This study successfully developed novel self-supporting tacrolimus suppositories using 3D printing, utilizing blends of Gelucire 44/14 and coconut oil, and evaluated their effectiveness in a rat model of inflammatory bowel disease induced by TNBS. The effectiveness of the treatment was monitored through PET/CT imaging, showing significant reductions in inflammation, confirmed by histological analysis and correlated with body weight changes, thus demonstrating the potential of 3D printed suppositories in treating colitis and the value of non-invasive imaging in preclinical therapy evaluation.
Very interesting article! This research explores the effects of verbascoside, a polyphenolic plant compound known for its antioxidant, anti-inflammatory, and neuroprotective properties, on pancreatic β-cells, previously untested targets. We discovered that verbascoside offers a dose-dependent protection for both mouse and human β-cells against oxidative stress and ER-stress-induced dysfunctions by modulating the PERK pathway of the unfolded protein response and enhancing mitochondrial dynamics, leading to increased cell viability, improved mitochondrial function, and higher insulin content. These findings highlight verbascoside's potential as a therapeutic agent in diabetes by enhancing β-cell resilience to stress conditions commonly associated with the disease.
The novel approach to encapsulating Methotrexate (MTX) in liposomes through an enhanced ethanol injection method eliminates the need for extrusion and significantly increases MTX encapsulation efficiency above 30%. This technique results in liposomes with smaller sizes and low polydispersity, suitable for in vivo applications, and is validated by NMR studies showing strong drug-lipid interactions. In vivo experiments in arthritic mice demonstrate the enhanced therapeutic benefits of this delivery system, representing a significant advancement in MTX's application for treating rheumatoid arthritis.
Cardiovascular mortality is a significant health concern in individuals with type 2 diabetes (T2DM), largely due to endothelial dysfunction (ED), which contributes to diabetic cardiovascular complications. Metformin, the first-choice medication for T2DM according to EASD/ADA guidelines, has shown promise beyond glucose regulation, particularly in mitigating ED through mechanisms like AMPK activation, reducing inflammation, and improving endothelial function, thereby potentially preventing atherosclerosis.
In this review, they discuss current knowledge about IDE’s function as a regulator of insulin secretion and hepatic insulin sensitivity, both evaluating the classical view of IDE as an insulin protease and also exploring evidence for several non-proteolytic functions. Insulin proteostasis and insulin sensitivity have both been highlighted as targets controlling blood sugar levels in type 2 diabetes, so a clearer understanding the physiological functions of IDE in pancreas and liver could led to the development of novel therapeutics for the treatment of this disease.
Obesity, affecting over 1.9 billion adults globally, is a growing public health issue linked to increased cardiovascular morbidity and mortality, primarily due to its impact on endothelial function through various obesity-related complications. This review highlights the pathophysiological mechanisms behind obesity-induced endothelial dysfunction and explores potential therapeutic targets for mitigating cardiovascular risks.
Chronic lung diseases are a major global health issue, and lung transplants, limited by donor availability, are the only definitive treatment for end-stage conditions. Lung tissue engineering (LTE) offers hope by aiming to regenerate damaged lung tissue, but it faces challenges due to the lung's complex structure. We've developed a promising solution: an extracellular matrix (ECM)-integrated scaffold, created through a process of cellularization, decellularization, and recellularization on our novel BETA scaffold. This scaffold, less than 5 µm thick and made of a co-polymeric material, allows human lung fibroblasts to grow and deposit ECM, mimicking the lung's microenvironment more accurately after a mild decellularization process. Our technique successfully preserves key ECM proteins, such as collagen I and IV, and supports the growth of primary fibroblasts and bronchial epithelial cells, indicating its potential for LTE applications. This biomimetic scaffold represents a significant step towards creating a functional replacement for damaged lung tissue.
The application of DL in MS proteomics and single-cell genomics is rapidly evolving, offering exciting possibilities for uncovering the molecular underpinnings of MS and advancing personalized medicine.
Lipid nanoparticles (LNPs) are gaining attention as an efficient, non-viral method for delivering drugs, especially in the face of respiratory diseases highlighted by the COVID-19 pandemic. This review covers the advancements in LNP technology and pre-clinical studies on inhaled drugs, including small molecules, nucleic acids, and proteins/peptides, emphasizing the benefits of targeting the lungs to minimize systemic side effects and enhance drug effectiveness. It also addresses the challenges in formulation design and looks forward to the potential of LNPs in treating respiratory diseases through inhalation therapy.
Despite advances in heart failure (HF) treatment, risks remain high, linked to dysfunction in the NO-sGC-cGMP pathway which vericiguat aims to correct by enhancing cGMP levels, thus reducing oxidative stress and improving heart function. Clinical trials, including SOCRATES-REDUCED and VICTORIA, have shown vericiguat to be effective in patients with reduced ejection fraction (HFrEF), while its benefits for those with preserved ejection fraction (HfpEF) are still under investigation.
Alzheimer's disease (AD) significantly contributes to elderly mortality worldwide, with current treatments still under development. Stem cell therapy, offering advantages over drug therapies and other treatments, shows great promise. Four primary stem cell types are utilized in AD therapy: neural, mesenchymal, embryonic, and induced pluripotent stem cells, each with applications across cellular, animal model, and clinical levels. Research has predominantly focused on the cellular and animal model stages, with less progress at the clinical stage. Future research should broaden the types of stem cells studied, integrate cross-disciplinary approaches with other diseases, and aim for more timely and personalized stem cell therapies for AD.
Migraine, a severe headache disorder linked to the trigeminal vascular system, greatly affects individuals' lives. Despite the introduction of various treatments, not all patients see significant improvement. The success of CGRP-targeted therapies emphasizes the need for research into the mechanisms of migraine to develop effective treatments. This review highlights potential therapeutic targets such as PACAP, adenosine, DOR, potassium channels, TRP, and ASIC channels, suggesting that understanding these mechanisms could lead to new treatments and better patient care.
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