Port-wine stains (PWS), also termed capillary malformations, are congenital, progressive microvascular anomalies that can cause lifelong cosmetic and psychosocial burden and may signal syndromic involvement such as Sturge–Weber syndrome (SWS). We performed a focused evidence synthesis integrating mechanistic literature on somatic mosaicism and vascular remodeling with clinical evidence from randomized trials, observational cohorts, and quantitative-imaging studies. Key endpoints and theragnostic concepts were summarized to inform trial design and individualized treatment strategies. Somatic activating variants in GNAQ and related signaling networks drive endothelial dysfunction, aberrant vessel maturation, and lesion progression. Pulsed-dye laser(PDL) remains the global first-line modality, but response is heterogeneous and often incomplete, particularly in thick or nodular lesions. Hematoporphyrin monomethyl ether (hemoporfin)-mediated photodynamic therapy(PDT) shows high efficacy for selected phenotypes but carries distinct adverse-event profiles. Emerging theragnostics—including dynamic optical coherence tomography(D-OCT) and computational reconstruction—enable noninvasive quantification of vessel depth and caliber, supporting phenotype-guided parameter selection and objective response assessment. A mechanistically anchored, phenotype-informed framework that integrates molecular drivers with quantitative vascular imaging can accelerate precision strategies for PWS, improve endpoint rigor, and guide next-generation combination and targeted therapies.

This review systematically integrates the multi-level pathological mechanisms of the gut-liver axis (GLA) in ulcerative colitis (UC)-secondary liver injury (SLI) and the multi-target intervention network of natural bioactive compounds, elucidating the synergistic therapeutic logic of "barrier repair - inflammation suppression - microbiota remodeling - signal regulation." To systematically review the pathological mechanisms underlying UC-induced SLI and explore the targeted therapeutic effects and molecular mechanisms of natural bioactive compounds intervening through the GLA, this study adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement guidelines. A systematic search and analysis of literature published between 2015 and 2025 in the PubMed and Web of Science databases was conducted, focusing on the pharmacological effects of natural active ingredients such as polysaccharides, polyphenols, terpenoids, alkaloids, peptides, microbial extracts, and probiotics. Research indicates that natural bioactive compounds ameliorate UC and SLI through multi-target mechanisms, with key pathways including: (1) upregulating tight junction protein expression to restore intestinal barrier integrity; (2) modulating intestinal microbiota homeostasis to promote the production of short-chain fatty acids and secondary bile acids; (3) inhibiting TLR4/NF-κB and NOD-like receptor protein 3 inflammasome signaling pathways; (4) regulating the bile acid-FXR-TGR5 signaling axis and the tryptophan/AhR pathway; (5) balancing immune homeostasis of Th17/Treg and macrophage polarization, thereby blocking the pathological cascade of ``intestinal barrier disruption - microbial translocation - hepatic inflammation.'' By virtue of their multi-dimensional regulation of the GLA, natural bioactive compounds offer a safe and multi-targeted therapeutic strategy for UC-related liver injury. However, translational bottlenecks remain, including low oral bioavailability and efficacy heterogeneity, due to individual differences in microbiota. This review provides a theoretical basis for their further development as pharmaceuticals or functional foods and emphasizes the need for high-quality randomized controlled trials to validate their clinical efficacy and safety.

Five phenylpropanoid dimers chrysanthephenyls A-E, with the 1-O-1'-type (1) and 1-O-2'-type (2-5) ether bond linking modes, were isolated from the aerial parts of Chrysanthemum indicum. Among them, chrysanthephenyls D and E were two pairs of enantiomers, and chrysanthephenyl E was further resolved into its enantiomers (+)-chrysanthephenyl E and (-)-chrysanthephenyl E via chiral-phase HPLC. Their structures were characterized on the basic analysis of the spectroscopic techniques (IR, HRESIMS, 1D and 2D NMR), and their absolute configurations were determined by DP4+ NMR analysis and ECD calculation method. The antioxidant activity of chrysanthephenyls A-E was determined by measuring their free radical scavenging effects using the trolox equivalent antioxidant activity (TEAC) assay, and chrysanthephenyls D and E showed 17 and 15 times better activity respectively than that of the positive control trolox. Moreover, a mechanistic study revealed that the potential antioxidant activity of chrysanthephenyl D decreased the level of reactive oxygen species (ROS) mediated via activating nuclear factor E2-related factor 2 (Nrf2) and its downstream oxidases.

Microplastics (MPs) are persistent environmental pollutants that enter the circulatory system and subsequently reduce sperm quantity and quality. However, the influence of polystyrene MPs (PS-MPs) on the ovary and relevant mechanisms remain elusive. Herein, we aimed to examine the impact of PS-MPs on oxidative disorders in ovarian tissues and elucidate the underlying mechanisms. Healthy female rats were treated with different concentrations of 0.5 mu m PS-MPs (diluted in deionized H2O) for 90 days. Upon examination of hematoxylin-eosin-stained ovarian tissue sections, the number of growing follicles was reduced in PS-MP-treated rats when compared with that in control rats. Enzyme-linked immunosorbent assays revealed that PS-MP exposure markedly reduced anti-M & uuml;llerian hormone (AMH) levels. Treatment with PS-MPs downregulated superoxide dismutase, glutathione, and catalase activities in ovarian tissues while upregulating malondialdehyde levels. Furthermore, exposure to PS-MP blocked the Keap1/Nrf2/HO-1 signal transduction pathway. PS-MPs also triggered apoptosis in the ovarian tissue, as evidenced by increased TUNEL staining and expression levels of cleaved caspase-9, Bax, and Bcl-2. To reactivate the Keap1/Nrf2/HO-1 pathway, rats were co-administered PS-MPs and omaveloxolone (Oma), an Nrf2 activator, for 1 week. We found that Oma could counteract the PS-MP-mediated effects on oxidative disorder, apoptosis, AMH production, and follicle number in rat ovarian tissues. To develop an in vitro model, granulosa cells (GCs) were treated with 10 mu M H2O2 for 12 h to induce oxidative stress. H2O2-stimulated GCs exhibited attenuated cell growth and upregulated apoptosis and oxidative stress. Oma administration could ameliorate the H2O2-induced effects in terms of regulating cell viability, apoptosis, and oxidative stress in GCs. In summary, PS-MPs could induce apoptosis and oxidative stress via the Keap1/Nrf2/HO-1 signaling pathway in both rats and GCs.

This study aimed to investigate the active composition and mechanism of the Shuganfang (SGF) in treating drug-induced liver injury (DILI) using network pharmacology and molecular docking. The potential active ingredients and targets of SGF were obtained from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database. DILI-related targets were queried from various databases including GEO, GeneCards, OMIM, NCBI, and DisGeNET. The STRING database was used to establish a protein-protein interaction (PPI) network. DAVID was utilized for conducting gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. The data visualization and analysis of herb-ingredient-target and disease-pathway-target-ingredient networks were conducted using Cytoscape software (version 3.7.2). PyMoL and AutoDock software was used to select the best binding target for molecular docking. A total of 177 active ingredients,126 targets and 10112 disease targets were obtained, including 122 intersection targets. The identified potential active ingredients consisted of quercetin, kaempferol, luteolin, tanshinone IIa, nobiletin, isorhamnetin, beta-sitosterol and naringenin. The core targets implicated in the study were IL6, estrogen receptor 1 (ESR1), hypoxia-inducible factor alpha subunit 1 (HIF1A), MYC and vascular endothelial growth factor A (VEGFA). KEGG analysis revealed that the treatment of DILI with SGF mainly acted through apoptosis, the PI3K-Akt signaling pathway, and the tumor necrosis factor (TNF) signaling pathway. Furthermore, the binding affinities between the potential ingredients and the core targets were subsequently confirmed through molecular docking experiments. The findings indicated that the docking outcomes remained consistent and demonstrated a favorable capacity for binding. SGF exerts a therapeutic effect on DILI through multiple active ingredients, multiple targets and multiple pathways. Our findings contribute to a positive investigation and establish a theoretical basis for further extensive exploration of SGF as a potential treatment for DILI in future research.

Objective: Gentamicin (GM) is a commonly used aminoglycoside antibiotic, however, renal toxicity has limited its usage. The present study was designed to evaluate the ameliorative effect of Cistanche deser-ticola on GM-induced nephrotoxicity in rats.Methods: The nephrotoxicity in rats was induced by intraperitoneal administration of GM (100 mg/kg) for 10 consecutive days. Glomerular filtration rate, blood urea nitrogen, creatinine and kidney histopathology were detected to assess the GM-induced nephrotoxicity. The oxidative stress (catalase, superoxide dismutase, glutathione and malondialdehyde) was assessed. The inflammatory response (tu-mor necrosis factor -a, interleukin-6, myeloperoxidase and nuclear factor-kappa B) and apoptotic marker (Bax and Bcl-2) were also evaluated.Results: The results showed that water and 75% ethanol extracts of C. deserticola (named CDW and CDE, respectively) (100, 200 and 400 mg/kg) in combination with GM could recover the reduction of glomeru-lar filtration rate and enhance the renal endogenous antioxidant capability induced by GM. The increase in the expression of renal inflammatory cytokines (tumor necrosis factor -a and interleukin-6), nuclear protein of nuclear factor-kappa B (p65) and the activity of myeloperoxidase induced by GM was signif-icantly decreased upon CDW or CDE treatment. In addition, CDW or CDE treatment could decrease the Bax protein expression and increase the Bcl-2 protein expression in GM-induced nephrotoxicity in rats significantly.Conclusion: The study demonstrated that C. deserticola treatment could attenuate kidney dysfunction and structural damage in rats induced by GM through the reduction of inflammation, oxidative stress and apoptosis.(c) 2022 Editorial Board of Chinese Herbal Medicines Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Glucose and fructose, as a pair of isomers with similar structures, are still difficult to achieve their simultaneously selective and quantitative detection by electrochemical sensors. In this paper, aniline-guanine copolymer-gold nanoparticle composites (PAG-AuNPs) were prepared by a facile one-step HAuCl 4 reduction method. Through "doping and dedoping" characteristics of polyaniline (PANI) and the unequal nucleophilic reaction between guanine and glucose/fructose, it innovatively realized the selective quantitative detection of glucose and fructose on the electrochemical sensor without relying on the biological enzymes, molecular imprinting polymer and boric acid functionalized material. The morphology, chemical structure and electrochemical properties of PAG-AuNPs were characterized by scanning electron microscope, Fourier transform infrared spectroscopy, Raman spectroscopy, cyclic voltammetry and electrochemical impedance spectroscopy (EIS). The affinity of PAG-AuNPs to glucose and fructose was compared by combining the ultraviolet-visible spectrum with the Scatchard equation; the different reactions between PAG-AuNPs and glucose/fructose were characterized by the EIS. The modification amount of PAG-AuNPs and the testing environment and other conditions had been optimized. Under optimized conditions, the constructed sensor has a certain selective and quantitative detection ability for glucose and fructose and prefer reproducibility, stability, and certain practical applicability. This method turned out to be an efficient and convenient method for simultaneous detection of glucose and fructose, which are functional isomers of each other because they have same molecular formula.

INTRODUCTION:Codonopsis Radix (CR) is an edible food and traditional Chinese herb medicine that is widely used in China and Southeast Asia. Saccharides, including fructo-oligosaccharides (FOS) and polysaccharides, are among the most important active substances in CR. However, a quality evaluation of CR based on oligosaccharides has not been conducted.OBJECTIVE:This study aimed to establish a high-performance liquid chromatography coupled with charged aerosol detector method (HPLC-CAD) for the quality evaluation of CR and processed products based on analysis of monosaccharides and oligosaccharides.METHOD:A sensitive and rapid HPLC-CAD method for the simultaneous determination of two monosaccharides (D-fructose and D-glucose), sucrose, and FOS (GF2-GF6) was established to evaluate the quality of CR for the first time. In the present study, 65 batches of CR from three species of the genus Codonopsis were analysed using multivariate statistical techniques. Furthermore, the effects of cultivation management measures (plant growth retardants supply, harvesting time, and growth period) and primary process (drying methods) in the production areas on the target compounds were studied by analysing 34 batches of processed samples.RESULTS:Different varieties of CR resulted in considerably different saccharide contents. Cultivation management measures and processing method remarkably affected the quality of CR. Low concentration of plant growth retardants was recommended. The best harvest time is in October after 4 years of growth. Dryer-drying was suggested to meet the requirement for large-scale processing.CONCLUSION:This method would provide an efficient analytical tool for monosaccharides and oligosaccharides of CR and contribute to the improvement of CR quality.

Codonopsis Radix, a popular food homology medicine, is widely used in clinical traditional Chinese medicine and food supplement, raw products and three types of processed products are the main forms of decoction pieces in China. However, there is no scientific basis for comprehensive chemical characterization of raw and three types of processed products. Herein, we investigated qualitatively and quantificationally secondary and primary metabolites in raw Codonopsis Radix and three types of processed products by metabolomics and glycomics employing multiple chromatography-mass spectrometry technology combined with chemometric analysis further to look for differential compounds and propose the processing-induced chemical mechanisms. The results indicated that Codonopsis Radix became dark-colored and the smell of burnt incense odor was observed after processing. The principal component analysis demonstrated that secondary metabolome and glycome were significantly altered between raw and processed products, and 36 differential secondary metabolites and 11 differential primary metabolites were finally screened through orthogonal partial least-squares-discriminant analysis. The main types of compounds are alkaloids, terpenoids, glycosides, amino acids, monosaccharides, oligosaccharides, and furfural derivatives. Meanwhile, Chemical mechanisms could be involved, including oxidation, glycosidic hydrolysis, esterification, dehydration, and Maillard reaction. This work supplies a chemical basis for the application of various types of Codonopsis Radix decoction pieces.

A glucan named as CPC was obtained from the roots of Codonopsis pilosula and its structure was determined by HPGPC, IR, GC–MS, and NMR. HPGPC showed that CPC was a homogeneous polysaccharide and exhibited a molecular weight (Mp) of 1698 Da according to the equation of standard molecular weight (lg Mp = −0.1869 tR + 9.7386). The results from NMR and GC–MS demonstrated that the main linkages in CPC were 1-linked β-D-glucose, 1,4-linked α-D-glucose, and 1,4,6-linked α-D-glucose in the molar ratio of 1.0:3.8:1.0, which indicated that the structure of CPC exhibited the backbone of 1,4-linked α-D-glucose and the branched chains of 1,6-linked β-D-glucose. The immunomodulatory activity indicated that CPC showed the significant induction on the productions of NO, ROS, iNOS, TNF-α, IL-6, IL-1β and IL-10 and the mRNA expressions of iNOS, TNF-α, IL-6, IL-1β and IL-10 in RAW 246.7 cells. These data suggested that CPC was potential to human health by regulating immunity.

As a valuable medicine food homology plant, Codonopsis Radix has been widely used in China. This study aimed to analyze the content of nine potentially toxic elements in three Codonopsis Radix varieties and evaluate their health risks to the human body. In this study, a total of 147 samples were collected from five provinces in China. The content of nine potentially toxic elements (Al, Mn, Cu, Cr, Ni, As, Pb, Cd, and Hg) were determined by ICP-MS. Results showed that the average contents of Al, Mn, Cu, Cr, Ni, Pb, As, Cd, and Hg were 486.81, 30.30, 5.59, 1.38, 1.24, 0.40, 0.20, 0.16, and 0.11 mg/kg, respectively. The Codonopsis tangshen Oliv. samples from Hubei showed the highest contents of eight elements (Al, Mn, Cr, Ni, Pb, As, Cd, and Hg) among three varieties, and the highest Cu level was found in Codonopsis pilosula (Franch.) Nannf. samples from Shanxi. The content of toxic elements in three Codonopsis Radix varieties showed significant differences (p < 0.05). LDA models facilitated the identification of three Codonopsis Radix varieties with a 91.2% classification score and 89.1% prediction score. Further, when Codonopsis Radix was used as food or medicine, both the hazard quotient values for single element and the hazard index values for nine elements (0.87 for food and 0.84 for medicine) were far below one. The carcinogenic risk values for Pb in Codonopsis Radix when used as food or medicine were 1.14 × 10–6 and 5.51 × 10–8; the values for As were 4.80 × 10–5 and 4.98 × 10–6, respectively. It indicated that under the current consumption of Codonopsis Radix, the non-carcinogenic and carcinogenic risks from these potentially toxic elements were acceptable for consumers.

The present study reports the presence of a β-D-fructopyranosyl-(2→1)-linked fructan in nature for the first time, with a β-D-fructofuranosyl-(2→1)-linked fructan in a mixture from Codonopsis pilosula. High-performance gel permeation chromatography (HPGPC) shows that the molecule weights of these two fructans are 2.33 and 1.31 kDa. Their structures were analyzed by 1D and 2D NMR.

Fructans are generally divided into two different types:beta-D-fructofuranosyl-(2 -> 1)-linked inulin and beta-D-fructofuranosyl-(2 -> 6)-linked levan. Previously, Radix Codonopsis was found to be rich in inulin type of fructans with low molecular weight (<5000 Da). In this study, a novel macromolecular fructan with a molecular weight of 1.70 x 10(3)KD was isolated from Radix Codonopsis, and its homogeneity was shown to be a single peak by high performance gel permeation chromatography (HPGPC), and its structure was confirmed to contain a new type of linkage,alpha-D-fructofuranosyl-(2 -> 3)-beta-D-fructofuranosyl linkage, by 1D- and 2D-nuclear magnetic resonance (NMR).

Cancer prognosis is poor for patients with blood-borne metastasis. Platelets are known to assist cancer cells in transmigrating through the endothelium, but ligands for the platelet-mediated cancer metastasis remain poorly defined. von Willebrand factor (vWF) is a major platelet ligand that has been widely used as a biomarker in cancer and associated inflammation. However, its functional role in cancer growth and metastasis is largely unknown. Here we report that gastric cancer cells from patients and cells from two well-established gastric cancer lines express vWF and secrete it into the circulation, upon which it rapidly becomes cell-bound to mediate cancer-cell aggregation and interaction with platelets and endothelial cells. The vWF-mediated homotypic and heterotypic cell–cell interactions promote the pulmonary graft of vWF-overexpressing gastric cancer BGC823 cells in a mouse model. The metastasis-promoting activity of vWF was blocked by antibodies against vWF and its platelet receptor GP Ibα. It was also reduced by an inhibitory siRNA that suppresses vWF expression. These findings demonstrate a causal role of cancer-cell-derived vWF in mediating gastric cancer metastasis and identify vWF as a new therapeutic target.

The present study aimed to investigate the effect of sinomenine hydrochloride (SIN) on cell survival/proliferation in the human hepatoma cell line Huh7, as well as determine the underlying mechanisms. Three different doses of SIN, 140, 280 and 560 µM, were tested. Cellular apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blotting was used to determine protein levels of the apoptosis-associated regulators, cleaved caspase 3, B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak) and Bcl-extra large (Bcl-xl), as well as the cell cycle-related regulators, p21 and p27. It was observed that the three doses of SIN were able to suppress Huh7 cell survival/proliferation, and efficiently induce cellular apoptosis as well as multiphase cell cycle arrest. Mechanistically, SIN treatment upregulated the levels of the pro-apoptotic regulators, cleaved caspase 3 and Bax, and downregulated the level of anti-apoptotic Bcl-xl. Additionally, SIN treatment also increased the protein levels of p21 and p27, as two regulators functioning to slow cell cycle progression. Taken together, the present studied indicated SIN to be a promising compound for the treatment of hepatocellular carcinoma, based on its apparent effect in modulating cell apoptosis and the cell cycle in Huh7 cells in vitro.

In the current study, we analyzed the functions and mechanisms of Bletilla striata polysaccharide b (BSPb) against Angiotensin II (Ang II)-induced oxidative stress and inflammation in human mesangial cells (HMCs). It was found that BSPb could inhibit generation of Ang II-induced reactive oxygen species (ROS) and activation of proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in a dose-dependent manner. Further studies revealed that BSPb effectively blocked upregulation of NADPH oxidase 4 (NOX4). Moreover, knockdown of NOX4 significantly impaired the anti-oxidative function of BSPb. In addition, BSPb decreased overexpression of Toll-like receptor 2 (TLR2) induced by Ang II. Blocking TLR2 expression impaired the anti-inflammatory effects of BSPb. In conclusion, BSPb was found to possess anti-oxidative stress and anti-inflammatory functions against Ang II-induced ROS generation and proinflammatory cytokines activation. The NOX4 and TLR2 pathways played important roles in the biological effects mediated by BSPb.

CPS-F, a polysaccharide derived from Cordyceps sinensis, is a potential anti-inflammatory and anti-oxidative agent. We demonstrated that CPS-F not only inhibits platelet-derived growth factor BB (PDGF-BB)-induced intracellular reactive oxygen species (ROS) generation, and up-regulation of tumor necrosis factor-α (TNF-α), TNF-α receptor 1 (TNFR1), and monocyte chemotactic protein-1 (MCP-1), but also acts synergistically in combination with MAPK/ERK inhibitor U0126 and PI3K/Akt inhibitor LY294002. Additionally, up-regulation of pro-inflammatory factors was reversed by use of a combination of CPS-F and NADPH oxidase (NOX) inhibitor diphenyleneiodonium chloride (DPI) or silencing of NOX1. Furthermore, CPS-F prevents the PDGF receptor β (PDGFRβ) promoter activity induced by PDGF-BB in transfected cells and ameliorates increased levels of TNF-α, TNFR1, and MCP-1 when PDGFRβ is silenced, thereby suggesting that CPS-F possesses a bidirectional regulatory function. Our findings suggest CPS-F may exert its therapeutic effect for the treatment of glomerulonephritis related to human mesangial cells (HMCs) through the ERK1/2/Akt pathways.

BACKGROUND:Qian Yang Yu Yin Granule (QYYYG), a traditional Chinese herbal medicine, has been indicated for renal damage in hypertension for decades in China, but little remains known regarding its underlying molecular mechanism. Therefore, we performed the current study in order to investigate the underlying molecular mechanism of QYYYG in the treatment of hypertensive renal damage.METHODS:We hypothesize that QYYYG relieves hypertensive renal injury through an angiotensin II (Ang II)-nicotinamide adenine dinucleotide phosphate (NAPDH)-oxidase (NOX)-reactive oxygen species (ROS) pathway. In this study, we investigated the effects of QYYYG-containing serum (QYGS) in human mesangial cells (HMCs) against Ang II-induced cell proliferation, ROS production, and inflammation through the seropharmacological method.RESULTS:We found that QYGS could inhibit cell proliferation in Ang II-treated HMCs. In addition, QYGS considerably suppressed production of ROS, decreased mRNA and protein expression of NAPDH-oxidase 4 (NOX4), p22 (phox) , and activated Ras-related C3 botulinum toxin substrate 1 (GTP-Rac1); as well as counteracted the up-regulation of inflammatory markers including tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) p65, and interleukin 6 (IL-6). These effects were further confirmed in HMCs transfected with specific small interfering RNA (siRNA) targeting NOX4.CONCLUSIONS:Taken together, these results suggest that a NOX4-dependent pathway plays an important role in regulating the inhibitory effect of QYGS. Our findings provide new insights into the molecular mechanisms of QYYYG and their role in the treatment of hypertensive nephropathy.

A novel water-soluble polysaccharide, designated Bletilla striata polysaccharide b (BSPb), was isolated from a traditional Chinese medicinal herb, Bletilla striata. The crude polysaccharide was obtained by hot water extraction and purified by ion-exchange chromatography. The molecular weight was 260 kDa as determined by HPGPC (high performance gel permeation chromatography). Monosaccharide analysis showed that BSPb contained glucose and mannose with a molar ratio of 3:1. Methylation and spectroscopic analyses with 1D and 2D NMR spectroscopy showed that the backbone of BSPb is mainly composed of (1 → 2)-linked α-D-mannopyranose and (1 → 4)-linked β-D-glucopyranose residues. In this study, BSPb plays an important role in protection against the renal fibrosis effect, which is probably mediated by down-regulated TGF-β RI, TGF-β RII, and α-SMA in vitro.