Combinatorial Chemistry & High Throughput Screening - Online First

This study aimed to elucidate the role of NFS1 in gastric cancer (GC) prognosis, pyroptosis, and oxaliplatin chemosensitivity, and to explore its interaction with the MAPK signaling pathway.

GC mRNA expression and clinical survival data were obtained from The Cancer Genome Atlas Gastric Adenocarcinoma (TCGA-STAD). Kaplan-Meier analysis assessed the prognostic significance of NFS1. R software facilitated NFS1 expression analysis and KEGG pathway enrichment. Pyroptosis was evaluated using Cell Counting Kit-8, flow cytometry, and morphological analysis. Western blotting quantified pyroptosis-related protein expression. RNA sequencing libraries were prepared and sequenced on the Illumina platform.

Oxaliplatin treatment significantly reduced cell viability and induced pyroptosis, which was markedly attenuated by GSDME deficiency. Oxaliplatin activated caspase-3 and cleaved GSDME, effects that were reversed by the caspase-3 inhibitor Z-DEVD. NFS1 knockdown enhanced GSDME and caspase-3 cleavage, increasing pyroptosis (PI and Annexin-V double-positive cells) compared to controls. KEGG analysis of RNA sequencing and TCGA data highlighted the MAPK signaling pathway. Western blotting confirmed that oxaliplatin combined with NFS1 knockdown suppressed MAPK pathway proteins.

The caspase-3/GSDME axis mediates oxaliplatin-induced GC pyroptosis. High NFS1 expression inhibits GSDME activation, promotes MAPK protein activation, and reduces oxaliplatin sensitivity. These findings suggest that the caspase-3/GSDME pathway offers a novel mechanism for oxaliplatin's antitumor effects. NFS1 may serve as an independent prognostic biomarker in GC, influencing disease progression through MAPK regulation.

NFS1 is a promising therapeutic target for gastric cancer, especially in the study of oxaliplatin-based chemotherapy in combination with a treatment regimen that triggers pyroptosis.

Chronic atrophic gastritis (CAG) is an important stage in the occurrence and development of gastric cancer, and the morbidity of CAG is increasing year by year. Qilianshupi Decoction (QLSP) is a Chinese herbal compound which has been proved to reverse CAG, but its mechanism remains unknown. We wanted to identify the main components of QLSP by mass spectrometry and liquid phase analysis, and investigate their potential pathways for CAG treatment in combination with network pharmacology.

The main active components of QLSP were identified by liquid chromatography and mass spectrometry. Combined with network pharmacology, the targets where the drugs may act were identified and verified by animal experiments. Rats were randomly divided into control group, model group, QLSP low-dose group, QLSP medium-dose group, QLSP high-dose group and Weifuchun group. Rat CAG model was prepared by “N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) + ethanol intragastric + ranitidine feed”. After the test, gastric tissues were taken for pathological staining and immunohistochemistry.

We identified 51 prototype components of QLSP and found that QLSP treatment of CAG was closely related to p53. In animal experiments, CAG results in the decrease of E-cadherin and the increase of N-cadherin, Vimentin, p53, SMAD2 and TGF-β (p<0.05). Both QLSP and Weifuchun can increase E-cadherin and decrease N-cadherin, Vimentin, p53, SMAD2 and TGF-β (p<0.05).

QLSP, a traditional Chinese medicine formula with multi-component and multi-target characteristics, has been shown in our study to effectively regulate key EMT (epithelial-mesenchymal transition) markers and their upstream/downstream regulators. In animal experiments, QLSP successfully reversed the EMT process in CAG model rats. This finding provides new therapeutic targets for CAG treatment, though several challenges remain in clinical translation: First, rat CAG models differ from human CAG in pathological features and disease progression, and species-specific physiological and metabolic variations may limit the extrapolation of these findings. Second, network pharmacology analysis identified IL-6, alongside TP53, as another critical target of QLSP in CAG intervention. Therefore, future studies should further clarify the molecular mechanisms by which QLSP modulates EMT via IL-6-related pathways and validate its efficacy through well-designed clinical trials, ultimately providing a comprehensive understanding of QLSP's therapeutic potential in CAG.

QLSP inhibits epithelial-mesenchymal transition (EMT) in gastric mucosal epithelial cells and prevents CAG, possibly by regulating p53/TGF-β signaling pathway.

Nanomedicine integrates nanotechnology with healthcare, offering targeted diagnostics, therapeutic solutions, and preventive applications. India, through agencies such as the Indian Council of Medical Research (ICMR), the Department of Biotechnology (DBT), and the Department of Science & Technology (DST), has prioritized nanomedicine to address public health challenges. Despite significant progress, gaps persist in clinical translation and interdisciplinary applications.

To analyze the scope, gaps, and opportunities in nanomedicine research in India, focusing on ICMR-funded projects.

Data on nanomedicine proposals submitted to ICMR (2018–2022) were reviewed using keyword-based searches from databases and survey responses from principal investigators. Metrics included funding trends, research objectives, and outcomes. Quantitative and qualitative analyses assessed scientific progress and translational potential.

Over the past five years, the ICMR has funded over 250 projects, with a focus on cancer therapy, infectious diseases, and diagnostics. Achievements include nanoparticle-based drug delivery systems and diagnostics, with notable innovations like Albupax® and gold nanoparticle-based sensors. Research activity increased over the years, with a slight slowdown during the COVID-19 period. Funding was primarily allocated to states with established research infrastructures, underscoring the need for more equitable support nationwide.

Nanomedicine research in India has made significant progress, primarily in cancer; however, limited research has been observed in non-cancer applications and long-term safety studies. Differences in funding across various regions and difficulties in turning ideas into marketable products were major problems. Integrating nanomedicine with genetic tools offers promise for more targeted treatments.

The ICMR's support has advanced nanomedicine research in India, particularly in the field of oncology. To strengthen India's position in the field, future efforts must address unmet needs, including non-cancer applications, clinical translation, and regulatory harmonization. Collaborative initiatives and equitable funding distribution can accelerate advancements and strengthen the implementation of nanomedicine research.

Banxia Xiexin Decoction (BXD), traditionally used for gastrointestinal disorders like Chronic Colitis (CC), exerts anti-inflammatory, antibacterial, and intestinal flora-regulating effects. However, CC’s pathogenesis remains unclear, necessitating further research into BXD’s machanism.

Active BXD components were identified via UPLC-Q-TOF-MS/MS. Databases (TCMSP, HERB, GeneCards,DisGeNET,STRING) were used to identify compound/disease targets. Cytoscape 3.9.1 constructed protein-protein interaction networks, and DAVID database was used for GO and KEGG enrichment analysis of core genes. Finally, PyRx, AutoDockTools and PyMol were used for molecular docking, virtual computation, and visualization analyses of core components and key targets.

UPLC-Q-TOF-MS/MS detected 482 BXD components, with 165 active ingredients, including quercetin, kaempferol, baicalein, etc. There were 283 targets related to BXD's treatment of CC, of which the core targets included AKT1, IL-6, TP53, ALB, etc. GO enrichment analysis yielded relevant entries including molecular function 60 entries, 257 entries of biological processes, and 31 entries of cellular composition, and KEGG enrichment analysis identified 150 entries involving IL-17, TNF, PI3K-Akt, and other pathways. The molecular docking results demonstrated that the core components exhibited better binding activities with the key targets.

Quercetin, kaempferol, baicalein, and naringenin, the main active ingredients in BXD, may play roles in anti-inflammatory, antimicrobial, and regulating intestinal microbiota to achieve the therapeutic purpose of CC treatment by mediating the targets of AKTl, IL-6, TP53, and ALB, and regulating the signaling pathways of IL-17, TNF, and PI3K-Akt.

BXD’s active components alleviate CC through multi-target and multi-pathway regulation, providing a mechanistic foundation for clinical application.

This study aims to validate the hypothesis that Modified Qianzheng Powder (MQZP) exerts a protective effect on atherosclerosis (AS) by targeting macrophage-associated inflammatory pathways through a multi-target approach.

The active compounds and targets of MQZP were identified through TCMSP, HERB, and published literature. AS-related targets were extracted from disease databases. Using Venny 2.1.0, intersection targets were obtained, followed by PPI network construction and topological analysis to identify core therapeutic targets of MQZP for AS. Metascape facilitated GO and KEGG enrichment analyses. Molecular docking validated core target-compound interactions, with experimental verification of network pharmacology results.

We identified 124 active compounds and 417 potential therapeutic targets for atherosclerosis. Key bioactive constituents included cyclo(D)-Pro-(D)-Phe, aurantiamide, and beauverilide A, with TP53, SRC, STAT3, and AKT1 as core targets. GO and KEGG enrichment analyses revealed 3,417 biological processes and 238 signaling pathways. Molecular docking confirmed stable binding between core targets and compounds. In vitro, MQZP exhibited no significant cytotoxicity, effectively reducing ox-LDL-induced macrophage lipid accumulation and downregulating the levels of IL-1β, TNF-α, and MCP-1.

In summary, we found a variety of active ingredients of MOZP, which interfere with multiple targets of AS through multiple pathways. In vitro experiments verified that MOZP can reduce lipid accumulation in macrophages, reduce inflammation levels, and inhibit the IL-6/STAT3 signaling pathway, thereby exerting its anti-atherosclerosis effect.

In this paper, the molecular mechanism of MOZP against AS has been preliminarily explored; nonetheless, the therapeutic mechanism needs to be further investigated.

Chronic atrophic gastritis (CAG) is the initial phase in the carcinogenesis of gastric cancer (GC). Therefore, effective treatment for CAG is important in reducing the risk of GC progression. As an isoflavone compound, formononetin (FMN) has been identified as a potential therapeutic agent for acute gastric ulcers and GC. However, no study has reported the protective effect of FMN against CAG and its underlying mechanism. This study aimed to explore the therapeutic effects of FMN on CAG and its underlying mechanisms in vitro.

Network pharmacology was applied to predict the core targets of FMN therapy in CAG. The CAG cell model was developed using N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-triggered human gastric epithelial cells (GES-1). The CCK-8 assay was applied to estimate cellular viability. The expression of inflammatory cytokines in cell supernatant was detected by ELISA. The protein levels and localization of nuclear receptor coactivator 1 (NCOA1), c-Jun, and c-Fos were evaluated using western blotting and immunofluorescence staining. Cell apoptosis was measured using flow cytometry.

Network pharmacology analysis identified c-Jun as the core target of FMN in the treatment of CAG, with biological processes primarily involving the regulation of apoptosis and inflammation. In vitro, MNNG exposure reduced GES-1 cell viability as well as increased inflammation and cellular apoptosis, and these effects were reversed by FMN treatment. In detail, FMN decreased the protein levels of NCOA1, c-Jun, and c-Fos in MNNG-triggered GES-1 cells. The activator protein-1 (AP-1) inhibitor T-5224 enhanced the effects of FMN treatment on cell viability, inflammatory response, and apoptosis in MNNG-triggered GES-1 cells.

This study employed network pharmacology analysis to identify FMN's therapeutic targets for CAG and validated the underlying mechanisms in vitro. While these results are promising, in vivo validation is required to confirm the efficacy of FMN. A comparative pharmacological evaluation against existing therapeutic agents and bioactive compounds would further elucidate FMN's therapeutic potential for CAG treatment.

FMN ameliorated the cell damage that MNNG triggered in GES-1 cells. The mechanism involved the anti-inflammatory and anti-apoptotic effects of FMN via modulation of the NCOA1/AP-1 signaling axis. The present preliminary study found FMN to exhibit a potential therapeutic effect against CAG.

With a large number of species' genomes assembled, sequence comparison has become an effective method for further studying biological classification and evolution. Traditional sequence alignment relies on predefined scoring functions, but it is computationally intensive and lacks molecular justification for scoring the differences between sequences. Therefore, we have developed a graphical representation method for DNA sequences to facilitate better sequence comparison and evolutionary analysis.

In this article, we introduce a novel method for representing DNA sequences using three-dimensional (3D) graphics. This method possesses two significant properties: (1) the graphical representation is acyclic; (2) each DNA sequence maintains a bijective relationship with its graphical representation.

Leveraging this proposed visualization method, we computed the corresponding ALE index for any DNA sequence by converting it into an L/L matrix and constructed a 12-dimensional feature vector. The feasibility of our proposed method has been validated through the construction of phylogenetic trees in four test sets: terrestrial vertebrates, hantavirus, fish and Japanese encephalitis virus.

This method enables both quantitative analysis and visual comparison of DNA sequences, providing a versatile tool for evolutionary studies.

Individual constitutions are classified into nine types in traditional Chinese medicine (TCM), and qi stagnation constitution (QSC) manifests as disrupted Qi circulation and increased susceptibility to emotional disorders and cancers. However, as a pre-disease state mainly affecting women, the biological basis of QSC and its susceptible mechanism to related diseases are still unclear. Exosomal microRNAs (miRNAs) are the stable regulators of gene expression and intercellular communication, and analysis of miRNAs enables us to understand the QSC better. This study profiles plasma exosomal miRNAs in QSC and balanced constitution (BC) females via high-throughput sequencing, aiming to identify the potential biomarkers of QSC and reveal its biological basis and the mechanism of its susceptible disease.

In this cross-sectional observation, female college students were recruited according to the criterion of QSC and BC in Classification and Determination of Constitution in TCM. Exosomal miRNAs were isolated from peripheral blood plasma and then profiled using high-throughput sequencing. Differentially expressed miRNAs (DEMs) were identified with fold change > 2 and P < 0.05, and screened as biomarkers to construct the receiver operating characteristic (ROC) curve. The diagnostic values of these biomarkers in different types of cancers were also validated based on the published data. Functional analysis were explored based on the predicted target genes.

Subjects with QSC showed significantly higher concentrations of albumin (ALB) and alkaline phosphatase (ALP) compared to those with BC, while there was no significant difference in baseline information and other clinical indicators between groups. A total of 54 DEMs were identified, including 30 up-regulated and 24 down-regulated miRNAs in the QSC group. The area under the ROC curve (AUC) for 7 specific up-regulated DEMs was 1.0, as well as the AUCs for therein 6 DEMs in various cancers were all above 0.9. The enriched KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways included “signal transduction,” “infectious disease,” and “cancers”, and the most associating systems included immune, endocrine, and nervous systems, while the GO (Gene Ontology) function was mainly enriched in “protein binding,” “nucleus” and “transcription, DNA-templated”.

These 7 potential biomarkers of QSC have been confirmed to regulate oncogenic processes through epithelial-mesenchymal transition modulation and metabolic reprogramming, as well as therein 1 can also improve depression by lowering the expression of 5-hydroxytryptamine 1A receptor. The results of this study deepen the understanding of the constitutions in TCM. However, the small single-sex sample limits the application of the conclusion, and a large-scale clinical cohort including both sexes is still needed in future.

The expression of exosomal miRNAs in QSC showed unique features that have the potential to serve as biomarkers, and the related functional changes might be the biological basis for the susceptible diseases of QSC.

Depression is a common comorbidity in epilepsy, significantly impacting patients' quality of life. The hippocampus, linked to depression and neurodegeneration, is vulnerable in epilepsy. Epileptogenesis involves inflammation, oxidative stress, and neuronal damage, with the PI3K/AKT pathway playing a key role. Apigenin (API), a flavonoid in fruits and vegetables, shows neuroprotective, anti-inflammatory, and anti-apoptotic effects. This study investigates API's mechanisms in a LiCl-pilocarpine epileptic rat model, focusing on hippocampal neurogenesis and PI3K/AKT signaling as potential therapeutic targets.

We studied the effects of API and valproate (VPA) on depressive behavior and astrocytes in Lithium chloride (LiCl)-pilocarpine-induced epileptic rats. Additionally, we predicted the potential molecular targets of API for treating epilepsy using network pharmacology. Finally, we conducted in vivo experiments to validate the predicted mechanism.

In the API and VPA groups, there was a reduction in seizure frequency and seizure severity compared with the control group. The model group showed more depressive behavior than the control (CON) group, and these behaviors improved significantly after VPA and API treatment. HE staining showed that both API and VPA treatment improved LiCl-pilocarpine-induced nuclear contraction and cell swelling. Nissl staining demonstrated that Nissl vesicles in the CA3 region of the hippocampus were decreased in the model group, but the neurons were larger, more abundant, and more neatly arranged after API and VPA treatment. In the model group, the p-PI3K/PI3K and p-AKT/AKT protein ratios and PI3K, AKT mRNA expression were reduced, while brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) were markedly increased. API and VPA treatment effectively reversed these changes.

API reduces seizures and depressive behaviors in LiCl-pilocarpine-induced epileptic rats, comparable to VPA API mitigates hippocampal neuronal damage, preserves Nissl bodies, and suppresses astrocyte activation via the PI3K/AKT pathway, suggesting neuroprotective and anti-inflammatory effects. While API shows promise as an antiepileptic and antidepressant agent, further studies are needed to confirm its direct modulation of PI3K/AKT and efficacy in other epilepsy models.

Our study suggests that API improves depression in rats and has anti-epilepsy activity, which may be involved in activating the PI3K/AKT pathway to protect astrocytes.

Obesity is a global health issue linked to metabolic disorders and cardiovascular diseases. Guang hawthorn (Malus doumeri) leaves have been traditionally used for medicinal purposes, but their bioactive compounds and anti-obesity potential remain underexplored.

This study extracted compounds from M. doumeri leaves using 70% ethanol and ethyl acetate. The extracts were administered to high-fat diet-induced obese rats. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured. The chemical composition of the extracts (HML) was analyzed using chromatography, NMR, and mass spectrometry. Network pharmacology and enrichment analyses were conducted using R and Cytoscape to identify compound-target interactions.

Rats treated with high-dose extracts showed significantly reduced TC, TG, and LDL-C levels and increased HDL-C (all p < 0.05). Three major compounds-phlorizin, sieboldin, and kumatakenin β-7-O-glucoside-were identified. A total of 272 overlapping targets and 32 core targets were found between compound-related and obesity-related gene sets. Functional analysis linked these targets to phosphorylation, apoptosis, cell proliferation, and kinase regulation.

The anti-obesity effects of M. doumeri may be mediated by modulation of the PI3K-Akt and FoxO signaling pathways, as well as proteoglycan biosynthesis. These pathways are associated with metabolic regulation and obesity-related changes.

M. doumeri leaf extracts demonstrate anti-obesity potential through multi-target and multi-pathway mechanisms, particularly via sieboldin and kumatakenin β-7-O-glucoside. These findings support their potential as natural therapeutic agents for obesity management.

To develop and characterize a Crocus sativus (saffron)-based solid lipid nanoparticle (SLN) nasal spray for treating depression by enabling direct nose-to-brain delivery and evaluating its antidepressant potential in a Drosophila melanogaster model.

Phytochemical screening, antioxidant assays, and HPLC quantification of picrocrocin were performed on Crocus sativus extract. The SLN-based nasal spray was formulated and characterized for particle size, zeta potential, polydispersity index (PDI), drug entrapment efficiency, in vitro drug release, and stability over 4 weeks. The antidepressant efficacy was assessed via a climbing assay in Drosophila melanogaster.

Phytochemical analysis revealed phenolic content (11–36 μg GAE/mg), flavonoid content (43–56 μg QE/mg), and carotenoid content (1.9–30 μg βC/mg). HPLC analysis quantified picrocrocin at 6.3 mg/g, confirming its presence. The SLNs exhibited a particle size of 110–225 nm, a zeta potential of -1 to -0.8 mV, a PDI of 1, and a drug entrapment efficiency of 99.76%. Drug release reached 37% over 270 minutes, and the nasal spray maintained a pH of 5.8, a viscosity of 23.1 cP, and stability over 4 weeks. In vivo, the climbing assay demonstrated improved locomotor activity, indicating significant antidepressant potential.

The favorable physicochemical characteristics of the nasal spray, along with the observed behavioral improvements in the fly model, suggest that Crocus sativus SLNs effectively cross the nasal-brain barrier and exert antidepressant-like effects. These findings support its potential for non-invasive management of treatment-resistant depression.

ARL6IP1 has been linked to cancer progression, but its precise role in BC, particularly in metabolism and its interaction with an OLFM4, remains unclear.

This study aimed to investigate the role of ADP-ribosylation factor-like 6 interacting protein 1 (ARL6IP1) in breast cancer (BC) cell behavior and metabolism and explore its interaction with an olfactomedin-4 (OLFM4) as a potential therapeutic target.

The objective of this study was to determine the effects of ARL6IP1 knockdown on BC cell proliferation, invasion, migration, apoptosis, oxidative stress, and glycolysis. Additionally, this study also explored the interaction between ARL6IP1 and OLFM4 and their combined role in BC progression and metabolism.

Key gene modules in the GSE73540 dataset were identified through weighted gene co-expression network analysis (WGCNA). Three BC-related datasets (GSE73540, GSE22820, and GSE36295) and The Cancer Genome Atlas (TCGA) were applied for additional examination of differentially expressed genes (DEGs). Intersection analysis selected ARL6IP1 as a hub gene for prognostic analysis. In vitro experiments investigated how ARL6IP1 knockdown influences BC cell proliferation, invasion, migration, apoptosis, epithelial-mesenchymal transition (EMT), oxidative stress, and glycolysis. The connection between ARL6IP1 and an OLFM4 was confirmed using Co-immunoprecipitation (Co-IP), and their roles in BC tumor progression and glycolysis were evaluated.

ARL6IP1 was elevated in BC datasets and linked with poor BC prognosis. Experiments demonstrated that knockdown of ARL6IP1 significantly reduced BC cell growth while promoting apoptosis and oxidative stress. Besides, ARL6IP1 knockdown reduced glycolysis, as manifested by decreased extracellular acidification rate (ECAR), glucose consumption, adenosine triphosphate (ATP) levels, and lactate production while increasing mitochondrial respiration (OCR). Co-IP validated the connection between ARL6IP1 and OLFM4, and OLFM4 overexpression partially counteracted the suppression of glycolysis and cell behavior resulting from ARL6IP1 knockdown.

ARL6IP1 is a critical regulator of BC progression, influencing glycolysis, mitochondrial function, and key cellular behaviors. Targeting the ARL6IP1-OLFM4 axis offers a promising therapeutic strategy for managing BC.

Cranberry (Vaccinium macrocarpon) is rich in vitamins, minerals, anthocyanins, flavonoids, and phenolic acids, offering potent antioxidant activity. Polyphenols in cranberries are linked to neuroprotective effects via modulation of oxidative stress, inflammation, and signaling pathways.

This study evaluated the neuroprotective effects of cranberries on behavioral and neurochemical abnormalities induced by intracerebroventricular (ICV) quinolinic acid (QA) in Wistar rats, focusing on ERK and PI3K/AKT pathway modulation.

Thirty Wistar rats were divided into groups: control, QA (240 nM, ICV), QA + cranberry (0.5 g/kg, p.o.), and QA + high-dose cranberry (2 g/kg, p.o.). Treatments continued for 21 days. Behavioral performance was assessed via Novel Object Recognition, Morris Water Maze, rotarod, and footprint analysis. Biochemical assays measured oxidative/nitrosative stress markers, mitochondrial complex activities, and cholinergic function. Histological analysis evaluated neuronal integrity.

QA treatment impaired cognition, motor function, and mitochondrial activity, increased oxidative stress (↑MDA, ↑nitrite, ↓GSH), and induced cholinergic dysfunction. Cranberry supplementation, particularly at 2 g/kg, significantly improved memory, learning, and motor coordination, restored GSH, reduced MDA and nitrite levels, enhanced mitochondrial complexes I, II, and IV activities, and normalized cholinergic markers. Histology confirmed reduced neuronal degeneration and inflammation.

Cranberries exhibit neuroprotective effects likely via antioxidant, anti-inflammatory, and anti-excitotoxic mechanisms, promoting synaptic plasticity and neuronal survival.

Cranberries may serve as a potential natural therapeutic strategy for cognitive deficits and neurodegenerative conditions, warranting further translational studies.

Cancer is a major public health concern, and conventional treatments like surgery, chemotherapy, and radiotherapy are associated with several disadvantages, including chemoresistance, toxicity, and economic burden to the family of cancer patients. Thus, discovery of novel agents of natural agents to reduce these side effects is crucial. A series of studies have shown anthraquinones as a promising adjuvant in enhancing the effectiveness of standard cancer therapies.

This review explores the anticancer potential of anthraquinones and their role in enhancing standard chemotherapy.

Various freely available databases, including PubMed, Scopus, Google Scholar and Web of Science were searched for updated and relevant information on anthraquinones and their use as an adjuvant with standard chemotherapeutic agents.

In this article, we looked at the recent developments in the utilization of anthraquinones as adjuvants in chemotherapy. Further, we have elaborated the mechanism of action that anthraquinones target to chemosensitize the drug-resistant cancer cells.

This review provides updated information on emerging role and their potential to be utilized as adjuvants in augmenting the efficacy of conventional cancer therapies.

Pressure injury (PI) severely affect the quality of life of patients. Infection and inflammation are key factors contributing to the progression of PI; therefore, their inhibition plays a crucial role in preventing the worsening of the condition. Huanglian Jiedu Decoction (HLJDD), as a typical traditional Chinese medicine with heat-clearing and detoxicating effects, has good broad-spectrum antibacterial and anti-inflammatory effects. It is commonly used in the treatment of clinically infected external wounds. However, the therapeutic effects of HLJDD on PI remains unclear.

The extract of HLJDD was prepared using the water extraction and alcohol precipitation method. Sixty male SD rats were randomly divided into five groups (n = 12/group): control group, model group, normal saline group (negative control group), iodophor group (positive control group), and HLJDD group (test group). Except for the control group, magnet clamping and the Staphylococcus aureus inoculation method were used to construct the model of stage 3 PI infection wound in the other groups. After irrigating the wound, the healing rate, bacterial concentration, concentrations of IL-1, IL-6, and TNFα, and the protein expression levels of TLR2, MyD88, and NF-Bp65 were examined. Skin and ocular mucosal irritation tests were conducted to evaluate the safety of the topical application of HLJDD.

Rats treated with HLJDD exhibited an improved wound healing rate, along with reduced bacterial concentration on the wound surface and a significant decrease in the content of inflammatory cytokines (IL-1β, IL-6, and TNF-α). The protein expression levels of TLR2, MyD88, and NF-κBp65 were down-regulated after the administration of HLJDD. The prepared HLJDD did not cause any irritation.

HLJDD can promote the healing of PI wounds and has a protective effect on PI through its anti-inflammatory and anti-bacterial properties.

ABCA family proteins regulate cholesterol transport, which affects cancer-related processes such as membrane dynamics and tumor progression. However, their roles in gastric cancer (GC) remain unclear.

This study systematically investigated the expression profiles, prognostic significance, and immune-related roles of ABCA family genes in GC using data from The Cancer Genome Atlas (TCGA). Kaplan-Meier and Cox regression analyses assessed survival relevance, while logistic regression and ROC curves evaluated clinical associations and diagnostic value. Immune infiltration and gene correlation were analyzed via ssGSEA and Pearson correlation. TIDE and “oncoPredict” were used to estimate immunotherapy response and chemotherapy resistance. Gene Set Enrichment Analysis (GSEA) identified related signaling pathways. Quantitative PCR validated ABCA expression in cell lines.

Several ABCA genes (e.g., ABCA1, ABCA2, ABCA7, ABCA13) were upregulated, while others (e.g., ABCA8, ABCA9) were downregulated in GC tissues. Expression levels correlated with pathological stage, grade, and lymph node metastasis. ABCA1, ABCA3, ABCA4, ABCA6, ABCA8, and ABCA9 were identified as independent prognostic factors. Nomogram models showed good predictive performance. High ABCA expression was associated with increased infiltration of multiple immune cells and co-expression with immune checkpoint genes. TIDE analysis indicated lower predicted ICI response, and ABCA levels correlated with resistance to cisplatin, 5-FU, and paclitaxel. GSEA revealed enrichment in ECM-receptor interaction, cell adhesion, autophagy, and PI3K-Akt pathways.

ABCA genes exhibit distinct expression and prognostic patterns in GC and are closely linked to tumor immunity and drug resistance, supporting their potential as biomarkers and therapeutic targets.

This study aimed to explore the mechanism of moxibustion in the knee by combining osteoarthritis metabolomics and network pharmacology.

A rat knee osteoarthritis (KOA) model was established by intra-articular injection of papain. The efficacy of moxibustion in KOA rats was evaluated by swelling degree, pathological progress, and mobility loss of knee joint. On this basis, the metabolic mechanism of moxibustion in relieving knee osteoarthritis was analyzed by metabolomics analysis.

Moxibustion significantly reduced joint swelling and inflammation in the knee joint of KOA rats. Sixteen metabolites and nine metabolic pathways were found to be associated with the mechanism of action of moxibustion in metabolomics analysis results. According to network pharmacology, 3186 KOA disease targets, 158 drug targets, and 89 intersecting targets were obtained. The key targets included MAPK-3, AKT-1, RELA, MAPK-8, MAPK-14, etc. Signal pathways were found to be involved in mechanisms of moxibustion in knee osteoarthritis, such as alanine, aspartate, and glutamate metabolism, cysteine and methionine metabolism, and arginine and proline metabolism.

At present, the mechanism of moxibustion for KOA is not completely clear, but it is certain that its effect is related to the effect produced by heat and radiation. In addition, the aromatic substances produced during the combustion of moxa leaves have anti-inflammatory, antioxidant, and immune-enhancing effects on KOA.

The mechanism of moxibustion in knee osteoarthritis may involve alanine, aspartate, and glutamate metabolism, cysteine and methionine metabolism, arginine and proline metabolism, amino tRNA biosynthesis, and D-glutamine and D-glutamate metabolism signaling pathways with MAPK-3, AKT-1, RELA, MAPK-8, and MAPK-14 as core targets. More precise mechanisms need to be verified by further systematic molecular biology experiments.

For clarifying the “multi genes and multi targets” characteristic of the treatment of Erxia Decoction (EXD), the aim of this study was to employ network pharmacology technology to perform cluster analysis on selected EXD targets.

EXD, a famous Chinese herbal prescription, consisting of Pinelliae Rhizoma (PR) and Prunellae Spica (PS), was mainly used to treat sleep disorder (SLD).

Using network pharmacology combined with proteomics to find out the main active components and core targets of EXD in the treatment of SLD.

By constructing the network of drug–component–target, the key protein targets of EXD for the treatment of SLD were screened. Then the interaction of the main active components of EXD and predicted candidate targets were verified. Then the proteomic analysis was used to screen the core targets in BV2 cells treated with EXD or the chemical ingredients, and the expression level was validated by Western blotting. Finally, molecular docking was used to further evaluate the mechanism of the action of the main ingredients and the core targets.

The 24 components of EXD mainly participate in the SLD treatment process by acting on 15 important key genes, and the core signal pathways were identified in the process of the action of EXD in treating SLD. Four key ingredients and five core targets were revealed from the results of network pharmacological analysis combination with proteomics, and then the AKT1 protein as a key target was validated by PCR and Western blotting.

This study preliminarily revealed EXD, morin (MOR) and quercetin (QUE) mainly inhibited the AKT1 core targets for the treatment of SLD using the network pharmacological analysis, proteomics, Western blotting and molecular docking.

The results elucidated partly the molecular mechanism and provided clues and a basis for further research.

The intricate relationship between the gut microbiome and myopia is increasingly recognized, underscoring the need to explore its causal dynamics. Despite emerging evidence, the influence of Gut Microbiota (GM) on ocular development remains underexplored.

This study utilized Mendelian Randomization (MR) to investigate the causal impact of GM on the development of myopia. Instrumental variables (IVs) were identified from Genome-Wide Association Studies (GWAS), focusing on genetic variants significantly associated with microbiome composition. A comprehensive array of MR techniques was applied to ensure a robust estimation of causal effects and to adjust for potential confounders and pleiotropy.

The Inverse-Variance Weighted (IVW) method was used to identify significant associations between GM and myopia. Increased risk of myopia was linked to the class Betaproteobacteria (OR=1.01, 95% CI 1.004-1.017, P=0.003), the order Burkholderiales (OR=1.009, 95% CI 1.001-1.016, P=0.02), the family Oxalobacteraceae (OR=1.005, 95% CI 1.001-1.01, P=0.023), and several genera including Eubacterium xylanophilum group (OR=1.007, 95% CI 1.001-1.013, P=0.033), and Bifidobacterium (OR=1.005, 95% CI 1-1.01, P=0.038). Protective effects were noted for the order Mollicutes RF9 (OR=0.994, 95% CI 0.99-0.999, P=0.014), the genus Allisonella (OR=0.996, 95% CI 0.993-0.999, P=0.019), the genus Lachnospiraceae UCG001 (OR=0.994, 95% CI 0.989-1, P=0.045), and the family Enterobacteraceae (OR=0.991, 95% CI 0.982-1, P=0.047) and order Enterobacteriales (OR=0.991, 95% CI 0.982-1, P=0.047). Sensitivity analyses further confirmed the robustness of these findings.

This study provides causal evidence for the “Microbiome-Gut-Eye Axis” in myopia development, identifying specific gut microbiota that influence myopia risk. These findings suggest potential for microbiota-targeted interventions, warranting further research in diverse populations.

The findings support the “Microbiome-Gut-Eye Axis” as a potential factor in myopia pathogenesis and highlight microbiota-targeted interventions as novel therapeutic strategies for managing myopia. This study lays the groundwork for further research on how modifying GM can influence eye health and offers new perspectives on preventive health strategies.

Our objective is to assess the therapeutic impact of HEC on OAB rats and investigate potential mechanisms.

Overactive bladder (OAB) is a syndrome of urinary storage symptoms characterized by “urinary urgency with or without urinary acute incontinence, usually accompanied by increased daytime and nocturnal urination”, which impacts patients’ quality of life. We found the potential therapeutic impact of HuangE capsules (HEC) on OAB patients through clinical practice. However, the exact effect and mechanism of action remain unclear.

We developed a “drugs- active ingredients- targets- diseases” network and employed the pathway enrichment analysis to identify the potential mechanisms of HEC on OAB. Bladder outlet obstruction (BOO) models and sham-operated ones were established in healthy male Wistar rats through surgical procedures. Following 28 days of continuous gavage administration of HEC, saturated copper sulfate test paper was utilized to quantify the frequency of urination over a 24-hour period. Subsequently, cystostomy was conducted to perform cystometry, and Masson staining was applied to a portion of the bladder tissue. Finally, we investigated the Rho/Rho-kinase pathway's expression and assessed the oxidative stress and inflammatory factor levels in the rat bladder through western blotting and ELISA techniques.

Through network pharmacological analysis, we identified RhoA/Rho-kinase pathway and cytokine including TNF-α, IL-6, SOD and MDA as potential mechanisms of HEC on OAB. The rats in the 2× HuangE group exhibited significantly enhanced urodynamic outcomes and decreased 24-hour urination frequency compared to the model group. Masson staining indicated a decrease in the proportion of collagenous tissue and an improvement in histomorphology. We observed a decrease expression of RhoA, ROCK1, and ROCK2 protein in the bladder tissue of 2× HuangE group rats, along with elevated SOD levels and decreased levels of TNF-α, IL-6, and MDA.

HEC could improve bladder function and morphology in BOO-induced OAB rats by reducing the expression of RhoA, ROCK1, and ROCK2 and lowering levels of oxidative stress and inflammation.

Shenhuang Liuwei powder (SHLWP) is frequently used to treat diabetic ulcers (DUs), but its mechanism of action remains poorly understood. This study aimed to identify the active compounds and mechanisms by which SHLWP alleviates DUs.

The chemical components of SHLWP were analyzed using high-resolution mass spectrometry (HRMS). Network pharmacology based on HRMS data identified SHLWP-associated targets and signaling pathways. Its antibacterial activity was assessed using Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC) tests. Its in vivo pharmacological effects were evaluated in a streptozotocin-induced diabetic ulcer model in Sprague-Dawley (SD) rats.

Seventy-three components were identified in SHLWP, with key constituents including caffeic acid (13.11 ± 0.14 μg/g), ferulic acid (20.40 ± 0.24 μg/g), quercetin (8.49 ± 0.18 μg/g), luteolin (36.63 ± 0.19 μg/g), apigenin (82.14 ± 1.60 μg/g), and linoleic acid (507.59 ± 1.46 μg/g). SHLWP exhibited strong antibacterial activity against Staphylococcus aureus (MIC = 7.8125 μg/mL), Streptococcus pyogenes (MIC < 3.90625 μg/mL), and Streptococcus epidermidis (MIC < 3.90625 μg/mL). Network pharmacology revealed significant enrichment of the AGE/RAGE, HIF-1, and PI3K-Akt pathways, which was validated in vivo using qPCR, immunohistochemistry, and Western blot.

SHLWP alleviated streptozotocin-induced diabetic ulcers by inhibiting the AGE/RAGE pathway and promoting antibacterial activity and angiogenesis via the PI3K/Akt/eNOS/HIF-1α pathway, providing a biological basis for its therapeutic effects.

The specific role of necroptosis in the pathogenesis of cataracts remains unclear. This study aimed to identify and validate the genes related to necroptosis in the development of cataracts through bioinformatics analysis.

We utilized RNA sequencing data (GSE161701) from the Gene Expression Omnibus (GEO) database and employed R software to perform differential expression analysis of necroptosis-related genes (NRGs) in lens epithelial cells (LECs) under oxidative stress. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to evaluate the functions of necroptosis-related differentially expressed genes (NRDEGs) and their associated pathways. Additionally, a diagnostic model was established using LASSO regression to select hub genes, and protein-protein interaction (PPI) networks, mRNA-miRNA, and mRNA-drug regulatory networks were constructed. Immune infiltration analysis was performed using the xCell and CIBERSORT algorithms, and the differential expression of hub genes was validated in a UVB-induced rat cataract model using RT-qPCR and immunohistochemistry.

The results indicated that oxidative stress promoted necroptosis in LECs, involving 86 NRDEGs and nine hub genes. GO and KEGG analyses revealed significant enrichment in necroptosis-associated pathways. Furthermore, we identified 58 mRNA-miRNA interactions and 131 potential molecular compounds or drugs. The immune infiltration analysis showed that certain immune cells exhibited significantly elevated expression in the cataract group, with notable correlations between some immune cells and hub genes. RT-qPCR and immunohistochemistry confirmed the expression of 9 hub genes and 3 key necroptosis genes. BAX, CXCL1, EPAS1, JUN, LRP1, RBM14, SERTAD1, and TNFAIP3 were highlighted as potential diagnostic and therapeutic targets.

This study identified key NRDEGs involved in the pathogenesis of cataracts under oxidative stress through bioinformatics analyses, potentially providing new targets and research directions for future cataract prevention and treatment.