Whole-Body Physiologically Based Pharmacokinetic Modeling of GalNAc-Conjugated siRNAs.

: N-acetyl-galactosamine small interfering RNAs (GalNAc-siRNA) are an emerging class of drugs due to their durable knockdown of disease-related proteins. Direct conjugation of GalNAc onto the siRNA enables targeted uptake into hepatocytes via GalNAc recognition of the Asialoglycoprotein Receptor (ASGPR). With a transient plasma exposure combined with a prolonged liver half-life, GalNAc-siRNA exhibits distinct disposition characteristics.

Non-Steroidal Anti-Inflammatory Drugs Are Inhibitors of the Intestinal Proton-Coupled Amino Acid Transporter (PAT1): Ibuprofen and Diclofenac Are Non-Translocated Inhibitors.

: The proton-coupled amino acid transporter (PAT1) is an intestinal absorptive solute carrier responsible for the oral bioavailability of some GABA-mimetic drug substances such as vigabatrin and gaboxadol. In the present work, we investigate if non-steroidal anti-inflammatory drug substances (NSAIDs) interact with substrate transport via human (h)PAT1. : The transport of substrates via hPAT1 was investigated in Caco-2 cells using radiolabeled substrate uptake and in oocytes injected with , measuring induced currents using the two-electrode voltage clamp technique.

A Guinea Pig Model of Pediatric Metabolic Dysfunction-Associated Steatohepatitis: Poor Vitamin C Status May Advance Disease.

Children and teenagers display a distinct metabolic dysfunction-associated steatohepatitis (MASH) phenotype, yet studies of childhood MASH are scarce and validated animal models lacking, limiting the development of treatments. Poor vitamin C (VitC) status may affect MASH progression and often co-occurs with high-fat diets and related metabolic imbalances. As a regulator of DNA methylation, poor VitC status may further contribute to MASH by regulating gene expression This study investigated guinea pigs-a species that, like humans, depends on vitC in the diet-as a model of pediatric MASH, examining the effects of poor VitC status on MASH hallmarks and global DNA methylation levels.

Food Is Medicine: Diet Assessment Tools in Adult Inflammatory Bowel Disease Research.

Background: Diet significantly impacts the onset and progression of inflammatory bowel disease (IBD), and diet offers unique opportunities for treatment and preventative purposes. However, despite growing interest, no diet has been conclusively associated with improved long-term clinical and endoscopic outcomes in IBD, and evidence-based dietary guidelines for IBD remain scarce. This narrative review critically examines dietary assessment methods tailored to the unique needs of IBD, highlighting opportunities for precision and inclusivity.

Thermosetting Resin for Plug and Abandonment of Oil Wells with Reduced Environmental Impact.

Plug and abandonment of offshore oil wells is a costly and time-consuming process, yet it is necessary for the ever-increasing number of mature fields in the region of the Danish North Sea, as well as globally. Current practices ensuring durable solutions for the complete zonal isolation of oil wells have a large environmental impact. This paper proposes a novel resin that could be mixed on the platform and pumped into the tubing in a liquid state.

Finite Element Analysis of Electromagnetic Characteristics of a Single-Phase Permanent Magnet Linear Oscillation Actuator.

The electromagnetic characteristics of a single-phase permanent magnet linear oscillation actuator are analyzed by the finite element method. Firstly, the basic structure and operation principle of the linear oscillation actuator are introduced. The internal stator slot and arc tooth are used to reduce the detent force.

Preventive Effects of Botulinum Neurotoxin Long-Term Therapy: Comparison of the 'Experienced' Benefits and 'Suspected' Worsening Across Disease Entities.

Repetitive intramuscular injections of botulinum neurotoxin (BoNT) have become the treatment of choice for a variety of disease entities. But with the onset of BoNT therapy, the natural course of a disease is obscured. Nevertheless, the present study tries to analyze patients' "suspected" course of disease severity under the assumption that no BoNT therapy had been performed and compares that with the "experienced" improvement during BoNT treatment.

The Intra-Examiner Variability in and Accuracy of Traditional Manual Diagnostics of Benign Paroxysmal Positional Vertigo: A Prospective Observational Cohort Study.

Accurate head positioning is essential for diagnostics of benign paroxysmal positional vertigo (BPPV). This study aimed to quantify the head angles and angular velocities during traditional manual BPPV diagnostics in patients with positional vertigo. : A prospective, observational cohort study was conducted at a tertiary university hospital outpatient clinic.

A HER2 Specific Nanobody-Drug Conjugate: Site-Selective Bioconjugation and In Vitro Evaluation in Breast Cancer Models.

A human epidermal growth factor receptor 2 (HER2)-specific nanobody called 2Rs15d, containing a His3LysHis6 segment at the C-terminus, was recombinantly produced. Subsequent site-selective acylation on the C-terminally activated lysine residue allowed installation of the cytotoxin monomethyl auristatin E-functionalized cathepsin B-sensitive payload to provide a highly homogenous nanobody-drug conjugate (NBC), which demonstrated high potency and selectivity for HER2-positive breast cancer models.

Radiocobalt-Labeling of a Polypyridylamine Chelate Conjugated to GE11 for EGFR-Targeted Theranostics.

The overexpression of the epidermal growth factor receptor (EGFR) in certain types of prostate cancers and glioblastoma makes it a promising target for targeted radioligand therapy. In this context, pairing an EGFR-targeting peptide with the emerging theranostic pair comprising the Auger electron emitter cobalt-58m (Co) and the Positron Emission Tomography-isotope cobalt-55 (Co) would be of great interest for creating novel radiopharmaceuticals for prostate cancer and glioblastoma theranostics. In this study, GE11 (YHWYGYTPQNVI) was investigated for its EGFR-targeting potential when conjugated using click chemistry to N1-((triazol-4-yl)methyl)-N1,N2,N2-tris(pyridin-2-ylmethyl)ethane-1,2-diamine (TZTPEN).

The Role of microRNA-22 in Metabolism.

microRNA-22 (miR-22) plays a pivotal role in the regulation of metabolic processes and has emerged as a therapeutic target in metabolic disorders, including obesity, type 2 diabetes, and metabolic-associated liver diseases. While miR-22 exhibits context-dependent effects, promoting or inhibiting metabolic pathways depending on tissue and condition, current research highlights its therapeutic potential, particularly through inhibition strategies using chemically modified antisense oligonucleotides. This review examines the dual regulatory functions of miR-22 across key metabolic pathways, offering perspectives on its integration into next-generation diagnostic and therapeutic approaches while acknowledging the complexities of its roles in metabolic homeostasis.

Dysbiosis-NK Cell Crosstalk in Pancreatic Cancer: Toward a Unified Biomarker Signature for Improved Clinical Outcomes.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis, primarily due to its immunosuppressive tumor microenvironment (TME), which contributes to treatment resistance. Recent research shows that the microbiome, including microbial communities in the oral cavity, gut, bile duct, and intratumoral environments, plays a key role in PDAC development, with microbial imbalances (dysbiosis) promoting inflammation, cancer progression, therapy resistance, and treatment side effects. Microbial metabolites can also affect immune cells, especially natural killer (NK) cells, which are vital for tumor surveillance, therapy response and treatment-related side effects.

Advancing Inflammatory Bowel Disease Treatment by Targeting the Innate Immune System and Precision Drug Delivery.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30-50% of patients or cause significant side effects, emphasizing the need for new treatments. Targeting the innate immune system and enhancing drug delivery to inflamed gut regions are promising strategies.

Ecometabolomics of Loggerhead Sea Turtles (): The Impact of Age on Metabolomic Profiles.

To investigate the impact of age on the metabolomic profile of loggerhead sea turtles (), this study analyzed 100 plasma samples of individuals across two age groups-50 post-hatchlings and 50 juveniles-from various locations along the Mediterranean coastline. Both targeted and untargeted metabolomic analyses were performed on the samples. Our results demonstrated a significant age-related effect on the metabolomic profiles in both analyses.

DNA Methylation in Pituitary Adenomas: A Scoping Review.

Pituitary adenomas are a diverse group of neoplasms with variable clinical behavior. Despite advances in genetic analysis, understanding the role of epigenetic modifications, particularly DNA methylation, remains an area under investigation. This scoping review aimed to update and synthesize the current body of literature on DNA methylation in pituitary adenomas, focusing on methodological advancements and clinical correlations.

Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor outcomes due to frequent recurrence, metastasis, and resistance to treatment. A major contributor to this resistance is the tumor's ability to suppress natural killer (NK) cells, which are key players in the immune system's fight against cancer. In PDAC, the tumor microenvironment (TME) creates conditions that impair NK cell function, including reduced proliferation, weakened cytotoxicity, and limited tumor infiltration.

Studying the Oncolytic Activity of Strains Against Hepatoma, Glioma, and Pancreatic Cancer and .

Background: Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic potential of Group A (GAS) strains for tumor treatment.

Biocontrol Potential of Rhizospheric Bacillus Strains Against Jagger Causing Lettuce Drop.

Phytopathogenic Jagger causes lettuce drop, a destructive soil-borne disease. As potential biocontrol agents for this disease, 2 of 31 bacterial strains isolated from soil samples from fields containing Jagger were identified using in vitro antagonistic assays against Jagger. Bioactivity experiments showed that Bac20 had higher inhibitory activity against Jagger than Bac45.

Nano-Perforated Silicon Membrane with Monolithically Integrated Buried Cavity.

A wafer-scale process for fabricating monolithically suspended nano-perforated membranes (NPMs) with integrated support structures into silicon is developed. Existing fabrication methods are suitable for many desired geometries, but face challenges related to mechanical robustness and fabrication complexity. We demonstrate a process that utilizes the cyclic deposit, remove, etch, and multi-step (DREM) process for directional etching of high-aspect-ratio (HAR) 300 nm in diameter nano-pores of 700 nm pitch.

Correction: Larsen, E.H.; Sørensen, J.N. Biophysical Analysis of a Minimalistic Kidney Model Expressing SGLT1 Reveals Crosstalk between Luminal and Lateral Membranes and a Plausible Mechanism of Isosmotic Transport. 2024, , 889.

The authors would like to modify Equations (5a) and (5b) in Section 3 [...

Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases.

Chronic hepatobiliary damage progressively leads to fibrosis, which may evolve into cirrhosis and/or hepatocellular carcinoma. The fight against the increasing incidence of liver-related morbidity and mortality is challenged by a lack of clinically validated early-stage biomarkers and the limited availability of effective anti-fibrotic therapies. Current research is focused on uncovering the pathogenetic mechanisms that drive liver fibrosis.

Mapping Antimicrobial Resistance in Isolates from Subclinical Mastitis in Danish Dairy Cows.

Although is a key cause of subclinical mastitis in Danish dairy cows, its sensitivity to antimicrobials remains unexplored. Here, we analyzed sixty isolates derived from 42 dairy cows across six conventional dairy herds in Denmark. Phenotypic resistance was measured by antimicrobial susceptibility testing and minimum inhibitory concentration (MIC) analysis, and genotypic resistance was examined through whole-genome sequencing and identification of antimicrobial resistance genes (ARGs).

Metabolic Performance of Mealworms and Black Soldier Fly Larvae Reared on Food and Agricultural Waste and By-Products.

Mealworms and black soldier fly (BSF) larvae are two of the most reared insects at an industrial scale. Both may feed on by-products from agricultural and food industries. Feed efficiency is one of the most important aspects of such processes and varies between species and feed substrates and depends on the metabolic performance of the larvae.

New Promising Steroidal Aromatase Inhibitors with Multi-Target Action on Estrogen and Androgen Receptors for Breast Cancer Treatment.

Endocrine therapies that comprise anti-estrogens and aromatase inhibitors (AIs) are the standard treatment for estrogen receptor-positive (ER+) (Luminal A) breast cancer-the most prevalent subtype. However, the emergence of resistance restricts their success by causing tumor relapse and re-growth, which demands a switch towards other therapeutic approaches in order to minimize or overcome resistance. Indeed, this clinical limitation highlights the search for new molecules to improve cancer treatment.

Updates in Biliary Atresia: Aetiology, Diagnosis and Surgery.

Biliary atresia (BA) is an obliterative disease of the bile ducts affecting between 1 in 10,000-20,000 infants with a predominance in Asian countries. It is clinically heterogeneous with a number of distinct variants (e.g.