Transcriptomic Analysis of Effects of Developmental PCB Exposure in the Hypothalamus of Female Rats.

This study investigated the consequences of perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic polychlorinated biphenyl (PCB) mixture and known endocrine-disrupting chemical (EDC), in female rats. Previous work has shown behavioral and physiological effects of A1221, and the current study extended this work to comprehensive transcriptomic profiling of two hypothalamic regions involved in the control of reproduction: the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Female Sprague-Dawley rats were fed a cookie treated with a small volume of A1221 (1 mg/kg) or vehicle (3% DMSO in sesame oil) during pregnancy from gestational days 8-18 and after birth from postnatal (P) days 1-21, exposing the offspring via placental and lactational transfer.

Characterization of Mesenchymal and Neural Stem Cells Response to Bipolar Microsecond Electric Pulses Stimulation.

In the tissue regeneration field, stem cell transplantation represents a promising therapeutic strategy. To favor their implantation, proliferation and differentiation need to be controlled. Several studies have demonstrated that stem cell fate can be controlled by applying continuous electric field stimulation.

miR-9-5p/HMMR regulates the tumorigenesis and progression of clear cell renal cell carcinoma through EMT and JAK1/STAT1 signaling pathway.

Background: The most common malignant type of kidney cancer is clear cell renal cell carcinoma (ccRCC). The expression levels of hyaluronan-mediated motility receptor (HMMR) in many tumor types are significantly elevated. HMMR is closely associated with tumor-related progression, treatment resistance, and poor prognosis, and has yet to be fully investigated in terms of its expression patterns and molecular mechanisms of action in ccRCC.

Spatial heterogeneity of the hepatocellular carcinoma microenvironment determines the efficacy of immunotherapy.

Hepatocellular carcinoma (HCC) remains a global health challenge owing to its widespread incidence and high mortality. HCC has a specific immune tolerance function because of its unique physiological structure, which limits the efficacy of chemotherapy, radiotherapy, and molecular targeting. In recent years, new immune approaches, including adoptive cell therapy, tumor vaccines, and oncolytic virus therapy, have shown great potential.

The Emerging Scenario of Ferroptosis in Pancreatic Cancer Tumorigenesis and Treatment.

Pancreatic cancer remains one of the most lethal forms of cancer. Currently, there is a lack of effective drug treatments for pancreatic cancer. However, as a newly discovered form of non-apoptotic cell death, ferroptosis has garnered increasing attention in relation to pancreatic cancer.

A Pan-Cancer Analysis of the Oncogenic Role of CD276 in Human Tumors.

: B7 homolog 3 protein (B7-H3, also known as CD276) is a member of the B7 family that has been found to be associated with the growth and progression of a variety of tumors, but no pan-cancer evaluations of CD276 have been performed so far. In this study, we aimed to perform a pan-cancer analysis of the oncogenic role of CD276 in human tumors; : We used a series of databases to perform a pan-cancer analysis of CD276, including the expression level of CD276 in pan-cancer and its relationship to tumor progression, patient survival duration, the immune cell infiltration within the tumor, and the potential signaling pathways and molecular mechanisms associated with CD276; : We found that CD276 was a potential biomarker for the prognosis of most cancers. The high expression of CD276 was associated with tumor progression, leading to poor survival.

Exploring the role of noncoding RNAs in cancer diagnosis, prognosis, and precision medicine.

This review article studies the complex field of noncoding RNAs (ncRNAs) in cancer biology, focusing on their potential use as biomarkers and therapeutic targets. NcRNAs include circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs). We discuss how ncRNAs affect gene expression in cancerous cells, the spread of cancer, and metastasis.

Targeting Deltex E3 Ubiquitin Ligase 2 Inhibits Tumor-associated Neutrophils and Sensitizes Hepatocellular Carcinoma Cells to Immunotherapy.

Several E3 ligases have been found to affect the immune microenvironment of hepatocellular carcinoma (HCC) and lead to the resistance of immunotherapy. In this study, genes of E3 ligases are screened based on The Cancer Genome Atlas (TCGA) dataset. Through cytometry by time of flight (CyTOF), flow cytometry, and further experiments, Deltex E3 ubiquitin ligase 2 (DTX2) in HCC cells is identified to promote the infiltration and polarization of tumor-associated neutrophils (TANs) with a protumor phenotype, thus attenuating the infiltration and cytotoxicity of CD8+ T cells partially through C-X-C motif chemokine 2 (CXCL2) and C-X-C motif chemokine 6 (CXCL6).

Quantitative Live Imaging Reveals Phase Dependency of PDAC Patient-Derived Organoids on ERK and AMPK Activity.

Patient-derived organoids represent a novel platform to recapitulate the cancer cells in the patient tissue. While cancer heterogeneity has been extensively studied by a number of omics approaches, little is known about the spatiotemporal kinase activity dynamics. Here we applied a live imaging approach to organoids derived from 10 pancreatic ductal adenocarcinoma (PDAC) patients to comprehensively understand their heterogeneous growth potential and drug responses.

Combination of spatial transcriptomics analysis and retrospective study reveals liver infection of SARS-COV-2 is associated with clinical outcomes of COVID-19.

Background: Liver involvement is a common complication of coronavirus disease 2019 (COVID-19), especially in hospitalized patients. However, the underlying mechanisms involved are not fully understood.

Methods: Immunohistochemistry (IHC) staining of SARS-CoV-2 spike (S) and nucleocapsid (N) proteins was conducted on liver tissues from six patients with COVID-19.

EMC2 suppresses ferroptosis via regulating TFRC in nasopharyngeal carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with poorly understood underlying molecular mechanisms. Ferroptosis, a form of programmed cell death, is not fully elucidated in NPC.

Method: We conducted quantitative proteomics to detect dysregulated proteins in NPC tissues.

Single-cell atlas comparison across vertebrates reveals auditory cell evolution and mechanisms for hair cell regeneration.

Mammals suffer permanent hearing impairment from the loss of auditory hair cells due to their inability to regenerate. In contrast, lower vertebrates exhibit extraordinary capacity for hair cell regeneration and hearing restoration, but the mechanisms remain unclear. Here we characterize the single-cell atlas of Xenopus laevis inner ear and perform a comprehensive comparison with mouse model.

Complement C3d enables cell-mediated immunity capable of distinguishing spontaneously transformed from nontransformed cells.

Immune surveillance depends in part on the recognition of peptide variants by T cell antigen receptors. Given that both normal B cells and malignant B cells accumulate mutations we chose a murine model of multiple myeloma to test conditions to induce cell-mediated immunity targeting malignant plasma cell (PC) clones but sparing of normal PCs. Revealing a previously unknown function for intracellular C3d, we found that C3d engaged T cell responses against malignant PC in the bone marrow of mice that had developed multiple myeloma spontaneously.

YAP/TAZ Signalling Controls Epidermal Keratinocyte Fate.

The paralogues Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) control cell proliferation and cell fate determination from embryogenesis to ageing. In the skin epidermis, these proteins are involved in both homeostatic cell renewal and injury-induced regeneration and also drive carcinogenesis and other pathologies. YAP and TAZ are usually considered downstream of the Hippo pathway.

Impact of combined exercise on blood DNA methylation and physical health in older women with obesity.

This study examined the effects of a 14-week combined exercise program on blood DNA methylation (DNAm) and its potential biological pathways in normal-weight, overweight, and obese older women. A total of 41 participants were assessed at baseline, 7 weeks, and 14 weeks into the training. Their whole-blood DNAm profiles were measured using the Infinitum MethylationEPIC BeadChip, alongside physical and biochemical health evaluations.

π-HuB: the proteomic navigator of the human body.

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.

Analysis of the ubiquitin-modified proteome identifies novel host factors in Kaposi's sarcoma herpesvirus lytic reactivation.

Unlabelled: Kaposi's sarcoma herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma and is associated with primary effusion lymphoma (PEL), multicentric Castleman's disease, and two inflammatory diseases. KSHV-associated cancers are primarily associated with genes expressed during latency, while other pathologies are associated with lytic gene expression. The major lytic switch of the virus, Replication and Transcription Activator (RTA), interacts with cellular machinery to co-opt the host ubiquitin proteasome system to evade the immune response as well as activate the program of lytic replication.

Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis.

Ageing is associated with a decline in the number and fitness of adult stem cells. Ageing-associated loss of stemness is posited to suppress tumorigenesis, but this hypothesis has not been tested in vivo. Here we use physiologically aged autochthonous genetically engineered mouse models and primary cells to demonstrate that ageing suppresses lung cancer initiation and progression by degrading the stemness of the alveolar cell of origin.

Hypoxia Induced Lnc191 Upregulation Dictates the Progression of Esophageal Squamous Cell Carcinoma by Activating GRP78/ERK Pathway.

Hypoxia is a typical hallmark of solid tumors and plays a crucial role in the progression of esophageal squamous cell carcinogenesis (ESCC). Nevertheless, the precise mechanisms underlying the involvement of hypoxia in tumor development remain unclear. In the present study, a novel hypoxia-induced long noncoding RNA (lncRNA) is identified first, lnc191, which is highly expressed in clinical ESCC tissues and is positively correlated with poor prognosis of ESCC patients.

The N6-methyladenosine writer METTL3 promotes breast cancer progression through YTHDF2-dependent posttranscriptional silencing of GSDMD.

Cell pyroptosis is a form of programmed cell death, with Gasdermin-D (GSDMD) acting as its key executor. While activating pyroptosis represents a promising therapeutic strategy for cancer, the regulatory mechanisms governing GSDMD expression during cell death remain poorly understood. In this study, we identified METTL3 as a negative regulator of GSDMD-mediated pyroptosis, with high expression in breast cancer (BC) cells.

UBA1 inhibition sensitizes cancer cells to PARP inhibitors.

Therapeutic strategies targeting the DNA damage response, such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have revolutionized cancer treatment in tumors deficient in homologous recombination (HR). However, overcoming innate and acquired resistance to PARPi remains a significant challenge. Here, we employ a genome-wide CRISPR knockout screen and discover that the depletion of ubiquitin-activating enzyme E1 (UBA1) enhances sensitivity to PARPi in HR-proficient ovarian cancer cells.

Interplay between epigenetics, senescence and cellular redox metabolism in cancer and its therapeutic implications.

There is accumulating evidence indicating a close crosstalk between key molecular events regulating cell growth and proliferation, which could profoundly impact carcinogenesis and its progression. Here we focus on reviewing observations highlighting the interplay between epigenetic modifications, irreversible cell cycle arrest or senescence, and cellular redox metabolism. Epigenetic alterations, such as DNA methylation and histone modifications, dynamically influence tumour transcriptome, thereby impacting tumour phenotype, survival, growth and spread.