Recurrent somatic mutations in the key spliceosome component, SF3B1, have been identified at various frequencies across several cancer types. The most common hotspot mutation is the K700E missense mutation, and while its effects on splicing have been well characterised at the molecular level, the mis-spliced genes that contribute to cancer progression and/or dictate responses to therapy are still unclear. Here, we used we use cell line modelling to assess the impact of the SF3B1K700E mutation on the cellular response to various apoptosis-inducing agents. Our data suggest that the SF3B1K700E mutation leads to reduced cFLIP levels, along with defects in the splicing and translation of BCL2, causing a shift in the balance of pro- and anti-apoptotic genes and proteins, which confers greater sensitivity to the bivalent SMAC mimetic, BV-6. As such, BV-6 may represent a therapeutic opportunity for patients with SF3B1 mutant cancers.

Candida albicans is a leading fungal pathogen in humans, responsible for infections that span from mucosal surfaces to severe systemic diseases. This study aimed to investigate potential ability of yeast-derived glycolipids from Meyerozyma guilliermondii as an antifungal against Candida albicans biofilms. Glycolipid extract (64 µg/mL) reduced metabolic activity by 50% in both immature and mature biofilms, while biofilm mass was reduced at higher concentrations of 128 and 256 µg/mL, respectively. Adhesion, a key step in biofilm formation, decreased by over 50% when cells were treated with glycolipids (16 µg/mL). Gene expression analysis indicated that glycolipids downregulated key adhesion-related gene ACE2, confirming their role in disrupting C. albicans adhesion. Importantly, structural changes in C. albicans biofilms, including reduced hyphal production and wrinkled cell surfaces, were observed under SEM. Nocodazole, a cell cycle synchronizer, arrested cells in the G2/M phase, enhancing glycolipid's effects on lowing expression of biofilm-related genes. Lipidomics analysis also revealed a compound with same mass as sophorolipid. Furthermore, purification glycolipid fraction revealed two main forms: lactonic and acidic, compared to standards. Acidic fraction showed superior antibiofilm and anti-inflammatory activity with low toxicity. These findings highlight the potential of yeast-derived glycolipids for biopharmaceutical applications, particularly in treating Candida biofilms.

Cisplatin is a widely used, effective chemotherapy drug. However, its application is often limited by severe side effects, including testicular toxicity. Cisplatin-induced testicular damage is primarily driven by oxidative stress and inflammation. Ferroptosis has recently been identified to contribute to cisplatin-testicular toxicity. Morin hydrate (MH) is a naturally occurring flavonoid known for its powerful antioxidant, anti-inflammatory, and anti-apoptotic properties. The study was designed to evaluate the protective effects of MH against cisplatin-induced testicular toxicity in Wistar albino rats. Rats were given MH 50 mg/kg, p.o. daily for fourteen days, seven days before the injection of cisplatin 8 mg/kg. Assessment of sperm quality, testosterone, luteinizing hormone levels, and oxidative stress markers were carried out. Also, steroidogenesis and ferroptosis-related gene expressions were assessed. Results: Our findings demonstrated that MH significantly corrected the antioxidant/oxidant balance, evidenced by increased superoxide dismutase, glutathione peroxidase, and Nrf2/heme oxygenase-1 (HO-1) expression and reduced malondialdehyde in testicular tissue. Also, MH ameliorated the negative changes in sperm quality, hormone levels, and testicular histology induced by cisplatin, and this was accompanied by upregulation of steroidogenesis gene expressions (17β-HSD, 3β-HSD, and star). Moreover, MH inhibited cisplatin-induced ferroptosis via the modulation of ferroptosis genes' expression (ACSL4, SLC7A11, and TFRC) and the reduction of iron accumulation in testicular tissue. Conclusion: MH effectively protected against cisplatin-induced testicular toxicity by reducing oxidative stress and inhibiting ferroptosis signalling. This study points out that MH might mitigate iron-mediated apoptosis through the downregulation of Nrf2/HO-1 signaling, providing a potential therapeutic strategy for preventing infertility in male patients undergoing cisplatin chemotherapy.

In the field of cancer therapy, the diversity and heterogeneity of cancer genomes in clinical patients complicate and challenge the effective use of non-targeted drugs, as these drugs often fail to address specific genetic events. Recent advancements in large-scale in vitro drug screening assays have generated extensive drug testing and genomic data, providing valuable resources to explore the relationship between genomic features and drug responses. In this study, we developed a deep neural network model, DrugS (Drug Response prediction Utilizing Genomic features Screening), utilizing gene expression and drug testing data from human-derived cancer cell lines to predict cellular responses to drugs. Leveraging gene expression and mutation data, we elucidated potential molecular mechanisms underlying SN-38 resistance. Additionally, we used DrugS to evaluate the effects of drugs on cancer cell proliferation in patient-derived xenograft models. In in vitro combination drug experiments, DrugS revealed that CDK inhibitors, mTOR inhibitors, and apoptosis inhibitors effectively reverse Ibrutinib resistance, providing new therapeutic strategies to overcome drug resistance. Furthermore, we assessed the applicability of the DrugS model in drug screening and patient prognosis evaluation using drug information and gene expression data from The Cancer Genome Atlas. In summary, our study offers a novel approach for drug response prediction and mechanism research in cancer therapy from a genomic perspective and demonstrates the potential applications of the DrugS model in personalized therapy and resistance mechanism elucidation.

This study aims to elucidate the potential mechanisms underlying the therapeutic effects of Bletilla striata in glioma. Targets of Bletilla striata and glioma were predicted using TCMSP, SwissTargetPrediction, GeneCards, and other databases. A "drug-ingredient-target" network and protein-protein interaction (PPI) network were constructed, with core targets identified via topological analysis. Functional enrichment (GO/KEGG, DAVID), molecular docking, and experimental validations (MTT, scratch assay, RT-PCR, Western blot) were performed. A total of 11 active ingredients of Bletilla striata, 456 corresponding targets, and 2,830 glioma-related targets were identified. Nine core targets (AKT1, STAT3, mTOR, etc.) were identified. GO analysis indicated that these targets were primarily involved in phosphorylation, protein binding, and the positive regulation of RNA polymerase II transcription. KEGG analysis highlighted key pathways, including pathways in cancer, the PI3K-AKT signaling pathway, and microRNA-related regulatory mechanisms in cancer. Molecular docking analysis demonstrated high binding affinities between active ingredients and core targets, particularly AKT1 and mTOR. Functional assays showed that Blestriarene A, a key active compound in Bletilla striata, significantly suppressed glioma cell proliferation and migration. RT-PCR results indicated that treatment with varying concentrations of Blestriarene A for 48 h downregulated AKT mRNA expression while upregulating mTOR mRNA expression. Western blot analysis further confirmed a reduction in PI3K, AKT, and mTOR phosphorylation following treatment. Network pharmacology and in vitro experiments suggest that Blestriarene A anti-glioma effects by modulating the PI3K/AKT/mTOR signaling pathway.

Oxidative stress during semen processing affects sperm membrane integrity, leading to compromised sperm membrane functions and kinematics, often resulting in reproductive losses. The first objective of the present study explored the effect of Quercetin (QUE) on seminal parameters, i.e., total antioxidant capacity (TAC), as well as sperm viability, DNA fragmentation, kinematics, intracellular calcium, and apoptosis. The second objective evaluated fold changes in the transcription of apoptotic regulatory (Bax, Bad, Bcl2, Bcl2L1, Fas, FasL, and Caspase 3, 8, 9, and 10) and calcium-regulating CatSper-1,2,3 and 4 genes of the buck spermatozoa. The final objective was fertility trial of negative control and best-performing treatment group. The study analysed 36 ejaculates from 6 bucks, each ejaculate was then divided into 5 parts and extended using TRIS extender with different concentrations of QUE. The negative control (C) consists of extended semen without the addition of QUE, whereas positive control (T1) had been added with vitamin E at a concentration of 3 mmol/mL. Furthermore, treatment groups 2, 3, and 4 (T2, T3, T4) were supplemented with 10, 20, and 30 µmol of QUE/mL of extended semen. The samples at the post-thaw stage were evaluated for seminal parameters as described in the objectives. Group T3 supplemented with 20 µmol/mL QUE was observed with the best results. QUE at 20 µmol/mL concentration significantly enhanced semen TAC along with various sperm parameters, i.e., viability, kinematics, intracellular calcium and plasma membrane fluidity. QUE at 20 µmol/mL concentration also downregulated pro-apoptotic and upregulated anti-apoptotic genes. Similarly, QUE downregulated caspase family genes and upregulated CatSper genes. Field fertility trials showed improved conception rates in the treatment group. QUE-induced control of oxidants might have contributed to higher TAC and viability. The upregulation of anti-apoptotic and downregulation of pro- and other apoptotic regulatory genes, as well as the upregulation of CatSper genes, suggest a regulatory effect of QUE on sperm apoptosis, and calcium homeostasis. Lower proportion of apoptosis and higher normal intracellular calcium, as estimated through flow cytometry, further validated our findings. Our field fertility trial yielded 58.3% conception rate in the treatment group as compared to 27.6% in the control group. QUE at 20 µmol/mL concentration significantly improved the antioxidant capacity, intra-cellular calcium concentration, and kinematics of goat sperm and subsequently resulted in better fertility as compared to control.

Epigenetic modifications can influence the phenotypes of subsequent generations through intergenerational and transgenerational effects. The aim of the research was to assess the impact of epigenetic factors acting during embryonic development on the structure and cellular composition of lymphoid organs in three generations of chickens. Two groups of eggs were injected once (in the F1 generation) with a synbiotic (SYNs) or a synbiotic + choline (SYNCHs), while two other groups were injected in each successive generation (F2, F3-SYNr, SYNCHr). Synbiotic administration resulted in an increased cortex/medulla ratio of the thymus in the F1 but not in subsequent generations. In the spleen, an intergenerational effect (from F1 to F2) was found in the choline-supplemented (SYNCHs) groups but not in the SYNs groups. Not all changes observed in the F1 were evident in the F2 generation. No intergenerational effect was found in the cecal tonsil, and no transgenerational effects were observed in any of the tested organs. In ovo administration of synbiotics with choline may induce intergenerational phenotypic effects on specific immune organs. However, these effects either persisted through the first two generations or appeared solely in the F1 or F2 generations. Changes were evident in young birds but not in mature ones.

Breast cancer is the second leading cancer type in women, accounting for 11.6% of all cancers. Recently, its incidence has increased in younger individuals. Estrogen receptors (ERs) play important roles in the development and progression of breast cancer by controlling hormone signaling. Therefore, targeting ERs is one of the most promising therapeutic strategies for treating ER-positive breast cancer. High heterogeneity contributes to the tumorigenicity, metastatic ability, and therapeutic resistance of breast cancer. However, drug discovery studies at the single-cell level are lacking. In the present study, we used single-cell sequencing data analysis, together with a network pharmacology approach, to determine the targets and molecular mechanisms of formononetin in ER-positive breast cancer. Comparative single-cell sequencing analysis identified 3899, 3395, 333, 398, 398, and 17 differentially expressed genes in stromal cells, epithelial cells, fibroblasts, neutrophils, eosinophils, and macrophages, respectively, of ER-positive breast cancer compared with normal breast tissues. Further network pharmacology analysis highlighted the importance of formononetin targets in biological functions and signaling pathways related to immune and inflammatory responses, metastatic ability, metabolism, cell proliferation, and gland development in different ER-positive breast cancer cell types. For the first time, we used a systems biology approach to investigate the targets of formononetin and its anti-ER-positive breast cancer mechanisms at the single-cell level.

Barleria species have been traditionally utilized for medicinal purposes. This study provides a comprehensive analysis of six Barleria leaf extracts, namely B. cristata, B. lupulina, B. prionitis, B. repens, B. siamensis, and B. strigosa, to elucidate their metabolite composition, toxicity, immunomodulatory functions, and roles in cytochrome P450 (CYP) gene expression. The findings indicate that two key metabolites, barlerin and verbascoside, are present in all six Barleria extracts, with B. siamensis exhibiting the highest amount of these compounds at 0.43 mg/g (barlerin) and 1.02 mg/g (verbascoside) of dried leaf, respectively. In terms of toxicological effects, B. cristata and B. siamensis demonstrated significant anti-proliferative activity against PC-3 cells by inducing DNA damage, enhancing apoptosis, and obstructing the cell cycle. However, these extracts did not exert cytotoxic effects on PBMCs, HPrEC, and THLE-3. Conversely, B. strigosa extract exhibited mild toxicity towards HPrECs and moderate toxicity towards THLE-3 cells. Furthermore, treatment with these extracts activated PBMCs, leading to the upregulation of cytokine genes, including IL-2, IL-10, IL-12, IL-15, IL-21, and IFN-γ, which promoted cytotoxicity for PC-3 cells. Additionally, B. siamensis extract significantly suppressed the expression of CYP450 genes, including CYP1A2, CYP3A4, CYP2D6, and CYP2E1, whereas B. strigosa extract induced the overexpression of CYP2E1. In conclusion, Barleria extracts containing barlerin and verbascoside exhibit immunomodulatory properties by activating immune cells to target cancer cells. Moreover, these extracts influence the expression of CYP450 genes, potentially impacting their bioavailability and therapeutic efficacy.

BMI1, a constituent of polycomb repressive complex 1, is overexpressed in a variety of cancers, including neuroblastoma, highlighting its potential as a target for cancer therapeutics. Given the pivotal role of BMI1, a number of inhibitors have been synthesized and assessed for therapeutic efficacy across a spectrum of cancers. In our present study, the BMI1 inhibitors PTC-028 and PTC-209 exhibited selective antitumor activity against MYCN-amplified neuroblastoma. Notably, PTC-028, which exhibited toxicity at lower concentrations, triggered apoptosis in neuroblastoma cells and induced G1-phase accumulation, along with reductions in S-phase and G2/M-phase populations, thereby promoting cell cycle arrest. Thorough RNA sequencing analyses revealed that PTC-028 treatment activated the p53 signaling pathway, suggesting it plays a critical role in the mechanism of apoptosis induction. Moreover, PTC-028 treatment led to decreases in levels of anti-apoptotic proteins, including BCL2 and MCL1. Significantly, PTC-028 also exhibited antitumor efficacy in a mouse xenograft model of human neuroblastoma. These results suggest that BMI1 inhibitors, particularly PTC-028, are promising therapeutic agents for the management of aggressive MYCN-amplified neuroblastomas.

Osteosarcoma (OS) is a highly aggressive bone cancer in children and adolescents with extremely poor prognosis. Gambogic acid (GA) is a natural compound derived from the resin of Garcinia hanburyi trees and has been reported to possess multiple antitumor effects. However, the comprehensive mechanism of GA intervention in OS remains unclear. In this study, network pharmacology and experiment pharmacology were employed to elucidate the mechanism by which GA inhibited OS. Firstly, GA exhibited significant inhibitory effects on OS in vitro and in vivo. Then, the network pharmacological analysis and molecular docking predicted 9 targets involved in necroptosis and apoptosis induced by GA in OS. The qRT-PCR and western blotting verified that GA could increase the apoptosis-related mRNA and protein expression levels, such as cleaved caspase-3, cleaved PARP, indicating that GA could activate apoptosis. Furthermore, proteins related to necroptosis such as RIPK1, RIPK3, and p-RIPK3 were upregulated, while MLKL initially increased and then decreased, implying a dynamic regulation of necroptosis signaling. In summary, our results identified potential targets and pathways of GA to exert anti-osteosarcoma effect, suggesting that GA is a candidate drug for the treatment of osteosarcoma.

Epithelial-mesenchymal transition (EMT) is a critical process in cancer cell motility and metastasis. Monoterpene indole alkaloids (MIAs) have been widely investigated for biological activities, but rarely been explored for cell motility inhibition. This study aimed to discover natural products, especially focusing on MIAs, that inhibit EMT in cancer cells, based on our screening using multiple plant extracts. We found that an extract of the aerial parts of Uncaria scandens (Sm.) Wall. (Rubiaceae) decreased cancer cell motility. Targeted isolation exhibited eight MIAs. Among them, strictosamide and mitraphylline suppressed the invasion and migration of the cells. The alteration of the mRNA expression of the EMT effectors and transcription factors suggested that the EMT signaling pathway is related to the suppression of cancer cell motility by both compounds. RT-PCR gene array suggested inhibition of integrin α4 signaling as a potential mechanism of the EMT inhibition, which was supported by the quantitative analysis of the mRNA expressions of the related genes. Together, present study is the first report highlighting the cell motility-suppressive effects of strictosamide and mitraphylline. Our results suggested the potential applicability of strictosamide and mitraphylline for the prevention of metastasis.

H2S signal transduction involves various physiological processes, including promoting vasodilation, regulating lipid metabolism, inducing angiogenesis, improving oxidative stress and inflammatory response, and avoiding cell apoptosis. Oxidative stress is an important mechanism that causes the pathological progression of NAFLD. However, the effect and specific mechanism of exogenous H2S on oxidative stress in NAFLD are still unclear. Here, we investigated the specific regulatory mechanism of exogenous H2S on oxidative stress and inflammation induced by LM in HepG2 cells. HepG2 cells were stimulated with LM with or without GYY4137 (200 µM) treatment for 24 h. The levels of MDA, SOD, ROS, TNF-α, IL-6, and antioxidant related proteins of cells were detected. We found exogenous H2S remarkably reduced the levels of MDA, ROS, TNF-α and IL-6 and elevated SOD contents as well as the expression of antioxidant-related proteins in LM-induced HepG2 cells. Moreover, exogenous H2S improved the expression of USP22 protein in LM-induced HepG2 cells and inhibited the ubiquitination degradation of SIRT1 through USP22. After USP22 was knocked down, the efficacy of exogenous H2S on mitigating LM-induced oxidative damage and inflammatory reaction in HepG2 cells had been weakened. In conclusion, exogenous H2S inhibited SIRT1 ubiquitination degradation through USP22, thereby alleviating LM-induced oxidative stress and inflammatory responses in HepG2 cells.

Calreticulin (CALR) has been implicated in the genesis and progression of numerous tumors. Nevertheless, its impact on multiple myeloma (MM) remains ambiguous. This study aimed to explore the effect of CALR on the proliferation and drug sensitivity of MM cells and to delve into its underlying mechanism.

Long non-coding RNA (lncRNA) exhibits a crucial role in multiple human malignancies. The expression of lncRNA MIR155HG, reportedly, is aberrantly up-regulated in several types of tumors. In this research, we studied the role and mechanism of MIR155HG in the progression of cervical cancer (CC). We analyzed the expression pattern of MIR155HG in CC patients using public database TCGA, and overexpressed its expression in HeLa cells to explore its cellular functions. Cellular phenotype experiments were conducted to assess the influence of MIR155HG on HeLa cells, including proliferation, cell cycle, migration, invasion, and cisplatin sensitivity. Then we evaluated the impact on epithelial-mesenchymal transition (EMT) of MIR155HG and identified the underlying regulatory mechanism. We found that MIR155HG was highly expressed and positively correlated with overall survival (OS) prognosis results in CC patients. Overexpression of MIR155HG (MIR155HG-OE) demonstrated higher proliferation and migration levels in HeLa cells, while MIR155HG inhibited the apoptosis rate of HeLa cells. Meanwhile, we found MIR155HG can reduce the effect of cisplatin sensitivity on HeLa cells. Besides this, MIR155HG-OE significantly changed the expression pattern of EMT biomarkers, including ZEB1, TWIST1, Vimentin, N-cadherin, and E-cadherin. To explore the underlying mechanism, we found MIR155HG can promote ZEB1 expression by sponging miR-409-3p, forming a competitive endogenous RNA system to inhibit cisplatin sensitivity. In this study, we deeply explored the molecular and cellular functions of MIR155HG in CC cells. Our results highlight the important role and potential targeting value of MIR155HG in CC pathogenesis and development.

The field of hematology has experienced a substantial evolution with the acknowledgment of epigenetic processes as essential factors in the development of hematological malignancies. This review article examines the influence of epigenetic alterations, namely DNA methylation and histone modifications, on the onset and advancement of conditions such as acute myeloid leukemia and myelodysplastic syndromes. We discuss how these epigenetic modifications lead to the deregulation of gene expression, eventually promoting leukemogenesis. The emergence of epigenetic therapies, such as DNA methyltransferase inhibitors (e.g., azacitidine and decitabine), histone deacetylase inhibitors (e.g., vorinostat and romidepsin), and enhancer of zeste homologue 2 inhibitors (e.g., tazmetostat), demonstrates the potential to reverse aberrant epigenetic modifications and restoring normal cellular functions. Moreover, we highlight innovative therapeutic approaches, including combination therapies and CRISPR-based epigenetic editing tools, which are influencing the future of treatment for hematological malignancies. Despite promising results, challenges such as off-target effects, drug resistance, and the need for personalized approaches remain significant barriers to effective treatment. We emphasize that further study is required to improve delivery systems, comprehend resistance mechanisms and develop precision medicine strategies that can tailor therapies to individual patient profiles. By integrating benchside discoveries with clinical applications, this review aims to illuminate the transformative potential of epigenetic therapies in improving patient outcomes in hematology.

The objective of this study was to evaluate the effect of adding of C-Type Natriuretic (CNP) to the in vitro culture medium of bovine embryos on cryotolerability through modulation of lipid content and profile, as well as modulation of gene transcripts linked to embryonic metabolism. Initially, a concentration of 400 nM of CNP was used throughout the in vitro culture and blastocysts were collected for lipid content analysis by Sudan Black B. In addition, blastocysts were selected by morphological quality and developmental stage, and the samples collected were analyzed using MRM- profiling. After, blastocysts were vitrified using OPS. Subsequently the warming, hatched blastocysts were collected and evaluated for transcript abundance in a microfluidic platform. Differences of probabilities lower than P < 0.05, and/or fold change ˃1.5 were considered significant. The CNP group presented a reduction in the relative abundance of ions belonging to different lipid subclasses, such as acylcarnitine, sphingomyelin, cholesteryl esters, free fatty acids, and glycerophospholipid. Furthermore, the triacylglycerol lipids TG 52:3 NL 16:1, TG 56:3 NL 18:1, and the glycerophospholipid C22:6, were increased in the CNP group. A modulation of blastocyst transcripts was also observed by increased transcription of ATF4, and a trend statistical significance of BMP15 and GFPT2 transcripts. There was no difference in blastocyst development rates after warming of CNP-treated embryos.

Genome-wide identified 116 ERF members in cultivated peanut. Comprehensive analysis shows that AhERF28 is the key factor for peanut in its response to salt and drought stresses. Ethylene response factor (ERF) belongs to the AP2/ERF (APETALA2/ERF) superfamily, which is widely involved in plant responses to various abiotic stresses, including drought and salt stresses. Although members of the ERF family have been reported in multiple plant species, the members and functions of the peanut ERF family are largely unknown. In this study, a total of 116 ERFs were identified in peanut (Arachis hypogaea L.) via genome-wide identification. The peanut ERFs were classified into ERF and DREB subfamilies. Through phylogenetic tree analysis, the 116 ERFs were divided into 11 different subgroups, and the genes in the same group had conserved motifs, exon coding sequences, and domains. The ERF family genes demonstrated differential expression across 22 tissues. Further analysis revealed that AhERFs contain a variety of cis-acting elements in their promoters. Among them, there are 6, 11, and 15 elements related to development, hormones, and abiotic/biotic stress, respectively. In addition, by analyzing the transcriptome data under salt and drought treatments and qRT-PCR verification of AhERFs, it was found that the expression level of AhERF28 increased after both salt and drought treatments. Further research indicates that silencing AhERF28 enhanced the tolerance of peanut to salt and drought stress, likely due to an increased capacity of ROS scavenging. This study identified the ERF members in the cultivated peanut and revealed the potential role of AhERF28 in salt and drought stresses, which provides a new perspective for understanding the functions of ERFs in peanut response to abiotic stress processes and a theoretical basis for crop improvement.

Hepatocellular carcinoma (HCC) ranks among the top three causes of cancer-related mortality globally and is associated with a relatively low five-year overall survival rate. Naringenin has demonstrated significant inhibitory effects on various neoplasms; however, the mechanisms of action and potential molecular targets of naringenin in the context of HCC remain to be elucidated. Cellular proliferation in cancer cells was quantified using the Cell Counting Kit-8 (CCK-8) assay. Wound healing and transwell tests were employed to evaluate the migratory and invasive capabilities of the cells, respectively. Apoptosis was evaluated using Hoechst staining to visualize nuclear changes and flow cytometry to quantify apoptotic populations. Following mRNA sequencing, we integrated the TCGA database with known naringenin-related targets to identify overlapping genes, which were subsequently subjected to clinical significance analysis. The expression of these genes was confirmed at the protein and mRNA levels using Western blot (WB) and quantitative PCR (qPCR), respectively. In vivo experiments were conducted using an MHCC-97H xenograft model in nude mice, with histopathological examination of tumor sections performed using hematoxylin and eosin (H&E) staining. In vitro, naringenin demonstrated a potent inhibitory effect on the proliferation, invasion, and migration of MHCC-97H and Huh7 cells while exhibiting a pronounced pro-apoptotic impact on both cell lines. mRNA sequencing results revealed significant differential gene expression. Utilizing Venn diagrams, we identified key genes, including IGFBP3, PGF, CA9, AKR1C3, KLK1, and CHRNA7. We implicated signaling pathways such as the"Wnt signaling pathway"and"MAPK signaling pathway"as potentially critical in naringenin's anti-HCC activity. The clinical significance analysis revealed that CA9 and AKR1C3 were identified as autonomous prognostic variables for hepatocellular carcinoma (HCC), a conclusion supported by molecular docking investigations. The therapeutic promise of naringenin was further supported by its considerable reduction in tumor weight and volume shown in animal trials. This study shows that naringenin may regulate signaling pathways by targeting a series of genes: IGFBP3, PGF, CA9, AKR1C3, KLK1, and CHRNA7, resulting in the inhibition of tumor cell proliferation and metastasis, alongside the promotion of apoptosis.

Ovarian cancer is the most lethal tumor in female reproductive system, which seriously threatens the life and health of women. Our previous study found that LAMC3 was down-regulated in ovarian cancer tissues and correlated with ovarian cancer resistance. However, the effects of LAMC3 interference on drug resistance in carboplatin-resistant ovarian cancer cells remain unknown. In the present study, the effects of LAMC3 interference on drug resistance, cell proliferation, cycle, apoptosis, and ultrastructure of carboplatin-resistant ovarian cancer cells were examined. The results showed that LAMC3 interference lowered drug resistance of carboplatin-resistant ovarian cancer cells. The cell proliferation was inhibited and cell apoptosis was promoted in carboplatin-resistant ovarian cancer cells with LAMC3 interference. Besides, LAMC3 interference arrested cell cycle and affected cell ultrastructure of carboplatin-resistant ovarian cancer cells. Furthermore, transcriptome sequencing and WB verification results revealed cell cycle, autophagy, ferroptosis, lysosome related key pathway proteins may be involved in LAMC3 interference regulating drug resistance of carboplatin-resistant ovarian cancer cells. This study indicated LAMC3 interference reduced drug resistance of carboplatin-resistant ovarian cancer cells principal by affecting cell cycle, autophagy, ferroptosis, and lysosome. The present study provides a potential target for clinical treatment of drug resistance in ovarian cancer.