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bioRxiv2022

Differential expression patterns and potential regulatory function of piRNAs in western honey bee larval response to Ascosphaera apis infestation

piRNAs are a class of small non-coding RNAs that play an essential part in genomic defense, as well as in modulation of gene expression and diverse biological processes such as host-pathogen interaction. However, little is known about the expression pattern of the regulatory function of piRNAs in interactions between honey bees and pathogens. In this work, on the basis of our previously obtained high-quality small RNA-seq datasets from western honey bee (Apis mellifera) larval guts, the differential expression profile of piRNAs in A. mellifera larval guts after Ascosphaera apis infestation was analyzed, followed by structural characterization, target prediction, and regulatory network investigation. The potential roles of differentially expressed piRNAs (DEpiRNAs) in regulating host response, especially immune response, were further discussed. In this study, 504, 657, and 587 piRNAs were respectively identified in the 4-, 5-, and 6-day-old larval guts infected by A. apis, with 411 (53.24%) piRNAs shared. The length distribution of these piRNAs ranged from 24 nt to 33 nt and their first base had a "C" bias, similar to piRNAs discovered in other mammals and insects. Additionally, 96, 103, and 143 DEpiRNAs were detected in the 4-, 5-, and 6-day-old comparison groups; among these, piR-ame-149736, piR-ame-1066173, and piR-ame-1125190 were the most up-regulated, while piR-ame-1202932 was the most down-regulated. There were 68 DEpiRNAs shared between these three comparison groups. The targets of the DEpiRNAs in the three comparison groups were engaged in a suite of crucial functions associated with biological processes, molecular function, and cellular components, including molecular transducer activity, biological regulation, and membrane part. These targets were also relevant to diverse vital pathways such as the phosphatidylinositol signaling system, inositol phosphate metabolism, and Wnt signaling pathway. Further investigation demonstrated that targets of DEpiRNAs were involved in three energy metabolism-related pathways, seven development-associated signaling pathways, and seven immune-relevant pathways, including lysosome and endocytosis, as well as the MAPK and Jak-STAT signaling pathways. The expression trends of five randomly selected DEpiRNAs were verified using a combination of RT-PCR and RT-qPCR. Moreover, the expression levels of six genes targeted by piR-ame-945760 were detected by RT-qPCR, with the results showing that their expression trends were the same as the expression trend of piR-ame-945760, indicative of the positive correlation between piR-ame-945760 and these targets. These results suggest that A.apis infestation increased the overall expression level of piRNAs and altered the expression pattern of piRNAs in A. mellifera larval guts. DEpiRNAs potentially participate in the A. apis response of the host by modulating the expression of target genes associated with energy metabolism and development, as well as cellular and humoral immune response. Our findings not only offer novel insights into A. mellifera larva-A. apis interaction, but also lay the groundwork for clarifying the mechanisms underlying DEpiRNA-regulated larval response.

molecular biology↗

bioRxiv2026

Characterization of six environmental coli-phages isolated in Astana, Kazakhstan, during the School of Molecular and Theoretical Biology

Bacteriophage (phage) collections are essential resources for studying virus-host interactions in bacterial species. Here, we report six Escherichia coli-infecting phages that expand the Lund Collection of Bacteriophages. These phages were isolated in 2025 within the framework of the School of Molecular and Theoretical Biology for high-school students, from samples collected in Lake Taldykol, Astana, Kazakhstan, using E. coli strains MG1655{Delta}RM and EV36 as hosts. The isolated phages comprise Taldykol (LuPh6), a member of the genus Kagunavirus; Aidakhar (LuPh7) of the genus Phapecoctavirus; Samruk (LuPh8) of the genus Tequintavirus; the T-odd-like phage Baiterek (LuPh9) of the genus Vequintavirus; and two T-even-like phages Tulpar (LuPh10) and Shurale (LuPh11) that belong to the Tequatrovirus genus. This expanded phage collection enhances the toolkit for investigating phage-host interactions and their molecular mechanisms and highlights the use of phage isolation as a component of high school research education. ImportancePhage collections are a key resource for studying phage biology, phage-bacteria interactions and bacterial immune systems. Here, we extend the Lund Phage Collection through the isolation and characterisation of six E. coli-infecting phages, including three novel species (LuPh6, LuPh8 and LuPh11) as well as a member of the genus Phapecoctavirus that not represented in widely used collections such as BASEL (LuPh7). This study expands the resources available for probing phage-host interactions and demonstrates an example of integrating phage research into education of high school students.

microbiology↗

bioRxiv2026

Projection criteria and information risks forzero-dimensional biological dynamics across molecular,epidemic, and ecological systems

Zero-dimensional chemical master equations, ordinary differential equations, and compartmental population models replace spatial stochastic biological systems by vectors of total counts or densities. This study asks when that projection is exact and whether information retained in spatial correlations can diagnose its practical failure. Exact Markov closure is characterized by an aggregate-rate lumpability condition: for every retained transition, the sum of microscopic transition rates must be constant over all spatial configurations with the same counts. Violations are connected to BBGKY-type correlation hierarchies and to mean-field, pair, and triplet closures. Conditional rate, finite-time predictive, memory, path-space, and correlation Kullback-Leibler risks quantify distinct losses. An exactly solvable two-compartment reaction separates structural non-closure from recovery of a well-mixed law under fast hidden mixing. Copy number and a spatial mixing-interaction ratio connect concentration, volume, diffusion, and reaction parameters to practical screening, including an Escherichia coli-scale example. The same projection logic is evaluated in controlled spatial susceptible-infectious-removed and predator-prey benchmarks. Across mixed and segregated initial conditions and four mobility regimes, pair-correlation risk was strongly associated with the error of the corresponding zero-dimensional ordinary differential equations (Spearman correlations 0.95 and 1.00; pooled 0.99). A nearest-neighbour exchange sensitivity analysis preserved the positive risk-error ranking. These benchmarks do not establish a universal threshold, but support correlation information as a transferable diagnostic for selecting among count, pair, higher-order, and explicit spatial descriptions.

systems biology↗

bioRxiv2018

NECorr, a Tool to Rank Gene Importance in Biological Processes using Molecular Networks and Transcriptome Data

The challenge of increasing crop yield while decreasing plants susceptibility to various stresses can be lessened by understanding plant regulatory processes in a tissue-specific manner. Molecular network analysis techniques were developed to aid in understanding gene inter-regulation. However, few tools for molecular network mining are designed to extract the most relevant genes to act upon. In order to find and to rank these putative regulator genes, we generated NECorr, a computational pipeline based on multiple-criteria decision-making algorithms. With the objective of ranking genes and their interactions in a selected condition or tissue, NECorr uses the molecular network topology as well as global gene expression analysis to find hub genes and their condition-specific regulators. NECorr was applied to Arabidopsis thaliana flower tissue and identifies known regulators in the developmental processes of this tissue as well as new putative regulators. NECorr will accelerate translational research by ranking candidate genes within a molecular network of interest.

systems biology↗

bioRxiv2020

Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis

COVID-19 (Coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the pathophysiology of this deadly virus is complex and largely unknown, we employ a network biology-fueled approach and integrated multiomics data pertaining to lung epithelial cells-specific coexpression network and human interactome to generate Calu-3-specific human-SARS-CoV-2 Interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 target central nodes of host-viral network that participate in core functional pathways. Network centrality analyses discover 28 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host modifying responses and cytokine storm. Overall, our network centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into SARS-CoV-2 pathogenicity.

systems biology↗

bioRxiv2025

Design, Synthesis, Biological Evaluation and Molecular Docking of New Acid-Functionalized Carbazole Derivatives as Potential Antibiotic Agents

The emergence of antibiotic resistance necessitates the discovery of new scaffolds with improved efficacy and drug-like properties. In this work, a new series of acid-functionalized carbazole derivatives was designed, synthesized, and comprehensively evaluated for their antibacterial potential. The incorporation of acidic functionalities into the carbazole framework enhanced physicochemical properties and biological interactions, yielding distinct strain-specific antibacterial activities. Minimum inhibitory concentration (MIC) studies demonstrated that 3-methyl-1,4-dioxo-4,9-dihydro-1H-carbazole-6-carboxylic acid (2) exhibited broad-spectrum potency, particularly against S. aureus and E. coli, while 6-methyl-9H-carbazole-3-carboxylic acid (3) showed selectivity against B. cereus and (E)-3-methyl-1-(2-tosylhydrazono)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxylic acid (1) displayed strong activity toward S. typhimurium. Molecular docking studies revealed favourable binding affinities of all derivatives toward bacterial dihydrofolate reductase (DHFR), with compound 1 showing the highest docking scores. Molecular dynamics simulations further confirmed the broad conformational adaptability of compound 1, the target-specific stability of compound 3, and protein-dependent binding behaviour of compound 2. Complementary ADMET predictions indicated that all compounds adhered to Lipinskis rules, with compound 3 displaying the most favourable pharmacokinetic profile, including high oral bioavailability and low toxicity risk. Together, these experimental and computational findings establish acid-functionalized carbazole scaffolds as promising antibacterial candidates.

pharmacology and toxicology↗

bioRxiv2025

Biological evaluation and molecular docking study of Ferrociphenol as an anti-melanogenic agent

Cutaneous hyperpigmentation disorders are associated with abnormal accumulation of melanin pigments, which can be treated using depigmenting agents. In the present study, we investigated the effect of ferrociphenol (Fc-diOH), an organometallic intermediate used for the synthesis of hydroxy-ferrocifen derivatives, which has previously been shown as an inhibitor of Sepia tyrosinase activity, on the inhibition of melanogenesis in B16F10 melanoma cells. Cell viability, melanin quantification and tyrosinase activity assay demonstrated that Fc-diOH treatment reduced the amount of intracellular melanin and tyrosinase activity by 32 and by 25%, respectively, in B16F10 melanoma cells at 25 nM without significant cellular toxicity. Furthermore, the biological activity of Fc-diOH against melanogenesis was confirmed in in vivo experiments using zebrafish Danio rerio embryos. We found that Fc-diOH inhibited melanin production and tyrosinase activity of zebrafish embryos treated with 0.5 and 2 {micro}M respectively, without affecting embryonic development or viability. In addition and interestingly, molecular docking analysis demonstrates that the p-hydroxyphenyl groups of Fc-diOH make close contacts with the active site of tyrosinase, compared to arbutin and phenylthiourea, which could be due to its structural homology with the tyrosinase substrate. Therefore, these results strongly suggest that Fc-diOH decreases tyrosinase activity, thereby negatively regulating melanogenesis in B16F10 cells and zebrafish embryos. Thus, Fc-diOH could be used as a depigmentation agent for the treatment of various hyper-pigmentation disorders.

cell biology↗

bioRxiv2019

Genetic analysis identifies molecular systems and biological pathways associated with household income

Socio-economic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. Previous genome-wide association studies (GWAS) using household income as a marker of SEP have shown that common genetic variants account for 11% of its variation. Here, in a sample of 286,301 participants from UK Biobank, we identified 30 independent genome-wide significant loci, 29 novel, that are associated with household income. Using a recently-developed method to meta-analyze data that leverages power from genetically-correlated traits, we identified an additional 120 income-associated loci. These loci showed clear evidence of functional enrichment, with transcriptional differences identified across multiple cortical tissues, in addition to links with GABAergic and serotonergic neurotransmission. We identified neurogenesis and the components of the synapse as candidate biological systems that are linked with income. By combining our GWAS on income with data from eQTL studies and chromatin interactions, 24 genes were prioritized for follow up, 18 of which were previously associated with cognitive ability. Using Mendelian Randomization, we identified cognitive ability as one of the causal, partly-heritable phenotypes that bridges the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. Significant differences between genetic correlations indicated that, the genetic variants associated with income are related to better mental health than those linked to educational attainment (another commonly-used marker of SEP). Finally, we were able to predict 2.5% of income differences using genetic data alone in an independent sample. These results are important for understanding the observed socioeconomic inequalities in Great Britain today.

genetics↗

bioRxiv2022

TITAN: A Toolbox for Information-Theoretic Analysis of Molecular Networks

Biological systems are naturally described as networks, spanning molecular interactions, cellular circuits, and brain-wide functional connectivity. Despite the ubiquity of network data, workflows for inferring network structure and then applying comparable graph analyses across modalities remain fragmented. We present NETSCOPE, an open-source, multi-platform toolbox for information-theoretic network inference and analysis. NETSCOPE estimates pairwise statistical dependence with mutual information (MI), derives weighted adjacency matrices, removes likely spurious edges using shuffle-based thresholds, and prunes indirect connections using the data processing inequality (DPI). A key feature is the conversion of MI-based similarity into a metric space via (normalized) variation of information (VI), enabling weighted shortest-path and centrality analyses that require distance-like edge weights. We validate the toolbox on synthetic data with known ground-truth topology and by reconstructing published molecular networks in Saccharomyces cerevisiae. We further demonstrate cross-domain use cases in single-cell transcriptomic networks, cell-level anatomical maps, EEG connectivity, and resting-state fMRI. NETSCOPE runs in Python and MATLAB/Octave, and is compatible with Jupyter/Colab workflows.

bioinformatics↗

bioRxiv2018

Chemical characterization, biological assessment and molecular docking studies of essential oil of Ocimum viride

Ocimum viride (family: Lamiaceae) is a medicinally important aromatic plant that grows widely in north western Himalayan range of Indian subcontinent. Essentials oils (EOs) and purified aromatic compounds derived from plants of genus Ocimum have long been used in traditional system of medicine to treat various chronic disorders. In this study we made an attempt to assess the chemical composition of essential oil (EO) obtained from Ocimum viride for potential antimicrobial and anticancer properties. Gas chromatography-mass spectrometry (GCMS) analysis revealed that EOs of aerial parts (leaves) of Ocimum viride contain high amounts of oxygenated monoterpenes, thymol and gamma terpinene. Notably, thymol (~50%) and {gamma}-terpinene (~18%) were identified as the most abundant components of the oil. EOs showed most prominent antibacterial effect against Bacillus subtilis and in silico molecular docking analyses of antibacterial action against bacterial cell wall of Bacillus subtilis showed interaction of thymol with Sec A protein of Bacillus subtilis (binding energy of -15 kcal/mol) with active site Lys284, Trp275, Leu269, Arg19, Glu277, pro270. While, in vitro cytotoxic effect of EO against six human cancer cell lines showed maximum effect with IC50 value of ~0.034 {+/-} 0.001L/ mL against HT-29 colon cancer cell line. DNA fragmentation analysis and cell cycle analysis revealed that EO inhibits the growth of HT-29 colon cancer cells probably through induction of unrepairable DNA damage and subsequent cell death. Taken together, our results indicate that EO possesses potent antimicrobial and anticancer properties, and may find applications in bacterial growth inhibition and cancer therapeutics.

cancer biology↗

bioRxiv2017

Can CRISPR-based gene drive be confined in the wild? A question for molecular and population biology

The recent discovery of CRISPR and its application as a gene editing tool has enabled a range of gene drive systems to be engineered with much greater ease. In order for the benefits of this technology to be realized, drive systems must be developed that are capable of both spreading into populations to achieve their desired impact, and being recalled in the event of unwanted consequences or public disfavor. We review the performance of three broad categories of drive systems at achieving these goals - threshold-dependent drives, homing-based drive and remediation systems, and temporally self-limiting systems such as daisy-chain drives.

genetics↗

bioRxiv2021

Molecular and cell biological analysis of SwrB in Bacillus subtilis

Swarming motility is flagellar-mediated movement over a solid surface and Bacillus subtilis cells require an increase in flagellar density to swarm. SwrB is a protein of unknown function required for swarming that is necessary to increase the number of flagellar hooks but not basal bodies. Previous work suggested that SwrB activates flagellar type III secretion but the mechanism by which it might perform this function is unknown. Here we show that SwrB likely acts sub-stoichiometrically as it localizes as puncta at the membrane in numbers fewer than that of flagellar basal bodies. Moreover the action of SwrB is likely transient as puncta of SwrB were not dependent on the presence of the basal bodies and rarely co-localized with flagellar hooks. Random mutagenesis of the SwrB sequence found that a histidine within the transmembrane segment was conditionally required for activity and punctate localization. Finally, three hydrophobic residues that precede a cytoplasmic domain of poor conservation abolished SwrB activity when mutated and caused aberrant migration during electrophoresis. Our data are consistent with a model in which SwrB interacts with the flagellum, changes conformation to activate type III secretion, and departs. IMPORTANCEType III secretion systems (T3SS) are elaborate nanomachines that form the core of the bacterial flagellum and injectisome of pathogens. The machines not only secrete proteins like virulence factors but also secrete the structural components for their own assembly. Moroever, proper construction requires complex regulation to ensure that the parts are roughly secreted in the order in which they are assembled. Here we explore a poorly understood activator the flagellar T3SS activation in Bacillus subtilis called SwrB. To aid mechanistic understanding, we determine the rules for subcellular punctate localization, the topology with respect to the membrane, and critical residues required for SwrB function.

microbiology↗

bioRxiv2023

Secretory and transcriptomic responses of mantle cells to low pH in the Pacific oyster (Crassostrea gigas)

Since the Industrial Revolution, the concentration of atmospheric carbon dioxide (CO2) due to anthropogenic activities has increased at unprecedented rates. One-third of the atmospheric anthropogenic CO2 emissions are dissolved in the oceans affecting the chemical equilibrium of seawater, which in turn leads to a decrease in pH and carbonate ion (CO32-) concentration, a phenomenon known as ocean acidification (OA). This chemical disequilibrium can be detrimental to marine organisms (e.g., mollusks) that fabricate mineralized structures based on calcium carbonate (CaCO3). Most studies on the effect of reduced pH in seawater have been conducted on the early developmental stages of shell-building invertebrates, neglecting how adult individuals face OA stress. Here, we evaluate histological, secretory, and transcriptional changes in the mantle of adult oysters (Crassostrea gigas) exposure to ambient (8.0 {+/-} 0.2) and reduced (7.6 {+/-} 0.2) pH during 20 days. Most histological observations did not show differences in terms of mantle cell morphology. However, Alcian Blue/PAS staining revealed significant differences in the number of Alcian Blue positive cells in the mantle edge, suggesting a decrease in the secretory activity in this morphogenetic zone. Transcriptomic analysis revealed 172 differentially expressed genes (DEGs) between mantle tissues from adult oysters kept in normal and reduced pH conditions. Almost 18% of the DEGs encode secreted proteins that are likely to be contributing to shell fabrication and patterning. 17 of 31 DEGs encoding secreted proteins correspond to oyster-specific genes, highlighting the fact that molluscan shell formation is underpinned by a rapidly evolving secretome. The GO analysis of DEGs encoding secreted proteins showed that they are involved in the cellular response to stimulus, response to stress, protein binding, and ion binding, suggesting these biological processes and molecular functions are altered by OA. This study demonstrates that histology and gene expression profiling can advance our understanding of the cellular and molecular mechanisms underlying adult oyster tolerance to low pH conditions.

molecular biology↗

bioRxiv2023

Design, Synthesis, Molecular Docking and Biological Activity of Pyrazolopyridines as Promising Lead Candidates Against Mycobacterium tuberculosis

Pyrazolo[3,4-b]pyridine is a medicinally privileged structure. We have achieved a new and facile synthesis of a combinatorial library of its tetra- and persubstituted derivatives by trifluoracetic acid catalysed condensation of a group of 5-aminopyrazoles and a group of -oxoketene dithioacetals. Furthermore, we demonstrated structural modification of the products via reductive desulfurization, hydrolysis of the ester and Suzuki coupling of the bromo derivative with aryl bornoic acids. Some of the products were subjected to in vitro MABA assay against M. tuberclulosis H37Rv strain and in silico analysis by binding to pantothenate synthetase from M. tuberclulosis (MTBPS). The results indicated that the pyazolo[3,4-b]pyridine with N(1)CH3, C(3)C6H5, C(4) pCH3C6H5, C(5)CO2Et, C(6)SMe substitutions exhibits promising antituberculotic activity.

bioinformatics↗

bioRxiv2025

Predicting non-covalent interactions between antioxidants in biological membranes through molecular dynamics

The synergistic association of different polyphenols has gained much interest in the food industry to develop efficient antioxidant cocktails, reducing the concentration of active agents and subsequently potential toxicity. The theoretical description and prediction of such processes is of central interest in this development. This study aims at benchmarking the performance of molecular dynamics (MD) to predict the formation of non-covalent complexes between {pi}-conjugated antioxidants, including two prototypes (quercetin and vitamin E), in a pure 1,2-dipalmitoylphosphatidylcholine (DOPC) lipid bilayer. To reproduce the experimentally observed quenching of vitamin E fluorescence by quercetin, a sphere-of-action quenching model was applied. The predictive capability of MD simulations at capturing this non-covalent association was evaluated with five other {pi}-conjugated potential partners of vitamin E, namely catechin, caffeic acid, myricetin, kaempferol, and galangin. The observed trend agreed with experimental studies, validating again the use of MD simulations as a tool to measure the potential synergism between natural antioxidants.

bioinformatics↗

bioRxiv2018

Network-Based Biomarkers Enable Cross-Disease Biomarker Discovery

Biomarkers lie at the heart of precision medicine, biodiversity monitoring, agricultural pathogen detection, amongst others. Surprisingly, while rapid genomic profiling is becoming ubiquitous, the development of biomarkers almost always involves the application of bespoke techniques that cannot be directly applied to other datasets. There is an urgent need for a systematic methodology to create biologically-interpretable molecular models that robustly predict key phenotypes. We therefore created SIMMS: an algorithm that fragments pathways into functional modules and uses these to predict phenotypes. We applied SIMMS to multiple data-types across four diseases, and in each it reproducibly identified subtypes, made superior predictions to the best bespoke approaches, and identified known and novel signaling nodes. To demonstrate its ability on a new dataset, we measured 33 genes/nodes of the PIK3CA pathway in 1,734 FFPE breast tumours and created a four-subnetwork prediction model. This model significantly out-performed existing clinically-used molecular tests in an independent 1,742-patient validation cohort. SIMMS is generic and can work with any molecular data or biological network, and is freely available at: https://cran.r-project.org/web/packages/SIMMS.

bioinformatics↗

bioRxiv2018

Synthesis, Biological Activity and Molecular Docking of New Tricyclic Series as α-glucosidase Inhibitors

Diabetes is an emerging metabolic disorder. -Glucosidase inhibitors, such as acarbose, delay the hydrolysis of carbohydrates by interfering with the digestive enzymes. This action decreases the glucose absorption and the postprandial glucose level. We have synthesized 25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones hybrids and evaluated their -glucosidase inhibitory activity. Compounds 6h and 6d have shown stronger activity than that of acarbose. Compound 6h exhibited the highest inhibition with an IC50 of 104.07 mM. Molecular modelling studies revealed that compound 6h inhibits -glucosidase due to the formation of a stable ligand--glucosidase complex and extra hydrogen bond interactions, and directed in the binding site by Trp329.

biochemistry↗

bioRxiv2019

Regression from pathological hypertrophy is sexually dimorphic and stimulus-specific

AimsPathological cardiac hypertrophy is the result of increased cardiomyocyte size, leading to thickening of the left ventricular walls and a decrease in the left ventricular chamber. With early treatment of the underlying cause, cardiac hypertrophy can be reversed in some individuals, while it persists in others. Here, we investigate mechanisms leading to regression of pathological cardiac hypertrophy in two mouse models, in addition to defining the sex differences associated with hypertrophy and regression.\n\nMethods and ResultsTwo pathological hypertrophic stimuli were used in male and female mice (Isoproterenol or Angiotensin II). The stimulus was removed after 7 days of treatment, then the left ventricle was studied at intervals up to 7 days following the removal of the stimulus. Following Isoproterenol removal, male hearts returned to baseline sizes in 4 days while it took 7 days for female hearts to regress. After Angiotensin II removal, the left ventricular masses of males and females did not regress. ERK1/2 was activated in response to both Isoproterenol and Angiotensin II in males, then decreased back to baseline one day after stimulus removal. Expression of ECM genes was greater in response to Angiotensin II and remained elevated longer after Angiotensin II removal, compared to Isoproterenol. Further, collagen content may be playing a role in the irreversible state of Angiotensin II induced hypertrophy as hydroxyproline content was increased following the removal of Angiotensin II in both males and females.\n\nConclusionsRegression of pathological cardiac hypertrophy is possible in some people and in some mouse models; however, the ability for the heart to regress is dependent on the stimulus and biological sex. Further, molecular changes including cellular signaling, protein degradation pathways and the formation of a fibrotic network may contribute to the ability to reverse pathological cardiac hypertrophy and are stimulus- and sex-dependent.\n\nTranslational PerspectivePathological cardiac hypertrophy is a major risk factor for mortality. If cardiac hypertrophy persists for an extended time, there can be many maladaptive changes to the myocardium. With early treatment of the underlying cause, cardiac hypertrophy can be reversed in some individuals, but not in others. While cardiac hypertrophy has been studied extensively, very little is understood about regression of cardiac hypertrophy. It is important that we have a better understanding of mechanisms leading to regression and why this process might not be reversible in some individuals.

molecular biology↗