Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular homeostasis, overseeing the expression of a wide array of genes involved in cytoprotective processes such as antioxidant and proteostasis control, mitochondrial function, inflammation, and the metabolism of lipids and glucose. The accumulation of misfolded proteins triggers the release, stabilization, and nuclear translocation of NRF2, which in turn enhances the expression of critical components of both the proteasomal and lysosomal degradation pathways. This process facilitates the clearance of toxic protein aggregates, thereby actively maintaining cellular proteostasis.

Functional Characterization of the SHIP1-Domains Regarding Their Contribution to Inositol 5-Phosphatase Activity.

The Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is a multidomain protein consisting of two protein-protein interaction domains, the Src homology 2 (SH2) domain, and the proline-rich region (PRR), as well as three phosphoinositide-binding domains, the pleckstrin homology-like (PHL) domain, the 5-phosphatase (5PPase) domain, and the C2 domain. SHIP1 is commonly known for its involvement in the regulation of the PI3K/AKT signaling pathway by dephosphorylation of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P) at the D5 position of the inositol ring. However, the functional role of each domain of SHIP1 for the regulation of its enzymatic activity is not well understood.

Unveiling the Mechanisms of a Remission in Major Depressive Disorder (MDD)-like Syndrome: The Role of Hippocampal Palmitoyltransferase Expression and Stress Susceptibility.

Post-translational modifications of proteins via palmitoylation, a thioester linkage of a 16-carbon fatty acid to a cysteine residue, reversibly increases their affinity for cholesterol-rich lipid rafts in membranes, changing their function. Little is known about how altered palmitoylation affects function at the systemic level and contributes to CNS pathology. However, recent studies suggested a role for the downregulation of palmitoyl acetyltransferase (DHHC) 21 gene expression in the development of Major Depressive Disorder (MDD)-like syndrome.

The Intersection of Epigenetics and Senolytics in Mechanisms of Aging and Therapeutic Approaches.

The biological process of aging is influenced by a complex interplay of genetic, environmental, and epigenetic factors. Recent advancements in the fields of epigenetics and senolytics offer promising avenues for understanding and addressing age-related diseases. Epigenetics refers to heritable changes in gene expression without altering the DNA sequence, with mechanisms like DNA methylation, histone modification, and non-coding RNA regulation playing critical roles in aging.

The Introduction of the Global Traditional, Complementary, and Integrative Healthcare (TCIH) Research Agenda on Antimicrobial Resistance and Its Added Value to the WHO and the WHO/FAO/UNEP/WOAH 2023 Research Agendas on Antimicrobial Resistance.

: Given the magnitude and urgency of the global antimicrobial resistance (AMR) problem and the insufficiency of strategies to reduce antimicrobial use, there is a need for novel strategies. Traditional, Complementary, and Integrative Healthcare (TCIH) provides strategies and solutions that contribute to reducing (inappropriate) antimicrobial use, preventing or treating infections in both human and veterinary medicine, and may contribute to promoting the health/resilience of humans and animals and reducing AMR. The aims of this study were to present the core results of a global TCIH research agenda for AMR and its added value to two existing global AMR research agendas published in 2023.

Evaluation of Antimicrobial Performance of Calcium Dihydroxide (Ca(OH)) Coating on Ti for Potential Metallic Orthopedic Implant Applications.

Orthopedic implant infections are rare but represent a significant problem for patients, surgeons, and the healthcare systems. This is because these infections cause severe and persistent pain and, in some cases, may require revision of the implant, among other things. Thus, there is strong interest in the use of antimicrobial coatings on orthopedic implants.

Use of Antibiotics in Companion Animals from 133 German Practices from 2018 to 2023.

: While antibiotic usage in farm animals has been systematically monitored and reduced in many countries, including Germany, data on companion animals such as dogs and cats remain scarce. To address this gap, a study was conducted in Germany to analyze patterns of antibiotic use in dogs and cats. : Antibiotic usage data were obtained from debevet, a cloud-based veterinary practice management software based in Berlin, Germany.

Logistic Stewardship: Supporting Antimicrobial Stewardship Programs Based on Antibiotics Goods Flow.

Background/objectives: Antimicrobial resistance is a global threat to safe health care, and a reduction in antibiotic consumption seems to be an appropriate preventive measure. In Germany, the reporting of hospital antibiotics consumption to an independent institution is only voluntary. Although a high level of willingness to improve can be assumed in the case of participation, the median consumptions of reporting hospitals change only slightly.

Methicillin-Resistant : The Shifting Landscape in the United Arab Emirates.

Background: Methicillin-resistant (MRSA) is a significant burden globally, particularly in the Arabian Gulf region. The United Arab Emirates (UAE) has experienced rising MRSA prevalence, with increasing diversity in the clonal complexes (CCs) identified. The COVID-19 pandemic, with its increased hospitalization rates and antibiotic use, may have further influenced MRSA's genetic evolution and epidemiology in the country.

Retrospective Analysis of Penicillin G Minimum Inhibitory Concentration for Gram-Positive Isolates of Non-Severe Clinical Mastitis.

: Despite penicillin having a longstanding reputation as being scientifically approved for the treatment of bovine mastitis, its market share and practical application rate seem rather low. While in some countries, cases of mild and moderate mastitis are treated almost completely with simple penicillin, in other countries, penicillin is rarely used as a mono-substance in udder tubes. : Based on minimal inhibitory concentration (MIC) studies of 1489 isolates of Gram-positive microorganisms isolated from bovine mastitis cases, the extent to which penicillin preparations can fulfil their role as first-line treatment and in how many cases insufficient efficacy must be assumed was assessed in comparison with more recent studies on the achievable levels of active substances in milk.

Evaluating the Protective Effects of MitoQ and Antifreeze Protein III on Cryopreserved Canine Sperm.

Cryopreservation can adversely affect sperm motility, structural integrity, and fertilization ability. This study investigated the effects of MitoQ and antifreeze protein III (AFP III) on frozen-thawed semen from eight adult dogs using a Tris-fructose extender. Ejaculates were divided and diluted with a standard Tris-fructose-egg yolk extender containing MitoQ (200 nM/mL) and AFP III (0.

Performance Responses and Fillet Quality of Rainbow Trout () to Increasing Addition Levels of Dietary Supplementation of Guanidinoacetic Acid.

Guanidinoacetic acid (GAA) plays an important role in cellular energy use and protein synthesis. The objectives of this study were to determine the optimal level of dietary GAA regarding the growth performance and fillet characteristics of rainbow trout (). A total of 300 trout (initial weight, 66.

Prepartum Vaccination Against Neonatal Calf Diarrhea and Its Effect on Mammary Health and Milk Yield of Dairy Cows: A Retrospective Study Addressing Non-Specific Effects of Vaccination.

Prepartum vaccinations against neonatal calf diarrhea pathogens are administered in late pregnancy to provide passive immunity to calves through protective colostral antibodies. Potential non-specific effects of the vaccine on maternal innate immune responses and disease susceptibility during the sensitive transition period have not been addressed so far. In this retrospective study, data from 73,378 dairy cows on 20 farms in Germany were analyzed, using linear mixed-effects regression, quantile regression, and decision-tree-algorithms, to investigate the effects of prepartum vaccination on mammary health and milk yield by comparing non-vaccinated and vaccinated transition periods.

A Meta-Analysis on Quantitative Sodium, Potassium and Chloride Metabolism in Horses and Ponies.

The goal of this meta-analysis was to (i) identify any potential differences in the apparent and true digestibility, renal excretion, and retention between ponies and horses and (ii) examine the impact of work on these parameters. Additionally, the study aimed to (iii) evaluate the effects of water deficiency. This meta-analysis used data from 33 studies and plotted them in diagrams similar to the Lucas test against mineral intake.

Morphological and Molecular Identification of in Captive Cheetahs () in China Helps Clarify Phylogenetic Relationships with and .

To date, only one case is known where protozoan parasites of the genus were found to infect cheetahs (); the cysts in the musculature were morphologically identified as . Here, we characterized sarcocysts by morphological and molecular methods that were observed in cheetahs who died in zoos in China. Only one type of sarcocyst was present in two of six cheetahs.

Isolation of a Novel Caprine Strain (GC) in Canary Islands and Analysis of Parasitological, Clinical, and Pathological Findings on Experimentally Infected Goat Kids.

is considered among the most pathogenic species in goats. The aim of this study was to isolate an strain and to assess its infectivity, pathogenicity, and ability to develop a protective immune response. After previous collection of -positive faeces, purification of oocysts, and amplification in donor animals, an experimental infection was carried out.

Computed Tomography-Image-Based Glioma Grading Using Radiomics and Machine Learning: A Proof-of-Principle Study.

Background/objectives: In recent years, numerous studies have been published on determining the WHO grade of central nervous system (CNS) tumors using machine learning algorithms. These studies are usually based on magnetic resonance imaging (MRI) and sometimes also on positron emission tomography (PET) images. To date, however, there are virtually no corresponding studies based on routinely generated computed tomography (CT) images.

Transcriptional Pathways Predisposing to Cancer Oxidative Stress Sensitivity and Resistance Are Shared Between Hydrogen Peroxide and Cold Gas Plasma but Not Hypochlorous Acid.

Oxidative stress is universal to all cell types, including cancer. It is elicited by a surplus of reactive oxygen species (ROS) or a reduced cellular ability to defend against those. At low levels (oxidative eustress), this induces altered cellular signaling, while at higher levels (oxidative distress), cellular toxicity and non-specific redox signaling become apparent.

Information Behaviour and Knowledge of Patients Before Radical Prostatectomy.

Background/objectives: Robot-assisted and open radical prostatectomy (RARP and ORP) are established procedures for localized prostate cancer, with comparable oncological and functional outcomes. Little is known about patients' knowledge of both procedures. This study aimed to examine comparatively the informational behaviour and knowledge of patients undergoing ORP vs.

Does Total Neoadjuvant Therapy Impact Surgical Precision in Total Mesorectal Excision? A Nationwide Survey of the Experiences of Expert Surgeons.

Background: The treatment of locally advanced rectal cancer (LARC) has steadily progressed over the past four decades, with recent focus shifting towards total neoadjuvant therapy (TNT). This survey aims to elucidate the perceived surgical challenges faced by Austrian colorectal surgeons performing total mesorectal excision (TME), focusing on the increased complexity and surgical difficulty introduced by intensified treatment regimens.

Methods: A comprehensive survey was conducted among Austrian colorectal surgeons to explore various aspects of managing and performing TME following TNT.

Meeting Cancer Detection Benchmarks in MRI/Ultrasound Fusion Biopsy for Prostate Cancer: Insights from a Retrospective Analysis of Experienced Urologists.

Background: The relationship between case volume and clinical outcomes is well established for most urological procedures but remains underexplored in prostate ultrasound/MRI fusion biopsy (UMFB). UMFB aims to detect clinically significant prostate cancer (csPCa) by adhering to cancer detection benchmarks for PI-RADS lesions identified via multiparametric MRI (mpMRI). These benchmarks, defined by Ahmed et al.

Necroptosis-Related Gene Signature Predicts Prognosis in Patients with Advanced Ovarian Cancer.

This study aimed to construct a risk score (RS) based on necroptosis-associated genes to predict the prognosis of patients with advanced epithelial ovarian cancer (EOC). EOC data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) series 140082 (GSE140082) were used. Based on known necroptosis-associated genes, clustering was performed to identify molecular subtypes of EOC.

Prognostic Factors in Therapy Regimes of Breast Cancer Patients with Brain Metastases: A Retrospective Monocentric Analysis.

Breast cancer patients who develop brain metastases have a high mortality rate and a massive decrease in quality of life. Approximately 10-15% of all patients with breast cancer (BC) and 5-40% of all patients with metastatic BC develop brain metastasis (BM) during the course of the disease. However, there is only limited knowledge about prognostic factors in the treatment of patients with brain metastases in breast cancer (BMBC).

Characterization of a 3S PRAME VLD-Specific T Cell Receptor and Its Use in Investigational Medicinal Products for TCR-T Therapy of Patients with Myeloid Malignancies.

Background/objectives: MDG1011 is an autologous TCR-T therapy developed as a treatment option for patients with myeloid malignancies, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). It is specific for the target antigen PReferentially expressed Antigen in MElanoma (PRAME). The recombinant TCR used in MDG1011 recognizes PRAME VLD-peptide presented by HLA-A*02:01-encoded surface molecules.

CT-Derived Quantitative Image Features Predict Neoadjuvant Treatment Response in Adenocarcinoma of the Gastroesophageal Junction with High Accuracy.

Background: The purpose of this retrospective study was to evaluate the value of contrast-enhanced computed tomography (CE-CT) image features at baseline and after neoadjuvant chemotherapy in predicting histopathological response in patients with adenocarcinoma of the gastroesophageal junction (GEJ).

Methods: A total of 105 patients with a diagnosis of adenocarcinoma of the GEJ were examined by CE-CT at baseline and preoperatively after neoadjuvant chemotherapy. All patients underwent surgical resection.