Increasing evidence indicates that cancer stem cells (CSCs) and cancer stem-like cells form a special subpopulation of cells that are ubiquitous in tumors. These cells exhibit similar characteristics to those of normal stem cells in tissues; moreover, they are capable of self-renewal and differentiation, as well as high tumorigenicity and drug resistance. In prostate cancer (PCa), it is difficult to kill these cells using androgen signaling inhibitors and chemotherapy drugs. Consequently, the residual prostate cancer stem cells (PCSCs) mediate tumor recurrence and progression.

This review aims to provide a comprehensive and up-to-date overview of PCSCs, with a particular emphasis on potential therapeutic strategies targeting these cells.

After searching in PubMed and Embase databases using 'prostate cancer' and 'cancer stem cells' as keywords, studies related were compiled and examined.

In this review, we detail the origin and characteristics of PCSCs, introduce the regulatory pathways closely related to CSC survival and stemness maintenance, and discuss the link between epithelial-mesenchymal transition, tumor microenvironment and tumor stemness. Furthermore, we introduce the currently available therapeutic strategies targeting CSCs, including signaling pathway inhibitors, anti-apoptotic protein inhibitors, microRNAs, nanomedicine, and immunotherapy. Lastly, we summarize the limitations of current CSC research and mention future research directions.

A deeper understanding of the regulatory network and molecular markers of PCSCs could facilitate the development of novel therapeutic strategies targeting these cells. Previous preclinical studies have demonstrated the potential of this treatment approach. In the future, this may offer alternative treatment options for PCa patients.

Erianin is a biphenyl compound with low toxicity and a single structure that is extracted from Dendrobium officinale. The wide spectrum of pharmacological properties and excellent toxicity of erianin have been comprehensively proven in multiple tumors. However, less is known about the toxicity of erianin in acute myeloid leukemia (acute myeloid leukemia AML). Here, we explored the anti-AML capacity and potential mechanisms of erianin. Cells proliferation and cytotoxicity of AML cells of erianin was detected by CCK-8 assay and flow cytometer was conducted to assess AML cells apoptosis rate. Erianin blocked the AML cells cycle at the G2/M phase by regulating cell cycle-related protein and P21, P27, and P53 mRNA expression. Additionally, we first filtered PPARɑ and PIK3R1 through network pharmacology, protein-protein interaction (PPI) network, and GO and KEGG pathway enrichment analysis and confirmed their binding with erianin by molecular docking analysis.The cellular thermal shift assay (CETSA) and the drug affinity responsive target stability assay (DARTS) further verified that PPARɑ was an effective target of erianin. Specifically, erianin was found to inhibit the transcriptional level of PIK3R1 by promoting the protein expression of PPARɑ, thereby inhibiting the PI3K/AKT pathway. The inhibitory effect of erianin was partially neutralized by GW6471, a PPARɑ inhibitor. Notably, erianin revealed vigoroso coordinate repression with LY294002 on AML cells. Our findings indicate that erianin showed a potent cytotoxic effect on AML cells and affected AML cells via PPARɑ to regulate PI3K/AKT signaling pathways. We demonstrated the potent anti-AML effects of erianin and reported its potential mechanisms of action, indicating its potential for further development as a novel anti-AML drug.

Cancer Stem Cells (CSCs) play an important role in the development, resistance, and recurrence of many malignancies. These subpopulations of tumor cells have the potential to self-renew, differentiate, and resist conventional therapy, highlighting their importance in cancer etiology. This review explores the regulatory mechanisms of CSCs in breast, cervical, and lung cancers, highlighting their plasticity, self-renewal, and differentiation capabilities. CD44+/CD24- cells are a known marker for breast CSCs. Markers like as CD133 and ALDH have been discovered in cervical cancer CSCs. Similarly, in lung cancer, CSCs identified by CD44, CD133, and ALDH are linked to aggressive tumor behavior and poor therapy results. The commonalities between these tumors highlight the general necessity of targeting CSCs in treatment efforts. However, the intricacies of CSC activity, such as their interaction with the tumor microenvironment and particular signaling pathways differ between cancer types, demanding specialized methods. Wnt/β-catenin, Notch, and Hedgehog pathways are one of the essential signaling pathways, targeting them, may show ameliorative effects on breast, lung and cervical carcinomas and their respective CSCs. Pre-clinical data suggests targeting specific signaling pathways can eliminate CSCs, but ongoing clinical trials are on utilizing signaling pathway inhibitors in patients. In recent studies it has been reported that CAR T based targeting of specific markers may be used as combination therapy. Ongoing research related to nanobiotechnology can also play a significant role in diagnosis and treatment purpose targeting CSCs, as nanomaterials can be used for precise targeting and identification of CSCs. Further research into the targeting of signaling pathways and its precursors could prove to be right step into directing therapies towards CSCs for cancer therapy.

The diversification of ligands provides more opportunities to adjust the photophysical performance as well as the bio-function of Ru(II) complexes as novel photosensitizers. Herein, a kind of Ru(II) complexes carrying resveratrol derivative, amino-Res, as ligand was designed and synthesized. The representative complex (named Ru4) showed potent anticancer activity under the trigger of 520 nm-light. Lipophilicity and cellular accumulation experiments indicated that Ru4 possessed higher LogPO/W value and cell up-take than Ru1-Ru3 and [Ru(bpy)3]2+. Mechanism study revealed that Ru4 could inhibit cancer cell migration, invasion and cancer stemness. The bio-function of Ru4 was mainly inherited from the amino-Res ligand. The in vivo study demonstrated that Ru4 could inhibit the tumor growth without significant system toxicity.

Cancer stem cells (CSCs) play critical roles in tumor growth, metastasis, and chemoresistance. Although several small-molecule inhibitors designed to inhibit CSCs have been investigated in clinical trials, their inadequate tumor targeting and potential off-target side effects have led to poor outcomes. A CD44-targeted virus-mimicking nanomedicine encapsulating the BMI1 inhibitor PTC209 (PTC209@VNP-HA) was designed to treat head and neck squamous cell carcinoma (HNSCC). We used a dendritic mesoporous silica nanoparticle (MSN) as the core for virus-mimicking nanoparticle (VNP) formation after adding shell particles to the MSN surface. The VNP surface was then modified with hyaluronic acid (HA), and PTC209 was adsorbed by mesopores to form PTC209@VNP-HA. In this system, HA is used to target CD44+ CSCs. The rough surface of VNP-HA provided better drug delivery efficiency than smooth nanoparticles modified with HA. VNP-HA enhanced the cancer inhibitory effect of PTC209 12-fold compared to the administration of free PTC209, leading to significantly higher bioavailability of PTC209. Both in vitro and in vivo assays showed that PTC209@VNP-HA inhibited cancer stemness, proliferation, and metastasis in HNSCC. Mechanistically, this inhibitory effect is closely associated with DNA damage/apoptosis signaling. Using a series of preclinical models in murine systems, we confirmed that PTC209@VNP-HA eliminated BMI1+ CSCs, and greatly inhibited the proliferation and metastasis of HNSCC when combined with cisplatin. This study investigated PTC209@VNP-HA as a novel and potentially transformative HNSCC treatment option that eliminates CSCs, prevents metastasis, and overcomes cisplatin resistance.

The progression of colorectal cancer (CRC) is driven by a small subset of cancer stem-like cells (CSCs), and mitochondrial function is essential for maintaining their stemness. TSP50, a novel identified oncogene, has been found to promote cell proliferation in multiple cancer types. In this study, we detected the regulatory role of TSP50 in regulating CSC-like properties and mitochondrial mass in CRC.

First, TSP50 expression and clinical relevance were analyzed via clinical databases and immunohistochemical (IHC). Subsequently, bioinformatic analyses, CRC cell lines, tumorsphere cultures, and mouse xenograft models were utilized to evaluate the relationship between TSP50 and CSC-like properties as well as mitochondrial mass. Finally, immunofluorescence, immunoprecipitation, and Western blotting were performed to dissect the regulatory mechanisms of TSP50, followed by rescue experiments conducted both in vitro and in vivo.

TSP50 was overexpressed in CRC tissues, correlating with poor drug response and shorter overall survival (OS). Meanwhile, TSP50 was shown to enhance CSC-like properties in both CRC cells and mouse xenograft models, while concurrently increasing mitochondrial mass and reducing ROS levels, these effects were partially reversed by inhibition of the PI3K/AKT pathway. Mechanistic investigations revealed that TSP50-induced activation of PI3K/AKT signaling is primarily mediated by the enhanced catalytic activity of PI3K p110α subunit.

Collectively, TSP50 drives CRC malignancy by promoting CSC-like properties and enhancing mitochondrial function through PI3K/AKT signaling. These findings identify TSP50 as a potential therapeutic target for eliminating CSC-like cells and improving clinical outcomes in CRC treatment.

Cervical cancer (CC) and ovarian cancer (OC) are among the most common gynecological cancers with significant mortality in women, and their incidence is increasing. In addition to the prominent role of the malignant aspect of these cancers in cancer-related women deaths, chemotherapy drug resistance is a major factor that contributes to their mortality and presents a clinical obstacle. Although the exact mechanisms behind the chemoresistance in these cancers has not been revealed, accumulating evidence points to the dysregulation of non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as key contributors. These ncRNAs perform the roles of regulators of signaling pathways linked to tumor formation and chemoresistance. Strong data from various recent studies have uncovered that the main mechanism of these ncRNAs in the induction of chemoresistance of CC and OC is done through a dysregulated miRNA sponge activity as competing endogenous RNA (ceRNA) in the competing endogenous RNA networks (ceRNETs), where a miRNA regulating a messenger RNA (mRNA) is trapped, thereby removing its inhibitory effect on the desired mRNA. Understanding these mechanisms is essential to enhancing treatment outcomes and managing the problem of drug resistance. This review provides a comprehensive overview of lncRNA- and circRNA-mediated ceRNETs as the core process of chemoresistance against the commonly used chemotherapeutics, including cisplatin, paclitaxel, oxaliplatin, carboplatin, and docetaxel in CC and OC. Furthermore, we highlight the clinical potential of these ncRNAs serving as diagnostic indicators of chemotherapy responses and therapeutic targets.

The presence of cancer stem cells (CSCs) is one of the primary causes of recurring therapy resistance because they have two main capacities: self-renewal and avoiding apoptotic pathways. Despite their relevance, no full bibliometric analysis has yet been done in this topic. The goal of this work is to use bibliometric analysis to map the fundamental and emergent areas in therapeutics targeting colon cancer stem cells. To perform bibliometric analysis on colon cancer stem cells (CCSCs) literature, spanning roughly the last 40 years, in order to establish a firm base for future projections by emphasizing the findings of the most notable research. All information pertinent to CCSCs was accessed from Web of Science Core Collection database. In order to identify and analyze the research hotspots and trends related to this topic, Biblioshiny (RStudio) and VOSviewer were utilized to ascertain the countries/regions, institutions, journals, authors, references, and keywords involved. The targeted time span covered 1735 research-, and review articles. The most frequent keywords were "colorectal cancer," "cancer stem cells," and "colon cancer," while the most trending keywords in the last few years were "protein stability," "spheroid formation," "ubiquitination," "exosomes," "patient-derived organoids," and "gut microbiota." Over the past 40 years, there has been a significant advancement in researchers' understanding of colon cancer stem cells. In addition, the cluster map of co-cited literature showed that colon cancer stem cell research has emerged as a research hotspot. It was also anticipated that the main focus of the future efforts appears to involve clinical applications of cell-targeted colon cancer therapy. These results provide researchers with a comprehensive understanding of this field and provide insightful ideas for further research.

Model systems are critical in biomedical and preclinical research. Animal and in vitro models serve an important role in our current understanding of human physiology, disease pathophysiology, and therapy development. However, if the system is between cell culture and animal models, it may be able to overcome the knowledge gap that exists in the current system. Studies employing ex vivo organs as models have not been thoroughly investigated. Though the integration of other organs and systems has an impact on many biological mechanisms and disorders, it can add a new dimension to modeling and aid in the identification of new possible therapeutic targets. Here, we have discussed why the ex vivo organ model is desirable and the importance of the inclusion of organs from diverse species, described its historical aspects, studied organs as models in scientific research, and its ex vivo stability. We also discussed, how an ex vivo organ model might help researchers better understand organ physiology, as well as organ-specific diseases and therapeutic targets. We emphasized how this ex vivo organ dynamics will be more competent than existing models, as well as what tissues or organs would have potentially viable longevity for ex vivo modeling including human tissues, organs, and/or at least biopsies and its possible advantage in clinical medicine including organ transplantation procedure and precision medicine.

Mounting evidence underscores the prevalent hierarchical organization of cancer tissues. At the foundation of this hierarchy reside cancer stem cells, a subset of cells endowed with the pivotal role of engendering the entire cancer tissue through cell differentiation. In recent times, substantial attention has been directed toward the phenomenon of cancer cell plasticity, where the dynamic interconversion between cancer stem cells and nonstem cancer cells has garnered significant interest. Since the task of detecting cancer cell plasticity from empirical data remains a formidable challenge, we propose a Bayesian statistical framework designed to infer phenotypic plasticity within cancer cells, utilizing temporal data on cancer stem cell proportions. Our approach is grounded in a stochastic model, adept at capturing the dynamic behaviors of cells. Leveraging Bayesian analysis, we scrutinize the moment equation governing cancer stem cell proportions, derived from the Kolmogorov forward equation of our stochastic model. Our methodology introduces an improved Euler method for parameter estimation within nonlinear ordinary differential equation models, also extending insights to compositional data. Extensive simulations robustly validate the efficacy of our proposed method. To further corroborate our findings, we apply our approach to analyze published data from SW620 colon cancer cell lines. Our results harmonize with in situ experiments, thereby reinforcing the utility of our method in discerning and quantifying phenotypic plasticity within cancer cells.

Combined hepatocellular carcinoma-cholangiocarcinoma (HCC-CCA) is a rare liver tumor comprising histologic features of both HCC and CCA. Due to its heterogeneous nature, treatment of combined HCC-CCA is a significant clinical challenge and prognosis remains poor. Therefore, further understanding of the tumor biology underlying the individual subtypes of this mixed tumor is required to improve treatment stratification and optimize treatment strategies. This study sought to identify altered epigenetic regulation and gene expression patterns in the individual components of combined HCC-CCA. Formalin fixed paraffin embedded (FFPE) tumor specimens from 9 patients diagnosed with combined HCC-CCA were utilized in this study. Hematoxylin and eosin (H&E) staining was performed for each sample, and regions representative of the individual HCC and CCA components were delineated. Adjacent unstained slides were cut and dissected to separate HCC and CCA components. DNA and RNA extraction was performed for each sample for DNA methylation (n = 7 HCC and 7 CCA) and gene expression (n = 7 HCC and 8 CCA) profiling via reduced representation bisulfite sequencing (RRBS) and RNA-seq, respectively. Samples did not cluster by tumor type when comparing genome-wide DNA methylation or gene expression patterns. Of the 5 patients with DNA methylation data available for both subtypes, 4 clustered by patient as opposed to cancer subtype, suggesting similar epigenetic regulatory patterns arising from development in the same microenvironment and genetic background. Differential analysis resulted in the identification of 57 differentially expressed genes (DEGs) and 808 differentially methylated regions (DMRs) between the HCC and CCA subtypes. Genes associated with DMRs were associated with Wnt signaling, voltage-gated channels, metal binding, and cellular regulation. Finally, increased expression of several genes previously implicated in tumor aggressiveness, prognosis, and treatment responses were identified. These results highlight the potential importance of accounting for underlying HCC and CCA tumor biology when determining the optimal course of treatment for this deadly disease.

In this study, a novel Caputo fractional-order model is proposed to represent the complex interactions among stem cells, effector cells, and tumor cells, considering both scenarios of chemotherapy. Furthermore, the proposed model, which incorporates treatment with effective chemotherapy, is thoroughly examined. The necessary properties, including the positivity and equilibrium points, as well as the local asymptotic stability analysis, are investigated. Additionally, the existence and uniqueness of solutions for the proposed model are thoroughly analyzed. We perform a thorough assessment of the solutions produced by the deep neural network by comparing them against established benchmarks and carefully analyzing them through testing, validation, training, error distribution analysis, and regression analysis. The temporal concentration pattern of stem, effector and tumor cells as well as chemotherapy drugs are examined. It is noted that chemotherapy leads to a decrease in tumor cell density over time, which extends the period required to achieve equilibrium. The decay rates of stem cells and tumor cells are recognized as essential elements affecting cancer dynamics. Furthermore, the integration of fractional orders is found to be important for precisely depicting the concentrations of cancer cells.

Extracellular vesicles (EVs) are natural carriers of biological information and play pivotal roles in intercellular communication. EVs are biocompatible, have low immunogenicity, and are capable of traversing biological barriers, making them ideal tools for disease diagnosis and therapy. Despite their promising prospects, the full realization of EVs potential faces several challenges. This article aims to comprehensively review the biological and molecular features of EVs, their applications in liver cancer and possible underlying mechanisms, and the critical challenges affecting the clinical translation of EVs-based therapies in liver cancer.

The prolyl-isomerase Pin1 is a unique enzyme that catalyzes cis-trans isomerization of phosphorylated Ser/Thr-Pro motifs. These motifs are present in many proteins, where isomerization of the typically rigid prolyl-peptide bond can lead to conformational changes, and subsequently regulate activity, stability, or localization. The specificity of Pin1 for phosphorylated motifs allows it to serve as a master regulator of proteins after phosphorylation, adding an additional layer of regulation to intricately control cellular signaling. As such, Pin1 plays an expansive role in numerous cancer and age-related signaling pathways, and is recognized as a major driver of cancer and promising therapeutic target. In this review, we discuss the role of Pin1 in regulation of age-related cancer signaling pathways, and we highlight the early development and current landscape of Pin1 inhibitors, and the prospect of Pin1 inhibition for cancer therapy.

Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer treatment that uses near-infrared light to activate a conjugate of a monoclonal antibody (mAb) and a photoactivatable silica phthalocyanine dye (IRDye700DX: IR700). Unlike conventional photodynamic therapy (PDT), NIR-PIT selectively destroys targeted tumor cells while preserving the surrounding normal tissue and providing superior tissue penetration. Recently, NIR-PIT has been approved for the treatment of unresectable recurrent head and neck cancers in Japan. It induces highly selective cancer cell death; therefore, it is expected to be a new curative treatment option for various cancers, including brain tumors. In this review, we compare the principles of NIR-PIT and PDT and discuss the potential applications of NIR-PIT for brain tumors. We selected targetable proteins across various types of brain tumors and devised a strategy to effectively pass the mAb-IR700 conjugate through the blood-brain barrier (BBB), which is a significant challenge for NIR-PIT in treating brain tumors. Innovative approaches for delivering the mAb-IR700 conjugate across the BBB include exosomes, nanoparticle-based systems, and cell-penetrating peptides. Small-molecule compounds, such as affibodies, are anticipated to rapidly accumulate in tumors within intracranial models, and our preliminary experiments demonstrated rapid uptake. NIR-PIT also induces immunogenic cell death and activates the anti-tumor immune response. Overall, NIR-PIT is a promising approach for treating brain tumors. It has the potential to overcome the limitations of conventional therapies and offers new hope to patients with brain tumors.

Despite advances in cancer immunotherapies across various cancers, survival outcomes in colorectal cancer (CRC) with these agents remain largely unsatisfactory despite the high tumour burden. Colorectal stem cells (CSCs), especially LGR5+ CSCs, are the significant drivers in CRC initiation, progression and resistance to conventional therapies. Although native immune surveillance is sufficient to combat early tumour formation, CRC evades early immune detection with its well-documented adenoma-to-carcinoma sequence. The exact mechanism underlying this phenomenon still needs to be better understood. SRY-related HMG box gene 17 (SOX17), a transcription factor that specifies embryonic gut formation, is increasingly recognised as a significant factor in CRC tumourigenesis. However, its role as a tumour suppressor or oncogene is still debated. Evidence from a recent study highlighted the critical role of SOX17 in reshaping the tumour immune ecosystem through the simultaneous inhibition of CD8+ T cells and selective suppression of LGR5 expression in CSCs through transcriptional repression, thereby facilitating disease progression. Given its role in immune evasion, SOX17 could be a promising marker in personalised therapy. Additionally, SOX17 could play a role in the diagnostic arena, potentially identifying dysplasia in the gastrointestinal tract. Future clinical, basic and genetic studies focusing on SOX17 are needed to ascertain its mechanistic role in tumour immunomodulation in CRC and diagnosing preneoplastic lesions in the gastrointestinal tract.

Adult tissue function is dependent on intrinsic factors that mediate stem cell self-renewal and proliferation in response to changes in physiology and the environment. The estrogen-related receptor (ERR) subfamily of orphan nuclear receptors are major transcriptional regulators of metabolism and animal physiology. In mammals, ERRs (NR3B1, NR3B2, NR3B3) have roles in regulating mitochondrial biosynthesis, lipid metabolism, as well as stem cell maintenance. The sole Drosophila ERR ortholog promotes larval growth by establishing a metabolic state during the latter half of embryogenesis. In addition, ERR is required in adult Drosophila males to coordinate glycolytic metabolism with lipid synthesis and within the testis to regulate spermatogenesis gene expression and fertility. Despite extensive work characterizing the role of ERR in Drosophila metabolism, whether ERR has a conserved requirement in regulating stem cell behavior has been understudied. To determine whether ERR regulates stem cell activity in Drosophila, we used the established adult female germline stem cell (GSC) lineage as a model. We found that whole-body ERR knockout in adult females using conditional heat shock-driven FLP-FRT recombination significantly decreases GSC number and glycolytic enzyme expression in GSCs. In addition, we found that ERR activity is required cell-autonomously in the adult female germline for maintenance of GSCs; whereas ERR regulation of GSCs is independent of its activity in adult female adipocytes. Our results highlight an ancient and conserved role for ERRs in the regulation of stem cell self-renewal.

This study is the first to investigate polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polychlorinated naphthalenes (PCNs) across multiple particulate matter (PM) sizes (PM1.0, PM2.5, TSP) in Taiwan, focusing on spatio-seasonal variations, chemical composition, sources, and oxidative potential (OP) utilizing Real-time Cell Analysis (RTCA) and the Dithiothreitol (DTT) assay. PM samples were collected from the Northern Industrial Station (NIS: PM) in Taoyuan, and the Central Industrial (CIS: PM2.5) and Central Traffic (CTS: PM2.5) stations in Taichung (2022-2023). Elevated PCDD/F, PCB, and PCN levels were observed at NIS during winter, with PM2.5 and PM1.0 comprising 90 % and 50 % of TSP, respectively, driven by local emissions and meteorological influences. PCDD/Fs peaked in winter at CTS (7.16 ± 1.64 fg TEQWHO/m3) and in autumn at CIS (8.29 ± 3.21 fg TEQWHO/m3), while PCBs were highest in summer (CIS: 0.151 ± 0.212 fg TEQWHO/m3; CTS: 0.006 ± 0.013 fg TEQWHO/m3), likely due to temperature-driven volatilization. Notably, PCNs exhibited no clear seasonal trends. Cytotoxicity assays revealed a size-dependent toxicity gradient (PM1.0: 71.8 % > PM2.5: 62.1 % > TSP: 51.9 %), with PM2.5 toxicity consistent across sources (P = 0.58). DTT assays indicated higher OP at Northern Taiwan's industrial site on weekdays, whereas Central Taiwan's industrial and traffic sites showed no substantial variation (p > 0.05). Markedly, NO3- strongly correlated with OP across all PM sizes, while Cu and Cr were linked to OPv, and Mn and Cr to OPm. These findings highlight seasonal and source-driven PM toxicity, with smaller particles posing greater health risks, requiring targeted mitigation.

The ubiquitin (Ub) system, a ubiquitous presence across eukaryotes, plays a crucial role in the precise orchestration of diverse cellular protein processes. From steering cellular signaling pathways and orchestrating cell cycle progression to guiding receptor trafficking and modulating immune responses, this process plays a crucial role in regulating various biological functions. The dysregulation of Ub-mediated signaling pathways in prevalent cancers ushers in a spectrum of clinical outcomes ranging from tumorigenesis and metastasis to recurrence and drug resistance. Ubiquitination, a linchpin process mediated by Ub, assumes a central mantle in molding cellular signaling dynamics. It navigates transitions in biological cues and ultimately shapes the destiny of proteins. Recent years have witnessed an upsurge in the momentum surrounding the development of protein-based therapeutics aimed at targeting the Ub system under the sway of cancer stem cells. The article provides a comprehensive overview of the ongoing in-depth discussions regarding the regulation of the Ub system and its impact on the development of cancer stem cells. Amidst the tapestry of insights, the article delves into the expansive roles of E3 Ub ligases, deubiquitinases, and transcription factors entwined with cancer stem cells. Furthermore, the spotlight turns to the interplay with pivotal signaling pathways the Notch, Hedgehog, Wnt/β-catenin, and Hippo-YAP signaling pathways all play crucial roles in the regulation of cancer stem cells followed by the specific modulation of Ub-proteasome.

Bladder cancer (BLCA) is a prevalent cancer type with an unmet need for new therapeutic strategies. Nucleoporin 93 (Nup93) is implicated in the pathophysiology of several cancers, but its relationship with bladder cancer remains unclear. Nup93 expression was analyzed in TCGA datasets and 88 BLCA patient samples. Survival analysis and Cox regression models evaluated the association between Nup93 levels and patient prognosis. BLCA cells were used to investigate the effects of Nup93 overexpression or knockdown on cell growth, invasion, stemness (sphere formation and ALDH2 + cancer stem cell marker), and Wnt/β-catenin signaling in vitro. The Wnt activator BML-284 was used to confirm the involvement of Wnt/β-catenin signaling pathway. A xenograft mouse model validated the in vitro findings. Nup93 was highly expressed in BLCA tissues and cell lines, and high Nup93 expression correlated with poor prognosis in BLCA patients. Nup93 silencing inhibited BLCA cell proliferation, Wnt/β-catenin activation, and cancer cell stemness. Conversely, Nup93 overexpression promoted these effects. BML-284 partially rescued the reduction in cell growth and stemness markers caused by Nup93 knockdown. Nup93 knockdown also suppressed the tumor formation of BLCA cells in vivo. Nup93 regulates BLCA cell growth and stemness via the Wnt/β-catenin pathway, suggesting its potential as a prognostic marker and therapeutic target in BLCA.

Understanding the complex biological process of aging is of great value, especially as it can help develop therapeutics to prolong healthy life. Predicting biological age from gene expression data has shown to be an effective means to quantify aging of a subject, and to identify molecular and cellular biomarkers of aging. A typical approach for estimating biological age, adopted by almost all existing aging clocks, is to train machine learning models only on healthy subjects, but to infer on both healthy and unhealthy subjects. However, the inherent bias in this approach results in inaccurate biological age as shown in this study. Moreover, almost all existing transcriptome-based aging clocks were built around an inefficient procedure of gene selection followed by conventional machine learning models such as elastic nets, linear discriminant analysis etc. To address these limitations, we proposed DeepQA, a unified aging clock based on mixture of experts. Unlike existing methods, DeepQA is equipped with a specially designed Hinge-Mean-Absolute-Error (Hinge-MAE) loss so that it can train on both healthy and unhealthy subjects of multiple cohorts to reduce the bias of inferring biological age of unhealthy subjects. Our experiments showed that DeepQA significantly outperformed existing methods for biological age estimation on both healthy and unhealthy subjects. In addition, our method avoids the inefficient exhaustive search of genes, and provides a novel means to identify genes activated in aging prediction, alternative to such as differential gene expression analysis.

Stem cells, both normal somatic (SSC) and cancer stem cells (CSC) exist in minimally two states, i.e., quiescent and activated. Regulation of these two states, including their reliance on different metabolic processes, i.e., FAO and glycolysis in quiescent versus activated stem cells respectively, involves the analysis of a complex array of factors (nutrient and oxygen levels, adhesion molecules, cytokines, etc.) to initiate the epigenetic changes to either depart or enter quiescence. Quiescence is a critical feature of SSC that is required to maintain the genomic integrity of the stem cell pool, particularly in long lived complex organisms. Quiescence in CSC, whether they are derived from mutations arising in SSC, aberrant microenvironmental regulation, or via dedifferentiation of more committed progenitors, is a critical component of therapy resistance and disease latency and relapse. At the beginning of vertebrate evolution, approximately 450 million years ago, a gene duplication generated the two members of the Kat3 family, CREBBP (CBP) and EP300 (p300). Despite their very high degree of homology, these two Kat3 coactivators play critical and non-redundant roles at enhancers and super-enhancers via acetylation of H3K27, thereby controlling stem cell quiescence versus activation and the cells metabolic requirements. In this review/perspective, we discuss the unique regulatory roles of CBP and p300 and how specifically targeting the CBP/β-catenin interaction utilizing small molecule antagonists, can correct lineage infidelity and safely eliminate quiescent CSC.

Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers (PSs) selectively. The reactive oxygen species (ROS), which kill cells, are released by these PSs when they are stimulated by light. According to recent developments in PDT, its efficacy may go beyond traditional tumor cells, providing a viable remedy for the resistance shown by CSCs. Researchers want to improve the targeted elimination and selective targeting of CSCs by combining PDT with new PSs and customized delivery systems. Studies emphasize how PDT affects CSCs as well as bulk tumor cells. According to studies, PDT not only limits CSC growth but also modifies their microenvironment, which lowers the possibility of recovery. Additionally, studies are being conducted on the utilization of PDT and immunotherapeutic techniques to improve treatment efficacy and overcome inherent resistance of CSCs. In conclusion, PDT is a viable strategy for treating carcinogenesis driven by CSCs. By applying the most recent advancements in PDT technologies and recognizing how it interacts with CSCs, this treatment has the potential to surpass traditional resistance mechanisms and improve the future of cancer patients. Clinical and preclinical studies highlight that combining PDT with CSC-targeted approaches has the potential to overcome current therapy limitations. Future efforts should focus on clinical validation, optimizing light delivery and PS use, and developing effective combination strategies to target CSCs.

Metabolic heterogeneity in various cancer cells within a tumor causes resistance to medical therapies and promotes tumor recurrence and metastasis. However, the mechanisms by which tumors acquire metabolic heterogeneity are poorly understood. Here, we revealed that PKCλ-dependent asymmetric division of ALDH1-positive cancer stem cells (CSCs) led to an uneven distribution of glycolytic capacity, which is crucial for understanding metabolic heterogeneity within a tumor. The rate-limiting enzyme PFKP and the metabolic probe CDG in glycolysis codistributed with the ALDH1A3 protein during the post-cell division phase, highlighting a mechanism for acquiring metabolic diversity. PKCλ deficiency reduced the asymmetric distribution of these proteins in ALDH1high cells with high ALDH1 activity, suggesting a fundamental role for PKCλ in metabolic heterogeneity. We identified 28 distinct distribution patterns combining PFKP and CDG distributions, demonstrating the complexity of glycolytic heterogeneity. Furthermore, validation and prediction of cell distribution patterns via a probabilistic model confirmed that PKCλ deficiency diminished glycolytic diversity in individual cells within a cancer cell colony generated from an ALDH1-positive CSC. These findings suggest that PKCλ-dependent asymmetric cell division of ALDH1-positive CSCs is crucial for glycolytic heterogeneity in cancer cells within a tumor, potentially offering new therapeutic targets against tumor resistance and metastasis.

Over the last 2 decades, research has increasingly focused on cancer stem cells (CSCs), considered responsible for tumor formation, resistance to therapies, and relapse. The traditional "static" CSC model used to describe tumor heterogeneity has been challenged by the evidence of CSC dynamic nature and plasticity. A comprehensive understanding of the mechanisms underlying this plasticity, and the capacity to unambiguously identify cancer markers to precisely target CSCs are crucial aspects for advancing cancer research and introducing more effective treatment strategies. In this context, Raman spectroscopy (RS) and specific Raman schemes, including CARS, SRS, SERS, have emerged as innovative tools for molecular analyses both in vitro and in vivo. In fact, these techniques have demonstrated considerable potential in the field of cancer detection, as well as in intraoperative settings, thanks to their label-free nature and minimal invasiveness. However, the RS integration in pre-clinical and clinical applications, particularly in the CSC field, remains limited. This review provides a concise overview of the historical development of RS and its advantages. Then, after introducing the CSC features and the challenges in targeting them with traditional methods, we review and discuss the current literature about the application of RS for revealing and characterizing CSCs and their inherent plasticity, including a brief paragraph about the integration of artificial intelligence with RS. By providing the possibility to better characterize the cellular diversity in their microenvironment, RS could revolutionize current diagnostic and therapeutic approaches, enabling early identification of CSCs and facilitating the development of personalized treatment strategies.

Glioblastoma (GBM), a highly malignant brain tumor, has a poor prognosis despite standard treatments like surgery, chemotherapy, and radiation. Glioblastoma stem cells (GSCs) play a critical role in recurrence and therapy resistance. Stem cell-based therapies have emerged as innovative approaches, leveraging the tumor-targeting abilities of stem cells to deliver treatments directly to GBM.

This review focuses on using intact stem cells or subtypes for GBM therapy, excluding antigenic characteristics. The stem cell-based therapies explored include neural, mesenchymal, glioblastoma, hematopoietic and adipose-derived stem cells that have been investigated in both clinical and preclinical settings. A systematic search in PubMed, EMBASE, ClinicalTrials.gov, and Scopus had identified research up until January 2024. Key mechanisms reviewed include immune modulation, angiogenesis inhibition, and apoptosis induction. Discussion of completed and ongoing trials include emphasis on safety, efficacy, challenges, and study design limitations.

Stem cell-based therapies hold promise for treating GBM by targeting GSCs and improving treatment outcomes. Despite some potential advantages, challenges such as tumorigenesis risks, delivery complexities, and sustained therapeutic effects persist. Future research should prioritize optimizing stem cell modifications, combining them with current treatments, and conducting large-scale trials to ensure safety and efficacy. Integrating stem cell therapies into GBM treatment could provide more effective and less invasive options for patients.

A tumor cell subpopulation of tumor-initiating cells (TIC) or "cancer stem cells" is associated with therapeutic resistance, as well as both local and distant recurrences. Signal transducer and activator of transcription (STAT) activity is elevated in TICs in claudin-low models of human triple-negative breast cancer, which enables enrichment of TICs using a STAT-responsive reporter. Lineage tracing of TICs as they undergo cell state changes could enable a better understanding of the molecular phenotypes of TIC and uncover strategies to selectively target TICs. In this study, we developed a STAT-responsive lineage-tracing system and used it in conjunction with the original reporter to enrich for cells with enhanced mammosphere-forming potential. This approach was able to detect TICs in some, but not all, basal-like triple-negative breast cancer xenograft models, indicating that STAT signaling has both TIC-related and TIC-independent functions. Single-cell RNA sequencing (RNA-seq) of reporter-tagged xenografts and clinical samples identified a common IFN/STAT1-associated transcriptional state in TICs that was previously linked to inflammation and macrophage differentiation. Surprisingly, most of the identified genes were not present in previously published TIC signatures derived using bulk RNA-seq. Finally, bone marrow stromal cell antigen-2 was identified as a cell surface marker of this state that functionally regulated TIC frequency. These results suggest that TICs may exploit the IFN/STAT1 signaling axis to promote their activity and that targeting this pathway may help eliminate TICs. Significance: Coupling single-cell transcriptomics with tumor-initiating cell enrichment identified IFN response gene expression not previously reported in bulk RNA-sequencing-derived signatures and proposed IFN/STAT1 signaling as a candidate therapeutic target in breast cancer.

Osteosarcoma is the most prevalent primary malignant bone tumor affecting pediatric and adolescent individuals. However, despite the passage of three decades, there has been no notable enhancement in the overall survival rate of patients with osteosarcoma. In recent years, CD155 has been reported to exhibit abnormal amplification in a range of tumors, yet the precise underlying mechanism remains elusive. The objective of this study is to investigate the role of CD155 in osteosarcoma, and to identify drugs that specifically target this molecule, thereby offering a novel direction for the treatment of osteosarcoma.

The prognosis of patients with osteosarcoma with high and low expression of CD155 was verified by immunohistochemistry. CCK-8 and colony formation assays were used to detect cell proliferation and drug resistance. Transwell experiments were used to detect cell migration and invasion. The sphere formation experiment was used to evaluate the stemness of tumor cells. Additionally, in vivo animal models were utilized to assess the functional role of CD155 in a biological context. RNA-seq and co-immunoprecipitation methods were used to search for downstream target molecules and signaling pathways of CD155. Finally, virtual screening was used to find drugs targeting CD155.

In this study, we have established the significant amplification of CD155 in osteosarcoma. Utilizing a comprehensive array of experimental methods, including CCK-8 assay, colony formation assay, Transwell assay, and in vivo animal models, we unequivocally demonstrate that CD155 significantly potentiates the malignancy of osteosarcoma both in vitro and in vivo. Additionally, our findings reveal that CD155 promotes osteosarcoma stemness by modulating the Wnt/β-catenin signaling pathway. Advanced molecular techniques, such as RNA sequencing and co-immunoprecipitation, have been instrumental in elucidating the mechanism of CD155 in activating the Wnt/β-catenin pathway via the SRC/AKT/GSK3β signaling axis, thereby enhancing the stem-cell-like properties of osteosarcoma cells. To explore targeted therapeutic options, we conducted virtual screening and identified troxerutin as a promising CD155 inhibitor.

Our findings reveal that troxerutin effectively inhibits CD155, attenuates the SRC/AKT/GSK3β signaling cascade, diminishes the nuclear localization of β-catenin, and consequently mitigates osteosarcoma stemness. These discoveries position troxerutin as a promising candidate for targeted osteosarcoma therapy.

Glioblastoma (GBM), one of the most aggressive brain tumors, has a 5-year survival rate of less than 5%. Current standard therapies, including surgery, radiotherapy, and temozolomide (TMZ) chemotherapy, are limited by drug resistance and the blood-brain barrier. Integrating expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) data has shown promise in uncovering disease mechanisms and therapeutic targets. This study combined eQTL and pQTL analyses to identify potential GBM-related genes and circulating plasma proteins for therapeutic exploration. Using transcriptomic data from The Cancer Genome Atlas (TCGA), we identified 2,528 differentially expressed genes, including GPX7 and CXCL10. eQTL-MR analysis identifies GBM-associated differentially expressed genes and constructs a protein-protein interaction (PPI) network.Integrating pQTL data from the deCODE database, pQTL-MR, and colocalization analyses validated the therapeutic potential of GPX7 and CXCL10.These findings provide new perspectives on GBM biology and suggest actionable targets for therapy. Despite limitations due to sample size and population-specific data, this study highlights GPX7 and CXCL10 as promising candidates for further investigation and lays the foundation for targeted GBM treatments.

Glioblastoma (GBM) is an exceedingly aggressive primary brain tumor defined by rapid growth, extensive infiltration, and resistance to standard therapies. A central factor driving these malignancies is the subpopulation of glioblastoma stem cells (GSCs), which possess self-renewal capacity, multipotency, and the ability to regenerate tumor heterogeneity. GSCs contribute to key hallmarks of GBM pathobiology, including relentless progression, resistance to chemotherapy and radiotherapy, and inevitable recurrence. GSCs exhibit distinct molecular signatures, enhanced DNA repair, and metabolic adaptations that protect them against conventional treatments. Moreover, they reside within specialized niches-such as perivascular or hypoxic microenvironments-that sustain stemness, promote immunosuppression, and facilitate angiogenesis. Recent discoveries highlight signaling pathways like Notch, Wnt/β-catenin, Hedgehog, STAT3-PARN, and factors such as TFPI2 and HML-2 as critical regulators of GSC maintenance, plasticity, and immune evasion. These findings underscore the complexity of GSC biology and their pivotal role in driving GBM heterogeneity and therapeutic failure. Emerging therapeutic strategies aim to target GSCs through multiple avenues, including surface markers, immunotherapeutics (e.g., CAR T cells), metabolic vulnerabilities, and combination regimens. Advances in patient-derived organoids, single-cell omics, and 3D co-culture models enable more accurate representation of the tumor ecosystem and personalized therapeutic approaches. Ultimately, improved understanding of GSC-specific targets and the tumor microenvironment promises more effective interventions, paving the way toward better clinical outcomes for GBM patients.

The Wnt signaling pathway is critically involved in orchestrating cellular functions such as proliferation, migration, survival, and cell fate determination during development. Given its pivotal role in cellular communication, aberrant Wnt signaling has been extensively linked to the pathogenesis of various diseases. This review offers an in-depth analysis of the Wnt pathway, detailing its signal transduction mechanisms and principal components. Furthermore, the complex network of interactions between Wnt cascades and other key signaling pathways, such as Notch, Hedgehog, TGF-β, FGF, and NF-κB, is explored. Genetic mutations affecting the Wnt pathway play a pivotal role in disease progression, with particular emphasis on Wnt signaling's involvement in cancer stem cell biology and the tumor microenvironment. Additionally, this review underscores the diverse mechanisms through which Wnt signaling contributes to diseases such as cardiovascular conditions, neurodegenerative disorders, metabolic syndromes, autoimmune diseases, and cancer. Finally, a comprehensive overview of the therapeutic progress targeting Wnt signaling was given, and the latest progress in disease treatment targeting key components of the Wnt signaling pathway was summarized in detail, including Wnt ligands/receptors, β-catenin destruction complexes, and β-catenin/TCF transcription complexes. The development of small molecule inhibitors, monoclonal antibodies, and combination therapy strategies was emphasized, while the current potential therapeutic challenges were summarized. This aims to enhance the current understanding of this key pathway.

Stem cells have emerged as a pivotal area of research in the field of oncology, offering new insights into the mechanisms of cancer initiation, progression, and resistance to therapy. This review provides a comprehensive overview of the role of stem cells in cancer, focusing on cancer stem cells (CSCs), their characteristics, and their implications for cancer therapy. We discuss the origin and identification of CSCs, their role in tumorigenesis, metastasis, and drug resistance, and the potential therapeutic strategies targeting CSCs. Additionally, we explore the use of normal stem cells in cancer therapy, focusing on their role in tissue regeneration and their use as delivery vehicles for anticancer agents. Finally, we highlight the challenges and future directions in stem cell research in cancer.

Metabolism and stemness-related genes (msRGs) are critical in the development and progression of lung adenocarcinoma (LUAD). Nevertheless, reliable prognostic risk signatures derived from msRGs have yet to be established.

In this study, we downloaded and analyzed RNA-sequencing and clinical data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. We employed univariate and multivariate Cox regression analyses, along with least absolute shrinkage and selection operator (LASSO) regression analysis, to identify msRGs that are linked to the prognosis of LUAD and to develop the prognostic risk signature. The prognostic value was evaluated using Kaplan-Meier analysis and log-rank tests. We generated receiver operating characteristic (ROC) curves to evaluate the predictive capability of the prognostic signature. To estimate the relative proportions of infiltrating immune cells, we utilized the CIBERSORT algorithm and the MCPCOUNTER method. The prediction of the half-maximal inhibitory concentration (IC50) for commonly used chemotherapy drugs was conducted through ridge regression employing the "pRRophetic" R package. The validation of our analytical findings was performed through both in vivo and in vitro studies.

A novel five-gene prognostic risk signature consisting of S100P, GPX2, PRC1, ARNTL2, and RGS20 was developed based on the msRGs. A risk score derived from this gene signature was utilized to stratify LUAD patients into high- and low-risk groups, with the former exhibiting significantly poorer overall survival (OS). A nomogram was constructed incorporating the risk score and other clinical characteristics, showcasing strong capabilities in estimating the OS rates for LUAD patients. Furthermore, we observed notable differences in the infiltration of various immune cell subtypes, as well as in responses to immunotherapy and chemotherapy, between the low-risk and high-risk groups. Results from gene set enrichment analysis (GSEA) and in vitro studies indicated that the prognostic signature gene ARNTL2 influenced the prognosis of LUAD patients, primarily through the activation of the PI3K/AKT/mTOR signaling pathway.

Utilizing this gene signature for risk stratification could help with clinical treatment management and improve the prognosis of LUAD patients.

Chemoresistance is the adaptation of cancer cells against therapeutic agents. When exhibited by cancer cells, chemoresistance helps them to avoid apoptosis, cause relapse, and metastasize, making it challenging for chemotherapeutic agents to treat cancer. Various strategies like dosage modification of drugs, nanoparticle-based delivery of chemotherapeutics, antibody-drug conjugates, and so on are being used to target and reverse chemoresistance, one among such is combination therapy. It uses the combination of two or more therapeutic agents to reverse multidrug resistance and improve the effects of chemotherapy. Phytochemicals are known to exhibit chemosensitizing properties and are found to be effective against various cancers. Tocotrienols (T3) and tocopherols (T) are natural bioactive analogs of vitamin E, which exhibit important medicinal value and potential curative properties apart from serving as an antioxidant and nutrient supplement. Notably, T3 exhibits a variety of pharmacological activities like anticancer, anti-inflammatory, antiproliferative, and so on. The chemosensitizing property of tocotrienol is exhibited by modulating several signaling pathways and molecular targets involved in cancer cell survival, proliferation, invasion, migration, and metastasis like NF-κB, STATs, Akt/mTOR, Bax/Bcl-2, Wnt/β-catenin, and many more. T3 sensitizes cancer cells to chemotherapeutic drugs including cisplatin, doxorubicin, and paclitaxel increasing drug concentration and cytotoxicity. Discussed herewith are the chemosensitizing properties of tocotrienols on various cancer cell types when combined with various drugs and biological molecules.

Targeting metabolism represents a promising approach to eradicate leukemic stem cells (LSCs) that are considered critical drivers of relapse in acute myeloid leukemia (AML). In this study, we demonstrate that the phosphatidic acid phosphatase LPIN1, which regulates the synthesis of diacylglycerol, the key substrate for triacylglycerol, and phospholipid production, is crucial for the function of healthy and leukemic hematopoietic stem and progenitor cells (HSPC and LSC). LPIN1 mRNA was highly expressed in the CD34+ compartment of primary human AML samples. LPIN1 suppression inhibited the proliferation of primary leukemic cells and normal HSPCs in vitro and in xenotransplantation assays. Lipidomics analyses revealed a reduction of phosphatidylcholine (PC) and phosphatidylethanolamine and an upregulation of sphingomyelin upon LPIN1 depletion. Distinct phospholipid composition was associated with genetic AML groups, and targeting PC production by choline kinase inhibitors showed strong anti-leukemic activity. In summary, our data establish a regulatory role of LPIN1 in HSPC and LSC function and provide novel insights into the role of glycerophospholipid homeostasis in stemness and differentiation.

In clonal hematopoiesis of indeterminate potential (CHIP), subpopulations of blood cells carrying somatic mutations expand as the individual ages, and this expansion may elevate risk of blood cancers as well as cardiovascular disease. Individuals at higher risk of CHIP and therefore of CHIP-associated disease can be identified through mutational profiling, and the apparently central role of inflammation in CHIP-associated disease has emerged as a potential therapeutic target. While CHIP is often associated with negative health outcomes, emerging evidence suggests that some CHIP-related mutations may also exert beneficial effects, indicating a more complex role in human health. This review examines current understanding of the epidemiology and clinical significance of CHIP and the role of inflammation in driving its association with disease risk. It explores the mechanisms linking CHIP to inflammation and risk of cardiovascular and other diseases, as well as the potential of personalizing therapies against those diseases for individuals with CHIP.

Gliomas are the most prevalent malignant tumors in the adult central nervous system (CNS). Glioblastoma (GBM) accounts for approximately 60-70% of primary gliomas. It is a great challenge to human health because of its high degree of malignancy, rapid progression, short survival time, and susceptibility to recurrence. Owing to the specificity of the CNS, the glioma microenvironment often contains numerous glial cells. Astrocytes are most widely distributed in the human brain and form reactive astrocyte proliferation regions around glioma tissue. In addition, astrocytes are activated under pathological conditions and regulate tumor and microenvironmental cells through cell-to-cell contact or the secretion of active substances. Therefore, astrocytes have attracted attention as important components of the glioma microenvironment. Here, we focus on the mechanisms of reactive astrocyte activation under glioma conditions, their contribution to the mechanisms of glioma genesis and progression, and their potential value as targets for clinical intervention in gliomas.

Leukemia is a kind of cancer characterized by the proliferation of abnormal, immature White Blood Cells (WBCs) produced in the bone marrow, which subsequently circulate throughout the body. Prompt leukemia diagnosis is vital in determining the optimal treatment plan, as different types of leukemia require distinct treatments. Early detection is therefore instrumental in facilitating the use of the most effective therapies. The identification of leukemia cells from microscopic images is considered a challenging task due to the complexity of the image features. This paper presents a deep learning neural network approach that utilizes the Particle Swarm Optimization (PSO) method to diagnose leukemia cell disease from microscope images. Initially, deep learning is employed to extract features from the leukemia images, which are then optimized by the PSO method to select the most relevant features for machine learning. Three different machine learning algorithms, namely Decision Tree (DT), Support Vector Machine (SVM), and K-Nearest Neighbors (K-NN) methods, are utilized to analyze the selected features. The results of the experiments demonstrate PSO accuracies of 97.4%, 92.3%, and 85.9% for SVM, K-NN, and DT algorithms with GoogLeNet, respectively. The proposed method achieved accuracies of 100%, 94.9%, and 92.3% for SVM, K-NN, and DT methods respectively, with Ant Colony Optimization (ACO) feature extraction and ResNet-50 employed as revealed by the experimental results. These findings suggest that the proposed approach is a promising tool for accurate diagnosis of leukemia cell disease using microscopic images.

Cervical cancer is the fourth leading cause of cancer mortality in women worldwide, with limited therapeutic options for advanced or recurrent cases. In this study, the effects of a recent thieno[2,3-b]pyridine derivative, (E)-3-amino-5-(3-bromophenyl)acryloyl)-N-(3-chloro-2-methylphenyl)-6-methylthieno[2,3-b]pyridine-2-carboxamide (compound 1), on two cervical cancer cell lines, HeLa and SiHa, are investigated. Cytotoxicity was assessed by MTT assay, apoptosis rates were measured by flow cytometry, and metabolic profiling was performed by GC-MS. The study also examined the expression of eight glycosphingolipids (GSLs) in cancer stem cells (CSCs) and non-CSCs to assess glycophenotypic changes. Compound 1 showed significant cytotoxicity in both cell lines, with apoptosis identified as the primary mechanism of cell death. A significant reduction in the CSC population was observed, particularly in the SiHa cell line. Compound 1 treatment altered GSL expression and decreased GM2 levels in both CSCs and non-CSCs in the SiHa cell line and Gg3Cer levels in the HeLa cell line. Metabolic profiling identified 23 and 21 metabolites in the HeLa and SiHa cell lines, respectively, with significant differences in metabolite expression after treatment. These results underscore the potential of compound 1 as a promising therapeutic candidate for cervical cancer and warrant further investigation in preclinical and clinical settings.