A Prospective Observational Study Analyzing the Diagnostic Value of Hepcidin-25 for Anemia in Patients with Inflammatory Bowel DiseasesPetrović, Stanko;Tarabar, Dino;Ćujić, Danica;Stamenkovic, Dusica;Petrović, Marijana;Rančić, Nemanja;Subota, Vesna;Perišić, Nenad;Bezmarević, Mihailo
doi: 10.3390/ijms25073564pmid: 38612376
Iron deficiency (IDA) and chronic disease (ACD) anemia are complications of inflammatory bowel diseases (IBDs). Therapeutic modalities in remission and active IBD depend on the type of anemia. This study evaluated the link between hepcidin-25, proinflammatory cytokines, and platelet activation markers as biomarkers of anemia and inflammation in active IBD and remission. This prospective observational study included 62 patients with IBD (49 with ulcerative colitis and 13 with Crohn’s) and anemia. Patients were divided into Group I (no or minimal endoscopic signs of disease activity and IDA), Group II (moderate and major endoscopic signs of disease activity and mild ACD), and Control group (10 patients with IBD in remission, without anemia). We assessed the difference among groups in the levels of CRP, hemoglobin (Hgb), serum iron, ferritin, hepcidin-25, interleukins, TNF–α, IFN-γ, soluble CD40 ligand, and sP-selectin. Hepcidin-25 levels were significantly higher in Group II versus Group I (11.93 vs. 4.48 ng/mL, p < 0.001). Ferritin and CRP values showed similar patterns in IBD patients: significantly higher levels were observed in Group II (47.5 ng/mL and 13.68 mg/L) than in Group I (11.0 ng/mL and 3.39 mg/L) (p < 0.001). In Group II, hepcidin-25 was positively correlated with ferritin (ρ = 0.725, p < 0.001) and CRP (ρ = 0.502, p = 0.003). Ferritin was an independent variable influencing hepcidin-25 concentration in IBD patients, regardless of disease activity and severity of anemia. IBD hepcidin-25 best correlates with ferritin, and both parameters reflected inflammation extent and IBD activity.
Impact of TRP Channels on Extracellular Matrix Remodeling: Focus on TRPV4 and CollagenWang, Qin;Ji, Chenfan;Smith, Patricio;McCulloch, Christopher A.
doi: 10.3390/ijms25073566pmid: 38612378
Disturbed remodeling of the extracellular matrix (ECM) is frequently observed in several high-prevalence pathologies that include fibrotic diseases of organs such as the heart, lung, periodontium, liver, and the stiffening of the ECM surrounding invasive cancers. In many of these lesions, matrix remodeling mediated by fibroblasts is dysregulated, in part by alterations to the regulatory and effector systems that synthesize and degrade collagen, and by alterations to the functions of the integrin-based adhesions that normally mediate mechanical remodeling of collagen fibrils. Cell-matrix adhesions containing collagen-binding integrins are enriched with regulatory and effector systems that initiate localized remodeling of pericellular collagen fibrils to maintain ECM homeostasis. A large cadre of regulatory molecules is enriched in cell-matrix adhesions that affect ECM remodeling through synthesis, degradation, and contraction of collagen fibrils. One of these regulatory molecules is Transient Receptor Potential Vanilloid-type 4 (TRPV4), a mechanically sensitive, Ca2+-permeable plasma membrane channel that regulates collagen remodeling. The gating of Ca2+ across the plasma membrane by TRPV4 and the consequent generation of intracellular Ca2+ signals affect several processes that determine the structural and mechanical properties of collagen-rich ECM. These processes include the synthesis of new collagen fibrils, tractional remodeling by contractile forces, and collagenolysis. While the specific mechanisms by which TRPV4 contributes to matrix remodeling are not well-defined, it is known that TRPV4 is activated by mechanical forces transmitted through collagen adhesion receptors. Here, we consider how TRPV4 expression and function contribute to physiological and pathological collagen remodeling and are associated with collagen adhesions. Over the long-term, an improved understanding of how TRPV4 regulates collagen remodeling could pave the way for new approaches to manage fibrotic lesions.
Design of Protease-Responsive Antifungal Liposomal Formulation Decorated with a Lipid-Modified Chitin-Binding DomainSaputra, Hendra;Safaat, Muhammad;Santoso, Pugoh;Wakabayashi, Rie;Goto, Masahiro;Taira, Toki;Kamiya, Noriho
doi: 10.3390/ijms25073567pmid: 38612381
Candida albicans is a prevalent fungal pathogen that displays antibiotic resistance. The polyene antifungal amphotericin B (AmB) has been the gold standard because of its broad antifungal spectra, and its liposomal formulation, AmBisome, has been used widely and clinically in treating fungal infections. Herein, we explored enhancing the antifungal activity of AmBisome by integrating a small chitin-binding domain (LysM) of chitinase A derived from Pteris ryukyuensis. LysM conjugated with a lipid (LysM–lipid) was initially prepared through microbial transglutaminase (MTG)-mediated peptide tag-specific conjugation of LysM with a lipid–peptide substrate. The AmBisome formulation modified with LysM–lipid conjugates had a size distribution that was comparable to the native liposomes but an increased zeta potential, indicating that LysM–lipid conjugates were anchored to AmBisome. LysM–lipid-modified AmBisome exhibited long-term stability at 4 °C while retaining the capacity to bind chitin. Nevertheless, the antifungal efficacy of LysM–lipid-modified AmBisome against C. albicans was modest. We then redesigned a new LysM–lipid conjugate by introducing a peptide linker containing a thrombin digestion (TD) site at the C-terminus of LysM (LysM–TD linker–lipid), thereby facilitating the liberation of the LysM domain from AmBisome upon the addition of thrombin. This new AmBisome formulation anchored with LysM–TD linker–lipid exhibited superior performance in suppressing C. albicans growth in the presence of thrombin compared with the LysM–lipid formulation. These results provide a platform to design stimuli-responsive AmBisome formulations that respond to external environments and thus advance the treatment of pathogenic fungi infections.
Regulation of Glycosylation in Bone MetabolismHamamura, Kazunori;Nagao, Mayu;Furukawa, Koichi
doi: 10.3390/ijms25073568pmid: 38612379
Glycosylation plays a crucial role in the maintenance of homeostasis in the body and at the onset of diseases such as inflammation, neurodegeneration, infection, diabetes, and cancer. It is also involved in bone metabolism. N- and O-glycans have been shown to regulate osteoblast and osteoclast differentiation. We recently demonstrated that ganglio-series and globo-series glycosphingolipids were essential for regulating the proliferation and differentiation of osteoblasts and osteoclasts in glycosyltransferase-knockout mice. Herein, we reviewed the importance of the regulation of bone metabolism by glycoconjugates, such as glycolipids and glycoproteins, including our recent results.
Biodiesel Production by Methanolysis of Rapeseed Oil—Influence of SiO2/Al2O3 Ratio in BEA Zeolite Structure on Physicochemical and Catalytic Properties of Zeolite Systems with Alkaline Earth Oxides (MgO, CaO, SrO)Szkudlarek, Łukasz;Chałupka-Śpiewak, Karolina;Maniukiewicz, Waldemar;Nowosielska, Magdalena;Szynkowska-Jóźwik, Małgorzata Iwona;Mierczyński, Paweł
doi: 10.3390/ijms25073570pmid: 38612389
Alkaline earth metal oxide (MgO, CaO, SrO) catalysts supported on BEA zeolite were prepared by a wet impregnation method and tested in the transesterification reaction of rapeseed oil with methanol towards the formation of biodiesel (FAMEs—fatty acid methyl esters). To assess the influence of the SiO2/Al2O3 ratio on the catalytic activity in the tested reaction, a BEA zeolite carrier material with different Si/Al ratios was used. The prepared catalysts were tested in the transesterification reaction at temperatures of 180 °C and 220 °C using a molar ratio of methanol/oil reagents of 9:1. The transesterification process was carried out for 2 h with the catalyst mass of 0.5 g. The oil conversion value and efficiency towards FAME formation were determined using the HPLC technique. The physicochemical properties of the catalysts were determined using the following research techniques: CO2-TPD, XRD, BET, FTIR, and SEM-EDS. The results of the catalytic activity showed that higher activity in the tested process was confirmed for the catalysts supported on the BEA zeolite characterized by the highest silica/alumina ratio for the reaction carried out at a temperature of 220 °C. The most active zeolite catalyst was the 10% CaO/BEA system (Si/Al = 300), which showed the highest triglyceride (TG) conversion of 90.5% and the second highest FAME yield of 94.6% in the transesterification reaction carried out at 220 °C. The high activity of this system is associated with its alkalinity, high value of the specific surface area, the size of the active phase crystallites, and its characteristic sorption properties in relation to methanol.
Genetic Update and Treatment for DystoniaKoptielow, Jan;Szyłak, Emilia;Szewczyk-Roszczenko, Olga;Roszczenko, Piotr;Kochanowicz, Jan;Kułakowska, Alina;Chorąży, Monika
doi: 10.3390/ijms25073571pmid: 38612382
A neurological condition called dystonia results in abnormal, uncontrollable postures or movements because of sporadic or continuous muscular spasms. Several varieties of dystonia can impact people of all ages, leading to severe impairment and a decreased standard of living. The discovery of genes causing variations of single or mixed dystonia has improved our understanding of the disease’s etiology. Genetic dystonias are linked to several genes, including pathogenic variations of VPS16, TOR1A, THAP1, GNAL, and ANO3. Diagnosis of dystonia is primarily based on clinical symptoms, which can be challenging due to overlapping symptoms with other neurological conditions, such as Parkinson’s disease. This review aims to summarize recent advances in the genetic origins and management of focal dystonia.
3-Methyl-4-nitrophenol Exposure Deteriorates Oocyte Maturation by Inducing Spindle Instability and Mitochondrial DysfunctionChen, Fan;Luo, An-Feng;Li, Ming-Guo;Zheng, Li-Xiang;Gu, Hao;Zhou, Chang-Fan;Zeng, Wei;Molenaar, Adrian;Ren, Hong-Yan;Bi, Yan-Zhen
doi: 10.3390/ijms25073572pmid: 38612384
3-methyl-4-nitrophenol (PNMC), a well-known constituent of diesel exhaust particles and degradation products of insecticide fenitrothion, is a widely distributed environmental contaminant. PNMC is toxic to the female reproductive system; however, how it affects meiosis progression in oocytes is unknown. In this study, in vitro maturation of mouse oocytes was applied to investigate the deleterious effects of PNMC. We found that exposure to PNMC significantly compromised oocyte maturation. PNMC disturbed the spindle stability; specifically, it decreased the spindle density and increased the spindle length. The weakened spindle pole location of microtubule-severing enzyme Fignl1 may result in a defective spindle apparatus in PNMC-exposed oocytes. PNMC exposure induced significant mitochondrial dysfunction, including mitochondria distribution, ATP production, mitochondrial membrane potential, and ROS accumulation. The mRNA levels of the mitochondria-related genes were also significantly impaired. Finally, the above-mentioned alterations triggered early apoptosis in the oocytes. In conclusion, PNMC exposure affected oocyte maturation and quality through the regulation of spindle stability and mitochondrial function.