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  1. Fulltext Using bioconductor package BiGGR for metabolic flux estimation based on gene expression changes in brain
    Gavai AK, Supandi F, Hettling H, Murrell P, Leunissen JA, van Beek JH
    PLoS One, 2015;10(3):e0119016.
    PMID: 25806817 DOI: 10.1371/journal.pone.0119016
    Predicting the distribution of metabolic fluxes in biochemical networks is of major interest in systems biology. Several databases provide metabolic reconstructions for different organisms. Software to analyze flux distributions exists, among others for the proprietary MATLAB environment. Given the large user community for the R computing environment, a simple implementation of flux analysis in R appears desirable and will facilitate easy interaction with computational tools to handle gene expression data. We extended the R software package BiGGR, an implementation of metabolic flux analysis in R. BiGGR makes use of public metabolic reconstruction databases, and contains the BiGG database and the reconstruction of human metabolism Recon2 as Systems Biology Markup Language (SBML) objects. Models can be assembled by querying the databases for pathways, genes or reactions of interest. Fluxes can then be estimated by maximization or minimization of an objective function using linear inverse modeling algorithms. Furthermore, BiGGR provides functionality to quantify the uncertainty in flux estimates by sampling the constrained multidimensional flux space. As a result, ensembles of possible flux configurations are constructed that agree with measured data within precision limits. BiGGR also features automatic visualization of selected parts of metabolic networks using hypergraphs, with hyperedge widths proportional to estimated flux values. BiGGR supports import and export of models encoded in SBML and is therefore interoperable with different modeling and analysis tools. As an application example, we calculated the flux distribution in healthy human brain using a model of central carbon metabolism. We introduce a new algorithm termed Least-squares with equalities and inequalities Flux Balance Analysis (Lsei-FBA) to predict flux changes from gene expression changes, for instance during disease. Our estimates of brain metabolic flux pattern with Lsei-FBA for Alzheimer's disease agree with independent measurements of cerebral metabolism in patients. This second version of BiGGR is available from Bioconductor.
  2. Fulltext Enhancing identification and counseling skills of dental undergraduate students using a customized Tobacco Counseling Training Module (TCTM) - A piloting of the process using ADDIE framework
    Chandrashekar BR, Chacko TV, Anand KM, Suvetha K, Jaishankar HP, Suma S
    Indian J Cancer, 2020 8 10;57(3):296-310.
    PMID: 32769291 DOI: 10.4103/ijc.IJC_229_19
    Background: Tobacco use has emerged as a major public health problem. But, most graduates in medical and dental schools receive limited systematic training. The objective of this education innovation project was to enhance dental undergraduate student's ability to identify tobacco users through oral manifestations and improve their counseling skills using a customized Tobacco Counseling Training Module (TCTM).

    Methods: A TCTM for students of dentistry was developed using ADDIE framework as a guide. Content and construct validation of the module was done by six subject experts using Delphi technique for obtaining consensus. Pilot testing was done on 20 students of third year BDS. Pre- and post-intervention assessment of knowledge, attitude, self-confidence was done using learning outcomes questionnaire. Ability to correctly identify oral manifestations was assessed using extended item MCQs and tobacco counseling skills using a modified KEECC. The difference in mean scores were computed and subjected to further statistical analysis using SPSS version 22.

    Results: There was a significant improvement in post intervention scores for mean knowledge (5.5 ± 1.4 to 13.2 ± 1.1), attitude (5.6 ± 0.9 and 8.5 ± 0.5), self-confidence (1.5 ± 0.5 and 3.1 ± 0.2), ability to correctly identify oral manifestations (5.2 ± 1.4 and 9.4 ± 0.8) and tobacco counseling skills.

    Conclusion: It is possible to introduce the module in the existing curriculum and its effectiveness evaluation shows benefit in terms of Kirkpatrick's Level 1, 2, 3 (improvement in knowledge, attitude, self-confidence, ability to identify oral manifestations, and tobacco counseling skills) of training effectiveness.

  3. Fulltext Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis
    Chan Y, Ng SW, Mehta M, Anand K, Kumar Singh S, Gupta G, et al.
    Med Hypotheses, 2020 Nov;144:110298.
    PMID: 33254489 DOI: 10.1016/j.mehy.2020.110298
    Outbreaks of influenza infections in the past have severely impacted global health and socioeconomic growth. Antivirals and vaccines are remarkable medical innovations that have been successful in reducing the rates of morbidity and mortality from this disease. However, the relentless emergence of drug resistance has led to a worrisome increase in the trend of influenza outbreaks, characterized by worsened clinical outcomes as well as increased economic burden. This has prompted the need for breakthrough innovations that can effectively manage influenza outbreaks. This article provides an insight into a novel hypothesis that describes how the integration of nanomedicine, with the development of drugs and vaccines can potentially enhance body immune response and the efficacies of anti-viral therapeutics to combat influenza infections.
  4. Fulltext Effectiveness of tobacco counseling training module (TCTM) in enhancing the knowledge, attitude, ability to identify oral manifestations, self-confidence, and skills (KAASS) in tobacco counseling among undergraduate dental students - An interventional study
    Chandrashekar BR, Chacko TV, Jayashankar HP, Suma S, Anand KM, Kannappan S
    Indian J Cancer, 2024 Apr 01;61(2):230-237.
    PMID: 38155453 DOI: 10.4103/ijc.ijc_405_21
    BACKGROUND: Tobacco use has emerged as a major public health issue with increasing tobacco-related morbidity and mortality. Despite evidence that even brief tobacco counseling by health care professionals is effective in motivating a tobacco user to quit, there was a lack of customized tobacco counseling training module (TCTM) for students of dentistry in their existing curriculum. This study was undertaken to evaluate the effectiveness of a customized TCTM in improving KAASS in tobacco counseling among undergraduate dental students.

    METHODS: TCTM that was previously pilot tested was implemented as a value addition in Public Health Dentistry for two academic years. Changes in knowledge, attitude, ability to identify oral manifestations, self-confidence, and skills (KAASS) in tobacco counseling were assessed before and after implementation of TCTM. Mean pre and post intervention scores were compared.

    RESULTS: Mean scores for knowledge, attitude, ability to identify oral manifestations, and self-confidence (KAAS) at baseline were 4.4 ± 0.9, 5.1 ± 0.7, 4.5 ± 1.1, and 1.3 ± 0.4, respectively. Mean KAAS scores post intervention were 13.5 ± 1.0, 8.7 ± 0.4, 9.4 ± 0.7, and 3.5 ± 0.5, respectively. There was a significant improvement in the mean KAAS score post intervention compared to baseline. Tobacco counseling skills also significantly improved among the participants following implementation of the training module (68.8%) did well compared to the baseline (0%).

    CONCLUSION: TCTM was effective in enhancing knowledge, attitude, ability to identify oral manifestations, and self-confidence in tobacco counseling among undergraduate dental students.

  5. Recent Trends in Rationally Designed Molecules as Kinase Inhibitors
    Prasher P, Sharma M, Chan Y, Singh SK, Anand K, Dureja H, et al.
    Curr Med Chem, 2023;30(13):1529-1567.
    PMID: 34766883 DOI: 10.2174/0929867328666211111161811
    Protein kinases modulate the structure and function of proteins by adding phosphate groups to threonine, tyrosine, and serine residues. The phosphorylation process mediated by the kinases regulates several physiological processes, while their overexpression results in the development of chronic diseases, including cancer. Targeting of receptor tyrosine kinase pathways results in the inhibition of angiogenesis and cell proliferation that validates kinases as a key target in the management of aggressive cancers. As such, the identification of protein kinase inhibitors revolutionized the contemporary anticancer therapy by inducing a paradigm shift in the management of disease pathogenesis. Contemporary drug design programs focus on a broad range of kinase targets for the development of novel pharmacophores to manage the overexpression of kinases and their pathophysiology in cancer pathogenesis. In this review, we present the emerging trends in the development of rationally designed molecular inhibitors of kinases over the last five years (2016-2021) and their incipient role in the development of impending anticancer pharmaceuticals.
  6. Fulltext A novel nano therapeutic using convalescent plasma derived exosomal (CPExo) for COVID-19: A combined hyperactive immune modulation and diagnostics
    Anand K, Vadivalagan C, Joseph JS, Singh SK, Gulati M, Shahbaaz M, et al.
    Chem Biol Interact, 2021 Aug 01;344:109497.
    PMID: 33991505 DOI: 10.1016/j.cbi.2021.109497
    Extracellular vesicles like exosomes are important therapeutic tactics for treating COVID -19. By utilizing convalescent plasma derived exosomes (CPExo) from COVID-19 recovered persistence could accelerate the treatment strategies in the current state of affairs. Adequate literature has shown that administering the exosome to the in vivo system could be beneficial and could target the pathogens in an effective and precise manner. In this hypothesis we highlight the CPExo instead of convalescent plasma (CP), perhaps to dispense of exosomes are gratified and it's more effectively acquired immune response conferral through antibodies. COVID-19 convalescent plasma has billions of exosomes and it has aptitudes to carry molecular constituents like proteins, lipids, RNA and DNA, etc. Moreover, exosomes are capable of recognizing antigens with adequate sensitivity and specificity. Many of these derivatives could trigger an immune modulation into the cells and act as an epigenetic inheritor response to target pathogens through RNAs. COIVID-19 resistance activated plasma-derived exosomes are either responsible for the effects of plasma beyond the contained immune antibodies or could be inhibitory. The proposed hypothesis suggests that preselecting the plasma-derived antibodies and RNAs merged exosomes would be an optimized therapeutic tactic for COVID-19 patients. We suggest that, the CPExo has a multi-potential effect for treatment efficacy by acting as immunotherapeutic, drug carrier, and diagnostic target with noncoding genetic materials as a biomarker.
  7. Fulltext Unlocking Exosome-Based Theragnostic Signatures: Deciphering Secrets of Ovarian Cancer Metastasis
    Mukherjee S, Nag S, Mukerjee N, Maitra S, Muthusamy R, Fuloria NK, et al.
    ACS Omega, 2023 Oct 10;8(40):36614-36627.
    PMID: 37841156 DOI: 10.1021/acsomega.3c02837
    Ovarian cancer (OC) is a common gynecological cancer worldwide. Unfortunately, the lack of early detection methods translates into a substantial cohort of women grappling with the pressing health crisis. The discovery of extracellular vesicles (EVs) (their major subpopulation exosomes, microvesicles, and apoptotic bodies) has provided new insights into the understanding of cancer. Exosomes, a subpopulation of EVs, play a crucial role in cellular communication and reflect the cellular status under both healthy and pathological conditions. Tumor-derived exosomes (TEXs) dynamically influence ovarian cancer progression by regulating uncontrolled cell growth, immune suppression, angiogenesis, metastasis, and the development of drug and therapeutic resistance. In the field of OC diagnostics, TEXs offer potential biomarkers in various body fluids. On the other hand, exosomes have also shown promising abilities to cure ovarian cancer. In this review, we address the interlink between exosomes and ovarian cancer and explore their theragnostic signature. Finally, we highlight future directions of exosome-based ovarian cancer research.
  8. Fulltext Induction of Caspase-Mediated Apoptosis in HepG2 Liver Carcinoma Cells Using Mutagen-Antioxidant Conjugated Self-Assembled Novel Carbazole Nanoparticles and In Silico Modeling Studies
    Anand K, Abdul NS, Ghazi T, Ramesh M, Gupta G, Tambuwala MM, et al.
    ACS Omega, 2021 Jan 12;6(1):265-277.
    PMID: 33458478 DOI: 10.1021/acsomega.0c04461
    In this study, novel self-assembled carbazole-thiooctanoic acid nanoparticles (CTNs) were synthesized from amino carbazole (a mutagen) and thiooctanoic acid (an antioxidant). The nanoparticles were characterized using hyperspectral techniques. Then, the antiproliferative potential of CTNs was determined in HepG2 liver carcinoma cells. This study employed a solvent-antisolvent interaction method to synthesize a spherical CTN of size less than 50 nm. Moreover, CT was subsequently capped to gold nanoparticles (AuNPs) in the additional comparative studies. The CT derivative was synthesized from carbazole and lipoic acid by the amide bond formation reaction using a coupling agent. Furthermore, it was characterized using infrared (IR), 1H nuclear magnetic resonance, dynamic light scattering (DLS), and transmission electron microscopy techniques. The CT-capped gold nanoparticles (CTAuNPs) were prepared from CT, chloroauric acid, and NaBH4. The CTAuNPs were characterized using ultraviolet-visible, high-resolution TEM, DLS, and Fourier transform IR techniques. The cytotoxicity and apoptosis-inducing ability of both nanoparticles were determined in HepG2 cells. The results demonstrate that CTNs exhibit antiproliferative activity in the cancerous HepG2 cells. Moreover, molecular docking and molecular dynamics studies were conducted to explore the therapeutic potential of CT against human EGFR suppressor protein to gain more insights into the binding mode of the CT, which may show a significant role in anticancer therapy.
  9. Nanocarriers for treatment of dermatological diseases: Principle, perspective and practices
    Ramanunny AK, Wadhwa S, Gulati M, Singh SK, Kapoor B, Dureja H, et al.
    Eur J Pharmacol, 2021 Jan 05;890:173691.
    PMID: 33129787 DOI: 10.1016/j.ejphar.2020.173691
    Skin diseases are the fourth leading non-fatal skin conditions that act as a burden and affect the world economy globally. This condition affects the quality of a patient's life and has a pronounced impact on both their physical and mental state. Treatment of these skin conditions with conventional approaches shows a lack of efficacy, long treatment duration, recurrence of conditions, systemic side effects, etc., due to improper drug delivery. However, these pitfalls can be overcome with the applications of nanomedicine-based approaches that provide efficient site-specific drug delivery at the target site. These nanomedicine-based strategies are evolved as potential treatment opportunities in the form of nanocarriers such as polymeric and lipidic nanocarriers, nanoemulsions along with emerging others viz. carbon nanotubes for dermatological treatment. The current review focuses on challenges faced by the existing conventional treatments along with the topical therapeutic perspective of nanocarriers in treating various skin diseases. A total of 213 articles have been reviewed and the application of different nanocarriers in treating various skin diseases has been explained in detail through case studies of previously published research works. The toxicity related aspects of nanocarriers are also discussed.
  10. Oral Nanoemulsion of Fenofibrate: Formulation, Characterization, and In Vitro Drug Release Studies
    Gulati N, Kumar Chellappan D, M Tambuwala M, A A Aljabali A, Prasher P, Kumar Singh S, et al.
    Assay Drug Dev Technol, 2021 05 14;19(4):246-261.
    PMID: 33989048 DOI: 10.1089/adt.2021.012
    Nanoemulsions (NMs) are one of the most important colloidal dispersion systems that are primarily used to improve the solubility of poorly water soluble drugs. The main objectives of this study were, first, to prepare an NM loaded with fenofibrate using a high shear homogenization technique and, second, to study the effect of variable using a central composite design. Twenty batches of fenofibrate-loaded NM formulations were prepared. The formed NMs were subjected to droplet size analysis, zeta potential, entrapment efficiency, pH, dilution, polydispersity index, transmission electron microscopy (TEM), Fourier transform infrared spectrophotometry, differential scanning calorimetry (DSC), and in vitro drug release study. Analysis of variance was used for entrapment efficiency data to study the fitness and significance of the design. The NM-7 batch formulation demonstrated maximum entrapment efficiency (81.82%) with lowest droplet size (72.28 nm), and was thus chosen as the optimized batch. TEM analysis revealed that the NM was well dispersed with droplet sizes <100 nm. Incorporation of the drug into the NM was confirmed with DSC studies. In addition, the batch NM-7 also showed the maximum in vitro drug release (87.6%) in a 0.05 M sodium lauryl sulfate solution. The release data revealed that the NM followed first-order kinetics. The outcomes of the study revealed the development of a stable oral NM containing fenofibrate using the high shear homogenization technique. This approach may aid in further enhancing the oral bioavailability of fenofibrate, which requires further in vivo studies.
  11. Opening eyes to therapeutic perspectives of bioactive polyphenols and their nanoformulations against diabetic neuropathy and related complications
    Khursheed R, Singh SK, Wadhwa S, Gulati M, Kapoor B, Awasthi A, et al.
    Expert Opin Drug Deliv, 2021 04;18(4):427-448.
    PMID: 33356647 DOI: 10.1080/17425247.2021.1846517
    Introduction: Diabetic neuropathy (DN) is one of the major complications arising from hyperglycaemia in diabetic patients. In recent years polyphenols present in plants have gained attention to treat DN. The main advantages associated with them are their action via different molecular pathways to manage DN and their safety. However, they failed to gain clinical attention due to challenges associated with their formulation development such as lipophilicity,poor bioavailability, rapid systemic elimination, and enzymatic degradation.Area covered: This article includes different polyphenols that have shown their potential against DN in preclinical studies and the research carried out towards development of their nanoformulations in order to overcome aforementioned issues.Expert opinion: In this review various polyphenol based nanoformulations such as nanospheres, self-nanoemulsifying drug delivery systems, niosomes, electrospun nanofibers, metallic nanoparticles explored exclusively to treat DN are discussed. However, the literature available related to polyphenol based nanoformulations to treat DN is limited. Moreover, these experiments are limited to preclinical studies. Hence, more focus is required towards  development of nanoformulations using simple and single step process as well as inexpensive and non-toxic excipients so that a stable, scalable, reproducible and non-toxic formulation could be achieved and clinical trials could be initiated.
  12. Recent updates on animal models for understanding the etiopathogenesis of polycystic ovarian syndrome
    Corrie L, Gulati M, Singh SK, Kapoor B, Khursheed R, Awasthi A, et al.
    Life Sci, 2021 Sep 01;280:119753.
    PMID: 34171379 DOI: 10.1016/j.lfs.2021.119753
    Polycystic ovarian syndrome (PCOS) is the primary cause of female infertility affecting several women worldwide. Changes in hormonal functions such as hyperandrogenism are considered a significant factor in developing PCOS in women. In addition, many molecular pathways are involved in the pathogenesis of PCOS in women. To have better insights about PCOS, it is data from clinical studies carried on women suffering from PCOS should be collected. However, this approach has several implications, including ethical considerations, cost involved and availability of subject. Moreover, during the early drug development process, it is always advisable to use non-human models mimicking human physiology as they are less expensive, readily available, have a shorter gestation period and less risk involved. Many animal models have been reported that resemble the PCOS pathways in human subjects. However, the models developed on rats and mice are more preferred over other rodent/non-rodent models due to their closer resemblance with human PCOS development mechanism. The most extensively reported PCOS models for rats and mice include those induced by using testosterone, letrozole and estradiol valerate. As the pathophysiology of PCOS is complex, none of the explored models completely surrogates the PCOS related conditions occurring in women. Hence, there is a need to develop an animal model that can resemble the pathophysiology of PCOS in women. The review focuses on various animal models explored to understand the pathophysiology of PCOS. The article also highlights some environmental and food-related models that have been used to induce PCOS.
  13. Harnessing amphiphilic polymeric micelles for diagnostic and therapeutic applications: Breakthroughs and bottlenecks
    Kaur J, Mishra V, Singh SK, Gulati M, Kapoor B, Chellappan DK, et al.
    J Control Release, 2021 06 10;334:64-95.
    PMID: 33887283 DOI: 10.1016/j.jconrel.2021.04.014
    Amphiphilic block copolymers are widely utilized in the design of formulations owing to their unique physicochemical properties, flexible structures and functional chemistry. Amphiphilic polymeric micelles (APMs) formed from such copolymers have gained attention of the drug delivery scientists in past few decades for enhancing the bioavailability of lipophilic drugs, molecular targeting, sustained release, stimuli-responsive properties, enhanced therapeutic efficacy and reducing drug associated toxicity. Their properties including ease of surface modification, high surface area, small size, and enhanced permeation as well as retention (EPR) effect are mainly responsible for their utilization in the diagnosis and therapy of various diseases. However, some of the challenges associated with their use are premature drug release, low drug loading capacity, scale-up issues and their poor stability that need to be addressed for their wider clinical utility and commercialization. This review describes comprehensively their physicochemical properties, various methods of preparation, limitations followed by approaches employed for the development of optimized APMs, the impact of each preparation technique on the physicochemical properties of the resulting APMs as well as various biomedical applications of APMs. Based on the current scenario of their use in treatment and diagnosis of diseases, the directions in which future studies need to be carried out to explore their full potential are also discussed.
  14. Fulltext Calcium sensing receptor hyperactivation through viral envelop protein E of SARS CoV2: A novel target for cardio-renal damage in COVID-19 infection
    Singh Y, Ali H, Alharbi KS, Almalki WH, Kazmi I, Al-Abbasi FA, et al.
    Drug Dev Res, 2021 09;82(6):784-788.
    PMID: 33687087 DOI: 10.1002/ddr.21810
    Over the recent decades, a number of new pathogens have emerged within specific and diverse populations across the globe, namely, the Nipah virus, the Ebola virus, the Zika virus, and coronaviruses (CoVs) to name a few. Recently, a new form of coronavirus was identified in the city of Wuhan, China. Interestingly, the genomic architecture of the virus did not match with any of the existing genomic sequencing data of previously sequenced CoVs. This had led scientists to confirm the emergence of a new CoV strain. Originally, named as 2019-nCoV, the strain is now called as SARS-CoV-2. High serum levels of proinflammatory mediators, namely, interleukin-12 (IL-12), IL-1β, IL-6, interferon-gamma (IFNγ), chemoattractant protein-1, and IFN-inducible protein, have been repeatedly observed in subjects who were infected with this virus. In addition, the virus demonstrated strong coagulation activation properties, leading to further the understanding on the SARS-CoV2. To our understanding, these findings are unique to the published literature. Numerous studies have reported anomalies, namely, decline in the number of lymphocytes, platelets and albumins; and a rise in neutrophil count, aspartate transaminase, alanine aminotransaminase, lactate dehydrogenase, troponins, creatinine, complete bilirubin, D-dimers, and procalcitonin. Supplementation of calcium during the SARS CoV-2 associated hyperactive stage of calcium-sensing receptors (CaSR) may be harmful to the cardio-renal system. Thus, pharmacological inhibition of CaSR may prevent the increase in the levels of intracellular calcium, oxidative, inflammatory stress, and cardio-renal cellular apoptosis induced by high cytokines level in COVID-19 infection.
  15. Fulltext Advanced drug delivery systems can assist in targeting coronavirus disease (COVID-19): A hypothesis
    Mehta M, Prasher P, Sharma M, Shastri MD, Khurana N, Vyas M, et al.
    Med Hypotheses, 2020 Nov;144:110254.
    PMID: 33254559 DOI: 10.1016/j.mehy.2020.110254
    The highly contagious coronavirus, which had already affected more than 2 million people in 210 countries, triggered a colossal economic crisis consequently resulting from measures adopted by various goverments to limit transmission. This has placed the lives of many people infected worldwide at great risk. Currently there are no established or validated treatments for COVID-19, that is approved worldwide. Nanocarriers may offer a wide range of applications that could be developed into risk-free approaches for successful therapeutic strategies that may lead to immunisation against the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) which is the primary causative organism that had led to the current COVID-19 pandemic. We address existing as well as emerging therapeutic and prophylactic approaches that may enable us to effectively combat this pandemic, and also may help to identify the key areas where nano-scientists can step in.
  16. Fulltext Microfluidic chips: recent advances, critical strategies in design, applications and future perspectives
    Pattanayak P, Singh SK, Gulati M, Vishwas S, Kapoor B, Chellappan DK, et al.
    Microfluid Nanofluidics, 2021;25(12):99.
    PMID: 34720789 DOI: 10.1007/s10404-021-02502-2
    Microfluidic chip technology is an emerging tool in the field of biomedical application. Microfluidic chip includes a set of groves or microchannels that are engraved on different materials (glass, silicon, or polymers such as polydimethylsiloxane or PDMS, polymethylmethacrylate or PMMA). The microchannels forming the microfluidic chip are interconnected with each other for desired results. This organization of microchannels trapped into the microfluidic chip is associated with the outside by inputs and outputs penetrating through the chip, as an interface between the macro- and miniature world. With the help of a pump and a chip, microfluidic chip helps to determine the behavioral change of the microfluids. Inside the chip, there are microfluidic channels that permit the processing of the fluid, for example, blending and physicochemical responses. Microfluidic chip has numerous points of interest including lesser time and reagent utilization and alongside this, it can execute numerous activities simultaneously. The miniatured size of the chip fastens the reaction as the surface area increases. It is utilized in different biomedical applications such as food safety sensing, peptide analysis, tissue engineering, medical diagnosis, DNA purification, PCR activity, pregnancy, and glucose estimation. In the present study, the design of various microfluidic chips has been discussed along with their biomedical applications.
  17. Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro
    Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al.
    Life Sci, 2021 Jul 01;276:119436.
    PMID: 33789146 DOI: 10.1016/j.lfs.2021.119436
    Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.
  18. Perspectives and advancements in the design of nanomaterials for targeted cancer theranostics
    Tan YY, Yap PK, Xin Lim GL, Mehta M, Chan Y, Ng SW, et al.
    Chem Biol Interact, 2020 Sep 25;329:109221.
    PMID: 32768398 DOI: 10.1016/j.cbi.2020.109221
    Cancer continues to be one of the most challenging diseases to be treated and is one of the leading causes of deaths around the globe. Cancers account for 13% of all deaths each year, with cancer-related mortality expected to rise to 13.1 million by the year 2030. Although, we now have a large library of chemotherapeutic agents, the problem of non-selectivity remains the biggest drawback, as these substances are toxic not only to cancerous cells, but also to other healthy cells in the body. The limitations with chemotherapy and radiation have led to the discovery and development of novel strategies for safe and effective treatment strategies to manage the menace of cancer. Researchers have long justified and have shed light on the emergence of nanotechnology as a potential area for cancer therapy and diagnostics, whereby, nanomaterials are used primarily as nanocarriers or as delivery agents for anticancer drugs due to their tumor targeting properties. Furthermore, nanocarriers loaded with chemotherapeutic agents also overcome biological barriers such as renal and hepatic clearances, thus improving therapeutic efficacy with lowered morbidity. Theranostics, which is the combination of rationally designed nanomaterials with cancer-targeting moieties, along with protective polymers and imaging agents has become one of the core keywords in cancer research. In this review, we have highlighted the potential of various nanomaterials for their application in cancer therapy and imaging, including their current state and clinical prospects. Theranostics has successfully paved a path to a new era of drug design and development, in which nanomaterials and imaging contribute to a large variety of cancer therapies and provide a promising future in the effective management of various cancers. However, in order to meet the therapeutic needs, theranostic nanomaterials must be designed in such a way, that take into account the pharmacokinetic and pharmacodynamics properties of the drug for the development of effective carcinogenic therapy.
  19. Anti-inflammatory and anticancer activities of Naringenin-loaded liquid crystalline nanoparticles in vitro
    Wadhwa R, Paudel KR, Chin LH, Hon CM, Madheswaran T, Gupta G, et al.
    J Food Biochem, 2021 01;45(1):e13572.
    PMID: 33249629 DOI: 10.1111/jfbc.13572
    In this study, we had developed Naringenin-loaded liquid crystalline nanoparticles (LCNs) and investigated the anti-inflammatory and anticancer activities of Naringenin-LCNs against human airway epithelium-derived basal cells (BCi-NS1.1) and human lung epithelial carcinoma (A549) cell lines, respectively. The anti-inflammatory potential of Naringenin-LCNs evaluated by qPCR revealed a decreased expression of IL-6, IL-8, IL-1β, and TNF-α in lipopolysaccharide-induced BCi-NS1.1 cells. The activity of LCNs was comparable to the positive control drug Fluticasone propionate (10 nM). The anticancer activity was studied by evaluating the antiproliferative (MTT and trypan blue assays), antimigratory (scratch wound healing assay, modified Boyden chamber assay, and immunoblot), and anticolony formation activity in A549 cells. Naringenin LCNs showed promising antiproliferative, antimigratory, and anticolony formation activities in A549 cells, in vitro. Therefore, based on our observations and results, we conclude that Naringenin-LCNs may be employed as a potential therapy-based intervention to ameliorate airway inflammation and to inhibit the progression of lung cancer. PRACTICAL APPLICATIONS: Naringenin was encapsulated into liquid crystalline nanoparticles, thus, attributing to their sustained-release nature. In addition, Naringenin-loaded LCNs efficiently reduced the levels of pro-inflammatory markers, namely, IL-1β, IL-6, TNF-α, and IL-8. In addition, the Naringenin-loaded LCNs also possess potent anticancer activity, when tested in the A549 cell line, as revealed by the inhibition of proliferation and migration of cells. They also attenuated colony formation and induced apoptosis in the A549 cells. The findings from our study could form the basis for future research that may be translated into an in vivo model to validate the possible therapeutic alternative for lung cancer using Naringenin-loaded LCNs. In addition, the applications of Naringenin-loaded LCNs as an intervention would be of great interest to biological, formulation and respiratory scientists and clinicians.
  20. Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities
    Lee LY, Hew GSY, Mehta M, Shukla SD, Satija S, Khurana N, et al.
    Life Sci, 2021 Feb 15;267:118973.
    PMID: 33400932 DOI: 10.1016/j.lfs.2020.118973
    Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.
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