Objective: To investigate the effects of the endothelin 1 (ET-1) receptor antagonists (ETRA) macitentan, its active metabolite ACT-132577, and bosentan on myofibroblast activation and extracellular matrix production induced by ET-1 in cultured systemic sclerosis (SSc) and control skin fibroblasts.
Methods: Fibroblasts were obtained from skin biopsies of 6 patients with SSc and 5 healthy subjects. Some cultured cells were untreated or treated with macitentan, ACT-132577, or bosentan alone (10 μM). Other cultured cells were treated with ET-1 alone (100 nM) or with ETRA, and after 1 h, also with ET-1. After 48 h of treatment, myofibroblast activation was investigated to evaluate the α-smooth muscle actin (α-SMA) expression by immunofluorescence; type I collagen (COL-1) and fibronectin (FN) were investigated by immunocytochemistry, Western blotting, and quantitative real-time PCR (qRT-PCR). Statistical analysis was performed by the nonparametric Mann-Whitney U test.
Results: In cultured SSc skin fibroblasts, only the treatment with macitentan significantly reduced the basal level of α-SMA expression (p = 0.03 vs untreated cells). Macitentan also significantly reduced the basal level of COL-1 synthesis, similarly to bosentan (p < 0.05 vs untreated cells). Macitentan or ACT-132577 antagonized the ability of ET-1 to further induce α-SMA expression (p = 0.03), COL-1, and FN synthesis (p = 0.03, p = 0.005); bosentan showed similar effects. These results obtained by immunofluorescence and immunocytochemistry were confirmed by Western blotting and qRT-PCR. The downregulatory effects exerted by ETRA were observed also in cultured human control skin fibroblasts.
Conclusion: Macitentan and ACT-132577 seem to downregulate in vitro the profibrotic myofibroblast phenotype induced by ET-1 in cultured human SSc skin fibroblasts.
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http://dx.doi.org/10.3899/jrheum.141070 | DOI Listing |
J Biomed Mater Res A
January 2025
Biomedical Engineering Institute, Chiang Mai University, Chiang Mai, Thailand.
Plasma nitriding is one of the surface modifications that show more effectiveness than other methods. In this study, the plasma-based ion implantation (PBII) technique was performed on the surface of titanium alloy (Ti-6Al-4V, Ti64) using a mixture of nitrogen (N) and argon (Ar), resulting in a plasma-nitrided surface (TiN-Ti64). The surface composition of the TiN-Ti64 was verified through X-ray photoelectron spectroscopy (XPS).
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Eukaryotic translation release factor eRF1 is an important cellular protein that plays a key role in translation termination, nonsense-mediated mRNA decay (NMD), and readthrough of stop codons. The amount of eRF1 in the cell influences all these processes. The mechanism of regulation of eRF1 translation through an autoregulatory NMD-dependent expression circuit has been described for plants and fungi, but the mechanisms of regulation of human eRF1 translation have not yet been studied.
View Article and Find Full Text PDFJ Anthropol Sci
December 2024
Independent Researcher, Rome, Italy.
Human nutrition represents a dynamic interplay between biological evolution and cultural development, profoundly shaping dietary practices and health outcomes. This paper traces the dietary evolution of the genus Homo, from practices like foraging, scavenging, hunting, and gathering to the Neolithic transition towards agropastoral subsistence. These changes influenced human biology, evident in genetic adaptations such as lactase persistence and amylase gene copy variation, and reshaped societal structures and population dynamics.
View Article and Find Full Text PDFCell Commun Signal
December 2024
Departmentof Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Background: Peritoneal dissemination of ovarian cancer (OvCa) can be largely attributed to the formation of a metastatic microenvironment driven by tumoral exosomes. Here, we aimed to elucidate the mechanisms through which exosomal annexin A2 (ANXA2) derived from OvCa cells induces an HPMC phenotypic shift in favour of peritoneal metastasis.
Methods: Immunohistochemistry and orthotopic and intraperitoneal OvCa xenograft mouse models were used to clarify the relationship between tumour ANXA2 expression and peritoneal metastasis.
AIDS Res Ther
December 2024
School CAPHRI, Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands.
Introduction: Despite the need for reliable questionnaires to monitor self-management in chronic disease patients, such tools are lacking in developing countries. This study aims to pilot and assess the construct validity of the HIV-SM LMIC questionnaire.
Method: The validation of the HIV-SM LMIC questionnaire involved two cross-sectional studies in Ethiopia.
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