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  1. 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
  2. Plant Bioactive Peptides: Current Status and Prospects Towards Use on Human Health
    Chai TT, Ee KY, Kumar DT, Manan FA, Wong FC
    Protein Pept Lett, 2021;28(6):623-642.
    PMID: 33319654 DOI: 10.2174/0929866527999201211195936
    Large numbers of bioactive peptides with potential applications in protecting against human diseases have been identified from plant sources. In this review, we summarized recent progress in the research of plant-derived bioactive peptides, encompassing their production, biological effects, and mechanisms. This review focuses on antioxidant, antimicrobial, antidiabetic, and anticancer peptides, giving special attention to evidence derived from cellular and animal models. Studies investigating peptides with known sequences and well-characterized peptidic fractions or protein hydrolysates will be discussed. The use of molecular docking tools to elucidate inter-molecular interactions between bioactive peptides and target proteins is highlighted. In conclusion, the accumulating evidence from in silico, in vitro and in vivo studies to date supports the envisioned applications of plant peptides as natural antioxidants as well as health-promoting agents. Notwithstanding, much work is still required before the envisioned applications of plant peptides can be realized. To this end, future researches for addressing current gaps were proposed.
  3. Fulltext MUSiC: a model-unspecific search for new physics in proton-proton collisions at s = 13 TeV
    CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, et al.
    Eur Phys J C Part Fields, 2021;81(7):629.
    PMID: 34727144 DOI: 10.1140/epjc/s10052-021-09236-z
    Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV , corresponding to an integrated luminosity of 35.9 fb - 1 , are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.
  4. Fulltext Search for dark matter produced in association with a leptonically decaying Z boson in proton-proton collisions at s = 13 Te
    Sirunyan AM, CMS Collaboration, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2021;81(1):13.
    PMID: 33493254 DOI: 10.1140/epjc/s10052-020-08739-5
    A search for dark matter particles is performed using events with a Z boson candidate and large missing transverse momentum. The analysis is based on proton-proton collision data at a center-of-mass energy of 13 Te , collected by the CMS experiment at the LHC in 2016-2018, corresponding to an integrated luminosity of 137 fb - 1 . The search uses the decay channels Z → e e and Z → μ μ . No significant excess of events is observed over the background expected from the standard model. Limits are set on dark matter particle production in the context of simplified models with vector, axial-vector, scalar, and pseudoscalar mediators, as well as on a two-Higgs-doublet model with an additional pseudoscalar mediator. In addition, limits are provided for spin-dependent and spin-independent scattering cross sections and are compared to those from direct-detection experiments. The results are also interpreted in the context of models of invisible Higgs boson decays, unparticles, and large extra dimensions.
  5. Fulltext Measurements of production cross sections of the Higgs boson in the four-lepton final state in proton-proton collisions at s = 13 TeV
    CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, et al.
    Eur Phys J C Part Fields, 2021;81(6):488.
    PMID: 34727143 DOI: 10.1140/epjc/s10052-021-09200-x
    Production cross sections of the Higgs boson are measured in the H → Z Z → 4 ℓ ( ℓ = e , μ ) decay channel. A data sample of proton-proton collisions at a center-of-mass energy of 13 TeV , collected by the CMS detector at the LHC and corresponding to an integrated luminosity of 137 fb - 1 is used. The signal strength modifier μ , defined as the ratio of the Higgs boson production rate in the 4 ℓ channel to the standard model (SM) expectation, is measured to be μ = 0.94 ± 0.07 (stat) - 0.08 + 0.09 (syst) at a fixed value of m H = 125.38 GeV . The signal strength modifiers for the individual Higgs boson production modes are also reported. The inclusive fiducial cross section for the H → 4 ℓ process is measured to be 2 . 84 - 0.22 + 0.23 (stat) - 0.21 + 0.26 (syst) fb , which is compatible with the SM prediction of 2.84 ± 0.15 fb for the same fiducial region. Differential cross sections as a function of the transverse momentum and rapidity of the Higgs boson, the number of associated jets, and the transverse momentum of the leading associated jet are measured. A new set of cross section measurements in mutually exclusive categories targeted to identify production mechanisms and kinematical features of the events is presented. The results are in agreement with the SM predictions.
  6. 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.
  7. Fulltext Emergence of taurine as a therapeutic agent for neurological disorders
    Jangra A, Gola P, Singh J, Gond P, Ghosh S, Rachamalla M, et al.
    Neural Regen Res, 2024 Jan;19(1):62-68.
    PMID: 37488845 DOI: 10.4103/1673-5374.374139
    Taurine is a sulfur-containing, semi-essential amino acid that occurs naturally in the body. It alternates between inflammation and oxidative stress-mediated injury in various disease models. As part of its limiting functions, taurine also modulates endoplasmic reticulum stress, Ca2+ homeostasis, and neuronal activity at the molecular level. Taurine effectively protects against a number of neurological disorders, including stroke, epilepsy, cerebral ischemia, memory dysfunction, and spinal cord injury. Although various therapies are available, effective management of these disorders remains a global challenge. Approximately 30 million people are affected worldwide. The design of taurine formation could lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders. The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review. This article is a good resource for understanding the general effects of taurine on various diseases. Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms, it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics, with emphasis on mechanism and clinical studies to determine efficacy.
  8. Fulltext Sensitivity and specificity of automated analysis of single-field non-mydriatic fundus photographs by Bosch DR Algorithm-Comparison with mydriatic fundus photography (ETDRS) for screening in undiagnosed diabetic retinopathy
    Bawankar P, Shanbhag N, K SS, Dhawan B, Palsule A, Kumar D, et al.
    PLoS One, 2017;12(12):e0189854.
    PMID: 29281690 DOI: 10.1371/journal.pone.0189854
    Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Early diagnosis through effective screening programs is likely to improve vision outcomes. The ETDRS seven-standard-field 35-mm stereoscopic color retinal imaging (ETDRS) of the dilated eye is elaborate and requires mydriasis, and is unsuitable for screening. We evaluated an image analysis application for the automated diagnosis of DR from non-mydriatic single-field images. Patients suffering from diabetes for at least 5 years were included if they were 18 years or older. Patients already diagnosed with DR were excluded. Physiologic mydriasis was achieved by placing the subjects in a dark room. Images were captured using a Bosch Mobile Eye Care fundus camera. The images were analyzed by the Retinal Imaging Bosch DR Algorithm for the diagnosis of DR. All subjects also subsequently underwent pharmacological mydriasis and ETDRS imaging. Non-mydriatic and mydriatic images were read by ophthalmologists. The ETDRS readings were used as the gold standard for calculating the sensitivity and specificity for the software. 564 consecutive subjects (1128 eyes) were recruited from six centers in India. Each subject was evaluated at a single outpatient visit. Forty-four of 1128 images (3.9%) could not be read by the algorithm, and were categorized as inconclusive. In four subjects, neither eye provided an acceptable image: these four subjects were excluded from the analysis. This left 560 subjects for analysis (1084 eyes). The algorithm correctly diagnosed 531 of 560 cases. The sensitivity, specificity, and positive and negative predictive values were 91%, 97%, 94%, and 95% respectively. The Bosch DR Algorithm shows favorable sensitivity and specificity in diagnosing DR from non-mydriatic images, and can greatly simplify screening for DR. This also has major implications for telemedicine in the use of screening for retinopathy in patients with diabetes mellitus.

    Study site: India
  9. Novel Nanostructured Lipid Carriers Co-Loaded with Mesalamine and Curcumin: Formulation, Optimization and In Vitro Evaluation
    Awasthi A, Kumar B, Gulati M, Vishwas S, Corrie L, Kaur J, et al.
    Pharm Res, 2022 Nov;39(11):2817-2829.
    PMID: 36195824 DOI: 10.1007/s11095-022-03401-z
    PURPOSE: The aim of current study is to formulate, optimize and characterize the developed formulation of Mesalamine-Curcumin Nanostructured Lipid Carriers (Mes-Cur NLCs).

    METHODS: It was formulated using high pressure homogenization followed by probe sonication and formulation variables were optimized using Central Composite Design. The particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug release, cytotoxicity on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells and efficacy on RAW264.7 cells for optimized formulation was determined.

    RESULTS: The PS, ZP and EE were found to be 85.26 nm, -23.7 ± 7.45 mV, 99.2 ± 2.62 % (Mes) and 84 ± 1.51 % (Cur), respectively. The good correlation between predicted and obtained value indicated suitability and reproducibility of experimental design. NLCs showed spherical shape as confirmed by TEM. In vitro drug release profile of prepared formulation showed that Mes exhibited 100 % release at 48 h, whereas Cur exhibited 82.23 ± 2.97% release at 120 h. Both the drugs exhibited sustained release upon incorporation into the NLCs. The absence of any significant cell death during MTT assay performed on NIH 3T3 fibroblasts cells and HaCaT keratinocytes cells indicated that NLCs' were safe for use. Furthermore, significant reduction in nitric oxide level during anti-inflammatory evaluation of formulation on RAW264.7 cells showed excellent potential for the formulation to treat inflammation. The formulation was found stable as no significant difference between the PS, ZP and EE of the fresh and aged NLCs was observed.

    CONCLUSION: The outcomes of study deciphered successful formulation of Mes-Cur NLCs.

  10. Unraveling the role of glial cell line-derived neurotrophic factor in the treatment of Parkinson's disease
    Kakoty V, Sarathlal KC, Kaur P, Wadhwa P, Vishwas S, Khan FR, et al.
    Neurol Sci, 2024 Apr;45(4):1409-1418.
    PMID: 38082050 DOI: 10.1007/s10072-023-07253-2
    Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.
  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. Fulltext Morphological diagnosis of hematologic malignancy using feature fusion-based deep convolutional neural network
    Yadav DP, Kumar D, Jalal AS, Kumar A, Singh KU, Shah MA
    Sci Rep, 2023 Oct 09;13(1):16988.
    PMID: 37813973 DOI: 10.1038/s41598-023-44210-7
    Leukemia is a cancer of white blood cells characterized by immature lymphocytes. Due to blood cancer, many people die every year. Hence, the early detection of these blast cells is necessary for avoiding blood cancer. A novel deep convolutional neural network (CNN) 3SNet that has depth-wise convolution blocks to reduce the computation costs has been developed to aid the diagnosis of leukemia cells. The proposed method includes three inputs to the deep CNN model. These inputs are grayscale and their corresponding histogram of gradient (HOG) and local binary pattern (LBP) images. The HOG image finds the local shape, and the LBP image describes the leukaemia cell's texture pattern. The suggested model was trained and tested with images from the AML-Cytomorphology_LMU dataset. The mean average precision (MAP) for the cell with less than 100 images in the dataset was 84%, whereas for cells with more than 100 images in the dataset was 93.83%. In addition, the ROC curve area for these cells is more than 98%. This confirmed proposed model could be an adjunct tool to provide a second opinion to a doctor.
  13. Fulltext Nipah virus infection: current scenario
    Kulkarni DD, Tosh C, Venkatesh G, Senthil Kumar D
    Indian J Virol, 2013 Dec;24(3):398-408.
    PMID: 24426305 DOI: 10.1007/s13337-013-0171-y
    The emergence of Nipah virus (NiV) infection into the pig population and subsequently into the human population is believed to be due to changes in ecological conditions. In Malaysia, A major NiV outbreak occurred in pigs and humans from September 1998 to April 1999 that resulted in infection of 265 and death of 105 persons. About 1.1 million pigs had to be destroyed to control the outbreak. The disease was recorded in the form of a major outbreak in India in 2001 and then a small incidence in 2007, both the outbreaks in West Bengal only in humans without any involvement of pigs. There were series of human Nipah incidences in Bangladesh from 2001 till 2013 almost every year with mortality exceeding 70 %. The disease transmission from pigs acting as an intermediate host during Malaysian and Singapore outbreaks has changed in NIV outbreaks in India and Bangladesh, transmitting the disease directly from bats to human followed by human to human. The drinking of raw date palm sap contaminated with fruit bat urine or saliva containing NiV is the only known cause of outbreak of the disease in Bangladesh outbreaks. The virus is now known to exist in various fruit bats of Pteropus as well as bats of other genera in a wider belt from Asia to Africa.
  14. Physiological assessment of in vivo human knee articular cartilage using sodium MR imaging at 1.5 T
    Hani AF, Kumar D, Malik AS, Razak R
    Magn Reson Imaging, 2013 Sep;31(7):1059-67.
    PMID: 23731535 DOI: 10.1016/j.mri.2013.01.007
    Osteoarthritis is a common joint disorder that is most prevalent in the knee joint. Knee osteoarthritis (OA) can be characterized by the gradual loss of articular cartilage (AC). Formation of lesion, fissures and cracks on the cartilage surface has been associated with degenerative AC and can be measured by morphological assessment. In addition, loss of proteoglycan from extracellular matrix of the AC can be measured at early stage of cartilage degradation by physiological assessment. In this case, a biochemical phenomenon of cartilage is used to assess the changes at early degeneration of AC. In this paper, a method to measure local sodium concentration in AC due to proteoglycan has been investigated. A clinical 1.5-T magnetic resonance imaging (MRI) with multinuclear spectroscopic facility is used to acquire sodium images and quantify local sodium content of AC. An optimised 3D gradient-echo sequence with low echo time has been used for MR scan. The estimated sodium concentration in AC region from four different data sets is found to be ~225±19mmol/l, which matches the values that has been reported for the normal AC. This study shows that sodium images acquired at clinical 1.5-T MRI system can generate an adequate quantitative data that enable the estimation of sodium concentration in AC. We conclude that this method is potentially suitable for non-invasive physiological (sodium content) measurement of articular cartilage.
  15. Preparation and Characterization of Magnetite-Polyvinyl Alcohol Hybrid Nanoparticles (As-PVA-MNPs) Using Acanthophora spicifera Marine Algae Extract for Enhanced Antimicrobial Activity Against Pathogenic Microorganisms
    Kumar DSRS, Puthiran SH, Selvaraju GD, Matthew PA, Senthilkumar P, Kuppusamy S, et al.
    Mol Biotechnol, 2023 Oct 31.
    PMID: 37907811 DOI: 10.1007/s12033-023-00903-y
    The present study focused on preparing and characterizing magnetite-polyvinyl alcohol (PVA) hybrid nanoparticles using Acanthophora spicifera marine algae extract as a reducing agent. Various analytical techniques, including UV-Visible spectrometry, Fourier-transform infrared (FTIR) analysis, energy-dispersive X-ray (EDX), scanning electron microscopy (SEM), and X-ray diffraction (XRD) analysis, were used to characterize the nanoparticles. The results showed the successful synthesis of nanoparticles with a characteristic color change and absorption peak at 400 nm in UV-Visible spectrometry. FTIR analysis indicated an interaction between the carboxyl group and magnetite-polyvinyl alcohol hybrid ions. SEM analysis revealed spherical nanoparticles with sizes ranging from 20 to 100 nm. EDX analysis confirmed the presence of strong magnetite peaks in Acanthophora spicifera, validating successful preparation. XRD analysis indicated the crystalline nature of the nanoparticles. Furthermore, the antimicrobial potential of As-PVA-MNPs was evaluated, demonstrating a significant zone of inhibition against tested bacterial and fungal samples at a concentration of 100 µg. These findings suggest the promising antimicrobial activity of the synthesized nanoparticles for potential applications in combating pathogenic microorganisms.
  16. Fulltext Integrated genomic view of SARS-CoV-2 in India
    Kumar P, Pandey R, Sharma P, Dhar MS, A V, Uppili B, et al.
    Wellcome Open Res, 2020;5:184.
    PMID: 32995557 DOI: 10.12688/wellcomeopenres.16119.1
    Background: India first detected SARS-CoV-2, causal agent of COVID-19 in late January 2020, imported from Wuhan, China. From March 2020 onwards, the importation of cases from countries in the rest of the world followed by seeding of local transmission triggered further outbreaks in India. Methods: We used ARTIC protocol-based tiling amplicon sequencing of SARS-CoV-2 (n=104) from different states of India using a combination of MinION and MinIT sequencing from Oxford Nanopore Technology to understand how introduction and local transmission occurred. Results: The analyses revealed multiple introductions of SARS-CoV-2 genomes, including the A2a cluster from Europe and the USA, A3 cluster from Middle East and A4 cluster (haplotype redefined) from Southeast Asia (Indonesia, Thailand and Malaysia) and Central Asia (Kyrgyzstan). The local transmission and persistence of genomes A4, A2a and A3 was also observed in the studied locations. The most prevalent genomes with patterns of variance (confined in a cluster) remain unclassified, and are here proposed as A4-clade based on its divergence within the A cluster. Conclusions: The viral haplotypes may link their persistence to geo-climatic conditions and host response. Multipronged strategies including molecular surveillance based on real-time viral genomic data is of paramount importance for a timely management of the pandemic.
  17. Anti-mycobacterial Constituents from Medicinal Plants; A Review
    Sarkar N, Dey YN, Kumar D, Rajagopal M
    Mini Rev Med Chem, 2021;21(19):3037-3051.
    PMID: 34036911 DOI: 10.2174/1389557521666210525120325
    Effective treatment of tuberculosis has been hampered by the emergence of drug-resistant strains of Mycobacterium therapeutic facilities tuberculosis. With the global resurgence of tuberculosis with the development of multidrug-resistant cases, there is a call for the development of new drugs to combat these diseases. Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology, and continued to play a significant role in the drug discovery and development process. This review article depicts the various potential plant extracts as well as plant derived phytoconstituents against the H37rv, the most persistent strains of Mycobacterium tuberculosis and its multidrug strains.
  18. 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.
  19. 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.
  20. Depression and suicidal ideation among adolescents
    Navin Kumar DR
    Med J Malaysia, 2018 12;73(6):443.
    PMID: 30647229
    No abstract provided.
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