IUBMB Life最新文献

Acute lung injury (ALI) is a condition with acute respiratory failure caused by various factors, characterized by severe hypoxemia and diffuse alveolar damage, involving multiple cytokines and signaling pathways. This study investigates the role of secreted phosphoprotein 1 (SPP1) in ALI and explores its underlying mechanisms through a series of in vitro and in vivo experiments. Our results demonstrate that SPP1 expression is significantly upregulated in ALI animal models, correlating with increased oxidative stress and inflammatory responses. In LPS-induced lung injury models, elevated levels of malondialdehyde (MDA) and IL1β, along with decreased superoxide dismutase (SOD) levels, were observed, further confirming the active state of SPP1 in ALI. In vitro experiments using BEAS-2B cells revealed that LPS treatment increased IL1β and reactive oxygen species (ROS) levels while decreasing SOD levels, with concomitant upregulation of SPP1. SPP1 knockdown significantly inhibited these changes, directly confirming its regulatory role in ALI progression. We further explored the regulatory mechanisms of SPP1 on the senescence-associated secretory phenotype (SASP), a key pathological process in ALI. SA-β-GAL staining and γ-H2AX results indicated elevated cellular senescence in LPS-treated cells and ALI models. SPP1 knockdown reduced senescence markers, enhanced cell viability, decreased apoptosis, and improved cell proliferation capacity, suggesting that SPP1 promotes ALI via the SASP phenotype. Mechanistically, we found that SPP1 regulates ALI via the p53 signaling pathway. LPS treatment increased p-p53 levels, whereas SPP1 knockdown reduced p53 activation. The use of a p53 inhibitor further suppressed SASP and improved ALI-related indicators. Animal model validation corroborated these findings, showing that SPP1 knockdown and p53 inhibitor treatment reduced lung tissue damage and improved ALI-related indicators. Collectively, our study reveals a novel mechanism by which SPP1 regulates ALI progression via the p53 signaling pathway and SASP. This discovery not only enriches our understanding of ALI pathogenesis but also provides a new therapeutic target and potential intervention strategies for ALI treatment.

Although tumor biology and treatment of neuroblastoma (NB) have substantially advanced, the clinical outcomes of patients with high-risk NB (HR-NB) still remain unsatisfactory. Increasing evidence suggests that targeting the tumor microenvironment (TME) is an effective strategy for the treatment of patients with HR-NB, highlighting the necessity to deepen the understanding of the complex TME in HR-NB. We analyzed the single-cell RNA sequencing data of 16 NB samples from 11 patients with HR-NB and 5 patients with intermediate-/low-risk NB. We found that proliferating CD8+ TUBA1B+ T cells, H2AFZ+ macrophages, and proliferating HMGB2+ B cells were particularly enriched in HR-NB samples and played an immunosuppressive role. LAG3 and HAVCR2 could serve as potential immunotherapeutic targets for HR-NB. SCENIC analysis innovatively revealed that proliferating HMGB2+ B cells had a special differentiation process compared with that of plasma cells. H2AFZ+ macrophages evolved from monocytes and M1-like macrophages and exhibited an M2-like phenotype. HR-NB-enriched cancer-associated fibroblasts and endothelial cells were related to tumor migration and progression. An immune-related risk model based on five genes (BIRC5, UBE2C, CDKN3, TK1, and PTTG1) was constructed in the training set and applied to the validation set. Both sets showed a promising clinical prediction value. In sum, this study preliminarily revealed the landscape of the TME in HR-NB at a single-cell level; several TME cell clusters that could inhibit immune activities or promote tumor progression in HR-NB were determined, thereby providing novel immunotherapeutic targets and an immune-related prognostic signature for HR-NB and promoting the development of immunotherapy of HR-NB.

Peroxisome proliferator–activated receptors (PPARs), particularly PPAR-α and PPAR-γ, are key regulators of cardiac energy metabolism and have been implicated in cardiac remodeling. However, their roles in cardiomyocyte proliferation and hypertrophy remain incompletely understood. In this study, we investigated the effects of PPAR-α and PPAR-γ modulation on neonatal rat cardiomyocytes (NRCMs) using pharmacological agonists (WY-14643 for PPAR-α and pioglitazone for PPAR-γ) and inhibitors (MK-886 for PPAR-α and GW9662 for PPAR-γ), as well as siRNA-mediated knockdown approaches. Cardiomyocyte proliferation and hypertrophy were assessed by immunofluorescence, cell size measurements, and proliferation assays. Our findings demonstrate that PPAR-α activation significantly promotes cardiomyocyte proliferation and reduces hypertrophy, whereas PPAR-α inhibition induces hypertrophic changes and suppresses proliferation. Similarly, PPAR-γ activation enhances both proliferation and hypertrophy of cardiomyocytes, suggesting its involvement in physiological hypertrophy and a potential protective role in pathological remodeling. In contrast, pharmacological activation or genetic inhibition of PPAR-δ showed no significant effects on cardiomyocyte proliferation or hypertrophy, highlighting its distinct role in metabolic homeostasis rather than structural remodeling. PPAR-α and PPAR-γ play distinct but complementary roles in regulating cardiomyocyte proliferation and hypertrophy. These results suggest that targeting PPAR-α and PPAR-γ may represent promising therapeutic strategies for cardiac hypertrophy and heart failure. Further in vivo studies are warranted to clarify their molecular mechanisms and potential clinical applications.

The Arabian Gulf surrounding Qatar is an oligotrophic marine environment characterized by extreme conditions, such as increased water temperatures and high salinity compared to other semi-enclosed seas, such as the Mediterranean Sea. Thirty-six black yeast-like isolates were obtained from marine waters surrounding Qatar, representing 4% of all isolated yeasts. DNA sequence analysis of the internal transcribed spacers (ITS1, ITS2), the 5.8S rRNA gene, and the D1/D2 domains of the LSU rDNA identified 20 isolates as Hortaea werneckii, and 15 (75%) of them represent previously unknown genotypes with a wide NaCl tolerance at 37°C. In addition, 16 meristematic black yeast-like cultures were isolated that grew as multi-cellular bodies and reproduced by endoconidiation. Phylogenetic analysis based on the D1/D2 domains of LSU rDNA, partial sequences of the second largest subunit of RNA polymerase II (RPB2) and translation elongation factor 1-alpha (TEF) of selected representative strains of Dothideomycetes and of morphologically similar taxa, Pseudotaeniolina globosa and Trimmatostroma salinum, supported the proposal of meristematic black yeast-like cultures as a new species, Salinomyces qatarensis sp. nov., within Teratosphaeriaceae, Mycosphaerellales. The holotype is designated as CBS 150510, with ex-type strains EXF-15246 and QCC/Y38/18, and the species is registered in Mycobank as MB#848869. In addition, based on the above molecular analysis, a new combination was proposed for an euryhaline fungus from Mediterranean salterns, Trimmatostroma salinum, into the genus Verrucocladosporium as V. salinum, MB#856063. This study increases our knowledge of the distribution and genetic diversity of Hortaea werneckii, the etiological agent of tinea nigra. In addition, the description of S. qatarensis and the combination of euryhaline T. salinum to Verrucocladosporium provides support for halotolerance as one of the traits in Dothideomycetes.

Squalene, a naturally occurring triterpene, has gained significant attention due to its critical role as an adjuvant in COVID-19 vaccines and its broad applications in pharmaceuticals, cosmetics, and nutraceuticals. This review explores the potential of squalene production, prompting a shift toward sustainable and innovative approaches. Key biosynthetic pathways across various organisms, including plants, fungi, and microalgae, are analyzed to identify efficient production systems as compared to fast-growing heterotrophic thraustochytrids. Advanced strategies to enhance squalene yields are explored, including the use of chemical enhancers (methyl jasmonate), antioxidants (alpha-tocopherol), cofactor recycling, and squalene epoxidase inhibitors (terbinafine). Additionally, the global market potential of squalene is assessed, highlighting its economic importance and growing demand in the healthcare and cosmetic industries. The challenges of large-scale squalene production are addressed with a focus on sustainable alternatives to shark-derived sources as a high ethical concern. By aligning with Sustainable Development Goals (SDG-3: Good Health and Well-Being), squalene production supports advancements in vaccine development and biotechnological innovations. Future opportunities are highlighted, including novel applications in cancer therapy, functional foods, and anti-aging products, offering pathways to harness its full potential while contributing to a sustainable bioeconomy.