PROVIT-CLOCK: A Potential Influence of Probiotics and Vitamin B7 Add-On Treatment and Metabolites on Clock Gene Expression in Major Depression.

Introduction: An increasing body of evidence suggests a strong relationship between gut health and mental state. Lately, a connection between butyrate-producing bacteria and sleep quality has been discussed. The PROVIT study, as a randomized, double-blind, 4-week, multispecies probiotic intervention study, aims at elucidating the potential interconnection between the gut's metabolome and the molecular clock in individuals with major depressive disorder (MDD).

Elimination of damaged mitochondria during UVB-induced senescence is orchestrated by NIX-dependent mitophagy.

Skin aging is the result of two types of aging, "intrinsic aging" an inevitable consequence of physiologic and genetically determined changes and "extrinsic aging," which is dependent on external factors such as exposure to sunlight, smoking, and dietary habits. UVB causes skin injury through the generation of free radicals and other oxidative byproducts, also contributing to DNA damage. Appearance and accumulation of senescent cells in the skin are considered one of the hallmarks of aging in this tissue.

Functional Precision Medicine Successfully Guides Therapeutic Regimen of 'Cancer of Unknown Primary' Later Classified as Triple-Negative Breast Cancer: A Case Report.

Introduction: Controlled randomized trials, molecular analytics, and guideline recommendations have so far been irreplaceable tools to ensure appropriate treatment and decision-making for physicians and patients. Individual patient models are increasingly complementing these methods, particularly in the case of advanced cancers, rare cancers, and cancers of unknown primary (CUP), as in these cases comprehensive clinical evidence is unavailable, often resulting in poor treatment success, even after stratification.

Case Presentation: Here we report a 53-year-old patient with CUP with axillary lymph node metastases for whom patient-derived 3D (PD3D) tumor organoids successfully guided personalized treatment.

Multimodal analytical tools for the molecular and elemental characterisation of lesions in brain tissue of multiple sclerosis patients.

Multiple sclerosis (MS) is a prevalent immune-mediated inflammatory disease of the central nervous system inducing a widespread degradation of myelin and resulting in neurological deficits. Recent advances in molecular and atomic imaging provide the means to probe the microenvironment in affected brain tissues at an unprecedented level of detail and may provide new insights. This study showcases state-of-the-art spectroscopic and mass spectrometric techniques to compare distributions of molecular and atomic entities in MS lesions and surrounding brain tissues.

RNA binding protein IGF2BP2 expression is induced by stress in the heart and mediates dilated cardiomyopathy.

The IGF2BP family of RNA binding proteins consists of three paralogs that regulate intracellular RNA localization, RNA stability, and translational control. Although IGF2BP1 and 3 are oncofetal proteins, IGF2BP2 expression is maintained in many tissues, including the heart, into adulthood. IGF2BP2 is upregulated in cardiomyocytes during cardiac stress and remodeling and returns to normal levels in recovering hearts.

Radiomic features define risk and are linked to DNA methylation attributes in primary CNS lymphoma.

Background: The prognostic roles of clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma, but these approaches do not fully explain the observed variation in outcome. To date, neuroimaging or molecular information is not used. The aim of this study was to determine the utility of radiomic features to capture clinically relevant phenotypes, and to link those to molecular profiles for enhanced risk stratification.

Inhibition of EIF2α Dephosphorylation Decreases Cell Viability and Synergizes with Standard-of-Care Chemotherapeutics in Head and Neck Squamous Cell Carcinoma.

Drug resistance is a common cause of therapy failure in head and neck squamous cell carcinoma (HNSCC). One approach to tackling it is by targeting fundamental cellular processes, such as translation. The eukaryotic translation initiation factor 2α (EIF2α) is a key player in canonical translation initiation and integrates diverse stress signals; when phosphorylated, it curbs global protein synthesis.

[Digital pathology in Austria].

The situation regarding digital pathology in Austria is manageable compared to other countries. Active Austrian examples are the consortium EMPAIA, the private-public partnership Bigpicture, the Austrian Society for Clinical Pathology and Molecular Pathology (OEGPath), the company TissueGnostics, and the Austrian Platform for Personalized Medicine (OEPPM).

Decreased eukaryotic initiation factors expression upon temozolomide treatment-potential novel implications for eIFs in glioma therapy.

Purpose: Since glioma therapy is currently still limited until today, new treatment options for this heterogeneous group of tumours are of great interest. Eukaryotic initiation factors (eIFs) are altered in various cancer entities, including gliomas. The purpose of our study was to evaluate the potential of eIFs as novel targets in glioma treatment.

Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization.

Background: Chronic non-healing wounds pose a global health challenge. Under optimized conditions, skin wounds heal by the formation of scar tissue. However, deregulated cell activation leads to persistent inflammation and the formation of granulation tissue, a type of premature scar tissue without epithelialization.

JNKs protect from cholestatic liver disease progression by modulating Apelin signalling.

Background & Aims: Cholestatic liver injury is associated with c-Jun N-terminal kinases (JNK) activation in distinct cell types. Its hepatocyte-specific function during cholestasis, however, has not yet been established. Therefore, in our present study, we investigated the role of JNK1/2 during cholestasis and dissected its hepatocyte-specific function.

Endometriosis-Associated Ovarian Carcinomas: How PI3K/AKT/mTOR Pathway Affects Their Pathogenesis.

Ovarian clear cell (OCCC) and endometrioid (EnOC) carcinomas are often subsumed under the umbrella term "endometriosis-associated ovarian cancer" (EAOC), since they frequently arise from ectopic endometrium settled in the ovaries. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is known to be aberrantly activated both in endometriosis and EAOC; however, its role in the progression of endometriosis to ovarian cancer remains unclear. In fact, cancer-associated alterations in the mTOR pathway may be found in normal uterine epithelium, likely acting as a first step towards ovarian cancer, through the intermediary stage of endometriosis.

Anti-angiogenic therapy using the multi-tyrosine kinase inhibitor Regorafenib enhances tumor progression in a transgenic mouse model of ß-cell carcinogenesis.

Background: Pancreatic neuroendocrine tumors (PNETs) represent a distinct hypervascularized tumor entity, often diagnosed at metastatic stage. Therapeutic efficacy of anti-angiogenic multi-kinase inhibitors is frequently limited by primary or acquired resistance in vivo. This study aimed to characterize the molecular mode of action as well as resistance mechanisms to the anti-angiogenic multi-tyrosine kinase inhibitor (TKI) Regorafenib in vitro and in vivo.

Cd44v6 acts as a directional responding factor in the process of transcoelomic metastasis from gastric carcinoma to Krukenberg tumor.

Introduction: Due to the limited number of studies focusing on the optimal treatment of multiple Krukenberg tumor (KT)-gastric carcinoma (KT - GC), it is necessary to conduct large-scale studies to confirm the definite role of serum tumor markers in the diagnosis and prognosis of KT. Moreover, the clinical significance of variant 6 of CD44 (CD44v6) in transcoelomic metastasis should be considered.

Areas Covered: This review covers molecular pre-cancer diagnosis, gastric carcinoma metastasis, and anti-cancer treatments.

The Oncogenic Protein Kinase/ATPase RIOK1 Is Up-Regulated via the c-myc/E2F Transcription Factor Axis in Prostate Cancer.

The atypical protein kinase/ATPase RIO kinase (RIOK)-1 is involved in pre-40S ribosomal subunit production, cell-cycle progression, and protein arginine N-methyltransferase 5 methylosome substrate recruitment. RIOK1 overexpression is a characteristic of several malignancies and is correlated with cancer stage, therapy resistance, poor patient survival, and other prognostic factors. However, its role in prostate cancer (PCa) is unknown.

A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer.

Aim: Chemoresistance is a major cause of treatment failure in colorectal cancer (CRC) therapy. In this study, the impact of the IGF2BP family of RNA-binding proteins on CRC chemoresistance was investigated using in silico, in vitro, and in vivo approaches.

Methods: Gene expression data from a well-characterized cohort and publicly available cross-linking immunoprecipitation sequencing (CLIP-Seq) data were collected.

Influence of MMR, MGMT Promotor Methylation and Protein Expression on Overall and Progression-Free Survival in Primary Glioblastoma Patients Treated with Temozolomide.

Glioblastoma is the most common malignant brain tumor in adults. Standard treatment includes tumor resection, radio-chemotherapy and adjuvant chemotherapy with temozolomide (TMZ). TMZ methylates DNA, whereas O6-methylguanine DNA methyltransferase (MGMT) counteracts TMZ effects by removing the intended proteasomal degradation signal.

Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer's Disease Patients.

The brain's extracellular matrix (ECM) is assumed to undergo rearrangements in Alzheimer's disease (AD). Here, we investigated changes of key components of the hyaluronan-based ECM in independent samples of post-mortem brains (N = 19), cerebrospinal fluids (CSF; N = 70), and RNAseq data (N = 107; from The Aging, Dementia and TBI Study) of AD patients and non-demented controls. Group comparisons and correlation analyses of major ECM components in soluble and synaptosomal fractions from frontal, temporal cortex, and hippocampus of control, low-grade, and high-grade AD brains revealed a reduction in brevican in temporal cortex soluble and frontal cortex synaptosomal fractions in AD.

Expression of Eukaryotic Translation Initiation Factors in the Urothelial Carcinoma of the Bladder.

Background/aim: Urothelial carcinoma (UC) of the urinary bladder is the second most common tumor in the field of urology and is characterized by a relatively aggressive growth behavior. New therapeutic approaches are required to improve the prognosis of affected patients. We hypothesized a link between dysregulation of eIFs and the development of UC.

Autolysis Affects the Iron Cargo of Ferritins in Neurons and Glial Cells at Different Rates in the Human Brain.

Iron is known to accumulate in neurological disorders, so a careful balance of the iron concentration is essential for healthy brain functioning. An imbalance in iron homeostasis could arise due to the dysfunction of proteins involved in iron homeostasis. Here, we focus on ferritin-the primary iron storage protein of the brain.