1,315,467 results match your criteria: "Anatomy and Genetics; University of Oxford; Oxford; UK.[Affiliation]"

Prostate cancer (PCa) remains a critical global health challenge, with high mortality rates and significant heterogeneity, particularly in advanced stages. While early-stage PCa is often manageable with conventional treatments, metastatic PCa is notoriously resistant, highlighting an urgent need for precise biomarkers and innovative therapeutic strategies. This review focuses on the dualistic roles of sirtuins, a family of NAD+-dependent histone deacetylases, dissecting their unique contributions to tumor suppression or progression in PCa depending on the cellular context.

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: Pancreatic Ductal Adeno-Carcinoma (PDAC) is a highly aggressive cancer, with limited treatment options. Disruption of the circadian clock, which regulates key cellular processes, has been implicated in PDAC initiation and progression. Hence, targeting circadian clock components may offer new therapeutic opportunities for the disease.

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Skin Disorders and Osteoporosis: Unraveling the Interplay Between Vitamin D, Microbiota, and Epigenetics Within the Skin-Bone Axis.

Int J Mol Sci

December 2024

Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy.

Growing scientific evidence suggests a strong interconnection between inflammatory skin diseases and osteoporosis (OP), a systemic condition characterized by decreased bone density and structural fragility. These conditions seem to share common pathophysiological mechanisms, including immune dysregulation, chronic inflammation, and vitamin D deficiency, which play a crucial role in both skin and bone health. Additionally, the roles of gut microbiota (GM) and epigenetic regulation via microRNAs (miRNAs) emerge as key elements influencing the progression of both conditions.

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To date, very little is known about how apoptosis and autophagy affect human endometrial stromal cells (ESCs), particularly how these processes might determine the depth of implantation in humans. Before investigating how apoptosis and autophagy might modulate the implantation process in an infertile population, it is necessary to clarify how these processes are regulated in healthy individuals. This study examined the protein expression related to apoptosis and autophagy in primary ESCs from fertile women, particularly in the context of decidualization and embryo contact, using Western blot analysis.

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Flow cytometric (FC) immunophenotyping and T-cell receptor (TCR) gene rearrangement studies are essential ancillary methods for the characterisation of T-cell lymphomas. Traditional manual gating and polymerase chain reaction (PCR)-based analyses can be labour-intensive, operator-dependent, and have limitations in terms of sensitivity and specificity. The objective of our study was to investigate the efficacy of the Phenograph and t-SNE algorithms together with an antibody specific for the TCR β-chain constant region 1 (TRBC1) to identify monoclonal T-cell populations.

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Article Synopsis
  • Ovarian cancer is a major cause of cancer-related deaths in women, with both genetic and epigenetic factors contributing to its development and progression.
  • Estrogen signaling plays a significant role in ovarian cancer, involving estrogen receptors and their regulation of genes related to cell growth and death, influenced by epigenetic changes like histone modifications and DNA methylation.
  • This review summarizes current knowledge on these epigenetic mechanisms and explores the potential of epigenetic therapies as treatment options for ovarian cancer.
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Asthma is a chronic inflammatory respiratory disease that affects millions globally and poses a serious public health challenge. Current therapeutic strategies, including corticosteroids, are constrained by variable patient responses and adverse effects. In this study, a polyphenolic extract derived from the Tibetan medicinal plant Trimen (SRT) was employed and shown to improve experimentally (ovalbumin + cigarette smoke, OVA + CS) induced asthma in rats.

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Two Novel Mouse Models of Duchenne Muscular Dystrophy with Similar Dmd Exon 51 Frameshift Mutations and Varied Phenotype Severity.

Int J Mol Sci

December 2024

Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.

Duchenne muscular dystrophy (DMD) is a severe X-linked genetic disorder caused by an array of mutations in the dystrophin gene, with the most commonly mutated regions being exons 48-55. One of the several existing approaches to treat DMD is gene therapy, based on alternative splicing and mutant exon skipping. Testing of such therapy requires animal models that carry mutations homologous to those found in human patients.

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Amyloidosis is a rare pathology characterized by protein deposits in various organs and tissues. Cardiac amyloidosis (CA) can be caused by various protein deposits, but transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) are the most frequent pathologies. Protein misfolding can be induced by several factors such as oxidative stress, genetic mutations, aging, chronic inflammation, and neoplastic disorders.

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The combination of alcohol and a low-carbohydrate, high-protein, high-fat atherogenic diet (AD) increases the risk of lethal arrhythmias in apolipoprotein E/low-density lipoprotein receptor double-knockout (AL) mice with metabolic dysfunction-associated steatotic liver disease (MASLD). This study investigates whether left ventricular (LV) myocardial interstitial fibrosis (MIF), formed during the progression of metabolic dysfunction-associated steatohepatitis (MASH), contributes to this increased risk. Male AL mice were fed an AD with or without ethanol for 16 weeks, while age-matched AL and wild-type mice served as controls.

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PTHrP Promotes RBP4 Expression Under the Control of PPARγ in the Kidney.

Int J Mol Sci

December 2024

Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, 28922 Alcorcón, Madrid, Spain.

Article Synopsis
  • PTHrP and RBP4 are linked to worse kidney disease outcomes, and their relationship with PPARγ, a protective nuclear receptor, was investigated.
  • The study examined levels of these proteins in different mouse models, including controls, diabetics, and those overexpressing PTHrP.
  • Findings indicated that RBP4 and PTHrP levels increase during kidney pathology, suggesting that insulin and PPARγ play crucial roles in regulating their expression to maintain kidney health.
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Low Bacterial Biomass in Human Pancreatic Cancer and Adjacent Normal Tissue.

Int J Mol Sci

December 2024

Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.

The gut microbiome plays an important role in the carcinogenesis of luminal gastrointestinal malignancies and response to antineoplastic therapy. Preclinical studies have suggested a role of intratumoral gammaproteobacteria in mediating response to gemcitabine-based chemotherapy in pancreatic ductal adenocarcinoma (PDAC). To our knowledge, this is the first study to evaluate the impact of the PDAC microbiome on chemotherapy response using samples from human pancreatic tumor resections.

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Neuroblastoma is a common malignant tumor in childhood that seriously endangers the health and lives of children, making it essential to find effective prognostic markers to accurately predict their clinical outcomes. The development of high-throughput technology in the biomedical field has made it possible to obtain multi-omics data, whose integration can compensate for missing or unreliable information in a single data source. In this study, we integrated clinical data and two omics data, i.

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Breast cancer (BC) is one of the most prevalent forms of cancer globally, and has recently become the leading cause of cancer-related mortality in women. BC is a heterogeneous disease comprising various histopathological and molecular subtypes with differing levels of malignancy, and each patient has an individual prognosis. Etiology and pathogenesis are complex and involve a considerable number of genetic alterations and dozens of alterations in non-coding RNA expression.

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Arthrogryposis, which represents a group of congenital disorders, includes various forms. One such form is amyoplasia, which most commonly presents in a sporadic form in addition to distal forms, among which hereditary cases may occur. This condition is characterized by limited joint mobility and muscle weakness, leading to limb deformities and various clinical manifestations.

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Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer with a poor prognosis. During the development of cancer cells, mitochondria influence various cell death patterns by regulating metabolic pathways such as oxidative phosphorylation. However, the relationship between mitochondrial function and cell death patterns in HCC remains unclear.

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Prime editing (PE) is a CRISPR-based tool for genome engineering that can be applied to generate human induced pluripotent stem cell (hiPSC)-based disease models. PE technology safely introduces point mutations, small insertions, and deletions (indels) into the genome. It uses a Cas9-nickase (nCas9) fused to a reverse transcriptase (RT) as an editor and a PE guide RNA (pegRNA), which introduces the desired edit with great precision without creating double-strand breaks (DSBs).

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In the present study, we aimed to investigate intratumoral karyotype diversity as well as the estrogen/progesterone effect on the cytogenetic profile of uterine leiomyomas (ULs). A total of 15 UL samples obtained from 15 patients were cultured in the media supplemented with estrogen and/or progesterone and without adding hormones. Conventional cytogenetic analysis of culture samples revealed clonal chromosomal abnormalities in 11 out of 15 ULs.

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We previously demonstrated that C-X-C Motif Chemokine Ligand 12 (CXCL12) is primarily secreted by dermal fibroblasts in response to androgens and induces hair miniaturization in the mouse androgenic alopecia (AGA) model. However, the direct effects of androgen-induced CXCL12 on dermal papilla cells (DPCs) and dermal sheath cup cells (DSCs) have not been demonstrated. First, we compared single-cell RNA sequencing data between mouse and human skin, and the results show that CXCL12 is highly co-expressed with the androgen receptor (AR) in the DPCs and DSCs of only human hair.

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Cancer cells undergo remarkable metabolic changes to meet their high energetic and biosynthetic demands. The Warburg effect is the most well-characterized metabolic alteration, driving cancer cells to catabolize glucose through aerobic glycolysis to promote proliferation. Another prominent metabolic hallmark of cancer cells is their increased reliance on glutamine to replenish tricarboxylic acid (TCA) cycle intermediates essential for ATP production, aspartate and fatty acid synthesis, and maintaining redox homeostasis.

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Alcohol-associated liver disease (ALD) is a common non-communicable chronic liver disease characterized by a spectrum of conditions ranging from steatosis and alcohol-associated steatohepatitis (AH) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of ALD involves a complex interplay of various molecular, biochemical, genetic, epigenetic, and environmental factors. While the mechanisms are well studied, therapeutic options remain limited.

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Identification of Gene Expression, Evolution, and Potential Functional Sites in Horn Development of Sheep.

Int J Mol Sci

December 2024

State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.

The growth and development of horns are primarily controlled by the skin. The gene is crucial for epidermal barrier function and may have a significant impact on horn growth. The purpose of this study was to investigate the expression of across different sheep breeds and tissues by utilizing RNA sequencing.

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Effective Targeting of Glutamine Synthetase with Amino Acid Analogs as a Novel Therapeutic Approach in Breast Cancer.

Int J Mol Sci

December 2024

Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City 32897, Egypt.

Cancer cells undergo metabolic rewiring to support rapid proliferation and survival in challenging environments. Glutamine is a preferred resource for cancer metabolism, as it provides both carbon and nitrogen for cellular biogenesis. Recent studies suggest the potential anticancer activity of amino acid analogs.

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Paraneoplastic cerebellar degeneration (PCD) is a rapidly progressive, immune-mediated syndrome characterized by the degeneration of Purkinje cells, often associated with the presence of antibodies targeting intracellular antigens within these cells. These autoantibodies are implicated in the induction of cytotoxicity, leading to Purkinje cell death, as demonstrated in in vitro models. However, the precise roles of antibodies and T lymphocytes in mediating neuronal injury remain a subject of ongoing research, with T cells appearing to be the main effectors of cerebellar injury.

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Article Synopsis
  • Mitochondrial dysfunction and macrophage dysregulation are important in autoimmune diseases, but how they connect is not fully understood.
  • The study focuses on the role of chronic low-level interferon-gamma (IFN-γ) using a mouse model with lupus-like symptoms, finding that this condition suppresses mitochondrial function, especially in the kidneys.
  • It suggests that restoring mitochondrial function could improve macrophage activity and provide new targets for treating autoimmune diseases like lupus nephritis.
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