Biology subjects

Ahmad, I.

Publications and source records attributed to Ahmad, I..

At least 19 recordsLinked to original sources

bioRxiv2026

Slow stress-load accumulation dominates BDNF-dependent gain in a ten-state computational model of stress biochemistry

BackgroundAcute stress responses are often reversible, whereas sustained stress can produce coordinated disruption across endocrine, metabolic, inflammatory, antioxidant, and neuroplastic pathways. The Tiered Stress Biochemistry Model (TSBM) is a hypothesis-generating ten-state ordinary differential-equation framework linking a stylized cortisol signal to noradrenergic drive, vitamin C, a phenomenological aldosterone/renin-angiotensin drive, magnesium, normalized BDNF-related and Nrf2-related states, inflammation, and tryptophan-kynurenine metabolism. MethodsFive prespecified scenarios (normal, acute, chronic, depression-like, and low-cortisol PTSD-like) were simulated for 168 hours. Analyses included local stability, output-specific sensitivity screening, structural ablation, a 400-draw Latin-hypercube scan over independent {+/-} 20% parameter ranges, uncertainty distributions for threshold-crossing times, a success-conditioned parameter-trade-off screen, and a wider scan in which hypothesized BDNF-feedback gain magnitudes varied log-uniformly from 0.1 to 10 times nominal. Parameters were classified as literature-derived, literature-constrained/model-defined, calibrated, or hypothesized. ResultsUnder the specified forcing assumptions, sustained stress produced coordinated changes across several pathways. In the depression-like scenario, removing slow stress-load accumulation increased day-7 BDNF-related activity from 47.2% to 82.6%, reduced inflammation from 14.63 to 2.15 arbitrary units, and lowered KYN/TRP from 0.173 to 0.057. Removing BDNF-dependent gain increased BDNF only to 49.1% and delayed KYN/TRP crossing by 2.5 hours. The stricter multi-output conclusion was retained in 91% of uncertainty draws. Median crossing times retained the nominal sequence, but the complete four-event order occurred in only 43% of all draws. ConclusionsWithin this reduced model, a shared slow stress-load process coordinates the high-exposure state, whereas BDNF-dependent feedback acts mainly as an amplifier. The model generates an experimentally testable staging hypothesis: under sustained high-exposure forcing, magnesium changes may precede later BDNF-related and KYN/TRP changes. Longitudinal studies are required to determine whether this sequence occurs biologically, whether it is reversible, and whether it has clinical relevance. The simulations are not diagnostic or treatment recommendations.

systems biology↗

bioRxiv2026

Regulatory plasticity of the rdar biofilm morphotype in clinical uropathogenic Escherichia coli and its modulation by ciprofloxacin

Red, dry and rough (rdar) biofilm formation in Escherichia coli is characterized by the coordinated production of extracellular cellulose and amyloid curli fimbriae. Although rdar biofilm formation has been extensively characterized in laboratory strains, its clinical relevance and implications for antimicrobial treatment remain poorly understood. Here, we systematically investigate rdar biofilm formation of 150 consecutively isolated E. coli strains recovered from patients with urinary tract infections and correlate it to antimicrobial resistance. Genetic analysis of rdar regulation revealed distinct nucleotide signatures within the csgD promoter region that discriminate semi-constitutive rdar expression from temperature-dependent phenotypes, highlighting regulatory plasticity among clinical isolates. Whole-genome sequencing-based phylogenetic analysis further demonstrated that rdar-positive isolates are distributed across diverse E. coli phylogroups and sequence types, indicating that rdar biofilm formation is not restricted to specific clonal lineages. Strikingly, phenotypic assays revealed that the fluoroquinolone antibiotic ciprofloxacin suppresses rdar biofilm formation and associated extracellular matrix architecture in ciprofloxacin-resistant isolates at subinhibitory concentrations, suggesting that ciprofloxacin modulates biofilm-associated pathways beyond its canonical bactericidal targets. Together, our findings establish the rdar morphotype as a clinically relevant biofilm phenotype in uropathogenic E. coli and reveal an antibiofilm activity of ciprofloxacin that is uncoupled from antibiotic resistance. These results underscore the importance of considering antibiotic-mediated modulation of biofilm behavior when interpreting treatment responses and designing strategies to combat persistent urinary tract infections.

microbiology↗

bioRxiv2026

Vancomycin tolerance and dispersion of dual species biofilms of Clostridioides difficile and Vancomycin-resistant Enterococcus faecium

ObjectivesBiofilms are the dominant mode of bacterial life. The gut microbiota itself has characteristics of a biofilm that grows on the intestinal mucosa. C. difficile and VRE are commonly co-isolated from patients but biofilm formation has not been studied in a multi-species context. Here we study the interactions between C. difficile and VRE in surface adherent community. ResultsWe found that VRE inhibits C. difficile biofilm formation in dual-species culture in the presence of excess glucose. Robust dual-species biofilms were produced when the carbon source was changed to a non-fermentable sugar such as fucose and xylose. We observed a high level of vancomycin tolerance in C. difficile biofilms that was not affected by the presence of VRE. Finally we also found that a nutrient step-change is sufficient to induce dispersion of single and dual-species biofilms. ConclusionsVRE can inhibit the development of C. difficile biofilms in the presence of a fermentable carbon source. VRE does not appear to affect vancomycin tolerance or nutrient-induced dispersion of C. difficile biofilms. Highlights- VRE inhibits C. difficile biofilm formation in the presence of fermentable glucose. - Stable VRE - C. difficile biofilms are formed by managing the available carbon source. - VRE does not affect C. difficile vancomycin tolerance in this model. - A 10-fold increase in available nutrients is sufficient to induce biofilm dispersion in C. difficile and VRE.

microbiology↗

bioRxiv2025

Integrative Computational Analysis Reveals H. pylori GroEL as a Stabilizer of Neurotoxic Amyloid-β Oligomers

Alzheimers disease (AD) is characterized by amyloid-{beta} (A{beta}) aggregation, with soluble oligomers implicated as the most neurotoxic species. Recent evidence suggests microbial infections, including Helicobacter pylori, contribute to AD pathogenesis. This study investigates the role of H. pylori GroEL, a conserved chaperonin found in bacterial outer membrane vesicles (OMVs), in stabilizing toxic A{beta} oligomers. A pan-genome analysis of 353 H. pylori strains identified GroEL as a highly conserved protein present in 83% of strains, which supported its widespread relevance. We structurally modelled a conserved 27-amino acid GroEL fragment and docked it against the A{beta} (1-42) tetramer. Interaction analysis revealed stabilizing salt bridges, hydrogen bonds, and extensive non-bonded contacts within the GroEL-A{beta} complex. Molecular dynamics simulations (50 ns) demonstrated that GroEL binding enhanced A{beta} oligomer stability, evidenced by reduced structural deviations and a more extensive hydrogen bonding network compared to A{beta} oligomer alone. These computational findings support a novel mechanism whereby H. pylori GroEL directly stabilizes soluble A{beta} oligomers. We hypothesize that this stabilization inhibits their aggregation into plaques while paradoxically prolonging the lifetime of neurotoxic species, potentially increasing neurodegeneration through pathways distinct from canonical amyloid deposition. This highlights the complex role of bacterial proteins in AD and underscores the need for experimental validation of GroEL-A{beta} interactions as a potential therapeutic target.

bioinformatics↗

bioRxiv2025

MyeliMetric: A Python-Based Toolbox for Standardized G-ratio Analysis of Axon-Myelin Integrity

The g-ratio, defined as the ratio of an axons diameter to the total fiber diameter (axon plus myelin), is a key metric for assessing myelin integrity and axonal conduction velocity in both the central and peripheral nervous systems. Deviations from the physiological range often signal underlying pathology. Despite its diagnostic importance, there is currently no standardized, open-source tool for g-ratio analysis from post-segmented electron microscopy images. To address this gap, we developed MyeliMetric, a Python-based, user-friendly toolbox that streamlines g-ratio data preprocessing and integrates biologically informed validation, requiring minimal statistical expertise to operate without introducing common analytical errors. It is built on the principle that g-ratios exhibit relative consistency across varying axon diameters in healthy conditions. To rigorously assess this relationship, MyeliMetric implements a binning strategy that groups axons into biologically relevant diameter cohorts, enabling the detection of size-dependent deviations in g-ratio distributions. This approach addresses common limitations in conventional analyses, including insufficient sampling, pseudo-replication, and artifacts such as misleading regression slopes. Validation using both synthetic and published datasets from rodent models of demyelination demonstrated the tools accuracy, reproducibility, and biological relevance. Synthetic data yielded expected outcomes, and in experimental models, MyeliMetric reliably detected reductions in myelin thickness through g-ratio shifts while minimizing artifacts, thereby providing biologically meaningful insights. It is available on GitHub: https://github.com/Intakhar-Ahmad/NeuroMyelin-G-Ratio-Analysis-Toolkit

neuroscience↗

bioRxiv2025

Phenotypic Antibiotic Susceptibility Testing at the limit of one bacterial cell

The blood of a patient with bacteremia contains only a few bacteria per milliliter. Recently, techniques have been developed for extracting these few bacteria from whole blood. Here, we evaluate if a phenotypic Antibiotic Susceptibility Test (AST) can be performed on a single bacterial cell by monitoring changes in its phenotypic distributions sampled over time rather than across populations, while also accounting for experimental noise and cell-to-cell variability. We use the method to estimate the time required to correctly classify single susceptible or resistant bacteria when treated with antibiotics that affect growth, cell division, or cause lysis. We find that due to heterogeneous single cell responses, it is necessary to consider all bacteria close to the susceptibility breakpoint as resistant. However, it is possible to follow up resistance calls by sequentially exposing the cell or its lineage to new antibiotics until a susceptible phenotype is detected.

microbiology↗

bioRxiv2025

Murine Leukemia Virus GlycoGag Antagonizes SERINC5 via ER-phagy Receptor RETREG1

Serine incorporator 5 (SERINC5) is a host restriction factor that targets certain enveloped viruses, including human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MLV). It integrates into the viral envelope from the cell surface, inhibiting viral entry. SERINC5 is transported to the cell surface via polyubiquitination, while a single K130R mutation retains it in the cytoplasm. Both HIV-1 Nef and MLV glycoGag proteins antagonize SERINC5 by reducing its expression in producer cells. Here, we report that MLV glycoGag employs selective autophagy to downregulate SERINC5, demonstrating a more potent mechanism for decreasing its cell surface expression. Although glycoGag is a type II integral membrane protein, it primarily localizes to the cytoplasm and undergoes rapid proteasomal degradation. Employing the K130R mutant, we show that Nef, primarily associated with the plasma membrane, downregulates SERINC5 only after it has trafficked to the cell surface, whereas glycoGag can reduce its expression before reaching the plasma membrane while still in the cytoplasm. Nonetheless, an interaction with SERINC5 stabilizes and recruits glycoGag to the plasma membrane, enabling it to downregulate SERINC5 from the cell surface. Through affinity-purified mass spectrometry analysis combined with CRISPR/Cas9 knockouts, we find that glycoGags activity depends on reticulophagy regulator 1 (RETREG1), an ER-phagy receptor. Further knockout experiments of critical autophagy genes demonstrate that glycoGag downregulates cytoplasmic SERINC5 via micro-ER-phagy. These findings provide crucial new insights into the ongoing arms race between retroviruses and SERINC5 during infection. AUTHOR SUMMARYHIV-1 Nef and MLV glycoGag are unrelated viral proteins, yet both counteract the same host restriction factor, SERINC5, to facilitate productive infection. In this study, we report a novel pathway through which glycoGag downregulates SERINC5. We demonstrate that while Nef downregulates SERINC5 only after it has trafficked to the cell surface, glycoGag can directly downregulate SERINC5 in the cytoplasm before it reaches the plasma membrane. Furthermore, we show that this pathway is mediated by the ER-phagy receptor RETREG1, which targets SERINC5 for degradation via micro-ER-phagy. This mechanism provides a more effective means of blocking SERINC5 antiviral activity. These findings reveal that retroviruses have evolved different strategies to antagonize SERINC5, highlighting the critical role of SERINC5 in restricting retroviral infections.

microbiology↗

bioRxiv2025

Aerobic exercise decreases the number and transcript expression of inflammatory M1 macrophages and CD8+ T cells in the epicardial adipose tissue of female pigs

BackgroundEpicardial adipose tissue (EAT) regulates coronary artery function via lipid metabolism and immune cell recruitment. Increased EAT is a risk factor for coronary artery disease (CAD), but aerobic exercise mitigates CAD. The effect of aerobic exercise on immune cells in EAT is unknown. We hypothesized that aerobic exercise creates an anti-inflammatory environment characterized by increased M2 macrophages and up-regulation of anti-inflammatory cytokine transcripts in EAT. MethodsFemale Yucatan pigs (n=7) were allocated to sedentary or exercised groups. To mimic CAD, a coronary artery was chronically occluded or remained non-occluded. EAT samples were processed for bulk and single nuclei transcriptomic sequencing. ResultsSub-clustering identified immune, endothelial, smooth muscle, adipocytes, adipocyte progenitor cells (APSCs), and neuronal cells, with adipocytes and APSCs being dominant. Non-occluded sedentary EAT had the largest percentage of M1 macrophages and CD8+ T cells. Irrespective of occlusion, sedentary EAT had the largest fraction of cells expressing genes in the tumor necrosis factor (TNF) superfamily. Irrespective of occlusion, exercise upregulated peroxisome proliferator-activated receptor (PPAR) gamma (G) expression and enriched PPAR signaling pathways in adipocytes, macrophages, and T cells. However, PPARG expression was lowest in CD8+ T cells from non-occluded exercised EAT. The greatest number of significant cell-cell communications between adipocytes and immune cells via growth factors and adhesion molecules occurred in occluded sedentary EAT. ConclusionAerobic exercise mitigates the proinflammatory nature of EAT in CAD via modulation of immune cell subpopulations, decreased TNF superfamily and increased PPARG gene expression, and decreased growth factor communication between adipocytes and immune cells.

cell biology↗

bioRxiv2025

Remodeling of nucleosome by a DNA translocating bacterial restriction-modification enzyme

A eukaryotic cell has specialized ATP-dependent chromatin remodelers, such as SWI/SNF, to unfurl DNA from nucleosome for functional processing. The ATPase that powers the movement of the chromatin remodeler on the DNA (translocation) is evolutionarily related to those powering the translocation of the functionally distinct bacterial restriction-modification (RM) enzymes. The collision of a SWI/SNF chromatin remodeler and a nucleosome, results in sliding/ejection of the constituent histone octamer, while two converging ATP-dependent RM enzymes catalyze DNA cleavage. Here, we investigate if an ATP-dependent Type ISP RM enzyme, an active and directional translocase, can remodel nucleosomes. Our results reveal that in presence of ATP, a Type ISP RM enzyme can displace the octamers from not just mononucleosomes but also two tandem nucleosomes. However, a Type III RM enzyme, which employs a homologous ATPase as a switch to facilitate bidirectional 1D diffusion along the DNA, fails to remodel the nucleosome. This implies that an actively translocating Type ISP RM enzyme generates sufficient force for chromatin remodeling, and may serve as artificial sequence-specific chromatin remodelers.

molecular biology↗

bioRxiv2024

Oxidative Injury to Lung Mitochondrial DNA is a Key Contributorfor the Development of Chemical Lung Injury

The mechanisms and extent to which inhalation of oxidant gases damage the mitochondrial genome contributing to the development of acute and chronic lung injury have not been investigated. C57BL/6 mice exposed to chlorine (Cl2) gas and returned to room air, developed progressive loss of lung DNA glycosylase OGG1, significant oxidative injury to mtDNA, decreased intact lung mitochondrial (mt) DNA, generation of inflammatory pathway by DAMPs causing airway and alveolar injury with significant mortality. Global proteomics identified over 1400 lung proteins with alteration of key mitochondrial proteins at 24 h post Cl2 exposure. Intranasal instillation of a recombinant protein containing mitochondrial targeted OGG1 (mitoOGG1) post exposure, decreased oxidative injury to mtDNA, lung mitochondrial proteome, severity of the acute and chronic lung injury and increased survival. These data show that injury to the mt-genome is a key contributor to the development of acute and chronic lung injury.

physiology↗

bioRxiv2024

Loss of ARID1A accelerates prostate tumourigenesis with a proliferative collagen-poor phenotype through co-operation with AP1 subunit cFos

Prostate cancer (PC) is the most common male visceral cancer, and second leading cause of cancer mortality in men in the Western world. Using a forward-mutagenesis Sleeping Beauty (SB) transposon-based screen in a Probasin Cre-Recombinase (Pb-Cre) Pten-deficient mouse model of PC, we identified Arid1a loss as a driver in the development of metastatic disease. The insertion of transposon in the Arid1a gene resulted in a 60% reduction of Arid1a expression, and reduced tumour free survival (SB:Ptenfl/fl Arid1aINT median 226 days vs SB:Ptenfl/fl Arid1aWT293 days, p=0.02),with elevated rates of metastasis (SB:Ptenfl/fl Arid1aINT 75% lung metastasis rate vs 17% SB:Ptenfl/fl Arid1aWT, p<0.001 ). We further generated a Pb-Cre Pten- and Arid1a-deficient mouse model, in which loss of Arid1a demonstrated a profound acceleration in tumorigenesis in Ptenfl/fl mice compared to Pten loss alone (Pb-Cre Ptenfl/flArid1a+/+median survival of 267 days vs Pb-Cre Ptenfl/fl Arid1afl/fl103 days, p<0.0001). Our data revealed homozygous Arid1a loss is required to dramatically accelerate prostate tumourigenesis, resulting in tumours with a less differentiated phenotype and a disorganised stroma. Furthermore, Arid1a loss mediated tumour formation in the mouse involved both the anterior and dorsolateral lobes, a unique feature from Pten-loss and other reported PC GEMM where tumour formation tends to be limited to the anterior lobes. Analysis of RNA and ChIP -Sequencing data suggests Arid1a loss enhanced the function of AP-1 subunit cFos. In clinical PC cohort, ARID1A and cFos levels stratified an aggressive subset of PC with a poor survival outcome with a median of only 30 months.

cancer biology↗

bioRxiv2024

TFIIS is required for reproductive development and thermal adaptation in barley

Regulation of transcriptional machinery and its adaptive role under different stress conditions are studied extensively in the dicot model plant Arabidopsis, but our knowledge on monocot species remains elusive. TFIIS is an RNA polymerase II associated transcription elongation co-factor. Previously it was shown that TFIIS ensures efficient transcription elongation that is necessary for heat stress survival in A. thaliana. However, the function of TFIIS has not been analysed in monocots. In the present work, we have generated and studied independent tfIIscrispr mutant barley lines. We show that, TFIIS is needed for reproductive development and heat stress survival in barley. The molecular basis of HS-sensitivity of tfIIs mutants is the retarded expression of heat stress protein transcripts, that leads to late accumulation of HSP chaperones, enhanced proteotoxicity and ultimately to lethality. We also show that TFIIS is induced and autoregulated in response to heat, supporting a conserved adaptive function of these control elements for plant thermal adaptation. In sum, our results are a step forward for the better understanding of transcriptional machinery regulation in monocot crops.

plant biology↗

bioRxiv2023

Single-nucleus transcriptomics of epicardial adipose tissue from females reveals exercise control of innate and adaptive immune cells

Coronary artery disease (CAD) is a leading cause of death in women. Although exercise mitigates CAD, the mechanisms by which exercise impacts epicardial adipose tissue (EAT) are unknown. We hypothesized that exercise promotes an anti-inflammatory microenvironment in EAT from female pigs. Yucatan pigs (n=7) were assigned to sedentary (Sed) or exercise (Ex) treatments and coronary arteries were occluded (O) with an ameroid to mimic CAD or remained non-occluded (N). EAT was collected for bulk and single nucleus transcriptomic sequencing (snRNA-seq). Exercise upregulated G-protein coupled receptor, S100 family, and FAK pathways and downregulated the coagulation pathway. Exercise increased the interaction between immune, endothelial, and mesenchymal cells in the insulin-like growth factor pathway and between endothelial and other cell types in the platelet endothelial cell adhesion molecule 1 pathway. Sub- clustering revealed nine cell types in EAT with fibroblast and macrophage populations predominant in O-Ex EAT and T cell population predominant in N-Ex EAT. Coronary occlusion impacted the largest number of genes in T and endothelial cells. Genes related to fatty acid metabolism were the most highly upregulated in non-immune cells from O-Ex EAT. Sub-clustering of endothelial cells revealed that N-Ex EAT separated from other treatments. In conclusion, aerobic exercise increased interaction amongst immune and mesenchymal and endothelial cells in female EAT. Exercise was minimally effective at reversing alterations in gene expression in endothelial and mesenchymal cells in EAT surrounding occluded arteries. These findings lay the foundation for future work focused on the impact of exercise on cell types in EAT. Significance StatementCoronary artery disease (CAD) is a leading cause of death in women. However, the role of epicardial adipose tissue (EAT) in the development of CAD in females and how exercise, which is recommended to slow CAD progression, impacts EAT are unknown. The effect of aerobic exercise on gene expression in EAT was investigated with RNA-sequencing, revealing significant alterations in fatty acid processing and immunoregulatory processes. This study provides valuable insights into the molecular and cellular changes induced in EAT by exercise in the context of chronic ischemic heart disease in females. These findings bolster current understanding of the impact of aerobic exercise on cardiac health in females and provide a foundation for future research in the field of exercise science.

physiology↗

bioRxiv2023

Non-antibiotic pharmaceuticals exhibit toxicity against Escherichia coli at environmentallyrelevant concentrations with no evolution of cross-resistance to antibiotics

Antimicrobial resistance can arise in the natural environment via prolonged exposure to the effluent surrounding manufacturing facilities. These facilities also produce non-antibiotic pharmaceuticals, and the effect of these on the surrounding microbial communities is less clear; whether they have inherent toxicity, or whether long-term exposure might select for cross-resistance to antibiotics. To this end, we screened four non-antibiotic pharmaceuticals (acetaminophen, ibuprofen, propranolol, met formin) and titanium dioxide for toxicity against Escherichia coli K-12 MG1655 and conducted a 30 day selection experiment to assess the effect of long-term exposure. All compounds reduced the maximum optical density reached by E. coli at a range of concentrations including one of environmental relevance, with transcriptome analysis identifying upregulated genes related to stress response and multidrug efflux in response ibuprofen treatment. The non-antibiotic pharmaceuticals did not select for significant genetic changes following a 30 day exposure, and no evidence of selection for cross-resistance to antibiotics was observed for population evolved in the presence of ibuprofen in spite of the differential gene expression after exposure to this compound. This work suggests that these non-antibiotic pharmaceuticals, at environmental concentrations, do not select for cross-resistance to antibiotics in E. coli.

microbiology↗

bioRxiv2023

Hemopexin Reverses Activation of Lung eIF2a and Decreases Mitochondrial Injury in Chlorine Exposed Mice

We assessed the mechanisms by which non-encapsulated heme, released in the plasma of mice post exposure to chlorine (Cl2) gas, resulted in the initiation and propagation of acute lung injury. We exposed adult C57BL/6 male and female to Cl2 (500 ppm for 30 min) in environmental chambers and returned them to room air and injected them intramuscularly with a single dose of human hemopexin (hHPX; 5 {micro}g/ g BW), the most efficient scavenger of heme, 30-60 min post exposure. Concentrations of hHPX in plasma of air and Cl2 exposed mice were 9081{+/-}900 vs. 1879{+/-} 293 at 6 h and 2966{+/-}463 vs. 1555{+/-}250 at 50 h post injection (ng/ml; X{+/-}1 SEM=3; p<0.01). Cl2 exposed mice developed progressive acute lung injury post exposure characterized by increased concentrations of plasma heme, marked inflammatory response, respiratory acidosis and increased concentrations of plasma proteins in the alveolar space. Injection of hHPX decreased the onset of acute lung injury at 24 h post exposure; mean survival, for the saline and hHPX groups were 40 vs. 80% (P<0.001) at 15 d post exposure. Non-supervised global proteomics analysis of mouse lungs at 24 h post exposure, revealed the upregulation of 92 and downregulation of 145 lung proteins. Injection of hHPX at one h post exposure moderated the Cl2 induced changes in eighty-three of these 237 lung proteins. System biology analysis of the global proteomics data showed that hHPX reversed changes in mitochondrial dysfunction and elF2 and integrin signaling. Western blot analysis of lung tissue showed significant increase of phosphorylated elF2 at 24 h post exposure in vehicle treated mice but normal levels in those injected with hHPX. Similarly, RT-PCR analysis of lung tissue showed that hHPX reversed the onset of mtDNA lesions. A form of recombinant human hemopexin generated in tobacco plants was equally effective in reversing acute lung and mtDNA injury. The results of this study offer new insights as to the mechanisms by which exposure to Cl2 results in acute lung injury and to the therapeutic effects of hemopexin.

physiology↗

bioRxiv2023

Exploring phytoconstituents of Juglans regia to treat cervical cancer using integrative Bioinformatics

Cervical cancer is the fourth most common malignancy among women, which also turns out to be the most common cause of death in women worldwide. Medicinal plants have traditionally been used to treat various diseases and disorders. The current study utilizes the molecular docking technique to investigate the anticancer potential of Juglans regia phytoconstituents against cervical cancer target proteins. This study includes the microarray dataset analysis of GSE63678 from the NCBI Gene Expression Omnibus database to identify differentially expressed genes. Furthermore, network biology approaches were employed to construct protein-protein interaction of differentially expressed genes. Next, the computation of topological parameters utilizing Cytohubba renders the top five hub genes (IGF1, FGF2, ESR1, MYL9, and MYH11). In addition, Juglans regia phytocompounds mined from the IMPPAT database were subjected to molecular docking analysis against identified hub genes. The application of molecular dynamics simulation validated the stability of prioritized docked complexes with minimum binding energy.

bioinformatics↗

bioRxiv2023

Novel Imaging Guidance for Cholesteatoma Surgery usingTissue Autofluorescence

SignificanceCholesteatoma is an expansile destructive lesion of the middle ear and mastoid, which can result in significant complications by eroding adjacent bony structures. Currently, there is an inability to accurately distinguish cholesteatoma tissue margins from middle ear mucosa tissue, causing a high recidivism rate. Accurately differentiating cholesteatoma and mucosa will enable a more complete removal of the tissue. AimDevelop an imaging system to enhance the visibility of cholesteatoma tissue and margins during surgery. ApproachCholesteatoma and mucosa tissue samples were excised from the inner ear of patients and illuminated with 405, 450, and 520 nm narrowband lights. Measurements were made with a spectroradiometer equipped with a series of different longpass filters. Images were obtained using a red-green-blue (RGB) digital camera equipped with a long pass filter to block reflected light. ResultsCholesteatoma tissue fluoresced under 405 and 450 nm illumination. Middle ear mucosa tissue did not fluoresce under the same illumination and measurement conditions. All measurements were negligible under 520 nm illumination conditions. All spectroradiometric measurements of cholesteatoma tissue fluorescence can be predicted by a linear combination of emissions from keratin and flavin adenine dinucleotide (FAD). We built a prototype of a fluorescence imaging system using a 495 nm longpass filter in combination with an RGB camera. The system was used to capture calibrated digital camera images of cholesteatoma and mucosa tissue samples. The results confirm that cholesteatoma emits light when it is illuminated with 405 and 450 nm, whereas mucosa tissue does not. ConclusionsWe prototyped an imaging system that is capable of measuring cholesteatoma tissue autofluorescence.

bioengineering↗

bioRxiv2023

Potentiation of host defense through sRNA packaged in OMVs of Xanthomonas oryzae pv. oryzicola

Bacterial outer membrane vesicles (OMVs)-packaged delivery of noncoding small RNAs (sRNAs) can function as novel mediators of interspecies communication. However, the role of which in the interaction between phytopathogenic bacteria and their host plants is unclear. In this study, we characterized differentially packaged sRNAs in Xanthomonas oryzae pv. oryzicola (Xoc) BLS256 OMVs using RNA-Seq, and we selected the most abundant sRNA Xosr001 for further study based on its essential role in the induction of stomatal immunity in rice. Xoc loads Xosr001 into OMVs, which are transferred specifically into the mechanical tissues of rice leaves. We uncovered that OMVs-mediated Xosr001 inhibitors attenuated OsJMT1 transcripts in vivo and reduced the endogenous MeJA contents in rice leaves. Stomatal conductance was measured to show that {Delta}Xosr001 mutant weakened the ability of stomatal re-opening on rice leaves after spray inoculation. Most notably, the transgenic rice lines OsJMT1-HA-OE exhibited attenuated stomatal immunity and disease susceptibility after {Delta}Xosr001 infection compared with Xoc infection. These results define that Xosr001 packaged in Xoc OMVs highlights a smart molecular mechanism to activate stomatal immunity in rice.

plant biology↗