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Fulltext Easy lens cleaning solution for laboratory microscopes

Pramanik T, Ghosh A, Roychowdhury P

Med J Malaysia, 2005 Mar;60(1):116.
PMID: 16250297
Fulltext Role of nitric oxide-scavenging activity of Karanjin and Pongapin in the treatment of Psoriasis

Ghosh A, Tiwari GJ

3 Biotech, 2018 Aug;8(8):338.
PMID: 30073123 DOI: 10.1007/s13205-018-1337-5

In the present study, Karanjin and Pongapin, two important furanoflavone, constituents of Pongamia pinnata were studied in the management of Psoriasis. Presently, we have experimentally studied the free radical quenching property of Karanjin and Pongapin. A modified method was used to estimate the scavenging effect of the Karanjin (the highest activity of 95.60%) and Pongapin (68.05%) compared to the ascorbic acid as standard (11.60%) against nitric oxide. Furthermore, Molecular docking studies were performed using CLC drug discovery workbench software version 3.0 of the studied flavones (Karanjin and Pongapin) with the receptors responsible for psoriasis (viz. IL-17A, IL-17F, IL-23, RORγt, and TLR-7). Docking scores of Karanjin and Pongapin with different studied receptors were found to be comparable to that of Methotrexate, a known drug for treating Psoriasis. Docking results suggest that Karanjin and Pongapin might also help in controlling the disease. Overall, our results indicate that flavones (Karanjin and Pongapin) could be a natural and better alternative in curing psoriasis without any side effects.
Anaerobic capacity of physically active eumenorrheic females at mid-luteal and mid-follicular phases of ovarian cycle

Shaharudin S, Ghosh AK, Ismail AA

J Sports Med Phys Fitness, 2011 Dec;51(4):576-82.
PMID: 22212259

The present study was undertaken to evaluate the anaerobic capacity in repeated sprint cycling bouts during mid-luteal (ML) and mid-follicular (MF) phases of ovarian cycle.
Exosome-mediated PROTACs delivery to target viral infections

Mukerjee N, Maitra S, Ghosh A, Subramaniyan V, Sharma R

Drug Dev Res, 2023 Sep;84(6):1031-1036.
PMID: 37391892 DOI: 10.1002/ddr.22091

Exosome-based targeted delivery of Proteolysis-Targeting Chimeras (PROTACs) is an innovative approach that provides a promising solution for addressing the complex issues of viral diseases. This strategy significantly mitigates the off-target effects associated with traditional therapeutics by facilitating targeted delivery of PROTACs, which in turn enhances the overall therapeutic outcomes. Challenges like poor pharmacokinetics and unintended side effects, commonly observed with conventional PROTACs usage, are effectively managed with this approach. Emerging evidence affirms the potential of this delivery mechanism in curbing viral replication. However, it is crucial to undertake more comprehensive investigations for optimizing exosome-based delivery systems and conducting stringent safety and efficacy assessments within preclinical and clinical settings. The advancements in this field could potentially redefine the therapeutic landscape for viral diseases, opening new vistas for their management and treatment.
Jumping in lantern bugs (Hemiptera, Fulgoridae)

Burrows M, Ghosh A, Sutton GP, Yeshwanth HM, Rogers SM, Sane SP

J Exp Biol, 2021 12 01;224(23).
PMID: 34755862 DOI: 10.1242/jeb.243361

Lantern bugs are amongst the largest of the jumping hemipteran bugs, with body lengths reaching 44 mm and masses reaching 0.7 g. They are up to 600 times heavier than smaller hemipterans that jump powerfully using catapult mechanisms to store energy. Does a similar mechanism also propel jumping in these much larger insects? The jumping performance of two species of lantern bugs (Hemiptera, Auchenorrhyncha, family Fulgoridae) from India and Malaysia was therefore analysed from high-speed videos. The kinematics showed that jumps were propelled by rapid and synchronous movements of both hind legs, with their trochantera moving first. The hind legs were 20-40% longer than the front legs, which was attributable to longer tibiae. It took 5-6 ms to accelerate to take-off velocities reaching 4.65 m s-1 in the best jumps by female Kalidasa lanata. During these jumps, adults experienced an acceleration of 77 g, required an energy expenditure of 4800 μJ and a power output of 900 mW, and exerted a force of 400 mN. The required power output of the thoracic jumping muscles was 21,000 W kg-1, 40 times greater than the maximum active contractile limit of muscle. Such a jumping performance therefore required a power amplification mechanism with energy storage in advance of the movement, as in their smaller relatives. These large lantern bugs are near isometrically scaled-up versions of their smaller relatives, still achieve comparable, if not higher, take-off velocities, and outperform other large jumping insects such as grasshoppers.
Fulltext Identification of dominant risk factor involved in spread of COVID-19 using hesitant fuzzy MCDM methodology

Ghorui N, Ghosh A, Mondal SP, Bajuri MY, Ahmadian A, Salahshour S, et al.

Results Phys, 2021 Feb;21:103811.
PMID: 33520630 DOI: 10.1016/j.rinp.2020.103811

The outburst of the pandemic Coronavirus disease since December 2019, has severely impacted the health and economy worldwide. The epidemic is spreading fast through various means, as the virus is very infectious. Medical science is exploring a vaccine, only symptomatic treatment is possible at the moment. To contain the virus, it is required to categorize the risk factors and rank those in terms of contagion. This study aims to evaluate risk factors involved in the spread of COVID-19 and to rank them. In this work, we applied the methodology namely, Fuzzy Analytic Hierarchy Process (FAHP) to find out the weights and finally Hesitant Fuzzy Sets (HFS) with Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) is applied to identify the major risk factor. The results showed that "long duration of contact with the infected person" the most significant risk factor, followed by "spread through hospitals and clinic" and "verbal spread". We showed the appliance of the Multi Criteria Decision Making (MCDM) tools in evaluation of the most significant risk factor. Moreover, we conducted sensitivity analysis.
Fulltext Bilateral Mirror Image Cervical Neurofibroma in an Adult with Neurofibromatosis Type 1

Pandey S, Singh K, Sharma V, Khan MT, Ghosh A, Santhosh D

Malays J Med Sci, 2017 Mar;24(1):117-120.
PMID: 28381935 DOI: 10.21315/mjms2017.24.1.13

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterised by various phenotypic features like hyperpigmented spots, neurofibromas, Lisch nodules, skeletal abnormalities and tendency to develop neoplasms. Only few cases of Non-Familial Spinal Neurofibromatosis-1 (Non-FSNF1) have been described in literature with tumors involving the spinal roots at every level being even rarer. We reported an interesting case of bilateral symmetrical cervical neurofibroma with multiple spinal neurofibromas appearing as mirror image on CT, associated with non familial NF-1 as a rare presentation in a 25-year-old adult male.
Fulltext Macrolactin A as a Novel Inhibitory Agent for SARS-CoV-2 Mpro: Bioinformatics Approach

Bharadwaj KK, Sarkar T, Ghosh A, Baishya D, Rabha B, Panda MK, et al.

Appl Biochem Biotechnol, 2021 Oct;193(10):3371-3394.
PMID: 34212286 DOI: 10.1007/s12010-021-03608-7

COVID-19 is a disease that puts most of the world on lockdown and the search for therapeutic drugs is still ongoing. Therefore, this study used in silico screening to identify natural bioactive compounds from fruits, herbaceous plants, and marine invertebrates that are able to inhibit protease activity in SARS-CoV-2 (PDB: 6LU7). We have used extensive screening strategies such as drug likeliness, antiviral activity value prediction, molecular docking, ADME, molecular dynamics (MD) simulation, and MM/GBSA. A total of 17 compounds were shortlisted using Lipinski's rule in which 5 compounds showed significant predicted antiviral activity values. Among these 5, only 2 compounds, Macrolactin A and Stachyflin, showed good binding energy of -9.22 and -8.00 kcal/mol, respectively, within the binding pocket of the Mpro catalytic residues (HIS 41 and CYS 145). These two compounds were further analyzed to determine their ADME properties. The ADME evaluation of these 2 compounds suggested that they could be effective in developing therapeutic drugs to be used in clinical trials. MD simulations showed that protein-ligand complexes of Macrolactin A and Stachyflin with the target receptor (6LU7) were stable for 100 nanoseconds. The MM/GBSA calculations of Mpro-Macrolactin A complex indicated higher binding free energy (-42.58 ± 6.35 kcal/mol). Dynamic cross-correlation matrix (DCCM) and principal component analysis (PCA) on the residual movement in the MD trajectories further confirmed the stability of Macrolactin A bound state with 6LU7. In conclusion, this study showed that marine natural compound Macrolactin A could be an effective therapeutic inhibitor against SARS-CoV-2 protease (6LU7). Additional in vitro and in vivo validations are strongly needed to determine the efficacy and therapeutic dose of Macrolactin A in biological systems.
QSAR modeling approaches to identify a novel ACE2 inhibitor that selectively bind with the C and N terminals of the ectodomain

Jawarkar RD, Zaki MEA, Al-Hussain SA, Al-Mutairi AA, Samad A, Mukerjee N, et al.

J Biomol Struct Dyn, 2024 Mar;42(5):2550-2569.
PMID: 37144753 DOI: 10.1080/07391102.2023.2205948

Due to the high rates of drug development failure and the massive expenses associated with drug discovery, repurposing existing drugs has become more popular. As a result, we have used QSAR modelling on a large and varied dataset of 657 compounds in an effort to discover both explicit and subtle structural features requisite for ACE2 inhibitory activity, with the goal of identifying novel hit molecules. The QSAR modelling yielded a statistically robust QSAR model with high predictivity (R2tr=0.84, R2ex=0.79), previously undisclosed features, and novel mechanistic interpretations. The developed QSAR model predicted the ACE2 inhibitory activity (PIC50) of 1615 ZINC FDA compounds. This led to the detection of a PIC50 of 8.604 M for the hit molecule (ZINC000027990463). The hit molecule's docking score is -9.67 kcal/mol (RMSD 1.4). The hit molecule revealed 25 interactions with the residue ASP40, which defines the N and C termini of the ectodomain of ACE2. The HIT molecule conducted more than thirty contacts with water molecules and exhibited polar interaction with the ARG522 residue coupled with the second chloride ion, which is 10.4 nm away from the zinc ion. Both molecular docking and QSAR produced comparable findings. Moreover, MD simulation and MMGBSA studies verified docking analysis. The MD simulation showed that the hit molecule-ACE2 receptor complex is stable for 400 ns, suggesting that repurposed hit molecule 3 is a viable ACE2 inhibitor.
Mitochondrial dysfunction and oxidative stress in Alzheimer's disease, and Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis -An updated review

Alqahtani T, Deore SL, Kide AA, Shende BA, Sharma R, Dadarao Chakole R, et al.

Mitochondrion, 2023 Jul;71:83-92.
PMID: 37269968 DOI: 10.1016/j.mito.2023.05.007

Misfolded proteins in the central nervous system can induce oxidative damage, which can contribute to neurodegenerative diseases in the mitochondria. Neurodegenerative patients face early mitochondrial dysfunction, impacting energy utilization. Amyloid-ß and tau problems both have an effect on mitochondria, which leads to mitochondrial malfunction and, ultimately, the onset of Alzheimer's disease. Cellular oxygen interaction yields reactive oxygen species within mitochondria, initiating oxidative damage to mitochondrial constituents. Parkinson's disease, linked to oxidative stress, α-synuclein aggregation, and inflammation, results from reduced brain mitochondria activity. Mitochondrial dynamics profoundly influence cellular apoptosis via distinct causative mechanisms. The condition known as Huntington's disease is characterized by an expansion of polyglutamine, primarily impactingthe cerebral cortex and striatum. Research has identified mitochondrial failure as an early pathogenic mechanism contributing to HD's selective neurodegeneration. The mitochondria are organelles that exhibit dynamism by undergoing fragmentation and fusion processes to attain optimal bioenergetic efficiency. They can also be transported along microtubules and regulateintracellular calcium homeostasis through their interaction with the endoplasmic reticulum. Additionally, the mitochondria produce free radicals. The functions of eukaryotic cells, particularly in neurons, have significantly deviated from the traditionally assigned role of cellular energy production. Most of them areimpaired in HD, which may lead to neuronal dysfunction before symptoms manifest. This article summarizes the most important changes in mitochondrial dynamics that come from neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's and Amyotrophic Lateral Sclerosis. Finally, we discussed about novel techniques that can potentially treat mitochondrial malfunction and oxidative stress in four most dominating neuro disorders.
Rhamnetin, a nutraceutical flavonoid arrests cell cycle progression of human ovarian cancer (SKOV3) cells by inhibiting the histone deacetylase 2 protein

Bharadwaj KK, Rabha B, Ahmad I, Mathew SP, Bhattacharjee CK, Jaganathan BG, et al.

J Biomol Struct Dyn, 2023 Nov 28.
PMID: 38014451 DOI: 10.1080/07391102.2023.2275187

Overexpression of HDAC 2 promotes cell proliferation in ovarian cancer. HDAC 2 is involved in chromatin remodeling, transcriptional repression, and the formation of condensed chromatin structures. Targeting HDAC 2 presents a promising therapeutic approach for correcting cancer-associated epigenetic abnormalities. Consequently, HDAC 2 inhibitors have evolved as an attractive class of anti-cancer agents. This work intended to investigate the anti-cancer abilities and underlying molecular mechanisms of Rhamnetin in human epithelial ovarian carcinoma cells (SKOV3), which remain largely unexplored. We employed various in vitro methods, including MTT, apoptosis study, cell cycle analysis, fluorescence microscopy imaging, and in vitro enzymatic HDAC 2 protein inhibition, to examine the chemotherapeutic sensitivity of Rhamnetin in SKOV3 cells. Additionally, we conducted in silico studies using molecular docking, MD simulation, MM-GBSA, DFT, and pharmacokinetic analysis to investigate the binding interaction mechanism within Rhamnetin and HDAC 2, alongside the compound's prospective as a lead candidate. The in vitro assay confirmed the cytotoxic effects of Rhamnetin on SKOV3 cells, through its inhibition of HDAC 2 activity. Rhamnetin, a nutraceutical flavonoid, halted at the G1 phase of the cell cycle and triggered apoptosis in SKOV3 cells. Furthermore, computational studies provided additional evidence of its stable binding to the HDAC 2 protein's binding site cavity. Based on our findings, we conclude that Rhamnetin effectively promotes apoptosis and mitigates the proliferation of SKOV3 cells through HDAC 2 inhibition. These results highlight Rhamnetin as a potential lead compound, opening a new therapeutic strategy for human epithelial ovarian cancer.Communicated by Ramaswamy H. Sarma.
Fulltext Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies

Abubakar MB, Usman D, El-Saber Batiha G, Cruz-Martins N, Malami I, Ibrahim KG, et al.

Front Pharmacol, 2021;12:629935.
PMID: 34012391 DOI: 10.3389/fphar.2021.629935

The 2019 coronavirus disease (COVID-19) is a potentially fatal multisystemic infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently, viable therapeutic options that are cost effective, safe and readily available are desired, but lacking. Nevertheless, the pandemic is noticeably of lesser burden in African and Asian regions, where the use of traditional herbs predominates, with such relationship warranting a closer look at ethnomedicine. From a molecular viewpoint, the interaction of SARS-CoV-2 with angiotensin converting enzyme 2 (ACE2) is the crucial first phase of COVID-19 pathogenesis. Here, we review plants with medicinal properties which may be implicated in mitigation of viral invasion either via direct or indirect modulation of ACE2 activity to ameliorate COVID-19. Selected ethnomedicinal plants containing bioactive compounds which may prevent and mitigate the fusion and entry of the SARS-CoV-2 by modulating ACE2-associated up and downstream events are highlighted. Through further experimentation, these plants could be supported for ethnobotanical use and the phytomedicinal ligands could be potentially developed into single or combined preventive therapeutics for COVID-19. This will benefit researchers actively looking for solutions from plant bioresources and help lessen the burden of COVID-19 across the globe.
Access to Healthcare and Harm Reduction Services During the COVID-19 Pandemic for People Who Use Drugs

Stowe MJ, Calvey T, Scheibein F, Arya S, Saad NA, Shirasaka T, et al.

J Addict Med, 2020 12;14(6):e287-e289.
PMID: 33009167 DOI: 10.1097/ADM.0000000000000753

: Globally, there are concerns about access to healthcare and harm reduction services for people who use drugs (PWUD) during the coronavirus disease 2019 (COVID-19) pandemic. Members from the Network of Early Career Professionals working in Addiction Medicine shared their experiences of providing treatment to PWUD during the COVID-19 pandemic. Drawing on these qualitative reports, we highlight the similarities and discrepancies in access to services for PWUD in 16 countries under COVID-10 restrictions. In most countries reported here, efforts have been made to ensure continued access to services, such as mobilising opioid agonist maintenance treatment and other essential medicines to patients. However, due to travel restrictions and limited telemedicine services, several Network of Early Career Professionals working in Addiction Medicine members from lower-resourced countries experienced challenges with providing care to their patients during periods of COVID-19 lock-down. The insights provided in this commentary illustrate how the COVID-19 lock-down restrictions have impacted access to services for PWUD.
The Changing Landscape of Alcohol Use and Alcohol Use Disorder During the COVID-19 Pandemic - Perspectives of Early Career Professionals in 16 Countries

Calvey T, Scheibein F, Saad NA, Shirasaka T, Dannatt L, Stowe MJ, et al.

J Addict Med, 2020 12;14(6):e284-e286.
PMID: 32909983 DOI: 10.1097/ADM.0000000000000735

: Alcohol use is a major risk factor for infectious disease and reduction of harms associated with alcohol consumption are essential during times of humanitarian crises, such as the COVID-19 pandemic. As a network of early career professionals working in the area of addiction medicine, we provide our views with regards to national actions related to reducing alcohol-related harm and providing care for people with alcohol use disorder during COVID-19. We believe that COVID-19 related measures have affected alcohol consumption in the majority of countries represented in this commentary. Examples of these changes include changes in alcohol consumption patterns, increases in cases of alcohol withdrawal syndrome, disruptions in access to medical care for alcohol use disorder and increases in illegal production of alcohol. Our members urge that treatment for acute and severe conditions due to substance use should be considered as essential services in times of humanitarian crises like COVID-19.
Fulltext Responding to COVID-19: Emerging Practices in Addiction Medicine in 17 Countries

Scheibein F, Stowe MJ, Arya S, Morgan N, Shirasaka T, Grandinetti P, et al.

Front Psychiatry, 2021;12:634309.
PMID: 33796034 DOI: 10.3389/fpsyt.2021.634309
Fulltext Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases

Wong WM, Tham YC, Simunovic MP, Chen FK, Luu CD, Chen H, et al.

Asia Pac J Ophthalmol (Phila), 2024;13(1):100030.
PMID: 38233300 DOI: 10.1016/j.apjo.2023.100030

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region.
DESIGN: Multi-national, multi-center collaborative network.
METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries.
RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists.
CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.
Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma

Khor CC, Do T, Jia H, Nakano M, George R, Abu-Amero K, et al.

Nat Genet, 2016 May;48(5):556-62.
PMID: 27064256 DOI: 10.1038/ng.3540

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.
Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC

Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.

Phys Rev Lett, 2024 Jan 12;132(2):021803.
PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803

The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140 fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.

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