bims-hypusi 2025-02-23 papers

Issue of 2025–02–23
five papers selected by
Sebastian J. Hofer, University of Graz

Arch Oral Biol. 2025 Feb 12. pii: S0003-9969(25)00022-6. [Epub ahead of print]173 106194

Jiawei Danxuan Koukang and its key component Quercetin intervened in OSF carcinogenesis by inhibiting the AR/eIF5A2 signaling pathway-mediated EMT.

Yuzhe Dai, Chenwei Wang, Yanbo Xiao, Yisi Tan, Yao Ye, Yue Liu, Qianqi Zeng, Jin Tan.

OBJECTIVE: This work aims to investigate the mechanism of Jiawei Danxuan Koukang (JDK) and Quercetin in oral submucous fibrosis (OSF) carcinogenesis.
DESIGN: We established an OSF model for rats by injecting Arecoline into the oral mucosa of rats to study the impact of JDK and Quercetin on the progression of OSF and OSCC. Then, the viability, proliferation, and migration ability of Arecoline-induced hOMF, CAL27 and SCC-25 cells in JDK and quercetin intervention were detected.
RESULTS: The oral mucosal epithelial cells of OSF model and OSF rats were atrophy and thinning, α-SMA, CollageI, Vimentin, Snail, AR and eukaryotic translation initiation factor 5A2 (eIF5A2) expression increased apparently, and E-cadherin expression decreased. The intervention of JDK and Quercetin reversed the changes in oral mucosal epithelial cells and OSF rats. The levels of AR in CAL27 and SCC-25 cells were higher than those in hOMF cells, and Arecoline intervention increased the levels of AR in hOMF, CAL27 and SCC-25 cells. Overexpression of AR up-regulated eIF5A2 to enhance the viability, proliferation and migration of hOMF, CAL27 and SCC-25 cells, and promoted EMT. Quercetin reversed changes in cell feature, and EMT levels in oe-AR intervention.
CONCLUSIONS: JDK and Quercetin inhibited OSF carcinogenesis by inhibiting the AR/eIF5A2 signal-mediated EMT.

Keywords: AR/eIF5A2 signaling pathway; Jiawei Danxuan Koukang; Oral submucous fibrosis; Quercetin

DOI: https://doi.org/10.1016/j.archoralbio.2025.106194

Bone Joint Res. 2025 Feb 20. 14(2): 124-135

eIF5A downregulated by mechanical overloading delays chondrocyte senescence and osteoarthritis by regulating the CREBBP-mediated Notch pathway.

Jialuo Huang, Jianrong Zheng, Jianbin Yin, Rengui Lin, Junfeng Wu, Hao-Ran Xu, Jinjian Zhu, Haiyan Zhang, Guiqing Wang, Daozhang Cai.

Aims: To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism.
Methods: Histological experiments used human bone samples and C57BL/6J mice knee samples. All cell experiments were performed using mice primary chondrocytes. Messenger RNA (mRNA) sequencing was performed on chondrocytes treated with 20% cyclic tensile strain for 24 hours. Western blot (WB) and quantitative polymerase chain reaction were employed to detect relevant indicators of cartilage function in chondrocytes. We created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). Cartilage degeneration was evaluated using Safranin O/Fast Green staining. Relative protein levels were ascertained by immunohistochemistry (IHC) and immunofluorescence (IF) staining.
Results: After OA initiation, eIF5A caused an upregulation of type II collagen (COL2) and a downregulation of matrix metalloproteinase 13 (MMP13), P16, and P21, which postponed the aggravation of OA. Further sequencing and experimental findings revealed that eIF5A knockdown accelerated the progression of OA by boosting the expression of histone acetyltransferase cyclic-adenosine monophosphate response element binding protein (CREB)-binding protein (CREBBP) to mediate activation of the Notch pathway.
Conclusion: Our findings identified a crucial functional mechanism for the onset of OA, and suggest that intra-articular eIF5A injections might be a useful therapeutic strategy for OA treatment.

DOI: https://doi.org/10.1302/2046-3758.142.BJR-2024-0288.R1

Microb Pathog. 2025 Feb 12. pii: S0882-4010(25)00100-7. [Epub ahead of print]200 107375

Evaluation of a serum and urine-based ELISA testing distinct antigens for the diagnosis of tegumentary leishmaniasis.

The diagnosis of tegumentary leishmaniasis (TL) is hampered by variable sensitivity and/or specificity of the tests. In this context, the identification of more refined antigens could contribute to improve the diagnostic quality, as well as the employ of less invasive biological samples. In this study, the eukaryotic initiation factor 5a (eIF5A) protein, one specific B-cell epitope predicted in the protein sequence, and a parasite antigenic preparation (SLA) were evaluated as antigens in ELISA experiments, which were reacted against paired serum and urine samples from 170 patients. ROC curves were constructed with the individual OD values and, when serum was used as analyte, eIF5a, peptide and SLA showed sensitivity of 44.0 %, 29.3 % and 29.3 %, respectively, and specificity of 100 %, 99.0 %, and 96.0 %, respectively PPV, NPV and Youden index for reIF5a were 100 %, 52.0 % and 0.44, respectively; while for peptide were of 98.0 %, 46.5 %, and 0.28, respectively; and for SLA, they were of 92.0 %, 46.0 %, and 0.26, respectively. Using urine as biological sample; eIF5a, peptide and SLA showed sensitivity of 100 %, 48.0 % and 52.0 %, respectively, and specificity of 99.1 %, 98.9 %, and 89.0 %, respectively. PPV, NPV and Youden index values for reIF5a were of 99.3 %, 100 % and 0.99, respectively; while for peptide were of 99.1 %, 54.3 %, and 0.47, respectively; and for SLA, they were of 88.0 %, 53.5 %, and 0.41, respectively. A preliminary assay using paired samples collected before and after treatment of eight patients showed a significant reduction in IgG levels when the three antigens were tested, with highest reductions found when urine was used as analyte. In this context, data suggest the use of patient urine as an alternative biological analyte for the diagnosis of TL.

Keywords: Diagnosis; ELISA; Eukaryotic translation initiation factor 5a; Recombinant protein; Tegumentary leishmaniasis; Urine

DOI: https://doi.org/10.1016/j.micpath.2025.107375

PeerJ. 2025 ;13 e18945

Integrated genomic analysis of the stemness index signature of mRNA expression predicts lung adenocarcinoma prognosis and immune landscape.

Xingzhao Lu, Wei Du, Jianping Zhou, Weiyang Li, Zhimin Fu, Zhibin Ye, Guobiao Chen, Xian Huang, Yuliang Guo, Jingsheng Liao.

mRNA expression-based stemness index (mRNAsi) has been used for prognostic assessment in various cancers, but its application in lung adenocarcinoma (LUAD) is limited, which is the focus of this study. Low mRNAsi in LUAD predicted a better prognosis. Eight genes (GNG7, EIF5A, ANLN, FKBP4, GAPDH, GNPNAT1, E2F7, CISH) associated with mRNAsi were screened to establish a risk model. The differentially expressed genes between the high and low risk groups were mainly enriched in the metabolism, cell cycle functions pathway. The low risk score group had higher immune cell scores. Patients with lower TIDE scores in the low risk group had better immunotherapy outcomes. In addition, risk score was effective in assessing drug sensitivity of LUAD. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) data showed that eight genes were differentially expressed in LUAD cell lines, and knockdown of EIF5A reduced the invasion and migration ability of LUAD cells. This study designed a risk model based on the eight mRNAsi-related genes for predicting LUAD prognosis. The model accurately predicted the prognosis and survival of LUAD patients, facilitating the assessment of the sensitivity of patients to immunotherapy and chemotherapy.

Keywords: Drug sensitivity; Lung adenocarcinoma; Prognosis prediction; RiskScore model; mRNAsi

DOI: https://doi.org/10.7717/peerj.18945

Curr Stem Cell Res Ther. 2025 Feb 18.

Fasting the Stem Cells to Boost their Metabolic Functions.

Pedro Henrique Maglio França, Giovanna Rosa Degasperi.

Tissue homeostasis and regeneration depend on differentiated stem cells into specialized cell types. Dietary interventions, such as caloric restriction, are critical regulators of stem cell functions by altering their metabolism. This review discusses recent studies illustrating how diet interventions impact stem cell function. We summarize molecular targets and physiological effects of different types of caloric restriction and ketogenic mimicking diets in stem cells from bone marrow, muscle, and intestine. Furthermore, we highlight the nutrient-sensing pathway target of stem cells during caloric restriction. Understanding how nutrient signaling controls stem cell fate decisions is important to developing dietary interventions to improve the clinical application of stem cells.

Keywords: Dietary interventions; caloric restriction; fasting; ketogenic diet; mTORC.; metabolism; stem cells

DOI: https://doi.org/10.2174/011574888X340501250210042712