Biology subjects

Ahmed, S. R.

Publications and source records attributed to Ahmed, S. R..

9 recordsLinked to original sources

bioRxiv2023

Structural and functional vascular dysfunction within brain metastases is linked to pembrolizumab inefficacy

Structurally and functionally aberrant vasculature is a hallmark of tumor angiogenesis and treatment resistance. Given the synergistic link between aberrant tumor vasculature and immunosuppression, we analyzed perfusion MRI for 44 patients with brain metastases (BM) undergoing treatment with pembrolizumab. To date, vascular-immune communication, or the relationship between immune checkpoint inhibitor (ICI) efficacy and vascular architecture, has not been well-characterized in human imaging studies. We found that ICI-responsive BM possessed a structurally balanced vascular makeup, which was linked to improved vascular efficiency and an immune-stimulatory microenvironment. In contrast, ICI-resistant BM were characterized by a lack of immune cell infiltration and a highly aberrant vasculature dominated by large-caliber vessels. Peri-tumor region analysis revealed early functional changes predictive of ICI resistance before radiographic evidence on conventional MRI. This study was one of the largest functional imaging studies for BM and establishes a foundation for functional studies that illuminate the mechanisms linking patterns of vascular architecture with immunosuppression, as targeting these aspects of cancer biology may serve as the basis for future combination treatments.

cancer biology↗

bioRxiv2020

Plant derived bioactive compounds as potential inhibitors of ZIKA virus: an in silico investigation

The ZIKA virus has caused a heavy concern everywhere the globe because of its high infectivity and mortality rate. Still, theres no specific drug or preventive medication to treat ZIKA infection despite comprehensive analysis by the researchers. This study was designed to demonstrate the efficacy of some plant derived bioactive compounds against ZIKV by using both structure and ligand based virtual screening methods. A number of 35 plant metabolites were screened against ZIKA NS2B-NS3 protease (5LC0), Envelop protein (5JHM), Capsid protein (5YGH) and NS5 RNA-dependent RNA polymerase protein (5U04) employing molecular docking approach. Results showed that there have been four metabolites, i.e. Chicoric acid, Luteone, Reserpine and Rosmarinic acid provide highest binding affinity to targeted ZIKV proteins. Crucial binding sites and drug surface hotspots are unraveled for every targeted viral protein. The ADME study showed that neither of the candidate compounds had side effects that would reduce their drug-like properties. As compared, the toxicity pattern analysis has unmasked the non-toxic essence of top drug candidates. The RMSD values of ligand-macromolecule complexes were 2 [A] apart from Envelop protein- Chicoric Acid, although the RMSF values showed normal atomic fluctuations within the molecular dynamics analysis, with the exception of Envelop protein- Chicoric Acid. The expected majority of the target class the highest drug candidates is enzyme classes (e.g. protease, hydrolase, phosphatase). In addition, the drug similarity prediction revealed several structural analogs from drugbank such as Isoformononetin (DB04202), Deserpidine (DB01089) and Rescinnamine (DB01180) etc. and these analogs could even be an option for the treatment of ZIKV infections. The study can pave the way for the creation of effective ZIKV medications and preventive measures. We highly recommend further in vivo trials for the experimental validation of our findings.

bioinformatics↗

bioRxiv2020

Screening and potent applicability analysis of commonly used pesticides against desert locust: an integrative entomo-informatics approach

The locust problem is a global threat for food security. Locusts can fly and migrate overseas within a zip and creating a large-scale devastation to the diversified agro-ecosystem. GIS based analysis showed the recent movement of locusts, among them Schistocerca gregaria and Locusta migratoria are predominant in Indian subcontinent and are found more notorious and devastating one. This devastation needs to be stopped to save human race from food deprivation. In our study, we screened some commonly used agricultural pesticides and strongly recommended three of them viz. biphenthrin, diafenthiuron and silafluofen which might be potential to control the desert locusts based on their binding affinity towards the locusts survival proteins. Our phylogenetic analysis reveals that these three recommended pesticides might also show potency to the other locust species as well as they are also way safer than the other commercially available pesticides. These proposed pesticides bioactive analogs from fungus and bacteria may also show efficacy as next generation controlling measures of locust as well as different kind of pests. These recommended pesticides are expected to be highly effective against locusts and needs to bring forward by the entomologists by performing experimental field trials. HighlightsO_LIGIS map unmasked the 2020 migratory pattern of locusts which now predominant towards Indian subcontinent. C_LIO_LIBiphenthrin, diafenthiuron and silafluofen showed maximum binding affinity. C_LIO_LIBiphenthrin and diafenthiuron were relatively safer than silafluofen. C_LIO_LIBioactive analogs from fungus and bacteria could be an alternative to control locusts. C_LIO_LIPesticides inhibition hotspots for desert locusts were unrevealed. C_LI

bioinformatics↗

bioRxiv2020

Identification of potential inhibitory analogs of metastasis tumor antigens (MTAs) using bioactive compounds: revealing therapeutic option to prevent malignancy

The deeper understanding of metastasis phenomenon and detection of drug targets could be a potential approach to minimize cancer mortality. In this study, attempts were taken to unmask novel therapeutics to prevent metastasis and cancer progression. Initially, we explored the physiochemical, structural and functional insights of three metastasis tumor antigens (MTAs) and evaluated some plant based bioactive compounds as potent MTA inhibitors. From 50 plant metabolites screened, isoflavone, gingerol, citronellal and asiatic acid showed maximum binding affinity with all three MTA proteins. The ADME analysis detected no undesirable toxicity that could reduce the drug likeness properties of top plant metabolites. Moreover, molecular dynamics studies revealed that the complexes were stable and showed minimum fluctuation at molecular level. We further performed ligand based virtual screening to identify similar drug molecules using a large collection of 3,76,342 compounds from DrugBank. The results suggested that several structural analogs (e.g. Tramadol, Nabumetone, DGLA, Hydrocortisone) may act as agonist to block the MTA proteins and inhibit cancer progression at early stage. The study could be useful to develop effective medications against cancer metastasis in future. Due to encouraging results, we highly recommend further in vitro and in vivo trials for the experimental validation of the findings.

bioinformatics↗

bioRxiv2019

Phytochemical Constituency Profiling and Antimicrobial Activity Screening of Seaweeds Extracts Collected from the Bay of Bengal Sea Coasts

Seaweeds are able to produce a great variety of secondary metabolites that are characterized by a broad spectrum of biological activities. Two seaweeds species, namely Hypnea musciformis and Enteromorpha intestinalis were studied to evaluate the phytochemical constituency and antimicrobial activities. First of all, crude extracts of both sea weeds were prepared by two different extraction methods (soaking and water bath) using different solvents. Phytochemicals profiling results revealed the presence of bioactive compounds (flavonoids, alkaloids, tannin, saponin and phenols) in both seaweed extracts. Quantification results for ethanolic extracts of H. musciformis and E. intestinalis estimated 51 mg and 43 mg tannins in per gram of dried samples and flavonoids contents were found 67 mg and 57 mg/g mg QE/g respectively. Total phenolic contents were determined in terms of gallic acid equivalent (GAE). H. musciformis exhibited higher amount of phenolics (59 {+/-} 0.0002 mg GAE/g) than E. intestinalis extracts (41 {+/-} 0.0002 mg GAE/g). In antimicrobial activity test, ethanol extracts of H. musciformis and E. intestinalis were found 10 mm of inhibition diameter against all of the bacterial strains. Besides, methanol extracts of E. intestinalis were more susceptible to Staphylococcus aureus and Pseudomonas which was close to the inhibition diameter (>15 mm) of the mainstream antibiotic; Gentamicin. Moreover, Klebsiella sp. was found more susceptible to ethanol and methanol extracts of Hypnea musciformis as it showed inhibition zone greater than 15 mm. Both Seaweed extracts possessed higher amount of phytochemicals and showed promising antimicrobial activities when compared with the standards.

pharmacology and toxicology↗

bioRxiv2018

Direct immunosensing of avian influenza A virus in whole blood using hybrid nanocomposites

A sandwich-based electrochemical immunosensor was designed for detection of avian influenza virus (AIV) strains H5N1 and H4N6. This sensor was developed using gold-graphene nanocomposites, immobilized viral antibodies, and CdTe quantum dot electrochemical tagging. The nanocomposites were formed by the simultaneous reduction of a gold salt and graphene using hydroquinone as the reducing agent, thus producing non-spherical gold nanoparticles on graphene sheets. Viral antibodies were immobilized on nanocomposites and CdTe quantum dots through N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide and N-hydroxysuccinimide chemistry. Cyclic voltammetry studies were used to validate the detection of H5N1 surface protein and H4N6 inactivated virus. The immunosensor detected H5 protein in phosphate buffer solution (pH 7.4) with a limit of detection (LOD) of 10 fg/mL and a linear detection range was established for 10 ng/mL to 10 pg/mL. The biosensor detected H4N6 in three parts diluted whole chicken blood with a LOD of 1.28x10-7 hemagglutinating units (HAU). Commercial ELISA testing for H5N1 and H4N6 showed limits of detection of 10 ng/mL and 0.128 HAU, respectively. The sensor showed 106-fold increased detection of H4N6 virus in blood in comparison to its commercial ELISA kit counterpart. The developed immunosensor effectively change the way avian influenza is detected, monitored, and controlled; transforming time-consuming reactive methods, into rapid predictive technology.

bioengineering↗

bioRxiv2017

Self-assembled Star-shaped Chiroplasmonic Gold Nanoparticles for Ultrasensitive Chiro-immunosensor of Viruses

Near field optics and optical tunneling light-matter interaction in the superstructure of chiral nanostructures and semiconductor quantum dots exhibit strong optical rotation activity that may open a new window for chiral-based bioanalytes detection. Herein we report an ultrasensitive, chiro-immunosensor using superstructure of chiral gold nanohybrids (CAu NPs) and quantum dots (QDs). Self-assembling techniques were employed to create asymmetric plasmonic chiral nanostructures for extending the spectral range of circular dichroism (CD) response for obtaining superior plasmonic resonant coupling with the QDs excitonic state; this may help to achieve lower the limit of detection (LOD) values. As a result, the designed probe exhibited avian influenza A (H5N1) viral concentration at picomolar level, a significant improvement in sensitivity in comparison to a non-assembled CAu NPs based chiroassay. The practicability of the proposed sensing system was successfully demonstrated on several virus cultures including, avian influenza A (H4N6) virus, fowl adenovirus and coronavirus in blood samples. The results of our study highlights that exciton-plasmon interaction changes chirality and the self-assembled nanostructures are an efficient strategy for enhancing the sensitivity of plasmonic nanosensors.

bioengineering↗

bioRxiv2017

Chitozyme: First Peroxidase-like Activity of Chitosan for Multiplexed Visual Detection of H2O2, Glucose and Lactate on Paper-based Device

Visual read-out diagnostics tools are promising candidates for field applicable medical devices. Current colorimetric biosensors require introduction of natural enzymes or nanozymes, which has some serious drawbacks for practical applications. Chitosan, a natural polymer, provides safe and efficient compound in medical and pharmaceutical technology. Herein, we report on a simple, cost-efficient, field-portable, environmental friendly and ultra-sensitive multiplex detection platform based on peroxidase-like activity of chitosan in the presence of 3,3,5,5-Tetramethylbenzidine (TMBZ) and H2O2. This straight forward signal amplification strategy was successfully applied to detect H2O2, glucose and lactate with the limit of detection (LOD) of 2.64 pM, 0.104 M and 2.8 nM respectively, represents the lowest LOD of H2O2, glucose and lactate with visual read-out. The chitosan-based assay performance was also retained in complex biological media for glucose and lactate detection. Furthermore, the proposed assay was successfully demonstrated as a paper-based colorimetric biosensor. Most importantly, the simplicity, biocompatibility and sensitivity of the proposed assay will open new doors for instrument free naked eye visual detection of H2O2, glucose and lactate detection.

bioengineering↗

bioRxiv2017

Amplified visual immunosensor integrated with nanozyme for ultrasensitive detection of avian influenza virus

Nanomaterial-based artificial enzymes or nanozymes exhibits superior properties such as stability, cost effectiveness and ease of preparation in comparison to conventional enzymes. However, the lower catalytic activity of nanozymes limits their sensitivity and thereby practical applications in the bioanalytical field. To overcome this drawback, herein we propose a very simple but highly sensitive, specific and low-cost dual enhanced colorimetric immunoassay for the detection of avian influenza virus A (H5N1) through facile in situ synthesis of gold nanoparticles and their peroxidase-like enzymatic activity. 3,3,5,5-Tetramethylbenzidine (TMBZ) was used as a reducing agent to produce gold nanoparticles (Au NPs) from a viral target-specific antibody-gold ion complex. The developed blue color from the sensing design was further amplified through catalytic activity of Au NPs in presence of TMBZ-hydrogen peroxide (H2O2) complex. The developed dual enhanced colorimetric immunosensor enables the detection of avian influenza virus A (H5N1) with a limit of detection (LOD) of 1.11 pg/mL. Our results further confirms that the developed assay has superior sensitivity than the conventional ELISA method, plasmonic-based bioassay and commercial flu diagnostic kits.

bioengineering↗