Target For Therapy Research Articles

Ultrasound nanodroplets loaded with Siglec-G siRNA and Fe3O4 activate macrophages and enhance phagocytosis for immunotherapy of triple-negative breast cancer

BackgroundThe progression of triple-negative breast cancer is shaped by both tumor cells and the surrounding tumor microenvironment (TME). Within the TME, tumor-associated macrophages (TAMs) represent a significant cell population and have emerged as a primary target for cancer therapy. As antigen-presenting cells within the innate immune system, macrophages are pivotal in tumor immunotherapy through their phagocytic functions. Due to the highly dynamic and heterogeneous nature of TAMs, re-polarizing them to the anti-tumor M1 phenotype can amplify anti-tumor effects and help mitigate the immunosuppressive TME.ResultsIn this study, we designed and constructed an ultrasound-responsive targeted nanodrug delivery system to deliver Siglec-G siRNA and Fe3O4, with perfluorohexane (PFH) at the core and mannose modified on the surface (referred to as MPFS@NDs). Siglec-G siRNA blocks the CD24/Siglec-G mediated “don’t eat me” phagocytosis inhibition pathway, activating macrophages, enhancing their phagocytic function, and improving antigen presentation, subsequently triggering anti-tumor immune responses. Fe3O4 repolarizes M2-TAMs to the anti-tumor M1 phenotype. Together, these components synergistically alleviate the immunosuppressive TME, and promote T cell activation, proliferation, and recruitment to tumor tissues, effectively inhibiting the growth of primary tumors and lung metastasis.ConclusionThis work suggests that activating macrophages and enhancing phagocytosis to remodel the TME could be an effective strategy for macrophage-based triple-negative breast cancer immunotherapy.

Potential VEGFR2 inhibitors for managing metastatic cervical cancer: insights from molecular dynamics and free energy landscape studies.

Metastatic cervical cancer, the advanced stage where the cancer spreads beyond the cervix to other parts of the body, poses significant treatment challenges and is associated with poor survival rates. Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), a critical angiogenic mediator, is upregulated in metastatic cervical cancer, driving the formation of new blood vessels that fuel tumor growth and spread, making it an attractive target for anti-angiogenic therapies aimed at halting metastasis. This study aims to determine the anti-angiogenic effects of natural compounds to identify new VEGFR2 inhibitors for managing metastatic cervical cancer. The potential effect of these compounds as VEGFR2 inhibitors at the structural level was assessed using various methods such as virtual screening, docking, MD simulations (1000ns), binding free energy calculations, and free energy landscape analysis. Four compounds, including IMPHY007574, IMPHY004129, IMPHY008783, and IMPHY004928, were found to be potential VEGFR2 inhibitors. Among the structures analyzed in the present work, IMPHY007574 revealed the highest binding stability with VEGFR2 and the most favorable interaction pattern, thus proving the possibility of its use as an effective anti-angiogenic compound. The other three compounds also demonstrated a reasonably good promise in VEGFR2 inhibition. These findings provide a foundation for developing novel therapeutic strategies for metastatic cervical cancer, potentially overcoming drug resistance and improving patient survival rates.

Unveiling hsa_circ_0007439: a novel suppressor of nasopharyngeal carcinoma via miR-556-5p/PTEN Axis

ObjectiveThere has been no explanation for the exact mechanism of circRNAs in nasopharyngeal carcinoma (NPC). Circ_0007439 was investigated in this study to determine its role and mechanism in NPC.MethodsTo identify circ_0007439, microRNA (miR)-556-5p, and PTEN mRNA in NPC tissues and cells, RT-qPCR was employed. PTEN protein was quantified using western blot analysis. The impact of circ_0007439 on cellular activities was assessed using CCK-8, colony formation, Transwell, and flow cytometry, in that order. The interaction of miR-556-5p with circ_0007439 or PTEN mRNA was confirmed through a dual luciferase reporter gene assay and RIP assay.Resultscirc_0007439 and PTEN levels were low in NPC tissues and cells, while miR-556-5p was highly expressed. NPC cells were inhibited in proliferation, migration, invasion, and anti-apoptosis when circ_0007439 was upregulated or miR-556-5p was reduced. The circ_0007439 molecule acted as a molecular sponge that inhibited miR-556-5p’s suppression of PTEN expression. Additionally, reduction of PTEN weakened the inhibitive effects of elevating circ_0007439 or reducing miR-556-5p on NPC cells.ConclusionCirc_0007439 mediates miR-556-5p/PTEN axis to inhibit NPC progression as an potential target for NPC therapy.

Nose-to-Brain Delivery of Biomimetic Nanoparticles for Glioblastoma Targeted Therapy.

Glioblastoma (GBM) is an extremely aggressive form of brain cancer that remains challenging to treat, especially owing to the lack of effective targeting and drug delivery concerns. Due to its anatomical advantages, the nose-to-brain strategy is an interesting route for drug delivery. Nanoengineering has provided technological tools and innovative strategies to overcome biotechnological limitations, which is promising for improving the effectiveness of conventional therapies. Herein, we designed a biomimetic multifunctional nanostructure produced by polymeric poly(d,l-lactic-co-glycolic) acid (PLGA) core loaded with Temozolomide (TMZ) coated with cell membrane isolated from glioma cancer cells. The developed nanostructures (NP-MB) were fully characterized, and their biological performance was investigated extensively. The results indicate that NP-MB could control TMZ release and promote TMZ permeation in the ex vivo nasal porcine mucosa. The higher cytotoxicity of NP-MB in different glioma cell lines, particularly against U251 cells, reinforces their potential for homotypic targeting. The chicken chorioallantoic membrane assay revealed a tumor size reduction and antiangiogenic activity. In vivo biodistribution studies showed that NP-MB effectively reaches the brain following nasal administration. These findings suggest that NP-MB holds promise as a biomimetic nanoplatform for effective targeting and homotypic recognition in GBM therapy with high potential for clinical translation.

A Phosphatidyl Conjugated Telomerase-Dependent Telomere-Targeting Nucleoside Demonstrates Colorectal Cancer Direct Killing and Immune Signaling

Telomerase and telomeres are crucial in cancer cell immortalization, making them key targets for anticancer therapies. Currently, 6-thio-dG (THIO) combined with the anti-PD-1 inhibitor Cemiplimab is under phase II clinical investigation (NCT05208944) in NSCLC patients resistant to prior immunotherapies. This study presents the design, synthesis, and evaluation of novel bimodular conjugate molecules combining telomere-targeting nucleoside analogs and phosphatidyl diglyceride groups. Among them, dihexanoyl-phosphatidyl-THIO (diC6-THIO) showed high anticancer activity with sub-µM EC50 values in vitro across various cancer cell lines. In mouse colorectal cancer models, diC6-THIO demonstrated strong anticancer effects alone and in combination with PD1/PD-L1 inhibitors. Administration of this compound resulted in the efficient formation of Telomere dysfunction Induced Foci (TIFs) in vitro, indicating an on-target, telomerase-mediated telomere-modifying mechanism of action for the molecule. Systemic treatment also activated CD4+ and CD8+ T cells while reducing regulatory T cells, indicating immune system enhancement. Notably, diC6-THIO exhibits an improved solubility profile while maintaining comparable anticancer properties, further supporting its potential as a promising therapeutic candidate. These findings highlight diC6-THIO as a promising telomere-targeting prodrug with dual effects on telomere modification and immune activation.

Platelet-derived extracellular vesicles induced through different activation pathways drive melanoma progression by functional and transcriptional changes

BackgroundBeyond their conventional roles in hemostasis and wound healing, platelets have been shown to facilitate hematogenous metastasis by interacting with cancer cells. Depending on the activation route, platelets also generate different platelet-derived extracellular vesicles (PEVs) that may educate cancer cells in the circulation or within the tumor microenvironment. We engaged different platelet-activating receptors, including glycoprotein VI and C-type lectin-like receptor 2, to generate a spectrum of PEV types. This allowed us to investigate the differential capacity of PEVs to alter cancer hallmark functions such as proliferation, invasion, and pro-angiogenic potential using melanoma as a model. Additionally, we analyzed changes in the cell transcriptomes and cancer EV profiles.MethodsTwo human melanoma cell lines (MV3 and A2058) with differential metastatic potential were studied in the 3D spheroid cultures. Human platelets were activated with collagen related peptide (CRP), fucoidan from Fucus vesiculosus (FFV), thrombin & collagen co-stimulus and Ca2+ ionophore, and PEVs were isolated by size-exclusion chromatography followed by ultrafiltration. Spheroids or cells were treated with PEVs and used in functional assays of proliferation, invasion, and endothelial tube formation as well as for the analysis of cancer EV production and their tetraspanin profiles. Differentially expressed genes and enriched signaling pathways in the PEV-treated spheroids were analyzed at 6 h and 24 h by RNA sequencing.ResultsAmong the studied PEVs, those generated by CRP and FFV exhibited the most pronounced effects on altering cancer hallmark functions. Specifically, CRP and FFV PEVs increased proliferation in both MV3 and A2058 spheroids. Distinct tetraspanin signatures of melanoma EVs were induced by all PEV types. While the PI3K-Akt and MAPK signaling pathways were activated by both CRP and FFV PEVs, they differently upregulated the immunomodulatory TGF-β and type-I interferon signaling pathways, respectively.ConclusionsOur study revealed both shared and distinct, cancer-promoting functions of PEVs, which contributed to the transcriptome and metastatic capabilities of the melanoma spheroids. Inhibiting the platelet receptors that modulate the PEVs’ cancer-promoting properties may open up new strategies for identifying promising treatment targets for cancer therapy.

Organic vs. Conventional Milk: Uncovering the Link to Antibiotic Resistance in Bacillus cereus sensu lato

Bacillus cereus sensu lato (B. cereus s.l.) comprises mesophilic and psychrotolerant bacteria commonly found in natural environments as well as in organic and conventional milk. Due to their potential toxigenicity and antibiotic resistance, these bacteria pose a significant threat to consumer health. Organic milk production, which prohibits the use of antibiotics and artificial additives, may influence the composition of microbiota between milk types. This study aimed to compare the antibiotic resistance profiles and enterotoxic potential of B. cereus s.l. isolates from organic and conventional milk. The results indicate that, although conventional milk contains on average 3 times fewer B. cereus s.l. isolates, it has 10–15% more resistant isolates to selected beta-lactams, macrolides, and aminoglycosides. Regarding drug resistance, 21% of B. cereus s.l. isolates were multidrug-resistant, and as many as 42% were non-susceptible to two classes of antibiotics. Even among the sensitive isolates, bacteria from conventional milk exhibited on average 2.05 times higher MICs (minimal inhibitory concentrations) for beta-lactams, 1.49 times higher for erythromycin, 1.38 times higher for vancomycin, and 1.38 times higher for azithromycin. Antibiotic resistance was mostly associated with the origin of the isolates. These findings underscore the need for ongoing monitoring of antibiotic resistance and enterotoxicity among opportunistic B. cereus s.l. strains, which may pose challenges for public health and veterinary medicine. The results highlight that selective pressure associated with antibiotic use can drive resistance development in bacteria that are not the primary targets of antimicrobial therapy.

Advances in research on malignant tumors and targeted agents for TOP2A (Review).

The DNA topoisomerase isoform topoisomerase IIα (TOP2A) is essential for the condensation and segregation of cellular mitotic chromosomes and the structural maintenance. It has been demonstrated that TOP2A is highly expressed in various malignancies, including lung adenocarcinoma (LUAD), hepatocellular carcinoma (HCC) and breast cancer (BC), associating with poor prognosis and aggressive tumor behavior. Additionally, TOP2A has emerged as a promising target for cancer therapy, with widespread clinical application of associated chemotherapeutic agents. The present study explored the impact of TOP2A on malignant tumor growth and the advancements in research on its targeted drugs. The fundamental mechanisms of TOP2A have been detailed, its specific roles in tumor cells are analyzed, and its potential as a biomarker for tumor prognosis and therapeutic targeting is highlighted. Additionally, the present review compiles findings from the latest clinical trials of relevant targeted agents, information on newly developed inhibitors, and discusses future research directions and clinical application strategies in cancer therapy, aiming to propose novel ideas and methods.

Influence of remnant lipoprotein particle cholesterol on non-target lesions progression in patients undergoing percutaneous coronary intervention

BackgroundLow-Density Lipoprotein Cholesterol (LDL-C) is the primary lipid therapy target for coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI). However, progression of coronary atherosclerosis occurs even LDL-C controlled well, some potentially important factors have been overlooked.ObjectiveThis study aims to elucidate the relationship between remnant lipoprotein particle cholesterol (RLP-C) and the progression of non-target lesions (NTLs) in patients with well-controlled lipid levels after PCI.MethodsThis retrospective study included 769 CAD patients who underwent PCI and followed up angiography within 6–24 months thereafter. Employing Multivariate Cox regression analysis, we assessed the correlation between RLP-C and NTLs progression. Based on the receiver operating characteristic curve analysis, we identified the optimal cutoff point for RLP-C, following which the patients were divided into two groups. Propensity score matching balanced confounding factors between groups, and Log-rank tests compared Kaplan–Meier curves for overall follow-up to assess NTLs progression.ResultsMultivariate Cox analysis revealed an independent association between RLP-C and NTLs progression when LDL-C was well-controlled. Additionally, the RLP-C level of 0.555 mmol/L was determined to be the best value for predicting NTLs progression. Following propensity score matching, Kaplan–Meier curves illustrated a significantly higher cumulative rate of NTLs progression in patients with RLP-C levels ≥0.555 mmol/L compared to the others (Log-rank P = 0.002). Elevated RLP-C levels were associated with high triglyceride concentrations, diabetes mellitus, and increased risk of revascularization.ConclusionsThis study illustrated the atherogenic impact of RLP-C in CAD patients. High RLP-C levels increased the risk of revascularization.

The Interplay Between Obesity and Aging in Breast Cancer and Regulatory Function of MicroRNAs in This Pathway.

Breast cancer (BC) is a significant contributor to cancer-related deaths in women, and it has complex connections with obesity and aging. This review explores the interaction between obesity and aging in relation to the development and progression of BC, focusing on the controlling role of microRNAs (miRNAs). Obesity, characterized by excess adipose tissue, contributes to a proinflammatory environment and metabolic dysregulation, which are important in tumor development. Aging, associated with cellular senescence and systemic changes, further exacerbates these conditions. miRNAs, small noncoding RNAs that regulate gene expression, play key roles in these processes, impacting pathways involved in cell proliferation, apoptosis, and cancer metastasis, either as tumor suppressors or oncogenes. Importantly, specific miRNAs are implicated in mediating the impact of obesity and aging on BC. Exploring the regulatory networks controlled by miRNAs provides valuable information on new targets for therapy and predictive markers, demonstrating the potential for using miRNA-based interventions to treat BC in obese and elderly individuals. This review emphasizes the importance of integrated research strategies to understand the complex connections between obesity, aging, and miRNA regulation in BC.

Regulation of AUF1 alternative splicing by hnRNPA1 and SRSF2 modulate the sensitivity of ovarian cancer cells to cisplatin.

Clarification of cisplatin resistance may provide new targets for therapy in cisplatin resistant ovarian cancer. The current study aims to explore involvement of isoforms of AU-rich element RNA-binding protein 1 (AUF1) in cisplatin resistance in ovarian cancer. The cancer stem cell-like features were analyzed using colony formation assay, tumor sphere formation assay and nude mouse xenograft experiments. AUF1 isoforms expression was analyzed using immunoblotting, qRT-PCR, and immunohistochemistry. RIP and Biotin pulldown was used to analyze the interaction of SRSF2 and hnRNPA1 with AUF1 transcript. Transcriptome regulated by AUF1 isoforms was analyzed by RNA-seq. The current study demonstrated differential expression of AUF1 isoforms in cisplatin sensitive and resistant ovarian cancer tissues and cells. P37 isoform promoted proliferation, while p45 isoform enhanced responsiveness of ovarian cancer cells to cisplatin. the clonal formation capacity of the cells, and the restoration of p45 expression reduced the capacity with cisplatin treatment. The competitive binding of phosphorylated hnRNPA1 and O-GlcNAc-modified SRSF2 on AUF1 exon 2 and exon 7 regulated the alternative splicing of AUF1. The competitive binding of phosphorylated hnRNPA1 and O-GlcNAc modified SRSF2 on exon 2 and exon 7 regulated the alternative splicing of AUF1 and subsequent isoform expression. P37 isoform played a "cancer promoter" role, p42 and p45, especially p45 played a "cancer suppressor" role in ovarian cancer. This study provides a new target for exploring the drug resistance mechanism of ovarian cancer.

Exploring Ion Channel Magnetic Pharmacology: Are Magnetic Cues a Viable Alternative to Ion Channel Drugs?

We explore the potential of using magnetic cues as a novel approach to modulating ion channel expression, which could provide an alternative to traditional pharmacological interventions. Ion channels are crucial targets for pharmacological therapies, and ongoing research in this field continues to introduce new methods for treating various diseases. However, the efficacy of ion channel drugs is often compromised by issues such as target selectivity, leading to side effects, toxicity, and complex drug interactions. These challenges, along with problems like drug resistance and difficulties in crossing biological barriers, highlight the need for innovative strategies. In this context, the proposed use of magnetic cues to modulate ion channel expression may offer a promising solution to address these limitations, potentially improving the safety and effectiveness of treatments, particularly for long-term use. Key developments in this area are reviewed, the relationships between changes in ion channel expression and magnetic fields are summarized, knowledge gaps are identified, and central issues relevant to future research are discussed.

Designing hypothesis of substituted naphthyridines as anti-HIV agent: A QSAR Approach

HIV-1 Integrase is a validated drug target for anti-HIV therapy. It is an essential enzyme required for replication of the AIDS-virus. 1,3,4-oxadiazole substituted naphthyridine derivatives act against HIV integrase and thus have the potential to become a part of anti-HIV drug regime. In present study, we have carried out QSAR study of 1,3,4-oxadiazole substituted naphthyridine derivatives. Stepwise multiple linear regression analysis was performed to derive QSAR models and was evaluated for statistical significance and predictive power. The best QSAR model was selected for anti-HIV activity, having correlation coefficient (R) = 0.862, standard error of estimation (SEE) = 0.271 and cross validated squared correlation coefficient (Q2) = 0.676. The QSAR model indicates that shape index, partition coefficient and solvent accessible surface area play an important role in the anti-HIV activities of 1,3,4-oxadiazole substituted naphthyridine derivatives. The results of the present study may be useful in designing more potent analogues.

TAM-Derived Exosomes Promote EMT by Upregulating lncRNA MIR4435-2HG in Head and Neck Cancer.

This study aimed to investigate the impact of tumor-associated macrophage (TAM)-derived exosomes on epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC) and the underlying mechanisms involved. Exosomes were isolated and characterized using transmission electron microscopy, nanoparticle size analysis, and western blotting. The effect on EMT in HNSCC cells was assessed using wound healing, transwell invasion, and EMT marker assays. Bioinformatics analysis was conducted to predict key TAM-related long noncoding RNAs and evaluate their relationship with EMT in HNSCC. We observed that treatment with TAM-derived conditioned medium (CM) promoted EMT in HNSCC cells. Within the CM, we observed abundant exosomes that were taken up by HNSCC cells. Furthermore, TAM-derived exosomes promoted EMT in HNSCC cells. Mechanistically, high MIR4435-2HG expression levels were observed in TAM-derived exosomes and in HNSCC cells after treatment with TAM-derived exosomes. Notably, high MIR4435-2HG expression levels may be closely related to molecules that promote EMT in HNSCC. TAM-derived exosomes promote EMT in HNSCC cells by upregulating MIR4435-2HG expression, suggesting that MIR4435-2HG is a candidate target for HNSCC therapy.

Canine Adipose-Derived Mesenchymal Stromal Cells Reduce Cell Viability and Migration of Metastatic Canine Oral Melanoma Cell Lines In Vitro

Canine oral melanoma (COM) is a promising target for immunomodulatory therapies aimed at enhancing the immune system’s antitumor response. Given that adipose-derived mesenchymal stem cells (Ad-MSCs) possess immunomodulatory properties through cytokine release, we hypothesized that co-culturing Ad-MSCs and canine peripheral blood mononuclear cells (PBMCs) could stimulate interleukin (IL) production against melanoma cell lines (MCCLs) and help identify therapeutic targets. This study evaluated IL-2, IL-8, and IL-12 expressions in co-culture with MCCL, Ad-MSCs, and PBMCs and assessed the relationship between gene expression, cell viability, and migration. Using four experimental groups in a Transwell insert system to separate cell types, we found that Ad-MSCs can reduce MCCL migration and viability, though the effect may vary depending on each cell line’s susceptibility. Furthermore, Ad-MSCs modified IL expression profiles in co-cultured cells. Our findings suggest that Ad-MSCs could have therapeutic potential for COM by inhibiting cell migration and reducing viability. However, deeper insights into Ad-MSC interactions with the tumor microenvironment and melanoma-specific factors will be essential to optimize therapeutic efficacy.

The potential of cognitive remediation therapy for improving the communication capabilities of adults with schizophrenia and other psychotic spectrum disorders.

Impairment in aspects of communication is a core diagnostic feature of schizophrenia and other psychotic spectrum disorders. These communication difficulties inhibit participation in a range of daily activities and affect relationships and quality of life. There has been little research focussed on communication outcomes in relation to cognitive remediation therapy within this population. Data collected as part of an implementation trial of the Computerised Interactive Remediation of Cognition and Thinking Skills (CIRCuiTS) program provided an opportunity to examine the potential for changes in communication capability to support activities of daily living. To survey changes in ratings of aspects of communication capability of adults with schizophrenia who completed the CIRCuiTS cognitive remediation therapy program. Thirty adults with schizophrenia and other psychotic spectrum disorders completed the CIRCuiTS therapy program as part of an implementation trial in 2018 and 2019. Most participants were male (93%) and inpatients at Bloomfield Hospital (73%) in Orange, New South Wales. Ratings on the Adaptive Behaviour Assessment System, Third Edition (ABAS3) were returned before and after completion of the CIRCuiTS program. The magnitude of changes in ABAS3 indices, the Communication scale and Functional academics scales were assessed between time points. Participants' mean adaptive functioning indices prior to the CIRCuiTS program were in the extremely low range (∼second percentile) and increased to the low range (∼seventh percentile) following this therapy, achieving large mean effect sizes (Cohen's d = 0.92-1.24). Significant improvements in functioning were observed on the ABAS3 Communication and Functional Academics scales, with large mean effect sizes on both scales (Cohen's d = 1.09 and 0.99 respectively). Improvements in ratings occurred on items including initiating conversations, talking and listening over longer periods, explaining more complex information, using lists and reminders and a schedule or diary, completing written forms and personal money management. Most participants were observed to make gains in aspects of communication. The results point to these aspects of communication as potential future targets for therapy with people with schizophrenia and other psychotic spectrum disorders. This study highlights the value and role of Speech and Language Therapists in cognitive remediation therapy. Further research seems warranted with participants with a broader range of demographic, clinical and functional capabilities, that controls for the effects of medications and other therapeutic interventions and utilises a more comprehensive assessment of communication. What is already known on the subject People with schizophrenia and other psychotic spectrum disorders experience impairment in cognitive functioning as well as communication capability that affects their daily functioning and quality of life. Cognitive remediation therapy has been shown to improve aspects of the daily functioning of people with schizophrenia and other psychotic spectrum disorders and is recommended in international treatment guidelines. However, very little research has been conducted to investigate the effectiveness of this therapy in addressing communication difficulties. What this paper adds to existing knowledge The present study found participants with schizophrenia and other psychotic spectrum disorders made significant improvements in important aspects of communication after completing the Computerised Interactive Remediation of Cognition and Thinking Skills cognitive remediation therapy program. The results point to the potential of cognitive remediation therapy as a therapeutic approach that is likely to improve communication capability. What are the potential or actual clinical implications of this work? Cognitive remediation therapy is likely to be an important treatment for improving the communication capabilities of people with severe mental illness. This relatively new area of clinical practice and research highlights the value and potential of speech and language therapy in improving the communication capabilities of people with schizophrenia and other psychotic spectrum disorders.

Vitexin mitigates oxidative stress, mitochondrial damage, pyroptosis and regulates small nucleolar RNA host gene 1/DNA methyltransferase 1/microRNA-495 axis in sepsis-associated acute lung injury.

This study examinedvitexin's effect on sepsis-induced acute lung injury. We used network pharmacology and in vivo and in vitro experiments were performed to elucidate vitexin's role in preventing pyroptosis and regulating small nucleolar RNA host gene 1 (SNHG1)/DNA methyltransferase 1 (DNMT1)/microRNA-495 (miR-495 axis. We developed an acute lung injury model using C57BL/6 mice and MLE-12 cells. Through a combination of network pharmacology and in vitro screening, vitexin was identified as the most promising anti-inflammatory compound. Multiple techniques such as western blotting, real-time PCR, Hematoxylin and eosin staining, immunohistochemistry, andTUNEL assay were used. Additionally, immunofluorescence, DCFDA and TMRE staining, flow cytometry, methylation-specific PCR, and gene transfection techniques were performed to elucidate vitexin's potential targets and underlying mechanisms. Vitexin treatment significantly reduced lung damage, neutrophil infiltration, and inflammation while improving tight junction integrity. In LPS-treated RAW264.7 macrophages and a septic mouse BALF-induced MLE-12 cell injury model, vitexin demonstrated anti-inflammatory effects, promoted M2 macrophage polarization, and enhanced regenerative markers. It also decreased oxidative stress, mitigated apoptosis and pyroptosis, and improved mitochondrial function. Our research uncovered a novel epigenetic regulatory mechanism involving lncRNA SNHG1, DNMT1, and miR-495. Vitexin's ability to reduce inflammation, counteract oxidative stress, and modulate epigenetic processes. These findings underscore the promising role of vitexin as a treatment for ALI generated by sepsis. The SNHG1/miR-495 axis, which has been identified, represents a new target for future therapies in acute lung injury.

Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors.

With the emergence of the precision medicine era, targeting specific proteins has emerged as a pivotal breakthrough in tumor diagnosis and treatment. Apurinic/apyrimidinic Endonuclease 1 (APE1) is a multifunctional protein that plays a crucial role in DNA repair and cellular redox regulation. This article comprehensively explores the fundamental mechanisms of APE1 as a multifunctional enzyme in biology, with particular emphasis on its potential significance in disease diagnosis and strategies for tumor treatment. Firstly, this article meticulously analyzes the intricate biological functions of APE1 at a molecular level, establishing a solid theoretical foundation for subsequent research endeavors. In terms of diagnostic applications, the presence of APE1 can be detected in patient serum samples, biopsy tissues, and through cellular in situ testing. The precise detection methods enable changes in APE1 levels to serve as reliable biomarkers for predicting tumor occurrence, progression, and patient prognosis. Moreover, this article focuses on elucidating the potential role of APE1 in tumor treatment by exploring various inhibitors, including nucleic acid-based inhibitors and small molecule drug inhibitors categories, and revealing their unique advantages in disrupting DNA repair function and modulating oxidative-reduction activity. Finally, the article provides an outlook on future research directions for APE1 while acknowledging major technical difficulties and clinical challenges that need to be overcome despite its immense potential as a target for tumor therapy.

Transcription factors and hormone receptors: Sex‑specific targets for cancer therapy (Review)

Transcription factors and hormone receptors: Sex‑specific targets for cancer therapy (Review)

Advances towards potential cancer therapeutics targeting Hippo signaling.

Decades of research into the Hippo signaling pathway have greatly advanced our understanding of its roles in organ growth, tissue regeneration, and tumorigenesis. The Hippo pathway is frequently dysregulated in human cancers and is recognized as a prominent cancer signaling pathway. Hence, the Hippo pathway represents an ideal molecular target for cancer therapies. This review will highlight recent advancements in targeting the Hippo pathway for cancer treatment and discuss the potential opportunities for developing new therapeutic modalities.