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  1. Fulltext Middle East Respiratory Syndrome (MERS) Virus-Pathophysiological Axis and the Current Treatment Strategies
    Alnuqaydan AM, Almutary AG, Sukamaran A, Yang BTW, Lee XT, Lim WX, et al.
    AAPS PharmSciTech, 2021 Jun 08;22(5):173.
    PMID: 34105037 DOI: 10.1208/s12249-021-02062-2
    Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.
  2. Fulltext Preclinical Models for Alzheimer's Disease: Past, Present, and Future Approaches
    Akhtar A, Gupta SM, Dwivedi S, Kumar D, Shaikh MF, Negi A
    ACS Omega, 2022 Dec 27;7(51):47504-47517.
    PMID: 36591205 DOI: 10.1021/acsomega.2c05609
    A robust preclinical disease model is a primary requirement to understand the underlying mechanisms, signaling pathways, and drug screening for human diseases. Although various preclinical models are available for several diseases, clinical models for Alzheimer's disease (AD) remain underdeveloped and inaccurate. The pathophysiology of AD mainly includes the presence of amyloid plaques and neurofibrillary tangles (NFT). Furthermore, neuroinflammation and free radical generation also contribute to AD. Currently, there is a wide gap in scientific approaches to preventing AD progression. Most of the available drugs are limited to symptomatic relief and improve deteriorating cognitive functions. To mimic the pathogenesis of human AD, animal models like 3XTg-AD and 5XFAD are the primarily used mice models in AD therapeutics. Animal models for AD include intracerebroventricular-streptozotocin (ICV-STZ), amyloid beta-induced, colchicine-induced, etc., focusing on parameters such as cognitive decline and dementia. Unfortunately, the translational rate of the potential drug candidates in clinical trials is poor due to limitations in imitating human AD pathology in animal models. Therefore, the available preclinical models possess a gap in AD modeling. This paper presents an outline that critically assesses the applicability and limitations of the current approaches in disease modeling for AD. Also, we attempted to provide key suggestions for the best-fit model to evaluate potential therapies, which might improve therapy translation from preclinical studies to patients with AD.
  3. Fulltext Advances in Lung Cancer Treatment Using Nanomedicines
    Sharma A, Shambhwani D, Pandey S, Singh J, Lalhlenmawia H, Kumarasamy M, et al.
    ACS Omega, 2023 Jan 10;8(1):10-41.
    PMID: 36643475 DOI: 10.1021/acsomega.2c04078
    Carcinoma of the lungs is among the most menacing forms of malignancy and has a poor prognosis, with a low overall survival rate due to delayed detection and ineffectiveness of conventional therapy. Therefore, drug delivery strategies that may overcome undesired damage to healthy cells, boost therapeutic efficacy, and act as imaging tools are currently gaining much attention. Advances in material science have resulted in unique nanoscale-based theranostic agents, which provide renewed hope for patients suffering from lung cancer. Nanotechnology has vastly modified and upgraded the existing techniques, focusing primarily on increasing bioavailability and stability of anti-cancer drugs. Nanocarrier-based imaging systems as theranostic tools in the treatment of lung carcinoma have proven to possess considerable benefits, such as early detection and targeted therapeutic delivery for effectively treating lung cancer. Several variants of nano-drug delivery agents have been successfully studied for therapeutic applications, such as liposomes, dendrimers, polymeric nanoparticles, nanoemulsions, carbon nanotubes, gold nanoparticles, magnetic nanoparticles, solid lipid nanoparticles, hydrogels, and micelles. In this Review, we present a comprehensive outline on the various types of overexpressed receptors in lung cancer, as well as the various targeting approaches of nanoparticles.
  4. Multinuclear MR and multilevel data processing: an insight into morphologic assessment of in vivo knee articular cartilage
    Hani AF, Kumar D, Malik AS, Walter N, Razak R, Kiflie A
    Acad Radiol, 2015 Jan;22(1):93-104.
    PMID: 25481518 DOI: 10.1016/j.acra.2014.08.008
    Quantitative assessment of knee articular cartilage (AC) morphology using magnetic resonance (MR) imaging requires an accurate segmentation and 3D reconstruction. However, automatic AC segmentation and 3D reconstruction from hydrogen-based MR images alone is challenging because of inhomogeneous intensities, shape irregularity, and low contrast existing in the cartilage region. Thus, the objective of this research was to provide an insight into morphologic assessment of AC using multilevel data processing of multinuclear ((23)Na and (1)H) MR knee images.
  5. Fulltext Phytochemistry and pharmacological activity of the genus artemisia
    Bisht D, Kumar D, Kumar D, Dua K, Chellappan DK
    Arch Pharm Res, 2021 May;44(5):439-474.
    PMID: 33893998 DOI: 10.1007/s12272-021-01328-4
    Artemisia and its allied species have been employed for conventional medicine in the Northern temperate regions of North America, Europe, and Asia for the treatments of digestive problems, morning sickness, irregular menstrual cycle, typhoid, epilepsy, renal problems, bronchitis malaria, etc. The multidisciplinary use of artemisia species has various other health benefits that are related to its traditional and modern pharmaceutical perspectives. The main objective of this review is to evaluate the traditional, modern, biological as well as pharmacological use of the essential oil and herbal extracts of Artemisia nilagirica, Artemisia parviflora, and other allied species of Artemisia. It also discusses the botanical circulation and its phytochemical constituents viz disaccharides, polysaccharides, glycosides, saponins, terpenoids, flavonoids, and carotenoids. The plants have different biological importance like antiparasitic, antimalarial, antihyperlipidemic, antiasthmatic, antiepileptic, antitubercular, antihypertensive, antidiabetic, anxiolytic, antiemetic, antidepressant, anticancer, hepatoprotective, gastroprotective, insecticidal, antiviral activities, and also against COVID-19. Toxicological studies showed that the plants at a low dose and short duration are non or low-toxic. In contrast, a high dose at 3 g/kg and for a longer duration can cause toxicity like rapid respiration, neurotoxicity, reproductive toxicity, etc. However, further in-depth studies are needed to determine the medicinal uses, clinical efficacy and safety are crucial next steps.
  6. Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
    Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  7. Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1
    Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
  8. Exploring the therapeutic potential of naturally occurring piceatannol in non-communicable diseases
    Gandhi H, Mahant S, Sharma AK, Kumar D, Dua K, Chellappan DK, et al.
    Biofactors, 2024;50(2):232-249.
    PMID: 37702264 DOI: 10.1002/biof.2009
    Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.
  9. Fulltext Effect of Cu Doping on ZnO Nanoparticles as a Photocatalyst for the Removal of Organic Wastewater
    Khalid A, Ahmad P, Khan A, Muhammad S, Khandaker MU, Alam MM, et al.
    Bioinorg Chem Appl, 2022;2022:9459886.
    PMID: 35873731 DOI: 10.1155/2022/9459886
    Environmental problems with chemical and biological water pollution have become a major concern for society. Providing people with safe and affordable water is a grand challenge of the 21st century. The study investigates the photocatalytic degradation capabilities of hydrothermally prepared pure and Cu-doped ZnO nanoparticles (NPs) for the elimination of dye pollutants. A simple, cost-effective hydrothermal process is employed to synthesize the Cu-doped ZnO NPs. The photocatalytic dye degradation activity of the synthesized Cu-doped ZnO NPs is tested by using methylene blue (MB) dye. In addition, the parameters that affect photodegradation efficiency, such as catalyst concentration, starting potential of hydrogen (pH), and dye concentration, were also assessed. The dye degradation is found to be directly proportional to the irradiation time, as 94% of the MB dye is degraded in 2 hrs. Similarly, the dye degradation shows an inverse relation to the MB dye concentration, as the degradation reduced from 94% to 20% when the MB concentration increases from 5 ppm to 80 ppm. The synthesized cost-effective and environmentally friendly Cu-doped ZnO NPs exhibit improved photocatalytic activity against MB dye and can therefore be employed in wastewater treatment materials.
  10. Fulltext Impacting clinical evaluation of anterior talofibular ligament injuries through analysis of ultrasound images
    Singh V, Elamvazuthi I, Jeoti V, George J, Swain A, Kumar D
    Biomed Eng Online, 2016;15:13.
    PMID: 26838596 DOI: 10.1186/s12938-016-0129-6
    Anterior talofibular ligament (ATFL) is considered as the weakest ankle ligament that is most prone to injuries. Ultrasound imaging with its portable, non-invasive and non-ionizing radiation nature is increasingly being used for ATFL diagnosis. However, diagnosis of ATFL injuries requires its segmentation from ultrasound images that is a challenging task due to the existence of homogeneous intensity regions, homogeneous textures and low contrast regions in ultrasound images. To address these issues, this research has developed an efficient ATFL segmentation framework that would contribute to accurate and efficient diagnosis of ATFL injuries for clinical evaluation.
  11. The role of conductive nanoparticles in anaerobic digestion: Mechanism, current status and future perspectives
    Kumar SS, Ghosh P, Kataria N, Kumar D, Thakur S, Pathania D, et al.
    Chemosphere, 2021 Oct;280:130601.
    PMID: 33945900 DOI: 10.1016/j.chemosphere.2021.130601
    In the current scenario, alternative energy sources are the need of the hour. Organic wastes having a larger fraction of biodegradable constituents present a sustainable bioenergy source. It has been reported that the calorific value of biogas generated by anaerobic digestion (AD) is 21-25 MJ/m3 with the treatment which makes it an excellent replacement of natural gas and fossil fuels and can reduce more than 80% greenhouse gas emission to the surroundings. However, there are some limitations associated with the AD process for instance ammonia build-up at the first stage reduces the rate of hydrolysis of biomass, whereas, in the last stage it interferes with methane formation. Owing to special physicochemical properties such as high activity, high reactive surface area, and high specificity, tailor-made conductive nanoparticles can improve the performance of the AD process. In the AD process, H2 is used as an electron carrier, referred as mediated interspecies electron transfer (MIET). Due to the diffusion limitation of these electron carriers, the MIET efficiency is relatively low that limits the methanogenesis. Direct interspecies electron transfer (DIET), which enables direct cell-to-cell electron transport between bacteria and methanogen, has been considered an alternative efficient approach to MIET that creates metabolically favorable conditions and results in faster conversion of organic acids and alcohols into methane. This paper discusses in detail the application of conductive nanoparticles to enhance the AD process efficiency. Interaction between microbes in anaerobic conditions for electron transfer with the help of CNPs is discussed. Application of a variety of conductive nanomaterials as an additive is discussed with their potential biogas production and treatment enhancement in the anaerobic digestion process.
  12. Fully automated subchondral bone segmentation from knee MR images: Data from the Osteoarthritis Initiative
    Gandhamal A, Talbar S, Gajre S, Razak R, Hani AFM, Kumar D
    Comput Biol Med, 2017 Sep 01;88:110-125.
    PMID: 28711767 DOI: 10.1016/j.compbiomed.2017.07.008
    Knee osteoarthritis (OA) progression can be monitored by measuring changes in the subchondral bone structure such as area and shape from MR images as an imaging biomarker. However, measurements of these minute changes are highly dependent on the accurate segmentation of bone tissue from MR images and it is challenging task due to the complex tissue structure and inadequate image contrast/brightness. In this paper, a fully automated method for segmenting subchondral bone from knee MR images is proposed. Here, the contrast of knee MR images is enhanced using a gray-level S-curve transformation followed by automatic seed point detection using a three-dimensional multi-edge overlapping technique. Successively, bone regions are initially extracted using distance-regularized level-set evolution followed by identification and correction of leakages along the bone boundary regions using a boundary displacement technique. The performance of the developed technique is evaluated against ground truths by measuring sensitivity, specificity, dice similarity coefficient (DSC), average surface distance (AvgD) and root mean square surface distance (RMSD). An average sensitivity (91.14%), specificity (99.12%) and DSC (90.28%) with 95% confidence interval (CI) in the range 89.74-92.54%, 98.93-99.31% and 88.68-91.88% respectively is achieved for the femur bone segmentation in 8 datasets. For tibia bone, average sensitivity (90.69%), specificity (99.65%) and DSC (91.35%) with 95% CI in the range 88.59-92.79%, 99.50-99.80% and 88.68-91.88% respectively is achieved. AvgD and RMSD values for femur are 1.43 ± 0.23 (mm) and 2.10 ± 0.35 (mm) respectively while for tibia, the values are 0.95 ± 0.28 (mm) and 1.30 ± 0.42 (mm) respectively that demonstrates acceptable error between proposed method and ground truths. In conclusion, results obtained in this work demonstrate substantially significant performance with consistency and robustness that led the proposed method to be applicable for large scale and longitudinal knee OA studies in clinical settings.
  13. Local gray level S-curve transformation - A generalized contrast enhancement technique for medical images
    Gandhamal A, Talbar S, Gajre S, Hani AF, Kumar D
    Comput Biol Med, 2017 04 01;83:120-133.
    PMID: 28279861 DOI: 10.1016/j.compbiomed.2017.03.001
    Most medical images suffer from inadequate contrast and brightness, which leads to blurred or weak edges (low contrast) between adjacent tissues resulting in poor segmentation and errors in classification of tissues. Thus, contrast enhancement to improve visual information is extremely important in the development of computational approaches for obtaining quantitative measurements from medical images. In this research, a contrast enhancement algorithm that applies gray-level S-curve transformation technique locally in medical images obtained from various modalities is investigated. The S-curve transformation is an extended gray level transformation technique that results into a curve similar to a sigmoid function through a pixel to pixel transformation. This curve essentially increases the difference between minimum and maximum gray values and the image gradient, locally thereby, strengthening edges between adjacent tissues. The performance of the proposed technique is determined by measuring several parameters namely, edge content (improvement in image gradient), enhancement measure (degree of contrast enhancement), absolute mean brightness error (luminance distortion caused by the enhancement), and feature similarity index measure (preservation of the original image features). Based on medical image datasets comprising 1937 images from various modalities such as ultrasound, mammograms, fluorescent images, fundus, X-ray radiographs and MR images, it is found that the local gray-level S-curve transformation outperforms existing techniques in terms of improved contrast and brightness, resulting in clear and strong edges between adjacent tissues. The proposed technique can be used as a preprocessing tool for effective segmentation and classification of tissue structures in medical images.
  14. The Potential of Mur Enzymes as Targets for Antimicrobial Drug Discovery
    Kumar D, Sarkar N, Roy KK, Bisht D, Kumar D, Mandal B, et al.
    Curr Drug Targets, 2023;24(8):627-647.
    PMID: 37291783 DOI: 10.2174/1389450124666230608150759
    The extensive development in the strains of resistant bacteria is a potential hazard to public health worldwide. This necessitates the development of newer agents with the antibacterial property having new mechanisms of action. Mur enzymes catalyze the steps related to the biosynthesis of peptidoglycan, which constitutes a major part of the cell wall in bacteria. Peptidoglycan increases the stiffness of the cell wall, helping it to survive in unfavorable conditions. Therefore, the inhibition of Mur enzymes may lead to novel antibacterial agents that may help in controlling or overcoming bacterial resistance. Mur enzymes are classified into MurA, MurB, MurC, MurD, MurE, and MurF. Until-date, multiple inhibitors are reported for each class of the Mur enzymes. In this review, we have summarized the development of Mur enzyme inhibitors as antibacterial agents in the last few decades.
  15. Role of Flavonoids in Management of Various Biological Targets in Alzheimer's Disease: Evidence from Preclinical to Clinical Studies
    Alharbi KS, Javed Shaikh MA, Imam SS, Alshehri S, Ghoneim MM, Almalki WH, et al.
    Curr Med Chem, 2023;30(18):2061-2074.
    PMID: 36415096 DOI: 10.2174/0929867330666221122115212
    More than 10 million people worldwide have Alzheimer's disease (AD), a degenerative neurological illness and the most prevalent form of dementia. AD's progression in memory loss, cognitive deterioration, and behavioral changes are all symptoms. Amyloid-beta 42 (Aβ42), the hyperphosphorylated forms of microtubule-associated tau protein, and other cellular and systemic alterations are all factors that contribute to cognitive decline in AD. Rather than delivering a possible cure, present therapy strategies focus on reducing disease symptoms. It has long been suggested that various naturally occurring small molecules (plant extract products and microbiological isolates, for example) could be beneficial in preventing or treating disease. Small compounds, such as flavonoids, have attracted much interest recently due to their potential to alleviate cellular stress. Flavonoids have been proven helpful in various ways, including antioxidants, anti-inflammatory agents, and anti-apoptotic agents, but their mechanism remains unknown. The flavonoid therapy of Alzheimer's disease focuses on this review, which includes a comprehensive literature analysis.
  16. Managing Apoptosis in Lung Diseases using Nano-assisted Drug Delivery System
    Shukla MK, Dubey A, Pandey S, Singh SK, Gupta G, Prasher P, et al.
    Curr Pharm Des, 2022;28(39):3202-3211.
    PMID: 35422206 DOI: 10.2174/1381612828666220413103831
    Several factors exist that limit the efficacy of lung cancer treatment. These may be tumor-specific delivery of therapeutics, airway geometry, humidity, clearance mechanisms, presence of lung diseases, and therapy against tumor cell resistance. Advancements in drug delivery using nanotechnology based multifunctional nanocarriers, have emerged as a viable method for treating lung cancer with more efficacy and fewer adverse effects. This review does a thorough and critical examination of effective nano-enabled approaches for lung cancer treatment, such as nano-assisted drug delivery systems. In addition, to therapeutic effectiveness, researchers have been working to determine several strategies to produce nanotherapeutics by adjusting the size, drug loading, transport, and retention. Personalized lung tumor therapies using sophisticated nano modalities have the potential to provide great therapeutic advantages based on individual unique genetic markers and disease profiles. Overall, this review provides comprehensive information on newer nanotechnological prospects for improving the management of apoptosis in lung cancer.
  17. Microbubbles: Revolutionizing Biomedical Applications with Tailored Therapeutic Precision
    Kumar M, Kumar D, Chopra S, Mahmood S, Bhatia A
    Curr Pharm Des, 2023;29(44):3532-3545.
    PMID: 38151837 DOI: 10.2174/0113816128282478231219044000
    BACKGROUND: Over the past ten years, tremendous progress has been made in microbubble-based research for a variety of biological applications. Microbubbles emerged as a compelling and dynamic tool in modern drug delivery systems. They are employed to deliver drugs or genes to targeted regions of interest, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials.

    OBJECTIVE: The objective of this article is to review the microbubble compositions and physiochemical characteristics in relation to the development of innovative biomedical applications, with a focus on molecular imaging and targeted drug/gene delivery.

    METHODS: The microbubbles are prepared by using various methods, which include cross-linking polymerization, emulsion solvent evaporation, atomization, and reconstitution. In cross-linking polymerization, a fine foam of the polymer is formed, which serves as a bubble coating agent and colloidal stabilizer, resulting from the vigorous stirring of a polymeric solution. In the case of emulsion solvent evaporation, there are two solutions utilized in the production of microbubbles. In atomization and reconstitution, porous spheres are created by atomising a surfactant solution into a hot gas. They are encapsulated in primary modifier gas. After the addition of the second gas or gas osmotic agent, the package is placed into a vial and sealed after reconstituting with sterile saline solution.

    RESULTS: Microbubble-based drug delivery is an innovative approach in the field of drug delivery that utilizes microbubbles, which are tiny gas-filled bubbles, act as carriers for therapeutic agents. These microbubbles can be loaded with drugs, imaging agents, or genes and then guided to specific target sites.

    CONCLUSION: The potential utility of microbubbles in biomedical applications is continually growing as novel formulations and methods. The versatility of microbubbles allows for customization, tailoring the delivery system to various medical applications, including cancer therapy, cardiovascular treatments, and gene therapy.

  18. Unravelling the molecular mechanisms underlying chronic respiratory diseases for the development of novel therapeutics via in vitro experimental models
    Tan CL, Chan Y, Candasamy M, Chellian J, Madheswaran T, Sakthivel LP, et al.
    Eur J Pharmacol, 2022 Feb 11;919:174821.
    PMID: 35151643 DOI: 10.1016/j.ejphar.2022.174821
    Chronic respiratory diseases have collectively become a major public health concern and have now taken form as one of the leading causes of mortality worldwide. Most chronic respiratory diseases primarily occur due to prolonged airway inflammation. In addition, critical environmental factors such as cigarette smoke, industrial pollutants, farm dust, and pollens may also exacerbate such diseases. Moreover, alterations in the genetic sequence of an individual, abnormalities in the chromosomes or immunosuppression resulting from bacterial, fungal, and viral infections may also play a key role in the pathogenesis of respiratory diseases. Over the years, multiple in vitro models have been employed as the basis of existing as well as emerging advancements in chronic respiratory disease research. These include cell lines, gene expression techniques, single cell RNA sequencing, cytometry, culture techniques, as well as serum/sputum biomarkers that can be used to elucidate the molecular mechanisms underlying these diseases, and to identify novel diagnostic and management options for these diseases. This review summarizes the current understanding of the pathogenesis of various chronic respiratory diseases derived through in vitro experimental models, where the knowledge obtained from these studies can greatly benefit researchers in the discovery and development of novel screening techniques and advanced therapeutic strategies that could be translated into clinical use in the future.
  19. Age-related rarefaction in retinal vasculature is not linear
    Che Azemin MZ, Ab Hamid F, Aminuddin A, Wang JJ, Kawasaki R, Kumar DK
    Exp Eye Res, 2013 Nov;116:355-358.
    PMID: 24512773 DOI: 10.1016/j.exer.2013.10.010
    The fractal dimension is a global measure of complexity and is useful for quantifying anatomical structures, including the retinal vascular network. A previous study found a linear declining trend with aging on the retinal vascular fractal dimension (DF); however, it was limited to the older population (49 years and older). This study aimed to investigate the possible models of the fractal dimension changes from young to old subjects (10-73 years). A total of 215 right-eye retinal samples, including those of 119 (55%) women and 96 (45%) men, were selected. The retinal vessels were segmented using computer-assisted software, and non-vessel fragments were deleted. The fractal dimension was measured based on the log-log plot of the number of grids versus the size. The retinal vascular DF was analyzed to determine changes with increasing age. Finally, the data were fitted to three polynomial models. All three models are statistically significant (Linear: R2 = 0.1270, 213 d.f., p 
  20. Fulltext Inhibitory activity of Enhydra fluctuans Lour. on calcium oxalate crystallisation through in silico and in vitro studies
    Chattaraj B, Nandi A, Das A, Sharma A, Dey YN, Kumar D, et al.
    Front Pharmacol, 2022;13:982419.
    PMID: 36744215 DOI: 10.3389/fphar.2022.982419
    The decoction of the whole plant of Enhydra fluctuans is used ethno medicinally by various tribes for the treatment of kidney stones and urinary problems. However, no scientific studies were carried out to delineate its influence on urinary stone formation and crystallisation. Hence, the present study is proposed to investigate the effect of the aqueous extract of Enhydra fluctuans extract on in vitro crystallisation of calcium oxalate. The present study also evaluated. in silico studies of the metabolites with the target proteins present in the renal calcium oxalate stone matrix. The plant material was subjected to decoction to obtain an aqueous extract. The effect of the extract on calcium oxalate crystallization was evaluated by in vitro nucleation and aggregation assays. Further, the metabolites present in E. fluctuans were mined from the existing literature and their number was found to be 35. The selected 35 metabolites of E. fluctuans were subjected to molecular docking with the 5 proteins which are known to be responsible for calcium oxalate crystal growth. Results of in vitro studies indicated that the extract (50, 100, and 200 μg/mL) and standard drug cystone (1,000 μg/mL) exhibited an inhibitory role in the nucleation process where the percentage inhibitions were 52.69, 43.47, 21.98, and 31.67 μg/mL respectively. The results of molecular docking studies revealed that 2 out of 35 metabolites i.e. Baicalein-7-O-diglucoside and 4',5,6,7-Tetrahydroxy-8-methoxy isoflavone-7-O-beta-D- galactopyranosyl-(1→3)-O-beta-D-xylopyranosyl-(1→4)- O-alpha-L-rhamnopyranoside showed modulatory effects on the four renal stone matrix-associated protein (Human CTP: Phosphoethanolamine Cytidylyltransferase (Protein Data Bank ID: 3ELB), UDP glucose: glycoprotein glucosyltransferase 2 (Gene: UGGT2) (AlphaFold) and RIMS-binding protein 3A (Gene: RIMBP3) (AlphaFold), and Ras GTPase activating-like protein (PDB: 3FAY) based on their docking scores which indicates that they may inhibit the crystallization process. Findings from this study show that Enhydra fluctuans may be effective in the prevention of the crystallization of calcium oxalate. However, further, in vivo studies as well as molecular studies are needed to be conducted to confirm and strengthen its anti-urolithiatic activity and to elucidate the possible mechanism of action involved therein.
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