Corrigendum: Unravelling the therapeutic potential of botanicals against chronic obstructive pulmonary disease (COPD): molecular insights and future perspectives.

[This corrects the article DOI: 10.3389/fphar.2022.824132.].

Supporting Life Adjustment in Patients With Lung Cancer Through a Comprehensive Care Program: Protocol for a Controlled Before-and-After Trial.

BACKGROUND: Lung cancer diagnosis affects an individual's quality of life as well as physical and emotional functioning. Information on survivorship care tends to be introduced at the end of treatment, but early intervention may affect posttreatment adjustment. However, to the best of our knowledge, no study has explored the effect of early information intervention on the return to work, family, and societal roles of lung cancer survivors. OBJECTIVE: We report the study protocol of a comprehensive care prehabilitation intervention designed to facilitate lung cancer survivors' psychological adjustment after treatment. METHODS: A comprehensive care program was developed based on a literature review and a qualitative study of patients with lung cancer and health professionals. The Lung Cancer Comprehensive Care Program consists of educational videos and follow-up visits by a family medicine physician. To prevent contamination, the control group received routine education, whereas the intervention group received routine care and intervention. Both groups completed questionnaires before surgery (T0) and at 1-month (T1), 6-month (T2), and 1-year (T3) follow-up visits after surgery. The primary outcome was survivors' psychological adjustment to cancer 6 months after pulmonary resection. RESULTS: The historical control group (n=441) was recruited from September 8, 2021, to April 20, 2022, and the intervention group (n=350) was recruited from April 22, 2022, to October 17, 2022. All statistical analyses will be performed upon completion of the study. CONCLUSIONS: This study examined the effectiveness of an intervention that provided general and tailored informational support to lung cancer survivors, ranging from before to the end of treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05078918; https://clinicaltrials.gov/ct2/show/NCT05078918. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54707.

Selenium and zinc supplementation mitigates metals-(loids) mixture- mediated cardiopulmonary toxicity via attenuation of antioxidant, anti-inflammatory and antiapoptotic mechanisms in female Sprague Dawley rats.

This study evaluated the cardiopulmonary protective effects of essential elements (Zn and Se) against heavy metals mixture (HMM) exposure. Twenty five female Sprague Dawley albino rats, divided in to five groups: controls were orally treated only with distilled water; next, group 2 was exposed to HMM with the following concentrations: 20 mg/kg of Pb body weight, 0.40 mg/kg of Hg, 0.56 mg/kg of Mn, and 35 mg/kg of Al. Groups 3, 4 and 5 were exposed to HMM and co-treated with zinc chloride (ZnCl2; 0.80 mg/kg), sodium selenite (Na2SeO3;1.50 mg/kg) and both zinc chloride and sodium selenite, respectively. The experiment lasted for 60 days. Afterwards animals were sacrificed, and we conduced biochemical and histopathological examination of the heart and lungs. HMM only exposed animals had an increased levels of malondialdehyde (MDA) and nitric oxide (NO), increased IL-6 and TNF-α, attenuated SOD, GPx, CAT and GSH and caspase 3 in the heart and lungs. HMM affected NF-kB and Nrf2 in the heart muscle with histomorphological alterations. Zn and Se attenuated adverse effects of HMM exposure. Essential element supplementation ameliorated heavy metal cardiopulmonary intoxication in rats.

Changes in miRNA expression in the lungs of pigs supplemented with different levels and forms of vitamin D.

BACKGROUND: Vitamin D is an immunomodulator, and its effects have been linked to many diseases, including the pathogenesis of cancer. However, the effect of vitamin D supplementation on the regulation of gene expression of the lungs is not fully understood. This study aims to determine the effect of the increased dose of cholecalciferol and a combination of cholecalciferol + calcidiol, as well as the replacement of cholecalciferol with calcidiol, on the miRNA profile of healthy swine lungs. METHODS AND RESULTS: The swine were long-term (88 days) supplemented with a standard dose (2000IU/kg) of cholecalciferol and calcidiol, the increased dose (3000 IU/kg) of cholecalciferol, and the cholecalciferol + calcidiol combination: grower: 3000 IU/Kg of vitamin D (67% of cholecalciferol and 33% of calcidiol), finisher 2500 IU/Kg of vitamin D (60% of cholecalciferol and 40% of calcidiol). Swine lung tissue was used for Next Generation Sequencing (NGS) of miRNA. Long-term supplementation with the cholecalciferol + calcidiol combination caused significant changes in the miRNA profile. They embraced altered levels of the expression of miR-150, miR-193, miR-145, miR-574, miR-340, miR-381, miR-148 and miR-96 (q-value < 0.05). In contrast, raising the dose of cholecalciferol only changed the expression of miR-215, and the total replacement of cholecalciferol with calcidiol did not significantly affect the miRNAome profile. CONCLUSIONS: The functional analysis of differentially expressed miRNAs suggests that the use of the increased dose of the cholecalciferol + calcidiol combination may affect tumorigenesis processes through, inter alia, modulation of gene regulation of the TGF- ß pathway and pathways related to metabolism and synthesis of glycan.

Mechanism of electroacupuncture at acupoints of the lung meridian through PKA/PKC regulation of TRPV1 in chronic cough after lung surgery in guinea pigs.

Background: Acupuncture has achieved good results in the treatment of cough, asthma, chronic obstructive pulmonary disease (COPD) and other lung diseases, but the mechanism associated with acupuncture in the treatment of chronic cough induced by lung surgery is unknown. We investigated whether acupuncture therapy could improve the symptoms of chronic cough after lung surgery through cyclic-AMp dependent protein kinase A (PKA)/cyclic-AMp dependent protein kinase C (PKC) regulation of the transient receptor potential vanilloid-1 (TRPV1) signaling pathway. Methods: The guinea pigs were divided into 5 groups: the Sham operation Group (Sham), the Model Group (Model), the Electroacupuncture + Model Group (EA + M), the H89 + Model Group (H89 + M) and the Go6983 + Model Group (Go6983 + M). The effect of treatment was determined by measuring cough symptoms (number of coughs/cough incubation period) as the outcome criterion. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and blood were determined by enzyme-linked immunosorbent assays (ELISA). Lung tissue was stained with hematoxylin and eosin (H&E). The expression of p-PKA, p-PKC and p-TRPV1 proteins was measured by Western blotting. The mRNA levels of TRPV1, Substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin-1R (NK1R) were measured by real-time polymerase chain reaction (RT-PCR). Results: Acupuncture significantly reduced the cough frequency and prolonged the cough latency of chronic cough in guinea pigs after lung surgery. In addition, acupuncture reduced the damage to lung tissue. The levels of inflammatory cytokines decreased in all treatment groups, the expression levels of p-PKA, p-PKC and p-TRPV1 were significantly inhibited and the mRNA levels of TRPV1, SP, CGRP and NK1R decreased significantly after acupuncture treatment. Conclusions: Acupuncture therapy ameliorated chronic cough in guinea pigs after lung surgery by regulating the TRPV1 signaling pathway via PKA/PKC. Our results showed that acupuncture may be an effective treatment of chronic cough after lung surgery, and also clarified the potential mechanism, which provides a theoretical basis for the clinical treatment of patients with chronic cough after lung surgery.

Reconstructed lung doses for the million person study cohort of 26,650 Tennessee Eastman corporation workers employed between 1942 and 1947.

Tennessee Eastman Corporation workers were exposed to uranium dust resulting in high-linear energy transfer (LET) irradiation to lung tissue. In this work, radiation lung doses were reconstructed for 26 650 men and women working at the plant between 1942 and 1947. Site air monitoring data of uranium concentrations and payroll records were used to determine the daily inhaled activities and annualized lung doses. Variations in the activity median aerodynamic diameter of the uranium dust, the solubility of particulate matter in the lungs and the sex-specific breathing rate were investigated as part of a sensitivity analysis. Male and female mean lung doses of 18.9 and 32.7 mGy, respectively, from high-LET alpha irradiation, and there was general agreement with evaluations from previously published epidemiological studies. Annual lung dose estimates and sensitivity analysis for the 26 650 workers in the TEC cohort have been archived on the United States Department of Energy Comprehensive Epidemiologic Data Resource.

Effects of traditional mind-body movement therapy on chronic cardiopulmonary dyspnoea: a systematic review and meta-analysis.

PURPOSE: To evaluate whether traditional mind-body movement therapy (TMBM) can be used as a complementary or alternative therapy for exercise-based cardiopulmonary rehabilitation (EBCR) on chronic cardiopulmonary dyspnoea. METHODS: PubMed, Embase, Scopus, Web of Science and China National Knowledge Infrastructure were searched from their inception to 2 July 2021. Randomised clinical trials evaluating the effectiveness of TMBM versus EBCR, and TMBM +EBCR versus TMBM in the treatment of chronic cardiopulmonary dyspnoea were selected. The outcomes were exercise capacity (6 min walk distance, 6MWD) and quality of life (QoL). RESULTS: Thirty-four randomised clinical trials with 2456 patients were included. For TMBM vs EBCR alone, statistically significant improvements in the 6MWD favoured the TMBM for chronic obstructive pulmonary disease (COPD) (mean difference(MD)=12.22 m; 95% CI 5.94 to 18.50; I2=56%) and heart failure (HF) patients (MD=43.65 m; 95% CI 7.91 to 79.38; I2=0%). Statistically significant improvements in QoL also favoured TMBM over EBCR for patients with HF(MD=-9.19; 95% CI -11.05 to -7.32; I2=0%) but non-significant trend for COPD (standardised mean difference (SMD)=-0.31; 95% CI -0.62 to 0.01; I2=78%). Comparisons of TMBM +EBCR versus EBCR alone revealed significant improvements in the QoL for COPD (SMD=-0.52; 95% CI -0.94 to -0.10; I2=86%) and patients with HF (MD=-2.82; 95% CI -4.99 to -0.64; I2=0%). The 6MWD results favoured the TMBM +EBCR for patients with COPD (MD=16.76 m; 95% CI 10.24 to 23.29; I2=0%), but only showed a slight trend towards additional benefits of TMBM +EBCR in the HF studies (MD=13.77 m; 95% CI -1.01 to 28.54; I2=65%) . CONCLUSIONS: TMBM has positive effects on patients' 6MWD and QoL, with similar or even better effects than EBCR. It may be beneficial to use TMBM as a supplementary or alternative strategy for EBCR in treatment plans. PROSPERO REGISTRATION NUMBER: CRD42021241181.

Changes in DNA Methylation and mRNA Expression in Lung Tissue after Long-Term Supplementation with an Increased Dose of Cholecalciferol.

Maintaining an appropriate concentration of vitamin D is essential for the proper functioning of the body, regardless of age. Nowadays, there are more and more indications that vitamin D supplementation at higher than standard doses may show protective and therapeutic effects. Our study identified differences in the body's response to long-term supplementation with cholecalciferol at an increased dose. Two groups of pigs were used in the experiment. The first group received a standard dose of cholecalciferol (grower, 2000 IU/kg feed, and finisher, 1500 IU/kg feed), and the second group received an increased dose (grower, 3000 IU/kg feed, and finisher, 2500 IU/kg feed). After slaughter, lung samples were collected and used for RRBS and mRNA sequencing. Analysis of the methylation results showed that 2349 CpG sites had significantly altered methylation patterns and 1116 (47.51%) identified DMSs (Differentially Methylated Sites) were related to genes and their regulatory sites. The mRNA sequencing results showed a significant change in the expression of 195 genes. The integrated analysis identified eleven genes with DNA methylation and mRNA expression differences between the analyzed groups. The results of this study suggested that an increased vitamin D intake may be helpful for the prevention of lung cancer and pulmonary fibrosis. These actions may stem from the influence of vitamin D on the expression of genes associated with collagen production, such as SHMT1, UGT1A6, and ITIH2.The anti-cancer properties of vitamin D are also supported by changes in KLHL3 and TTPA gene expression.

Biogenic Selenium Nanoparticles and Their Anticancer Effects Pertaining to Probiotic Bacteria-A Review.

Selenium nanoparticles (SeNPs) can be produced by biogenic, physical, and chemical processes. The physical and chemical processes have hazardous effects. However, biogenic synthesis (by microorganisms) is an eco-friendly and economical technique that is non-toxic to human and animal health. The mechanism for biogenic SeNPs from microorganisms is still not well understood. Over the past two decades, extensive research has been conducted on the nutritional and therapeutic applications of biogenic SeNPs. The research revealed that biogenic SeNPs are considered novel competitors in the pharmaceutical and food industries, as they have been shown to be virtually non-toxic when used in medical practice and as dietary supplements and release only trace amounts of Se ions when ingested. Various pathogenic and probiotic/nonpathogenic bacteria are used for the biogenic synthesis of SeNPs. However, in the case of biosynthesis by pathogenic bacteria, extraction and purification techniques are required for further useful applications of these biogenic SeNPs. This review focuses on the applications of SeNPs (derived from probiotic/nonpathogenic organisms) as promising anticancer agents. This review describes that SeNPs derived from probiotic/nonpathogenic organisms are considered safe for human consumption. These biogenic SeNPs reduce oxidative stress in the human body and have also been shown to be effective against breast, prostate, lung, liver, and colon cancers. This review provides helpful information on the safe use of biogenic SeNPs and their economic importance for dietary and therapeutic purposes, especially as anticancer agents.

Edible algae (Ecklonia cava) bioprocessed with mycelia of shiitake (Lentinula edodes) mushrooms in liquid culture and its isolated fractions protect mice against allergic asthma.

BACKGROUND: Ecklonia cava is an edible marine brown alga harvested from the ocean that is widely consumed in Asian countries as a health-promoting medicinal food The objective of the present study is to evaluate the anti-asthma mechanism of a new functional food produced by bioprocessing edible algae Ecklonia cava and shiitake Lentinula edodes mushroom mycelia and isolated fractions. METHODS: We used as series of methods, including high performance liquid chromatography, gas chromatography, cell assays, and an in vivo mouse assay to evaluate the asthma-inhibitory effect of Ecklonia cava bioprocessed (fermented) with Lentinula edodes shiitake mushroom mycelium and its isolated fractions in mast cells and in orally fed mice. RESULTS: The treatments inhibited the degranulation of RBL-2H3 cells and immunoglobulin E (IgE) production, suggesting anti-asthma effects in vitro. The in vitro anti-asthma effects in cells were confirmed in mice following the induction of asthma by alumina and chicken egg ovalbumin (OVA). Oral administration of the bioprocessed Ecklonia cava and purified fractions suppressed the induction of asthma and was accompanied by the inhibition of inflammation- and immune-related substances, including eotaxin; thymic stromal lymphopoietin (TSLP); OVA-specific IgE; leukotriene C4 (LTC4); prostaglandin D2 (PGD2); and vascular cell adhesion molecule-1 (VCAM-1) in bronchoalveolar lavage fluid (BALF) and other fluids and organs. Th2 cytokines were reduced and Th1 cytokines were restored in serum, suggesting the asthma-induced inhibitory effect is regulated by the balance of the Th1/Th2 immune response. Serum levels of IL-10, a regulatory T cell (Treg) cytokine, were increased, further favoring reduced inflammation. Histology of lung tissues revealed that the treatment also reversed the thickening of the airway wall and the contraction and infiltration of bronchial and blood vessels and perialveolar inflammatory cells. The bioprocessed Ecklonia cava/mushroom mycelia new functional food showed the highest inhibition as compared with commercial algae and the fractions isolated from the bioprocessed product. CONCLUSIONS: The in vitro cell and in vivo mouse assays demonstrate the potential value of the new bioprocessed formulation as an anti-inflammatory and anti-allergic combination of natural compounds against allergic asthma and might also ameliorate allergic manifestations of foods, drugs, and viral infections.

Unravelling the Therapeutic Potential of Botanicals Against Chronic Obstructive Pulmonary Disease (COPD): Molecular Insights and Future Perspectives.

Background: COPD (chronic obstructive pulmonary disease) is a serious health problem worldwide. Present treatments are insufficient and have severe side effects. There is a critical shortage of possible alternative treatments. Medicinal herbs are the most traditional and widely used therapy for treating a wide range of human illnesses around the world. In several countries, different plants are used to treat COPD. Purpose: In this review, we have discussed several known cellular and molecular components implicated in COPD and how plant-derived chemicals might modulate them. Methods: We have discussed how COVID-19 is associated with COPD mortality and severity along with the phytochemical roles of a few plants in the treatment of COPD. In addition, two tables have been included; the first summarizes different plants used for the treatment of COPD, and the second table consists of different kinds of phytochemicals extracted from plants, which are used to inhibit inflammation in the lungs. Conclusion: Various plants have been found to have medicinal properties against COPD. Many plant extracts and components may be used as novel disease-modifying drugs for lung inflammatory diseases.

Effects of vitamin C and D on the mRNA expression of angiotensin converting enzyme 2 receptor, cathepsin L, and transmembrane serine protease in the mouse lungs.

Vitamins (Vit) C and D are widely used as immunogenic supplements among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. The SAR-CoV-2 virus enters into the pulmonary endothelial cells through attachment to angiotensin converting enzyme 2 receptor (Ace2) and the proteolytic activity of Cathepsin L (Ctsl) and transmembrane serine protease 2 (Tmprss2) enzymes. This study aimed to determine the influence of Vit C and D on the mRNA expression of Ace2, Tmprss2, and Ctsl genes in the mouse lungs. Vitamins C and D were administrated to different groups of mice through intra-peritoneal route in doses equivalent to human for 30 days. Then, the mRNA expression of SARS-CoV-2 entry gene was analyzed using qRT-PCR. It is found that Vit D, but not C, upregulated significantly (P < 0.05) the mRNA expression of Ace2 by more than six folds, while downregulated the expression of Ctsl and Tmprss2 genes by 2.8 and 2.2 folds, respectively. It can be concluded from this study that Vit D alters the mRNA expression of Ace2, Tmprss, and Ctsl genes in the mouse lungs. This finding can help us in understanding, at least in part, the molecular influence of Vit D on genes involved in the entry of SARS-CoV-2 into the cells.

Clasificación de Imágenes de Neumonía a causa de Covid-19 utilizando Transfer-Learning basado en Redes Convolucionales / Classification of Images of Pneumonia Due to Covid-19 Using TransferLearning, Based on Convolutional Networks

La Inteligencia Artificial ha ayudado a lidiar diferentes problemas relacionados con los datos masivos y a su vez con su tratamiento, diagnóstico y detección de enfermedades como la que actualmente nos preocupa, la Covid-19. El objetivo de esta investigación ha sido analizar y desarrollar la clasificación de imágenes de neumonía a causa de covid-19 para un diagnostico efectivo y óptimo. Se ha usado Transfer-Learning aplicando ResNet, DenseNet, Poling y Dense layer para la elaboración de los modelos de red propios Covid-UPeU y Covid-UPeU-TL, utilizando las plataformas Kaggle y Google colab, donde se realizaron 4 experimentos. El resultado con una mejor clasificación de imágenes se obtuvo en el experimento 4 prueba N°2 con el modelo Covid-UPeU-TL donde Acc.Train: 0.9664 y Acc.Test: 0.9851. Los modelos implementados han sido desarrollados con el propósito de tener una visión holística de los factores para la optimización en la clasificación de imágenes de neumonía a causa de COVID-19(AU)

Artificial Intelligence has helped to deal with different problems related to massive data in turn to the treatment, diagnosis and detection of diseases such as the one that currently has us in concern, Covid-19. The objective of this research has been to analyze and develop the classification of images of pneumonia due to covid-19 for an effective and optimal diagnosis. Transfer-Learning has been used applying ResNet, DenseNet, Poling and Dense layer for the elaboration of the own network models Covid-Upeu and Covid-UpeU-TL, using Kaggle and Google colab platforms, where 4 experiments have been carried out. The result with a better classification of images was obtained in experiment 4 test N ° 2 with the Covid-UPeU-TL model where Acc.Train: 0.9664 and Acc.Test: 0.9851. The implemented models have been developed with the purpose of having a holistic view of the factors for optimization in the classification of COVID-19 images(AU)

Palpation of the Respiratory System in Osteopathic Manual Medicine: From the Trachea to the Lungs.

There is a lack of published literature in osteopathic manual medicine on how to perform palpation of the lower respiratory tree such as the trachea, main bronchi, and lungs. Several authors have studied the osteopathic effect and respiratory response of palpation but have failed to demonstrate how to perform palpation of the visceral areas involved in breathing, either in the context of a clinical trial or as a case report. This paper reviews the innervation of these anatomical areas, the mechano-metabolic weight of the passage of fluids and air in the respiratory tract, the anatomical topography, and the movements involved in respiration. Drawing from current knowledge, this article illustrates, for the first time, how to place the hands for an effective osteopathic assessment of the tracheal, bronchial, and pulmonary structures. Understanding how to perform palpation of the lower areas is a fundamental tool in the clinic and potential therapy in osteopathic manual medicine.

Elevated pulmonary levels of Axin2 in mice exposed to herbicide 2,4-D with or without endotoxin.

2,4-Dichlorophenoxyacetic acid (2,4-D), a member of the phenoxy family of herbicides is commonly used in agriculture for controlling broadleaf weeds but its uncontrolled and incoherent use has been linked to incidences of lung toxicity. The present study aimed to understand the molecular mechanisms behind the 2,4-D alone or in combination with endotoxin (lipopolysaccharide [LPS]) induced pulmonary toxicity. Blood and lung samples were collected from Swiss albino mice (n = 48) following chronic exposure to high (37 mg/kg; 1/10th of LD50 ) and low (18.5 mg/kg; 1/20th of LD50 ) doses of 2,4-D alone or in combination with endotoxin (80 µg/animal). Transcriptome analysis revealed Wnt Canonical signaling as one of the top dysregulated pathways in mice lung following exposure to 2,4-D with and without endotoxin (LPS) co-exposure. Global view of differentially expressed genes showed increased messenger RNA expression of Axin2 by 0.26, 2.58, 3.14, 2.59, and 2.97 folds following exposure to LPS, high dose alone or in combination with LPS and low dose alone or in combination with LPS, respectively. The microarray data were validated using quantitative polymerase chain reaction and immunohistochemistry. Furthermore, the plasma concentration of Axin2 was elevated in the high dose group as revealed by Sandwich ELISA. The data taken together suggest a role of Axin2 to activate the Canonical Wnt signaling pathway in 2,4-D and or endotoxin-induced lung damage in mice.

Selenomethionine alleviates LPS-induced JNK/NLRP3 inflammasome-dependent necroptosis by modulating miR-15a and oxidative stress in chicken lungs.

Selenium (Se) was involved in many physiological processes in humans and animals. microRNAs (miRNAs) also played important roles in lung diseases. However, the regulatory mechanism of miRNA in chicken lungs and the mechanism of lipopolysaccharide (LPS)-induced pneumonia remained unclear. To further study these mechanisms, we established a supplement of selenomethionine (SeMet) and/or LPS-treated chicken model and a cell model of LPS and/or high and low expression of miR-15a in chicken hepatocellular carcinoma (LMH) cells. We detected the expression of some selenoproteins, p-c-Jun N-terminal kinase (JNK), nod-like receptor protein 3 (NLRP3), caspase1, receptor-interacting serine-threonine kinase 1 (RIPK1), receptor-interacting serine-threonine kinase 3 (RIPK3), mixed lineage kinase domain-like pseudokinase (MLKL), miR-15a, and oxidative stress kits. Additionally, we observed the morphology of lungs by H.E. staining in vitro. The results indicated that necroptosis occurred in LPS-treated chicken and LMH cells. Moreover, LPS stimulation inhibited miR-15a, and increased the expression of JNK, NLRP3, caspase1, RIPK1, RIPK3, and MLKL. We also found that LPS treatment not only increased the content of H2O2 and MDA in the lungs but also increased the activities of iNOS and CAT and the content of GSH decreased. Conclusion: SeMet could reduce the oxidative damage and activate NLRP3 inflammasome reaction by stimulating miR-15a/JNK, thus reduced the pulmonary necroptosis induced by LPS.

The anti-inflammatory effects of cannabidiol and cannabigerol alone, and in combination.

INTRODUCTION/BACKGROUND AND PURPOSE: Studies with Cannabis Sativa plant extracts and endogenous agonists of cannabinoid receptors have demonstrated anti-inflammatory, bronchodilator, and antitussive properties in the airways of allergic and non-allergic animals. However, the potential therapeutic use of cannabis and cannabinoids for the treatment of respiratory diseases has not been widely investigated, in part because of local irritation of airways by needing to smoke the cannabis, poor bioavailability when administered orally due to the lipophilic nature of cannabinoids, and the psychoactive effects of Δ9-Tetrahydrocannabinol (Δ9-THC) found in cannabis. The primary purpose of this study was to investigate the anti-inflammatory effects of two of the non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG) alone and in combination, in a model of pulmonary inflammation induced by bacterial lipopolysaccharide (LPS). The second purpose was to explore the effects of two different cannabinoid formulations administered orally (PO) and intraperitoneally (IP). Medium-chain triglyceride (MCT) oil was used as the sole solvent for one formulation, whereas the second formulation consisted of a Cremophor® EL (polyoxyl 35 castor oil, CrEL)-based micellar solution. RESULTS: Exposure of guinea pigs to LPS induced a 97 ± 7% and 98 ± 3% increase in neutrophils found in bronchoalveolar lavage fluid (BAL) at 4 h and 24 h, respectively. Administration of CBD and CBG formulated with MCT oil did not show any significant effects on the LPS-induced neutrophilia measured in the BAL fluid when compared with the vehicle-treated groups. Conversely, the administration of either cannabinoid formulated with CrEL induced a significant attenuation of the LPS induced recruitment of neutrophils into the lung following both intraperitoneal (IP) and oral (PO) administration routes, with a 55-65% and 50-55% decrease in neutrophil cell recruitment with the highest doses of CBD and CBG respectively. A combination of CBD and CBG (CBD:CBG = 1:1) formulated in CrEL and administered orally was also tested to determine possible interactions between the cannabinoids. However, a mixture of CBD and CBG did not show a significant change in LPS-induced neutrophilia. Surfactants, such as CrEL, improves the dissolution of lipophilic drugs in an aqueous medium by forming micelles and entrapping the drug molecules within them, consequently increasing the drug dissolution rate. Additionally, surfactants increase permeability and absorption by disrupting the structural organisation of the cellular lipid bilayer. CONCLUSION: In conclusion, this study has provided evidence that CBD and CBG formulated appropriately exhibit anti-inflammatory activity. Our observations suggest that these non-psychoactive cannabinoids may have beneficial effects in treating diseases characterised by airway inflammation.

Evaluation of biological activities and in vivo amelioration of CCl4 induced toxicity in lung and kidney with Abutilon pannosum (G.Forst.) Schltdl. in rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Abutilon pannosum is used in Pakistan for bladder inflammation, diuretic, lung disorders, diabetes and in lowering pyrexia. METHODS: Amount of total phenolic content, total flavonoid content and HPLC analysis of APM for the presence of polyphenolics were carried out. Antioxidant activity was determined by using different in vitro antioxidant assays. Amelioration effects of APM (200 mg/kg body weight and 400 mg/kg body weight) against CCl4 induced kidney and lung toxicity in rat was assessed by determining level of antioxidant enzymes, lipid peroxidation products, cytokines (TNF-α, IL-1ß and IL-2), comet assay and histological analysis. RESULTS: HPLC-DAD studies of APM indicated the presence of rutin (0.635 ± 0.011 µg/mg dry extract), gallic acid (1.07 ± 0.043 µg/mg dry extract) and catechin (0.246 ± 0.08 µg/mg dry extract) and considerable quantity of total phenolic (55.485 ± 0.85 mg GAE/g dry extract) and total flavonoid content (19.90 ± 0.58 mg Rutin/g dry extract). During in vitro antioxidant assays APM showed significant (p < 0.05) activity for iron chelation, reducing potential, inhibition of ß-carotene oxidation while moderate potential for scavenging of DPPH, hydroxyl, nitrite and phosphomolybdenum radical. Administration of CCl4 to rat severely depleted the activity level of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD), and reduced glutathione (GSH) concentration while appreciably increased the concentration of thiobarbituric acid reactive substances (TBARS), H2O2, nitrite, TNF-α, IL-1ß and IL-2 in lung and kidney tissues of rat. Comet length, % DNA in tail and tail moment significantly (p < 0.01) increased in lung and kidney cells of CCl4 intoxicated rat. Further, injuries in lung and kidney tissues were recorded with CCl4 induced toxicity in rat. The rats treated with APM along with CCl4 exhibited an appreciable level of restoration of the altered parameters towards the control animals. CONCLUSION: The results of this study suggested the protective potential of APM in CCl4 intoxicated rats for kidney and lung injuries.

The modulatory effect of Artemisia annua L. on toll-like receptor expression in Acanthamoeba infected mouse lungs.

The genus Acanthamoeba, which may cause different infections in humans, occurs widely in the environment. Lung inflammation caused by these parasites induces pulmonary pathological changes such as pulmonary necrosis, peribronchial plasma cell infiltration, moderate desquamation of alveolar cells and partial destruction of bronchial epithelial cells, and presence of numerous trophozoites and cysts among inflammatory cells. The aim of this study was to assess the influence of plant extracts from Artemisia annua L. on expression of the toll-like receptors TLR2 and TLR4 in lungs of mice with acanthamoebiasis. A. annua, which belongs to the family Asteraceae, is an annual plant that grows wild in Asia. In this study, statistically significant changes of expression of TLR2 and TLR4 were demonstrated. In the lungs of infected mice after application of extract from A. annua the expression of TLRs was observed mainly in bronchial epithelial cells, pneumocytes (to a lesser extent during the outbreak of infection), and in the course of high general TLR expression. TLR4 in particular was also visible in stromal cells of lung parenchyma. In conclusion, we confirmed that a plant extract of A. annua has a modulatory effect on components of the immune system such as TLR2 and TLR4.

Enigma in paraphrasing Ayurvedic Grantha.

Three different axioms of Sushruta Samhita-Sharira Sthana were analyzed and its translations by respectable translators were studied. The different Sanskrit terms were also analyzed using Monier-Williams and Apte Sanskrit dictionaries as a part of intercomparison study. The Sanskrit terms used in Ayurveda are those which seem to be commonly used, but their meanings are not the same as commonly understood or known. The article is an attempt to understand this ancient wisdom from Sushruta Samhita so as to highlight the peculiarities of Ayurvedic concepts and remove the bigotry regarding the use of common Sanskrit terms for explaining Rachana Sharira (anatomy) this will further help for the correct translation of Samhita. Axioms 4-22, 4-31 and 5-28 of Sushruta Samhita-Sharira Sthana are clinically important, because the clinical acumen is based on the correct knowledge of the human body.