共找到 20 条结果
Coriandrum sativum L. (coriander) is a medicinal herb with diverse pharmacological properties, but its molecular mechanism in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to systematically investigate the underlying mechanisms of coriander in ccRCC by multi-omics analysis. Active compounds were screened using Traditional Chinese Medicine Systems Pharmacology (TCMSP) and predicted targets identified via SwissTargetPrediction (STP) and Similarity ensemble approach (SEA). Transcriptomic data from GSE53757 were analysed with WGCNA and intersected with coriander targets. Key genes were selected using LASSO, SVM, and random forest models. NEK6 was further analysed for clinical relevance, methylation, immune association, single-cell expression, molecular docking and molecular dynamics simulation. Fourteen coriander compounds were identified, yielding 22 potential ccRCC-related targets. NEK6 and PYGL were consistently selected by all machine learning algorithms. NEK6 was overexpressed in ccRCC and associated with better prognosis, promoter hypomethylation, and lower mutation rates. NEK6 expression correlated with immune infiltration, particularly macrophages, and was enriched in tumour and myeloid cells at the single-cell level. Molecular docking and molecular dynamics simulation revealed strong and stable binding of luteolin, quercetin, and chryseriol to NEK6. NEK6 may function as a prognostic and immune-regulatory biomarker in ccRCC. Coriander flavonoids could target NEK6 to modulate the immune microenvironment, providing new insight into plant-based therapeutic strategies for ccRCC.
The first artificial cell (Chang 1957, 1964) was in the form of artificial red blood cells (RBCs), one of the most important cells because all cells, tissues, organs, and indeed the human being need it for survival. I first reconstructed artificial RBCs in vitro. This is made of cellular dimensions with ultrathin membranes of polymer, crosslinked protein, protein-lipid, or lipid. The next step in this work is to develop this for actual use to replace RBCs in the body. This is a more complex task requiring modifying the configuration and dimensions. Instead of starting with all three functions, a bottom-up approach is used. First, one with only oxygen transport function shows promising results in clinical trials with patients. A future direction is the development of artificial cells that have all three red blood cell functions including antioxidant, oxygen, and CO2 transport. My research group has also been doing innovative research going outside the box of RBCs. This way, extensive variations in contents, membranes, dimensions, and configurations are possible. This allows for worldwide and innovative applications that encompass hemoperfusion, delivery systems, COVID-19 vaccines, cancer therapy, therapy for hereditary enzyme defects like phenylketonuria, cell/stem cell therapy, microbes, nanomedicine, biotherapeutics, gene therapy, regenerative medicine, agricultural applications, aquatic culture, fermentation, nanorobotics, and other areas.
The present study aimed to dissect the underlying mechanism of the Gei Herba (LBZ) in the treatment of type 2 diabetes mellitus (T2DM) based on the gut microbiota and network pharmacology strategies. Thirty-one compounds from LBZ were screened and 187 corresponding targets were identified through the database and literature screening. Multiple disease-associated gene and target databases were used to screen and obtain 726 T2DM-related targets. The gutMGene v1.0 database was used for searching metabolites and targets of gut microbiota. 168 overlapping targets of LBZ, T2DM and the gut microbiota were matched and used to build a protein-protein interaction network and perform enrichment analysis. By bioinformatics analysis of microbiota-pathway-target-compound network, the PI3K-Akt signalling pathway was identified, and potential gut probiotics, such as Eubacterium limosum and Lactobacillus paracasei, were found. Subsequently, the core active compounds in LBZ bind to the core targets were verified by molecular docking, all of which exhibited good binding affinity. Finally, four compounds, eleutheroside A, gallic acid, kaempferol, and protocatechuic acid, were found to conform to Lipinski's rule and be non-toxic, showing great potential in the treatment of T2DM. These findings suggest the potential mechanism of LBZ in the treatment of T2DM and the core compounds, such as eleutheroside A may be the promising candidates for T2DM treatment.
The mechanisms underlying sepsis remain poorly understood and specific therapeutic options remain lacking. Accumulating evidence suggests that butyrate metabolism and oxidative stress (OS) are involved in the pathogenesis of sepsis. This study aims to elucidate molecular characteristics of butyrate metabolism and OS-related genes in sepsis and find potential therapeutic targets. Using sepsis-related datasets, 876 differential expression genes (DEGs) were screened and intersected with butyrate metabolism and OS-related genes to yield 8 differentially expressed butyrate metabolism and OS-related genes (DEBORGs). Machine learning algorithms finally identified 3 feature genes (ALDH1A1, CYP1B1, and GADD45A) with favourable diagnostic values for sepsis. CIBERSORT immune infiltration analysis demonstrated strong associations between feature genes and the infiltration proportions of various immune cell types, such as monocyte, macrophage, and neutrophil. Cellular experiment and prospectively collected clinical samples were utilized to validate the expression levels and diagnostic efficacy of feature genes. The scRNA-seq analysis indicated that monocyte plays a crucial role in mediating the effect of feature genes on sepsis. This study elucidates that ALDH1A1, CYP1B1, and GADD45A are feature genes linked to butyrate metabolism and OS in sepsis, with monocytes being the primary cells involved, providing novel insights into the sepsis pathogenesis and potential therapeutic targets.
With a globally ageing population, neurodegenerative disease poses an increasingly greater risk to health span, yet there are still no curative treatments. Efficient biomimetic modelling is the underlying target for improving preclinical-to-clinical translation of therapies, yet current techniques are poorly translated to clinical studies: animal models, 2D cell culture, as well as 3D spheroid and organoid cultures all have disadvantages which could be resolved by a tuneable, standardized approach. As such, 3D tissue engineered human models have huge potential, but even biomimetic, repeatable, translatable engineered tissues lack maturity in the neural networks created. Neurogenesis and gliogenesis are the processes by which new neurons and glia are created in vivo, mediated by architectural, cellular microenvironmental, and signalling cues which could be adopted in the engineering and synthesis of 3D neural models. This review will look at neurogenic and gliogenic cues and their engineered incorporation to overcome common shortcomings of in vitro 3D neural models-namely maturity, complexity, and reproducibility. In vitro brain modelling research is becoming increasingly crucial as CNS drug trials fail, animal models lack translatability, and current models lack maturity and complexity.Matrix, architectural, and molecular cues during corticogenesis facilitate the complex layering and maturation of the brain in utero—as such, engineered incorporation of a select few could yield the translatable brain models needed.Perhaps the greatest limitation is the long-term stability requirement for brain models. The molecular cues must be stable and either slow release or replenished; and the matrix cues, particularly of the hydrogel base polymer, must retain model integrity for months whilst providing a soft, viscoelastic environment, sensitive to remodelling.As bioprinting and microfluidic techniques advance, there is potential for spatial and temporal control as well as vascularization, but the question will become what select cues are essential to keep models as reproducible as possible.
Lipidation enhances the antimicrobial potential of cationic peptides by increasing amphiphilicity. The nuclear localization signal peptide PKKKRKV, although cell-penetrating, has weak intrinsic antimicrobial activity. This study evaluates whether conjugation with fatty acids of varying chain lengths (C16-C18) and saturation can improve its antimicrobial properties and elucidate the associated structure-activity relationships. Five PKKKRKV-based lipopeptides (LP-1-LP-5) were synthesized using Fmoc solid-phase peptide synthesis and conjugated with different fatty acids. The compounds were purified by RP-HPLC and characterized by mass spectrometry and NMR. Antimicrobial activity was assessed against Gram-positive bacteria (Staphylococcus epidermidis, Staphylococcus aureus), Gram-negative bacteria (Escherichia coli, Salmonella typhimurium), and the fungus Candida albicans using broth microdilution assays. In silico studies, including molecular docking, molecular dynamics simulations, and DFT calculations, were conducted to investigate potential mechanisms and electronic properties. Lipidation significantly improved antimicrobial activity. LP-5 (C18:1, unsaturated) showed the broadest spectrum, with MIC values of 11.59-23.19 µM against both Gram-positive and Gram-negative bacteria. LP-2 (C16:0, saturated) exhibited selective potency against E. coli (MIC = 6.96 µM), while LP-3 and LP-4 demonstrated moderate, broad-spectrum activity. Computational analyses indicated favorable target interactions, though they did not fully correlate with experimental results. LP-4 and LP-5 showed the smallest HOMO-LUMO gaps (∼0.111-0.112 eV), suggesting higher electronic reactivity. Overall, lipidation of PKKKRKV is a promising strategy for developing antimicrobial agents. Chain length and saturation significantly influence activity, with LP-5 emerging as the most promising broad-spectrum candidate. Further studies are required to validate mechanisms and assess toxicity..
A Disintegrin and Metalloproteinase with Thrombospondin motifs 7 (ADAMTS7) plays a critical role in atherosclerosis by degrading the extracellular matrix and modulating smooth muscle cell (SMC) proliferation, migration, and phenotypic transformation. This study investigated the association between the ADAMTS7 single-nucleotide polymorphism (SNP) rs1045130 and large artery atherosclerotic (LAA) stroke. Genotyping analyses were conducted on two independent case-control cohorts comprising 1,027 LAA patients and 1,043 age-matched controls, followed by the quantification of ADAMTS7 expression and its downstream molecular effects. ADAMTS7 was highly expressed in endothelial cells, SMCs, and macrophage-derived foam cells of vulnerable human aortic plaques. Furthermore, individuals carrying the rs1045130 A allele or GA/AA genotype had a significantly higher susceptibility to LAA stroke, poorer short-term outcomes, and an increased risk of one-month recurrence. Mechanistically, the G > A mutation disrupts the ADAMTS7-miR-654-5p interaction, leading to elevated ADAMTS7 expression and subsequent promotion of foamed vascular SMCs (VSMCs) proliferation and migration. The rs1045130 G > A variant is associated with increased LAA stroke incidence and worse prognosis. The mutation promotes the proliferation and migration of foamed VSMCs by disrupting the miR-654-5p/ADAMTS7 axis, potentially accounting for the higher disease risk and poorer prognosis observed in affected individuals.
Ascorbic acid (AA) has strong antioxidant and anti-diabetic activities; nevertheless, its therapeutic value is restricted due to rapid degradation, low-bioavailability and short systemic retention. To address these constraints, this study describes the development of a green-synthesized zinc oxide nanoparticle (ZnO NP)-based delivery system functionalized with AA (ZnO-AA NPs) and assesses its antidiabetic and neuroprotective effects. AA-assisted precipitation method was used to develop ZnO-AA NPs, which were then characterized by dynamic light scattering (DLS), zeta potential (ZP), scanning electron microscopy (SEM), FTIR spectroscopy and X-ray diffraction (XRD). The nanoparticles had a homogeneous size (∼38 nm), good colloidal stability and a crystalline wurtzite structure. In vitro, ZnO-AA NPs showed dose-dependent inhibition of α-amylase and α-glucosidase. In vivo, oral ZnO-AA NPs (25 and 50 mg/kg) significantly improved glycaemic control, lipid profile and antioxidant enzyme levels compared to free AA (*p* < 0.01, *p* < 0.001; one-way/two-way ANOVA). ZnO-AA NPs dramatically reduced diabetes-related cognitive impairment, resulting in improved performance in the Morris water maze (MWM) and open field tests (OFTs) (*p* < 0.001), decreased hippocampal acetylcholinesterase (AChE) activity and preserved neuronal architecture. Overall, the ZnO-AA nanoformulation represents a multifunctional nanomedicine technique that improves the therapeutic efficacy of AA and has considerable promise for the treatment of diabetes and its associated neurodegenerative consequences.
Alcohol use disorder (AUD) poses a substantial global health burden, with its molecular mechanism remaining elusive. This study integrated datasets (GSE253155, GSE180722, GSE182173 and GSE176122) and clinical specimens to identify non-invasive biomarkers and therapeutic candidates for AUD. Transcriptomic analysis of post-mortem prefrontal cortex identified 34 differentially expressed genes (DEGs), significantly enriched in TNF/IL-17 signalling, ribosome, cytokine-cytokine receptor interaction and endoplasmic reticulum protein processing. Among multiple machine learning algorithms, the support vector machine demonstrated superior classification performance, prioritizing MDK, FAM225B and SERPINA3 as critical biomarkers. These were incorporated into a highly predictive diagnostic nomogram. Intersection with plasma extracellular vesicle (EV) RNAs showed that all three biomarkers were detectable and upregulated in AUD patients versus controls, which was confirmed by quantitative real-time PCR (qRT-PCR) in a clinical validation cohort. SERPINA3 exhibited a particularly robust association with AUD, maintaining significance after adjustment for confounders and suggesting direct effects via mediation analysis. Cross-species validation confirmed a conserved dysregulation of murine Serpina3n. Computational drug repurposing identified loratadine, doxepin, citalopram and imipramine as promising therapeutic candidates targeting SERPINA3. Collectively, this work delineated PFC signature genes, proposed a EVs-supported brain-periphery molecular crosstalk, and provided translatable biomarkers and repurposable candidates for AUD precision medicine.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial hyperplasia, inflammatory cell infiltration, and joint destruction. This study investigates the inhibitory effects and metabolic mechanisms of Eucalrobusone C (EC), a novel formyl-phloroglucinol meroterpenoid derivative isolated from Eucalyptus robusta, on Tumour Necrosis Factor-α (TNF-α)-induced rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). EC was extracted and purified, with purity confirmed using 1H Nuclear Magnetic Resonance Spectrum (NMR) at 400 MHz. RA-FLSs were exposed to varying concentrations of EC, followed by comprehensive assessment including CCK8 assay for cell proliferation, flow cytometry for cell death, and Transwell assay for migration and invasion capacity. Metabolomic profiling employed Ultra-High Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-Q-TOF MS), integrated with multivariate statistical analysis and bioinformatics tools to identify metabolic alterations. Results indicated that EC suppressed RA-FLS proliferation in a time- and concentration-dependent manner, significantly enhanced apoptosis, and inhibited cell migration and invasion. Metabolomics analysis detected 898 metabolites, with 112 upregulated and 67 downregulated in EC-treated groups compared to TNF-α-induced controls. Key differentially expressed metabolites were enriched in pathways including ABC transporters, neuroactive ligand-receptor interactions, protein digestion and absorption, and cAMP signalling. These findings suggest that EC exerts anti-rheumatic effects by modulating these metabolic pathways, offering potential as a therapeutic agent for RA management.
Escalation of antimicrobial resistance amongst Klebsiella pneumoniae (K. pneumoniae) represents a remarkable worldwide health concern. This study reports the green biosynthesis of copper, silver and magnesium oxide trimetallic nanocomposites (CuO-AgO-MgO TNCs) using banana peel extract as a safe and sustainable reducing and stabilizing agent and emphasizes its inhibitory activity against carbapenem-resistant K. pneumoniae (CRKP) strains. The TNCs were characterized by ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infra-red (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, transmission electron microscope (TEM), scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) analysis, confirming their crystalline structure (average size 125 nm) and elemental composition (Cu, Ag, Mg, O). Cytotoxicity assessment using WI-38 normal cells showed minimal toxic effect with an IC50 of 193.49 ± 2.85 µg/mL. Antibacterial activity was evaluated against genotypically diverse CRKP strains. Well diffusion assay (WDA) showed inhibition zones of 18-38 mm, while the broth microdilution assay provided minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranging from 8 to 1024 µg/mL and 128 to 2048 µg/mL, respectively. Time-kill assays indicated rapid bacterial growth reduction within 2 h, and antibiofilm assays showed 25-91% inhibition of biofilm formation. The image provided by SEM revealed pronounced morphological alterations in treated bacterial cells. Our findings exhibited biogenic CuO-AgO-MgO TNCs with potent antibacterial and antibiofilm activities against CRKP while showing negligible toxicity towards normal cells, highlighting their potential as a safe and effective alternative antimicrobial strategy.
Cell membrane-derived vesicles play essential roles in intercellular communication, material transport, and waste disposal. Despite their biomedical and industrial potential, isolating extracellular vesicles from natural sources remains technically challenging, limiting purification efficiency and scalability. This study introduces cell membrane extrusion as an alternative approach to optimize the production of cell membrane-derived vesicles (CSMs), from eukaryotic and prokaryotic cells. CSMs, generated from HeLa and SH-SY5Y cells exhibited a distinctive cup-shaped morphology and sizes of 151.36 ± 72.36 nm, and 416.86 ± 108.49 nm at 20 °C by DLS respectively, showing remarkable thermal stability at 4-70 °C range. Furthermore, loaded vesicles interacted with mammalian cells and achieved successful cargo internalization. CSMs were also produced from E. coli membranes, forming unilamellar vesicles of approximately 100 nm, as observed by Cryo-TEM. These vesicles displayed an inverse correlation between vesicle size and thermal stability and efficient cargo incorporation detected in 85% ± 3% of CSMs. However, under tested conditions, no interaction with prokaryotic cells occurred, and consequently, no delivery of the loaded molecule was observed. Overall, thesefindings highlight the potential of generating cell membrane-derived nanovesicles through extrusion, offering a promising strategy to mimic extracellular vesicles for innovative biomedical and industrial applications, including targeted drug delivery system.
In this study, gold nanoparticles (AuNPs) were bio-fabricated using the water extract of marine brown seaweed Hizikia fusiformis (Hfs), commonly eaten as food in Southeast Asia, Korea, China, and Japan, and in other parts of the world. This process offers massive potential for the manufacture of new-generation nanomaterials utilizing sustainable seaweed components and explores its biological (tyrosinase, antidiabetic, antioxidant) and environmental (photocatalytic degradation of toxic industrial dyes) applications. Different spectroscopic approaches were employed to characterize and confirm the fabrication of Hfs-AuNPs. UV-Vis spectroscopy displayed the Hfs-AuNP's surface plasmon resonance at 534 nm. The XRD result revealed the crystalline nature of the nanoparticle. According to FT-IR analysis, various phytoconstituents like polyphenols and polysaccharides from the Hfs extract contributed to the reduction and stabilization of Hfs-AuNPs. Hfs-AuNPs displayed a spherical form with a zeta potential of -18.6 mV. Notably, Hfs-AuNPs exhibited encouraging tyrosinase inhibition (31.74 % inhibition while kojic acid showed 52.40 % inhibition at 100 µg/ml), antidiabetic effect (56.38 % α-amylase activity while acarbose exhibited 61.19 % activity at 100 µg/ml), and antioxidant properties (82.89 % of DPPH scavenging while 60.04 % scavenging by BHT and 63.73 SOD effect while 61.77 % scavenging by BHT at 100 µg/ml). Besides, Hfs-AuNPs also displayed positive photocatalytic degradation of toxic industrial dyes like methylene blue (29.20 % degradation at 5 h) and methyl orange (21.26 % degradation at 3 h). The above eco-friendly, cost-effective, and sustainable synthesis method can be explored further for large-scale production and future substantial applications in therapeutic and industrial needs.
Chronic wounds remain a major healthcare concern due to delayed healing and high risk of infection. This study investigates the potential of genipin-crosslinked gelatin and asiaticoside (ASI) as innovative biomaterials ink for wound healing. Hydrogels were prepared using different concentrations of gelatin (9% w/v and 10% w/v) and asiaticoside at 0.05% w/v, with genipin employed as a natural crosslinker to improve mechanical strength. Their physicochemical characteristics, which includes swelling ratio, water vapour transmission rate (WVTR), contact angle, porosity, enzymatic degradation, and surface roughness were systematically evaluated, along with mechanical and cytotoxicity properties. Incorporation of asiaticoside enhanced hydrogel hydrophilicity, reduce porosity, and improved swelling behaviour, while preserving biodegradability and overall structural stability. The WVTR values remained within the optimal wound healing range (1500-2500 g/m2h). Furthermore, asiaticoside-loaded hydrogels demonstrated excellent cytocompatibility, supporting fibroblasts viability at lower concentrations including live/dead assay tests that were conducted. This study demonstrates that genipin-crosslinked gelatin-asiaticoside hydrogels are promising biomaterials ink for accelerated wound healing, with an initial characterization of an injectable formulation guiding their successful optimization to achieve the optimal injectability and printability for tissue engineering and three-dimenstional bioprinting (3D-bioprinting).
The prevalence of obesity has risen sharply in recent years, prompting the need for safer and more biocompatible therapeutic alternatives to conventional anti-obesity drugs. In this study, zinc oxide nanoparticles (ZnO NPs) were synthesized using pomegranate husk extract via two green approaches: conventional heating and microwave-assisted synthesis. Structural and morphological characterizations confirmed successful nanoparticle formation. Microwave-assisted ZnO nanoparticles (MA-ZnO NPs) exhibited smaller particle dimensions and narrower polydispersity compared with conventionally synthesized ZnO NPs. Both types of ZnO NPs demonstrated notable antioxidant activity (>62% scavenging in DPPH and ABTS assays) and strong inhibitory effects against pancreatic lipase and α-amylase (>70%), comparable to standard drugs such as orlistat and acarbose. Cytotoxicity assays using Vero cells confirmed high biocompatibility, with >60% cell viability. This work presents a comparative evaluation of two green synthesis methods and highlights the potential of biogenic ZnO NPs as multifunctional agents for oxidative stress reduction and enzyme inhibition in obesity management.
An open-level, single-arm, phase-4 clinical trial was carried out to assess the safety and potential benefits of micronized coated ferric pyrophosphate (MEFP) in patients with iron deficiency anaemia (IDA). For 12 weeks, 60 patients between the ages of 18 and 60 with moderate IDA were randomly received MEFP by PO daily. The efficacy endpoints as haemoglobin levels, mean corpuscular haemoglobin (MCH), mean cell haemoglobin concentration (MCHC), packed cell volume (PCV), red blood cell count (RBC), serum ferritin and transferrin saturation (%) were measured. Adverse event reports and physical examinations were performed as a measure of safety assessment. The results revealed that haemoglobin, MCV, MCHC, serum ferritin, transferrin saturation (%), PCV and RBC increased significantly from baseline. Fewer occurrences were observed in a few patients, and their adverse events were minimal. There was no adverse effect on liver or renal functions. Few minor improvements were noticed at the completion of the study. In conclusion, MEFP appears to be effective in IDA and well tolerated, with a favourable safety profile. MEFP is an effective, safe therapeutic alternative in IDA subjects for increasing haemoglobin concentration and iron stores along with improvement of symptoms related to anaemia.
Membrane composition is a critical factor for electroporation. Although existing research focuses on pore formation driven by local phospholipid headgroup clusters, the large-scale membrane dynamics post-pore formation remain underexplored. In this study, coarse-grained (CG) molecular dynamics (MD) simulations were employed to investigate the effects of phospholipid headgroups (PC, PE and PS), tail characteristics (DLPC, DPPC, POPC and DOPC) and cholesterol (CHOL) content (0 mol%-50 mol%) on membrane electroporation. The results demonstrate that membrane structural parameters, such as area per lipid, hydrophobic layer thickness and interfacial water penetration depth, significantly influence the electroporation threshold electric field and transmembrane substance flux. Phospholipid headgroups can modulate the area per lipid and hydrophobic layer thickness through their size, hydrogen bonding and charge. Regarding phospholipid tails, increasing their length and unsaturation strengthens the hydrophobic layer, and thereby inhibits electroporation. The incorporation of CHOL into the membrane leads to tighter lipid packing, increased layer thickness and restricted water penetration, all of which elevate the threshold electric field. After electroporation, CHOL reduces transmembrane flux by enhancing line tension, although this inhibitory effect is limited at higher concentrations. The simulation results align well with existing experimental data, suggesting our approach can guide protocol design and highlight membrane composition's critical role in electroporation efficiency.
Natural products remain an invaluable source of anticancer agents, with flavonoids and phenolic compounds being particularly recognized for their ability to modulate tumour suppressor pathways. Carissa macrocarpa (C. macrocarpa) is an edible plant rich in secondary metabolites. This study sought to identify the secondary metabolites of C. macrocarpa leaves using LC-MS/MS, evaluate their cytotoxic and pro-apoptotic effects in colorectal cancer cell lines (HT-29 and LS174T), and elucidate potential molecular interactions with p53 through in silico docking, thereby uncovering mechanistic insights into its anticancer activity. LC-MS/MS revealed abundant flavonoid glycosides, particularly derivatives of kaempferol, quercetin, and isorhamnetin. Biological assays demonstrated potent cytotoxicity of the extracts, with the total extract showing the strongest effect against LS174T cells (IC50 = 0.5 µg/mL). Extracts induced apoptosis, caused G1/S/G2 cell cycle arrest, and upregulated p53 expression. Docking confirmed strong binding affinities (-7.87 to -9.28 kcal/mol) for glycosylated flavonoids such as kaempferol-3-O-robinoside-7-O-rhamnoside, hesperidin, and isorhamnetin-3-O-rutinoside. Also, 100 ns molecular dynamics studies confirmed the stable binding of both kaempferol-3-O-robinoside-7-O-rhamnoside and hesperidin against the p53 pocket. In conclusion, this integrative study demonstrates that C. macrocarpa exerts anticancer effects in colorectal cancer cells by modulating p53 and provides a mechanistic rationale for its therapeutic potential.
Currently, therapeutic options for hepatic ischemia-reperfusion injury (HIRI) remain limited and challenging. An emerging alternative involves the combination of ingredients from traditional Chinese medicine (TCM) and beneficial gut microbiota (GM) metabolites. This study integrates ingredients of Salvia miltiorrhiza (SM) and metabolites of GM to assess their combined therapeutic efficacy against HIRI through pyroptosis using network pharmacology. Twenty-nine final targets were recognized as key proteins responsible for the alleviation of HIRI by SM ingredients and GM metabolites through pyroptosis, with GAPDH, AKT1, ILB1 emerging as central targets in the protein-protein interaction (PPI) network. The Toll-like receptor (TLR), NOD-like receptor (NLR), IL-17, TNF and MAPK signalling pathways were identified as key pathways in the therapeutic effects of SM ingredients and GM metabolites. Eight microRNAs (miRNAs) were predicted to be potential miRNAs exerting the most influence. Four SM ingredients and 11 GM metabolites were identified as non-toxic, promising candidates against HIRI. Moreover, the results of molecular docking showed all compounds were well combined with the corresponding proteins. This study highlights the therapeutic potential of TCM and beneficial GM in HIRI treatment and provides a foundational dataset for future research on their combined application. Further in vitro and in vivo studies are needed to validate these findings.
Alzheimer's disease (AD) and Huntington's disease (HD) share neuroinflammatory mechanisms, yet their specific immune microenvironments remain poorly understood. Integrating transcriptomic profiles of peripheral blood and frontal cortex tissues with 2,160 immune-related genes, we analysed their shared immunopathology. Differential analysis identified 64 peripheral and 159 central consistently dysregulated immune genes, intersecting to isolate 10 co-expressed all-immune genes. Functional enrichment highlighted neutrophil and monocyte activation, alongside IL-17 and T-cell receptor signalling pathways. Machine learning (LASSO and Boruta) robustly pinpointed MMP9 as the core shared immune hub gene. External validation revealed MMP9 exhibited modest diagnostic performance in peripheral blood (AD AUC = 0.616; HD AUC = 0.619) but stronger predictive accuracy in brain tissues (AD AUC = 0.825; HD AUC = 0.876). Furthermore, MMP9 expression positively correlated with neutrophil and M0 macrophage infiltration. While modest peripheral accuracy limits its standalone diagnostic utility, this cross-tissue analysis establishes MMP9 as a consistently upregulated candidate molecular indicator of shared neuroinflammation, offering a valuable target for future mechanistic research.