Background: Pulmonary arterial hypertension (PAH) is a common complication for individuals with limited systemic sclerosis (lSSc). The identification and characterization of biomarkers for lSSc-PAH should lead to less invasive screening, a better understanding of pathogenesis, and improved treatment.
Methods And Findings: Forty-nine PBMC samples were obtained from 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls; three subjects provided PBMCs one year later. Genome-wide gene expression was measured for each sample. The levels of 89 cytokines were measured in serum from a subset of subjects by Multi-Analyte Profiling (MAP) immunoassays. Gene expression clearly distinguished lSSc samples from healthy controls, and separated lSSc-PAH from lSSc-NoPAH patients. Real-time quantitative PCR confirmed increased expression of 9 genes (ICAM1, IFNGR1, IL1B, IL13Ra1, JAK2, AIF1, CCR1, ALAS2, TIMP2) in lSSc-PAH patients. Increased circulating cytokine levels of inflammatory mediators such as TNF-alpha, IL1-beta, ICAM-1, and IL-6, and markers of vascular injury such as VCAM-1, VEGF, and von Willebrand Factor were found in lSSc-PAH subjects.
Conclusions And Significance: The gene expression and cytokine profiles of lSSc-PAH patients suggest the presence of activated monocytes, and show markers of vascular injury and inflammation. These genes and factors could serve as biomarkers of PAH involvement in lSSc.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012106 | PLOS |
J Trauma Acute Care Surg
January 2025
From the Department of Trauma Services (E.W.R., B.S., M.L., M.R.), OhioHealth Grant Medical Center, Columbus; and Ohio University Heritage College of Osteopathic Medicine (K.W., N.K.), Athens, Ohio.
Background: Computed tomography angiography of the head (CTAH) is not routinely obtained during the initial evaluation of patients with traumatic intracranial hemorrhage (ICH); however, it is useful for diagnosing vascular pathologies that may have led to the bleed. The aims of this study were to identify traumatic ICH patient characteristics on presentation that are associated with positive CTAH findings to elucidate which ones should prompt a CTAH and compare outcomes of patients with positive and negative CTAH findings.
Methods: This is a retrospective cohort study of 522 patients who had blunt traumatic ICH and subsequently received CTAH between January 1, 2017, and January 1, 2022.
J Trauma Acute Care Surg
January 2025
From the Division of Acute Care Surgery, Department of Surgery (M.S., M.J.M.), Los Angeles General Medical Center, Los Angeles; Division of Acute Care Surgery, Department of Surgery (R.C.), Loma Linda University School of Medicine, Loma Linda, California; Division of Acute Care Surgery, Department of Surgery (C.A.C.), University of Florida College of Medicine, Gainesville, Florida; Division of Acute Care Surgery, Department of Surgery (C.F.), University of Maryland School of Medicine, Baltimore, Maryland; Division of Acute Care Surgery, Department of Surgery (J.H.), University of Kansas Medical Center, Kansas City, Kansas; Division of Acute Care Surgery, Department of Surgery (N.K.), University of Arizona College of Medicine-Phoenix, Phoenix, Arizona; Division of Acute Care Surgery, Department of Surgery (M.L.), Methodist Dallas Medical Center, Dallas, Texas; Division of Vascular Surgery and Endovascular Therapy (G.A.M.), Keck Medical Center of USC, Los Angeles, California; Division of Acute Care Surgery, Department of Surgery (L.J.M.), The University of Texas McGovern Medical School-Houston Red Duke Trauma Institute, Memorial Hermann Hospital, Houston, Texas; Division of Acute Care Surgery, Department of Surgery (A.R.P.), Medical University of South Carolina, North Charleston, South Carolina; Division of Acute Care Surgery, Department of Surgery (K.M.S.), Yale School of Medicine, New Haven, Connecticut; UCSF Department of Surgery at Zuckerberg San Francisco General Hospital (R.T.), University of California, San Francisco, San Francisco, California; Division of Acute Care Surgery, Department of Surgery (J.A.W.), St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Program in Trauma (D.M.S.), University of Maryland School of Medicine, Baltimore, Maryland.
Proc Natl Acad Sci U S A
February 2025
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158.
The ε4 variant of human apolipoprotein E () is a key genetic risk factor for neurodegeneration in Alzheimer's disease and elevated all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate the harmful effects of has significant implications. In this study, we find that inactivating the VHL-1 (Von Hippel-Lindau) protein can suppress mortality, neural and behavioral pathologies caused by transgenic human in .
View Article and Find Full Text PDFFASEB J
January 2025
Department of Nephrology, State Key Laboratory of Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, National Clinical Research Center for Kidney Diseases, Nephrology Institute of the Chinese People's Liberation Army, Chinese PLA General Hospital, Beijing, China.
Spaceflight-induced multi-organ dysfunction affects the health of astronauts and the safety of in-orbit flight. However, the effect of microgravity on the kidney and the underlying mechanisms are unknown. In the current study, we used a hindlimb unweighting (HU) animal model to simulate microgravity and employed histological analysis, ischemia-reperfusion experiments, renal ultrasonography, bioinformatics analysis, isometric force measurement, and other molecular experimental settings to evaluate the effects of microgravity on the kidneys and the underlying mechanisms involved in this transition.
View Article and Find Full Text PDFEur Heart J
January 2025
State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Background And Aims: Members of the CCN matricellular protein family are crucial in various biological processes. This study aimed to characterize vascular cell-specific effects of CCN5 on neointimal formation and its role in preventing in-stent restenosis (ISR) after percutaneous coronary intervention (PCI).
Methods: Stent-implanted porcine coronary artery RNA-seq and mouse injury-induced femoral artery neointima single-cell RNA sequencing were performed.
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