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Results for “Molecular Docking Simulation”

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PubMed2026

11-O-galloylbergenin alleviates LPS-stimulated inflammation in RAW 264.7 macrophages by targeting Grb2, RhoA, and Cdc42 in the RAS signaling pathway.

OBJECTIVE: This study aimed to explore the anti-inflammatory mechanism of 11-O-galloylbergenin in macrophages. METHODS: Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were treated with 11-O-galloylbergenin. Cytotoxicity was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cytokine secretion was measured by enzyme-linked immunosorbent (ELISA) assay. Data-independent acquisition (DIA)-based proteomics, Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, western blotting, and molecular docking were also performed. RESULTS: 11-O-Galloylbergenin (≤50 μg/mL) was non-cytotoxic and significantly suppressed tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) secretion. Proteomics analysis identified 209 differentially expressed proteins (DEPs) that showed opposite expression trends before and after 11-O-galloylbergenin treatment. Seven of these DEPs were enriched in the RAS pathway: RhoA, Cdc42, Grb2, RalB, Calm3, Gnb2, and Pla2g4a. Western blotting confirmed that 11-O-galloylbergenin downregulated RhoA, Cdc42, and Grb2 expression. Molecular docking revealed good binding affinity of 11-O-galloylbergenin to RhoA, Cdc42, and Grb2. CONCLUSION: 11-O-Galloylbergenin alleviates LPS-stimulated inflammation in RAW 264.7 macrophages by inhibiting the RAS signaling pathway.

Animals↗

PubMed2005

Identification of a drug target motif: an anti-tumor drug NK109 interacts with a PNxxxxP.

The synthetic compound NK109 shows anti-tumor effects against a number of human cancer cell lines. The mechanism of action is thought to involve the inhibition of DNA topoisomerase II. However, NK109 also exhibits potent anti-tumor activities against doxorubicin-, cisplatin- and etoposide-resistant human cell lines. This paper describes target validation of NK109 using biotinylated NK109 and a T7 phage library screening procedure. Phage particles displaying an affinity for NK109 were isolated and the DNA sequence determined. The amino acid sequences of selected peptides, and the results of mutation experiments by alanine scanning, confirmed that the binding target motif of NK109 is PNxxxxP. In silico analysis of the interaction between NK109 and the peptide, by docking simulation and molecular dynamics, supported this conclusion. The PNxxxxP motif exists in the C2 domain of protein kinase Calpha. NK109 was confirmed to bind the C2 domain from surface plasmon resonance analysis. Furthermore, NK109 moderately inhibited protein kinase C activity in vitro. Our results show that the anti-tumor activity of NK109 stems from interactions with multiple protein targets.

Amino Acid Motifs↗

PubMed2026

Design, synthesis and biological evaluation of hydroxybenzothiazole-linked benzothiazole/benzoxazole conjugates as potent dual α-amylase and α-glucosidase inhibitors.

The current study focuses on the synthesis and evaluation of novel Hydroxybenzothiazole-Linked Benzothiazole/Benzoxazole Conjugates to target Diabetes Mellitus (DM) by inhibiting α-amylase and α-glucosidase. Spectroscopic methods, including 1H and 13C NMR spectroscopy, were employed to confirm the structures of newly synthesized conjugates. The findings of in-vitro analysis displayed that the synthesized derivatives inhibited α-amylase and α-glucosidase enzymes with IC50 values ranging from 3.65 ± 0.20 μM to 32.15 ± 3.20 μM on α-amylase and 5.92 ± 0.80 μM to 35.60 ± 3.40 μM on α-glucosidase, in contrast to the reference drug Acarbose (α-amylase IC50 = 8.25 ± 0.80 μM; α-glucosidase IC50 = 10.75 ± 1.10 μM). Among the series 9a-9f and 10a-10f, analogs 10 f, 10b, 9b, and 9e displayed superior anti-diabetic activity compared to the reference drug Acarbose. The inhibitory activity of these conjugates can be attributed to their favorable and stable interactions with critical amino acid residues of targeted enzymes, as revealed through molecular docking analysis. ADMET predictions and drug-likeness evaluations showed favorable pharmacokinetic features, while DFT investigations revealed electronic insights related to bioactivity. Experimental outcomes and in silico support display that these potent Hydroxybenzothiazole-Linked Benzothiazole/Benzoxazole Conjugates were comparable to an existing diabetic mellitus inhibitor while conserving an acceptable safety profile, specifying potential for further therapeutic development and optimization against diabetic Mellitus.

Benzothiazoles↗

PubMed2026

Insights into the mechanism of enhanced tetramethylpyrazine production in dehulled adlay fermented by Bacillus subtilis BJ3-2.

Tetramethylpyrazine (TTMP) is a vital bioactive alkaloid and characteristic flavor compound in fermented foods. Our previous study found that fermentation of adlay by Bacillus subtilis BJ3-2 efficiently accumulates TTMP, whereas the underlying high-yield mechanism remains unclear. This study investigated the fermentation characteristics, gene transcription and protein expression of B. subtilis BJ3-2 in dehulled adlay (BDA) and soybean (BSB), respectively, and elucidated the mechanism responsible for high-yield TTMP production. The results showed that glutamate, leucine and phenylalanine were major free amino acids in BDA. The TTMP yield in BDA at 48 h (6.11 mg/g dry weight) was 360-fold higher than that in BSB. Transcriptomic and proteomic analysis demonstrated that compared with the soybean substrate, dehulled adlay substrate significantly up-regulated the expression of alsSD and ilvBH genes and their encoding proteins in B. subtilis BJ3-2, which were involved in C5-branched dibasic acid metabolism, 2-oxocarboxylic acid metabolism, and valine, leucine and isoleucine biosynthesis. Meanwhile, acetoin degradation was inhibited by down-regulating acetoin dehydrogenase complex (acoABCL) in citrate cycle, glycolysis/gluconeogenesis and carbon metabolism. Additionally, nitrogen metabolism pathway was transcriptionally enhanced to guarantee sufficient ammonium supply. Notably, protein-protein interaction and molecular docking analyses revealed that acetohydroxyacid synthase (ilvBH) interacted tightly with α-acetolactate decarboxylase (alsD), potentially forming a metabolic channel for acetoin synthesis. In conclusion, the efficient synthesis of TTMP in BDA was primarily attributed to the high synthesis and low degradation of acetoin, and the moderate synthesis of ammonium/ammonia. This study provided a theoretical basis for the targeted and efficient biosynthesis of TTMP.

Bacillus subtilis↗

PubMed2026

USP10-SIRT6-PARP1 axis drives keratinocyte senescence and skin photoaging under chronic UVA exposure.

Chronic exposure to ultraviolet A (UVA) radiation is the principal environmental driver of skin photoaging, yet the upstream molecular events that commit irradiated keratinocytes to senescence remain poorly understood. Here we show that SIRT6, an NAD+-dependent protein deacetylase with established roles in genome maintenance and organismal longevity, functions as a central gatekeeper of keratinocyte homeostasis under photic stress. Using a chronic UVA irradiation model in mice together with cultured human keratinocytes, we demonstrate that UVA inflicts extensive DNA damage and G2/M cell-cycle arrest, accompanied by selective depletion of SIRT6 among all sirtuin family members. Mechanistically, UVA suppresses the deubiquitinase USP10 at both transcriptional and post-transcriptional levels, thereby licensing ubiquitin-dependent proteasomal degradation of SIRT6. The resulting SIRT6 deficiency unleashes hyperactivation of the DNA-damage sensor PARP1, amplifying genomic injury signaling and driving keratinocytes into irreversible senescence with concomitant elaboration of a broad pro-inflammatory secretory programme encompassing chemokines and cytokines. Pharmacological reactivation of SIRT6 with the selective agonist UBCS039 reverses epidermal hyperplasia, attenuates DNA damage and senescence marker accumulation, and suppresses inflammatory mediator induction both in vivo and in vitro, establishing SIRT6 loss as a causal rather than correlative event. Furthermore, molecular docking and functional validation identify osthole, a plant-derived coumarin from the medicinal herb Cnidium monnieri, as a candidate SIRT6-engaging compound that counteracts UVA-induced senescence and inflammation in keratinocytes. Collectively, these findings define a USP10-SIRT6-PARP1 signaling axis whose disruption underlies cutaneous photoaging and suggest that SIRT6-directed strategies may offer therapeutic benefit against UV-driven tissue degeneration.

Animals↗

PubMed2025

Heme oxygenase 1 (HO-1) is a drug target for reversing cisplatin resistance in non-small cell lung cancer.

INTRODUCTION: Platinum-based drugs, the most widely used chemotherapeutic drugs in clinical oncology, have long faced the problem of drug resistance, which is urgently in need of resolution. Identifying biomarkers of drug resistance may help reduce platinum resistance and improve therapeutic efficacy. OBJECTIVES: This study aims to identify potential biomarkers associated with the development of cisplatin resistance in non-small cell lung cancer (NSCLC) and explore mechanisms to overcome chemoresistance. METHODS: NSCLC cisplatin resistance cell lines were constructed, and transcriptome sequencing was performed. Results were validated using Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Molecular docking, proteomics sequencing, and in vitro and in vivo experiments were conducted to evaluate the role of Heme Oxygenase 1 (HO-1) in cisplatin resistance. RESULTS: NSCLC cisplatin resistance cell lines, GEO and TCGA data identified HMOX1, downstream of Nrf2, as a key drug resistance gene induced by cisplatin. Activation of the Nrf2/HO-1 pathway was found to induce ferroptosis resistance, a critical mechanism of cisplatin resistance. Candidate compounds SB 202190 and Nordihydroguaiaretic acid (NDGA) effectively reactivated ferroptosis by inhibiting HO-1, thereby increasing cisplatin sensitivity. CONCLUSION: The Nrf2/HO-1 pathway is a significant contributor to cisplatin resistance in NSCLC. Targeting HO-1 with SB 202190 and NDGA presents a promising strategy to overcome resistance and improve chemotherapy outcomes.

Cisplatin↗

PubMed2025

Coordinated regulation of glutathione S-transferases confers metabolic flexibility in multi-insecticide-resistant Frankliniella occidentalis (Pergande).

INTRODUCTION: The evolution of multi-insecticide resistance in insect pests threatens global food security. Although glutathione S-transferases (GSTs) are implicated in detoxification, the coordinated mechanism by which specific gene subfamilies interact to confer broad-spectrum resistance remains inadequately characterized. OBJECTIVE: To dissect the functional allocation and cooperation of GST subfamilies in multi-insecticide-resistant strains of Frankliniella occidentalis. METHODS: We integrated comparative genomics (20 GST genes cloned), transcriptomics (qRT-PCR), RNAi-mediated silencing, molecular docking (AutoDock Vina), and in vitro metabolism assays (UPLC-MS/MS) across susceptible and resistant thrips strains. RESULTS: The two resistant strains (NIL-R and FS-R) exhibited moderate to high resistance to five insecticides (chlorfenapyr, emamectin benzoate, spinetoram, spinosad, and thiamethoxam), accompanied by significantly elevated GSTs activity. Phylogenetic analysis indicates that GSTs include 10 conserved delta and 7 diverse sigma members. The sigma subfamily has undergone a marked expansion due to gene duplication. Delta (FoGSTd1, d4, and d9) and sigma (FoGSTs1, s2, and s6) genes were significantly up-regulated in the resistant strains. RNAi showed specialized functional allocation among GSTs: delta GSTs mediated resistance to spinosad and chlorfenapyr, sigma GSTs were responsible for thiamethoxam resistance, and notably, cooperation between these subfamilies contributed to resistance against emamectin benzoate and spinetoram. Molecular docking and in vitro metabolism assays of FoGSTd9 and FoGSTs1 proteins further supported the functional allocation and cooperative roles of GST subfamilies. CONCLUSION: Our results indicate that F. occidentalis may coordinate GST subfamilies to achieve metabolic flexibility in response to multi-insecticide pressure. This survival strategy, mediated by mechanistic functional allocation and cooperative interactions among subfamilies, may contribute to energy conservation and reduced adaptive costs. Disruption of this coordinated mechanism represents a potential approach for overcoming resistance in agricultural pest populations.

Animals↗

PubMed2006

The thioesterase domain of the fengycin biosynthesis cluster: a structural base for the macrocyclization of a non-ribosomal lipopeptide.

Many secondary metabolic peptides from bacteria and fungi are produced by non-ribosomal peptide synthetases (NRPS) where the final step of biosynthesis is often catalysed by designated thioesterase domains. Here, we report the 1.8A crystal structure of the fengycin thioesterase (FenTE) from Bacillus subtilis F29-3, which catalyses the regio- and stereoselective release and macrocyclization of the antibiotic fengycin from the NRPS template. A structure of the PMSF-inactivated FenTE domain suggests the location of the oxyanion hole and the binding site of the C-terminal residue l-Ile11 of the lipopeptide. Using a combination of docking, molecular dynamics simulations and in vitro activity assays, a model of the FenTE-fengycin complex was derived in which peptide cyclization requires strategic interactions with residues lining the active site canyon.

Amino Acid Sequence↗

PubMed2026

Bioactive peptides for meat quality and preservation: Integrating peptidomics and computational screening.

Bioactive peptides generated from meat proteins, fermented meat products, and slaughter by-products have attracted increasing attention as functional molecules for improving meat quality and preservation. In meat systems, peptides can be produced through endogenous postmortem proteolysis, microbial fermentation, gastrointestinal digestion, or controlled enzymatic hydrolysis of underutilized animal by-products. These peptides are closely associated with key meat science endpoints, including postmortem tenderization, oxidative stability, color retention, flavor development, microbial inhibition, and the valorization of processing by-products. However, although high-resolution peptidomics has greatly expanded the identification of meat-derived peptide sequences, their translation into practical meat applications remains limited by matrix interactions, processing stability, sensory constraints, safety concerns, and insufficient validation in real meat systems. This review synthesizes recent advances in meat-related peptidomics and computational screening, including sequence-based prediction, machine learning, molecular docking, molecular dynamics, stability assessment, and safety-oriented filtering. Particular attention is given to how these approaches can prioritize peptides with antioxidant, antimicrobial, flavor-modulating, and preservation-related functions under meat-specific technological constraints. By integrating peptide generation pathways, mass spectrometry-based identification, in silico prioritization, and meat quality endpoints, this review proposes a stage-gated framework for translating meat-derived bioactive peptides from discovery to application. Future research should strengthen matrix-specific validation, standardized peptidomic reporting, and safety assessment to support the use of bioactive peptides in meat quality improvement, clean-label preservation, and circular utilization of meat industry by-products.

Animals↗

PubMed2003

Design, synthesis and biological evaluation of ambenonium derivatives as AChE inhibitors.

Ambenonium (1), an old AChE inhibitor, is endowed with an outstanding affinity and a peculiar mechanism of action that, taken together, make it a very promising pharmacological tool for the treatment of Alzheimer's disease (AD). Unfortunately, the bisquaternary structure of 1 prevents its passage through the blood brain barrier. In a search of centrally active ambenonium derivatives, we planned to synthesize tertiary amines of 1, such as 2 and 3. In addition, to add new insights into the binding mechanism of the inhibitor, we designed constrained analogues of ambenonium by incorporating the diamine functions into cyclic moieties (4-12). The biological evaluation of the new compounds has been assessed in vitro against human AChE and BChE. All tertiary amine derivatives resulted more than 1000-fold less potent than 1 and, unlike prototype, did not show any selectivity between the two enzymes. This result, because of recent findings concerning the role of BChE in AD, makes our compounds, endowed with a well-balanced profile of AChE/BChE inhibition, valuable candidates for further development. To better clarify the interactions that account for the high affinity of 1, docking simulations and molecular dynamics studies on the AChE-1 complex were also carried out.

Acetylcholinesterase↗

PubMed2026

Integrative multi-omics identifies DOC2A as a novel pharmacological target for bipolar disorder.

BACKGROUND: Current bipolar disorder (BD) therapies suffer from limited efficacy and adverse effects, necessitating mechanistically grounded targets. METHODS: We integrated BD genome-wide association study data (158,036 cases; 2,796,499 controls) with brain proteomics (ROSMAP and Banner dorsolateral prefrontal cortex, n = 376 and 152) to perform proteome-wide association studies (PWAS). Bayesian colocalization and summary-data-based Mendelian randomization (SMR) prioritized causal genes. Cell-type-specific transcriptomics validated dysregulation in iPSC-derived neurons, astrocytes, and postmortem hippocampus/prefrontal cortex. Weighted gene co-expression networks (WGCNAs), functional enrichment, and molecular docking assessed functional pathways and druggability. RESULTS: PWAS identified eight BD-associated genes (false discovery rate < 0.05), with DOC2A emerging as the top candidate. Colocalization (H4 > 0.8) and SMR supported a causal association of DOC2A with BD, with no pleiotropy (heterogeneity in dependent instruments P > 0.01); DOC2A expression decreased in BD across neurons (P = 4.26 × 10-2), astrocytes (P = 2.09 × 10-2), hippocampus (P = 9.80 × 10-3, t = -2.738), and prefrontal cortex (P = 1.44 × 10-2, t = -2.580); WGCNA positioned DOC2A as a key regulator (module membership/gene significance P < 0.05) of co-expression networks enriched for BD-associated processes including neurotransmitter secretion and postsynaptic actin cytoskeleton organization (P < 0.05); molecular docking revealed favorable-affinity binding (ΔG < -4 kcal/mol) between DOC2A and BD-related drugs and neuroprotective compounds. CONCLUSIONS: Our convergent multi-omics framework highlights DOC2A dysregulation as a key contributor to synaptic dysfunction in BD and nominates it as a promising therapeutic target. The demonstrated interaction with existing neuroactive compounds provides immediate translational avenues.

Bipolar Disorder↗

PubMed2026

Highly Conserved Allelic Substitutions S202F, L244P, and H248P/R/Y in FsSdhB and A83 V in FsSdhC1 Trigger Gradual Resistance to Pydiflumetofen in Fusarium solani.

Pydiflumetofen (Pyd), one of the new-generation SDHIs, has been applied to control various diseases in economic crops. Fusarium solani, a soil-borne pathogen with a broad host range, is the agent of quinoa basal-stem rot (QBSR). In this study, three PydLR (4.64 < RF < 9.31), six PydMR (51.24 < RF < 86.91), and seven PydHR mutants (RF > 6000) were generated by Pyd-taming. Most F. solani PydR mutants showed no fitness penalties. The sequence alignment of FsSdh genes revealed that substitutions S202F, L244P, and H248P/R/Y in FsSdhB, or A83 V in FsSdhC1, caused Pyd resistance. Notably, the mutation S202F causing HR was first reported. Molecular docking demonstrated that these aforementioned mutations significantly reduced affinity between Pyd and the Qp-binding pocket. These results provide pivotal data for the resistance management strategies of F. solani and advance our understanding of the resistance mechanisms of SDHIs.

Fusarium↗

PubMed2025

Donepezil and Memantine Derivatives for Dual-Function and Prodrug Applications in Alzheimer's Disease.

The treatment of Alzheimer's disease by acetylcholinesterase (AChE) and N-methyl-d-aspartate receptor (NMDAR) inhibitors is limited by the narrow therapeutic window and adverse side effects of the drugs. This study aims to increase the efficacy and limit the side effects of donepezil, an AChE inhibitor, and memantine, an NMDAR inhibitor, through the addition of amyloid-β (Aβ)-targeting fragments to create dual-function compounds. The incorporation of the amyloid-targeting fragments successfully produced compounds with affinity for Aβ fibrils, and that can stain amyloid plaques in the brains of 5xFAD mice. The donepezil-based compounds showed significant changes in AChE inhibition compared to donepezil due to the incorporation of the Aβ-targeting fragment and as confirmed by molecular docking studies. The memantine-derived compound showed good brain uptake in 5xFAD mice but lacked compatibility with NMDAR inhibition based on in vitro assays and molecular docking. Importantly, the memantine-derived compound acts as a prodrug in vivo, releasing memantine within a pharmacologically relevant time frame. Overall, these findings suggest that dual-function compounds may be useful as drug delivery agents that can be metabolized to release an active drug in areas of the brain rich in amyloid plaques and thus could lead to improved treatments for Alzheimer's disease.

Animals↗

PubMed2005

Impact of induced fit on ligand binding to the androgen receptor: a multidimensional QSAR study to predict endocrine-disrupting effects of environmental chemicals.

We investigated the influence of induced fit of the androgen receptor binding pocket on free energies of ligand binding. On the basis of a novel alignment procedure using flexible docking, molecular dynamics simulations, and linear-interaction energy analysis, we simulated the binding of 119 molecules representing six compound classes. The superposition of the ligand molecules emerging from the combined protocol served as input for Raptor, a receptor-modeling tool based on multidimensional QSAR allowing for ligand-dependent induced fit. Throughout our study, protein flexibility was explicitly accounted for. The model converged at a cross-validated r(2) = 0.858 (88 training compounds) and yielded a predictive r(2) = 0.792 (26 test compounds), thereby predicting the binding affinity of all compounds close to their experimental value. We then challenged the model by testing five molecules not belonging to compound classes used to train the model: the IC(50) values were predicted within a factor of 4.5 compared to the experimental data. The demonstrated predictivity of the model suggests that our approach may well be beneficial for both drug discovery and the screening of environmental chemicals for endocrine-disrupting effects, a problem that has recently become a cause for concern among scientists, environmental advocates, and politicians alike.

Benzhydryl Compounds↗

PubMed2006

How can (-)-epigallocatechin gallate from green tea prevent HIV-1 infection? Mechanistic insights from computational modeling and the implication for rational design of anti-HIV-1 entry inhibitors.

Possible inhibitors preventing human immunodeficiency virus type 1 (HIV-1) entry into the cells are recognized as hopeful next-generation anti-HIV-1 drugs. It is highly desirable to develop a potent inhibitor blocking binding of glycoprotein CD4 of the cell with glycoprotein gp120 of HIV-1, because the gp120-CD4 binding is the initial step of HIV-1 entry into the cells. It has been recently reported that (-)-epigallocatechin gallate (EGCG) from green tea is an inhibitor blocking gp120-CD4 binding. But the inhibitory mechanism remains unknown. For understanding the inhibitory mechanism, extensive molecular docking, molecular dynamics simulations, and binding free-energy calculations have been performed in this study to predict the most favorable structures of CD4-EGCG, gp120-CD4, and gp120-CD4-EGCG binding complexes in water. The results reveal that EGCG binds with CD4 in such a way that the calculated binding affinity of gp120 with the CD4-EGCG complex is negligible. So, the favorable binding of EGCG with CD4 can effectively block gp120-CD4 binding. The calculated CD4-EGCG binding affinity (DeltaG(bind) = -5.5 kcal/mol, K(d) = 94 microM) is in excellent agreement with available experimental data suggesting IC(50) approximately 100 microM for EGCG-blocking CD4-gp120 binding. These results and insights provide a rational basis for future design of novel, more potent inhibitors to block gp120-CD4 binding.

Anti-HIV Agents↗

PubMed2025

Characterization of blaOXA-542-mediated carbapenem resistance in Acinetobacter baumannii.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) causes multiple anatomical site infections, representing a significant public health threat. AIM: This study reports the isolation and characterization of a carbapenem-resistant A. baumannii harbouring blaOXA-542, followed by a comprehensive investigation of its antimicrobial resistance mechanisms and genomic characteristics. METHODS: Firstly, antimicrobial susceptibility testing was performed using the broth microdilution method. Subsequently, whole-genome sequencing was employed to identify and characterize the resistance and virulence determinants. The functional validation of resistance mechanisms was performed by gene knockdown and construction of expression vectors. The fitness cost of β-lactamase expression was identified by a bacterial growth kinetic test. Molecular docking was utilized to predict potential binding sites of β-lactamase and carbapenems. Finally, the genetic characteristics of the isolates were analysed through comparative genomics analyses and phylogenetic tree construction. RESULTS AND CONCLUSIONS: The results demonstrated that blaOXA-542 confers resistance to carbapenem and penicillin in A. baumannii and Escherichia coli while exhibiting no significant impact on cephalosporins. The ability of blaOXA-542 to hydrolyze meropenem was further confirmed by modified carbapenem inactivation assay (mCIM). Expression of blaOXA-542 in E. coli BL21 showed no significant growth rate alteration. Comparative analysis of the blaOXA-542 genetic environment revealed a close association with Acinetobacter pitti. This study reports the emergence of blaOXA-542-mediated carbapenem and penicillin resistance in a novel A. baumannii lineage (ST2795Pas/ST3464Oxf), highlighting the urgent need for rational antibiotic use against specific pathogens.

Acinetobacter baumannii↗

PubMed2026

Transcriptomic analysis identifies novel ferroptosis-related biomarkers and therapeutic targets in pulmonary arterial hypertension.

BACKGROUND: Ferroptosis plays a significant role in pulmonary arterial hypertension (PAH), although its underlying mechanisms and key pathogenic genes remain unclear. METHODS: Transcriptomic data from human PAH and control lung tissue were obtained from the Gene Expression Omnibus (GEO) database, whereas ferroptosis-related genes (FRGs) were sourced from the MsigDb and FerrDb databases. Differentially expressed FRGs (DE-FRGs) were identified through the intersection of FRGs with differentially expressed genes (DEGs). Functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Key hub genes were identified through Least Absolute Shrinkage and Selection Operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and weighted correlation network analysis (WGCNA). Gene set enrichment analysis (GSEA) was conducted to explore the functional roles and associated pathways of hub genes. The relationship between hub genes and immune infiltration was investigated. Expression levels of potential biomarkers were validated via Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) in two PAH animal models (monocrotaline-induced and Sugen5416 plus hypoxia-induced PAH). Finally, molecular docking was employed to screen potential therapeutic compounds. RESULTS: A total of 133 DE-FRGs were identified, with KEGG and GO analyses highlighting their involvement in intracellular iron homeostasis and ferroptosis. Hub genes, notably FZD7 and NFE2, were identified using LASSO, SVM-RFE, and WGCNA. Immune infiltration analysis suggested that monocytes and neutrophils play key roles in PAH pathogenesis. Validation in PAH animal models showed significant upregulation of Fzd7 and downregulation of Nfe2 in lung tissues of both MCT- and SuHx-induced PAH models. Molecular docking identified tetrachlorodibenzodioxin (TCDD) has good binding affinity. CONCLUSION: In summary, we investigated two ferroptosis-related biomarkers, FZD7 and NFE2, in PAH using transcriptomics, offering new insights into molecular mechanisms and potential targeted therapies for the disease.

Ferroptosis↗

PubMed2025

Integrated data mining and network pharmacology to explore the prescription patterns from a senior TCM oncologist's clinical practice in treating chemotherapy-induced hand-foot syndrome.

Hand-foot syndrome (HFS) is a common and refractory adverse effect of chemotherapy lacking specific therapeutic strategies currently. Traditional Chinese medicine (TCM) has shown empirical efficacy in clinical HFS management. This study integrated data mining and network pharmacology to systematically elucidate the medication principles and molecular mechanisms underlying Professor Gang Xie's prescriptions for HFS. All medical records from Professor Xie's specialist clinic (January 2020 to March 2025) were retrospectively collected and standardized in Excel. Prescriptions were analyzed through frequency statistics, association and clustering. Active ingredients of core herb pairs and their disease-related targets were identified using TCMSP, HERB, GeneCards, PharmGKB and GEO databases. Protein-protein interaction (PPI) networks, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed. Molecular docking validated interactions between key bioactive compounds and targets. This study involved 217 prescriptions containing 150 herbs. Core herb combinations comprised Radix Astragali (Huangqi), Poria (Fuling), and Radix Pseudostellariae (Taizishen), predominantly classified as spleen-tonifying agents with warm properties, targeting lung, spleen, and stomach meridians. Network analysis identified 67 bioactive compounds and 899 disease targets. Quercetin, kaempferol, acacetin and luteolin were identified the key ingredients. The core targets (TP53, STAT3, PIK3CA, HSP90AA1, AKT1, CTNNB1, PI3KR1, MAPK1) were enriched in MAPK and PI3K-Akt signaling pathways. Molecular docking confirmed strong binding affinity between key compounds and targets. Professor Xie's therapeutic strategy for HFS emphasizes "spleen fortification, phlegm elimination, and stasis resolution." The core herb combination likely exerts anti-HFS effects via modulation of MAPK and PI3K-Akt pathways, providing a pharmacological basis for TCM-driven HFS management.

Network Pharmacology↗