Melatonin has emerged as a hormone-like compound and multiple effects have been reported in fruits. To understand melatonin potential to control temporal ripening of aggregated non-climacteric fruits like strawberries, a preharvest in planta analysis was performed, including endogenous tissue localization of melatonin, its precursors and hydroxylated product (2-hydroxymelatonin) in achenes and receptacles over development. The signaling-ripening properties of melatonin were elucidated by co-accumulation with phytohormones and differential gene expression after application at distinct developmental stages, including fruit set, degreening and initial red. Our key findings illustrate a detailed specific spatiotemporal accumulation of melatonin and 2-hydroxymelatonin in strawberry fruits, with higher contents in achenes at fruit set, while receptacles peaked in ripe fruits. Exogenous melatonin (10-4 M) had contrasting ripening effects based on application timing. Namely, melatonin accelerated colour development when applied at fruit set, but delayed colour change when applied at degreening and initial red. Gene expression analysis showed that exogenous melatonin induced transcriptional reprogramming, particularly in achenes with a higher number of differentially expressed genes. Moreover, melatonin applications at fruit degreening downregulated Gretchen Hagen 3 (FaGH3.9) 24 h post-application, linked here to reduced conjugated indole-3-acetic acid. Our findings indicate that melatonin delays strawberry ripening and suggest this occurs partly through positive auxin crosstalk, thereby contributing to better understanding the role of melatonin in non-climacteric fruits, and positioning this molecule as a promising target to modulate ripening in breeding programmes or sustainable fruit production systems.

Cutaneous melanoma (CM) poses a critical public health concern due to its high recurrence rates and resistance to standard treatments. This study investigated the antineoplastic potential of Curcuma Longa L. extract enriched with Bisdemethoxycurcumin (AC3®) on human melanoma cell lines A375 and SK-MEL-28. The A375 and SK-MEL-28 cell lines were cultured according to the manufacturer's recommendations and were subsequently treated with different concentrations of AC3®. The MTT test and fluorescence microscopy were used to assess cell viability. The wound-healing assay was used to assess cell migration following compound treatment. To determine reactive oxygen species (ROS) levels, we used the fluorescence assay with 2,7-dichlorodihydrofluorescein diacetate. Subsequently, the molecular pathways associated with apoptosis were evaluated using RT-PCR, including modulation of the inflammatory profile and purinergic signaling components. AC3® effectively inhibited cell proliferation and migration in both melanoma cell lines. In A375 cells, the compound reduced ROS levels and significantly modulated apoptotic pathways, including upregulation of caspase-3 expression. Similarly, in SK-MEL-28 cells, increased expression of caspase-8 and caspase-3 indicated the activation of both extrinsic and intrinsic apoptotic mechanisms at the transcriptional level. Additionally, AC3® influenced the inflammatory response by increasing the expression of Tumor Necrosis Factor Alpha (TNF-α), Interleukin 6 (IL-6), and NLR Family Pyrin Domain Containing 3 (NLRP3) in A375 cells while downregulating IL-6 and NLRP3 expression in SK-MEL-28 cells, highlighting its effect on processes related to tumor development and progression. Furthermore, the compound modulates the expression and enzymatic activity of ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and ecto-5'-nucleotidase (CD73), key regulators of purinergic signaling, suggesting its potential to affect immune evasion mechanisms in melanoma. These findings position the AC3® compound as promising for cutaneous melanoma by targeting critical pathways involved in tumor progression and cell survival.

Chronic exposure to morphine induces oxidative stress and alters the hippocampal expression of genes encoding enzymes involved in epigenetic modifications (e.g., DNA methyltransferases; DNMTs and Histonedeacetylases; HDACs) and apoptosis-related signaling (e.g., Bax and Bcl-2). This study examined the effects of vitamin E and L-carnitine supplementation on cognitive function and hippocampal gene expression following morphine administration in adult male NMRI mice. Morphine was administered subcutaneously twice daily at escalating doses: 10 mg/kg for 10 days, 20 mg/kg from day 10 to 20, and 30 mg/kg from day 20 to 45. Antioxidants (vitamin E at 200 mg/kg, L-carnitine at 100 mg/kg, or both) were administered starting on day 10. Behavioral tests, including the open field test, elevated plus maze, and novel object recognition, were conducted on days 43-45. Hippocampal analyses assessed mRNA expression of DNMT3A, DNMT3B, HDAC1, HDAC2, Bax, and Bcl-2, as well as malondialdehyde (MDA) levels, total antioxidant capacity (TAC), and CA1 Nissl staining. Morphine-treated mice exhibited increased anxiety-like behavior, though this effect was not consistently reversed by antioxidants, and memory impairment compared to saline controls. Antioxidant treatment partially mitigated these behavioral deficits. Biochemically, morphine elevated MDA and reduced TAC levels, while antioxidant administration attenuated these markers toward control levels. Histologically, morphine increased CA1 cellular damage, which was attenuated by antioxidants. At the molecular level, morphine increased Bax mRNA and decreased Bcl2 mRNA expression; antioxidant treatment partially reversed these changes. Morphine also increased DNMT3B mRNA expression, which was reversed by antioxidants. Additionally, HDAC1 and HDAC2 mRNA expression decreased with morphine treatment and was enhanced by vitamin E and L-carnitine. These findings suggest that vitamin E and L-carnitine may attenuate morphine-induced hippocampal dysfunction through modulation of oxidative stress and altered gene expression, supporting their potential as adjunctive therapies for opioid-related cognitive impairment.

Colorectal cancer (CRC) is a major cause of cancer-related death due to recurrence and therapeutic resistance. This study evaluates whether combining panobinostat, a histone deacetylase (HDAC) inhibitor, with epigallocatechin gallate (EGCG), a green tea-derived polyphenol, enhances anti-tumor activity through modulation of HDAC expression in CRC cell lines.

Certain bacteria from the naturally occurring microbial world have exhibited remarkable abilities to overcome the limitations of the environmental stressors. Consequently, they reprogram their stress response programmes to maximize their survival. One such bacterium namely Chryseobacterium sp. strain PMSZPI, a member of the phylum Bacteroidota, isolated from sub-surface soil of a uranium (U) ore deposit demonstrated high tolerance to several heavy metals including U (MIC 4 mM). To gain insights into U resistance in PMSZPI, we characterized the physiological and transcriptome-wide defense responses of PMSZPI to U exposure. PMSZPI cells exposed to challenging concentration of 300 µM U exhibited reactive oxygen species (ROS) accumulation, protein carbonylation and increased membrane permeability. Transcriptome analysis identified 288 upregulated and 195 downregulated genes at 0.5 h and 197 upregulated and 131 downregulated genes at 24 h of U exposure. The most prominent response was protection against U-induced oxidative stress, including induction of superoxide dismutase (log2FC 3.33), catalase (log2FC 2.91), thiol peroxidase (log2FC 2.86) and ferritin (log2FC 3.32). Efflux and the transporters were significantly upregulated including TonB-dependent receptors (log2FC 10.10) and RND transporter periplasmic adaptor subunit (log2FC 2.94). DNA repair via the non-homologous end joining pathway was induced with Ku protein and NHEJ DNA polymerase (LigD) with log2FC of 3.97 and 2.34 respectively. In contrast, the down-regulation of ATP synthase subunits, translational machinery and gluconeogenic enzyme PEPCK (log2FC -3.58) indicated metabolic reallocation under U stress. Overall, this study elucidates temporally regulated complex response of PMSZPI cells to tolerate U toxicity existing in U ore deposit.

Gradual loss of the homeostatic balance owing to deregulation of endogenous antioxidant defense pathways, such as nuclear factor erythroid 2-related factor 2 (Nrf2), contributes, at least in part, to the characteristic oxidative stress, neuronal loss, and cognitive decline associated with aging. Here, we adopted an integrated approach using behavioral, biochemical, histological, molecular, and in silico methods, exploring the neuroprotective efficacy of vitamin D against D-galactose-induced oxidative stress, neuroinflammation, and neurodegeneration. Chronic D-galactose administration (150 mg/kg, s.c) led to profound deficits in spatial learning, working memory, and recognition memory, besides increased oxidative stress, reduced antioxidant enzyme activity, suppression of Nrf2 and heme oxygenase-1 (HO-1) expression, and frank hippocampal neurodegeneration, as revealed by nissl staining. Vitamin D treatment (5 µg/kg i.p) significantly improved such deficits by restoring cognitive performance, reducing ROS and lipid peroxidation, enhancing endogenous antioxidant activities such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione peroxidase (GPx), and upregulating Nrf2 and HO-1 expression comparable to positive control, dimethyl fumarate (DMF). Co-administration of all-trans retinoic acid (ATRA), an antagonist for Nrf2, abrogated these protective effects, confirming the pathway specificity. Molecular docking studies have shown a strong binding affinity of Vitamin D to the regulatory domain of Nrf2, supporting a direct stabilizing interaction that may facilitate the activation of Nrf2. Nissl quantification has further demonstrated substantial preservation of neuronal integrity in hippocampal CA1, CA3, and DG regions following the treatment with vitamin D. Altogether, findings from this study show that vitamin D confers robust neuroprotection through Nrf2-dependent antioxidant mechanisms and mitigates aging-related neurodegeneration induced by D-galactose. The results highlighted vitamin D as a readily accessible therapeutic candidate for mitigating oxidative stress-driven cognitive decline.

GmHMGR6 coordinates a regulatory network linking nodulation, nitrogen metabolism, and photosynthesis, therebyimproving nitrogen utilization and sustaining carbon assimilation under salt stress in soybean. 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) functions in the mevalonate pathway and is essential for plant development and stress adaptation. We identified GmHMGR6 as the most salt-responsive HMGR isoform in soybean, with predominant expression in roots. To elucidate its function in salt tolerance, we generated GmHMGR6-overexpressing hairy roots and subjected these composite plants to NaCl treatment. Physiological assays, metabolite measurements, chlorophyll fluorescence and gas-exchange analyses, together with RNA-seq of roots and leaves, were performed to characterize the GmHMGR6-dependent responses. GmHMGR6 overexpression markedly reduced salt-induced DEGs in roots relative to wild type and primarily affected nitrogen-related metabolic pathways. Leaf DEGs were enriched in photosynthesis-associated processes, including antenna proteins, electron transport, and CO₂ assimilation. GmHMGR6 also regulated key nodulation genes, thereby promoting nodule formation and enhancing nitrogen assimilation through higher ammonium levels and increased glutamine synthetase (GS) and glutamine oxoglutarate aminotransferase (GOGAT) activities. Moreover, GmHMGR6 overexpression alleviated NaCl-induced photosynthetic inhibition by maintaining photosystem function and reducing photoinhibition and oxidative damage. These findings demonstrate that GmHMGR6 enhances soybean salt tolerance through coordinated regulation of nitrogen metabolism, nodulation, and photosynthetic performance.

Hepatocellular Carcinoma (HCC) is a matter of great global public health importance; however, its current therapeutic effectiveness is deemed inadequate, and the range of therapeutic targets is limited. This study aimed to explore the efficacy of Bosutinib (BOS) in HCC and the underlying molecular mechanism.

Insulin-like growth factor binding protein-6 (IGFBP-6) is induced by progesterone in breast cancer cells and regulates progesterone receptor (PR) via negative feedback. To further understand the mechanisms by which IGFBP-6 regulates PR and downstream signaling, proteomic analysis was performed in progesterone-treated T47D breast cancer cells following siRNA-mediated knockdown of IGFBP-6. Of the 8638 unique proteins identified, 29 proteins were downregulated, and 14 proteins were upregulated by progesterone treatment after IGFBP-6 knockdown. The decreased proteins were mostly identified as regulators of G2/M phase of the cell cycle. SH2D4A is induced by progesterone only when IGFBP-6 was high. To understand the role of SH2D4A in progesterone-induced signaling, SH2D4A was knocked down using siRNA prior to progesterone treatment. Knockdown of IGFBP-6 or SH2D4A leads to cell cycle arrest in G1, and both SH2D4A and IGFBP-6 regulate cyclin B. Treatment of cells with abemaciclib and nocodazole caused cell cycle arrest in G1 and G2/M, respectively, and decreased IGFBP-6, suggesting that IGFBP-6 is regulated in a cell cycle-dependent manner. These results identify a pathway linking progesterone to IGFBP-6 and SH2D4A, and to cell cycle progression in breast cancer cells.

Colorectal cancer (CRC) is a major global health threat, necessitating the development of functional foods with chemopreventive potential. This study aimed to evaluate the modulation of the anticancer activity of Hericium erinaceus with different iron forms (FeCl3, FeSO4, and FeHBED) as it modulates its anticancer activity against HT-29 cells. The extracts were subjected to simulated in vitro digestion and analyzed for cytotoxicity (MTT), antioxidant capacity (DPPH), and morphological changes, alongside high-throughput RT-qPCR profiling of 92 cancer-related genes. The results demonstrated that iron speciation is critical, with FeHBED-biofortified extracts exhibiting the most potent concentration-dependent cytotoxic and antiproliferative effects. Treated cells displayed apoptotic morphology, including chromatin condensation and cell shrinkage. Molecular analysis revealed significant downregulation of key oncogenes (HRAS, MYC), cell cycle regulators (CDK4), and migration markers (RHOA, ITGB1), whereas VEGFA was upregulated as a stress-induced response. In conclusion, biofortification with FeHBED significantly enhanced the anticancer potential of H. erinaceus by targeting specific proliferative and survival pathways. These findings highlight the potential of iron-biofortified mushrooms as a functional dietary component for colorectal cancer prevention.

Acute liver failure (ALF) is characterized by a rapid decline in liver function, leading to metabolic and organ failure. This study employed liver metabolomics, Nuclear Factor kappa-B (NF-κB) signaling pathway analysis, and inflammatory factor profiling to investigate the therapeutic mechanisms of xanthoxylin in ALF. Xanthoxylin administration led to increased antioxidant levels and reduced markers of inflammation and tissue damage. Xanthoxylin downregulated the messenger RNA (mRNA) expression of Nitric Oxide Synthase (NOS), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), NF-κB, Inhibitor of NF-κB α (IκBα), and Toll-like receptor 4 (TLR4), and inhibited the protein expression of p-p38 and p-p65 while upregulating B-cell CLL/Lymphoma 2 (Bcl-2) and B-cell Lymphoma-x (Bcl-xl). Metabolomic analysis identified 41 differentially expressed metabolites, 20 of which showed strong correlations with pharmacodynamic parameters. These 20 candidate metabolite signatures are involved in amino acid and carboxylic acid metabolic pathways, with potential links to glycolysis and the tricarboxylic acid (TCA) cycle. Together, these findings suggest that xanthoxylin exerts therapeutic effects against ALF by modulating the IκBα/NF-κB signaling pathway and related metabolic pathways, providing a scientific basis for understanding its multi-target mechanism.

A high-fat diet (HFD) contributes to cardiometabolic disease. Gut microbiota-derived metabolites may participate in this process, but their contribution to lipid regulation is not well defined. Indoxyl sulfate (IS), a microbiota-derived metabolite, has been linked to vascular and metabolic dysfunction. Its role in lipid metabolism remains unclear.

Objectives: Neuroinflammation is recognized as a significant characteristic of Alzheimer's disease (AD). Currently, there is a notable absence of effective pharmacological agents to prevent or treat neuroinflammatory processes associated with AD. Heat shock protein 70 (HSP70) is pivotal in the progression of neuroinflammation. In this study, we explored the potential of maltol, a Maillard reaction product derived from red ginseng, as a therapeutic agent for neuroinflammation. Methods: In vitro, HMC3 microglial cell models were developed to examine the regulatory effects of gradient concentrations of maltol (12.5, 25, 50 μM) on the TLR4/MyD88/NF-κB p65 signaling pathway, neuroinflammation, and pyroptosis. Analyses of the GEO database and Gene Set Enrichment Analysis (GSEA) were performed to identify the core targets of maltol, followed by HSP70 gene silencing experiments to validate the targeted regulatory mechanism. Results: Maltol significantly mitigated LPS-induced neuronal damage and cognitive deficits in mice. It effectively suppressed microglia-mediated neuroinflammation and pyroptosis, reversed oxidative stress-induced neuronal ferroptosis, and inhibited neuronal apoptosis. In vitro experiments demonstrated that maltol obstructed TLR4/MyD88 binding, thereby inhibiting NF-κB p65-mediated neuroinflammation and pyroptosis, while also alleviating excessive ROS accumulation to enhance oxidative stress and ferroptosis. Bioinformatics analysis identified HSP70 as a crucial target for the anti-inflammatory and antioxidant effects of maltol. Subsequent gene silencing experiments confirmed that maltol exerted its inhibitory effects on LPS-induced neuroinflammation and pyroptosis in an HSP70-dependent manner. Conclusions: Maltol exhibits significant protective effects against Alzheimer's disease-related neuroinflammation, oxidative stress, pyroptosis, and ferroptosis through the targeting of HSP70. This study elucidates the molecular mechanisms by which maltol improves neuroinflammatory injury and provides a novel theoretical foundation and therapeutic strategy for the intervention of Alzheimer's disease neuroinflammation using traditional Chinese medicine.

This paper introduces an approach for inferring the gene regulatory networks in vortioxetine-induced glioblastoma cells to investigate vortioxetine's systemic effects. The approach uses an ordinary differential equation (ODE)-based inverse problem to evaluate the drug-induced gene interactions within the GLIOMA and ERBB pathways, which are deeply intertwined in cancers, by using time-series datasets. Time-series datasets were generated in triplicate at 0, 3, 6, 9, 12, and 24 h. The results of the ERBB pathway confirmed that PIK3R5 was commonly activated, while JUN, as a proto-oncogene in glioblastoma, was inhibited by genes across all three datasets. In particular, PIK3R5 was commonly activated by PAK6 in all three datasets. The results of the GLIOMA pathway confirmed that CALML6 was commonly activated, while CDK4 and CCND1, which are mostly overexpressed in human cancers, were inhibited across all three datasets. Additionally, an analysis of the independent datasets generated at 6 and 22 h after the vortioxetine injection identified the most distinct variable genes between the two time points: CRK (1.96) and JUN (-3.02) for the ERBB signaling pathway, and BRAF (1.30) and MAP2K2 (-1.92) for the GLIOMA pathway. We conclude that vortioxetine, an antidepressant, decreases JUN, a proto-oncogene involved in the ERBB signaling pathway, and CCND1, another proto-oncogene involved in the GLIOMA pathway, over time in glioblastoma cells.

Chronic inflammation is a hallmark of the breast cancer tumor microenvironment and is also known to be associated with disease progression and therapeutic response. Interleukin-1 (IL-1) signaling has been widely studied in breast cancer biology; however, the long-term effect of sustained IL-1 exposure on hormone receptor-positive breast cancer cells remain poorly understood. In this study, we investigated how chronic IL-1 exposure influences inflammatory response, hormone dependency, and therapeutic sensitivity in ERα+/PR+ breast cancer models, MCF7 and T47D. Chronic IL-1 exposure attenuated response to subsequent acute IL-1 treatment, but the chronically exposed cells remained sensitive to serum deprivation, retained dependence on estrogen or progesterone receptor signaling, and responded robustly to endocrine and chemotherapeutic treatments. Extensive changes in basal gene expression and histone modification revealed that chronic IL-1 exposure alters transcriptional reprogramming and chromatin remodeling. Together, these findings demonstrate that chronic IL-1 signaling drives selective inflammatory response in hormone receptor-positive MCF7 and T47D breast cancer cells. This work underscores the continued therapeutic relevance of hormone receptor-targeted strategies in chronically inflamed tumors and provides insight into how sustained inflammatory stress shapes tumor behavior and gene regulation predicted to promote tumor progression.

Human endogenous retroviruses (HERVs) originate from ancient retroviral integration into the primate germline. Although most are defective proviruses, the most recently endogenized groups, like the HERV-K family, retain intact ORFs encoding retroviral proteins. HERVs usually remain transcriptionally silent, yet this status is reversible. Multiple HIV-HERV interactions, mainly mediated by the HIV Tat protein, lead to HERV transcription and protein production. The present study investigates HERV-K transcription in particular of Human MMTV-like (HML) group-2 and 6 in peripheral blood of people with HIV (PWH). Using different experimental approaches-such as single-cell and plasma transcriptomics-, we found that HERV-K transcripts may be detected during both acute and chronic phases of the infection, with HML-6 showing higher expression compared to HML-2, predominantly within myeloid cells. Effective combined antiretroviral therapy (cART) was able to significantly reduce HML-6 transcription, regardless of whether the treatment was initiated in the acute or late chronic phases of HIV infection. Notably, chronic infections showed higher HML-6 transcript levels compared to acute infections in both naïve and successfully cART-treated subjects, potentially associated with persistent immune dysregulation observed in chronic HIV infection, although a direct causal role of HML-6 expression remains to be established.

Vitamin K is a well-established cofactor for γ-glutamyl carboxylase in vertebrates, yet its physiological functions in insects remain poorly understood. Warfarin, a vitamin K antagonist, inhibits vitamin K epoxide reductase, thereby blocking the vitamin K cycle. We have previously demonstrated that, in Drosophila melanogaster, vitamin K3 (menadione sodium bisulfite, MSB) is converted into endogenous vitamin K2, and that warfarin interferes with this cycle, leading to reduced oxidative stress. In the present study, we investigated the effects of chronic exposure to MSB (3.5 mM) and/or warfarin (1 mM and 10 mM) during larval development on adult survival, lifespan, mitochondrial ATP hydrolysis rate, and the transcriptional expression of target genes. Warfarin at 1 mM did not affect development or egg laying, whereas 10 mM caused significant postembryonic lethality. Transcriptional analysis revealed marked sex-specific effects. In females, warfarin downregulated the levy gene (encoding a complex IV subunit) and the ATPsynB gene (encoding an ATP synthase subunit B), while MSB suppressed cell cycle genes (cmet, sti, mcm2). In contrast, males exhibited upregulation of COQ7 (encoding a key enzyme in ubiquinone biosynthesis) in response to warfarin and increased sti expression in response to MSB, suggesting a more robust compensatory response. Notably, the combined application of MSB and warfarin increased mitochondrial ATP hydrolysis, thereby offsetting the negative physiological effects despite persistent transcriptional suppression. In females, either MSB or warfarin alone significantly reduced median lifespan; however, when applied together, female lifespan was restored to control levels. In males, the effects were considerably weaker. Thus, this study reveals a novel, sex-specific interaction between vitamin K and its antagonist in D. melanogaster, providing new insights into mitochondrial adaptation and sexual dimorphism in metabolic stress responses.

Microbial fermentation of plant-derived materials is increasingly recognized as a strategy to enhance biological activity through phytochemical bioconversion. In this study, we investigated the antibiofilm effects of fermented Zingiber officinale rhizome extract against major periodontal pathogens and examined the underlying mechanisms. Ginger extract fermented with plant-derived lactic acid bacteria showed significantly greater inhibition of biofilm formation by Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans than non-fermented extract. The inhibitory activity increased with fermentation time, resulting in approximately 60-70% reduction in biofilm formation at higher concentrations. Chromatographic analysis revealed decreased 6-gingerol and increased 6-shogaol levels after fermentation, suggesting bioconversion of 6-gingerol to 6-shogaol. Direct treatment with 6-shogaol inhibited biofilm formation in a dose-dependent manner in all tested pathogens. Quantitative PCR analysis further showed that 6-shogaol significantly downregulated the quorum sensing-related gene luxS and multiple adhesion- and virulence-associated genes, including flp, fimA, mfa1, radD, fadA, ltxA, and rgpB. These findings indicate that lactic acid bacterial fermentation enhances the antibiofilm activity of ginger extract through increased 6-shogaol production, highlighting its potential as a natural anti-biofilm and anti-virulence agent for periodontal disease prevention and management.

Malignant gliomas are highly aggressive primary brain tumors for which the therapeutic efficacy of cisplatin is frequently limited by intrinsic or acquired drug resistance. Despite advances in adjuvant therapies, overcoming chemoresistance remains a major challenge in the treatment of these malignancies. Emerging evidence indicates that long non-coding RNAs (lncRNAs), a class of non-protein-coding transcripts involved in gene regulation, play important roles in modulating treatment responses. Several lncRNAs, including differentiation antagonizing non-protein-coding RNA (DANCR), HOXD antisense growth-associated long non-coding RNA (HOXD-AS1), MEG3, MALAT1, and HOTAIR, have been implicated in pathways associated with glioma progression and therapeutic resistance. In particular, DANCR has been reported to promote cisplatin resistance in glioma cells through suppression of apoptosis and activation of pro-survival signaling pathways. This review summarizes current evidence regarding the roles of lncRNAs in cisplatin resistance, highlighting mechanisms such as regulation of drug transport, DNA damage repair, apoptosis, cancer stem-cell maintenance, and signaling pathways associated with treatment adaptation. We also discuss current limitations, challenges for clinical translation, and gaps in the existing evidence. A better understanding of lncRNA-mediated resistance mechanisms may facilitate the identification of novel therapeutic targets and inform future studies aimed at overcoming cisplatin resistance in malignant gliomas.

Bumblebees are dominant pollinators threatened by environmental antibiotic residues. This study investigated sublethal chloramphenicol (12 and 120 μg/L) effects on Bombus terrestris after 15 days' exposure. The results showed that chloramphenicol exposure had no significant effect on the survival rate and cumulative food intake of bumblebees, confirming the sublethal property of the tested concentrations. However, chloramphenicol significantly dysregulated the expression of genes related to learning-memory (DopR2, Oamb, NMDA), immunity (abaecin, defensin) and detoxification (cyp9Q6) in bumblebees. High-dose chloramphenicol significantly increased carboxylesterase activity and reduced malondialdehyde content, while superoxide dismutase activity remained unchanged. In addition, chloramphenicol exposure significantly reshaped the gut microbiota structure of bumblebees, reduced the abundance of core beneficial symbiotic bacteria, and increased the proportion of drug-resistant bacteria. Our findings indicate that sublethal concentrations of chloramphenicol can impair bumblebee health through multiple pathways, including regulating gene expression, altering antioxidant enzyme activity and disrupting gut microbiota homeostasis. This study provides multi-dimensional toxicological data and a scientific basis for the ecological risk assessment of agricultural antibiotic residues to pollinator insects.