These data show the differentially expressed genes (DEG) from HCC38 breast cancer cell line chronically exposed to nicotine versus vehicle control. Additional data is also provided from dynamic trajectory analysis, identifying the most dynamic genes due to chronic nicotine treatment. To produce this dataset, we first performed single cell RNA sequencing from HCC38 cells chronically treated with vehicle or nicotine, followed by scanpy analysis to yield 6 discrete cell clusters at conservative resolution. We then evaluated differential gene expression between chronic nicotine and control cells for each individual cluster or in the whole sample using PyDESeq2. For dynamic trajectory analysis, Velocyto (0.6) was used to estimate the spliced and unspliced counts for each gene between chronic nicotine-treated cells and vehicle, allowing computation of gene velocities. These data are useful for analysing the expression of individual genes or gene velocities either in the whole sample or in the different clusters identified. Since the HCC38 cell line used in these experiments is heterogeneous, including cells with features of stem-like, luminal progenitor-like and more differentiated cells, this dataset allows examination of the conserved as well as disparate gene expression effects of nicotine in different breast cancer cell types. Our dataset has a great potential for re-use given the recent surge in interest surrounding the role tobacco-use plays in breast cancer progression.

Cancer stem cells (CSC) are endowed with multipotency, self-renewal and unique tumorigenic potential. They have been identified as cells with high activity of aldehyde dehydrogenase (ALDH) and high expression of CD44 in head and neck squamous cell carcinoma (HNSCC). The objective of this work is to understand whether salivary gland adenoid cystic carcinoma contain CSCs and whether they exhibit a unique tumorigenic activity in this cancer.

The human lens capsule is a transparent and durable basement membrane routinely discarded during cataract surgery, exhibiting unique biochemical, biomechanical, and immunologic properties. This narrative review discusses validated ophthalmic applications across corneal, retinal, and glaucoma filtration surgeries. It emphasizes the capsule's emerging role as a tissue-engineering scaffold for cultivating corneal endothelial cells, limbal epithelial stem cells, and retinal pigment epithelial cells, demonstrating significant promise in regenerative ophthalmology. However, variability in harvesting techniques, small graft sizes, and limited long-term clinical data currently hinder its broader clinical implementation. Future directions highlight the necessity of standardizing capsule harvesting and preservation protocols, potentially in collaboration with eye banks, to enhance accessibility and utility. Additionally, this review explores speculative applications, including encapsulation devices for drug and cell delivery, ultraviolet cross-linking for keratoconus management, and novel scaffolds for optic nerve regeneration and retinal transplantation. While preliminary evidence strongly supports the capsule's versatility, rigorous clinical trials and comparative analyses remain essential to establish long-term safety, efficacy, and optimal surgical integration. Ultimately, harnessing this naturally available biomaterial represents a meaningful advancement in ophthalmology, opening new horizons for future research.

Titanium implants are widely used in dentistry due to their mechanical strength and biocompatibility, yet their biological inertness and lack of antimicrobial properties contribute to high failure rates from poor osseointegration and infections like peri-implantitis. To address these limitations, this study developed a gold nanostar (GNS)-coated titanium implant (Ti-GNS) and systematically evaluated its osteogenic and photothermal antibacterial functions. The research aimed to enhance osseointegration through surface modification while leveraging GNS's photothermal effect for on-demand antibacterial activity, offering a dual-functional strategy to improve implant performance.

This study aims to assess the predictive potential of circulating tumor cells (CTCs) and circulating tumor stem cells (CTSCs) in locally advanced triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy (NAC) compared to the RECIST 1.1 standard.

Hyperbaric oxygen enhances glioma chemosensitivity, but the mechanism remains unclear. Hypoxia is common in gliomas, and as the main effector molecules of hypoxia, HIF1α and HIF2α promote the malignant progression by inhibiting cell apoptosis and maintaining stemness. ABCG2 is a marker protein of tumor stem cells and drug efflux transporter protein. This study aims to reveal the detailed mechanism of hyperbaric oxygen promote both proliferation and chemosensitization.

Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.

Tumor lineage plasticity (LP) is an emerging hallmark of cancer progression. Through pharmacologically probing the function of epigenetic regulators in prostate cancer cells and organoids, we identified bromodomain protein BRD4 as a crucial player. Integrated ChIP-seq and RNA-seq analysis of tumors revealed, for the first time, that BRD4 directly activates hundreds of genes in the LP programs which include neurogenesis, axonogenesis, EMT and stem cells and key drivers such as POU3F2 (BRN2), ASCL1/2, NeuroD1, SOX2/9, RUNX1/2 and DLL3. Interestingly, BRD4 genome occupancy is reprogrammed by anti-AR drugs from facilitating AR function in CRPC cells to activating the LP programs and is facilitated by pioneer factor FOXA1. Significantly, we demonstrated that BRD4 inhibitor AZD5153, currently at clinical development, possesses potent activities in complete blockade of tumor growth of both de novo neuroendocrine prostate cancer (NEPC) and treatment-induced NEPC PDXs and that suppression of tumor expression of LP programs through reduction of local chromatin accessibility is the primary mechanism of action (MOA) by AZD5153. Together, our study revealed that BRD4 plays a fundamental role in direct activation of tumor LP programs and that its inhibitor AZD5153 is highly promising in effective treatment of the lethal forms of the diseases.

Psoriasis is defined as a persistent autoimmune disease characterized by the appearance of psoriatic lesions on the surface of the skin. Currently, various approaches including chemicals, corticosteroids, phototherapy, and biological agents are being proposed and implemented to improve psoriatic lesions by modulating immune system activity or metabolic processes, often with unintended consequences and side effects. Currently, mesenchymal stromal/stem cells (MSCs) have attracted considerable interest among researchers due to their ability to modulate immune responses and their ease of application, representing a promising strategy for alleviating clinical symptoms in the treatment of allergic reactions, autoimmune diseases, cancer, and more. This study will investigate how MSCs interact with immune system cells involved in psoriasis development, such as neutrophils, keratinocytes, dendritic cells (DC), and T cell subtypes, for potential therapeutic use in psoriasis management. In this case, several immunomodulatory mechanisms are involved, including expression of chemokines, pro-inflammatory cytokines, matrix metalloproteinase and other factors involved in cell proliferation and neutrophil extracellular trap (NET) formation are among the effects of MSCs on keratinocytes and neutrophils. keratinocytes and neutrophils as pro-inflammatory cells involved in psoriasis pathogenesis and pathogenesis and progression of psoriasis. On the other hand, MSCs interact with DCs and various subsets of T cells, including Th1, Th2, Th17 and Tregs, to generate tolerogenic DCs and increase the differentiation of Tregs and modulate the Th17/Treg towards a regulatory state through overexpression of anti-inflammatory and immunomodulatory and immunomodulatory cytokines, including IL-10 and transforming growth Factor beta (TGF-β). Finally, we will focus on the challenges and obstacles in psoriasis treatment using MSCs, including limitations in the case of using MSCs from different sources and side effects that may be encountered by whole cell therapy strategies, which are attracting attention towards the implication of cell-free regimens such as using MSC-derived secretome or extracellular vesicles and exosomes to provide similar therapeutic outcomes without presumed side effects.

Our aim was to identify crucial RNA-binding proteins (RBP) genes associated with Ewing sarcoma (EwS) in order to provide valuable insights into its mechanisms of tumorigenesis and to enhance therapeutic intervention.

Osteoarthritis (OA) is a degenerative joint disease that primarily affects older adults, characterized by cartilage degradation, synovitis, and osteophyte formation. Despite its prevalence, no medical treatment can reverse the joint cartilage degradation, leading many patients to undergo invasive procedures such as arthroplasty. Mesenchymal stem cells (MSCs), particularly those derived from adipose tissue, have emerged as a promising therapeutic approach due to their ability to differentiate into chondrocytes and potentially regenerate cartilage. While MSCs from bone marrow and umbilical cord have shown efficacy in treating OA, adipose-derived MSCs (ADMSC) are more accessible and cost-effective. This study aims to evaluate the safety and efficacy of allogeneic ADMSC in treating knee OA.

Letermovir is an antiviral agent that significantly decreases the frequency of cytomegalovirus (CMV) infections following allogeneic hematopoietic stem cell transplantation (allo-HCT); however, its impact on Epstein-Barr virus (EBV) infection remains unclear. This multicenter, retrospective study involved 565 patients aged ≥ 18 years, who underwent allo-HCT between January 2021 and December 2023, with 284 receiving letermovir prophylaxis (letermovir group) and 281 not (control group). Cumulative incidences of clinically significant CMV infection (cs-CMVi), EBV DNAemia, EBV-disease and post-transplant lymphoproliferative disorder (PTLD) were compared between the groups. The 1-year cumulative incidence of EBV DNAemia did not differ significantly between the letermovir and control groups (58.1% vs. 52.7%, P = 0.3). However, letermovir prophylaxis was associated with a significantly higher incidence of PTLD within the first year post-HCT (7.39% vs. 1.80%, P = 0.00059). Multivariate analysis identified letermovir prophylaxis as an independent risk factor for PTLD (HR [95% CI]: 4.619 [1.458-10.278], P = 0.007). Letermovir altered the early reconstitution trajectory after allo-HCT, particularly in CD8+ T cells. Our findings emphasized that although letermovir prophylaxis did not increase the risk of EBV DNAemia in allo-HCT recipients, it was associated with a higher incidence of PTLD. Further studies focusing on immune reconstitutiom dynamics are warranted to elucidate the underlying pathophysiology of EBV-PTLD under letermovir pressure.

We previously reported that a vascular endothelial stem cell population resides in pre-existing blood vessels in mice and may contribute to vascular endothelial cells in liver injury or hind limb ischemia models in the long-term. However, whether such stem cells exist in humans and can differentiate specifically into vascular endothelial cells have not been determined. We hypothesized that CD157+ vascular endothelial cells in humans may also possess high angiogenic potential.

Atopic dermatitis (AD) management is significantly challenging due to the high prevalence, chronicity, and recurrent nature of the disease, and limited options for its treatment. Human umbilical cord mesenchymal stem cells (hUC-MSCs) exhibit potential effects against AD; however, the mechanisms underlying these effects remain largely unexplored.

Periodontitis is a chronic inflammatory disease that significantly impacts periodontal bone regeneration, yet the distinct biological features of osteoblasts in this condition remain poorly understood. This study aims to elucidate the cellular and molecular mechanisms underlying osteoblast dysfunction in periodontitis, with a focus on the role of Fusobacterium nucleatum (Fn) and its effector protein, D-galactose-binding periplasmic protein (Gbp).

The JAK/STAT signaling pathway plays a crucial role in the release of interferons (IFNs) and the proinflammatory response during SARS-CoV-2 infection, contributing to the cytokine storm characteristic of severe COVID-19 cases. STAT3, a key protein in this pathway, has been implicated in promoting inflammation, making its inhibition a potential therapeutic strategy to mitigate disease severity. Mesenchymal Stem Cell-derived Extracellular Vesicles (MSC-EVs), enriched with immunomodulatory and antiviral miRNAs, offer a promising therapeutic approach by modulating gene expression and regulating inflammatory responses. This study investigates the ability of Lyophilized MSC-EVs to inhibit the JAK/STAT pathway, highlighting their potential application in COVID-19 management.

Chronic myeloid leukemia (CML) is influenced by microenvironmental nutrients, glucose (Glc), and glutamine (Gln) which regulate cell proliferation, viability, and the expression of the driver oncoprotein (BCR::ABL1).

The remarkable biophysical properties of metastatic migrating cells, such as their exceptional motility and deformability, enable them to migrate through physical confinements created by neighboring cells or extracellular matrix. This study explores the adaptive responses of breast cancer (BC) cell sublines derived from the highly aggressive, metastatic triple-negative MDA-MB-231 and the non-metastatic MCF7 human BC cell lines, after undergoing three rounds of confined migration (CM) stress. Our findings demonstrate that CM elicits common and cell-type specific adaptive responses in BC cell sublines. In particular, both cell sublines exhibit a similar enhancement of clonogenicity and nanoparticle (NP) uptake activity, indicating tumorigenic potential. We have, for the first time, shown that stimulation with CM induces a hybrid epithelial-to-mesenchymal transition (EMT) phenotype of MDA-MB-231 cells. This transition is characterized by a significant rise in the expression of stage-specific embryonic antigen-4 (SSEA4), alongside a substantial decline in the population of CD133+ cells and a marked reduction in Ki67 expression in the MDA-MB-231-derived subline following Cis-Platin treatment. These changes are likely associated with heightened resistance of this subline to cisplatin. In contrast, CM induces far fewer such alterations in the MCF7-derived counterpart with a notable increase of CD133+ population, which seems to be insufficient to change cell susceptibility to cisplatin exposure. This study contributes to our understanding of the adaptive mechanisms underlying metastasis and drug resistance in breast cancer, emphasizing the need for personalized approaches in cancer treatment that consider the heterogeneous responses of different cancer subtypes to environmental stresses.

Soft tissue injury (STI) is a prevalent condition that requires effective therapeutic approaches. The focus of this investigation was to elucidate the molecular mechanisms linked to the IGFBP3 protein in adipose-derived stem cells (ADSCs) for STI repair, utilizing single-cell multiomics technology and a 3D bioprinting model. Establishment of a mouse-based STI model facilitated the comparison of cellular compositions and communication variances between wounded and normal tissues through single-cell RNA sequencing (scRNA-seq). High-throughput transcriptomics and bioinformatics analysis pinpointed IGFBP3 as a key target in ADSCs related to STI repair. In vitro experiments assessed IGFBP3's effects on ADSCs' epithelial cell differentiation, proliferation, and migration using various assays and lentivirus transfection to manipulate IGFBP3 expression. A 3D bioprinting technique was used to create an ADSCs-IGFBP3 peptide self-assembling hydrogel scaffold, characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, SEM, and TEM. The scaffold's efficacy was validated in an animal model. Results showed nine cell subtypes in both normal and injured tissues, with increased ADSCs in STI tissues exhibiting enhanced connectivity and interactions. RNA-seq analysis confirmed IGFBP3 as crucial for ADSCs and STI. In vitro and 3D bioprinting experiments, along with animal model validation, confirmed IGFBP3's role in STI repair. Upregulation of IGFBP3 in ADSCs promoted epithelial cell differentiation by enhancing ITGB1 expression, activating the ERK pathway to boost cell proliferation and migration. This study highlights IGFBP3's significant role in ADSCs for STI repair, providing potential molecular targets for developing new treatments. The findings offer valuable insights into IGFBP3's mechanisms, aiding in advancing STI therapeutic strategies.

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is attributed to tumor microenvironment driven by hypoxia regulated carbonic anhydrase IX. Our study elucidates the ability of Methazolamide, a CAIX inhibitor to sensitize resistant PDAC cells. The effect of Methazolamide alone and in combination with gemcitabine on proliferation, migration, tumor inhibition along with its impact on metastasis by influencing HIF-1α/PTEN/Glut1/Glut3 signalling through the expression of CAIX was assessed. Methazolamide induced cytotoxicity in several PDAC cells including patient derived with IC50 0.7-4.09 mM and 0.29-2.56 mM in monolayer and clonogenic assays respectively. Methazolamide alone and in combination significantly downregulated hypoxia induced expression of HIF-1α and CAIX together with proliferation (Ki-67, Cyclin D1), invasion (Rac-1, Snail), stem cell (Oct-4, Sox-2), angiogenesis (VEGF), glycolysis (Glut1, Glut3) and apoptosis (Bax, Bc1-2 and PTEN) markers in MIA PaCa-2 and PANC-1 cells. In vivo study in PAXF 546L PDX model exhibited profound tumor growth inhibition with downregulation of CD34, Oct-4, Sox-2, C-myc, Nanog, Ki-67, and Rac-1 signalling. Considering inadequate availability of effective therapeutics and importance of CAIX in processes leading to aggressive behavior of PDAC, targeting it by using Methazolamide, a pre-approved drug in combination with gemcitabine represents promising therapeutic approach specifically in metastatic settings.