Journal of Biosciences最新文献

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Preconditioned umbilical-cord mesenchymal stem-cell exosomes preserve functional hepatocytes in bile duct-ligated rats through alternate miRNA signaling rather than HGF signaling. 预处理脐带间充质干细胞外泌体通过替代miRNA信号而不是HGF信号来保护胆管结扎大鼠的功能肝细胞。
IF 1.9 4区 生物学
Journal of Biosciences Pub Date : 2026-01-01
Ratna Puspita, Ahmad Aulia Jusuf, Radiana Dhewayani Antarianto, Andri Pramesyanti Pramono
{"title":"Preconditioned umbilical-cord mesenchymal stem-cell exosomes preserve functional hepatocytes in bile duct-ligated rats through alternate miRNA signaling rather than HGF signaling.","authors":"Ratna Puspita, Ahmad Aulia Jusuf, Radiana Dhewayani Antarianto, Andri Pramesyanti Pramono","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Biliary atresia (BA) is a prominent cause of liver cirrhosis in pediatric patients with a high pediatric end-stage liver disease (PELD) score and a Laennec score of 4 at the Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia. Bile duct-ligated rat models have been used to mimic the clinical condition of BA partially. This study aims to evaluate the potential miRNAs of preconditioned umbilical-cord mesenchymal stem-cell exosomes (UC-MSC-exosomes) in comparison with the combined exosomes-HGF effect on liver histology, liver function, and hepatocyte-signaling in bile duct-ligated rats. Characterization of preconditioned UC-MSC-exosomes fulfilled the ISEV 2018 criteria. Liver histology showed trends of hepatocytes, inflammatory cells, and oval cell numbers returning to slightly below normal levels post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination, with no statistically significant difference. A significant difference in bile duct proliferation post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination was observed when compared with the control. Trends towards lower deposition of collagen around the porta area and total area fractions post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination showed no statistically significant difference; however, there was a slightly lower total collagen area fraction in the exosomes-HGF combination group. Functional hepatocyte preservation was indicated by increased albumin expression and partially improved CYP3A4 levels post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination. There was also a different trend in functional hepatocyte biochemical markers, SGOT (AST) and SGPT (ALT), between preconditioned UC-MSC-exosomes and the exosomes-HGF combination. NanoString microarray analysis of liver tissue and bioinformatics analysis were done to investigate in-depth hepatocyte signaling. miRNA profiling of the liver from preconditioned UC-MSC-exosomes identified the upregulation of hsa-miR-1-3p and hsa-miR-372-3p, which inhibit key signaling pathways, e.g., MAPK, PI3K-AKT, and NF-κB, and the downregulation of hsa-miR-520a-3p, which promotes hepatocyte proliferation and survival. miRNA profiles of the liver from the exosomes-HGF combination identified five different miRNA expressions (upregulated hsa-miR-144-3p, hsa-let7-5p, hsa-let7a-5p, hsa-let7e-5p, and hsa-miR-32-5p) and shared only one similar miR with the exosomes-treated liver (downregulated hsa-520a-3p). These miR differences contribute to the hepatocyte signaling in the exosomes-HGF combination group. Preconditioned UC-MSC-exosomes preserve functional hepatocytes in bile duct-ligated rats through alternate miR-mediated signaling rather than HGF signaling.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancement of calcium responses by KIR current inactivation in medium spiny neurons. KIR电流失活对中棘神经元钙反应的增强作用。
IF 1.9 4区 生物学
Journal of Biosciences Pub Date : 2026-01-01
John Eric Steephen, Mithun Padmakumar, Rohit Manchanda
{"title":"Enhancement of calcium responses by K<sub>IR</sub> current inactivation in medium spiny neurons.","authors":"John Eric Steephen, Mithun Padmakumar, Rohit Manchanda","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Synaptic plasticity within cortico-striatal circuits critically influences learning and behavior, with the nucleus accumbens (NAc) serving as a key mediating structure. Within the NAc, medium spiny neurons (MSNs) are known to mediate input integration, whose dendritic calcium levels are thought to influence cortico-striatal plasticity. Calcium responses have been observed to correlate with firing frequency and earlier firing onset. Inward rectifying potassium (K<sub>IR</sub>) currents inactivate significantly in ~40% of NAc MSNs. Studies have shown that this inactivation enhances firing frequency and advances firing onset. On the basis of these findings, we hypothesized that K<sub>IR</sub> inactivation may enhance intracellular calcium levels in MSNs, with implications for synaptic plasticity. Using an 189-compartment computational model of the MSN, the influence of K<sub>IR</sub> inactivation on calcium dynamics was investigated. We found that the amplitude of calcium influx was more than twice as large in the tertiary dendrite and at least 9% higher for higher input currents in response to K<sub>IR</sub> inactivation. Additionally, the average calcium concentration increased by up to 26.1% in the soma, with enhancements of 4.3-21.4% in the dendrites. Our findings suggest that K<sub>IR</sub> inactivation may significantly modulate synaptic plasticity, thereby impacting the learning mediated by the NAc core.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardiometabolomic signatures and gut microbiota dynamics in perinatally undernourished F1 offspring: Decoding the metabolic footprint. 围产期营养不良F1后代的心脏代谢组学特征和肠道微生物群动力学:解码代谢足迹。
IF 1.9 4区 生物学
Journal of Biosciences Pub Date : 2026-01-01
Anu V Ranade, Pramukh Subrahmanya Hegde, Megha Bhat Agni, Praveen Rai, Shubham Sukerndeo Upadhyay, Anjana Aravind, Thottethodi Subrahmanya Keshava Prasad, K M Damodara Gowda
{"title":"Cardiometabolomic signatures and gut microbiota dynamics in perinatally undernourished F<sub>1</sub> offspring: Decoding the metabolic footprint.","authors":"Anu V Ranade, Pramukh Subrahmanya Hegde, Megha Bhat Agni, Praveen Rai, Shubham Sukerndeo Upadhyay, Anjana Aravind, Thottethodi Subrahmanya Keshava Prasad, K M Damodara Gowda","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The Developmental Origins of Health and Disease (DOHaD) hypothesis asserts that detrimental prenatal conditions, such as dietary deficiencies, may lead to enduring health consequences. Perinatal undernutrition, an important concern during fetal development, may affect growth and metabolic programming, resulting in lasting health implications. Maternal nutrition is crucial in modulating fetal endocrine systems and metabolic functions, influencing the development, blood circulation, and nutrient absorption. The present study examines the impact of perinatal undernutrition on the composition of gut microbiota and metabolite levels in offspring of undernourished dams, using an Albino Wistar rat model. Furthermore, we investigated the combined impact of astaxanthin (AsX) and docosahexaenoic acid (DHA) supplementation on cardiometabolic outcomes in these progenies. Astaxanthin, a powerful antioxidant, and DHA, an omega-3 fatty acid, have shown the ability to favorably alter the gut flora and metabolic pathways. The direct influence of AsX on gut microbiota remains unexplored, whereas DHA's role in fostering beneficial microbes and regulating metabolite production is well documented. The current study used metabolomics and metagenomics to investigate the intricate relationship between metabolites and gut microbiota in health and disease, offering insights into fetal programming and possible strategies to improve offspring health. The results highlight the need to address perinatal undernutrition and enhance gut health through targeted dietary interventions to improve long-term health outcomes.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Re-imagining T-cell receptor signaling: parallel paths may be key to discriminatory power. 重新想象t细胞受体信号:平行路径可能是歧视性权力的关键。
IF 1.9 4区 生物学
Journal of Biosciences Pub Date : 2026-01-01
Akshay Tiwari, Narendra M Dixit
{"title":"Re-imagining T-cell receptor signaling: parallel paths may be key to discriminatory power.","authors":"Akshay Tiwari, Narendra M Dixit","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>T-cells are important arms of our immune system and are central to our fight against pathogens and cancers (Baral <i>et al.</i> 2019a; Waldman <i>et al.</i> 2020). They recognize infected and cancerous cells and help destroy them while leaving uninfected/normal cells intact. They accomplish this tricky task with exquisite precision. How they do so has been an enigma and the subject of intense investigation for decades (Chakraborty and Weiss 2014; Courtney <i>et al.</i> 2018).</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond morphology: Material alterations as inducible defenses in Daphnia longicephala. 形态之外:水蚤诱导防御的物质改变。
IF 1.9 4区 生物学
Journal of Biosciences Pub Date : 2026-01-01
Wencke Krings, Sarah Becker, Greta Huttegger, Stanislav N Gorb, Martin Horstmann
{"title":"Beyond morphology: Material alterations as inducible defenses in <i>Daphnia longicephala</i>.","authors":"Wencke Krings, Sarah Becker, Greta Huttegger, Stanislav N Gorb, Martin Horstmann","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The freshwater crustacean <i>Daphnia</i> is well known to adapt to the presence of predators by forming inducible defence structures. Large-scale morphological defensive traits are usually easily recognizable in most species. However, hidden mechanical or microstructural defences in the integument, which can strongly impact defensive success through altered structural stability, remain largely unknown. We therefore investigated the inducible mechanical defenses of <i>Daphnia</i> longicephala against the heteropteran backswimmer <i>Notonecta</i> sp. In its presence, <i>Daphnia</i> individuals develop an elongated, widened head capsule and a more pointed tail spine. Nevertheless, the actual function of these traits is unknown, as <i>Notonecta</i> pierces its prey with a proboscis and is therefore not gape-limited. The increased body dimensions accordingly seem ineffective. In particular, the function of the very pronounced crest on the heads of defended specimens remains unclear. In this study, we documented significant alterations in Young's modulus and hardness of the integument of the crest between undefended and defended <i>D. longicephala</i>. At the same time, elemental composition in the cuticle between animals from different treatments did not differ in any of the investigated crest regions, except for calcium, which was elevated in the defended specimens and correlated with enhanced mechanical properties. This indicates alterations in the degree of mineralization in certain crest regions, which could be responsible for significant changes in hardness and stiffness. It is likely that hidden mechanical defences of <i>D. longicephala'</i>s crest impair the predators' handling and hinder or complicate a piercing of the integument in the central head region, protecting the vital organ systems.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamic attributes of the pedicel: Key drivers, structure and function in angiosperms. 花梗的动态特性:被子植物的关键驱动因素、结构和功能。
IF 1.9 4区 生物学
Journal of Biosciences Pub Date : 2026-01-01
Shveta Saroop, Monika Koul, Veenu Kaul
{"title":"Dynamic attributes of the pedicel: Key drivers, structure and function in angiosperms.","authors":"Shveta Saroop, Monika Koul, Veenu Kaul","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Pedicels, the short specialized stems that support reproductive structures in flowering plants, play diverse roles throughout plant development, yet many of their functions remain insufficiently understood. Morphologically and anatomically, they share several features with the main stem, including similar epidermal, cortical, and vascular traits. Variation in pedicel length, branching angle, and orientation influences floral and inflorescence architecture, thereby shaping floral display patterns and ultimately affecting reproductive success. Functionally, pedicels provide mechanical support, maintain vascular continuity between flowers and inflorescence axes, and facilitate the transport of nutrients, water, hormones, and signaling molecules to flowers and developing fruits. Recent studies highlight their additional roles in pollen presentation and seed dispersal, in which pedicel orientation aids effective interactions with pollinators and dispersal agents. Pedicels also serve as important sites of abscission, initiating enzymatic processes that lead to the detachment of flower or fruit. Advances in developmental genetics have identified numerous genes and transcription factors involved in pedicel formation, orientation, and functional modulation. Despite these insights, significant gaps remain, particularly regarding how pedicels adapt structurally and functionally to different pollination strategies. Further integrative research is required to clarify the developmental, ecological, and evolutionary significance of this understudied floral organ.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Relative size does matter: Animals see optical illusions. 相对大小很重要:动物看到的是视错觉。
IF 1.9 4区 生物学
Journal of Biosciences Pub Date : 2026-01-01
Surbhi Munda, S P Arun
{"title":"Relative size does matter: Animals see optical illusions.","authors":"Surbhi Munda, S P Arun","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Consider the classic Ebbinghaus illusion in figure 1: the orange circle on the right seems bigger, even though both orange circles have the same size. Such size illusions occur in the real world too: in fact, a common dieting trick is to serve the same food on a smaller plate, which makes it appear larger, so you end up eating less. Why do we get fooled by such size illusions?</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of acetylation on human insulin structure, and dynamics at different temperatures: A molecular dynamics simulation study. 乙酰化对人胰岛素结构和不同温度下动力学的影响:分子动力学模拟研究。
IF 1.9 4区 生物学
Journal of Biosciences Pub Date : 2026-01-01
Reyhane Kamelnia, Bahram Goliaei, Faramarz Mehrnejad, Seyed Peyman Shariatpanahi, Ashkan Zare Karizak, Elahe Kamelnia, Joulia Alizadeh-Rahrovi, Azadeh Ebrahim-Habibi
{"title":"Effects of acetylation on human insulin structure, and dynamics at different temperatures: A molecular dynamics simulation study.","authors":"Reyhane Kamelnia, Bahram Goliaei, Faramarz Mehrnejad, Seyed Peyman Shariatpanahi, Ashkan Zare Karizak, Elahe Kamelnia, Joulia Alizadeh-Rahrovi, Azadeh Ebrahim-Habibi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Insulin was used as a model protein to investigate the effects of acetylation, a significant post-translational modification. Acetylation typically targets terminal and side-chain amine groups, which, in insulin, correspond to three specific sites. Molecular dynamics simulations were conducted at pH 5.0 and three different temperatures on various acetylated insulin forms, in both monomeric and dimeric states. Two acetylation states - modification of the B-chain N-terminus alone, and modification of both the B-chain N-terminus and Lys29 - exhibited distinct properties compared with other acetylation variants. Overall, the results indicate that chemical acetylation can enhance structural compactness and reduce the propensity for protein-protein association. Key evaluated parameters included root-mean-square deviation, root-mean-square fluctuation, complex formation energy, radius of gyration, secondary structure content, and solvent-accessible surface area. At pH 5.0 and 323 K, insulin showed increased structural flexibility, accompanied by a transition from α-helix to 3<sub>10</sub>-helix and β-sheet conformations, along with an increased tendency for intermolecular interactions. These findings suggest that some acetylated insulin forms may exhibit a more constrained and compact structure compared with the non-acetylated insulin form. In summary, this study provides a useful model for exploring how chemical modifications influence the secondary structure and aggregation behavior of insulin, offering valuable insights for the design of stable insulin formulations.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cooperation destabilizes communities, but competition pays the price. 合作会破坏社区的稳定,但竞争会付出代价。
IF 1.9 4区 生物学
Journal of Biosciences Pub Date : 2026-01-01
Ananda Shikhara Bhat, Suryadeepto Nag, Sutirth Dey
{"title":"Cooperation destabilizes communities, but competition pays the price.","authors":"Ananda Shikhara Bhat, Suryadeepto Nag, Sutirth Dey","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>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. Here, we used an individual-based model to study the population dynamics of unstructured communities following external perturbations to species abundances. We found 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 become 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 showed that this result could 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 become extinct than expected by chance alone, whereas those that are engaged in cooperative interactions with such a species are less likely to become 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.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structure evaluation coupled with all-atom molecular dynamics and advanced quantum mechanical DFT revealed kaempferol as a potent binding flavonol for the epigenetic-target HDAC9. 结构评价结合全原子分子动力学和先进量子力学DFT发现山奈酚是表观遗传靶点HDAC9的有效结合黄酮醇。
IF 1.9 4区 生物学
Journal of Biosciences Pub Date : 2026-01-01
Shabir Ahmad Ganai, Sundararaj Rajamanikandan, Shahid Ahmad Padder
{"title":"Structure evaluation coupled with all-atom molecular dynamics and advanced quantum mechanical DFT revealed kaempferol as a potent binding flavonol for the epigenetic-target HDAC9.","authors":"Shabir Ahmad Ganai, Sundararaj Rajamanikandan, Shahid Ahmad Padder","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Aberrant histone deacetylase-9 (HDAC9) activity has been recorded in a plethora of malignant tumors, including gastric cancer, hepatocellular carcinoma, and non-small cell lung cancer. Despite the discovery of HDAC9 as an important pharmacological target, the non-availability of its three-dimensional structure has substantially obstructed the process of discovering potent plant-based therapeutics against it. The present study determined the tertiary structure of human HDAC9 and validated its accuracy. Following this, the binding characteristics of diverse flavonoids against HDAC9 were compared using givinostat as a reference molecule. Moreover, the dynamics of the highest affinity flavonoid and HDAC9 were also investigated in the bound state. Furthermore, the energy gap of the defined flavonoid, signifying the reactivity and kinetic stability, was quantified. We employed multiple techniques, including template-steered modeling, molecular docking, all-atom molecular dynamics, and an atomistic quantum mechanical density functional theory in tandem, for comparing the binding strength of 12 flavonoid molecules against HDAC9 using givinostat (an orphan-approved HDAC inhibitor) as the positive control. Following these procedures, it became discernible that all the flavonoid molecules exhibit stronger binding character and interaction status with this epigenetic target than givinostat. Kaempferol, a flavonol, manifested the strongest affinity among the selected flavonoids and interacted with multiple residues of the deacetylase domain of HDAC9. Similar to givinostat, kaempferol exhibited tenable stability in bound form with this acetylation-eraser enzymatic protein. Most importantly, this flavonol demonstrated higher chemical reactivity and, as such, lower kinetic stability than givinostat which is quite important from a pharmacological perspective.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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