Intratumor heterogeneity of HPV integration in HPV-associated head and neck cancer.

Integration of human papillomavirus (HPV) into the host genome drives HPV-positive head and neck squamous cell carcinoma (HPV HNSCC). Whole-genome sequencing of 51 tumors revealed intratumor heterogeneity of HPV integration, with 44% of breakpoints subclonal, and a biased distribution of integration breakpoints across the HPV genome. Four HPV physical states were identified, with at least 49% of tumors progressing without integration.

The cryptic lncRNA-encoded microprotein TPM3P9 drives oncogenic RNA splicing and tumorigenesis.

Emerging evidence demonstrates that cryptic translation from RNAs previously annotated as noncoding might generate microproteins with oncogenic functions. However, the importance and underlying mechanisms of these microproteins in alternative splicing-driven tumor progression have rarely been studied. Here, we show that the novel protein TPM3P9, encoded by the lncRNA tropomyosin 3 pseudogene 9, exhibits oncogenic activity in clear cell renal cell carcinoma (ccRCC) by enhancing oncogenic RNA splicing.

Role of Non-Canonical Stacking Interactions of Heterocyclic RNA Bases in Ribosome Function.

Identification and analysis of repetitive elements (motifs) in DNA, RNA, and protein macromolecules is an important step in studying structure and functions of these biopolymers. Functional role of NA-BSE (non-adjacent base-stacking element, a widespread tertiary structure motif in various RNAs) in RNA-RNA interactions at various stages of the ribosome function during translation has been investigated in this work. Motifs of this type have been described to date that are reversibly formed during mRNA decoding, moving of the ribosome subunits relative to each other, and moving mRNA and tRNA along the ribosome during translocation.

Novel Rhamnose-Containing Glycopolymers from the Cell Wall of VKM Ac-1390.

VKM Ac-1390 (family Microbacteriaceae, class Actinomycetes) contains three rhamnose-containing glycopolymers in the cell wall, the structures of which were established by chemical and NMR spectroscopy methods. The first polymer, a rhamnomannan, consists of repeating tetrasaccharide units with xylopyranose side residues, →2)-α-[β-D-Xyl-(1→3)]-D-Rha-(1→3)-α-D-Man-(1→2)-α-D-Rha-(1→3)-α-D-Man-(1→. The second polymer found in minor amounts, is a rhamnan, →2)-α-D-Rha-(1→3)-α-D-Rha-(1→.

Gender differences in cognitive impairment among the elderly in rural West Texas counties.

Background: The prevalence of Alzheimer's disease or dementia in the elderly population has been increasing both nationally and globally. Males and females are impacted differently when it comes to cognitive health, and this can be influenced by various risk factors.

Objective: This study highlights the sociodemographic, chronic disease, and genetic biomarker risk factors associated with gender differences and cognitive impairments in the elderly population living in Cochran, Parmer, and Bailey counties of rural West Texas.

Nuclear calcium signaling in D1 receptor-expressing neurons of the nucleus accumbens regulates molecular, cellular and behavioral adaptations to cocaine.

Background: The persistence of cocaine-evoked adaptations relies on gene regulations within the reward circuit, especially in the ventral striatum (i.e., nucleus accumbens (NAc)).

Comprehensive Analysis of Apigetrin's Effects on Liver Cancer Cells: Insights from Bioinformatics, In Vitro Studies, and Next-Generation Transcriptome Sequencing.

Despite numerous attempts to understand the molecular mechanisms behind the development of liver cancer, it continues to pose a significant worldwide health challenge. Transcriptome sequencing, a powerful tool in molecular biology, has played a pivotal role in uncovering the intricate gene expression profiles underlying hepatocellular carcinoma (HCC). In the present study, we identified a total of 808 differentially expressed genes (DEGs), with 584 exhibiting downregulation, and 224 showing upregulation following apigetrin treatment.

PSMA-targeted delivery of docetaxel in prostate cancer using small-sized PDA-based micellar nanovectors.

In this study, we present the first comparative analysis of active and passive drug delivery systems for docetaxel (DTX) in prostate cancer using supramolecular self-assembled micellar nanovectors. Specifically, we developed two novel micelles based on polydiacetylenic amphiphiles (PDA) for passive and active targeting. The active targeting micelles were designed with a prostate-specific membrane antigen (PSMA) ligand, ACUPA, to facilitate recognition by PSMA-positive cancer cells.

Surveying helix 12 dynamics within constitutively active estrogen receptors using bipartite tetracysteine display.

Somatic Y537S and D538G mutations within the estrogen receptor alpha ligand-binding domain (ERα-LBD) have been linked to enhanced cell proliferation, survival, and metastases in ER-positive breast cancers. Such mutations are thought to confer ligand-independent receptor activation by increasing the flexibility of helix 12 (H12), a segment within the ERα-LBD that acts as a dynamic regulator of ERα activity. We employed bipartite tetracysteine display coupled with the biarsenical profluorophore FlAsH-EDT to monitor ligand-independent structural transitions of H12 in ERα-LBDs that include Y537S or D538G mutations.

TFII-I/GTF2I regulates globin gene expression and stress response in erythroid cells.

Transcription factor TFII-I/GTF2I is ubiquitously expressed and has been shown to play a role in the differentiation of hematopoietic cells and in the response to various cellular stressors. We previously demonstrated that TFII-I acts as a repressor of adult β-globin gene transcription and positively regulates expression of stress response proteins, including ATF3. Here we analyzed the function of TFII-I in TF-1 cells during erythroid differentiation and in response to cellular stress, including unfolded protein response, hypoxia, and oxidative stress.

Ailanthone induces triple-negative breast cancer cells death involving the inhibition of OTUB1-mediated ERRα deubiquitylation.

Introduction: Triple-negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer, and effective therapeutic strategies are needed. Estrogen-related receptor alpha (ERRα) is considered a promising target for managing TNBC.

Objectives: Here, we aimed to screen natural products to find downregulator of ERRα and elucidate its mechanism of action.

Lactylation: The Metabolic Accomplice Shaping Cancer's Response to Radiotherapy and Immunotherapy.

Protein lactylation, an emerging post-translational modification, is providing new insights into tumor biology and challenging our current understanding of cancer mechanisms. Our review illuminates the intricate roles of lactylation in carcinogenesis, tumor progression, and therapeutic responses, positioning it as a critical linchpin connecting metabolic reprogramming, epigenetic modulation, and treatment outcomes. We provide an in-depth analysis of lactylation's molecular mechanisms and its far-reaching impact on cell cycle regulation, immune evasion strategies, and therapeutic resistance within the complex tumor microenvironment.

Tumor-derived extracellular vesicle PD-1 promotes tumor immune evasion via disruption of peripheral T cell homeostasis.

The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) axis mediates immune evasion of tumor, and targeting this axis has achieved some clinical benefits. The regulation of PD-1 expression in immune cells has been well studied. However, whether any other potential source of immune cell-expressed PD-1 exists remains unknown.

The novel use of the CFTR corrector C17 in muscular dystrophy: Pharmacological profile and in vivo efficacy.

Sarcoglycanopathies are rare forms of severe muscular dystrophies currently without a therapy. Mutations in sarcoglycan (SG) genes cause the reduction or absence of the SG-complex, a tetramer located in the sarcolemma that plays a protective role during muscle contraction. Missense mutations in SGCA, which cause α-sarcoglycanopathy, otherwise known as LGMD2D/R3, lead to folding defective forms of α-SG that are discarded by the cell quality control.

Discovery of novel benzo[b][1,4]oxazine derivatives as ferroptosis inhibitors.

Ferroptosis is a novel type of programmed cell death characterized by radical-driven lipid peroxidation accumulation, which is involved in various diseases, including acute organ injury and neurodegenerative disorders. Pharmacological inhibition of ferroptosis is a promising strategy for treating these diseases. In this study, 16 benzo[b][1,4]oxazine derivatives were synthesized and assayed for their antiferroptotic activity.

New 2-indolinone-indole hybrid compounds carrying a benzoyl moiety as tyrosine kinase inhibitors.

In this study, new 2-indolinone-indole hybrid compounds (4a-s) carrying a benzoyl moiety were synthesized and their cytotoxic effects were examined against pancreatic (MIA-PaCa-2) and colon (HT-29 and HCT-116) cancer cells by MTT assays. Most of the tested compounds exhibited a better inhibitory activity and safety profile than the reference standard sunitinib malate against MIA-PaCa-2 and HCT-116 cancer cells. Compound 4e displayed the greatest cytotoxic effect on HCT-116 cell with an IC value of 0.

The double-edged sword role of natural Killer cells in Parkinson's disease.

Neurological disorders are the leading cause of disability worldwide, with Parkinson's disease (PD) emerging as a rapidly growing neurological condition on a global scale. Although treatments exist to alleviate symptoms and maintain patients' quality of life, PD remains incurable. According to some recent studies, natural killer (NK) cells may play a role in clearing alpha-synuclein aggregates, which are the main component of Lewy bodies that cause neuronal degeneration in Parkinson's disease.

The effects of autophagy-modifying drugs chloroquine and lithium on the skin melanoma microenvironment.

Background: Skin melanoma is a highly metastatic cancer with an increasing global incidence. Despite advancements in immunotherapy, new treatment strategies based on tumor biology are essential for improving outcomes and developing novel therapies. Autophagy plays a critical role in melanoma cell metabolism and affects the tumor microenvironment (TME).

Anaerobic probiotics-in situ Se nanoradiosensitizers selectively anchor to tumor with immuno-regulations for robust cancer radio-immunotherapy.

Developing translational nanoradiosensitizers with multiple activities in sensitizing tumor cells and re-shaping tumor immunosuppressive microenvironments are urgently desired for addressing the poor therapeutic efficacy of radiotherapy in clinic. Inspired by the anaerobic and immunoagonist properties of the probiotic (bifidobacterium longum, BL), herein, a biomimetic Selenium nanoradiosensitizer in situ-formed on the surface of the probiotic (BL@SeNPs) is developed in a facile method to potentiate radiotherapy. BL@SeNPs selectively target to hypoxia regions of tumors and then anchor on the surface of tumor cells to inhibit its proliferation.

Potential roles of mitochondrial carrier proteins in plant responses to abiotic stress.

The transport of metabolites across the inner mitochondrial membrane (IMM) is crucial for maintaining energy balance and efficient distribution of metabolic intermediates between cellular compartments. Under abiotic stress, mitochondrial function becomes particularly critical, activating complex signaling pathways essential for plant stress responses. These pathways modulate stress-responsive gene expression, influencing key physiological processes such as cell respiration and senescence, helping plants adapt to stress.

Protocol for the generation of HLF+ HOXA+ human hematopoietic progenitor cells from pluripotent stem cells.

Hematopoietic stem cells (HSCs) generate blood and immune cells. Here, we present a protocol to differentiate human pluripotent stem cells (hPSCs) into hematopoietic progenitors that express the signature HSC transcription factors HLF, HOXA5, HOXA7, HOXA9, and HOXA10. hPSCs are dissociated, seeded, and then sequentially differentiated into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and hematopoietic progenitors through the sequential addition of defined, serum-free media.

Mina53 catalyzes arginine demethylation of p53 to promote tumor growth.

Arginine methylation is a common post-translational modification that plays critical roles in many biological processes. However, the existence of arginine demethylases that remove the modification has not been fully established. Here, we report that Myc-induced nuclear antigen 53 (Mina53), a member of the jumonji C (JmjC) protein family, is an arginine demethylase.

The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity.

Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics.

Progenitor effect in the spleen drives early recovery via universal hematopoietic cell inflation.

Hematopoietic stem cells (HSCs) possess the capacity to regenerate the entire hematopoietic system. However, the precise HSC dynamics in the early post-transplantation phase remain an enigma. Clinically, the initial hematopoiesis in the post-transplantation period is critical, necessitating strategies to accelerate hematopoietic recovery.

ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells.

The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions-including Europe, Japan, India, and South Korea-have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval.