signaling pathways. The current review summarizes the potential properties and medical benefits of pomegranate against different lung-based diseases, also highlighting its possible role in the lung fibrinolytic system. The available data suggest that pomegranate is effective in controlling the disease progressions and could be a potential therapeutic target benefiting human health status. Furthermore, this review also outlines the preclinical and clinical studies highlighting the role of pomegranate in lung diseases further evoking future studies to investigate the effect of intake of this anti-oxidant fruit in larger and well-defined human clinical trials. PRACTICAL APPLICATIONS: This review outlines the putative pharmacologic benefits of P. granatum L (pomegranate) in treating various chronic lung-based diseases such as lung cancer, COPD, ARDS, asthma, lung fibrosis, and cystic fibrosis. This review also highlights the possible inhibitory role of P. granatum L (pomegranate) in the lung fibrinolytic system triggering the fibrinolytic markers. This review summarizes the preclinical and clinical studies using in vitro, in vivo, and human models highlighting the potential role of P. granatum L (pomegranate) in lung diseases. This review evokes future research to investigate the effect of intake of pomegranate fruit in well-defined human clinical trials.

Modulation of cigarette smoke extract-induced human bronchial epithelial damage by eucalyptol and curcumin.

Smoking is one of the most important leading death cause worldwide. From a toxicological perspective, cigarette smoke serves hazards especially for the human being exposed to passive smoke. Over the last decades, the effects of natural compounds on smoking-mediated respiratory diseases such as COPD, asthma, and lung cancer have been under investigation, as well as the mechanistic aspects of disease progression. In the present study, the protective mechanism of eucalyptol (EUC), curcumin (CUR), and their combination on BEAS-2B cells were investigated in vitro to understand their impact on cell death, oxidative cell injury, and inflammatory response induced by 3R4F reference cigarette extract (CSE). According to the present findings, EUC, CUR, and their combination improved cell viability, attenuated CSE-induced apoptosis, and LC3B expression. Further, CSE-induced oxidative damage and inflammatory response in human bronchial epithelial cells were remarkably reduced by the combination treatment through modification of enzymatic antioxidant activity, GSH, MDA, and intracellular ROS levels as well as nitrite and IL-6 levels. In addition, nuclear translocation of Nrf2, a regulatory protein involved in the indirect antioxidant response, was remarkably up-regulated with the combination pre-treatment. In conclusion, EUC and CUR in combination might be a potential therapeutic against smoking-induced lung diseases through antioxidant and inflammatory pathways and results represent valuable background for future in vivo pulmonary toxicity studies.

Liu Shen Wan inhibits influenza virus-induced secondary Staphylococcus aureus infection in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Liu Shen Wan (LSW) is a traditional Chinese medicine (TCM) with detoxification and antiphlogistic activity; it is composed of bezoar, toad venom, musk, pearl powder, borneol and realgar. In recent years, LSW has been widely used in traditional medicine for the treatment of influenza, tonsillitis, pharyngitis, mumps, cancer and leukaemia. AIM OF STUDY: The anti-influenza virus properties of LSW and its inhibition of the inflammatory response was demonstrated in our previous research; however, the effect and potential mechanism of LSW against influenza induced secondary bacteria have remained obscure. Therefore, in the present study, a model of influenza virus PR8 with secondary infection by Staphylococcus aureus (S. aureus) in vitro and in mice was established to examine the effect and potential mechanism by which LSW inhibits bacterial adhesion and subsequent severe pneumonia after viral infection. MATERIALS AND METHODS: We investigated the effect of LSW on the PR8-induced adhesion of live S. aureus in A549 cells. RT-qPCR was used to detect the expression of adhesion molecules. Western blotting was used to determine the expression of CEACAM1, RIG-1, MDA5, p-NF-κB, and NF-κB in A549 cells. Inflammatory cytokines were detected using a Bio-Plex Pro Human Cytokine Screening Panel (R&D) in A549 cells and Mouse Magnetic Luminex Assays (R&D) in mice infected with PR8 virus and secondarily with S. aureus, respectively. Moreover, the survival rate, lung index, viral titre, bacterial loads and pathological changes in the lung tissue of mice infected with PR8 and S. aureus were investigated to estimate the effect of LSW in inhibiting severe pneumonia. RESULTS: LSW significantly decreased S. aureus adhesion following influenza virus infection in A549 cells, which may have occurred by suppressing expression of the adhesion molecule CEACAM1. In addition, treatment with LSW dramatically suppressed the induction of proinflammatory cytokines (CCL2/MCP-1 and CXCL-9/MIG) and chemokines (IL-6 and TNF-α) by PR8 infection following secondary LPS stimulation in A549 cells. Upregulation of related signalling proteins (RIG-I, MDA5 and NF-κB) induced by viruses and bacteria was suppressed by LSW in A549 cells. LSW significantly decreased the viral titres and bacterial load, prolonged survival time, and ameliorated lung inflammation and injury in mice with S. aureus infection secondary to PR8 infection. CONCLUSIONS: We demonstrated that LSW prevents S. aureus adherence to influenza virus-infected A549 cells, perhaps by inhibiting the expression of the adhesion molecule CEACAM1. The upregulation of proinflammatory cytokines and related signalling proteins induced by viruses and bacteria was suppressed by LSW in A549 cells. LSW significantly ameliorated lung injury caused by viral and secondary bacterial infection. These findings provide a further evaluation of LSW and suggest a beneficial effect of LSW for the prevention of secondary bacterial infection and related complications.

PPAR Gamma: From Definition to Molecular Targets and Therapy of Lung Diseases.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily that regulate the expression of genes related to lipid and glucose metabolism and inflammation. There are three members: PPARα, PPARß or PPARγ. PPARγ have several ligands. The natural agonists are omega 9, curcumin, eicosanoids and others. Among the synthetic ligands, we highlight the thiazolidinediones, clinically used as an antidiabetic. Many of these studies involve natural or synthetic products in different pathologies. The mechanisms that regulate PPARγ involve post-translational modifications, such as phosphorylation, sumoylation and ubiquitination, among others. It is known that anti-inflammatory mechanisms involve the inhibition of other transcription factors, such as nuclear factor kB(NFκB), signal transducer and activator of transcription (STAT) or activator protein 1 (AP-1), or intracellular signaling proteins such as mitogen-activated protein (MAP) kinases. PPARγ transrepresses other transcription factors and consequently inhibits gene expression of inflammatory mediators, known as biomarkers for morbidity and mortality, leading to control of the exacerbated inflammation that occurs, for instance, in lung injury/acute respiratory distress. Many studies have shown the therapeutic potentials of PPARγ on pulmonary diseases. Herein, we describe activities of the PPARγ as a modulator of inflammation, focusing on lung injury and including definition and mechanisms of regulation, biological effects and molecular targets, and its role in lung diseases caused by inflammatory stimuli, bacteria and virus, and molecular-based therapy.

Protective effect of supplementation with Ginseng, Lilii Bulbus and Poria against PM2 .5 in air pollution-induced cardiopulmonary damage among adults.

Exposure to PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 µm) has been associated with increased cardiopulmonary outcomes, mediated by a hypothesized biological mechanism of systemic inflammation and oxidation. This randomized, double-blinded and placebo-controlled trial among 120 healthy adults in Wuhan, China, was conducted to evaluate whether the supplementation of herbal product composed of Ginseng, Lilii Bulbus and Poria (GLP) which have been shown to have anti-inflammatory and anti-oxidant activity offers protective effects on PM2.5 -induced damage to cardiopulmonary health. Participants received four rounds of health examinations and two rounds of blood sample collection from November 2018 to January 2019. Compared to the placebo group, the GLP group showed significant increased antioxidant biomarkers such as superoxide dismutase (SOD) and paraoxonase1 (PON1). What is more, interleukin-6 (IL-6), an inflammatory biomarker, was significantly decreased in the GLP group. In addition, nitric oxide and club cell secretory protein (CC16) were increased but heart rate was decreased in the GLP group. As for pulmonary function indicators, significantly increased fractional exhaled nitric oxide (FeNO) was observed in the GLP group. Taken together, we concluded that GLP supplementation is associated with decreased inflammatory biomarker and increased antioxidant biomarkers suggesting cardiopulmonary benefits against PM2.5 exposure among young adults in China.