The aim of this study was to investigate the effects of deuterium substitution on the in vitro pharmacology of the psychedelic drug 2-(4-bromo-2,5-dimethoxyphenyl)ethan-1-amine (2C-B). Two deuterated isotopologues of 2C-B, namely 2-(4-bromo-5-methoxy-2-(methoxy-d3)phenyl)ethan-1-amine (2CB-2OCD3) and 2-(4-bromo-2-methoxy-5-(methoxy-d3)phenyl)ethan-1-amine (2CB-5OCD3), were synthesized and tested in cell lines expressing human 5-HT2A receptors for potential isotope effects on 5-HT2A receptor binding and functional activity, and for metabolism by human liver microsomes (HLM). The 2C-B isotopologues and 2C-B exhibited picomolar-to-nanomolar potency in binding to [125I]DOI-labelled 5-HT2A receptors and were equally efficacious to 2C-B in stimulating 5-HT2A-mediated intracellular Ca++ release and β-arrestin 2 engagement. No appreciable metabolism was observed for 2C-B or the deuterated analogues by HLM over the time course of the experiment. Deuteration of the ring methoxys of 2C-B appeared to increase affinity at [125I]DOI-labelled 5-HT2A receptors, likely due to dampened internal vibrational frequencies and rotational motions arising from primary and secondary kinetic isotope effects. Deuteration did not affect the ability of the drugs to stimulate intracellular calcium release or to recruit β-arrestin 2, with all compounds displaying similar low nanomolar potency and efficacy in these assays.
Chemobrain (CMB) is a common complication that affects the majority of cancer patients and can persist for years following chemotherapy. Common symptoms are deficits in memory, attention, and affective regulation, yet they are mainly diagnosed through patient-reported symptoms. Additionally, the molecular mechanisms underlying CMB remain poorly understood, limiting the development of effective neuroprotective strategies for cancer patients. Using a rat model of CMB, this study investigates the molecular impact of doxorubicin (DOX) and temozolomide (TMZ), administered individually and in combination in comparison with a control group (n = 10/group). Untargeted metabolomic profiling was performed on the cortex, cerebellum, and hippocampus tissues after performing the neurobehavioural tests. Behavioural assessments revealed impaired spatial learning and memory, particularly in the combination-treated group, together with alterations in anxiety-related behaviour. The metabolites were extracted from their respective tissues using a two-in-one extraction protocol and were analysed by TIMS-QTOF-MS/MS. DOX treatment was associated with relatively modest region-specific metabolic alterations, with patterns consistent with possible oxidative stress-related and membrane-associated responses. TMZ treatment was associated with metabolic changes involving nucleotide metabolism and energy-related pathways, particularly in the hippocampus. The combination treatment showed a distinct metabolic profile with partial qualitative overlap with TMZ-associated alterations. Overall, these findings suggest that chemotherapy exposure is associated with region-specific metabolic alterations that co-occur with behavioural changes relevant to a CMB-like phenotype. The present results should be interpreted as exploratory and hypothesis-generating, pending targeted metabolite validation and orthogonal mechanistic confirmation. Ultimately, understanding these responses can provide critical insights into CMB pathophysiology and may lay the groundwork for the development of targeted diagnostic, monitoring, and neuroprotective strategies.
Preeclampsia considered as multi-organ disorder involving systemic inflammation and endothelial dysfunction. Our work was designed to investigate the protective role of Naringenin (NGN) against Nω-nitro-l-arginine methyl ester (L-NAME)-induced placental damage and congenital abnormalities in a rat model of preeclampsia. Forty-five adult female albino rats (weighing 160–180 g) were randomly allocated into nine groups (n = 6 per group) and treated for a duration of 18 days. Group 1 served as the untreated control, while Group 2 received 10
The Essential Medicines List (EML) provides international guidance for the selection of effective, safe, and essential drugs. Retained drugs were identified as medicines listed in both the 1st and 24th EML editions. The study aims to pharmacologically assess and to distinguish established therapeutic value from questionable or obsolete current relevance. Retained drugs were assessed by therapeutic value and indication-specific justification. Listed indications and the importance developments were compared between the 1st (1977) and 24th EML (2025). The justification of listing was assessed by guideline recommendations, efficacy and safety, scope of clinical usage, and availability of alternatives. A structured assessment algorithm was applied to assign drugs to therapeutic value categories. 129 retained drugs were assessed. Most EML indications did not change (n = 65), followed by specifications (n = 26), additions (n = 24), narrowing (n = 8), or change (n = 6). 71 drugs (55.0
Chemoresistance in hepatocellular carcinoma (HCC) complicates treatment and poses a substantial and growing burden to healthcare systems worldwide. Despite remarkable advances in recent years, the massive volume of publications has made it hard to identify overarching trends, critical turning points, and emerging frontiers. The present study aimed to conduct a comprehensive analysis of the global research landscape and summarize future hotspots. Articles on chemoresistance in HCC published in the Science Citation Index Expanded, Web of Science Core Collection, from 1991 to 2025 were searched. Bibliometrix (R package) was used for data analysis and visualization. CiteSpace was employed for keywords bursts detection. A total of 2571 publications by 12243 authors from 643 sources were included. An increase in the annual growth in the number of publications and citations was observed. Cancers had the most publications, and Cancer Research was the most cited. China and the USA are the dominant countries in this field. Sun Yat Sen University is the most productive affiliation. Wang Y is the most productive author. Besides topic-relevant keywords, terms like "expression," "apoptosis, " and "metastasis," etc. had high occurrence. Thematic shifts were also identified, transitioning from single-agent and single-target approaches to complex combination therapies and novel technological interventions. Conclusively, through a bibliometric analysis of publications, the present work shows key developments in the field of chemoresistance in HCC. Potential research hotspots include advanced combinatorial nano-immunotherapy, ferroptosis inducers, combined immunotherapy, and metabolic plasticity and stemness pathway regulators of cancer stem cells.
Xylazine is an α2 adrenoceptor agonist approved for use in veterinary medicine as an analgesic and sedative. However, the recent use of xylazine as adulterant with opioids has created a public health emergency due to an increased number of addiction-related deaths and adverse effects. As a result, xylazine’s pharmacological profile has been revisited, and it has been found to act as a full agonist at κ-opioid receptors. Because increased urine output is a well-established effect of κ-opioid receptor agonists, we determined if κ-opioid receptors are involved in xylazine-induced diuresis. Adult male Sprague–Dawley rats were used. A dose–response curve was first established through systemic administration of xylazine. Rats were injected with xylazine (1.25, 2.5, or 5 mg/kg) or saline and then placed into metabolic cages for 2 h for urine collection. Xylazine doses of 2.5 and 5 mg/kg significantly increased urine output compared to saline-injected rats, indicating that xylazine caused diuresis. Next, rats were pretreated with saline; a κ-opioid receptor antagonist, 5′-guanidinonaltrindole (5′-GNTI) (0.01–0.1 mg/kg); or an α2-adrenoceptor antagonist, yohimbine (0.3–1 mg/kg). Thirty minutes later, rats were injected with saline or a fixed dose of xylazine (2.5 mg/kg) and urine was collected for 2 h. Pretreatment with either 5′-GNTI or yohimbine significantly decreased xylazine-induced diuresis. Our findings suggest that xylazine-induced diuresis is mediated by both κ-opioid receptors and α2-adrenoceptors, highlighting the importance of considering κ-opioid receptor activation when evaluating in vivo pharmacological effects of xylazine.
Colorectal cancer (CRC) ranks as the second most lethal cancer worldwide. Probiotics have long been utilized to treat gastrointestinal diseases. Probiotics may play a role in the prevention and treatment of CRC. Additionally, the anti-inflammatory drugs sulfasalazine (SSA) and mesalazine (MESA) have a preventive role in CRC. This study investigates the modulatory antitumor effects of combining the probiotic Lacticaseibacillus rhamnosus GG (LGG) with SSA or MESA and the associated molecular mechanisms in CRC. In vitro studies of LGG-CFS, both alone and in combination with SSA or MESA, were assessed in HCT-116 and HT-29 CRC cells. In vivo, 61 albino rats aged 8 weeks were used and CRC was induced using 1,2-dimethylhydrazine. The 1,2-dimethylhydrazine-induced rats were divided into six groups, each of eight—in addition to the negative control group (received phosphate buffer saline only)—as follows: (I) positive control group (received DMH only), (II) SSA-treated group, (III) MESA-treated group, (IV) LGG-treated group, (V) SSA + LGG-treated group, and (VI) MESA + LGG-treated group. Rats received daily oral doses of SSA (250 mg/kg), MESA (62.5 mg/kg), LGG (1 × 109 CFU lactobacilli/1 ml), SSA + LGG, and MESA + LGG for 4 weeks. In both cell lines, the control group (positive control, human cancerous cells without further treatment) exhibited a reduction in annexin V, whereas the specified treatments elevated annexin V levels in both cells, thereby inducing apoptosis. In vivo, positive control rats exhibited upregulation of TLR2/AKT/NF-κB, IL-6, IFN-γ/STAT-3/PD-L1, COX-2/HIF-1α/VEGF signaling, and Ki-67, resulting in the induction of proliferation, hypoxia, and angiogenesis and inhibition of apoptosis. All treatment regimens downregulated TLR2/AKT/NF-κB, IL-6, IFN-γ/STAT-3/PD-L1, COX-2/HIF-1α/VEGF crosstalk’s, and Ki-67, hence inhibiting proliferation, hypoxia, angiogenesis, and inducing apoptosis. Surprisingly, the combination of LGG with either SSA or MESA demonstrated the greatest efficacy through the aforementioned pathways with the superiority to the LGG + SSA combination in both experimental models. The current findings revealed novel insights into the potential antitumor effects of combining LGG with either SSA or MESA compared to each drug individually in CRC management. Further preclinical and clinical trials are warranted to evaluate this promising regimen compared to standard therapy of CRC.
This study investigates the therapeutic potential of combining palmitoleic acid with niosomal serratiopeptidase in a rat model of insulin-resistant polycystic ovarian syndrome (PCOS). Niosomal serratiopeptidase was formulated by thin-film hydration and characterized for particle size, polydispersity index, zeta potential, and encapsulation efficiency. Thirty prepubertal female rats were divided into six groups (n = 5). A negative control (Group 1); PCOS rats (Group 2); PCOS rats treated with free niosomes (0.7 mg/kg, i.p.; Group 3); serratiopeptidase-loaded niosomes (1 mg/kg, i.p.; Group 4); palmitoleic acid (300 mg/kg, p.o.; Group 5); and a combination of serratiopeptidase-loaded niosomes plus palmitoleic acid (Group 6). PCOS was induced in groups 2–6 using letrozole plus a high-fat diet for 30 days, followed by 30 days of the respective treatments, after which body and ovarian weights, ovarian cysts, and histological and biochemical parameters were assessed. The niosomes prepared exhibited a size of 746.6 ± 54.1 nm and a PDI of 0.389 ± 0.03. Serratiopeptidase encapsulation efficiency was found to be around 74
Diabetes combined with obesity is a global public health problem, with insulin resistance and chronic low-grade inflammation as key mechanisms. TCM regards spleen deficiency and phlegm-dampness as its core pathogenesis. This study constructs a research paradigm integrating clinical RCT data mining, UPLC-Q-TOF–MS/MS experimental component identification and network pharmacology-based prediction.This study predicted the multi-component, multi-target and multi-pathway mechanisms of core spleen-strengthening and damp-resolving prescriptions for this comorbidity. High-frequency herbs were screened via data mining from RCTs; chemical components were experimentally identified by UPLC-Q-TOF–MS/MS; intersecting targets and pathways were predicted by network pharmacology and preliminarily verified by semi-flexible molecular docking and molecular dynamics simulation. A 7-herb core prescription and 30 active components (nobiletin, puerarin, etc.) were determined. 350 common targets and hub genes (AKT1, MTOR, MMP9, PTGS2) were screened, with PI3K-Akt, lipid-atherosclerosis and diabetic AGE-RAGE as main pathways. Molecular docking showed strong component-target binding, which was further validated by dynamics simulation. The prescription improves diabetes with obesity through synergistic networks, regulating glycolipid metabolism and inflammation via the above pathways, supporting its modern clinical application.
Glioblastoma (GBM) is an aggressive brain tumor with limited effective therapies. The standard agent, Temozolomide (TMZ) though beneficial, often induces neurocognitive side effects that compromise quality of life. This study examined whether combining Vericiguat; a soluble guanylate cyclase stimulator, with standard or reduced TMZ doses could enhance antitumor efficacy and behavioral outcomes while reducing adverse effects in a rat model of GBM. 80 male Wistar rats received intracerebral injections of C6 glioma cells and were assigned to eight groups: Sham, Tumor, Vehicle, TMZ 3.75 mg/kg, TMZ 7.5 mg/kg, Vericiguat 0.5 mg/kg, and their combinations. Behavioral assessments (open field, elevated plus maze, rotarod, passive avoidance, and social interaction) were performed on days 20–24. On day 25, brain tissues were analyzed histologically and immunohistochemically (Ki-67). Survival was monitored for three months. Combination therapy significantly improved anxiety-like behavior, motor coordination, learning, memory, and social interaction compared with untreated tumor-bearing rats. Co treatment also extended survival, reduced tumor proliferation (lower Ki-67 expression), and preserved brain tissue structure. Vericiguat combined with low-dose TMZ produced synergistic effects on tumor suppression and neurocognitive recovery in GBM rats. These findings suggest that Vericiguat may enhance TMZ efficacy, enabling dose reduction and minimizing TMZ induced neurotoxicity while maintaining therapeutic effectiveness.
Arsenic trioxide (As2O3) is an effective therapeutic agent for acute promyelocytic leukemia. However, its clinical application is limited by hepatotoxicity, mainly linked to oxidative stress, inflammatory activation, and mitochondrial dysfunction. This study investigated whether ellagic acid (EA) and montelukast (MK), alone or together, protect against As2O3-induced liver injury in mice. Male NMRI mice were treated with As2O3 in the presence or absence of EA and MK for 10 days. After treatment, we performed biochemical, molecular, mitochondrial, and histopathological evaluations. As2O3 exposure led to pronounced hepatic injury, which was evident from elevated liver enzyme levels, increased lipid peroxidation, raised pro-inflammatory cytokines, reduced mitochondrial membrane potential, and increased apoptosis indices. Administration of EA or MK alone partly reduced several of these parameters. In contrast, concurrent use of EA and MK produced more marked improvements, including normalization of liver enzymes, enhanced antioxidant enzyme activity, lower pro-inflammatory and apoptotic markers, and preserved mitochondrial function. These protective effects were supported by consistently improved liver histopathology. In conclusion, combined EA and MK administration reduces As2O3-induced hepatotoxicity. This protection occurs by modulating oxidative stress, inflammation, and mitochondrial-dependent apoptosis. These findings indicate that targeting several processes could help reduce liver side effects from arsenic-based chemotherapy.
Powassan virus (POWV) poses a growing neurotropic threat with limited immunopharmacological interventions, requiring the development of targeted vaccine strategies. The current study focuses on developing a specific vaccine using bioinformatics tools to target T- and B-cell epitopes from a genome polyprotein sequence of POWV. Four vaccine constructs with possible immunogenic qualities were assembled. Two specific epitopes were selected from B-cell, and T-cell for each construct. The heat-labile enterotoxin S63 adjuvant was attached to the N-terminal, while the PADRE order and the His-tag were added to the C-terminal with appropriate linkers. The vaccine constructs showed 62
Depression causes distress, dysfunction, and disability in terms of physical, mental, and social wellbeing. The challenges of late presentation, no-compliance of patients, and time-lag of antidepressants persist, despite advances. The objective was to determine the efficacy of antidepressants in combination with magnesium, compared to antidepressant monotherapy for treating depression. Forty-four patients with depression (6A70, 6A71, and 6A72 according to ICD-11) were divided into two equal groups, in an open label nonrandomized clinical trial. All patients received evidence-based antidepressants (either escitalopram, sertraline, duloxetine, amitriptyline, or fluoxetine). The experimental group additionally received 800 mg of magnesium glycinate (112 mg elemental magnesium). The psychometric testing was done by Patient Health Questionnaire (PHQ-9) at days 0, 14, and 28. Primary outcome was to see improvement at day 28, while secondary outcomes included time lag and remission (PHQ-9 scores < 4) at day 14 and 28, respectively. Paired sample t-test and Student t-test were applied for within-group and between-group differences using SPSSv27.0. The p-value ≤ 0.05 was considered statistically significant. The improvement in the PHQ-9 scores in groups A and B was 26.42 https://clinicaltrials.gov/study/NCT05931965?cond=Depression intr=magnesium, ), 14–06-2023 (retrospectively registered).
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a progressive liver disorder driven by high-fat diet (HFD)-induced metabolic stress, oxidative damage, inflammation, and apoptosis. This study investigated the hepatoprotective effects of vitexin (VX) and vitexin-loaded phytosomal nanoparticles (VX-PHY) in HFD-fed rats. Sixty male albino rats were randomly assigned to six groups: standard diet control, standard diet + VX, standard diet + VX-PHY, HFD only, HFD + VX, and HFD + VX-PHY. HFD feeding caused significant weight gain, elevated liver and fat indices, disrupted serum proteins, impaired liver function, and dysregulated lipid profiles. At the molecular level, HFD induced oxidative stress, depleting GSH and antioxidant enzymes while activating the Nrf2/HO-1 pathway. It also triggered hepatic inflammation via NF-κB/COX-2 signaling, increasing TNF-α, IL-1β, and IL-6, and promoted apoptosis by upregulating BAX, Caspase-3, Caspase-8, and downregulating BCL2. HFD additionally activated the PI3K/AKT/mTOR/SREBP-1c axis, enhancing AKT/mTOR phosphorylation, nuclear SREBP-1c, and lipogenic gene expression (FASN, ACC), contributing to hepatic lipid accumulation, which was effectively suppressed by VX-PHY, highlighting its superior anti-lipogenic effect compared with crude VX. VX-PHY co-treatment further enhanced antioxidant defenses, modulated Nrf2/HO-1, suppressed NF-κB/COX-2-mediated inflammation, and attenuated pro-apoptotic signaling, restoring these pathways to near-control levels. Histopathological and ultrastructural analyses confirmed reduced steatosis, hepatocyte ballooning, necrosis, and organelle damage in VX-PHY-treated rats. Overall, vitexin, particularly when delivered via phytosomal nanoparticles, exerts potent hepatoprotective effects in HFD-induced MASLD by simultaneously mitigating oxidative stress, inflammation, apoptosis, and lipid dysregulation via inhibition of PI3K/AKT/mTOR/SREBP-1c, highlighting the therapeutic potential of nanoparticle-based delivery for natural compounds like vitexin. High-fat diet (HFD) feeding induces Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) through oxidative stress, inflammation, and apoptosis, and activation of the PI3K/AKT/mTOR/SREBP-1c lipogenic signaling axis in the liver. Vitexin (VX), particularly when delivered as vitexin-loaded phytosomal nanoparticles (VX-PHY), mitigated HFD-induced hepatotoxicity by enhancing antioxidant defenses, modulating the Nrf2/HO-1 pathway, suppressing NF-κB/COX-2-mediated inflammation, and attenuating pro-apoptotic signaling (BAX, Caspases) while restoring BCL2. VX-PHY additionally suppressed PI3K/AKT/mTOR activation, reduced SREBP-1c nuclear signaling, and downregulated lipogenic targets (FASN, ACC), thereby limiting hepatic lipid accumulation. VX-PHY markedly improved liver function, lipid profiles, and histopathological and ultrastructural integrity compared with crude VX. These findings demonstrate that nanoparticle-mediated delivery amplifies vitexin’s hepatoprotective effects, offering a multi-target strategy against oxidative, inflammatory, and apoptotic, and lipogenic signaling pathways in diet-induced MASLD.
Gentamicindosing in premature neonates remains challenging due to developmental pharmacokinetic variability and augmented renal clearance. Conventional PK/PD targets such as Cmax/MIC and AUC/MIC capture distinct pharmacodynamic dimensions but fail to integrate efficacy and toxicity simultaneously (Craig 1998; Sime and Roberts 2020). A Monte Carlo simulation of 3000 premature neonates was conducted using published pharmacokinetic parameters (Germovsek et al. 2019; Smith et al. 2011). A Hybrid PK/PD Index (H-index) integrating peak exposure, cumulative exposure, and toxicity constraints was evaluated across clinically relevant MIC values (0.5–2 mg/L). The H-index demonstrated improved joint probability of target attainment (PTA) compared with standard dosing, with enhanced robustness across MIC variability and reduced exposure dispersion. At MIC 2 mg/L, PTA increased from 40 to 65
The increasing use of oral anticancer drugs (OADs) in cancer therapy shifts greater responsibility towards patients, thereby also placing a higher informational burden on them. While intensified pharmacological/pharmaceutical care programs have proven beneficial for patients undergoing OAD treatment, their universal availability is currently limited. Given that patients frequently seek health information online, AI-powered chatbots may present a promising resource to address these increasing, yet often unmet information needs. This study aims to evaluate the readability, completeness of relevant information, and accuracy provided by AI-powered chatbots in response to patient questions about OAD treatment. Microsoft Bing's Copilot and Google's Gemini were queried in June 2024 on four patient questions regarding ten commonly prescribed and ten recently approved OADs in triplicate. Readability of chatbot answers was assessed using the Flesch reading-ease score (scale 0-100). Completeness of relevant information and accuracy were evaluated based on corresponding standardized written patient information materials. Both chatbots' answers demonstrated low readability according to the overall mean Flesch reading-ease scores of 38.8 (Copilot) and 50.9 (Gemini). Overall median completeness of relevant information of Copilot's and Gemini's answers was 61.1% (IQR, 35.3-78.7%) and 73.8% (IQR, 50.0-100.0%), respectively. Conversely, accuracy of chatbot answers was consistently high, with an overall median accuracy of 100.0% (IQR, 83.3-100.0%) for Copilot and 100.0% (IQR, 98.5-100.0%) for Gemini. AI-powered chatbots provide overall accurate information on OADs. However, their moderate completeness of relevant information and low readability may limit their current practical utility in meeting cancer patients' information need.
Sepsis-associated acute lung injury (sepsis-ALI) is a complex pathological condition; its underlying mechanisms remain mostly obscure. Thus, in this study, we aimed to explore potential candidate molecular markers, infer the regulatory signaling pathways, and describe the immunological profiles of sepsis-ALI. We developed a comprehensive bioinformatics analytical workflow by combining human transcriptome datasets with single-cell RNA sequencing databases and applied the ComBat algorithm to remove batch effects. A hierarchical gene screening process, incorporating the support vector machine, least absolute shrinkage and selection operator, and random forest machine learning algorithms, was applied. Five epithelial–mesenchymal transition (EMT)–related candidate genes (AURKA, MYB, CCNA2, CD24, and TYMS) were suggested across these algorithms. These candidate genes, which are involved in histone phosphorylation signaling, were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Single-sample gene set enrichment analysis was used to profile immune cell infiltration patterns, which led to the identification of seven differentially abundant immune cell populations. CellChat analysis suggested the MIF-(CD74 + CXCR4) axis serves as a putative mediator of intercellular communication based on ligand‑receptor expression patterns in sepsis-ALI. Pseudo-time trajectory analysis revealed that CD24 expression and MYB expression are associated with EMT progression and display stage‑specific functional relevance along the inferred cellular trajectory. Together, these integrative multi-resolution transcriptomic analysis findings describe EMT-related molecular characteristics, stage-specific regulatory pathways, and immune processes in sepsis-ALI. It is noteworthy that all these results are hypothesis-generating and derived solely from bioinformatics analyses without experimental validation. Identification of candidate genes and the putative role of the MIF-(CD74 + CXCR4) axis provides preliminary insights into sepsis-ALI pathophysiology; these findings will serve as a basis for further experimental research to develop potential precision-based and stage-specific experimental treatment strategies for sepsis-ALI in the future.
Exposure to cigarette smoke (CS) is a potent and major risk factor for chronic obstructive pulmonary disease (COPD). Luteolin (Lut), a flavonoid found in many edible plants, has displayed therapeutic effects on COPD; however, the underlying mechanisms are not well comprehended. In this study, C57Bl/6 J mice were exposed to CS combined with lipopolysaccharide (LPS) to induce COPD. Examination of the levels of inflammatory markers, including TNF-α, IL-1β, IL-6, IL-18, NO, and LPS, revealed that CS exposure caused significant lung injury and inflammatory reactions, while treatment with Lut (50 and 100 mg/kg/day) significantly reversed these trends. 16S rRNA sequencing showed that mice exposed to CS not only decreased the richness and composition of the lung microbiota, but also affected the gut microbiota. Lut treatment increased the richness and modulated the composition. Lut treatment altered the abundance of Pseudomonas, Streptococcus, and Actinomyces in the lung microbiota, as well as Actinobacteria, Helicobacter, and Coprococcus in the gut microbiota. Moreover, targeted metabolomics of amino acids showed seven amino acids, which were significantly altered by Lut, including serine (Ser), threonine (Thr), asparagine (Asn), glutamine (Gln), glutamic acid (Glu), histidine (His), and tyrosine (Tyr). Our study suggests that the protection effect of Lut on CS-induced COPD probably relies on the modulation of gut and lung microbiota and amino acid metabolism.
This study is a cross-sectional analysis aimed at systematically evaluating the information quality and reliability of popular science content related to drug-induced liver injury (DILI) on the two major Chinese video platforms, TikTok (Douyin) and BiliBili, and analyzing its content characteristics. On December 20, 2025, searches were conducted in the Chinese versions of the TikTok (Douyin) and BiliBili mobile applications using "" as the single keyword. Exclude content that does not meet the requirements based on the exclusion criteria, and ultimately retain the top 100 videos from each platform that meet the standards for analysis (N = 200). Two trained reviewers independently performed blinded assessments using the Global Quality Score (GQS), Journal of the American Medical Association (JAMA) benchmark criteria, and the modified DISCERN (mDISCERN) tool. Non-parametric tests were used to compare differences between groups, and Spearman correlation analysis was employed to explore the relationship between video characteristics and quality scores. User engagement metrics (likes, favorites, shares) for TikTok (Douyin) videos were significantly higher than those for BiliBili (p < 0.001). In terms of information quality, TikTok (Douyin) videos scored significantly higher than BiliBili on the GQS, JAMA, and mDISCERN scales (p < 0.001). There were differences in quality across content types: videos on "medication knowledge" received the highest mDISCERN reliability scores and "disease knowledge" videos scored higher in GQS practicality. Correlation analysis showed a weak positive correlation between user engagement metrics and mDISCERN scores. Among the 107 videos mentioning liver injury-related drugs, chemical drugs (antibacterial, chemotherapeutic, anti-tuberculosis drugs, and anti-inflammatory drugs) and traditional Chinese medicines (such as He Shou Wu) were mentioned most frequently. In this cross-sectional sample, TikTok (Douyin) videos demonstrated higher quality scores and user engagement than those on BiliBili, while professionals outperformed general users only on the JAMA criteria. Although some videos mentioned medications associated with liver injury, the information was generally oversimplified and biased toward trending topics. Hence, active information seekers should critically appraise the scientific soundness of medical short videos on platforms like TikTok and BiliBili before making healthcare decisions.
Intervertebral disc degeneration (IVDD) is a leading cause of chronic disabling musculoskeletal disorders, with its incidence rising annually among the aging global population. This degenerative process is strongly linked to persistent functional impairment and reduced quality of life in patients, while placing a growing socioeconomic burden on global healthcare systems. Previous studies have demonstrated that kaempferol exerts potent anti-inflammatory effects by modulating pro-inflammatory cytokine expression and attenuating extracellular matrix degradation in degenerated intervertebral discs. However, the precise molecular targets responsible for its therapeutic effects remain unclear. This study integrated network pharmacology, molecular docking, bulk and single-cell transcriptomics, and experimental validation to identify the therapeutic targets of kaempferol in IVDD. Potential targets of kaempferol were predicted using the TCMSP, SwissTargetPrediction, and PharmMapper databases. IVDD-related targets were retrieved from the GeneCards, OMIM, and MalaCards databases. A protein–protein interaction (PPI) network was constructed using STRING and Cytoscape, followed by GO and KEGG enrichment analyses. Hub genes were identified via topological analysis. Molecular docking was conducted using AutoDock Vina. The expression patterns of core targets were validated using two GEO bulk RNA-seq datasets (GSE70362 and GSE147383), one single-cell RNA-seq dataset (GSE251686), and qRT-PCR in IL-1β-induced nucleus pulposus cells. Twenty-one common targets between kaempferol and IVDD were identified. Topological analysis identified three core hub genes—STAT1, CASP1, and NOX4—all significantly upregulated in IVDD tissues. Molecular docking revealed strong binding affinities between kaempferol and these targets, with binding energies ranging from − 6.7 to − 7.9 kcal/mol. Single-cell transcriptomics further confirmed their high expression in nucleus pulposus cells. qRT-PCR analysis demonstrated that kaempferol significantly downregulated STAT1, CASP1, and NOX4 mRNA expression; restored extracellular matrix components (COL2 and ACAN); and suppressed matrix-degrading enzymes (MMP3 and MMP13) in IL-1β-stimulated nucleus pulposus cells. These findings suggest that kaempferol exerts protective effects against IVDD by regulating STAT1, CASP1, and NOX4. The multi-target effects of kaempferol in IVDD provide novel insights and highlight its potential as a therapeutic candidate for IVDD treatment.
