Biology subjects

Dey, S.

Publications and source records attributed to Dey, S..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Costs of dispersal evolution under larval malnutrition

Dispersal is a key eco-evolutionary process, and the causes and consequences of its evolution have been well-studied. However, although dispersal depends critically on the nutritional status of organisms, it is unclear how malnutrition affects the evolution of life history and the behavior of organisms under selection for increased dispersal. To address this issue, we used four replicate laboratory populations of Drosophila melanogaster previously selected for increased dispersal for 66-67 generations on a protein-poor larval diet. Compared to the unselected controls, the selected populations had lower female body weight, fecundity, male desiccation resistance and mating propensity, but greater male locomotor activity and mating latency. There were no significant differences in aggression. We also compared our results qualitatively with those from a previous study on dispersal selection under a standard larval diet. Barring desiccation resistance, locomotor activity, and rest duration, all other traits investigated responded differently to dispersal selection between the poor and the standard larval nutritional regimes. These results show that the evolution of traits associated with dispersal can differ markedly depending on the nutrition available for the dispersing populations.

evolutionary biology↗

bioRxiv2024

Experimental evolution of Drosophila without its microbiome

In single-generation experiments, microbiome removal often affects multiple host traits. However, relatively little is understood about the long-term implications of living in a microbe-free environment. To address this question, we evolved four replicate laboratory populations of Drosophila melanogaster without microbes and compared their traits with corresponding control populations that were reared with microbiota. This comparison was done under two assay environments: with-microbes and microbe-free. Prior single-generation experiments on our populations had revealed that microbiota removal significantly affects multiple traits, which suggested that the flies were under strong selection pressure to adapt to the absence of microbes. However, contrary to our expectations, the selected populations underwent very modest changes even after 54-57 generations of selection. Moreover, the magnitude of change in trait values across the with- and without- microbe environments was less for the selected populations than for the controls. RNA-Seq on one of the evolutionary replicates revealed that compared to the control, some anti-microbial peptides (AMPs) in the selected population were up-regulated, while several heat shock proteins (HSPs) were down-regulated. These results suggest that robust host-microbiome integrations on short timescales can nevertheless be labile on longer timescales. We situate these results in the context of the "evolutionary addiction hypothesis" and the "hygiene hypothesis".

evolutionary biology↗

bioRxiv2024

Design of a biomolecular adaptive controller to restore sustained periodic behavior

Periodic behavior is a widespread biological phenomenon occurring across various spatiotemporal scales, where upstream stimuli are encoded into dynamic intracellular signals such as oscillations, varying in duration, amplitude, and frequency. Disruptions to this periodicity can lead to a range of pathologies, for which we propose an adaptive feedback controller with an Incoherent Feedforward Loop (IFFL)-like topology, based on chemical reactions, designed to restore sustained oscillations in systems that have lost their periodicity. By approximating the controllers dynamics, we defined the design requirements for the first implementation of a biomolecular adaptive controller and tested its applicability for destabilizing the steady-state behavior of a self-inhibiting gene. Numerical simulations illustrate the adaptive behavior of the controller and its ability to tune both the amplitude and the period of the resulting oscillations.

synthetic biology↗

bioRxiv2024

Exploring putative enteric methanogenesis inhibitors using molecular simulations and a graph neural network

Atmospheric methane (CH4) acts as a key contributor to global warming. As CH4 is a short-lived climate forcer (12 years atmospheric lifespan), its mitigation represents the most promising means to address climate change in the short term. Enteric CH4 (the biosynthesized CH4 from the rumen of ruminants) represents 5.1% of total global greenhouse gas (GHG) emissions, 23% of emissions from agriculture, and 27.2% of global CH4 emissions. Therefore, it is imperative to investigate methanogenesis inhibitors and their underlying modes of action. We hereby elucidate the detailed biophysical and thermodynamic interplay between anti-methanogenic molecules and cofactor F430 of methyl coenzyme M reductase and interpret the stoichiometric ratios and binding affinities of sixteen inhibitor molecules. We leverage this as prior in a graph neural network to first functionally cluster these sixteen known inhibitors among [~]54,000 bovine metabolites. We subsequently demonstrate a protocol to identify precursors to and putative inhibitors for methanogenesis, based on Tanimoto chemical similarity and membrane permeability predictions. This work lays the foundation for computational and de novo design of inhibitor molecules that retain/ reject one or more biochemical properties of known inhibitors discussed in this study. COVER ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/613350v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1fd4518org.highwire.dtl.DTLVardef@c34d87org.highwire.dtl.DTLVardef@16eef9org.highwire.dtl.DTLVardef@1a33512_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2024

A two-dose regimen of Qβ virus-like particle-based vaccines elicit protective antibodies against heroin and fentanyl

Opioid overdoses and the growing rate of opioid use disorder (OUD) are major public health concerns, particularly in the United States. Current treatment approaches for OUD have failed to slow the growth of the opioid crisis. Opioid vaccines have shown pre-clinical success in targeting multiple different opioid drugs. However, the need for many immunizations can limit their clinical implementation. In this study, we investigate the development of novel opioid vaccines by independently targeting fentanyl and the active metabolites of heroin using a bacteriophage virus-like particle (VLP) vaccine platform. We establish the successful conjugation of haptens to bacteriophage Q{beta} VLPs and demonstrate immunogenicity of Q{beta}-fentanyl, Q{beta}-morphine, and Q{beta}-6-acetylmorphine in animal models after one or two immunizations. We show that in independently or in combination, these vaccines elicit high-titer, high-avidity, and durable antibody responses. Moreover, we reveal their protective capacities against heroin or fentanyl challenge after two immunizations. Overall, these findings establish Q{beta}-VLP conjugated vaccines for heroin and fentanyl as very promising opioid vaccine candidates.

immunology↗

bioRxiv2024

AP2/ERF transcription factors enriched in the drought-response transcriptome of the Thar desert tree Prosopis cineraria show higher copy number and greater DNA-binding affinity than orthologs in drought-sensitive species

We sequenced the drought-response transcriptome of the keystone tree species Prosopis cineraria from the Indian Thar desert to understand the key factors in its drought tolerance mechanism. We identified a network of genes activated in P. cineraria involved in osmotic stress response, phytohormone, calcium, and phosphorelay signal transduction. Of these, up-regulation of 54 APETALA2/Ethylene-Responsive Factor (AP2/ERF) transcription factor genes, validated by real-time PCR, suggests their key role in the drought tolerance of P. cineraria. We conducted a genome-wide study of the AP2/ERF superfamily in P. cineraria, classifying its 232 proteins into 15 clades and analyzing their protein structures, gene structure, and promoter organization. The P. cineraria genome contains more copies of AP2/ERF genes than drought-sensitive plants. Further, we identified sequence polymorphisms in AP2/ERF genes between Arabian and Indian cultivars of P. cineraria. We modeled the DNA-protein complex structures of AP2/ERFs from drought-tolerant and sensitive species using AlphaFold to compare their DNA binding ability. Though the DNA binding domain (DBD) is relatively conserved across species, the unstructured region of these proteins possesses different charge distributions, which might contribute differently to their DNA search and binding. Using all-atom molecular dynamics simulations, we teased out a higher number of specific DBD-DNA hydrogen bonds in P. cineraria, leading to a stronger DNA-binding affinity compared to drought-sensitive Arabidopsis thaliana. These results directly support copy number expansion of AP2/ERF transcription factors and the evolution of their structures for more efficient DNA search and binding as drought adaptation mechanisms in P. cineraria.

plant biology↗

bioRxiv2024

Loss of FBXO31-mediated γH2AX foci formation impairs initiation of NHEJ and HR repair pathways, and sensitizes breast cancer to therapy

In response to genotoxic stress, cell initiates complex signalling cascades to combat genomic insults through simultaneous initiation of growth arrest and DNA damage repair process. {gamma}H2AX functions as a crucial initiator in DNA double strand damage repair process. Therefore, {gamma}H2AX foci formation onto the damage sites is essential to initiate the recruitment of repair proteins involved in NHEJ (Non-homologous DNA-end joining) or HR (Homologous recombination) repair process. However, molecular events associated with {gamma}H2AX foci formation onto the DNA damage sites are poorly understood. Here, we show that FBXO31, the first ubiquitin ligase, mediated Lys-63-linked ubiquitination of {gamma}H2AX is essential for its foci formation onto the DNA damage sites to initiate recruitment of proteins involved in NHEJ and HR-mediated DNA damage repair. Therefore, tumors with FBXO31 deficiency show enhanced growth suppression following chemotherapeutic drug treatment because of synthetic lethality, indicating that FBXO31 could be used as a marker for predicting the outcome of chemotherapy treatment.

cancer biology↗

bioRxiv2024

Direct and Indirect Salt Effects on Homotypic Phase Separation

The low-complexity domain of hnRNPA1 (A1-LCD) phase separates in a salt-dependent manner. Unlike many intrinsically disordered proteins (IDPs) whose phase separation is suppressed by increasing salt concentrations, the phase separation of A1-LCD is promoted by > 100 mM NaCl. To investigate the atypical salt effect on A1-LCD phase separation, we carried out all-atom molecular dynamics simulations of systems comprising multiple A1-LCD chains at NaCl concentrations from 50 to 1000 mM NaCl. The ions occupy first-shell as well as more distant sites around the IDP chains, with Arg sidechains and backbone carbonyls the favored partners of Cl- and Na+, respectively. They play two direct roles in driving A1-LCD condensation. The first is to neutralize the high net charge of the protein (+9) by an excess of bound Cl- over Na+; the second is to bridge between A1-LCD chains, thereby fortifying the intermolecular interaction networks in the dense phase. At high concentrations, NaCl also indirectly strengthens {pi}-{pi}, cation-{pi}, and amino-{pi} interactions, by drawing water away from the interaction partners. Therefore, at low salt, A1-LCD is prevented from phase separation by net charge repulsion; at intermediate concentrations, NaCl neutralizes enough of the net charge while also bridging IDP chains to drive phase separation. This drive becomes even stronger at high salt due to strengthened {pi}-type interactions. Based on this understanding, four classes of salt dependence of IDP phase separation can be predicted from amino-acid composition.

biophysics↗

bioRxiv2024

Molecular Sequestration Enhances Precision in Timing of Intracellular Events

Expressed gene products often interact ubiquitously with binding sites at nucleic acids and macromolecular complexes, known as decoys. Binding of transcription factors (TFs) to decoys is shown to be an indirect but crucial way to control the dynamics and stochasticity in gene regulation. Here, we explore how such decoys impact the timing of intracellular events, as captured by the time taken for the levels of a given TF to reach a critical threshold level, known as first passage time (FPT). As binding introduces nonlinearity, an exact mathematical analysis is challenging. However, assuming quasi-static equilibrium (QSE) for binding/unbinding reactions, we can analytically discern the impact of decoys on FPT statistics by using small noise approximation (SNA) and reformulating the FPT question in terms of a suitable variable whose dynamics is linear. The stability of the decoy-bound TFs influences the impact of decoys on FPT statistics. The presence of decoys makes the mean FPT long and even longer for unstable bound TFs. Decoys reduce noise in FPT, and stable decoy-bound TFs offer greater timing precision with less expression cost than their unstable counterparts. Interestingly, when both bound and free TFs decay at the same rate, the noise in FPT is not directly influenced by the number of decoys or their binding affinities. We verify these results by performing exact stochastic simulations. These results have important implications for the precise temporal scheduling of events involved in the functioning of biomolecular clocks, development processes, cell-cycle control, and cell-size homeostasis.

systems biology↗

bioRxiv2024

Temperature-Dependent Fold-Switching Mechanism of the Circadian Clock Protein KaiB

The oscillator of the cyanobacterial circadian clock relies on the ability of the KaiB protein to switch reversibly between a stable ground-state fold (gsKaiB) and an unstable fold-switched fold (fsKaiB). Rare fold-switching events by KaiB provide a critical delay in the negative feedback loop of this post-translational oscillator. In this study, we experimentally and computationally investigate the temperature dependence of fold switching and its mechanism. We demonstrate that the stability of gsKaiB increases with temperature compared to fsKaiB and that the Q10 value for the gsKaiB [->] fsKaiB transition is nearly three times smaller than that for the reverse transition. Simulations and native-state hydrogen-deuterium exchange NMR experiments suggest that fold switching can involve both subglobally and near-globally unfolded intermediates. The simulations predict that the transition state for fold switching coincides with isomerization of conserved prolines in the most rapidly exchanging region, and we confirm experimentally that proline isomerization is a rate-limiting step for fold switching. We explore the implications of our results for temperature compensation, a hallmark of circadian clocks, through a kinetic model.

biochemistry↗

bioRxiv2024

50,000 years of Evolutionary History of India: Insights from ~2,700 Whole Genome Sequences

India has been underrepresented in whole genome sequencing studies. We generated 2,762 high coverage genomes from India--including individuals from most geographic regions, speakers of all major languages, and tribal and caste groups--providing a comprehensive survey of genetic variation in India. With these data, we reconstruct the evolutionary history of India through space and time at fine scales. We show that most Indians derive ancestry from three ancestral groups related to ancient Iranian farmers, Eurasian Steppe pastoralists and South Asian hunter-gatherers. We uncover a common source of Iranian-related ancestry from early Neolithic cultures of Central Asia into the ancestors of Ancestral South Indians (ASI), Ancestral North Indians (ANI), Austro-asiatic-related and East Asian-related groups in India. Following these admixtures, India experienced a major demographic shift towards endogamy, resulting in extensive homozygosity and identity-by-descent sharing among individuals. At deep time scales, Indians derive around 1-2% of their ancestry through gene flow from archaic hominins, Neanderthals and Denisovans. By assembling the surviving fragments of archaic ancestry in modern Indians, we recover [~]1.5 Gb (or 50%) of the introgressing Neanderthal and [~]0.6 Gb (or 20%) of the introgressing Denisovan genomes, more than any other previous archaic ancestry study. Moreover, Indians have the largest variation in Neanderthal ancestry, as well as the highest amount of population-specific Neanderthal segments among worldwide groups. Finally, we demonstrate that most of the genetic variation in Indians stems from a single major migration out of Africa that occurred around 50,000 years ago, with minimal contribution from earlier migration waves. Together, these analyses provide a detailed view of the population history of India and underscore the value of expanding genomic surveys to diverse groups outside Europe.

evolutionary biology↗

bioRxiv2024

Thermally activated antibiotic production by probiotic bacteria for pathogen elimination

Peptide drugs have seen rapid advancement in biopharmaceutical development, with over 80 candidates approved globally. Despite their therapeutic potential, the clinical translation of peptide drugs is hampered by challenges in production yields and stability. Engineered bacterial therapeutics is a unique approach being explored to overcome these issues by using bacteria to produce and deliver therapeutic compounds at the body site of use. A key advantage of this technology is the possibility to control drug delivery within the body in real time using genetic switches. However, the performance of such genetic switches suffers when used to control drugs that require post-translational modifications or are toxic to the host. In this study, these challenges were experienced when attempting to establish a thermal switch for the production of a ribosomally synthesized and post-translationally modified peptide antibiotic, darobactin, in probiotic E. coli. These challenges were overcome by developing a thermo-amplifier circuit that combined the thermal-switch with a T7 RNA Polymerase and its promoter that overcame limitations imposed by the host transcriptional machinery due to its orthogonality to it. This circuit enabled production of pathogen-inhibitory levels of darobactin at 40{degrees}C while maintaining leakiness below the detection limit at 37{degrees}C. More impressively, the thermo-amplifier circuit sustained production beyond the thermal induction duration. Thus, raised temperature for 2 h was sufficient for the bacteria to produce pathogen-inhibitory levels of darobactin even in the physiologically relevant simulated conditions of the intestines that include bile salts and low nutrient levels. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/579303v2_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1cdb311org.highwire.dtl.DTLVardef@1a7523aorg.highwire.dtl.DTLVardef@77b68org.highwire.dtl.DTLVardef@136f52b_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Cell-autonomous GP130 activation suppresses prostate cancer development via STAT3/ARF/p53-driven senescence and confers an immune-active tumor microenvironment

Prostate cancer ranks as the second most frequently diagnosed cancer in men worldwide. Recent research highlights the crucial roles GP130-mediated signaling pathways play in the development and progression of various cancers, particularly through hyperactivated STAT3 signaling. Here, we find that genetic cell-autonomous activation of the GP130 receptor in prostate epithelial cells triggers active STAT3 signaling and significantly reduces tumor growth in vivo. Mechanistically, genetic activation of GP130 signaling mediates senescence via the STAT3/ARF/p53 axis and anti-tumor immunity via recruitment of cytotoxic T-cells, ultimately impeding tumor progression. In prostate cancer patients, high GP130 mRNA expression levels correlate with better recurrence-free survival, increased senescence signals and a transition from an immune-cold to an immune-hot tumor. Our findings reveal a context-dependent role of GP130/STAT3 in carcinogenesis and a tumor-suppressive function in prostate cancer development. We challenge the prevailing concept of blocking GP130/STAT3 signaling as functional prostate cancer treatment and instead propose cell-autonomous GP130 activation as a novel therapeutic strategy.

cancer biology↗

bioRxiv2023

Mutualism Destabilizes Communities, but Competition Pays the Price

A classic result in theoretical ecology states that an increase in the proportion of cooperative interactions in unstructured ecological communities leads to a loss of stability to external perturbations. However, the fate and composition of the species that constitute an unstable ecological community following such perturbations remains relatively unexplored. In this paper, we use an individual-based model to study the population dynamics of unstructured communities following external perturbations to species abundances. We find that while increasing the number of cooperative interactions does indeed increase the probability that a community will experience an extinction following a perturbation, the entire community is rarely wiped out following a perturbation. Instead, only a subset of the ecological community is driven to extinction, and the species that go extinct are more likely to be those engaged in a greater number of competitive interactions. Thus, the resultant community formed after a perturbation has a higher proportion of cooperative interactions than the original community. We show that this result can be explained by studying the dynamics of the species engaged in the highest number of competitive interactions: After an external perturbation, those species that compete with such a top competitor are more likely to go extinct than expected by chance alone, whereas those that are engaged in cooperative interactions with such a species are less likely to go extinct than expected by chance alone. Our results provide a potential explanation for the ubiquity of cooperative interactions in nature despite the known negative effects of cooperation on community stability.

ecology↗

bioRxiv2023

Kinetics and dynamics of single-molecule multivalent interactions revealed by plasmon-enhanced fluorescence

Multivalency as an interaction principle is widely utilized in nature. It enables specific and strong binding by multiple weak interactions through enhanced avidity and is a core process in immune recognition and cellular signaling and a current concept in drug design. Rapid binding and unbinding of monovalent constituent interactions during multivalent binding creates dynamics that require a single-molecule approach to be studied. Here, we use the high signals from plasmon enhanced fluorescence of nanoparticles to extract binding kinetics and dynamics of multivalent interactions on the single-molecule level and in real-time. We study mono-, bi-and trivalent binding interactions using a DNA Holliday Junction as a model construct with programmable valency. Furthermore, we introduce a model framework for binding kinetics that involves the binding restriction during multivalent interactions to take into account the structural conformation of multivalent molecules allowing quantitative comparison. We used this approach to explore how length and flexibility of the DNA ligands affect binding restriction and binding strength, where overall binding strength decreased with spacer length. For trivalent systems increasing spacer length was found to activate binding in the trivalent state giving insight into the design of multivalent drug or targeting moieties. Interestingly we could exploit the rapidly decaying near fields of the plasmon that induce a strong dependence of the signal to position of the fluorophore to observe binding dynamics during single multivalent binding events.

biophysics↗

bioRxiv2023

Unraveling Coinfection Dynamics into 100 Whole Genome of Diarrheal Pathogens: A Genome-to-Systems Biology Approach with Plesiomonas shigelloides

Diarrhea is the second leading cause of mortality among infants under the age of five. One of the main causes of this disease is multipathogenic infections, which can make the conditions of patients even worse. Plesiomonas shigelloides (P. shigelloides) is one of the pathogenic bacteria that contributes to the pathophysiology of diarrhea and may be implicated in coinfection with other diarrheal pathogens. Therefore, the purpose of this study is to investigate the hypothetical proteins to explore the genetic insights of P. shigelloides and its relationships with common diarrheal diseases. For this reason, we used 16S rRNA sequencing together with several biochemical tests to identify the bacteria that we isolated from diarrheal patients (8 years). Afterwards, the whole genome of P. shigelloides was sequenced, assembled and annotated in order to obtain the genomic insights of P. shigelloides. In addition, the common virulence genes of ten (10) common diarrhea-causing bacteria were identified from 100 whole genome sequences. Finally, the system biology approach was applied to predict the coinfection pattern between P. shigelloides and the virulence genes of 10 bacteria. The complete genome sequencing analysis of this bacterium revealed 899 hypothetical proteins from which 33 hypothetical proteins shared the clusters with the 109 virulence genes of 10 distinct diarrheal pathogens, forming a strong interaction based on biological processes, molecular functions, subcellular localization, or pathways. All diarrhea causing bacteria were found to have P. shigelloides microbial interactions; however, V. cholerae exhibited the strongest relationships, while C. difficile showed the weakest. The results of this investigation clearly imply that P. shigelloides shares a coinfection pattern with other bacteria that cause diarrhea. Finally, the findings from the complete genome provide new avenues for researchers to pursue their investigation of the pathophysiology of diarrhea.

systems biology↗

bioRxiv2023

Genome-Wide Exploration of the Opportunistic Providencia stuartii Unveils the Novel Genetic Interactions with the Virulence Gene of Diarrheal Pathogens

Diarrhea typically indicates an intestinal disorder, which can occur from viruses, parasites or bacterial infection. Along with the common diarrhea-causing pathogens, opportunistic bacteria may also play a role in the etiology of diarrheal disease. One of the opportunists bacteria that can cause diarrhea in both children and adults is Providencia stuartii. Therefore, the goal of this study is to explore the genetic mechanism of the opportunistic P. stuartii in microbial interactions with common diarrheal pathogens. Hence, P. stuartii was identified by utilizing the morphological observation and molecular techniques. Afterwards, the entire genome of P. stuartii was sequenced, assembled and annotated to explore the genomic insights. In addition, the virulence genes of 100 whole genome sequences from ten prevalent diarrhea-causing bacteria were identified and prioritized. Finally, the system biology approach was used to predict the protein-protein interaction network between P. stuartii and the virulence genes. The results of the present study suggests that complete genome sequencing of this bacteria contains 4011 proteins, which are crucial for this bacterium to survive. Additionally, 16 gene clusters provide 207 interacting genes that could interact with biological and molecular function, subcellular localization and pathway. The microbial interaction accompanying the virulence gene was found in all 10 diarrhea-causing bacteria except Clostridium difficile. These findings of this study could aid in the exploration of Providencia stuartii as the major causative agent of diarrhea. Additionally, the pathophysiology of diarrhea can be investigated using the microbial interactions between P. stuartii and the typical diarrheal bacteria. The results of this study may therefore be used to determine the most effective therapeutic targets for the development of medications to treat diarrhea.

genomics↗

bioRxiv2023

Mice Models to Bioinformatics Methods Led to the Discovery of Antidiabetic Compounds in the F. racemosa Plant Extracts

One of the primary health issues caused by inadequate blood sugar regulation is Diabetes Mellitus (DM). Diabetes and its consequences remain clinically significant even with the development of oral hypoglycemic medications. Therefore, Ficus racemosa (F. racemosa) plant has been studied for assessing of its antidiabetic potential coupling with animal model and in silico experiments. Drug Alloxan (150 mg/kg) was injected to induce the experimental diabetes in Swiss Albino mice, and two doses methanol extract of the F. racemosa fruit (300 and 500 mg/kg) along with glibenclamide (5 mg/kg) were given orally. Oral Glucose Tolerance Test (OGTT) and acute toxicity were performed as well in both diabetic and non-diabetic mice. Later, in silico experiments including ADMET profiling, molecular docking and simulations were performed. The administration of a dosage less than 3000 mg/kg has been observed to be well-tolerated by mice, with no reported instances of mortality or adverse effects. Following oral administration for 7 days, the blood glucose level (BGL) was significantly decreased in mice model in both doses of extracts, indicating the effect of F. racemosa. Subsequent to this, molecular docking and simulations have indicated that the SIRT1 receptor exhibits a higher binding affinity towards four specific compounds, namely Friedelin, Lupeol Acetate, Gluanol, and Ferulic Acid, as indicated by the dynamics parameters and interacting residues. The current investigation provided evidence that the fruit extract of F. racemosa significantly mitigated the hyperglycemic impact. Moreover, a total of four substances have been found that play a crucial role in the mechanisms behind the reduction of diabetic effects. Hence, the current investigation could potentially serve as a viable therapeutic approach in the treatment of diabetes.

microbiology↗