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This letter, published in the American Journal of Respiratory Cell & Molecular Biology, discusses the need for early diagnosis and intervention to reduce the negative effects of ventilator-induced lung injury (VILI). The authors conducted a time-course proteomic study using a unique experimental ICU model and observed significant alterations in the proteomic profiles of bronchoalveolar lavage fluid (BALF) from Day 5 to Day 8 of mechanical ventilation (MV), indicating VILI. They identified potential biomarkers for VILI, such as MMP9 and intracellular proteins originating from lung and bronchial epithelial cells. The study highlights the importance of biomarkers for early detection of VILI to improve patient outcomes. [Extracted from the article]

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

Context There is a lack of reliable biomarkers capable of predicting postoperative tumor progression of nonfunctioning pituitary adenomas (NFPAs). Objective To discover proteomic profiles associated with postoperative tumor progression in patients with NFPAs. This was a case-controlled exploratory study at a tertiary university hospital. Tissue samples were obtained from 46 patients with residual tumor following surgery for NFPAs of gonadotroph lineage. Two patient groups were compared: patients requiring reintervention due to residual tumor progression (cases; reintervention group, n = 29) and patients with a residual tumor showing no progression for a minimum of 5 years (controls; radiologically stable group, n = 17). Differentially expressed proteins (DEPs) between patient groups were measured. Results Global quantitative proteomic analysis identified 4074 proteins, of which 550 were differentially expressed between the 2 groups (fold change >80%, false discovery rate–adjusted P ≤.05). Principal component analysis showed good separation between the 2 groups. Functional enrichment analysis of the DEPs indicated processes involving translation, ROBO-receptor signaling, energy metabolism, mRNA metabolism, and RNA splicing. Several upregulated proteins in the reintervention group, including SNRPD1, SRSF10, SWAP-70, and PSMB1, are associated with tumor progression in other cancer types. Conclusion This is the first exploratory study analyzing proteomic profiles as markers of postoperative tumor progression in NFPAs. The findings clearly showed different profiles between tumors with indolent postoperative behavior and those with postoperative tumor progression. Both enriched pathways involving DEPs and specific upregulated proteins have previously been associated with tumor aggressiveness. These results suggest the value of proteomic profiling for predicting tumor progression in patients with NFPAs. [ABSTRACT FROM AUTHOR]

Problem: Preterm birth (PTB) is a leading cause of infant mortality and morbidity. The pathogenesis of PTB is complex and involves many factors, including socioeconomy, inflammation and infection. Asymmetric dimethylarginine, ADMA and symmetric dimethylarginine, SDMA are involved in labor as inhibitors of nitric oxide, a known relaxant of the uterine smooth muscles. Arginines are scarcely studied in relation to PTB and we aimed to investigate arginines (ADMA, SDMA and L‐arginine) in women with spontaneous PTB and term birth. Methods of the Study: The study was based on data from the population‐based, prospective cohort BASIC study conducted in Uppsala County, Sweden, between September 2009 and November 2018. Arginines were analyzed by Ultra‐High Performance Liquid Chromatography using plasma samples taken at the onset of labor from women with spontaneous PTB (n = 34) and term birth (n = 45). We also analyzed the inflammation markers CRP, TNF‐R1 and TNF‐R2 and GDF‐15. Results: Women with spontaneous PTB had higher plasma levels of ADMA (p < 0.001), and L‐Arginine (p = 0.03). In addition, inflammation marker, TNF‐R1 (p = 0.01) was higher in spontaneous PTB compared to term birth. Further, in spontaneous PTB, no significant correlations could be observed when comparing levels of arginines with inflammation markers, except ADMA versus CRP. Conclusions: These findings provide novel evidence for the potential involvement of arginines in the pathogenesis of spontaneous PTB and it seems that arginine levels at labor vary independently of several inflammatory markers. Further research is warranted to investigate the potential of arginines as therapeutic targets in the prevention and management of spontaneous PTB. [ABSTRACT FROM AUTHOR]

We examined the temporal changes of the CSF proteome in patients with herpes simplex encephalitis (HSE) during the course of the disease, in relation to anti-N-methyl-D-aspartate receptor (NMDAR) serostatus, corticosteroid treatment, brain MRI and neurocognitive performance. Patients were retrospectively included from a previous prospective trial with a pre-specified CSF sampling protocol. Mass spectrometry data of the CSF proteome were processed using pathway analysis. We included 48 patients (110 CSF samples). Samples were grouped based on time of collection relative to hospital admission – T1: ≤ 9 d, T2: 13–28 d, T3: ≥ 68 d. At T1, a strong multi-pathway response was seen including acute phase response, antimicrobial pattern recognition, glycolysis and gluconeogenesis. At T2, most pathways activated at T1 were no longer significantly different from T3. After correction for multiplicity and considering the effect size threshold, 6 proteins were significantly less abundant in anti-NMDAR seropositive patients compared to seronegative: procathepsin H, heparin cofactor 2, complement factor I, protein AMBP, apolipoprotein A1 and polymeric immunoglobulin receptor. No significant differences in individual protein levels were found in relation to corticosteroid treatment, size of brain MRI lesion or neurocognitive performance. We show a temporal change in the CSF proteome in HSE patients during the course of the disease. This study provides insight into quantitative and qualitative aspects of the dynamic pathophysiology and pathway activation patterns in HSE and prompts for future studies on the role of apolipoprotein A1 in HSE, which has previously been associated with NMDAR encephalitis. [ABSTRACT FROM AUTHOR]