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Background: The Arp2/3 complex is a key regulator of tumor metastasis, and targeting its subunits offers potential for anti-metastatic therapy. However, the expression profiles, prognostic relevance, and diagnostic value of its subunits across cancers remain poorly understood. This study aims to investigate the clinical relevance of Arp2/3 complex subunits, particularly ARPC1A, in pan-cancer, and to further analyze the potential biological mechanisms of ARPC1A, as well as its association with immune infiltration and chemotherapy drug sensitivity. Methods: To explore the differential expression of Arp2/3 complex subunits and their clinical relevance across cancers, we analyzed data from TCGA and GTEx databases. The relationship between ARPC1A and immune infiltration, as well as its interactions with functional proteins, was examined using the TCPA and TIMER2.0 databases. Gene Set Enrichment Analysis (GSEA) was performed to identify ARPC1A-associated signaling pathways. Chemotherapy drug sensitivity correlated with ARPC1A expression was assessed using CellMiner, GDSC, and CTRP databases. The effect of ARPC1A on c-Myc expression was validated by quantitative PCR (qPCR) and Western blot. Finally, the biological role of ARPC1A in non-small cell lung cancer (NSCLC) cells was further validated using CCK-8, EdU incorporation, colony formation, and Transwell assays. Results: The Arp2/3 complex subunits, particularly ARPC1A, are frequently overexpressed in a majority of cancers, correlating with poor prognostic outcomes and demonstrating significant diagnostic utility. Copy number variations may play a role in the dysregulation of Arp2/3 complex subunit expression. The small molecule X4.5.dianilinophthalimide has shown promise as a targeted therapeutic agent in a pan-cancer context. Functional predictions indicate that ARPC1A is implicated in oxidative phosphorylation pathways and cell proliferation-related signaling pathways, including those mediated by MYC, with ASNS potentially acting as an upstream regulator. Furthermore, ARPC1A has been implicated in the resistance to chemotherapy drugs, including gefitinib. In vitro experiments corroborate that ARPC1A may enhance malignant phenotypes in non-small cell lung cancer (NSCLC) cells through the regulation of c-Myc expression. Conclusion: Our study offers novel insights into targeting Arp2/3 complex subunits as an anti-cancer strategy and underscores the potential of ARPC1A as a novel biomarker for tumor diagnosis, prognosis, and the prediction of immune therapy responses. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, characterized by frequent recurrence, metastasis, and poor survival outcomes despite chemotherapy-based treatments. This study aims to investigate the mechanisms by which Traditional Chinese Medicine (TCM) modulates the tumor immune microenvironment in TNBC, utilizing CiteSpace and bioinformatics analysis. Methods: We employed CiteSpace to analyze treatment hotspots and key TCM formulations, followed by bioinformatics analysis to identify the main active components, targets, associated pathways, and their clinical implications in TNBC treatment. Results: CiteSpace analysis highlighted key TCM formulations, including Sanhuang Decoction. Network pharmacology identified major bioactive components such as Mutatochrome, Physcion diglucoside, Procyanidin B-5,3'-O-gallate, gallic acid-3-O-(6'-O-galloyl)-glucoside, and isomucronulatol-7,2'-di-O-glucosiole, with core targets including Mitogen-Activated Protein Kinase 1 (MAPK1), Janus Kinase 2 (JAK2), and Lymphocyte-specific protein tyrosine kinase (LCK). These targets were found to be involved in immune regulation, particularly the modulation of CD8+ and CD4+ T cells. Additionally, core targets were associated with improved recurrence-free survival (RFS) and overall survival (OS) in TNBC patients. Conclusion: The therapeutic effects of TCM in TNBC primarily involve immune modulation within the tumor microenvironment, particularly through the regulation of CD8+ and CD4+ T cells. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) are intricate, web-like formations composed of DNA, histones, and antimicrobial proteins, released by neutrophils. These structures participate in a wide array of physiological and pathological activities, including immune rheumatic diseases and damage to target organs. Recently, the connection between NETs and cancer has garnered significant attention. Within the tumor microenvironment and metabolism, NETs exhibit multifaceted roles, such as promoting the proliferation and migration of tumor cells, influencing redox balance, triggering angiogenesis, and driving metabolic reprogramming. This review offers a comprehensive analysis of the link between NETs and tumor metabolism, emphasizing areas that remain underexplored. These include the interaction of NETs with tumor mitochondria, their effect on redox states within tumors, their involvement in metabolic reprogramming, and their contribution to angiogenesis in tumors. Such insights lay a theoretical foundation for a deeper understanding of the role of NETs in cancer development. Moreover, the review also delves into potential therapeutic strategies that target NETs and suggests future research directions, offering new perspectives on the treatment of cancer and other related diseases. [ABSTRACT FROM AUTHOR]

Background: Accurate detection of human epidermal growth factor receptor 2 (HER2) gene amplification via fluorescence in situ hybridization (FISH) is necessary to determine HER2 status. Although many attempts have been made to increase the consistency of the results, the actual situation still needs to be determined. To investigate the latest interlaboratory variability of HER2 FISH testing for breast cancer, a multicenter proficiency-testing ring study was conducted in China. Methods: A total of ten samples, each exhibiting distinct HER2 signal patterns and genetic heterogeneity, were distributed to 169 laboratories for HER2 FISH analysis. Data comprising both the results of the tests and feedback from questionnaires were compiled for comprehensive evaluation. Results: The overall agreement among the participating laboratories was substantial to almost perfect, with a Fleiss' kappa value of 0.765–0.911. However, it is important to note that cases with characteristics of HER2 signals near the critical cutoff range or with genetic heterogeneity showed lower congruence, poorer reproducibility, and higher variability (Fleiss' kappa: 0.582). Our questionnaire showed that 52.2% (86/168) of the participants did not perform validation after their operation procedures or interpretation criteria were updated, and 75.6% (121/160) of the participants did not establish standard interpretation procedures. Since these laboratories showed worse performance (P < 0.05), the lack of validation and interpretation procedures was speculated to be the possible underlying cause. Conclusions: This study presents the latest landscape of interlaboratory variability and accuracy of HER2 FISH testing in China and highlights potential causes for the variability. Despite many years of effort, the standardization of HER2 status determination still has a long way to go. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy (RT) is an important means of local treatment of solid tumors, and radioresistance is the main reason for RT failure for tumors, especially pancreatic cancer (PC). It is urgent to distinguish key genes and mechanisms of radioresistance in PC. Methods: We acquired the data from The Cancer Genome Atlas (TCGA), obtained the gene modules associated with radioresistance by weighted gene coexpression network analysis (WGCNA), and identified differentially expressed genes (DEGs) between normal and tumor samples. Radioresistance-related genes (RRRGs) were determined with the intersection of WGCNA and DEGs. The hub RRRGs associated with prognosis were distinguished by the least absolute shrinkage and selection operator (LASSO) regression. We established a risk score model using multivariate Cox regression. Immune cell infiltration and drug sensitivity were evaluated through the CIBERSORT algorithm and the "OncoPredict" software package, respectively. The association of the key gene RIC3 and PC clinical features was verified in public databases, and its biological behaviors were explored in vitro. Results: The intersection of DEGs and WGCNA confirmed 14 RRRGs, then six hub RRRGs were identified using LASSO. A key four genes (DUSP4, ADORA2B, SCGB2A1, and RIC3) risk score model was constructed and proved to be capable of independently estimating the prognosis of PC. There is no significant difference between risk score groups in various immune cell infiltration and response to immunotherapy. Although the low-risk group seemed to exhibit greater sensitivity to antitumor drugs, the four drugs (5-fluorouracil [5-FU], leucovorin, irinotecan, and oxaliplatin) currently used for PC patients had no statistical difference for the low- and high- group. The overexpression of RIC3 had a synergy effect with irradiation on inhibited malignant biological properties of PC cells, which was verified by detecting the proliferation ability, apoptosis rate, cell cycle distribution, and migration ability of PANC-1 cells. Conclusions: We herein presented signature genes correlated with radioresistance in PC and established a risk score model competent in estimating patients' clinical outcomes and response to antitumor drugs. The above evidence could contribute to comprehending the mechanisms of radioresistance and identifying the underlying therapy targeting. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is toxic and corrosive at high concentrations and pressures. Adsorption methods are suitable due to their low energy consumption, low cost, and high efficiency. Synthesis and optimization of structural and operational parameters of specific molecularly imprinted polymers (MIPs) Nano adsorbents for H2S gas adsorption carried out using response surface design methodology. The optimal polymerization conditions of MIPs included 16 experiments. The amounts of template molecules (1–5 mmol), cross-linker (5–20 mmol), functional monomer (2–12mmol), porogen solution (acetonitrile/ethyl acetate v/v 1–9%), elution solution (acetic acid/methanol 20/80) and initiator (25–100 mg) were optimized using Taguchi method of experimental design. We used the SRK equation of state for the molar mass of the gas on a fixed bed with a height of 400 mm and an inner diameter of 10 mm. Finally, physical properties were determined using FTIR, XRD, FE-SEM, and BET. Statistical analysis showed that the signal-to-noise ratio between the template molecule, cross-linker, and functional monomer was 2:15:2.5, and the optimal adsorption value occurred at a volume ratio of acetonitrile/ethyl acetate of 1:9 and initiator of 75. In this study, the surface is MIPs@H2S. Variance analysis showed that all Nano-adsorbents followed a second-order model, temperature and adsorbent dosage were the most critical variables in the process, and the equilibrium adsorption of all Nano-adsorbents followed the Langmuir isotherm and second-order synthesis model. The regeneration study highlighted that the Nano-adsorbent is a promising adsorbent with high reversibility and stability for H2S gas. Finally, the selectivity results of specific adsorption of H2S gas by CO2/H2S/CH4 gas mixture of MIPs@H2S were significantly higher than that of Non-imprinted polymers (NIPs) Nano adsorbent. [ABSTRACT FROM AUTHOR]

Cisplatin resistance is one of the major causes of treatment failure in head and neck squamous cell carcinoma (HNSCC). There is an urgent need to uncover the underlying mechanism for developing effective treatment strategies. A quantitative proteomics assay was used to identify differential proteins in cisplatin-resistant cells. Mitochondrial topoisomerase I (TOP1MT) localization was determined using laser confocal microscopy and nucleocytoplasmic separation assay. Chromatin immunoprecipitation sequencing, dual-luciferase reporter assay, and RNA immunoprecipitation were used to identify the interaction between pseudogenes, miRNAs, and real genes. In vivo experiments verified the interaction between TOP1MT and pseudogenes on cisplatin resistance. TOP1MT was identified as a driving factor of cisplatin resistance in vitro, in vivo, and in HNSCC patients. Moreover, TOP1MT exceptionally translocated to the nucleus in cisplatin-resistant HNSCC cells in a signal peptide–dependent manner. Nuclear TOP1MT (nTOP1MT) transcriptionally regulated the mitochondrial functional pseudogene MTATP6P1, which bound to miR-137 and miR-491-5p as a competing endogenous RNA (ceRNA) and promoted the expression of MTATP6. An increase in MTATP6 enhanced mitochondrial oxidative phosphorylation (OXPHOS), which conferred cisplatin resistance in HNSCC. Our findings revealed that nTOP1MT transcriptionally activated MTAPT6P1 and increased MTATP6 expression via ceRNA, which facilitated OXPHOS and cisplatin resistance. These results provide novel insight for overcoming cisplatin resistance in HNSCC. [ABSTRACT FROM AUTHOR]

Cancer remains a major global health challenge, with the persistence of cancer stem cells (CSCs) contributing to treatment resistance and relapse. Despite advancements in cancer therapy, targeting CSCs presents a significant hurdle. Non-thermal gas plasma, also known as CAP, represents an innovative cancer treatment. It has recently gained attention for its often found to be selective, immunogenic, and potent anti-cancer properties. CAP is composed of a collection of transient, high-energy, and physically and chemically active entities, such as reactive oxygen species (ROS). It is acknowledged that the latter are responsible for a major portion of biomedical CAP effects. The dynamic interplay of CAP-derived ROS and other components contributes to the unique and versatile properties of CAP, enabling it to interact with biological systems and elicit various therapeutic effects, including its potential in cancer treatment. While CAP has shown promise in various cancer types, its application against CSCs is relatively unexplored. This review assesses the potential of CAP as a therapeutic strategy for targeting CSCs, focusing on its ability to regulate cellular states and achieve redox homeostasis. This is done by providing an overview of CSC characteristics and demonstrating recent findings on CAP's efficacy in targeting these cells. By contributing insights into the unique attributes of CSCs and the potential of CAP, this work contributes to an advanced understanding of innovative oncology strategies. [ABSTRACT FROM AUTHOR]

The current study explores the effects of microwave treatment at varying wattage and durations on the phytoconstituents, antioxidant status, anti-nutritional factors (ANFs), and metabolite profiles of de-oiled rice bran. The total phenolics and flavonoids showed both increases and decreases depending on specific microwave parameters, while flavonol content consistently increased across all treated groups compared to the control. The DPPH and ABTS free radical scavenging activity, total antioxidant capacity, FRAP, CUPRAC, metal chelating activity, and ascorbic acid content were enhanced in most of the microwaved samples; however, longer microwave exposure at higher wattage led to their reduction. A treatment-specific decrease in ANFs, including condensed tannins, oxalates, and phytates, was observed. HRMS-based untargeted metabolomics identified a diverse range of primary and secondary metabolites, which clustered in a group-specific manner, indicating notable group-wise metabolite variations. Analysis of discriminating metabolites revealed no significant differences in the overall levels of phenolics, flavonoids, vitamins and cofactors, sugars, amino acids, terpenoids, fatty acids, and their derivatives among the treated groups compared to the control; however, several individual metabolites within these metabolite classes differed significantly. These findings suggest that optimized microwaving of de-oiled rice bran can enhance phytochemicals and antioxidants while improving the metabolite profile. [ABSTRACT FROM AUTHOR]

Background: Hoarding disorder (HD) is characterized by a compulsion to collect belongings, and to experience significant distress when parting from them. HD is often misdiagnosed for several reasons. These include patient and family lack of recognition that it is a psychiatric disorder and professionals' lack of relevant expertise with it. This study evaluates the ability of a supervised machine learning (ML) model to match the diagnostic skills of psychiatrists when presented with equivalent information pertinent to symptoms of HD. Methods: Five hundred online participants were randomly recruited and completed the Hoarding Rating Scale-Self Report (HRS-SR) and the Generalized Anxiety Disorder 7-item (GAD-7) scale. Responses to the questionnaires were read by an ML model. Responses to the HRS-SR were then converted into anonymized, random-equivalent texts. Each of these individual texts was presented in random order to two experienced psychiatrists who were independently asked for a provisional diagnosis - e.g.; the presence or absence of HD. In case of disagreement between the two assessors, a third psychiatrist broke the tie. A decision tree classification model was employed to predict clinical HD using self-report data from two psychological tests, the HRS-SR and GAD-7. The target variable was whether a participant had clinical HD, while the predictive variables were the continuous scores from the HRS-SR and GAD-7 tests. The model's performance was evaluated using a confusion matrix, which compared the observed diagnoses with the predicted diagnoses to assess accuracy. Results: According to the psychiatrists, approximately 10% of the participants fulfilled DSM-5 diagnostic criteria for HD. 93% of the clinician-identified cases were identified by the ML model based on HRS-SR and GAD-7 scores. A decision tree plot model demonstrated that about 60% of the cases could be detected by the HRS-SR alone while the rest required a combination of HRS-SR and GAD-7 scores. ML evaluation metrics showed satisfactory performance, with a Matthews Correlation Coefficient of 55%; Area Under Curve (AUC), 79%; a Negative Predictive Value of 76%; and a False Negative Rate of 24%. Conclusions: Study findings strongly suggest that ML can, in the future, play a significant role in the risk assessment of psychiatric disorders prior to face-to-face consultation. By using AI to scan big data questionnaire responses, wait time for seriously ill patients can be substantially cut, and prognoses substantially improved. [ABSTRACT FROM AUTHOR]

Background: Breast cancer's complex transcriptional landscape requires an improved understanding of cellular diversity to identify effective treatments. The study of genetic variations among breast cancer subtypes at single‐cell resolution has potential to deepen our insights into cancer progression. Methods: In this study, we amalgamate single‐cell RNA sequencing data from patient tumours and matched lymph metastasis, reduction mammoplasties, breast cancer patient‐derived xenografts (PDXs), PDX‐derived organoids (PDXOs), and cell lines resulting in a diverse dataset of 117 samples with 506 719 total cells. These samples encompass hormone receptor positive (HR+), human epidermal growth factor receptor 2 positive (HER2+), and triple‐negative breast cancer (TNBC) subtypes, including isogenic model pairs. Herein, we delineated similarities and distinctions across models and patient samples and explore therapeutic drug efficacy based on subtype proportions. Results: PDX models more closely resemble patient samples in terms of tumour heterogeneity and cell cycle characteristics when compared with TNBC cell lines. Acquired drug resistance was associated with an increase in basal‐like cell proportions within TNBC PDX tumours as defined with SCSubtype and TNBCtype cell typing predictors. All patient samples contained a mixture of subtypes; compared to primary tumours HR+ lymph node metastases had lower proportions of HER2‐Enriched cells. PDXOs exhibited differences in metabolic‐related transcripts compared to PDX tumours. Correlative analyses of cytotoxic drugs on PDX cells identified therapeutic efficacy was based on subtype proportion. Conclusions: We present a substantial multimodel dataset, a dynamic approach to cell‐wise sample annotation, and a comprehensive interrogation of models within systems of human breast cancer. This analysis and reference will facilitate informed decision‐making in preclinical research and therapeutic development through its elucidation of model limitations, subtype‐specific insights and novel targetable pathways. Key points: Patient‐derived xenografts models more closely resemble patient samples in tumour heterogeneity and cell cycle characteristics when compared with cell lines.3D organoid models exhibit differences in metabolic profiles compared to their in vivo counterparts.A valuable multimodel reference dataset that can be useful in elucidating model differences and novel targetable pathways. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of dementia affecting about 40 million people around the world. The number of people living with this ailment is expected to triple in the next 50 years due to the aging population and the lack of any effective treatment. In this work we have synthesized a group of three hybrid caffeic acid and a resveratrol derivatives (1-4), and we have tested their ability to inhibit in vitro the enzymatic activity of the beta-site amyloid precursor protein cleaving protein enzyme 1 (BACE 1) and acetylcholinesterase (AChE). The inhibitory activity was compared to that of parent compounds caffeic acid and resveratrol, as well as related chlorogenic acid. Clinically tested LY2811376 and tacrine were used as positive controls. All three caffeic acid derivatives displayed better inhibitory activity than parent caffeic acid and chlorogenic acid. In particular, the in vitro IC50 for compound 4 against BACE 1 fell in the nanomolar range (69 ± 5 nM), comparable or better than LY2811376 (173 ± 8 nM) which reached Phase I clinical trials against AD as a BACE 1 inhibitor. On the other hand, compound 3 showed a remarkable AChE inhibitory potency in the low micromolar range (1.93 ± 0.16 μM). Molecular docking was performed to gain valuable insights into the interactions between compounds 1-4 and the active sites of both BACE 1 and AChE. Calculated binding affinities generally correlated well with experimental in vitro inhibition. Experimental and molecular docking results validated the proposed drug design, since the most active compounds 3 and 4 established interactions with relevant amino acid residues of the BACE 1 and AChE active sites through the different pharmacophore features of the hybrid structures. Overall, the results presented in this work could potentially have important implications in the rational design of compounds with potential anti-AD properties. [ABSTRACT FROM AUTHOR]

Introduction: We previously documented the beneficial effects of rice bran oil (RBO) on cardiac function and atherogenic cardiometabolic factors in men with coronary artery disease. Therefore, the existing evidence in this area aims to be expanded by investigating the impact of adding RBO to a daily standard diet on emerging insulin resistance surrogate markers, lipid peroxidation, antioxidant status, and metabolic disturbances in individuals with metabolic syndrome (MetSyn) through an open-label controlled trial. Methods: A total of 50 overweight/obese adults (mean body mass index (BMI) = 31.08 kg/m2) with at least 3 MetSyn components were randomly allocated to either the control group, which received a standard diet plan, or the intervention group, which was supplemented with 30 g/d RBO for 8 weeks. BMI, MetSyn components, metabolic score for insulin resistance (METS-IR), triglyceride‒glucose‒BMI (TyG‒BMI), malondialdehyde (MDA), total antioxidant capacity (TAC), and plasma polyphenol levels were measured before and after this open-label trial. Results: Analysis of covariance (ANCOVA) adjusted for baseline values revealed that, compared with patients who received only a standard diet, those who were supplemented with 30 g/d RBO presented significantly lower total cholesterol (P value = 0.005; effect size (ES):-0.92), LDL-cholesterol (P value = 0.048; ES:-0.62), fasting blood glucose (P value = 0.014; ES:-0.77), MDA (P value = 0.002; ES: -1.01), METS-IR (P value < 0.001; ES: -1.24), and TyG-BMI (P value = 0.007; ES:-0.85) after 8 weeks. Additionally, RBO consumption resulted in significantly higher levels of HDL-C (P value = 0.004; ES:0.94) and TAC (P value < 0.0001; ES:2.05). However, no significant changes were noted in BMI, waist circumference, serum triglycerides, plasma polyphenols, or blood pressure. Conclusion: Although the current findings suggest that the hypocholesterolemic, antihyperglycemic, and antioxidative effects of 30 g/d RBO seem to be promising for MetSyn patients, they should be considered preliminary. Therefore, further well-designed clinical trials with larger sample sizes and longer durations are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: To explore the role of polycystic kidney and hepatic disease 1-like 1 (PKHD1L1) in lung adenocarcinoma (LUAD). Methods: Bioinformatics tools were utilized to examine the clinical profile of PKHD1L1 and chromobox protein homolog 7 (CBX7) in LUAD. The Cell Counting Kit-8, colony formation, terminal deoxynucleotidyl transferase dUTP nick end labeling, Transwell, and wound-healing assays were carried out to assess the proliferative, apoptotic, invasive, and migrative capacities of the cells. Furthermore, the interrelation between PKHD1L1 and CBX7 was validated using a co-immunoprecipitation assay. A LUAD mice model was constructed by subcutaneous injection of A549 cells. Finally, immunohistochemical staining was performed to evaluate CBX7 and Ki67 expression. Results: PKHD1L1 was downregulated in LUAD and predicted dismal outcomes in patients with LUAD. PKHD1L1 upregulation repressed the proliferative, invasive, and migrative capabilities of A549 cells and exacerbated the apoptotic rate. Additionally, PKHD1L1 may bind to CBX7 and positively modulate CBX7 expression. CBX7 deletion partly abrogated the effects of PKHD1L1 upregulation on the cellular biological activities in A549 cells. Furthermore, the PKHD1L1/CBX7 axis regulates the Hippo signaling pathway in A549 cells. PKHD1L1 restricted tumor growth in LUAD xenograft mice; this was partly abolished by CBX7 knockdown. Conclusion: PKHD1L1 can hinder LUAD progression by regulating CBX7-mediated Hippo signaling. [ABSTRACT FROM AUTHOR]

Aggregate-induced emission luminogens (AIEgens) have been widely used in biological imaging, chemical sensing, and disease treatments. The rational design and construction of AIEgens have received considerable research interests during the last few years. Herein, molecular docking-aided AIEgen design has been reasonably proposed and AIEgen TBQZY with excellent 1O2 generation ability has been synthesized. The newly developed TBQZY could efficiently kill S. epidermidis and methicillin-resistant S. epidermidis (MRSE) by tightly binding to bacteria and triggering the accumulation of 1O2 in bacteria. TBQZY specifically regulated the immune system and polarized macrophages from M1 to M2 to accelerate the elimination of biofilm in vivo. In addition, healing acceleration was observed in chronic wounds treated with TBQZY, and side effects were negligible. Meanwhile, TBQZY had extraordinary potential for combating drug-resistant bacteria in the clinical setting. This research not only provided new concepts for the design of AIEgens, but also shed some lights on the discovery of drugs against drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess ethnic inequalities in the coverage and utilization of cancer screening services among women in Peru. Methods: Data from the 2017–2023 Demographic and Family Health Survey in Peru were analyzed to evaluate ethnic disparities in screening coverage for breast and cervical cancer, including clinical breast examination (CBE), Pap smear test (PST), and mammography. Measures such as the GINI coefficient and Slope Index of Inequality (SII) were used to quantify coverage and utilization disparities among ethnic groups. Results: The study included 70,454 women aged 30–69. Among women aged 40–69, 48.31% underwent CBE, 84.06% received PST, and 41.69% underwent mammography. It was found inequalities in coverage for any cancer screening (GINI: 0.10), mammography (GINI: 0.21), CBE (GINI: 0.19), and PST (GINI: 0.06), in 25 Peruvian regions. These inequalities were more pronounced in regions with larger populations of Quechua, Aymara, and Afro-Peruvian women. In rural areas, Quechua or Aymara women (SII: -0.83, -0.95, and − 0.69, respectively) and Afro-Peruvian women (SII: -0.80, -0.92, and − 0.58, respectively) experienced heightened inequalities in the uptake of CBE, mammography, and PST, respectively. Like Quechua or Aymara women (SII: -0.50, SII: -0.52, and SII: -0.50, respectively) and Afro-Peruvian women (SII: -0.50, SII: -0.58, and SII: -0.44, respectively) with only a primary education. Conclusion: Ethnic inequalities affect breast and cervical cancer screening coverage across regions in Peru. In Quechua, Aymara, and Afro-Peruvian women the uptake of mammography, CBE, and PST was less frequently than their white or mestizo counterparts. These inequalities are attributed to sociodemographic conditions such as lower education levels and residence in rural or non-capital areas. [ABSTRACT FROM AUTHOR]

Motivation Recent advances in DNA sequencing technologies have allowed the detailed characterization of genomes in large cohorts of tumors, highlighting their extreme heterogeneity, with no two tumors sharing the same complement of somatic mutations. Such heterogeneity hinders our ability to identify somatic mutations important for the disease, including mutations that determine clinically relevant phenotypes (e.g. cancer subtypes). Several tools have been developed to identify somatic mutations related to cancer phenotypes. However, such tools identify correlations between somatic mutations and cancer phenotypes, with no guarantee of highlighting causal relations. Results We describe ALLSTAR , a novel tool to infer reliable causal relations between somatic mutations and cancer phenotypes. ALLSTAR identifies reliable causal rules highlighting combinations of somatic mutations with the highest impact in terms of average effect on the phenotype. While we prove that the underlying computational problem is NP-hard, we develop a branch-and-bound approach that employs protein–protein interaction networks and novel bounds for pruning the search space, while properly correcting for multiple hypothesis testing. Our extensive experimental evaluation on synthetic data shows that our tool is able to identify reliable causal relations in large cancer cohorts. Moreover, the reliable causal rules identified by our tool in cancer data show that our approach identifies several somatic mutations known to be relevant for cancer phenotypes as well as novel biologically meaningful relations. Availability and implementation Code, data, and scripts to reproduce the experiments available at https://github.com/VandinLab/ALLSTAR. [ABSTRACT FROM AUTHOR]

High-grade B-cell lymphoma (HGBCL), the subtype of non-Hodgkin lymphoma, to be relapsed or refractory in patients after initial therapy or salvage chemotherapy. Dual dysregulation of MYC and BCL2 is one of the important pathogenic mechanisms. Thus, combined targeting of MYC and BCL2 appears to be a promising strategy. Dihydroorotate dehydrogenase (DHODH) is the fourth rate-limiting enzyme for the de novo biosynthesis of pyrimidine. It has been shown to be a potential therapeutic target for multiple diseases. In this study, the DHODH inhibitor brequinar exhibited growth inhibition, cell cycle blockade, and apoptosis promotion in HGBCL cell lines with MYC and BCL2 rearrangements. The combination of brequinar and BCL2 inhibitors venetoclax had a synergistic inhibitory effect on the survival of DHL cells through different pathways. Venetoclax could upregulate MCL-1 and MYC expression, which has been reported as a resistance mechanism of BCL2 inhibitors. Brequinar downregulated MCL-1 and MYC, which could potentially overcome drug resistance to venetoclax in HGBCL cells. Furthermore, brequinar could downregulate a broad range of genes, including ribosome biosynthesis genes, which might contribute to its anti-tumor effects. In vivo studies demonstrated synergetic tumor growth inhibition in xenograft models with brequinar and venetoclax combination treatment. These results provide preliminary evidence for the rational combination of DHODH and BCL2 blockade in HGBCL with abnormal MYC and BCL2. [ABSTRACT FROM AUTHOR]

CD24 is a glycosylphosphatidylinositol-anchored protein that is expressed in a wide range of tissues and cell types. It is involved in a variety of physiological and pathological processes, including cell adhesion, migration, differentiation, and apoptosis. Additionally, CD24 has been studied extensively in the context of cancer, where it has been found to play a role in tumor growth, invasion, and metastasis. In recent years, there has been growing interest in CD24 as a potential therapeutic target for cancer treatment. This review summarizes the current knowledge of CD24, including its structure, function, and its role in cancer. Finally, we provide insights into potential clinical application of CD24 and discuss possible approaches for the development of targeted cancer therapies. [ABSTRACT FROM AUTHOR]

Polysaccharopeptide (PSP) is a potential active component in traditional Chinese medicine because of its anticancer effects on a variety of cancer cells and as immune enhancers of the immune system. Previous studies on the role of PSP in breast cancer have been limited, and the mechanism has not been clarified. This study is based on network pharmacology and molecular docking technology to predict the possible target of PSP treatment of breast cancer, and use experiments to verify the effect and mechanism of PSP on breast cancer. In this study, 287 PSP targets were obtained using SwissTargetPrediction database and PharmMapper database, and 183 breast cancer targets were obtained using DisGenNET database. By intersections of PSP targets and breast cancer targets, a total of 10 intersections were obtained. GO functional enrichment, KEGG pathway enrichment and molecular docking of these 10 target genes were performed to obtain the potential targets of PSP on breast cancer. In vitro experiments, we found that PSP significantly inhibited the proliferation and induced apoptosis of breast cancer cell lines MDA-MB-231, SUM-159 and MCF-7. Western Blot results showed that PSP could down-regulate the expression of p-JAK2 and p-STAT3 proteins. Similarly, the results of in vivo experiments showed that PSP can directly inhibit the tumor of MDA-MB-231 tumor-bearing mice, and the mechanism of action is mainly to inhibit the JAK2-STAT3 pathway. The above results were consistent with the results of network pharmacology, which provides a scientific basis for the clinical application of PSP in breast cancer patients. [ABSTRACT FROM AUTHOR]

To take better advantage of buckwheat polyphenols, processings including extrusion, steam explosion, microwave, roasting, superheated steam, ultrasound and enzymolysis treatment were applied to buckwheat bran to release more bioactive polyphenols. Polyphenols were extracted and characterized, and rutin was identified as the predominant compound. To further improve the properties of buckwheat polyphenols, rutin was selected as the target polyphenol and a formation of its ionic cross-linking complex was proposed. Rutin was loaded on chitooligosaccharide as Rutin-COS with tripolyphosphate (TPP) as crosslinking agent, whose molecular structure and properties were investigated. Results showed that all processing significantly increased (p < 0.05) the content of buckwheat polyphenols, up to 1.83-fold increase. The composition of polyphenols was altered, and their antioxidant (up to 15% increase) and antibacterial activities were significantly enhanced (p < 0.05). Among all the processings, extrusion and superheated steam showed the best effect. For Rutin-COS complex, the encapsulation efficiency was as high as 74.77% with the mass ratio of rutin and COS at 1:8. The structure of Rutin-COS was stabilized by hydrogen bonding between aromatic rings of rutin and amino and hydroxy groups of COS in the network formed by COS and TPP. Compared to free rutin, Rutin-COS presented better thermal stability and water solubility. The antioxidant and antibacterial activities of Rutin-COS were also significantly improved (p < 0.05) due to the molecular interaction between rutin and COS. The combination of processing and complexation strategy for buckwheat polyphenols in this work provided new approaches to take better advantages of polyphenols of cereal foods. [ABSTRACT FROM AUTHOR]

Pigmented rice, especially black rice, is gaining popularity as it is rich in antioxidants such as anthocyanins and γ-oryzanol. At present, knowledge about temporal control of biosynthesis and accumulation of antioxidants during grain development is limited. To address this, the accumulation patterns of anthocyanins and γ-oryzanol were assessed in two distinct black rice genotypes over the course of grain development, and the expression of known regulatory genes for anthocyanin biosynthesis was examined. The results indicated that total γ-oryzanol content increased continuously throughout grain development, while total anthocyanins peaked at dough stage (15 to 21 days after flowering) followed by a decline until grain maturity in both genotypes. However, the rate of decrease in anthocyanin content differed between genotypes, and a more prominent decline in cyanidin 3-O-glucoside (C3G) relative to peonidin 3-O-glucoside (P3G) was observed for both. Anthocyanin content was closely linked with the expression of key regulatory genes in the MBW (MYB-bHLH-WD40) complex. This improved knowledge of the genotype-specific biosynthesis (anthocyanins only) and accumulation patterns of anthocyanins and γ-oryzanol can inform subsequent research efforts to increase concentrations of these key antioxidants in black rice grains. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its propensity for metastasis and poor prognosis. TNBC evades the body's immune system recognition and attack through various mechanisms, including the Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. This pathway, characterized by heightened activity in numerous solid tumors, exhibits pronounced activation in specific TNBC subtypes. Consequently, targeting the JAK2/STAT3 signaling pathway emerges as a promising and precise therapeutic strategy for TNBC. The signal transduction cascade of the JAK2/STAT3 pathway predominantly involves receptor tyrosine kinases, the tyrosine kinase JAK2, and the transcription factor STAT3. Ongoing preclinical studies and clinical research are actively investigating this pathway as a potential therapeutic target for TNBC treatment. This article comprehensively reviews preclinical and clinical investigations into TNBC treatment by targeting the JAK2/STAT3 signaling pathway using small molecule compounds. The review explores the role of the JAK2/STAT3 pathway in TNBC therapeutics, evaluating the benefits and limitations of active inhibitors and proteolysis-targeting chimeras in TNBC treatment. The aim is to facilitate the development of novel small-molecule compounds that target TNBC effectively. Ultimately, this work seeks to contribute to enhancing therapeutic efficacy for patients with TNBC. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer (BC) is the leading cause of cancer-related deaths among women, with triple-negative breast cancer (TNBC) representing one of the most aggressive and treatment-resistant subtypes. In this study, we aimed to evaluate the antitumor potential of C14 and P8 molecules in both TNBC and radioresistant TNBC cells. These compounds were chosen for their ability to stabilize the complex formed by the overactivated form of K-Ras4BG13D and its membrane transporter (PDE6δ). Methods: The antitumor potential of C14 and P8 was assessed using TNBC cell lines, MDA-MB-231, and the radioresistant derivative MDA-MB-231RR, both carrying the K-Ras4B>G13D mutation. We investigated the compounds' effects on K-Ras signaling pathways, cell viability, and tumor growth in vivo. Results: Western blotting analysis determined the negative impact of C14 and P8 on the activation of mutant K-Ras signaling pathways in MDA-MB-231 and MDA-MB-231RR cells. Proliferation assays demonstrated their efficacy as cytotoxic agents against K-RasG13D mutant cancer cells and in inducing apoptosis. Clonogenic assays proven their ability to inhibit TNBC and radioresistant TNBC cell clonogenicity. In In vivo studies, C14 and P8 inhibited tumor growth and reduced proliferation, angiogenesis, and cell cycle progression markers. Discussion: These findings suggest that C14 and P8 could serve as promising adjuvant treatments for TNBC, particularly for non-responders to standard therapies. By targeting overactivated K-Ras and its membrane transporter, these compounds offer potential therapeutic benefits against TNBC, including its radioresistant form. Further research and clinical trials are warranted to validate their efficacy and safety as novel TNBC treatments. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by extensive intratumoral heterogeneity, high metastasis, and chemoresistance, leading to poor clinical outcomes. Despite progress, the mechanistic basis of these aggressive behaviors remains poorly understood. Using single-cell and spatial transcriptome analysis, here we discovered basal epithelial subpopulations located within the stroma that exhibit chemoresistance characteristics. The subpopulations are defined by distinct signature genes that show a frequent gain in copy number and exhibit an activated epithelial-to-mesenchymal transition program. A subset of these genes can accurately predict chemotherapy response and are associated with poor prognosis. Interestingly, among these genes, elevated ITGB1 participates in enhancing intercellular signaling while ACTN1 confers a survival advantage to foster chemoresistance. Furthermore, by subjecting the transcriptional signatures to drug repurposing analysis, we find that chemoresistant tumors may benefit from distinct inhibitors in treatment-naive versus post-NAC patients. These findings shed light on the mechanistic basis of chemoresistance while providing the best-in-class biomarker to predict chemotherapy response and alternate therapeutic avenues for improved management of TNBC patients resistant to chemotherapy. Synopsis: Chemotherapy resistance is a key challenge in Triple-Negative Breast Cancer (TNBC). Combining single-cell, spatial and bulk transcriptome analysis with machine learning, we uncovered mechanisms of TNBC chemoresistance that provide biomarkers for chemotherapy response and novel avenues for therapy. Basal-epithelial subpopulations underlie chemoresistance in TNBC. Chemoresistance-associated basal-epithelial cells reside in close vicinity to stromal compartments within TNBC tumors and engage in enhanced intercellular communication. These subpopulations are defined by distinct signature genes that provide the best-in-class predictive biomarker of chemotherapy response. Drug repurposing analysis identified existing FDA-approved drugs that may benefit chemoresistant patients. Chemotherapy resistance is a key challenge in Triple-Negative Breast Cancer (TNBC). Combining single-cell, spatial and bulk transcriptome analysis with machine learning, we uncovered mechanisms of TNBC chemoresistance that provide biomarkers for chemotherapy response and novel avenues for therapy. [ABSTRACT FROM AUTHOR]

Plant pathogenic fungi are the main causative agents of diseases associated with significant productivity and economic losses in agriculture. Thus, the rapid and early identification of plant pathogens is essential for directing effective management and control strategies for diseases to prevent or reduce their severity. The objective of this study was to characterize and discriminate different species of plant pathogenic fungi using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and chemometric analysis. Five fungal species of the genera Colletotrichum, Fusarium, Macrophomina, Neoscytalidium, and Pseudofusicoccum, isolated from agricultural crops, fruit trees, and ornamental plants, were used. Discrimination of the fungal samples was conducted using different fingerprint regions of ATR-FTIR spectra and partial least squares-discriminant analysis (PLS-DA). The results showed that regions I (800–1800 cm−1) and III (800–1800 and 2800–2990 cm−1) can be used as spectroscopic biomarkers for the differentiation and classification of fungi by ATR-FTIR, as PLS-DA revealed adjustment quality and satisfactory prediction, generating values of R2 = 0.96 and Q2 = 0.60 in cross-validation. The most relevant infrared absorption bands in the separation of classes were the C–O stretching vibrations, bending of C-H bonds, amide III bands, and C–C stretching. This method can be an important diagnostic tool in the agricultural sector for disease management, considering that it can provide biological differentiation and/or similarity between fungal species. [ABSTRACT FROM AUTHOR]

Background: Cancer stem-like cell is a key barrier for therapeutic resistance and metastasis in various cancers, including breast cancer, yet the underlying mechanisms are still elusive. Through a genome-wide lncRNA expression profiling, we identified that LINC00115 is robustly upregulated in chemoresistant breast cancer stem-like cells (BCSCs). Methods: LncRNA microarray assay was performed to document abundance changes of lncRNAs in paclitaxel (PTX)-resistant MDA-MB-231 BCSC (ALDH+) and non-BCSC (ALDH−). RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to determine the binding proteins of LINC00115. The clinical significance of the LINC00115 pathway was examined in TNBC metastatic lymph node tissues. The biological function of LINC00115 was investigated through gain- and loss-of-function studies. The molecular mechanism was explored through RNA sequencing, mass spectrometry, and the CRISPR/Cas9-knockout system. The therapeutic potential of LINC00115 was examined through xenograft animal models. Results: LINC00115 functions as a scaffold lncRNA to link SETDB1 and PLK3, leading to enhanced SETDB1 methylation of PLK3 at both K106 and K200 in drug-resistant BCSC. PLK3 methylation decreases PLK3 phosphorylation of HIF1α and thereby increases HIF1α stability. HIF1α, in turn, upregulates ALKBH5 to reduce m6A modification of LINC00115, resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1α are prognostic for clinical triple-negative breast cancers. Conclusions: Our findings uncover LINC00115 as a critical regulator of BCSC and highlight targeting LINC00115 and SETDB1 as a potential therapeutic strategy for chemotherapeutic resistant breast cancer. [ABSTRACT FROM AUTHOR]

DUSP4 is a biomarker of esophageal squamous cell carcinoma (ESCC), which is responsible for the prognosis in ESCC. However, the underlying mechanism of DUSP4-regulated ESCC carcinogenesis is unknown. As a negative regulator of JNK, DUSP4 can inhibit autophagy, which contributes to tumorigenesis. This study aimed to explore the role of autophagy in DUSP4-regulated ESCC carcinogenesis. Our results showed that DUSP4 overexpression inhibited autophagy and promoted LSD1 protein expression in ESCC cells, while DUSP4 silencing showed the opposite effects. However, DUSP4 overexpression and silencing did not affect LSD1 mRNA expression. But the regulatory ability of DUSP4 overexpression on autophagy, death level, and LSD1 protein was reversed by rapamycin. In addition, DUSP4 overexpression inhibited JNK and Bcl2 phosphorylation and the dissociation of Bcl2-Beclin1 complex, while DUSP4 silencing promoted JNK and Bcl2 phosphorylation. Moreover, the regulatory ability of DUSP4 overexpression on autophagy, death, and LSD1 protein was reversed by JNK activator anisomycin. The xenograft assays also showed that DUSP4 overexpression-promoted ESCC tumor growth in vivo and LC3II and LSD1 protein expression in tumor tissues were reversed by rapamycin or anisomycin. Overall, DUSP4 inhibits Bcl2-Beclin1-autophagy signal transduction through the negative regulation of JNK, thus suppressing autophagic death and the autophagic degradation of LSD1 in ESCC, by which DUSP4 promotes ESCC carcinogenesis. [ABSTRACT FROM AUTHOR]

Background: Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5–16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. Methods: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV–ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. Results: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan–Meier survival curve. However, this effect was evident only in males. Conclusions: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (NAC) is the standard of care for patients with early-stage triple negative breast cancers (TNBC). However, more than half of TNBC patients do not achieve a pathological complete response (pCR) after NAC, and residual cancer burden (RCB) is associated with dismal long-term prognosis. Understanding the mechanisms underlying differential treatment outcomes is therefore critical to limit RCB and improve NAC efficiency. Methods: Human TNBC cell lines and patient-derived organoids were used in combination with real-time metabolic assays to evaluate the effect of NAC (paclitaxel and epirubicin) on tumor cell metabolism, in particular glycolysis. Diagnostic biopsies (pre-NAC) from patients with early TNBC were analyzed by bulk RNA-sequencing to evaluate the predictive value of a glycolysis-related gene signature. Results: Paclitaxel induced a consistent metabolic switch to glycolysis, correlated with a reduced mitochondrial oxidative metabolism, in TNBC cells. In pre-NAC diagnostic biopsies from TNBC patients, glycolysis was found to be upregulated in non-responders. Furthermore, glycolysis inhibition greatly improved response to NAC in TNBC organoid models. Conclusions: Our study pinpoints a metabolic adaptation to glycolysis as a mechanism driving resistance to NAC in TNBC. Our data pave the way for the use of glycolysis-related genes as predictive biomarkers for NAC response, as well as the development of inhibitors to overcome this glycolysis-driven resistance to NAC in human TNBC patients. [ABSTRACT FROM AUTHOR]

The incidence and mortality of lung cancer in women are rising, with both increasing by 124% between 2003 and 2019. The main risk factor for lung cancer is tobacco use, but indoor radon gas exposure is one of the leading causes in nonsmokers. The most recent evidence demonstrates that multiple factors can make women more susceptible to harm from these risk factors or carcinogens. For this consensus statement, the Association for Lung Cancer Research in Women (ICAPEM) invited a group of lung cancer experts to perform a detailed gender-based analysis of lung cancer. Clinically, female patients have different lung cancer profiles, and most actionable driver alterations are more prevalent in women, particularly in never-smokers. Additionally, the impact of certain therapies seems to be different. In the future, it will be necessary to carry out specific studies to improve the understanding of the role of certain biomarkers and gender in the prognosis and evolution of lung cancer. [ABSTRACT FROM AUTHOR]

Background: The crucial role of STOML2 in tumor progression has been documented recently in various cancers. Previous studies have shown that STOML2 promoted cancer cell proliferation, but the underlying mechanism is not fully illustrated. Methods and results: The expression and clinical relevance of STOML2 in pan-cancer was analyzed by TIMER2 web platform in pan-cancer. The prognostic significance of STOML2 in HCC was evaluated utilizing KM curve and a nomogram model. Signaling pathways associated with STOML2 expression were discovered by GSEA. CCK-8 assay was performed to evaluate the proliferative capacity of HCC cells after manipulating STOML2 expression. Flow cytometry was utilized to analyze cell cycle progression. Results indicated that increased STOML2 expression in HCC linked to unfavorable clinical outcomes. Cell cycle and cell division related terms were enriched under conditions of elevated STOML2 expression via GSEA analysis. A notable decrease in cell proliferation was observed in MHCC97H with STOML2 knocked-down, accompanied by G1-phase arrest, up-regulation of p21, down-regulation of CyclinD1 and its regulatory factor MYC, while STOML2 overexpression in Huh7 showed the opposite results. These results indicated that STOML2 was responsible for HCC proliferation by regulating the expression level of MYC/cyclin D1 and p21. Furthermore, an inverse correlation was found between STOML2 expression and 5-FU sensitivity. Conclusions: STOML2 promotes cell cycle progression in HCC which is associated with activation of MYC/CyclinD1/p21 pathway, and modulates the response of HCC to 5-FU. [ABSTRACT FROM AUTHOR]

Background: Medulloblastoma (MB) patients with MYC oncogene amplification or overexpression exhibit extremely poor prognoses and therapy resistance. However, MYC itself has been one of the most challenging targets for cancer treatment. Here, we identify a novel marinopyrrole natural derivative, MP1, that shows desirable anti-MYC and anti-cancer activities in MB. Methods: In this study, using MYC-amplified (Group 3) and non-MYC amplified MB cell lines in vitro and in vivo, we evaluated anti-cancer efficacies and molecular mechanism(s) of MP1. Results: MP1 significantly suppressed MB cell growth and sphere counts and induced G2 cell cycle arrest and apoptosis in a MYC-dependent manner. Mechanistically, MP1 strongly downregulated the expression of MYC protein. Our results with RNA-seq revealed that MP1 significantly modulated global gene expression and inhibited MYC-associated transcriptional targets including translation/mTOR targets. In addition, MP1 inhibited MYC-target metabolism, leading to declined energy levels. The combination of MP1 with an FDA-approved mTOR inhibitor temsirolimus synergistically inhibited MB cell growth/survival by downregulating the expression of MYC and mTOR signaling components. Our results further showed that as single agents, both MP1 and temsirolimus, were able to significantly inhibit tumor growth and MYC expression in subcutaneously or orthotopically MYC-amplified MB bearing mice. In combination, there were further anti-MB effects on the tumor growth and MYC expression in mice. Conclusion: These preclinical findings highlight the promise of marinopyrrole MP1 as a novel MYC inhibition approach for MYC-amplified MB. [ABSTRACT FROM AUTHOR]

Curing cancer has always presented a formidable clinical challenge. Among the various treatment strategies for combating tumors, the combination of targeted therapy and immunotherapy has recently assumed significant importance. Regrettably, while targeted drugs demonstrate efficiency in the early stages of cancer treatment, patients inevitably develop drug resistance as treatment progresses, ultimately resulting in treatment failure and death. Currently, effective countermeasures against drug-resistant tumor cells remain limited, and research into the mechanisms of drug resistance continues to garner profound interest. The current understanding of drug resistance primarily focuses on two aspects: intrinsic or primary drug resistance, and acquired or secondary drug resistance. Further explanations delve into molecular mechanisms, including acquired gene mutations, epigenetic modifications, the plasticity of cancer stem cells, and the mediation of exosomes. With the advancement of single-cell analysis, our understanding of these potential mechanisms has become more comprehensive. In this review, we initially explore classical signaling pathways related to tumorigenesis and cancer cell progression. Additionally, we summarize recent findings regarding gene mutations and modifications related to drug resistance in cancer. Finally, we discuss the plasticity of cancer stem cells and the latest research on exosome-mediated tumor drug resistance. [ABSTRACT FROM AUTHOR]

In the process of preparation of imprinted polymers, the introduction of external fields, such as magnetic field, microwave field, ultrasonic field, electric field and high‐energy radiation field, to improve the structure and performance of imprinted polymers has become a novel direction of the development of imprinted polymers, and relevant reports have been increasing in recent years. However, the progress of research on field‐induced imprinted polymers has not been summarized and noticed, resulting in few perspective on the shortcomings and future development of the field‐induced effect which in turn has hindered its further study. Considering this, we firstly introduced the development history and mechanism of imprinted polymers. Then, the field‐induced effects on the mechanism of polymerization and the structure and performances of imprinted polymers were summarized in the order of magnetic field‐induced imprinted polymers, microwave field‐induced imprinted polymers, ultrasonic field‐induced imprinted polymers, electric field‐induced imprinted polymers and high‐energy radiation field‐induced polymers. Significantly, the challenges to the development of field‐induced imprinted polymers were presented, and the development trends of field‐induced imprinted polymers were proposed with the aim to build the bridge for future FI‐IPs research and shed the light on the application research of the field‐induced imprinted polymers. [ABSTRACT FROM AUTHOR]

Approximately, 15% of global breast cancer cases are diagnosed as triple-negative breast cancer (TNBC), identified as the most aggressive subtype due to the simultaneous absence of estrogen receptor, progesterone receptor, and HER2. This characteristic renders TNBC highly aggressive and challenging to treat, as it excludes the use of effective drugs such as hormone therapy and anti-HER2 agents. In this review, we explore standard therapies and recent emerging approaches for TNBC, including PARP inhibitors, immune checkpoint inhibitors, PI3K/AKT pathway inhibitors, and cytotoxin-conjugated antibodies. The mechanism of action of these drugs and their utilization in clinical practice is explained in a pragmatic and prospective manner, contextualized within the current landscape of standard therapies for this pathology. These advancements present a promising frontier for tailored interventions with the potential to significantly improve outcomes for TNBC patients. Interestingly, while TNBC poses a complex challenge, it also serves as a paradigm and an opportunity for translational research and innovative therapies in the field of oncology. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) is a cellular plasticity program critical for embryonic development and tissue regeneration, and aberrant EMT is associated with disease including cancer. The high degree of plasticity in the mammary epithelium is reflected in extensive heterogeneity among breast cancers. Here, we have analyzed RNA-sequencing data from three different mammary epithelial cell line-derived EMT models and identified a robust mammary EMT gene expression signature that separates breast cancers into distinct subgroups. Most strikingly, the basal-like breast cancers form two subgroups displaying partial-EMT and post-EMT gene expression patterns. We present evidence that key EMT-associated transcription factors play distinct roles at different stages of EMT in mammary epithelial cells. [ABSTRACT FROM AUTHOR]

Background: The role of inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) is well established. Lyn, a member of the nonreceptor protein tyrosine kinase Src family, has been reported to modulate inflammatory signaling pathways. Methods: Lyn expression was assessed in kidney biopsies of 11 patients with diabetic kidney disease (DKD) and in kidney tissues of streptozotocin (STZ)-induced DKD mice. 102 recruited T2DM patients were divided into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Twenty-one healthy volunteers were recruited as a control group. Clinical data, blood and urine samples of all individuals were collected for analysis. Results: Lyn expression was augmented in the kidneys of DKD patients and STZ-induced diabetic mice. Compared with control and normoalbuminuria groups, both mRNA and protein expression of Lyn in peripheral blood mononuclear cells (PBMCs) in the macroalbuminuria group were significantly increased (p < .05). Elevated Lyn levels were independently related to urine albumin/urine creatinine ratio and were positively associated with key inflammatory factors, namely interleukin-1β, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Additionally, Lyn exhibited a noteworthy connection with renal tubular injury indicators, specifically urinary neutrophil gelatinase-associated lipocalin and urinary retinol binding protein. ROC curve analysis showed that Lyn could predict albuminuria in diabetic patients with an area under the curve of 0.844 (95% CI: 0.764-0.924). Conclusion: Lyn levels in PBMCs exhibited a positive correlation with the severity of albuminuria, renal tubular damage, and inflammatory responses. Hence, Lyn may be a compelling candidate for predicting albuminuria levels in diabetes. [ABSTRACT FROM AUTHOR]

Background: ARID1A, a tumor suppressor gene encoding BAF250, a protein participating in chromatin remodeling, is frequently mutated in endometrium-related malignancies, including ovarian or uterine clear cell carcinoma (CCC) and endometrioid carcinoma (EMCA). However, how ARID1A mutations alter downstream signaling to promote tumor development is yet to be established. Methods: We used RNA-sequencing (RNA-seq) to explore transcriptomic changes in isogenic human endometrial epithelial cells after deleting ARID1A. Chromatin immunoprecipitation sequencing (ChIP-seq) was employed to assess the active or repressive histone marks on DUSP4 promoter and regulatory regions. We validated our findings using genetically engineered murine endometroid carcinoma models, human endometroid carcinoma tissues, and in silico approaches. Results: RNA-seq revealed the downregulation of the MAPK phosphatase dual-specificity phosphatase 4 (DUSP4) in ARID1A-deficient cells. ChIP-seq demonstrated decreased histone acetylation marks (H3K27Ac, H3K9Ac) on DUSP4 regulatory regions as one of the causes for DUSP4 downregulation in ARID1A-deficient cells. Ectopic DUSP4 expression decreased cell proliferation, and pharmacologically inhibiting the MAPK pathway significantly mitigated tumor formation in vivo. Conclusions: Our findings suggest that ARID1A protein transcriptionally modulates DUSP4 expression by remodeling chromatin, subsequently inactivating the MAPK pathway, leading to tumor suppression. The ARID1A-DUSP4-MAPK axis may be further considered for developing targeted therapies against ARID1A-mutated cancers. [ABSTRACT FROM AUTHOR]

An accurate method was developed to analyze trans- and cis-resveratrols in peanut oils using stable isotope dilution ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The linearity ranges for trans- and cis-resveratrols were determined to be 0.2–100 μg/kg, exhibiting satisfactory correlation coefficients (r2trans > 0.9998, r2cis > 0.9996). The limits of detection (LOD) and the limit of quantification (LOQ) were determined to be 0.06 and 0.2 μg/kg, respectively. The recoveries of spiked oil samples ranged from 94.9 to 105.0%, with relative standard deviations (RSDs) less than 6.5% (intra-day) and 7.6% (inter-day). This method was successfully applied to quantify the contents of trans- and cis-resveratrols in commercial peanut oils, ranging from 8.7 to 55.5 μg/kg and 0 to 11.0 μg/kg, respectively. The results demonstrated that the developed method is simple, reliable, and robust for quantifying trans- and cis-resveratrols in peanut oils. Consequently, it exhibits great potential for evaluating adulteration and ensuring the quality control of peanut oils. [ABSTRACT FROM AUTHOR]

Background Resistance to endocrine therapy in estrogen receptor–positive (ER+) breast cancer remains a significant clinical problem. Riluzole is FDA-approved for the treatment of amyotrophic lateral sclerosis. A benzothiazole-based glutamate release inhibitor with several context-dependent mechanism(s) of action, riluzole has shown antitumor activity in multiple malignancies, including melanoma, glioblastoma, and breast cancer. We previously reported that the acquisition of tamoxifen resistance in a cellular model of invasive lobular breast cancer is accompanied by the upregulation of GRM mRNA expression and growth inhibition by riluzole. Methods We tested the ability of riluzole to reduce cell growth, alone and in combination with endocrine therapy, in a diverse set of ER+ invasive ductal and lobular breast cancer–derived cell lines, primary breast tumor explant cultures, and the estrogen-independent, ESR1 -mutated invasive lobular breast cancer patient-derived xenograft model HCI-013EI. Results Single-agent riluzole suppressed the growth of ER+ invasive ductal and lobular breast cancer cell lines in vitro, inducing a histologic subtype-associated cell cycle arrest (G0-G1 for ductal, G2-M for lobular). Riluzole induced apoptosis and ferroptosis and reduced phosphorylation of multiple prosurvival signaling molecules, including Akt/mTOR, CREB, and Fak/Src family kinases. Riluzole, in combination with either fulvestrant or 4-hydroxytamoxifen, additively suppressed ER+ breast cancer cell growth in vitro. Single-agent riluzole significantly inhibited HCI-013EI patient-derived xenograft growth in vivo, and the combination of riluzole plus fulvestrant significantly reduced proliferation in ex vivo primary breast tumor explant cultures. Conclusion Riluzole may offer therapeutic benefits in diverse ER+ breast cancers, including lobular breast cancer. [ABSTRACT FROM AUTHOR]