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Fulltext Automatic liver segmentation on Computed Tomography using random walkers for treatment planning

Moghbel M, Mashohor S, Mahmud R, Saripan MI

EXCLI J, 2016;15:500-517.
PMID: 28096782 DOI: 10.17179/excli2016-473

Segmentation of the liver from Computed Tomography (CT) volumes plays an important role during the choice of treatment strategies for liver diseases. Despite lots of attention, liver segmentation remains a challenging task due to the lack of visible edges on most boundaries of the liver coupled with high variability of both intensity patterns and anatomical appearances with all these difficulties becoming more prominent in pathological livers. To achieve a more accurate segmentation, a random walker based framework is proposed that can segment contrast-enhanced livers CT images with great accuracy and speed. Based on the location of the right lung lobe, the liver dome is automatically detected thus eliminating the need for manual initialization. The computational requirements are further minimized utilizing rib-caged area segmentation, the liver is then extracted by utilizing random walker method. The proposed method was able to achieve one of the highest accuracies reported in the literature against a mixed healthy and pathological liver dataset compared to other segmentation methods with an overlap error of 4.47 % and dice similarity coefficient of 0.94 while it showed exceptional accuracy on segmenting the pathological livers with an overlap error of 5.95 % and dice similarity coefficient of 0.91.

Matched MeSH terms: Lung
Metastatic hepatocellular carcinoma presenting as a sphenoid sinus mass and meningeal carcinomatosis

Hashim H, Rahmat K, Abdul Aziz YF, Chandran PA

Ear Nose Throat J, 2014 Jun;93(6):E20-3.
PMID: 24932824

We report the case of a 30-year-old woman who was referred to us for evaluation of a 2-week history of fever, headache, vomiting, bilateral ptosis, and blurred vision. Imaging obtained by the referring institution had identified a sphenoid sinus mass and diffuse meningeal infiltration, which was thought to represent an infective process. We subsequently identified the mass as a metastatic hepatocellular carcinoma (HCC). The patient was placed under palliative care, and she died 1 month later. Metastases to the sphenoid sinus from any primary source are very rare, and they are generally not considered in the radiologic differential diagnosis. HCC is known to metastasize to the lung, lymph nodes, and musculoskeletal system; again, reported cases of metastasis to the sphenoid sinus are rare. Indeed, our review of the English-language literature found only 6 previously reported cases of sinonasal metastasis of a primary HCC. A diagnosis of a sinonasal metastasis is more difficult in a patient who has no previous diagnosis of a primary malignancy. In presenting this case, our aim is to remind readers of this possibility.

Matched MeSH terms: Lung Neoplasms/radiography; Lung Neoplasms/secondary*
Fulltext An unusual case of shortness of breath

Wan Muhammad Hatta SF, Kandaswamy L, Gherman-Ciolac C, Mann J, Buch HN

Endocrinol Diabetes Metab Case Rep, 2018;2018.
PMID: 30087779 DOI: 10.1530/EDM-18-0074

Myopathy is a well-known complication of hypercortisolism and commonly involves proximal lower-limb girdle. We report a rare case of Cushing's syndrome in a 60-year-old female presenting with significant respiratory muscle weakness and respiratory failure. She had history of rheumatoid arthritis, primary biliary cirrhosis and primary hypothyroidism and presented with weight gain and increasing shortness of breath. Investigations confirmed a restrictive defect with impaired gas transfer but with no significant parenchymatous pulmonary disease. Respiratory muscle test confirmed weakness of respiratory muscles and diaphragm. Biochemical and radiological investigations confirmed hypercortisolaemia secondary to a left adrenal tumour. Following adrenalectomy her respiratory symptoms improved along with an objective improvement in the respiratory muscle strength, diaphragmatic movement and pulmonary function test.
Learning points: Cushing's syndrome can present in many ways, a high index of suspicion is required for its diagnosis, as often patients present with only few of the pathognomonic symptoms and signs of the syndrome.Proximal lower-limb girdle myopathy is common in Cushing's syndrome. Less often long-term exposure of excess glucocorticoid production can also affect other muscles including respiratory muscle and the diaphragm leading to progressive shortness of breath and even acute respiratory failure.Treatment of Cushing's myopathy involves treating the underlying cause that is hypercortisolism. Various medications have been suggested to hinder the development of GC-induced myopathy, but their effects are poorly analysed.

Matched MeSH terms: Lung Diseases
Particulate matter air pollution components and risk for lung cancer

Raaschou-Nielsen O, Beelen R, Wang M, Hoek G, Andersen ZJ, Hoffmann B, et al.

Environ Int, 2016 Feb;87:66-73.
PMID: 26641521 DOI: 10.1016/j.envint.2015.11.007

Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence.

Matched MeSH terms: Lung Neoplasms
Adhesion and invasion attributes of Burkholderia pseudomallei are dependent on airway surface liquid and glucose concentrations in lung epithelial cells

Mariappan V, Thimma J, Vellasamy KM, Shankar EM, Vadivelu J

Environ Microbiol Rep, 2018 04;10(2):217-225.
PMID: 29393577 DOI: 10.1111/1758-2229.12624

Physiological constituents in airway surface liquids (ASL) appear to impact the adherence and invasion potentials of Burkholderia pseudomallei contributing to recrudescent melioidosis. Here, we investigated the factors present in ASL that is likely to influence bacterial adhesion and invasion leading to improved understanding of bacterial pathogenesis. Six B. pseudomallei clinical isolates from different origins were used to investigate the ability of the bacteria to adhere and invade A549 human lung epithelial cells using a system that mimics the physiological ASL with different pH, NaCl, KCl, CaCl2 and glucose concentrations. These parameters resulted in markedly differential adherence and invasion abilities of B. pseudomallei to the lung epithelial cells. The concentration of 20 mM glucose dramatically increased adherence and invasion by increasing the rate of pili formation in depiliated bacteria. Glucose significantly increased adherence and invasion of B. pseudomallei to A549 cells, and presence of NaCl, KCl and CaCl2 markedly ablated the effect despite the presence of glucose. Our data established a link between glucose, enhanced adhesion and invasion potentials of B. pseudomallei, hinting increased susceptibility of individuals with diabetes mellitus to clinical melioidosis.

Matched MeSH terms: Lung/metabolism*; Lung/microbiology
Fulltext Association of carcinogenic polycyclic aromatic hydrocarbon emissions and smoking with lung cancer mortality rates on a global scale

Motorykin O, Matzke MM, Waters KM, Massey Simonich SL

Environ Sci Technol, 2013 Apr 2;47(7):3410-6.
PMID: 23472838 DOI: 10.1021/es305295d

The objective of this research was to investigate the relationship between lung cancer mortality rates, carcinogenic polycyclic aromatic hydrocarbon (PAH) emissions, and smoking on a global scale, as well as for different socioeconomic country groups. The estimated lung cancer deaths per 100,000 people (ED100000) and age standardized lung cancer death rate per 100,000 people (ASDR100000) in 2004 were regressed on PAH emissions in benzo[a]pyrene equivalence (BaPeq), smoking prevalence, cigarette price, gross domestic product per capita, percentage of people with diabetes, and average body mass index using simple and multiple linear regression for 136 countries. Using stepwise multiple linear regression, a statistically significant positive linear relationship was found between loge(ED100000) and loge(BaPeq) emissions for high (p-value <0.01) and for the combination of upper-middle and high (p-value <0.05) socioeconomic country groups. A similar relationship was found between loge(ASDR100000) and loge(BaPeq) emissions for the combination of upper-middle and high (p-value <0.01) socioeconomic country groups. Conversely, for loge(ED100000) and loge(ASDR100000), smoking prevalence was the only significant independent variable in the low socioeconomic country group (p-value <0.001). These results suggest that reducing BaPeq emissions in the U.S., Canada, Australia, France, Germany, Brazil, South Africa, Poland, Mexico, and Malaysia could reduce ED100000, while reducing smoking prevalence in Democratic People's Republic of Korea, Nepal, Mongolia, Cambodia, and Bangladesh could significantly reduce the ED100000 and ASDR100000.

Matched MeSH terms: Lung Neoplasms/mortality*
Fulltext Berberine-loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro

Paudel KR, Mehta M, Yin GHS, Yen LL, Malyla V, Patel VK, et al.

Environ Sci Pollut Res Int, 2022 Jul;29(31):46830-46847.
PMID: 35171422 DOI: 10.1007/s11356-022-19158-2

Non-small cell lung cancer (NSCLC) is reported to have a high incidence rate and is one of the most prevalent types of cancer contributing towards 85% of all incidences of lung cancer. Berberine is an isoquinoline alkaloid which offers a broad range of therapeutical and pharmacological actions against cancer. However, extremely low water solubility and poor oral bioavailability have largely restricted its therapeutic applications. To overcome these limitations, we formulated berberine-loaded liquid crystalline nanoparticles (LCNs) and investigated their in vitro antiproliferative and antimigratory activity in human lung epithelial cancer cell line (A549). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), trypan blue staining, and colony forming assays were used to evaluate the anti-proliferative activity, while scratch wound healing assay and a modified Boyden chamber assay were carried out to determine the anti-migratory activity. We also investigated major proteins associated with lung cancer progression. The developed nanoparticles were found to have an average particle size of 181.3 nm with spherical shape, high entrapment efficiency (75.35%) and have shown sustained release behaviour. The most remarkable findings reported with berberine-loaded LCNs were significant suppression of proliferation, inhibition of colony formation, inhibition of invasion or migration via epithelial mesenchymal transition, and proliferation related proteins associated with cancer progression. Our findings suggest that anti-cancer compounds with the problem of poor solubility and bioavailability can be overcome by formulating them into nanotechnology-based delivery systems for better efficacy. Further in-depth investigations into anti-cancer mechanistic research will expand and strengthen the current findings of berberine-LCNs as a potential NSCLC treatment option.

Matched MeSH terms: Carcinoma, Non-Small-Cell Lung*
Novel lung adenocarcinoma and nuclear factor-kappa B (NF-κB) inhibitors: synthesis and evaluation of lantadene congeners

Suthar SK, Boon HL, Sharma M

Eur J Med Chem, 2014 Mar 3;74:135-44.
PMID: 24457265 DOI: 10.1016/j.ejmech.2013.12.052

The C-3, C-17 and C-22 congeners of pentacyclic triterpenoids reduced lantadene A (3), B (4) and 22β-hydroxyoleanolic acid (5) were synthesized and were tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead congeners 12 and 13 showed IC50 of 0.56 and 0.42 μmol, respectively against TNF-α induced activation of NF-κB. The congeners 12 and 13 exhibited inhibition of IKKβ in a single-digit micromolar dose and at the same time, 12 and 13 showed marked cytotoxicity against A549 lung cancer cells with IC50 of 0.12 and 0.08 μmol, respectively. The lead ester congeners were stable in the acidic pH, while hydrolyzed readily in the human blood plasma to release the active parent moieties.

Matched MeSH terms: Lung Neoplasms/metabolism; Lung Neoplasms/pathology*
Insights on the synthesis of asymmetric curcumin derivatives and their biological activities

Khor PY, Mohd Aluwi MFF, Rullah K, Lam KW

Eur J Med Chem, 2019 Dec 01;183:111704.
PMID: 31557608 DOI: 10.1016/j.ejmech.2019.111704

Curcumin is a small organic molecule with pleiotropic biological activities. However, its multiple structural-pharmacokinetic challenges prevent its development into a clinical drug. Various structural modifications have been made to improve its drug profile. In this review, we focus on the methods adopted in the synthesis of asymmetric curcumin derivatives and their biological activities and forecast the future of this exciting class of compounds in the field of medicine.

Matched MeSH terms: Acute Lung Injury/drug therapy
In vivo antitumour properties of tribenzyltin carboxylates in a 4T1 murine metastatic mammary tumour model: Enhanced efficacy by PLGA nanoparticles

Anasamy T, Chee CF, Kiew LV, Chung LY

Eur J Pharm Sci, 2020 Jan 15;142:105140.
PMID: 31704345 DOI: 10.1016/j.ejps.2019.105140

This study reports the in vivo performance of two tribenzyltin carboxylate complexes, tri(4-fluorobenzyl)tin[(N,N-diisopropylcarbamothioyl)sulfanyl]acetate (C1) and tribenzyltin isonicotinate (C9), in their native form as well as in a poly(lactic-co-glycolic acid) (PLGA)-based nanoformulation, to assess their potential to be translated into clinically useful agents. In a 4T1 murine metastatic mammary tumour model, single intravenous administration of C1 (2.7 mg/kg) and C9 (2.1 mg/kg; 2.1 mg/kg C9 is equivalent to 2.7 mg/kg C1) induced greater tumour growth delay than cisplatin and doxorubicin at equivalent doses, while a double-dose regimen demonstrated a much greater tumour growth delay than the single-dose treated groups. To improve the efficacy of the complexes in vivo, C1 and C9 were further integrated into PLGA nanoparticles to yield nanosized PLGA-C1 (183.7 ± 0.8 nm) and PLGA-C9 (163.2 ± 1.2 nm), respectively. Single intravenous administration of PLGA-C1 (2.7 mg C1 equivalent/kg) and PLGA-C9 (2.1 mg C9 equivalent/kg) induced greater tumour growth delay (33% reduction in the area under curve compared to that of free C1 and C9). Multiple-dose administration of PLGA-C1 (5.4 mg C1 equivalent/kg) and PLGA-C9 (4.2 mg C9 equivalent/kg) induced tumour growth suppression at the end of the study (21.7 and 34.6% reduction relative to the size on day 1 for the double-dose regimen; 73.5 and 79.0% reduction relative to the size on day 1 for the triple-dose regimen, respectively). Such tumour growth suppression was not observed in mice receiving multiple-dose regimens of free C1 and C9. Histopathological analysis revealed that metastasis to the lung and liver was inhibited in mice receiving PLGA-C1 and PLGA-C9. The current study has demonstrated the improved in vivo antitumour efficacies of C1 and C9 compared with conventional chemotherapy drugs and the enhancement of the efficacies of these agents via a robust PLGA-based nanoformulation and multiple-drug administration approach.

Matched MeSH terms: Lung Neoplasms/drug therapy
Design and development of dry powder sulfobutylether-β-cyclodextrin complex for pulmonary delivery of fisetin

Mohtar N, Taylor KM, Sheikh K, Somavarapu S

Eur J Pharm Biopharm, 2017 Apr;113:1-10.
PMID: 27916704 DOI: 10.1016/j.ejpb.2016.11.036

This study has investigated complexation of fisetin, a natural flavonoid, with three types of cyclodextrins to improve its solubility. Sulfobutylether-β-cyclodextrin (SBE-β-CD) showed the highest complexation efficiency while maintaining the in vitro antioxidant activity of fisetin. Addition of 20%v/v ethanol in water improved the amount of solubilized fisetin in the complex 5.9-fold compared to the system containing water alone. Spray drying of fisetin-SBE-β-CD complex solution in the presence of ethanol produced a dry powder with improved aerosolization properties when delivered from a dry powder inhaler, indicated by a 2-fold increase in the fine particle fraction (FPF) compared to the powder produced from the complex solution containing water alone. The pitted morphological surface of these particles suggested a more hollow internal structure, indicating a lighter and less dense powder. Incorporation of 20%w/w leucine improved the particle size distribution of the powder and further increased the FPF by 2.3-fold. This formulation also showed an EC50 value equivalent to fisetin alone in the A549 cell line. In conclusion, an inhalable dry powder containing fisetin-SBE-β-CD complex was successfully engineered with an improved aqueous solubility of fisetin. The dry powder may be useful to deliver high amounts of fisetin to the deep lung region for therapeutic purposes.

Matched MeSH terms: Lung/metabolism*
Investigating how amine structure influences drug-amine ion-pair formation and uptake via the polyamine transporter in A549 lung cells

Mohamed Sofian Z, Harun N, Mahat MM, Nor Hashim NA, Jones SA

Eur J Pharm Biopharm, 2021 Nov;168:53-61.
PMID: 34455038 DOI: 10.1016/j.ejpb.2021.08.003

Transiently associating amines with therapeutic agents through the formation of ion-pairs has been established both in vitro and in vivo as an effective means to systemically direct drug delivery to the lung via the polyamine transport system (PTS). However, there remains a need to better understand the structural traits required for effective PTS uptake of drug ion-pairs. This study aimed to use a structurally related series of amine counterions to investigate how they influenced the stability of theophylline ion-pairs and their active uptake in A549 cells. Using ethylamine (mono-amine), ethylenediamine (di-amine), spermidine (tri-amine) and spermine (tetra-amine) as counterions the ion-pair affinity was shown to increase as the number of protonated amine groups in the counterion structure increased. The mono and diamines generated a single hydrogen bond and the weakest ion-pair affinities (pKFTIR: 1.32 ± 0.04 and 1.43 ± 0.02) whereas the polyamines produced two hydrogen bonds and thus the strongest ion-pair affinities (pKFTIR: 1.93 ± 0.05 and 1.96 ± 0.04). In A549 cells depleted of endogenous polyamines using α-difluoromethylornithine (DFMO), the spermine-theophylline uptake was significantly increased (p

Matched MeSH terms: Lung/cytology; Lung/metabolism*
Effect of storage temperature on the stability of spray dried bacteriophage powders

Leung SSY, Parumasivam T, Nguyen A, Gengenbach T, Carter EA, Carrigy NB, et al.

Eur J Pharm Biopharm, 2018 Jun;127:213-222.
PMID: 29486303 DOI: 10.1016/j.ejpb.2018.02.033

This study aimed to assess the robustness of using a spray drying approach and formulation design in producing inhalable phage powders. Two types of Pseudomonas phages, PEV2 (Podovirus) and PEV40 (Myovirus) in two formulations containing different amounts of trehalose (70% and 60%) and leucine (30% and 40%) were studied. Most of the surface of the produced powders was found to be covered in crystalline leucine. The powders were stored at 4 °C and 20 °C under vacuum. The phage stability and in vitro aerosol performance of the phage powders were examined on the day of production and after 1, 3 and 12 months of storage. A minor titer loss during production was observed for both phages (0.2-0.8 log10 pfu/ml). The storage stability of the produced phage powders was found to be phage and formulation dependent. No further reduction in titer occurred for PEV2 powders stored at 4 °C across the study. The formulation containing 30% leucine maintained the viability of PEV2 at 20 °C, while the formulation containing 40% leucine gradually lost titer over time with a storage reduction of ∼0.9 log10 pfu/ml measured after 12 months. In comparison, the PEV40 phage powders generally had a ∼ 0.5 log10 pfu/ml loss upon storage regardless of temperature. When aerosolized, the total in vitro lung doses of PEV2 were of the order of 107 pfu, except the formulation containing 40% leucine stored at 20 °C which had a lower lung dose. The PEV40 powders also had lung doses of 106-107 pfu. The results demonstrate that spray dried Myoviridae and Podoviridae phage in a simple formulation of leucine and trehalose can be successfully stored for one year at 4 °C and 20 °C with vacuum packaging.

Matched MeSH terms: Lung/drug effects
An orally active geranyl acetophenone attenuates airway remodeling in a murine model of chronic asthma

Lee YZ, Shaari K, Cheema MS, Tham CL, Sulaiman MR, Israf DA

Eur J Pharmacol, 2017 Feb 15;797:53-64.
PMID: 28089919 DOI: 10.1016/j.ejphar.2017.01.011

2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) is a synthetic compound that is naturally found in Melicope ptelefolia. We had previously demonstrated that parenteral administration of tHGA reduces pulmonary inflammation in OVA-sensitized mice. In this study, we evaluated the effect of orally administered tHGA upon airway remodeling in a murine model of chronic asthma. Female BALB/C mice were sensitized intraperitoneally with ovalbumin (OVA) on day 0, 7 and 14, followed by aerosolized 1% OVA 3 times per week for 6 weeks. Control groups were sensitized with saline. OVA sensitized animals were either treated orally with vehicle (saline with 1% DMSO and Tween 80), tHGA (80, 40, 20mg/kg) or zileuton (30mg/kg) 1h prior to each aerosolized OVA sensitization. On day 61, mice underwent methacholine challenge to determine airway hyperresponsiveness prior to collection of bronchoalveolar lavage (BAL) fluid and lung samples. BAL fluid inflammatory cell counts and cytokine concentrations were evaluated while histological analysis and extracellular matrix protein concentrations were determined on collected lung samples. Oral tHGA treatment attenuated airway hyperresponsiveness and inhibited airway remodeling in a dose-dependent fashion. tHGA's effect on airway remodeling could be attributed to the reduction of inflammatory cell infiltration and decreased expression of cytokines associated with airway remodeling. Oral administration of tHGA attenuates airway hyperresponsiveness and remodeling in OVA-induced BALB/c mice. tHGA is an interesting compound that should be evaluated further for its possible role as an alternative non-steroidal pharmacological approach in the management of asthma.

Matched MeSH terms: Lung/drug effects; Lung/immunology; Lung/metabolism; Lung/pathology
Fulltext COVIDiag: a clinical CAD system to diagnose COVID-19 pneumonia based on CT findings

Abbasian Ardakani A, Acharya UR, Habibollahi S, Mohammadi A

Eur Radiol, 2021 Jan;31(1):121-130.
PMID: 32740817 DOI: 10.1007/s00330-020-07087-y

OBJECTIVES: CT findings of COVID-19 look similar to other atypical and viral (non-COVID-19) pneumonia diseases. This study proposes a clinical computer-aided diagnosis (CAD) system using CT features to automatically discriminate COVID-19 from non-COVID-19 pneumonia patients.
METHODS: Overall, 612 patients (306 COVID-19 and 306 non-COVID-19 pneumonia) were recruited. Twenty radiological features were extracted from CT images to evaluate the pattern, location, and distribution of lesions of patients in both groups. All significant CT features were fed in five classifiers namely decision tree, K-nearest neighbor, naïve Bayes, support vector machine, and ensemble to evaluate the best performing CAD system in classifying COVID-19 and non-COVID-19 cases.
RESULTS: Location and distribution pattern of involvement, number of the lesion, ground-glass opacity (GGO) and crazy-paving, consolidation, reticular, bronchial wall thickening, nodule, air bronchogram, cavity, pleural effusion, pleural thickening, and lymphadenopathy are the significant features to classify COVID-19 from non-COVID-19 groups. Our proposed CAD system obtained the sensitivity, specificity, and accuracy of 0.965, 93.54%, 90.32%, and 91.94%, respectively, using ensemble (COVIDiag) classifier.
CONCLUSIONS: This study proposed a COVIDiag model obtained promising results using CT radiological routine features. It can be considered an adjunct tool by the radiologists during the current COVID-19 pandemic to make an accurate diagnosis.
KEY POINTS: • Location and distribution of involvement, number of lesions, GGO and crazy-paving, consolidation, reticular, bronchial wall thickening, nodule, air bronchogram, cavity, pleural effusion, pleural thickening, and lymphadenopathy are the significant features between COVID-19 from non-COVID-19 groups. • The proposed CAD system, COVIDiag, could diagnose COVID-19 pneumonia cases with an AUC of 0.965 (sensitivity = 93.54%; specificity = 90.32%; and accuracy = 91.94%). • The AUC, sensitivity, specificity, and accuracy obtained by radiologist diagnosis are 0.879, 87.10%, 88.71%, and 87.90%, respectively.

Matched MeSH terms: Lung/pathology
Fulltext PET/CT in nononcological lung diseases: current applications and future perspectives

Capitanio S, Nordin AJ, Noraini AR, Rossetti C

Eur Respir Rev, 2016 Sep;25(141):247-58.
PMID: 27581824 DOI: 10.1183/16000617.0051-2016

Positron emission tomography (PET) combined with computed tomography (CT) is an established diagnostic modality that has become an essential imaging tool in oncological practice. However, thanks to its noninvasive nature and its capability to provide physiological information, the main applications of this technique have significantly expanded.(18)F-labelled fluorodeoxyglucose (FDG) is the most commonly used radiopharmaceutical for PET scanning and demonstrates metabolic activity in various tissues. Since activated inflammatory cells, like malignant cells, predominantly metabolise glucose as a source of energy and increase expression of glucose transporters when activated, FDG-PET/CT can be successfully used to detect and monitor a variety of lung diseases, such as infections and several inflammatory conditions.The added value of FDG-PET/CT as a molecular imaging technique relies on its capability to identify disease in very early stages, long before the appearance of structural changes detectable by conventional imaging. Furthermore, by detecting the active phase of infectious or inflammatory processes, disease progression and treatment efficacy can be monitored.This review will focus on the clinical use of FDG-PET/CT in nonmalignant pulmonary diseases.

Matched MeSH terms: Lung/physiopathology; Lung Diseases/physiopathology
Momordica charantia (Indian and Chinese Bitter Melon) Extracts Inducing Apoptosis in Human Lung Cancer Cell Line A549 via ROS-Mediated Mitochodria Injury

Thiagarajan S, Arapoc DJ, Husna Shafie N, Keong YY, Bahari H, Adam Z, et al.

Evid Based Complement Alternat Med, 2019;2019:2821597.
PMID: 30956678 DOI: 10.1155/2019/2821597

Lung cancer is the leading cause of cancer related deaths worldwide with about 40% occurring in developing countries. The two varieties of Momordica charantia, which are Chinese and Indian bitter melon, have been subjected to antiproliferative activity in human non-small cell lung cells A549. The A549 cells were treated with hot and cold aqueous extraction for both the bitter melon varieties, and the antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic mechanism of action on A549 human lung cancer cells was evaluated first morphologically using Hoechst 33358, and cytoskeleton staining using Filamentous-actin (F-actin) cytoskeleton FICT and DAPI followed by caspase-3/7, reactive oxygen species (ROS), and p53 activity. Chinese hot aqueous extraction (CHA) exhibited potent antiproliferative activity against A549 human lung cancer cells. The morphological analysis of mitochondria destruction and the derangement of cytoskeleton showed apoptosis-inducing activity. CHA increased the caspase-3/7 activity by 1.6-fold and the ROS activity by 5-fold. Flow cytometric analysis revealed 34.5% of apoptotic cells significantly (p<0.05) compared to cisplatin-treated A549 human cancer cells. CHA is suggested to induce apoptosis due to their rich bioactive chemical constituents. These findings suggest that the antiproliferative effect of CHA was due to apoptosis via ROS-mediated mitochondria injury.

Matched MeSH terms: Lung Neoplasms
Fulltext Induction of apoptosis and cell cycle blockade by helichrysetin in a549 human lung adenocarcinoma cells

Ho YF, Karsani SA, Yong WK, Abd Malek SN

Evid Based Complement Alternat Med, 2013;2013:857257.
PMID: 23533528 DOI: 10.1155/2013/857257

Researchers are looking into the potential development of natural compounds for anticancer therapy. Previous studies have postulated the cytotoxic effect of helichrysetin towards different cancer cell lines. In this study, we investigated the cytotoxic effect of helichrysetin, a naturally occurring chalcone on four selected cancer cell lines, A549, MCF-7, Ca Ski, and HT-29, and further elucidated its biochemical and molecular mechanisms in human lung adenocarcinoma, A549. Helichrysetin showed the highest cytotoxic activity against Ca Ski followed by A549. Changes in the nuclear morphology of A549 cells such as chromatin condensation and nuclear fragmentation were observed in cells treated with helichrysetin. Further evidence of apoptosis includes the externalization of phosphatidylserine and the collapse of mitochondrial membrane potential which are both early signs of apoptosis. These signs of apoptosis are related to cell cycle blockade at the S checkpoint which suggests that the alteration of the cell cycle contributes to the induction of apoptosis in A549. These results suggest that helichrysetin has great potentials for development as an anticancer agent.

Matched MeSH terms: Lung Neoplasms
Fulltext Intranasal administration of Lignosus rhinocerotis (Cooke) Ryvarden (Tiger Milk mushroom) extract attenuates airway inflammation in murine model of allergic asthma

Muhamad SA, Muhammad NS, Ismail NDA, Mohamud R, Safuan S, Nurul AA

Exp Ther Med, 2019 May;17(5):3867-3876.
PMID: 30988772 DOI: 10.3892/etm.2019.7416

Asthma is a chronic inflammatory disorder in the airways that involves the activation of cells and mediators. Lignosus rhinocerotis (Cooke) Ryvardan or Tiger Milk mushroom is a medicinal mushroom that is traditionally used to treat inflammatory diseases including asthma. In this study, the protective effects of intranasal administration of L. rhinocerotis extract (LRE) in ovalbumin (OVA)-induced airway inflammation mouse model were investigated. Mice were sensitized by intraperitoneal (i.p) injection on days 0 and 14, followed by a daily challenge with 1% OVA from days 21 to 27. Following OVA challenge, LRE and dexamethasone were administered via intranasal and i.p. injection respectively. On day 28, the level of serum immunoglobulin (Ig)E, differential cell counts and T-helper (Th) 2 cytokines in bronchoalveolar lavage fluid (BALF) fluid, cell subset population in lung-draining lymph nodes (LNs), leukocytes infiltration and mucus production in the lungs of the animals was measured. Results demonstrated that intranasal administration of LRE significantly suppressed the level of inflammatory cell counts in BALF as well as populations of CD4+ T-cells in lung draining LNs. Apart from that, LRE also significantly reduced the level of Th2 cytokines in BALF and IgE in the serum in OVA-induced asthma. Histological analysis also demonstrated the amelioration of leukocytes infiltration and mucus production in the lungs. Overall, these findings demonstrated the attenuation of airway inflammation in the LRE-treated mice therefore suggesting a promising alternative for the management of allergic airway inflammation.

Matched MeSH terms: Lung
Analysis of airway epithelial regeneration and repair following endobronchial brush biopsy in sheep

Yahaya B, Baker A, Tennant P, Smith SH, Shaw DJ, McLachlan G, et al.

Exp. Lung Res., 2011 Nov;37(9):519-35.
PMID: 21895444 DOI: 10.3109/01902148.2011.605513

Understanding the fundamental processes involved in repairing the airway wall following injury is fundamental to understanding the way in which these processes are perturbed during disease pathology. Indeed complex diseases such as asthma and chronic obstructive pulmonary disease (COPD) have at their core evidence of airway wall remodeling processes that play a crucial functional role in these diseases. The authors sought to understand the dynamic cellular events that occur during bronchial airway epithelial repair in sheep. The injury was induced by endobronchial brush biopsy (BBr), a process that causes epithelial débridement and induces a consequential repair process. In addition, the current experimental protocol allowed for the time-dependent changes in airway wall morphology to be studied both within and between animals. The initial débridement was followed by evidence of dedifferentiation in the intact epithelium at the wound margins, followed by proliferation of cells both within the epithelium and in the deeper wall structures, notably in association with the submucosal glands and smooth muscle bundles. Seven days after injury, although the airway wall was thickened at the site of damage, the epithelial layer was intact, with evidence of redifferentiation. These studies, in demonstrating broad agreement with previous studies in small animals, indicate the wider relevance of this system as a comparative model and should provide a solid basis upon which to further characterize the critical cellular and molecular interactions that underlie both effective restitution and pathological repair.

Matched MeSH terms: Lung Injury/metabolism; Lung Injury/pathology

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