Search

Abstract Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.

Background: Myositis is an inflammatory myopathy that can be caused by a variety of drugs, diseases, and toxins. The U.S. military uses chemoprophylaxis with intramuscular penicillin G to prevent group A streptococcal infection. We present a case of penicillin G-induced myositis, a rare cause of drug-induced myositis with limited discussion in the medical literature. Case Report: A 25-year-old man with no pertinent medical history presented to the Emergency Department with right hip and leg pain after receiving a single dose of intramuscular penicillin G as part of standard prophylaxis for group A streptococcal infection during basic military training. He reported pain and leg weakness that was exacerbated by physical exertion and weight bearing but had no systemic symptoms, such as fevers or chills. Initial radiographs of the hip were normal; however, subsequent magnetic resonance imaging of the hip revealed intramuscular edema and features consistent with myositis of the right proximal thigh and hip musculature. He was admitted for isolated right gluteal myositis, attributed to his preceding local penicillin injection. He recovered with symptomatic care over the following 2 weeks, with return to baseline function. Conclusions: This case highlights a rare complication of intramuscular penicillin G as a cause of acute isolated myositis. It serves to inform physicians of this rare complication and to recommend the consideration of intramuscular penicillin G as a causative etiology in individuals presenting with myositis and recent penicillin G exposure. [ABSTRACT FROM AUTHOR]

This study was tasked with the design of mucoadhesive buccal films (MBFs) containing a peptide drug, leuprolide (LEU), or its diverse nanoparticles (NPs), for enhanced membrane permeability via self-assembled nanonization and deformable behavior. An LEU-oleic acid conjugate (LOC) and its self-assembled NPs (LON) were developed. Additionally, a deformable variant of LON (d-LON) was originally developed by incorporating l-α-phosphatidylcholine into LON as an edge activator. The physicochemical properties of LON and d-LON, encompassing particle size, zeta potential, and deformability index (DI), were evaluated. MBFs containing LEU, LOC, and NPs (LON, d-LON) were prepared using the solvent casting method by varying the ratio of Eudragit RLPO and hydroxypropyl methylcellulose, with propylene glycol used as a plasticizer. The optimization of MBF formulations was based on their physicochemical properties, including in vitro residence time, dissolution, and permeability. The dissolution results demonstrated that the conjugation of oleic acid to LEU exhibited a more sustained LEU release pattern by cleaving the ester bond of the conjugate, as compared to the native LEU, with reduced variability. Moreover, the LOC and its self-assembled NPs (LON, d-LON), equivalent to 1 mg LEU doses in MBF, exhibited an amorphous state and demonstrated better permeability through the nanonization process than LEU alone, regardless of membrane types. The incorporation of lauroyl-L-carnitine into the films as a permeation enhancer synergistically augmented drug permeability. Most importantly, the d-LON-loaded buccal films showed the highest permeability, due to the deformability of NPs. Overall, MBF-containing peptide NPs and permeation enhancers have the potential to replace parenteral LEU administration by improving LEU druggability and patient compliance.

The growing beekeeping industry in South Korea has led to the establishment of new honey plant complexes. However, studies on honey production from each species are limited. This study aimed to assess the honey production potential of various Brassica napus cultivars and two wildflower species. The nectar characteristics of B. napus varied significantly among the cultivars. Absolute sugar concentrations differed among the cultivars, but sugar composition ratios were similar. In contrast, the amino acid content remained relatively uniform regarding percentage values, irrespective of the absolute concentrations. Estimations of honey potential production per hectare (kg/ha) resulted in the following ranking among cultivars: ‘JM7003’ (107.1) > ‘YS’ (73.0) > ‘JM7001’ (63.7) > ‘TL’ (52.7) > ‘TM’ (42.4). The nectar volume of Pseudolysimachion rotundum var. subintegrum and Leonurus japonicus increased during the flowering stage. P. rotundum var. subintegrum was sucrose-rich and L. japonicus was sucrose-dominant. Both species predominantly contained phenylalanine, P. rotundum var. subintegrum had glutamine as the second most abundant amino acid, and L. japonicus had tyrosine. The honey production potential was 152.4 kg/ha for P. rotundum var. subintegrum and 151.3 kg/ha for L. japonicus. These findings provide a basis for identifying food resources for pollinators and selecting plant species to establish honey plant complexes.