TY  - JOUR
AB  - Acute lung injury (ALI), especially when resulting from trauma-associated hemorrhagic shock (THS), is a life-threatening condition with limited treatment options and high mortality. Understanding the molecular mechanisms driving ALI in this context is essential to identify reliable biomarkers and therapeutic targets. This study aimed to explore the transcriptomic alterations and protein interaction networks in a rat model of THS-induced ALI using RNA sequencing and bioinformatics tools. RNA-seq analysis was performed on lung tissues from five THS-induced and five normal rats. Analysis revealed 1003 differentially expressed genes, including 365 upregulated and 638 downregulated. Functional enrichment pointed to significant involvement of pathways related to oxidative stress, hypoxia response, neutrophil degranulation, ferroptosis, and immune activation. Protein-protein interaction network analysis identified four key gene modules, with Module 3 notably associated with iron metabolism and neutrophilic inflammation. Hub genes such as Cd163, Nqo1, Gclc, Lcn2, and Mmp8 were identified as central regulators and validated in independent samples (three THS-induced and three controls). Lcn2 and cathepsins (CTSS, CTSK, CTSL) emerged as particularly relevant for their multifaceted roles in inflammation, iron homeostasis, and matrix remodeling. These findings provide novel insights into the immunometabolic dysregulation underlying THS-induced ALI and suggest promising molecular targets for future therapeutic interventions aimed at mitigating lung injury in critically injured trauma patients.
AU  - Mishra, M.*
AU  - Agrawal, S.*
AU  - Mishra, S.P.*
AU  - Kumar, R.*
AU  - Mishra, K.*
AU  - Pathak, E.
AU  - Mishra, R.*
C1  - 75931
C2  - 58199
SP  - 17-28
TI  - Unveiling the molecular mechanisms of hemorrhagic shock and acute lung injury: An integrative RNA-seq and network analysis.
JO  - Transl. Res.
VL  - 284
PY  - 2025
SN  - 1931-5244
ER  - 

TY  - JOUR
AB  - Chronic low-grade inflammation has been proposed as a linking mechanism between obesity and the development of inflammation-related conditions such as insulin resistance and cardiovascular disease. Despite major advances in the last two decades, the complex interplay between immune regulators and obesity remains poorly understood. Therefore, we aimed to identify novel inflammation-related proteins associated with adiposity. We investigated the association between BMI and waist circumference and 72 circulating inflammation-related proteins, measured using the Proximity Extension Assay (Olink Proteomics), in 3,308 participants of four independent European population-based studies (KORA-Fit, BVSII, ESTHER, and Bialystok PLUS). In addition, we used body fat mass measurements obtained by Dual-energy X-ray absorptiometry (DXA) in the Bialystok PLUS study to further validate our results and to explore the relationship between inflammation-related proteins and body fat distribution. We found 14 proteins associated with at least one measure of adiposity across all four studies, including four proteins for which the association is novel: DNER, SLAMF1, RANKL, and CSF-1. We confirmed previously reported associations with CCL19, CCL28, FGF-21, HGF, IL-10RB, IL-18, IL-18R1, IL-6, SCF, and VEGF-A. The majority of the identified inflammation-related proteins were associated with visceral fat as well as with the accumulation of adipose tissue in the abdomen and the trunk. In conclusion, our study provides new insights into the immune dysregulation observed in obesity that might help uncover pathophysiological mechanisms of disease development.
AU  - Ponce-de-Leon, M.
AU  - Linseisen, J.
AU  - Peters, A.
AU  - Linkohr, B.
AU  - Heier, M.
AU  - Grallert, H.
AU  - Schöttker, B.*
AU  - Trares, K.*
AU  - Bhardwaj, M.*
AU  - Gao, X.*
AU  - Brenner, H.*
AU  - Kamiński, K.A.*
AU  - Paniczko, M.*
AU  - Kowalska, I.*
AU  - Baumeister, S.E.*
AU  - Meisinger, C.
C1  - 63651
C2  - 51742
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 93-104
TI  - Novel associations between inflammation-related proteins and adiposity: A targeted proteomics approach across four population-based studies.
JO  - Transl. Res.
VL  - 242
PB  - Elsevier Science Inc
PY  - 2022
SN  - 1931-5244
ER  - 

TY  - JOUR
AB  - The present review aims to summarize available knowledge on the role of the ubiquitin-proteasome system (UPS) in the pathogenesis of scleroderma and scleroderma-related disease mechanisms. This will provide the reader with a more mechanistic understanding of disease pathogenesis and help to identify putative novel targets within the UPS for potential therapeutic intervention. Because of the heterogenous manifestations of scleroderma, we will primarily focus on conserved mechanisms that are involved in the development of lung scleroderma phenotypes.
AU  - Meiners, S.
AU  - Evankovich, J.*
AU  - Mallampalli, R.K.*
C1  - 53457
C2  - 44874
TI  - The ubiquitin proteasome system as a potential therapeutic target for systemic sclerosis.
JO  - Transl. Res.
PY  - 2018
SN  - 1931-5244
ER  -