Biology subjects

Anwar, M.

Publications and source records attributed to Anwar, M..

16 recordsLinked to original sources

bioRxiv2025

A Single Mutation in TRPC6 Protects Mice from Acute Lung Injury by Regenerating Endothelium

Regenerating vascular endothelium under sepsis, trauma, and viral infections is vital for promoting the resolution of inflammatory diseases such as acute lung injury (ALI). Transient receptor potential canonical (TRPC) channels mediated Ca2+ entry compromises organ functions and survival from lung injury. Through decoding the domain in TRPC6 responsible for vascular injury, we unveiled the intricate molecular mechanisms underlying vascular regeneration in injured tissue. We found that the substitution of isoleucine111 within the Ist ankyrin domain of TRPC6 for its isomer 111leucine (I111L-TRPC6) altered channel localization at the membrane, blocked TRPC6-mediated Ca2+ entry and cation currents without affecting TRPC6 protein expression. Next, we delivered WT-TRPC6 and I111L-TRPC6 to the endothelial cells (ECs) of TRPC6 knockout mice using liposomes and found that while WT-TRPC6 induced lung vascular inflammatory injury and EC death these responses were blocked in lungs expressing I111L-TRPC6 mutant. Instead, the I111L-TRPC6 mutant promoted lung EC proliferation and prevented vascular injury. These responses were recapitulated in a preclinical mouse model of ALI after injection of engineered TRPC6-blocking peptide, suggesting a novel strategy for regenerating anti-inflammatory vascular niche and preventing ALI therapeutically.

cell biology↗

bioRxiv2024

circRNA-miRNA-mRNA networks reveal a proangiogenic action of circNPHP1 in human ischemic heart disease

BackgroundIschemic heart disease (IHD) is characterized by insufficient myocardial blood flow in the left ventricle and aggravated by diabetes mellitus. Endothelial resilience and reparative angiogenesis are tightly controlled processes. Gene expression is regulated by multimodal interactions between RNA species. Circular RNAs (circRNAs) can sponge microRNAs (miRNAs) to reduce the repressive effects of miRNAs on its messenger RNA (mRNAs) targets. MethodsLeft ventricle whole RNA-sequencing (circRNAs, mRNAs) and small RNA- sequencing (miRNAs) datasets were obtained from 3 patient groups: IHD with/out T2DM and controls (N=11 to 12/group) as part of a prospective observational cardiac surgery study. The interactions between differentially expressed (DE) circRNAs, miRNA and mRNAs were identified with a customized bioinformatics pipeline. The emerging networks were screened using endothelial-specific RNA-sequencing datasets from GEO resulting in EC-rich networks. CircRNAs from these networks were subsequently screened (RT-PCR) in endothelial cells (ECs) exposed to disease-mimicking conditions vs control. Afterwards, circRNA pulldown allowed to interrogate the circRNA-miRNAs interactome in ECs. EC biology assays using loss-of-function and gain-of-function approaches corroborated the study. ResultsWe identified novel circRNA-miRNA-mRNA interactions in the human diseased heart. CircNPHP1, which is upregulated in IHD with/out Type-2 diabetes mellitus (T2DM), sponges miR-221-3p to de-repress VEGF-A and BCL2, increasing the angiogenic capacity of ECs under disease and disease-mimicking conditions. ConclusionsThe interactions between individual members of different RNA species are affected by IHD. The therapeutic value of circNPHP1/miR-221-3p axis could be further investigated. Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=61 SRC="FIGDIR/small/597402v2_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@18a3b0forg.highwire.dtl.DTLVardef@2b5dc1org.highwire.dtl.DTLVardef@11848c3org.highwire.dtl.DTLVardef@1511c9e_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe found a novel circRNA-miRNA-mRNA network in IHD and Type 2 diabetes. C_LIO_LICircNPHP1 regulates angiogenesis and proliferation in the cardiac ECs exposed to conditions mimicking IHD and Type 2 diabetes. C_LIO_LIWe elucidated a novel pro-angiogenic subnetwork commanded by circNPHP1/miR-221-3p/BCL2/VEGFA. C_LIO_LIWe identified circNPHP1 as a potential new target for therapeutic angiogenesis. C_LI

cell biology↗

bioRxiv2024

Endothelial ERG programs neutrophil transcriptome for sustained anti-inflammatory vascular niche

Neutrophils (PMNs) reside as a marginated pool within the vasculature, ready for deployment during infection. However, how endothelial cells (ECs) control PMN extravasation and activation to strengthen tissue homeostasis remains ill-defined. Here, we found that the vascular ETS-related gene (ERG) is a generalized mechanism regulating PMN activity in preclinical tissue injury models and human patients. We show that ERG loss in ECs rewired PMN-transcriptome, enriched for genes associated with the CXCR2-CXCR4 signaling. Rewired PMNs compromise mice survival after pneumonia and induced lung vascular inflammatory injury following adoptive transfer into naive mice, indicating their longevity and inflammatory activity memory. Mechanistically, EC-ERG restricted PMN extravasation and activation by upregulating the deubiquitinase A20 and downregulating the NF{kappa}B-IL8 cascade. Rescuing A20 in EC-Erg-/- endothelium or suppressing PMN-CXCR2 signaling rescued EC control of PMN activation. Findings deepen our understanding of EC control of PMN-mediated inflammation, offering potential avenues for targeting various inflammatory diseases. HighlightsO_LIERG regulates trans-endothelial neutrophil (PMN) extravasation, retention, and activation C_LIO_LILoss of endothelial (EC) ERG rewires PMN-transcriptome C_LIO_LIAdopted transfer of rewired PMNs causes inflammation in a naive mouse C_LIO_LIERG transcribes A20 and suppresses CXCR2 function to inactivate PMNs C_LI In brief/blurbThe authors investigated how vascular endothelial cells (EC) control polymorphonuclear neutrophil (PMN) extravasation, retention, and activation to strengthen tissue homeostasis. They showed that EC-ERG controls PMN transcriptome into an anti-adhesive and anti-inflammatory lineage by synthesizing A20 and suppressing PMNs-CXCR2 signaling, defining EC-ERG as a target for preventing neutrophilic inflammatory injury.

immunology↗

bioRxiv2024

An Engineered IGF2 Mutant for Lysosomal Targeting Chimeras Development and Membrane Proteins Degradation

Lysosome-targeting chimeras (LYTACs) have emerged as a promising strategy for targeted degradation of membrane proteins, offering potential applications in drug development. Currently, two main methods for developing LYTACs exist: chemically modified antibodies [1-2] and wild-type insulin-like growth factor 2 (IGF2) fusion proteins (iLYTACs) [3]. However, the fusion of the IGF2 arm within iLYTACs carries the risk of activating IGF1R tyrosine kinase activity and promoting tumor development. To address this concern, we introduce eiLYTACs, a technology that employs engineered IGF2 fusion antibodies to induce degradation of endogenous membrane proteins. Compared to the wild-type IGF2, the engineered IGF2 mutant exhibited minimal binding affinity for IGF1R but demonstrated a significant 100-fold increase in its binding affinity for IGF2R. In contrast to wild-type IGF2, which promotes tumor growth, the cells incubated with the engineered IGF2 showed no stimulation of tumor growth. The eiLYTACs strategy effectively inhibits tumor cell proliferation by degrading specific targets, resulting in a significant reduction in xenograft tumor size in experimental nude mice. More interestingly, our research revealed that eiLYTACs simultaneously degrade both homo- and heterodimers of disease-relevant proteins,which offer a promising strategy to address the activation of compensatory bypass signaling pathways, drug resistance, and tumor heterogeneity.

biochemistry↗

bioRxiv2023

Towards A Wireless Image Sensor for Real-Time Fluorescence Microscopy in Cancer Therapy

We present a mm-sized, ultrasonically powered lensless CMOS image sensor as a progress towards wireless fluorescence microscopy. Access to biological information within the tissue has the potential to provide insights guiding diagnosis and treatment across numerous medical conditions including cancer therapy. This information, in conjunction with current clinical imaging techniques that have limitations in obtaining images continuously and lack wireless compatibility, can improve continual detection of multicell clusters deep within tissue. The proposed platform incorporates a 2.4x4.7 mm2 integrated circuit (IC) fabricated in TSMC 0.18 m, a micro laser diode (LD), a single piezoceramic and off-chip storage capacitors. The IC consists of a 36x40 array of capacitive trans-impedance amplifier-based pixels, wireless power management and communication via ultrasound and a laser driver all controlled by a Finite State Machine. The piezoceramic harvests energy from the acoustic waves at a depth of 2 cm to power up the IC and transfer 11.5 kbits/frame via backscattering. During Charge-Up, the off-chip capacitor stores charge to later supply a high-power 78 mW LD during Imaging. Proof of concept of the imaging front end is shown by imaging distributions of CD8 T-cells, an indicator of the immune response to cancer, ex vivo, in the lymph nodes of a functional immune system (BL6 mice) against colorectal cancer consistent with the results of a fluorescence microscope. The overall system performance is verified by detecting 140 m features on a USAF resolution target with 32 ms exposure time and 389 ms ultrasound backscattering.

bioengineering↗

bioRxiv2023

Multicolor on-chip fluorescence microscopy for real-time surgical guidance

In curative-intent cancer surgery, intraoperative fluorescence imaging of both diseased and healthy tissue can help to ensure successful removal of all gross and microscopic disease with minimal damage to neighboring critical structures, such as nerves. Current fluorescence-guided surgery (FGS) systems, however, rely on bulky and rigid optics that incur performance-limiting trade-offs between sensitivity and maneuverability. Moreover, many FGS systems are incapable of multiplexed imaging. As a result, clinical FGS is currently limited to millimeter-scale detection of a single fluorescent target. Here we present a scalable, lens-less fluorescence imaging chip, VISION, capable of sensitive and multiplexed detection within a compact form factor. Central to VISION is a novel optical frontend design combining a low-numerical-aperture fiber optic plate (LNA-FOP) and a multi-bandpass interference filter, which is affixed to a custom CMOS image sensor. The LNA-FOP acts as a planar collimator to improve resolution and compensate for the angle-sensitivity of the interference filter, enabling high-resolution and multiplexed fluorescence imaging without lenses. We show VISION is capable of detecting tumor foci of less than 100 cells at near video framerates and, as proof of principle, can simultaneously visualize both tumor and nerves in ex vivo prostate tissue.

cancer biology↗

bioRxiv2023

Interleukin 11-induced microRNAs as functional mediators and circulating biomarkers of cardiac fibrosis

BackgroundCardiac fibrosis can be triggered by several pathologies, including ischemic heart disease and aortic stenosis (AS). Cardiac fibrosis is brought about by uncontrolled extracellular matrix (ECM) deposition by myofibroblasts. Interleukin-11 (IL-11) has been firmly demonstrated to be a major trigger of multi-organ fibrosis. However, the molecular mechanisms underpinning IL-11-induced fibrosis requires further characterisation. Recent studies indicate that microRNA (miRNA) dysregulation contributes to the pathogenesis of cardiac fibrosis and can be targeted therapeutically. In this study, we explored the hypothesis that miRNAs act as downstream effectors of IL-11-induced cardiac fibrosis. Moreover, we investigated the translational potential of IL-11-regulated miRNAs as circulating biomarkers of cardiac fibrosis in AS patients. Methods and ResultsUsing computational approaches, we identified miRNA-497-5p and miRNA-27b-5p as potential new downstream profibrotic effectors of IL-11 in fibroblasts. We next confirmed that both miRNAs increased in healthy rat CF stimulated with IL-11 and in CF derived from post-infarction failing hearts. At the functional level, miRNA-497-5p and miRNA-27b-5p inhibition indirectly reduced the mRNA expression of collagen 1 (Col1a1). Conversely, transfection of CFs with mimics for each of the two miRNAs promoted fibroblast-to-myofibroblast transition and increased Col1a1 levels. We provided evidences that miRNA-27b-5p and miRNA-497-5p converge to promote hypoxia-inducible factor 1 signalling, by targeting its regulator EGLN (PHD) family members. The clinical relevance of our findings was confirmed using left ventricle (LV) specimens obtained from surgical patients with AS. The miRNA-27b-5p and miRNA-497-5p measured in the LV, peripheral plasma and plasma extracellular vesicles correlated with the severity of LV fibrosis, indicating these miRNAs potential as new circulating biomarkers of cardiac fibrosis. ConclusionsIn this study, we have newly identified the potential value of miRNA-27b-5p and miRNA-497-5p as actionable biomarkers of the profibrotic response to IL-11 in the heart. Future studies should validate the translational potential of the miRNAs as new clinical biomarkers and therapeutic targets.

molecular biology↗

bioRxiv2023

Nighttime-specific gene expression changes in suprachiasmatic nucleus and habenula are associated with resiliency to chronic social stress

The molecular mechanisms that link stress and circadian rhythms still remain unclear. The habenula (Hb) is a key brain region involved in regulating diverse types of emotion-related behaviours while the suprachiasmatic nucleus (SCN) is the bodys central clock. To investigate the effects of chronic social stress on transcription patterns, we performed gene expression analysis in the Hb and SCN of stress naive and stress exposed mice. Our analysis revealed a large number of differentially expressed genes and enrichment of synaptic and cell signalling pathways between resilient and stress-naive mice at ZT16 in both the Hb and SCN. This transcriptomic signature was nighttime-specific and observed only in stress-resilient mice. In contrast, there were relatively few differences between the stress-susceptible and stress-naive groups across timepoints. Our results reinforce the functional link between diurnal gene expression patterns and differential responses to stress, thereby highlighting the importance of temporal expression patterns in homeostatic stress responses.

neuroscience↗

bioRxiv2023

Tension sensing by FAK governs nuclear mechanotransduction, endothelial transcriptome and fate

Vascular endothelium forms a restrictive barrier to defend the underlying tissue against uncontrolled influx of circulating protein and immune cells. Mechanisms that mediate the transition from restrictive to leaky endothelium, a hallmark of tissue injury exemplified by acute lung injury (ALI), remain elusive. Using endothelial cell (EC)-Fak-/-mice, we show that FAK sensing and transmission of mechanical tension to the EC nucleus governs cell fate. In FAK- deleted EC, increased EC tension induced by Rho kinase caused tyrosine phosphorylation of nuclear envelope protein, emerin at Y74/Y95, and its localization in a nuclear cap. Activated emerin stimulated DNMT3a activity and methylation of the KLF2 promoter, impairing the restrictive EC transcriptome, including S1PR1. Inhibiting emerin phosphorylation or DNMT3a activity enabled KLF2 transcription of S1PR1, rescuing the restrictive EC phenotype in EC-Fak-/- lungs. Thus, FAK sensing of tension transmission to the nucleus is crucial for maintaining a restrictive EC fate and lung homeostasis.

cell biology↗

bioRxiv2023

Novel method for collecting hippocampal interstitial fluid extracellular vesicles (EV-ISF) reveals sex-dependent changes in microglial EV proteome in response to Aβ pathology

Brain-derived extracellular vesicles (EVs) play an active role in Alzheimers disease (AD), relaying important physiological information about their host tissues. Circulating EVs are protected from degradation, making them attractive AD biomarkers. However, it is unclear how circulating EVs relate to EVs isolated from disease-vulnerable brain regions. We developed a novel method for collecting EVs from the hippocampal interstitial fluid (ISF) of live mice. EVs (EVISF) were isolated via ultracentrifugation and characterized by nanoparticle tracking analysis, immunogold labeling, and flow cytometry. Mass spectrometry and proteomic analyses were performed on EVISF cargo. EVISF were 40-150 nm in size and expressed CD63, CD9, and CD81. Using a model of cerebral amyloidosis (e.g. APPswe,PSEN1dE9 mice), we found protein concentration increased but protein diversity decreased with A{beta} deposition. Genotype, age, and A{beta} deposition modulated proteostasis- and immunometabolic-related pathways. Changes in the microglial EVISF proteome were sexually dimorphic and associated with a differential response of plaque associated microglia. We found that female APP/PS1 mice have more amyloid plaques, less plaque associated microglia, and a less robust- and diverse-EVISF microglial proteome. Thus, in vivo microdialysis is a novel technique for collecting EVISF and offers a unique opportunity to explore the role of EVs in AD. Graphical AbstractHippocampal EVISF response to amyloid beta (A{beta}) is sexually dimorphic and related to the microglial EVISF proteome. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/532133v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1a275d6org.highwire.dtl.DTLVardef@e63da5org.highwire.dtl.DTLVardef@1d93cecorg.highwire.dtl.DTLVardef@12ed0db_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Maternal separation affects fronto-cortical activity in rat pups during dam-pup interactions and behavioral transitions

Early-life stress is known to impair neurodevelopment. Prior work from our group showed that prolonged physical and emotional separation necessitated by the medical needs of preterm infants (born <37 weeks) is associated with lower electroencephalogram (EEG) power in frontal areas, and that trend can be reversed by an intervention that enhances the physical and emotional contact between preterm infant and mother. Here we sought to model the changes in preterm infant frontal EEG power in a rodent model. We examined effects of daily maternal separation (MS) on frontal cortex electrophysiological (electrocorticography [EcoG]) activity in neonatal rats. We also explored the effects of dam-pup behavioral interactions on EcoG activity. From postnatal days (P) 2-10, rat pups were separated daily from their dam and isolated from their littermates for 3 hours. Control rats were normally reared. On P10, pups were implanted with telemetry devices and an electrode placed on the left frontal dura. EcoG activity was recorded during daily sessions over the next four days while pups remained in the home cage, as well as in response to a pup-dam isolation-reunion paradigm at P12. EcoG power was computed in 1 Hz frequency bins between 1-100 Hz. Dam and pup behavioral interactions during recording sessions were coded and synchronized to EcoG data. MS pups showed lower EcoG power during dam-pup interactions. These data parallel human and provide evidence of lower fronto-cortical activity as an early marker of early-life stress and possible mechanism for long-term effects of maternal separation on neurobehavioral development.

neuroscience↗

bioRxiv2020

An assessment of efficacy of Iodine complex (Renessans) against SARS-CoV-2 in non-human primates (Rhesus macaque)

Renessans is an iodine complex which has proven in vitro antiviral activity including Anti-SARS-CoV-2 activity. The present study was designed to determine its efficacy against SARS-CoV-2 in monkeys (Rhesus macaque). A total of 14 monkeys were divided into four groups: A) Prophylactic group (n=03), (B) Treatment group (n=03), (C) infection control group (n=04) and (D) negative control group (n=04) and were housed in BSL-3 Animal facility while group D was housed at another animal house. Group A was administered with Renessans @ 2.85 mg/7 kg from 5 days prior to the infection to 08 days post infections (DPI). Group B was administered with Renessans from 03-08 DPI @ 2.85 mg/7 kg. Group C was administered with WIF only. The infection @ 2 x 106 TCID of SARS-CoV-2 was given to all group monkeys through intranasal and oral route under anesthesia. Nasal swab samples (at different times) and fecal matter on daily basis were collected for the detection of SARS-CoV-2 through real-time quantitative PCR. Three monkeys (one from each of group A, B and C) were euthanized at 07 DPI to determine the gross pathological lesions and SARS-CoV-2 detection from internal tissues. Nasal swabs from all the monkeys from group A, B and C were positive for SARS-CoV-2 at 02 and 07 DPI (Day 05 of treatment). At 14 DPI, all (100%) nasal swabs from group A were negative for SARS-CoV-2 while 50% and 100% were positive from group B and C, respectively. At 21 DPI, monkeys from group B were negative and all in group C were still positive for SARS-CoV-2. Similarly, fecal matter of monkeys in group A and B was returned negative in significantly lesser time as compared to monkeys from infection control group. Based on these research findings it is concluded that the Renessans has in-vivo SARS-CoV-2 activity and may result in early clearance of SARS-CoV-2. Therefore, a clinical trial of the drug in COVID-19 patients may reveal its anti-COVID-19 potential.

microbiology↗

bioRxiv2019

Signal to Noise Ratio as a Cross-Platform Metric for Intraoperative Fluorescence Imaging

Real-time molecular imaging to guide curative cancer surgeries is critical to ensure removal of all tumor cells, however visualization of microscopic tumor foci remains challenging. Wide variation in both imager instrumentation and molecular labeling agents demands a common metric conveying the ability of a system to identify tumor cells. Microscopic disease, comprised of a small number of tumor cells, has a signal on par with the background, making the use of signal (or tumor) to background ratio inapplicable in this critical regime. Therefore, a metric that incorporates the ability to subtract out background, evaluating the signal itself relative to the sources of uncertainty, or noise is required. Here we introduce the signal-to-noise ratio (SNR) to characterize the ultimate sensitivity of an imaging system, and optimize factors such as pixel size. Variation in the background (noise) are due to electronic sources, optical sources, and spatial sources (heterogeneity in tumor marker expression, fluorophore binding, diffusion). Here we investigate the impact of these noise sources and ways to limit its effect on SNR. We use empirical tumor and noise measurements to procedurally generate tumor images and run a monte carlo simulation of microscopic disease imaging to optimize parameters such as pixel size.

bioengineering↗

bioRxiv2019

Physical activity improves sarcopenia in a murine model by enhancing the proliferative potential of muscle stem cells, oxidative capacity of mitochondrial enzymes and expression of Sestrins

Sarcopenia is a major health issue in old age. Underlying molecular mechanisms in its genesis remain unclear and optimal animal models are yet to be established. A novel animal model was developed to identify structural and functional changes in skeletal muscles from sarcopenia. The influence of physical activity on animals of the sarcopenic model with respect to the expression of anti-oxidant proteins, mitochondrial oxidative capacity, and effect on muscle stem cells (MuSCs), were assessed. Male C57Bl/6 mice of different age groups were recruited: Y-Cntrl (young-control), A-Cntrl (aged-control), SAR-model and SAR-INT. SAR-model group was kept in a retrofitted confined cage and was fed with customized protein-restricted diet (14% protein), which is considered as a sarcopenic featured model. SAR-INT served as the intervention group. Three parameters, namely, muscle mass, grip strength, and physical endurance, were used to confirm the sarcopenic state. All physical parameters deteriorated most in SAR-model and it improved in the SAR-INT group. The impact of physical activity on the SAR-INT group was also evidenced by the improved proliferative potential of MuSCs determined by flow cytometric analysis. Compared with the SAR-model, the SAR-INT exhibited significant improvement in the oxidative capacity of mitochondrial enzymes and increased expression of anti-oxidant proteins, sestrins. In conclusion, physical activity improved physical parameters, MuSC proliferative potential, mitochondrial enzyme oxidative capacity and sestrin expression in sarcopenic animals. Hence, SAR-model in mice can serve as a novel sarcopenic model, physical activity provides scope for improvement in sarcopenic population and sestrin molecule can have a potential implication on sarcopenia.

molecular biology↗

bioRxiv2019

FGF signalling regulates enhancer activation during ear progenitor induction

The fibroblast growth factor pathway is essential for inner ear induction in many vertebrates, however how it regulates the chromatin landscape to coordinate the activation of otic genes remains unclear. Here we show that FGF exposure of sensory progenitors leads to rapid deposition of active chromatin marks H3K27ac near hundreds of FGF-responsive, otic-epibranchial progenitor (OEP) genes, while H3K27ac is depleted in the vicinity of non-otic genes. Genomic regions that gain H3K27ac act as cis-regulatory elements controlling OEP gene expression in time and space and define a unique transcription factor signature likely to control their activity. Finally, we provide evidence that in response to FGF signalling the transcription factor dimer AP1 recruits the histone acetyl transferase p300 to OEP enhancers and that de novo acetylation is required for subsequent expression of OEP genes. Thus, during ear induction FGF signalling modifies the chromatin landscape to promote enhancer activation and chromatin accessibility.

developmental biology↗

bioRxiv2018

Immunoinformatics Prediction of Epitope Based Peptide Vaccine Against Madurella mycetomatis Translationally Controlled Tumor Protein

BackgroundMadurella. mycetomatis is most common causative agent of mycetoma in Sudan and worldwide. No vaccines are available till now so design of effective vaccine is essential as protection tool. Peptide vaccine can overcome the common side effects of the conventional vaccines. The aim of this study was to design peptide based vaccine for M.Mycetomatis Translationally Controlled Tumor Protein (TCTP) using immunoinformatics tools.\n\nMaterials and methodsTCTP sequences were retrieved from NCBI and then processed using BioEdit program to determine conserved regions and different immunoinformatics tools from IEDB. Population coverage analysis was performed for the most promising epitopes. Homology modelling was performed to show their structural positions in TCTP. Protein analysis was done using Expasy (ProtParamsotware).\n\nResults and conclusionFour epitopes passed the Bepipred, Emini, Kolaskar and Tongaonkar tools. 111 epitopes were predicted to interact with MHCI alleles with IC50 < 500 nM, three of them were most promising. 274 predicted epitopes were interacted with MHCII alleles with IC50 < 100 nM, four of them were most promising. The epitope (YMKSVKKAL) was the most promising one concerning its binding with MHCI alleles, while (FRLQSTSFD) was the most promising for MHC II. The epitope (YLKAYMKSV) is shared betweenMHC I and II. For the population coverage of M. Mycetomatis TCTP vaccine Sudan (90.39%) had the highest percentage for MHC I. This is the first computational vaccinology study conducted in mycetoma caused by M. Mycetomatis using TCTP.

bioinformatics↗