Cutaneous T-cell lymphoma (CTCL) is a progressive and heterogeneous malignancy characterized by deregulated metabolic reprogramming and cancer stemness, with limited therapeutic options. Therefore, elucidating the mechanisms driving metabolic reprogramming and poor clinical outcomes in CTCL is imperative. Forkhead box protein M1 (FOXM1), an oncogenic transcription factor, plays a pivotal role in cancer pathogenesis by orchestrating metabolic reprogramming and stemness signaling, thereby contributing to therapeutic resistance. In this study, we investigated the therapeutic potential of FOXM1 inhibition in human CTCL cells. Both genetic and pharmacological targeting of FOXM1 markedly suppressed CTCL cell growth and proliferation by inducing programmed cell death (apoptosis and autophagy) via reactive oxygen species (ROS) generation. Mechanistic analyses revealed that the activation of the MAPK, particularly JNK activation, is crucial for thiostrepton-induced programmed cell death. Metabolomics profiling further demonstrated that thiostrepton treatment triggers ROS- and JNK-dependent alteration in metabolic pathways central to cancer hallmarks, including amino acid and lipid metabolism. Notably, FOXM1 inhibition abrogated stemness-associated metabolic reprogramming genes (KLF-4, Bmi1) and Skp2, while upregulating the tumor suppressor p21 in a JNK-dependent manner. Moreover, thiostrepton treatment sensitized the CTCL cells to proteasome inhibitor bortezomib, promoting apoptosis and autophagy. Collectively, these findings demonstrate that FOXM1 targeting disrupts the metabolic status and stemness features of CTCL cells via JNK activation, thereby offering novel insights into potential therapeutic strategies for overcoming therapeutic challenges in CTCL.

INTRODUCTION:Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis and limited availability of reliable biomarkers. Extracellular vesicles (EVs) are membrane-bound nanoparticles released by cells that carry nucleic acids, proteins, and lipids reflective of their cellular origin. Their stability and accessibility through minimally invasive sampling make them promising liquid biopsy biomarkers. AREAS COVERED:This review summarizes current evidence supporting EVs as diagnostic and prognostic biomarkers in NSCLC. We discuss the clinical relevance of EV-associated molecular signatures, including miRNAs, other non-coding RNAs, and proteins, in early detection, disease stratification, and outcome prediction. Recent advances in EV isolation and characterization technologies, particularly microfluidic and high-throughput platforms, are highlighted. We also examine key barriers to clinical translation, including biological heterogeneity, methodological variability, and the lack of standardized protocols. EXPERT OPINION:EVs have the potential to transform NSCLC management by enabling minimally invasive diagnosis, real-time disease monitoring, and personalized treatment strategies. However, widespread clinical implementation requires standardized methodologies, improved tumor-specific EV enrichment, and large-scale validation studies. Future integration of multi-omics, artificial intelligence, and advanced detection technologies is expected to enhance biomarker performance and facilitate the incorporation of EV-based liquid biopsy approaches into precision oncology.

Multiple myeloma (MM) is a plasma cell cancer characterized by genomic instability and drug resistance. The FOXM1 transcription factor and the BUB1B kinase are pivotal drivers of this malignancy. FOXM1 promotes cell cycle progression and is upregulated by oncogenic pathways like mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT, correlating with aggressive disease. BUB1B ensures proper chromosome segregation, and its dysregulation fuels genomic instability. Critically, FOXM1 transcriptionally regulates BUB1B, forming an oncogenic axis that enhances proliferation, drug resistance, and survival. This FOXM1-BUB1B pathway is a promising therapeutic target, with inhibitors under preclinical investigation. Future research must validate its clinical relevance, explore combination therapies, and assess its potential as a biomarker to overcome challenges like toxicity and resistance.

ABSTRACT Background Ovarian cancer (OC) is a globally prevalent malignancy associated with a high mortality rate and marked biological heterogeneity, with most cases arising from epithelial cells and presenting as serous, endometrioid, or clear cell subtypes. Standard management is largely stage dependent and primarily involves cytoreductive surgery followed by platinum‐ and taxane‐based chemotherapy, with modifications based on disease extent and patient factors. Recent Findings In recent years, the therapeutic landscape of OC has evolved with the introduction of maintenance strategies and targeted therapies, particularly driven by advances in molecular profiling and the identification of biomarkers such as BRCA mutations and homologous recombination deficiency (HRD). These developments have led to the clinical integration of PARP inhibitors and anti‐angiogenic agents such as bevacizumab, which have improved disease control and survival outcomes as part of standard treatment strategies in OC, whereas immunotherapeutic approaches remain largely investigational and are currently limited to clinical settings. Metronomic chemotherapy (MCT), characterized by the continuous administration of low‐dose chemotherapeutic agents, has emerged as a promising alternative to conventional maximum tolerated dose regimens. MCT offers reduced systemic toxicity while exerting sustained antitumor effects through modulation of the tumor microenvironment, inhibition of angiogenesis, and enhancement of antitumor immune responses, thereby addressing key limitations of standard chemotherapy, including resistance and cumulative adverse effects. Furthermore, the integration of artificial intelligence (AI) into metronomic treatment strategies holds significant potential for optimizing drug selection, dosing schedules, and patient stratification. AI‐driven tools can facilitate predictive modeling, high‐throughput data analysis, and personalized treatment planning, ultimately enhancing therapeutic efficacy while minimizing toxicity. Conclusion This review summarizes current management strategies in OC with particular emphasis on maintenance therapies, targeted approaches, and emerging evidence supporting MCT and AI‐enabled approaches as potential future directions in OC therapy.

Sanguinarine (SNG) is a natural component belonging to the benzophenanthridine alkaloids. Various studies have reported its therapeutic potential in treating chronic human diseases such as cancer. SNG is reported to cause programmed cell death in various cancer cell lines. The mechanism by which SNG triggers apoptosis remains poorly elucidated, especially in vivo. Previous studies reported that sanguinarine induces apoptosis by increasing reactive oxygen species (ROS). In this study, we aimed to characterize the effects of SNG using an in vivo Caenorhabditis elegans (C. elegans) model. Treating C. elegans with various SNG concentrations resulted in apoptotic cell death in the proliferative germline. Interestingly, SNG-induced apoptosis depends on the core apoptotic machinery initiated by the DNA-damage-induced activity of the p53/CEP-1 protein. We have also demonstrated that the increase in germ cell apoptosis is caused by elevated levels of ROS following SNG treatment. Importantly, using a DNA end-labeling approach, we demonstrate that SNG induces DNA strand breaks in a ROS-dependent manner. Consistently, both DNA damage and apoptosis were significantly suppressed by treatment with the ROS scavenger N-acetylcysteine (NAC). Altogether, our study demonstrates that SNG induces ROS-dependent DNA damage, leading to activation of the DNA damage response and p53/CEP-1–mediated apoptosis in the proliferative germline of C. elegans.

Biomineralized gold nanoparticles (GNPs) are highly attractive in healthcare due to their inherent functional stability and biocompatibility. However, uncontrolled interactions with physiological fluids lead to rapid particle aggregation and opsonization, limiting their efficacy in vivo. To overcome this challenge, a novel biomimicked GNP system is synthesized using a biomineralization approach employing Fetal Bovine Serum (FBS) as the stabilizing agent, thereby resulting in the formation of an FBS-associated biomolecular layer on the nanoparticle surface. Comprehensive characterization validates the success of this engineering strategy. The FBS-capped GNPs exhibit improved colloidal behavior, as indicated by consistent Dynamic Light Scattering (DLS) measurements (PDI ≈ 0.15 over 48 h), and an average core size of 50 ± 11.3 nm as determined by Transmission Electron Microscopy (TEM), which falls within a size range commonly reported to be favorable for cellular uptake. Fourier Transform Infrared (FTIR) spectroscopy shows spectral shifts in Au-O and amide-related bands, suggesting surface association of biomolecular components. The in vitro efficacy of these optimized FBS-GNPs is tested against HCT116 colorectal cancer cells. Following 48 h of treatment, a substantial increase in apoptosis is observed at 50 μM GNP concentration. Mechanistic analysis reveals that the observed anticancer effect is driven by the activation of the intrinsic apoptotic pathway, initiated by genotoxic stress. This stress is evidenced by significantly increased levels of the DNA damage marker phosphorylated H2AX (pH2AX), followed by the activation and cleavage of executioner proteins, specifically Caspase-3 and Poly(ADP-ribose) polymerase (PARP). This work establishes that FBS-mediated surface changes enhance the nanomaterial's efficacy by promoting enhanced internalization and subsequent genotoxic activation of intrinsic apoptosis, validating this approach for developing stable, biocompatible, and targeted nanomedicines for colorectal cancer treatment.

Multiple myeloma (MM) is a plasma cell malignancy characterized by uncontrolled clonal expansion within the bone marrow, and despite major therapeutic advances, it remains largely incurable. The identification of novel agents capable of overcoming apoptosis resistance and targeting critical survival pathways is therefore essential. This study explored in vitro the anticancer potential of pristimerin (Prist), a natural quinone methide triterpenoid, in MM. Prist significantly inhibited the viability of U266 and RPMI8226 cells in a dose-dependent manner and induced cell cycle arrest in the SubG0/G1 phase, indicating apoptotic cell death. Mechanistic studies revealed that Prist triggers apoptosis via caspase cascade activation and targets the JAK/STAT signaling pathway, a critical oncogenic driver in MM. Network pharmacology and molecular docking suggests Prist's plausible binding with the STAT3 active site, a key component of the JAK/STAT pathway, supporting its inhibitory role. Western blot analysis demonstrated that Prist reduced the constitutive phosphorylated STAT3 (p-STAT3) as well as IL6- IL6-stimulated p-STAT3 levels in MM cells, further validating STAT3 pathway inactivation. Importantly, Prist synergistically enhanced the cytotoxic effects of bortezomib, further amplifying caspase activation and apoptotic signaling. Collectively, these findings identify Prist as a potent natural compound that suppresses MM progression by inducing apoptosis and blocking STAT3-driven oncogenic signaling. This study highlights Prist's therapeutic promise and supports its further evaluation as a standalone or combination strategy for MM treatment.

Pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest malignancies, driven by its invasive nature and lack of effective biomarkers. Disruption of the epithelial barrier, mediated by tight junction components, is a critical yet underexplored contributor to PDAC progression. Claudins, integral regulators of tight junction integrity, display altered expression across cancers, but their prognostic and immunomodulatory roles in PDAC remain unclear. We performed an integrative analysis of 177 RNA-Seq datasets from TCGA and GTEx to characterize Claudin family alterations in PDAC. Differential expression, copy number variation, methylation, and co-expression networks were analyzed alongside clinical and survival data. Prognostic significance was assessed using Kaplan - Meier and Cox regression analyses, while immune cell infiltration was examined using deconvolution algorithms. Functional validation of Claudin-1 was conducted in Capan-1 cells using CRISPR/Cas9 knockout, followed by proliferation, wound-healing, and Western blot assays. Ten Claudin genes were significantly dysregulated, with Claudin-1 and Claudin-4 frequently amplified and associated with advanced stage and poor survival. High Claudin-1 expression correlated with reduced immune infiltration, indicating an immune-excluded phenotype characterized by immune cells retained in the tumor stroma but largely absent from the tumor parenchyma. Claudin-1 knockout markedly inhibited proliferation, migration, and EMT, evidenced by downregulation of Snail and Slug and restoration of E-cadherin expression. This integrative transcriptomic and functional study identifies Claudin-1 as a key driver of PDAC aggressiveness and immune modulation. These findings establish Claudin-1 as a promising prognostic biomarker and therapeutic target for restoring epithelial integrity and counteracting immune evasion in pancreatic cancer.

Dysregulation of intracellular Ca2+ signaling is a critical determinant of cell fate, however the contribution of non-canonical Ca2+ reservoirs to cancer-selective apoptosis remains incompletely understood. In this study, realgar transforming solution (RTS), a microbially processed arsenical, was employed as a biologically informative perturbation to investigate how lysosomal pH dysregulation a Ca2+-associated mitochondrial apoptotic program in triple-negative breast cancer (TNBC) cells. RTS exhibited superior selectivity compared with inorganic arsenic trioxide (ATO) and paclitaxel, significantly reducing the viability of TNBC cells (MDA-MB-231, BT-549, and MDA-MB-468) while sparing non-malignant MCF-10 A cells.. RTS-induced cell death was characterized by a Ca2+-dependent mitochondrial program—marked by cytochrome c release and caspase-9 activation—operating independently of reactive oxygen species accumulation and p53 signaling. Mechanistically, RTS triggered sustained cytosolic and mitochondrial Ca2+ overload originating from lysosomal mobilization rather than extracellular influx or endoplasmic reticulum depletion. Time-course profiling identified lysosomal acidic intensification as an early event, preceding TRPML1-mediated Ca2+ efflux and subsequent lysosomal membrane permeabilization (LMP). Consistently, pharmacological neutralization of the acidic shift (BafA1) or TRPML1 inhibition (ML-SI1) significantly attenuated the cytosolic Ca2+ elevation observed at the measured intervals. Collectively, these in vitro findings establish a “lysosome-mitochondria” signaling axis in which early pH perturbation represents a potential vulnerability in TNBC. While the multicomponent nature of RTS requires further characterization, this study provides preliminary insights into targeting organelle-specific Ca2+ hubs as a complementary strategy for refractory solid tumors.

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

Cutaneous T-cell lymphoma (CTCL) is a skin-predominant form of non-Hodgkin lymphoma for which improved therapeutic options are needed. Here, we investigated the anti-lymphoma effects of pristimerin (PS) and defined its underlying mechanism in H9 and HH CTCL cell lines. PS strongly reduced cell growth and induced apoptosis, with hallmarks of mitochondrial (intrinsic) pathway activation, including caspase processing. PS also decreased basal AKT activity and downregulated pro-survival factors such as XIAP. In addition, PS reduced the abundance of S-phase kinase-associated protein 2 (SKP2) and was accompanied by increased levels of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1. Genetic suppression of AKT intensified apoptosis-associated signaling, reflected by increased H2AX activation and PARP cleavage. Notably, PS elevated intracellular reactive oxygen species (ROS), and scavenging ROS with N-acetylcysteine (NAC) significantly attenuated PS-driven cytotoxicity, supporting a ROS-dependent mechanism. Finally, PS combined with the proteasome inhibitor bortezomib produced greater anti-CTCL activity than either agent alone, consistent with a synergistic interaction. Together, these findings show that PS promotes ROS-dependent, mitochondria-mediated apoptosis in CTCL and support further evaluation of PS-based strategies for this malignancy.

Immunotherapy represents a paradigm shift in oncology, rooted in a century of evolving scientific understanding and clinical application. From the pioneering use of Coley’s toxins in the late nineteenth century to the introduction of cytokine-based interventions, the trajectory of immunotherapeutic approaches has paralleled advancements in immunology and molecular biology. This review comprehensively examines the historical development and progressive refinement of immunotherapy for cancer, charting the transition from non-specific immune stimulation to targeted immune modulation. Central to this discussion are the sophisticated mechanisms by which tumour cells evade immune detection and destruction. These include downregulation of antigen presentation machinery, secretion of immunosuppressive cytokines, recruitment of regulatory T cells and myeloid-derived suppressor cells, and exploitation of immune checkpoint pathways, particularly CTLA-4 and PD-1/PD-L1 axes. The advent of immune checkpoint inhibitors has yielded durable clinical responses in diverse malignancies, substantiating their role as foundational agents in cancer therapy. Nonetheless, both primary and acquired resistance to immune checkpoint inhibition remain significant clinical obstacles. Resistance mechanisms are multifactorial, involving tumour-intrinsic genetic alterations, modulation of the tumour microenvironment, and adaptive changes in immune cell phenotypes. Contemporary research endeavors are directed at overcoming these barriers, including the optimization of combinatorial regimens, development of next-generation checkpoint modulators, tumour-specific vaccines, and the integration of adoptive cell therapies. Future directions in cancer immunotherapy are poised to leverage advances in systems biology, genomics, and single-cell technologies to individualize interventions and enhance therapeutic efficacy. Ultimately, a comprehensive delineation of tumour-immune interactions will underpin the next generation of rational, effective, and durable cancer immunotherapies.

ABSTRACT Metastasis remains the leading cause of cancer‐related mortality and is increasingly recognized as a consequence of dynamic interactions between tumor cell plasticity and a heterogeneous tumor microenvironment (TME). Rather than being genetically fixed, cancer cells exhibit phenotypic flexibility, enabling reversible transitions among epithelial, mesenchymal, and stem‐like states in response to intrinsic programs and extrinsic microenvironmental cues, central to this adaptability. This review synthesizes emerging evidence that tumor progression is governed by reciprocal feedback loops between plastic tumor cells and distinct microenvironmental niches, including hypoxic cores, invasive margins, and perivascular regions. We highlight how stromal components, immune infiltrates, endothelial cells, and extracellular matrix (ECM) remodeling dynamically shape tumor cell states through biochemical and biophysical signals. Advances in single‐cell and spatial transcriptomic technologies have revealed the spatial organization and reversibility of these plastic phenotypes, uncovering rare but clinically significant drug‐tolerant persister populations. Importantly, we discuss plasticity‐mediated therapy resistance as an adaptive, nongenetic process driven by transcriptional and epigenetic reprogramming, metabolic flexibility, ECM stiffening–induced mechanotransduction, and immune‐checkpoint plasticity under therapeutic pressure. Together, these findings establish tumor plasticity and microenvironmental heterogeneity as an integrated, evolving system that fuels metastasis and limits durable treatment responses. Targeting this tumor–TME plasticity axis represents a promising strategy to disrupt metastatic progression and overcome therapeutic resistance.

Dysregulation of intracellular Ca2+ signaling is a critical determinant of cell fate; however the contribution of non-canonical Ca2+ reservoirs to cancer-selective apoptosis remains incompletely understood. In this study, realgar transforming solution (RTS), a microbially processed arsenical, was employed as a biologically informative perturbation to investigate the potential link between lysosomal pH dysregulation and a Ca2+-associated mitochondrial apoptotic program in triple-negative breast cancer (TNBC) cells. RTS displayed selective inhibitory activity compared with inorganic arsenic trioxide (ATO) and paclitaxel, leading to reduced viability of TNBC cells (MDA-MB-231, BT-549, and MDA-MB-468) while showing minimal impact on non-malignant MCF-10 A cells. RTS-induced cell death was linked to a Ca2+-mediated mitochondrial program-marked by cytochrome c release and caspase-9 activation-while showing limited correlation with reactive oxygen species (ROS) accumulation or p53 signaling. Mechanistically, RTS triggered sustained cytosolic and mitochondrial Ca2+ overload derived primarily from lysosomal mobilization rather than extracellular influx or endoplasmic reticulum depletion. Time-course profiling observed lysosomal acidic intensification as an early event, preceding TRPML1-mediated Ca2+ efflux and subsequent lysosomal membrane permeabilization (LMP). Consistently, pharmacological neutralization of the acidic shift (BafA1) or TRPML1 inhibition (ML-SI1) significantly attenuated the cytosolic Ca2+ elevation observed at the measured intervals. Collectively, these in vitro findings highlight a potential"lysosome-mitochondria" signaling axis in which early pH perturbation may represent a vulnerability in TNBC. While the multicomponent nature of RTS requires further characterization, this study provides preliminary insights into targeting organelle-specific Ca2+ hubs as a possible complementary strategy for refractory solid tumors.

Cutaneous T-cell lymphoma (CTCL) is a rare non-Hodgkin lymphoma with limited durable treatment options and poor overall survival, underscoring the need for new therapeutic approaches. Sanguinarine (SNG), a natural benzophenanthridine alkaloid, has demonstrated anticancer activity in several malignancies, but its potential role in CTCL remains unexplored. We hypothesized that SNG induces oxidative stress and mitochondrial dysfunction, leading to the inhibition of the PI3K/AKT/GSK3 pathway and apoptosis in CTCL cells. In vitro experiments were performed using HH and H9 CTCL cell lines. Cytotoxicity, apoptosis, and mitochondrial function were evaluated by cell viability assays, caspase activation, PARP cleavage, Bax/Bcl-2 ratio, mitochondrial membrane depolarization, and cytochrome c release. ROS generation and glutathione depletion were measured with and without N-acetyl cysteine (NAC) rescue. Western blotting assessed modulation of the AKT/GSK3α/β/mTOR pathway and expression of anti-apoptotic proteins (XIAP, cIAPs, Mcl-1). Synergistic effects with bortezomib (BTZ) were analyzed. Network pharmacology, molecular docking, molecular dynamics (MD) simulations, and binding free energy (BFE) calculations were used to identify SNG's molecular targets. SNG reduced CTCL cell viability (IC₅₀ < 5 μM) and triggered mitochondrial-mediated apoptosis, accompanied by Bax/Bcl-2 modulation, ΔΨm loss, cytochrome c release, and caspase-9/3 activation. ROS accumulation and glutathione depletion contributed to cytotoxicity, effects that were reversed by NAC. SNG suppressed AKT/GSK3/mTOR signaling and downregulated anti-apoptotic proteins. Notably, SNG enhanced the anticancer activity of BTZ in combination studies. Computational analyses supported AKT and Bcl-2 as key binding targets. SNG exerts potent anticancer effects in CTCL by inducing ROS-dependent mitochondrial apoptosis and inhibiting the PI3K/AKT/GSK3 signaling pathway. Its synergy with BTZ and computational validation of AKT/Bcl-2 targeting underscore its potential as a novel therapeutic candidate for CTCL, warranting further preclinical investigation.

Multiple Myeloma (MM) is the third most common hematological malignancy worldwide. Despite advancements in available therapies, MM remains incurable for most patients, mainly due to the early relapse and eventual resistance to therapy, underlining the need for novel drugs. Among these, multi-specific antibodies (MsAbs) have emerged as promising agents. Multi-specific immune cell-engaging antibodies, such as bi-specific, and tri-specific are designed to recognize two or more antigens on the same or distinct cells. These antibodies could promote cancer cell clearance by engaging both myeloma cells and cytotoxic immune cells such as T and Natural killer (NK) cells and macrophages (M). Currently, four bi-specific T cell engagers (teclistamab, elranatamab, talquetamab and linvoseltamab) are approved for refractory or relapsed MM patients (RRMM). While these therapies have demonstrated promising results in achieving deep remissions in RRMM, primary resistance occurs in about one-third of patients. Initially, immune engager research focused only on T cells due to their crucial anti-cancer role, but more recently, interest has expanded to NK cells and M for broader therapeutic potential. To date, several NK and M engaging MsAbs with mainly bi-specific and tri-specific formats are in clinical or preclinical evaluation for improving MM patients’ response and reduce treatment related toxicity. This review discusses the recent advancement in T, NK and M engaging MsAbs in treating MM, including immunological background, mechanisms of action, relevant clinical and preclinical advancements and challenges. Moreover, we discuss the advantages and drawbacks of the different immune cell engagers. Furthermore, we review recent studies investigating the clinical and molecular determinants of resistance along with the latest predictive or prognostic biomarkers of response to MsAbs. Finally, we explore novel strategies to enhance MsAbs efficacy and reduce their toxicity, providing long-term disease control and improving survival in MM patients.

A COVID-19 booster dose has been found to be effective in our fight against SARS-CoV-2 infection. However, their long-term beneficial or adverse effects among healthy individuals are not fully understood. We investigated the impact of the Pfizer-BioNTech-(BNT162b2) booster dose on plasma proteome profiles of fully vaccinated healthy individuals in a mimic of reinfection to understand the disease mechanisms and to identify novel diagnostic and prognostic biomarkers. In contrast to prebooster, postbooster recipients exhibited a distinct proteomic signature following SARS-CoV-2 spike (S) protein stimulation. The gene ontology (GO) terms of biological processes revealed the five most significant functions enriched in stress and immune responses, especially via complement and blood coagulation systems. Likewise, the Reactome pathway demonstrated significant activation of complement cascade, platelet degranulation, and innate immune systems. Moreover, the protein-protein interaction network exhibited regulation of body fluid levels and acute inflammatory response. In summary, our study identified abundant dysregulated signatures predominantly associated with the complement, the innate immune system, and platelet degranulation. Besides eliciting humoral immunity, our study also found key proteins involved in blood coagulation pathways that could perhaps shed light on individuals exhibiting comorbidities associated with COVID-19 vaccination. Therefore, factors dysregulated following SARS-CoV-2 spike (S) protein stimulation may provide insights into pathways potentially implicated in post-vaccination reactions.

Cancer stem cells (CSCs) are a small subpopulation bearing self-renewal ability, mediating tumor initiation and propagation. Several molecular pathways, including the PI3K/AKT/mTOR pathway, are known to be aberrantly activated in cancers. In CSCs, PI3K/AKT/mTOR pathway has been associated with attribution of various properties to cancer cells including stemness characteristics, proliferation, migration, epithelial to mesenchymal transition, and autophagy. Thus, targeting PI3K/AKT/mTOR pathway with novel inhibitors might help to control the growth and proliferation of the breast CSC population. Though many studies have focused on PI3K/AKT/mTOR pathway in breast cancer, limited literature is available on the role of PI3K/AKT/mTOR pathway in breast CSCs. Here, in our present review, we have highlighted the role of the PI3K/AKT/mTOR signaling pathway in breast CSCs and its applications in therapeutic targeting.

Despite recent breakthroughs in diagnosis and treatment, cancer remains a worldwide health challenge with high mortality. Autophagy plays a major role in the progression and development. Starving cancer cells obtain nutrients through the upregulation of autophagy. Several compounds derived from natural sources, including animals, plants, and microorganisms, have been identified as potential novel anticancer drugs. Spices play an important role in human health and possess many medicinal properties. Our study aimed to identify potential autophagy modulators from panch phoron spices (P5S) through in silico approaches. Herein, we report a structure-based virtual screening of compounds isolated from P5S (i.e., cumin, fenugreek, fennel, black mustard, and black cumin) against the molecular targets of autophagy. Using various computational tools, we attempted to identify potential modulators of autophagy. Among all the screening results (such as binding energy, hydrogen bonding, drug-likeness, bioactivity, ADME properties, and toxicity), P5S, stigmasterol, and tigogenin showed the best drug-like properties and binding affinity toward the selected targets of autophagy. Furthermore, the stability of both complexes was evaluated by performing a 100 ns molecular dynamics simulation (MDS) using Schrodinger's Desmond Module. Our results provide insight into the efficacy of P5S components against cancer. Therefore, targeting autophagy using these molecules may be an effective and potential drug candidate for cancer treatment. In conclusion, stigmasterol and tigogenin may act as potential candidates for anticancer drugs by targeting autophagy.

Periodontitis is a common chronic inflammatory disease leading to alveolar bone resorption and tooth loss. This is mainly caused by oral biofilms which are composed of pathogenic bacterial species. The development of a technique for quick and biocompatible sample enrichment is crucial for sensitive diagnosis since pathogenic bacteria typically live in complicated experimental matrixes at extremely low concentrations. In this study, polymyxin-B functionalized chitosan-coated magnetic nanobeads (PolyB-CS-MNBs) were constructed for efficient sample pre-concentration and DNA extraction of Gram-negative pathogenic bacteria from saliva for PCR detection. Chitosan coating enhances nanobead's biocompatibility and water solubility while functionalized PolyB acts as a specific probe to capture gram-negative bacteria. Results demonstrate that magnetic nanobeads (MNBs) attained more than 95 % capture efficiency even if at a concentration of 101 cfu/mL. The occurrence of both Chitosan (CS) and polymyxin-B on MNBs was verified via a comprehensive analysis of X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and energy- dispersive spectroscopy (EDS). Contributed to the good biocompatibility achieved by the employing of coating of CS, highly efficient enrichment can be completed in 30 min. PolyB-CS-MNBs demonstrated a remarkable capacity to pre-concentrate E. coli in saliva, effectively lowering the Limit of Detection (LOD) up to 10 cfu/mL when coupled with polymerase chain reaction (PCR). This represents a 1000-times increase in sensitivity compared to PCR performed without pre-concentration using PolyB-CS-MNBs. The innovative strategy employing PolyB-CS-MNBs holds significant promise for Gram-negative bacteria identification, facilitating early intervention in periodontic infection, predicting treatment efficacy, and potentially mitigating disease rates.