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Treatment of chronic airway diseases using nutraceuticals: Mechanistic insight

Allam VSRR, Chellappan DK, Jha NK, Shastri MD, Gupta G, Shukla SD, et al.

Crit Rev Food Sci Nutr, 2021 May 12.
PMID: 33977840 DOI: 10.1080/10408398.2021.1915744

Respiratory diseases, both acute and chronic, are reported to be the leading cause of morbidity and mortality, affecting millions of people globally, leading to high socio-economic burden for the society in the recent decades. Chronic inflammation and decline in lung function are the common symptoms of respiratory diseases. The current treatment strategies revolve around using appropriate anti-inflammatory agents and bronchodilators. A range of anti-inflammatory agents and bronchodilators are currently available in the market; however, the usage of such medications is limited due to the potential for various adverse effects. To cope with this issue, researchers have been exploring various novel, alternative therapeutic strategies that are safe and effective to treat respiratory diseases. Several studies have been reported on the possible links between food and food-derived products in combating various chronic inflammatory diseases. Nutraceuticals are examples of such food-derived products which are gaining much interest in terms of its usage for the well-being and better human health. As a consequence, intensive research is currently aimed at identifying novel nutraceuticals, and there is an emerging notion that nutraceuticals can have a positive impact in various respiratory diseases. In this review, we discuss the efficacy of nutraceuticals in altering the various cellular and molecular mechanisms involved in mitigating the symptoms of respiratory diseases.

Matched MeSH terms: Lung
Fulltext Aural Polyp or Temporal Bone Carcinoma: Lesson to Learn

Mahmud KA, Nasseri Z, Mohamed Mukari SA, Ismail F, Abdullah A

Cureus, 2021 Mar 01;13(3):e13629.
PMID: 33816028 DOI: 10.7759/cureus.13629

Temporal bone carcinoma is a rare malignant tumor of the head and neck region. Its clinical presentations can mimic benign ear diseases, leading to inaccurate diagnosis and substandard management. We present the case of a 53-year-old female with a three-month history of progressive right otalgia, otorrhea, and hearing loss. Otoscopic examination revealed a mass occupying the right external auditory canal. However, the lesion was presumed to be an aural polyp by several clinicians previously. Multiple courses of oral antibiotics had been prescribed before she was referred to our clinic for the non-resolving aural polyp. Imaging studies showed an external auditory canal soft tissue mass with extradural and parotid extension. The mass was biopsied, and the result was reported as squamous cell carcinoma of the temporal bone. The patient was advised for a total temporal bone resection and parotidectomy; however, she declined the surgical intervention. Within a month, the tumor had metastasized to her lung, liver, and vertebral bodies. She was referred to the Oncology team for palliative chemo-radiotherapy. Temporal bone malignancy must be considered as a differential diagnosis in a middle-aged or elderly patient with a non-resolving aural polyp without a chronic discharging ear. Imaging studies and histopathological evaluation should be prompted to ascertain the diagnosis. Repeated course of oral antibiotic will delay treatment and subsequently may lead to poor prognosis.

Matched MeSH terms: Lung
Fulltext Dermatomyositis Anteceding Lung Adenocarcinoma

Lim JL, Yusof NS, Md Tarekh NA, Abdul Rahman R

Cureus, 2020 Nov 19;12(11):e11580.
PMID: 33364104 DOI: 10.7759/cureus.11580

Dermatomyositis is often presented as paraneoplastic syndrome. The diagnosis of dermatomyositis can prompt clinicians to further investigate the underlying cause, in particular malignancy. This case report illustrates the association of lung adenocarcinoma and dermatomyositis with antecedent presentation of cutaneous and musculoskeletal manifestations, one year prior to the diagnosis of carcinoma.

Matched MeSH terms: Lung Neoplasms
The Emerging Role of the Hippo Pathway in Lung Cancers: Clinical Implications

Teoh SL, Das S

Curr Drug Targets, 2017 Nov 30;18(16):1880-1892.
PMID: 27628948 DOI: 10.2174/1389450117666160907153338

BACKGROUND: The incidence of lung cancers has increased globally. Increased exposure to tobacco, passive smoking, less consumption of vegetables and fruits and occupational exposure to asbestos, arsenic and chromium are the main risk factors. The pathophysiology of lung cancer is complex and not well understood. Various microRNAs, genes and pathways are associated with lung cancers. The genes involved in lung cancers produce proteins involved in cell growth, differentiation, different cell cycles, apoptosis, immune modulation, tumor spread and progression. The Hippo pathway (also known as the Salvador-Warts-Hippo pathway) is the latest emerging concept in cancers. The Hippo pathway plays an important role in controlling the size of the tissue and organ by virtue of its action on cell proliferation and apoptosis.
OBJECTIVE: In the present review, we highlight the mammalian Hippo pathway, role of its core members, its upstream regulators, downstream effectors and the resistance cases in lung cancers.
RESULTS: Specific interaction of Mer with cell surface hyaluronan receptor CD44 is vital in cell contact inhibition, thereby activating Hippo pathway. Both transcription co-activators YAP and TAZ (also known as WWTR1, being homologs of Drosophila Yki) are important regulators of proliferation and apoptosis, and serve as major downstream effectors of the Hippo pathway. Mutation of NF2, the upstream regulator of Hippo pathway is linked to the cancers.
CONCLUSION: Targeting YAP and TAZ may be important for future drug delivery and treatment.

Matched MeSH terms: Lung Neoplasms/drug therapy; Lung Neoplasms/genetics; Lung Neoplasms/metabolism*
The anti-idiotype vaccines for immunotherapy

Bhattacharya-Chatterjee M, Chatterjee SK, Foon KA

Curr. Opin. Mol. Ther., 2001 Feb;3(1):63-9.
PMID: 11249733

Certain anti-idiotypic antibodies that bind to the antigen-combining sites of antibodies can effectively mimic the three-dimensional structures and functions of the external antigens and can be used as surrogate antigens for active specific immunotherapy. Extensive studies in animal models have demonstrated the efficacy of these vaccines for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections as well as tumors. Several monoclonal anti-idiotype antibodies that mimic distinct human tumor-associated antigens have been developed and characterized. Encouraging results have been obtained in recent clinical trials using these anti-idiotype antibodies as vaccines. In this article, we will review the current literature and discuss the potential of this novel therapeutic approach for various human cancers.

Matched MeSH terms: Lung Neoplasms/therapy
Advancing of Cellular Signaling Pathways in Respiratory Diseases Using Nanocarrier Based Drug Delivery Systems

Mehta M, Dhanjal DS, Satija S, Wadhwa R, Paudel KR, Chellappan DK, et al.

Curr Pharm Des, 2020;26(42):5380-5392.
PMID: 33198611 DOI: 10.2174/1381612826999201116161143

Cell Signaling pathways form an integral part of our existence that allows the cells to comprehend a stimulus and respond back. Such reactions to external cues from the environment are required and are essential to regulate the normal functioning of our body. Abnormalities in the system arise when there are errors developed in these signals, resulting in a complication or a disease. Presently, respiratory diseases contribute to being the third leading cause of morbidity worldwide. According to the current statistics, over 339 million people are asthmatic, 65 million are suffering from COPD, 2.3 million are lung cancer patients and 10 million are tuberculosis patients. This toll of statistics with chronic respiratory diseases leaves a heavy burden on society and the nation's annual health expenditure. Hence, a better understanding of the processes governing these cellular pathways will enable us to treat and manage these deadly respiratory diseases effectively. Moreover, it is important to comprehend the synergy and interplay of the cellular signaling pathways in respiratory diseases, which will enable us to explore and develop suitable strategies for targeted drug delivery. This review, in particular, focuses on the major respiratory diseases and further provides an in-depth discussion on the various cell signaling pathways that are involved in the pathophysiology of respiratory diseases. Moreover, the review also analyses the defining concepts about advanced nano-drug delivery systems involving various nanocarriers and propose newer prospects to minimize the current challenges faced by researchers and formulation scientists.

Matched MeSH terms: Lung Neoplasms*
Lipid-based Nanocarriers for Cancer and Tumor Treatment

Ansari MT, Ramlan TA, Jamaluddin NN, Zamri N, Salfi R, Khan A, et al.

Curr Pharm Des, 2020;26(34):4272-4276.
PMID: 32693760 DOI: 10.2174/1381612826666200720235752

Cancer and tumor have been major reasons for numerous deaths in this century across the world. Many strategies have been designed to treat, diagnose, or prevent cancer. The success of chemotherapy largely depends on drug targeting. The advent of nanotechnology has vastly improved drug delivery for targeting and diagnosis. Nevertheless, the accuracy of drug targeting with polymeric nanoparticles has always been questionable. The polymeric nanoparticles synthesized from varieties of lipid-based compounds or combined with vectors, such as liposomes, ethosomes, and transfersomes, may allow the drug to overcome the issue of resistance to drug absorption in biological membranes. The combined effects of lipid-based nanocarriers are known to improve the efficacy and accuracy of polymeric nanoparticles. The present review explores the application of lipid based nanocarriers in the treatment and diagnosis of cancer A special focus is given to the use of lipid-based nanocarriers in the treatment, diagnosis, and mitigation of cancer located in blood, brain, lung, and colon. The treatment of these cancers has always been questionable as the chances of relapse are very high. The review encompasses the use of lipid-based nanocarriers in targeting tissue-specific cancer cells.

Matched MeSH terms: Lung
Clinical and pathological manifestations of human henipavirus infection

Wong KT, Tan CT

Curr. Top. Microbiol. Immunol., 2012;359:95-104.
PMID: 22427144 DOI: 10.1007/82_2012_205

The clinicopathological features of human Nipah virus and Hendra virus infections appear to be similar. The clinical manifestations may be mild, but if severe, includes acute encephalitic and pulmonary syndromes with a high mortality. The pathological features in human acute henipavirus infections comprise vasculopathy (vasculitis, endothelial multinucleated syncytia, thrombosis), microinfarcts and parenchymal cell infection in the central nervous system, lung, kidney and other major organs. Viral inclusions, antigens, nucleocapsids and RNA are readily demonstrated in blood vessel wall and numerous types of parenchymal cells. Relapsing henipavirus encephalitis is a rare complication reported in less than 10% of survivors of the acute infection and appears to be distinct from the acute encephalitic syndrome. Pathological evidence suggests viral recrudescence confined to the central nervous system as the cause.

Matched MeSH terms: Lung/pathology; Lung/virology
Surface peptide functionalization of zeolitic imidazolate framework-8 for autonomous homing and enhanced delivery of chemotherapeutic agent to lung tumor cells

Kamal NAMA, Abdulmalek E, Fakurazi S, Cordova KE, Abdul Rahman MB

Dalton Trans, 2021 Feb 23;50(7):2375-2386.
PMID: 33555001 DOI: 10.1039/d1dt00116g

Chemotherapeutic agents used in treating certain cancer types operate in a non-selective manner tending to accumulate in normal, healthy tissue when high doses are used. To mitigate the toxicity effect resulting from this, there is an urgent need to develop active nano delivery systems capable of regulating optimal doses specifically to cancer cells without harming adjacent normal cells. Herein, we report a versatile nanoparticle - zeolitic imidazolate framework-8 (nZIF-8) - that is loaded with a chemotherapeutic agent (gemcitabine; GEM) and surface-functionalized with an autonomous homing system (Arg-Gly-Asp peptide ligand; RGD) via a straightforward, one-pot solvothermal reaction. Successful functionalization of the surface of nZIF-8 loaded GEM (GEM⊂nZIF-8) with RGD was proven by spectroscopic and electron microscopy techniques. This surface-functionalized nanoparticle (GEM⊂RGD@nZIF-8) exhibited enhanced uptake in human lung cancer cells (A549), compared with non-functionalized GEM⊂nZIF-8. The GEM⊂RGD@nZIF-8, experienced not only efficient uptake within A549, but also induced obvious cytotoxicity (75% at a concentration of 10 μg mL-1) and apoptosis (62%) after 48 h treatment when compared to the nanoparticle absent of the RGD homing system (GEM⊂nZIF-8). Most importantly, this surface-functionalized nanoparticle was more selective towards lung cancer cells (A549) than normal human lung fibroblast cells (MRC-5) with a selectivity index (SI) of 3.98. This work demonstrates a new one-pot strategy for realizing a surface-functionalized zeolitic imidazolate framework that actively targets cancer cells via an autonomous homing peptide system to deliver a chemotherapeutic payload effectively.

Matched MeSH terms: Lung Neoplasms/drug therapy*
Fulltext Lack of association of apolipoprotein E (Apo E) polymorphism with the prevalence of metabolic syndrome: the National Heart, Lung and Blood Institute Family Heart Study

Lai LY, Petrone AB, Pankow JS, Arnett DK, North KE, Ellison RC, et al.

Diabetes Metab Res Rev, 2015 Sep;31(6):582-7.
PMID: 25656378 DOI: 10.1002/dmrr.2638

OBJECTIVE: Metabolic syndrome (MetS), characterized by abdominal obesity, atherogenic dyslipidaemia, elevated blood pressure and insulin resistance, is a major public health concern in the United States. The effects of apolipoprotein E (Apo E) polymorphism on MetS are not well established.
METHODS: We conducted a cross-sectional study consisting of 1551 participants from the National Heart, Lung and Blood Institute Family Heart Study to assess the relation of Apo E polymorphism with the prevalence of MetS. MetS was defined according to the American Heart Association-National Heart, Lung and Blood Institute-International Diabetes Federation-World Health Organization harmonized criteria. We used generalized estimating equations to estimate adjusted odds ratios (ORs) for prevalent MetS and the Bonferroni correction to account for multiple testing in the secondary analysis.
RESULTS: Our study population had a mean age (standard deviation) of 56.5 (11.0) years, and 49.7% had MetS. There was no association between the Apo E genotypes and the MetS. The multivariable adjusted ORs (95% confidence interval) were 1.00 (reference), 1.26 (0.31-5.21), 0.89 (0.62-1.29), 1.13 (0.61-2.10), 1.13 (0.88-1.47) and 1.87 (0.91-3.85) for the Ɛ3/Ɛ3, Ɛ2/Ɛ2, Ɛ2/Ɛ3, Ɛ2/Ɛ4, Ɛ3/Ɛ4 and Ɛ4/Ɛ4 genotypes, respectively. In a secondary analysis, Ɛ2/Ɛ3 genotype was associated with 41% lower prevalence odds of low high-density lipoprotein [multivariable adjusted ORs (95% confidence interval) = 0.59 (0.36-0.95)] compared with Ɛ3/Ɛ3 genotype.
CONCLUSIONS: Our findings do not support an association between Apo E polymorphism and MetS in a multicentre population-based study of predominantly White US men and women.
Intrathyroidal oxyphilic parathyroid carcinoma: A potential diagnostic caveat in cytology?

Wong YP, Sharifah NA, Tan GC, Gill AJ, Ali SZ

Diagn Cytopathol, 2016 May 26.
PMID: 27229757 DOI: 10.1002/dc.23493

Oxyphilic (oncocytic) parathyroid lesions are very uncommon and their cytological features are rarely described. Due to the similarities in anatomical location and indistinguishable cytomorphological features, these lesions are easily confused with neoplastic and non-neoplastic thyroid lesions on fine needle aspiration (FNA). The diagnosis becomes more challenging in cases of unusual intrathyroidal location of the parathyroid lesions in the absence of clinical evidence of hyperparathyroidism, which simulate thyroid nodules clinically. We describe a case of intrathyroidal oxyphilic parathyroid carcinoma in a 66-year-old female, who presented with a dominant left "thyroid" nodule. FNA smears were cellular, comprising predominantly of oxyphilic cells arranged in papillary-like architecture with occasional nuclear grooves, which was mistaken for oncocytic variant of papillary carcinoma of the thyroid. The histological diagnosis of oxyphilic parathyroid "adenoma" was made following total thyroidectomy. The tumor, unfortunately, recurred 7 years later with associated multiple lung metastases. When dealing with thyroid lesions comprising predominantly of oncocytic cells, one should consider oxyphilic parathyroid neoplasms as one of the differential diagnosis. In difficult equivocal cases, a panel of immunocytochemical stains (PTH, GATA3, TTF-1, PAX8, and thyroglobulin) can be helpful. In addition, a combination of valuable clinical, radiological, and laboratory data, including serum calcium and parathyroid hormone levels are key to arriving at an accurate cytological diagnosis. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

Matched MeSH terms: Lung Neoplasms
Tissue-clot-coagulum cell block in EBUS/TBNA specimen adequacy: A real world experience

Kho SS, Chan SK, Ismail AM, Tie ST

Diagn Cytopathol, 2022 Dec;50(12):583-585.
PMID: 36135808 DOI: 10.1002/dc.25056
Matched MeSH terms: Carcinoma, Non-Small-Cell Lung*; Lung Neoplasms*
Fulltext Association of Radiation Doses and Cancer Risks from CT Pulmonary Angiography Examinations in Relation to Body Diameter

Harun HH, Abdul Karim MK, Abbas Z, Abdul Rahman MA, Sabarudin A, Ng KH

Diagnostics (Basel), 2020 Sep 09;10(9).
PMID: 32917029 DOI: 10.3390/diagnostics10090681

In this study, we aimed to estimate the probability of cancer risk induced by CT pulmonary angiography (CTPA) examinations concerning effective body diameter. One hundred patients who underwent CTPA examinations were recruited as subjects from a single institution in Kuala Lumpur. Subjects were categorized based on their effective diameter size, where 19-25, 25-28, and >28 cm categorized as Groups 1, 2, and 3, respectively. The mean value of the body diameter of the subjects was 26.82 ± 3.12 cm, with no significant differences found between male and female subjects. The risk of cancer in breast, lung, and liver organs was 0.009%, 0.007%, and 0.005% respectively. The volume-weighted CT dose index (CTDIvol) was underestimated, whereas the size-specific dose estimates (SSDEs) provided a more accurate description of the radiation dose and the risk of cancer. CTPA examinations are considered safe but it is essential to implement a protocol optimized following the As Low as Reasonably Achievable (ALARA) principle.

Matched MeSH terms: Lung
Amiodarone-induced phospholipidosis: an in vivo [14C]-acetate uptake study in rat

Sirajudeen KN, Gurumoorthy P, Devaraj H, Devaraj SN

Drug Chem Toxicol, 2002 Aug;25(3):247-54.
PMID: 12173246

Amiodarone (AD), a potent antiarrhythmic drug, is often associated with several adverse effects. It is shown to accumulate phospholipids in various tissues, and the impaired catabolism of phospholipids has been implicated in AD-induced phospholipidosis. The synthesis of phospholipids in tissues has not been dealt with. Hence, the incorporation of [14C]-acetate into phospholipids has been studied to understand the AD-induced phospholipidosis in lung and liver. A significant increase in lung and liver phospholipids was observed after 21 and 28 days of AD (175 mg/kg body weight/day) treatment. In the lung and liver, the incorporation of [14C]-acetate into all phospholipid fractions was elevated, while in the lung mitochondria phosphatidylcholine, phosphatidyl ethanolamine and the cardiolipin levels were significantly increased. The results indicate that, in addition to the impaired catabolism of phospholipid, AD treatment resulted in increased phospholipid synthesis.

Matched MeSH terms: Lung
Lipid-based pulmonary delivery system: a review and future considerations of formulation strategies and limitations

Ngan CL, Asmawi AA

Drug Deliv Transl Res, 2018 10;8(5):1527-1544.
PMID: 29881970 DOI: 10.1007/s13346-018-0550-4

Inhalation therapy of lipid-based carriers has great potential in direct target towards the root of respiratory diseases, which make them superior over other drug deliveries. With the successful entry of lipid carriers into the target cells, drugs can be absorbed in a sustained release manner and yield extended medicinal effects. Nevertheless, translation of inhalation therapy from laboratory to clinic especially in drug delivery remains a key challenge to the formulators. An ideal drug vehicle should safeguard the drugs from any premature elimination, facilitate cellular uptake, and promote maximum drug absorption with negligible toxicity. Despite knowing that lung treatment can be done via systemic delivery, pulmonary administration is capable of enhancing drug retention within the lungs, while minimizing systemic toxicity with local targeting. Current inhalation therapy of lipid-based carriers can be administered either intratracheally or intranasally to reach deep lung. However, the complex dimensions of lung architectural and natural defense mechanism poise major barriers towards targeted pulmonary delivery. Delivery systems have to be engineered in a way to tackle various diseases according to their biological conditions. This review highlights on the developmental considerations of lipid-based delivery systems cater for the pulmonary intervention of different lung illnesses.

Matched MeSH terms: Lung/drug effects; Lung Diseases/drug therapy*
In vitro evaluation of the inhalable quercetin loaded nanoemulsion for pulmonary delivery

Arbain NH, Salim N, Masoumi HRF, Wong TW, Basri M, Abdul Rahman MB

Drug Deliv Transl Res, 2019 04;9(2):497-507.
PMID: 29541999 DOI: 10.1007/s13346-018-0509-5

Bioavailability of quercetin, a flavonoid potentially known to combat cancer, is challenging due to hydrophobic nature. Oil-in-water (O/W) nanoemulsion system could be used as nanocarrier for quercertin to be delivered to lung via pulmonary delivery. The novelty of this nanoformulation was introduced by using palm oil ester/ricinoleic acid as oil phase which formed spherical shape nanoemulsion as measured by transmission electron microscopy and Zetasizer analyses. High energy emulsification method and D-optimal mixture design were used to optimize the composition towards the volume median diameter. The droplet size, polydispersity index, and zeta potential of the optimized formulation were 131.4 nm, 0.257, and 51.1 mV, respectively. The formulation exhibited high drug entrapment efficiency and good stability against phase separation and storage at temperature 4 °C for 3 months. It was discovered that the system had an acceptable median mass aerodynamic diameter (3.09 ± 0.05 μm) and geometric standard deviation (1.77 ± 0.03) with high fine particle fraction (90.52 ± 0.10%), percent dispersed (83.12 ± 1.29%), and percent inhaled (81.26 ± 1.28%) for deposition in deep lung. The in vitro release study demonstrated that the sustained release pattern of quercetin from naneomulsion formulation up to 48 h of about 26.75% release and it was in adherence to Korsmeyer's Peppas mechanism. The cytotoxicity study demonstrated that the optimized nanoemulsion can potentially induce cyctotoxicity towards A549 lung cancer cells without affecting the normal cells. These results of the study suggest that nanoemulsion is a potential carrier system for pulmonary delivery of molecules with low water solubility like quercetin.

Matched MeSH terms: Lung/metabolism
Fulltext Antimycobacterial, antimicrobial, and biocompatibility properties of para-aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites

Saifullah B, El Zowalaty ME, Arulselvan P, Fakurazi S, Webster TJ, Geilich BM, et al.

Drug Des Devel Ther, 2014;8:1029-36.
PMID: 25114509 DOI: 10.2147/DDDT.S63753

The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis.

Matched MeSH terms: Lung/cytology
The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress

Dua K, Wadhwa R, Singhvi G, Rapalli V, Shukla SD, Shastri MD, et al.

Drug Dev Res, 2019 09;80(6):714-730.
PMID: 31691339 DOI: 10.1002/ddr.21571

Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro-inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases.

Matched MeSH terms: Lung Diseases
Advances and challenges in developing andrographolide and its analogues as cancer therapeutic agents

Soo HL, Quah SY, Sulaiman I, Sagineedu SR, Lim JCW, Stanslas J

Drug Discov Today, 2019 09;24(9):1890-1898.
PMID: 31154065 DOI: 10.1016/j.drudis.2019.05.017

Andrographolide (AGP), a naturally occurring bioactive compound, has been investigated as a lead compound in cancer drug development. Its multidimensional therapeutic effects have raised interest among medicinal chemists, which has led to extensive structural modification of the compound, resulting in analogues with improved pharmacological and pharmaceutical properties. Nevertheless, the analogues with the improved properties need to be rigorously studied to identify drug-like lead compounds. We scrutinised articles published from 2012 to 2018, to objectively provide opinions on the mechanisms of action of AGP and its analogues, as well as their potential as viable anticancer drugs. Preclinical and clinical data, along with the extensive medicinal chemistry efforts, indicate the compounds are potential anticancer agents with specific value in treating recalcitrant cancers such as pancreatic and lung cancers.

Matched MeSH terms: Lung Neoplasms
Fulltext Performance of transbronchial cryobiopsy in eccentrically and adjacently orientated radial endobronchial ultrasound lesions

Kho SS, Chan SK, Yong MC, Tie ST

ERJ Open Res, 2019 Oct;5(4).
PMID: 31649952 DOI: 10.1183/23120541.00135-2019

Background: Radial endobronchial ultrasound (R-EBUS) is an effective technique in the diagnosis of peripheral pulmonary lesions (PPL). However, lesion orientation with regards to the radial probe remains an important factor for effective biopsy. "Within" orientation was associated with significantly higher diagnostic yield. Cryobiopsy is a novel technique in obtaining larger tissue samples with the frozen tip allowing biopsy in a 360° direction, thus potentially achieving more effective biopsy in eccentrically and adjacently orientated lesions. We aimed to evaluate the performance and safety of transbronchial cryobiopsy versus forceps biopsy in eccentrically and adjacently orientated R-EBUS lesions.
Methods: Retrospective review of R-EBUS transbronchial biopsy for PPL over 17 months.
Results: 114 R-EBUS scans were included for analysis during the study period. Forceps biopsy was performed in 76 (66.7%) cases and cryobiopsy in 38 (33.3%) cases. Baseline demographics and lesion characteristics did not differ between the two groups. Median (interquartile range) lesion size was 3.48 (2.63-4.51) cm. Overall, 41.2% of lesions were of eccentric orientation and 15.8% adjacent orientation; only 43% were concentric in orientation. Overall diagnostic yield was 67.5% (77 out of 114). Orientation remained an important factor affecting diagnostic yield. Transbronchial cryobiopsy significantly increased the diagnostic yield in eccentrically and adjacently orientated lesions to 75.0% (18 out of 24), compared to 48.8% (20 out of 41) obtained via forceps biopsy (p<0.05); but not in concentric lesions. Cryobiopsy was associated with more mild and moderate bleeding complications compared to the forceps biopsy group.
Conclusions: Transbronchial cryobiopsy under R-EBUS guidance is a safe procedure which potentially increases diagnostic yield in eccentrically and adjacently orientated PPLs.

Matched MeSH terms: Lung

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