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Chronic stress-induced brain-derived small extracellular vesicles promote colorectal cancer through Treg differentiation.

BACKGROUND: Chronic stress is increasingly recognised as a risk factor for poor prognosis in colorectal cancer (CRC) through sustained activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system, yet the mechanisms by which psychological stress signals are transmitted from the central nervous system to the peripheral tumour immune microenvironment remain poorly understood. Brain-derived small extracellular vesicles (BD-sEVs), which can cross the blood-brain barrier, represent potential mediators of this neuroimmune crosstalk. METHODS: A chronic restraint stress

Patterns of Glucose Metabolism in [ 18 F]FDG PET Indicate Regional Variability and Neurodegeneration in the Progression of Alzheimer's Dementia.

UNLABELLED: In disorders of cognitive impairment, such as Alzheimer's disease, neurodegeneration is the final common pathway of disease progression. Modulating, reversing, or preventing disease progression is a clinical imperative most likely to succeed following accurate and explanatory understanding of neurodegeneration, requiring enhanced consistency with quantitative measurements and expanded interpretability of complex data. The on-going study of neurodegeneration has robustly demonstrated the advantages of accumulating large amounts of clinical data that include neuroimaging, motiving mu

Framework for Brain-Derived Dimensions of Psychopathology.

IMPORTANCE: Psychiatric diagnoses are not defined by neurobiological measures hindering the development of therapies targeting mechanisms un … r, major depressive disorder, anorexia nervosa, and bulimia nervosa. EXPOSURES: Sparse generalized canonical correlation analysis was used to integrate diverse data from clinical symptoms and 7 brain imaging modalities. MAIN OUTCOMES AND MEASURES: The prediction of symptom features was the main outcome. The model was developed in the training set from the IMAGEN Study at age …

A WFS1 variant disrupting acceptor splice site uncovers the impact of alternative splicing on beta cell apoptosis in a patient with Wolfram syndrome.

AIMS/HYPOTHESIS: Wolfram syndrome 1 (WS1) is an inherited condition mainly manifesting in childhood-onset diabetes mellitus and progressive optic nerve atrophy. The causative gene, WFS1, encodes wolframin, a master regulator of several cellular responses, and the gene's mutations associate with clinical variability. Indeed, nonsense/frameshift variants correlate with more severe symptoms than missense/in-frame variants. As achieving a genotype-phenotype correlation is crucial for dealing with disease outcome, works investigating the impact of transcriptional and translational landscapes stemmi

Unveiling the aging-immune axis in irritable bowel syndrome: a multi-omics and machine learning approach to biomarker discovery and validation.

BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder with an elusive pathophysiology. Although immune dysregulation and mild mucosal inflammation are recognized as important factors in IBS, the specific contribution of immunosenescence remains unclear. Prior MR studies on IBS focused on single molecular traits; however, an integrated multi-omics framework for aging-immune genes has not been applied. Here, we integrate cis-eQTL/pQTL/mQTL with machine learning and in vivo validation to identify putatively causal biomarkers and unravel the aging-immune ax

Novel African American Colorectal Cancer MSH3 Variants Associate With Major Genomic Instability.

UNLABELLED: Pathogenic variants of MSH3 can increase mutational load within colorectal cells, which may drive initiation and progression of colorectal cancer (CRC). We identified several variants within MSH3 among CRCs from African Americans (AA). To predict and assess the functional significance of these MSH3 variants, we employed a combination of in silico analyses and in vitro functionality assays. Our objective was to elucidate the correlation between computational predictions and functional outcomes. METHODS: A CRISPR-Cas9 knock-in approach was used to introduce and generate specific poi

Evaluating a Glioma Transcriptomic Signature Against a Clinical Reference Model and a Random-Signature Null Distribution: A Leakage-Controlled Internal Audit and a Survey of the Field.

Objective: The glioma prognostic literature contains a large number of transcriptomic risk signatures, yet whether these signatures add measurable information beyond a clinical model containing grade and molecular markers is rarely tested. We pursued three objectives jointly: to evaluate a leakage-controlled signature in terms of both discrimination and calibration; to test it against a clinical reference model and against a null distribution of random signatures; and to quantify the reporting practice of the field. Methods: The CGGA mRNAseq_693 cohort (n = 404, 209 deaths) served as developme

Oral Vitamin D supplementation impacts gene expression in granulosa cells in women undergoing IVF.

STUDY QUESTION: Does oral Vitamin D supplementation alter the hormonal milieu of follicular fluid (FF) and the transcriptomic profile of luteinised granulosa cells (GCs) in women with Vitamin D deficiency undergoing IVF? SUMMARY ANSWER: A transcriptomic signature relevant to oral Vitamin D supplementation in luteinised GCs was demonstrated, although Vitamin D supplementation did not alter hormone levels in FF. WHAT IS KNOWN ALREADY: Vitamin D deficiency is linked to lower live birth rates among women undergoing IVF. It is unclear whether Vitamin D elicits a targeted action in reproductive ph

Atomic-level engineering of multifunctional BixC16 nanocages for hydrogen storage, thermoelectric energy conversion, spintronics, and nanoelectronic applications.

CONTEXT: The development of stable carbon-based nanomaterials with tunable electronic, magnetic, thermoelectric, and hydrogen storage properties is important for emerging energy conversion and nanoelectronic technologies. Here, Bi-doped C16 nanocages, BixC16 (x = 1-4), corresponding to Bi concentrations of 5.8, 11.1, 15.7, and 20.0 wt%, were systematically investigated. Negative formation energies, phonon spectra without imaginary modes, and 300 K ab initio molecular dynamics simulations confirm the energetic, dynamical, and thermal stability of the considered nanocages. Increasing Bi incorpor

Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential.

Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow. In the vast majority of patients, this results in osteolytic

Non-canonical NFκB mutations reinforce pro-survival TNF response in multiple myeloma through an autoregulatory RelB:p50 NFκB pathway.

Environmental drug resistance constitutes a serious impediment for therapeutic intervention in multiple myeloma. Tumor-promoting cytokines, such as tumor necrosis factor (TNF), induce nuclear factor-κB (NFκB)- driven expression of pro-survival factors, which confer resistance in myeloma cells to apoptotic insults from TNF-related apoptosis-inducing ligand (TRAIL) and other chemotherapeutic drugs. It is thought that RelA:p50 dimer, activated from IκBα-inhibited complex in response to TNF-induced canonical NFκB signal, mediates the pro-survival NFκB function in cancerous cells. Myeloma cells add

Targeting NF-κB Signaling for Multiple Myeloma.

Multiple myeloma (MM) is the second most common hematologic malignancy in the world. Even though survival rates have significantly risen over the past years, MM remains incurable, and is also far from reaching the point of being managed as a chronic disease. This paper reviews the evolution of MM therapies, focusing on anti-MM drugs that target the molecular mechanisms of nuclear factor kappa B (NF-κB) signaling. We also provide our perspectives on contemporary research findings and insights for future drug development.

Аутоиммунные реакции на белки, связанные с миелином, в качестве диагностических и прогнозирующих биомаркеров релапсирующего многократного склероза: ассоциации с герпесвирусом-6 и вирусом Эпштейн-Барр.

патогенез релапсирующего многократного склероза (RRMS) связан с аутоиммунными атаками миелиновых белков и возобновлением вируса Эпштейн-Барр (EBV) и человеческого герпесвируса 6 (HV-6). Однако связь между вирусными реактивными и аутоиммунными биомаркерами остается неясной. ЦЕЛИ: Изучение ответов иммуноглобулина (Ig)G/IgA/IgM на белки, связанные с миелином, совместно с EBV и HHV-6 репликационные маркеры в RRMS.Мы наняли 55 пациентов с RRMS и 63 здоровыми средствами контроля и провели оценку ответов IgG/IgA/IgM по семи компонентам, связанным с миелином, а также по EBV с применением ядерного анти

Совпадение в полном тексте источника
… Table 5 Results of canonical correlation analysis with autoimmune biomarkers as dependent variables and immune reactivity to latent viruses as explanatory variables. … Table 5 Results of canonical correlation analysis with autoimmune biomarkers as dependent variables and immune reactivity to latent viruses as explanatory variables. …

TCF12 and LncRNA MALAT1 Cooperatively Harness High Cyclin D1 but Low β-Catenin Gene Expression to Exacerbate Colorectal Cancer Prognosis Independently of Metastasis.

Metastasis is a well-known factor worsening colorectal cancer (CRC) prognosis, but mortality mechanisms in non-metastatic patients with poor outcomes are less understood. TCF12 is a transcription factor that can be physically associated with the long non-coding RNA MALAT1, creating an alliance with correlated expression levels in CRC patients. This TCF12-MALAT1 alliance is linked to poorer prognosis independently of age and metastasis. To identify the downstream effects responsible for this outcome, we analyzed 2312 common target genes of TCF12 and MALAT1, finding involvement in pathways like

The epigenetic potential of vitamin K2 in brain health.

Vitamin K2 refers to a subfamily of vitamin K isoforms known as Menaquinones and, therefore, indicated as MK-n, the "n" indicating the number of isoprene units present in the side chain. Like the other members of the Vitamin K family, K2 is an enzymatic cofactor for the γ-glutamyl carboxylase (GGCX). This enzyme's substrates, which carboxylate glutamic acid residues, are known as Vitamin K-dependent proteins (VKDPs). Besides being involved in bone homeostasis, vitamin K exerts its primary function in the coagulation process. More recently, a function of Vitamin K also in brain homeostasis has

The interrelationship between prostate cancer and osteoporosis: new perspectives on shared molecular pathways and treatment strategies.

Osteoporosis is frequently regarded as a complication associated with androgen deprivation therapy (ADT) in patients with prostate cancer. Nevertheless, a notably higher incidence of osteoporosis has been observed in prostate cancer patients even in the absence of ADT, when compared to age-matched healthy individuals. This phenomenon is likely attributable to the synergistic effects of aging, chronic inflammation, and tumor-related factors, which collectively contribute to accelerated bone loss in this population. Accumulating evidence has demonstrated that signaling pathways such as RANKL/RAN

The Roles of EDA2R in Ageing and Disease.

Ageing is a complex biological process driven, in part, by inflammaging. Recent research identifies the ectodysplasin A2 receptor (EDA2R) as a key regulator of inflammaging and a novel biomarker of ageing, with its expression increasing with age across diverse tissues in humans and animal models. Elevated EDA2R gene expression is associated with accelerated ageing, cellular senescence, frailty, obesity, acne, radiation response and increased levels of inflammatory, renal, cardiac and vascular biomarkers. Similarly, elevated EDA2R protein levels, a critical component of the proteomic ageing clo

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway A

The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.

The complement system is traditionally recognized as a major effector of innate immunity, essential for pathogen clearance, inflammation and the maintenance of tissue homeostasis. In recent years, however, its role in cancer has been substantially redefined. Beyond its canonical extracellular activity, complement has emerged as a multifaceted regulator of tumor biology, acting not only within the tumor microenvironment but also intracellularly through the recently described intracellular complement system (complosome). While extracellular complement primarily shapes immune responses and the tu

The Molecular Aspect of Antitumor Effects of Protease Inhibitor Nafamostat Mesylate and Its Role in Potential Clinical Applications.

Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (N