Predictive factors for size change of aorta in patients with acute blunt traumatic aortic injury.

OBJECTIVE: We aimed to investigate the changes in aorta size, the factors affecting size changes in patients with acute blunt traumatic aortic injury and to evaluate the adequacy of the current 120% thoracic endovascular aortic repair graft oversizing policy. DESIGN AND METHODS: This retrospective review study was conducted using the prospectively collected medical records of 45 patients (mean age: 53.5 years, male: 39 patients) with blunt traumatic aortic injury treated at a level 1 trauma center between 2012 and 2021. Aortic diameter was measured by computed tomography angiographic images at four different levels [ascending aorta (A), isthmus (B), descending thoracic aorta (C), and infrarenal aorta (D)] on arrival and follow-up (median time interval, 13 days). Associated factors including patient characteristics and hemodynamic parameters on arrival and follow-up were collected to determine their influence on changes in the aorta. RESULTS: The mean diameter of all four aortic levels increased on follow-up computed tomography compared to initial computed tomography (A: + 11.77%, B: + 10.19%, C: + 7.71%, D: + 12.04%). Patient age and injury severity score influenced changes in the diameter of the ascending aorta (P < 0.05). Patient age and blunt traumatic aortic injury grade were significantly associated with changes in the infrarenal aortic diameter (P < 0.05). Three cases of type 1 endoleak were observed at follow-up but all were spontaneously resolved without further intervention at next computed tomography follow-up. CONCLUSIONS: In patients with acute blunt traumatic aortic injury, aortic diameter is significantly smaller by about 10% under shock and is not considered a basis for oversizing the currently implemented 120% thoracic endovascular aortic repair graft sizing. However, in young patients under the age of 40, the change is significantly large and subsequent computed tomography follow-up is required.

The autoimmune response induced by α-synuclein peptides drives neuronal cell death and glial cell activation.

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation.

Role of extracorporeal life support for traumatic hemopericardium: A single level I trauma center review.

BACKGROUND: Traumatic hemopericardium may lead to cardiac tamponade, arrhythmia, arrest, or death and requires emergency surgery. We reviewed cases of traumatic hemopericardium in our center and the role of extracorporeal life support in these cases. METHODS: From November 2011 to January 2022, 28 patients with significant hemopericardium and suspected cardiac injury were enrolled. In our center, surgery is the primary treatment of choice; however, if the patient is in an unstable condition, extracorporeal life support is administered in the emergency room prior to surgery. RESULTS: Preoperative extracorporeal life support was applied to 10 patients (36 %). Two patients (20 %) were converted from extracorporeal life support to cardiopulmonary bypass during operation. After surgery, 2 patients (20 %) needed postoperative extracorporeal membrane oxygenation support. Overall, 21 patients (75 %) survived; of these, 6 (29 %) received extracorporeal life support. Meanwhile, 7 patients (25 %) died; of these, 4 patients (57 %) received extracorporeal life support. CONCLUSION: Resuscitation method is the most crucial survival strategy in patients with severe chest trauma. Extracorporeal life support in cases of traumatic hemopericardium may be beneficial and efficient in stabilizing patients prior to surgery.

Cross-Activation of Regulatory T Cells by Self Antigens Limits Self-Reactive and Activated CD8+ T Cell Responses.

The interaction between regulatory T (Treg) cells and self-reactive T cells is a crucial mechanism for maintaining immune tolerance. In this study, we investigated the cross-activation of Treg cells by self-antigens and its impact on self-reactive CD8+ T cell responses, with a focus on the P53 signaling pathway. We discovered that major histocompatibility complex (MHC) I-restricted self-peptides not only activated CD8+ T cells but also induced the delayed proliferation of Treg cells. Following HLA-A*0201-restricted Melan-A-specific (pMelan) CD8+ T cells, we observed the direct expansion of Treg cells and concurrent suppression of pMelan+CD8+ T cell proliferation upon stimulation with Melan-A peptide. Transcriptome analysis revealed no significant alterations in specific signaling pathways in pMelan+CD8+ T cells that were co-cultured with activated Treg cells. However, there was a noticeable upregulation of genes involved in P53 accumulation, a critical regulator of cell survival and apoptosis. Consistent with such observation, the blockade of P53 induced a continuous proliferation of pMelan+CD8+ T cells. The concurrent stimulation of Treg cells through self-reactive TCRs by self-antigens provides insights into the immune system's ability to control activated self-reactive CD8+ T cells as part of peripheral tolerance, highlighting the intricate interplay between Treg cells and CD8+ T cells and implicating therapeutic interventions in autoimmune diseases and cancer immunotherapy.

Prediction of respiratory complications by quantifying lung contusion volume using chest computed tomography in patients with chest trauma.

Pulmonary contusion is an important risk factor for respiratory complications in trauma patients. Hence, we aimed to determine the relationship between the ratio of pulmonary contusion volume to the total lung volume and patient outcomes and the predictability of respiratory complications. We retrospectively included 73 patients with a pulmonary contusion on chest computed tomography (CT) from 800 patients with chest trauma admitted to our facility between January 2019 and January 2020. Chest injury severity was expressed as the ratio of pulmonary contusion volume to total lung volume by quantifying pulmonary contusion volume on chest CT. The cut-off value was 80%. Among the 73 patients with pulmonary contusion (77% males, mean age: 45.3 years), 28 patients had pneumonia, and five had acute respiratory distress syndrome. The number of patients in the severe risk group with > 20% of pulmonary contusion volume was 38, among whom 23 had pneumonia. For predicting pneumonia, the area under the receiver operating characteristic curves for the ratio of pulmonary contusion volume was 0.85 (95% confidence interval 0.76-0.95, p = 0.008); the optimal threshold was 70.4%. Quantifying pulmonary contusion volume using initial CT enables identifying patients with chest trauma at high risk of delayed respiratory complications.

New insights into the phylogenetic relationships among wild onions (Allium, Amaryllidaceae), with special emphasis on the subgenera Anguinum and Rhizirideum, as revealed by plastomes.

The genus Allium, with over 900 species, is one of the largest monocotyledonous genera and is widely accepted with 15 recognized subgenera and 72 sections. The robust subgeneric and sectional relationships within Allium have long been not resolved. Based on 76 species of Allium (a total of 84 accessions), we developed a highly resolved plastome phylogenetic framework by integrating 18 newly sequenced species (20 accessions) in this study and assessed their subgeneric and sectional relationships, with special emphasis on the two subgenera Anguinum and Rhizirideum. We retrieved the three major evolutionary lines within Allium and found that the two subgenera Anguinum and Rhizirideum are monophyletic whereas others are highly polyphyletic (e.g., Allium, Cepa, Polyprason, and Melanocrommyum). Within the subgenus Anguinum, two strongly supported sublineages in East Asian and Eurasian-American were found. Allium tricoccum in North America belonged to the Eurasian clade. The distinct taxonomic status of A. ulleungense and its sister taxon were further determined. In subg. Rhizirideum, the Ulleung Island endemic A. dumebuchum shared its most recent common ancestor with the species from Mongolia and the narrow Korean endemic A. minus. Two Ulleung Island endemics were estimated to originate independently during the Pleistocene. In addition, a separate monotypic sectional treatment of the east Asian A. macrostemon (subg. Allium) and sister relationship between A. condensatum and A. chinense was suggested.

Plastome-based backbone phylogeny of East Asian Phedimus (Subgenus Aizoon: Crassulaceae), with special emphasis on Korean endemics.

Although the monophyly of Phedimus has been strongly demonstrated, the species relationships among approximately 20 species of Phedimus have been difficult to determine because of the uniformity of their floral characteristics and extreme variation of their vegetative characters, often accompanied by high polyploid and aneuploid series and diverse habitats. In this study, we assembled 15 complete chloroplast genomes of Phedimus species from East Asia and generated a plastome-based backbone phylogeny of the subgenus Aizoon. As a proxy for nuclear phylogeny, we reconstructed the nuclear ribosomal DNA internal transcribed spacer (nrDNA ITS) phylogeny independently. The 15 plastomes of subg. Aizoon were highly conserved in structure and organization; hence, the complete plastome phylogeny fully resolved the species relationships with strong support. We found that P. aizoon and P. kamtschaticus were polyphyletic and morphologically distinct or ambiguous species, and they most likely evolved from the two species complex. The crown age of subg. Aizoon was estimated to be 27 Ma, suggesting its origin to be in the late Oligocene; however, the major lineages were diversified during the Miocene. The two Korean endemics, P. takesimensis and P. zokuriensis, were inferred to have originated recently during the Pleistocene, whereas the other endemic, P. latiovalifolium, originated in the late Miocene. Several mutation hotspots and seven positively selected chloroplast genes were identified in the subg. Aizoon.

ERK3 Increases Snail Protein Stability by Inhibiting FBXO11-Mediated Snail Ubiquitination.

Snail is a key regulator of the epithelial-mesenchymal transition (EMT), the key step in the tumorigenesis and metastasis of tumors. Although induction of Snail transcription precedes the induction of EMT, the post-translational regulation of Snail is also important in determining Snail protein levels, stability, and its ability to induce EMT. Several kinases are known to enhance the stability of the Snail protein by preventing its ubiquitination; however, the precise molecular mechanisms by which these kinases prevent Snail ubiquitination remain unclear. Here, we identified ERK3 as a novel kinase that interacts with Snail and enhances its protein stability. Although ERK3 could not directly phosphorylate Snail, Erk3 increased Snail protein stability by inhibiting the binding of FBXO11, an E3 ubiquitin ligase that can induce Snail ubiquitination and degradation, to Snail. Importantly, functional studies and analysis of clinical samples indicated the crucial role of ERK3 in the regulation of Snail protein stability in pancreatic cancer. Therefore, we conclude that ERK3 is a key regulator for enhancing Snail protein stability in pancreatic cancer cells by inhibiting the interaction between Snail and FBXO11.

Pro- and Anti-Tumoral Factors Involved in Total Body Irradiation and Interleukin-2 Conditioning in Adoptive T Cell Therapy of Melanoma-Bearing Rag1 Knock-Out Mice.

In adoptive T cell therapy (ACT), the transfer of tumor-specific T cells is paralleled by the conditioning regimen to increase therapeutic efficacy. Pre-conditioning depletes immune-suppressive cells and post-conditioning increases homeostatic signals to improve the persistence of administered T cells. Identifying the favorable immunological factors involved in a conditioning regimen is important to design effective strategies in ACT. Here, by using an ACT model of murine melanoma, we evaluate the effect of the total body irradiation (TBI) and interleukin-2 (IL-2) treatment combination. The use of a Rag1 knock-out strain, which lacks endogenous T cells, enables the identification of factors in a way that focuses more on transferred T cells. We demonstrate that the TBI/IL-2 combination has no additive effect in ACT, although each conditioning improves the therapeutic outcome. While the combination increases the frequency of transferred T cells in lymphoid and tumor tissues, the activation intensity of the cells is reduced compared to that of the sole TBI treatment. Notably, we show that in the presence of TBI, the IL-2 treatment reduces the frequency of intra-tumoral dendritic cells, which are crucial for T cell activation. The current study provides insights into the immunological events involved in the TBI/IL-2 combination in ACT.

Infrageneric Plastid Genomes of Cotoneaster (Rosaceae): Implications for the Plastome Evolution and Origin of C. wilsonii on Ulleung Island.

Cotoneaster is a taxonomically and ornamentally important genus in the family Rosaceae; however, phylogenetic relationships among its species are complicated owing to insufficient morphological diagnostic characteristics and hybridization associated with polyploidy and apomixis. In this study, we sequenced the complete plastomes of seven Cotoneaster species (C. dielsianus, C. hebephyllus, C. integerrimus, C. mongolicus, C. multiflorus, C. submultiflorus, and C. tenuipes) and included the available complete plastomes in a phylogenetic analysis to determine the origin of C. wilsonii, which is endemic to Ulleung Island, Korea. Furthermore, based on 15 representative lineages within the genus, we carried out the first comparative analysis of Cotoneaster plastid genomes to gain an insight into their molecular evolution. The plastomes were highly conserved, with sizes ranging from 159,595 bp (C. tenuipes) to 160,016 bp (C. hebephyllus), and had a GC content of 36.6%. The frequency of codon usage showed similar patterns among the 15 Cotoneaster species, and 24 of the 35 protein-coding genes were predicted to undergo RNA editing. Eight of the 76 common protein-coding genes, including ccsA, matK, ndhD, ndhF, ndhK, petA, rbcL, and rpl16, were positively selected, implying their potential roles in adaptation and speciation. Of the 35 protein-coding genes, 24 genes (15 photosynthesis-related, seven self-replications, and three others) were found to harbor RNA editing sites. Furthermore, several mutation hotspots were identified, including trnG-UCC/trnR-UCU/atpA and trnT-UGU/trnL-UAA. Maximum likelihood analysis based on 57 representative plastomes of Cotoneaster and two Heteromeles plastomes as outgroups revealed two major lineages within the genus, which roughly correspond to two subgenera, Chaenopetalum and Cotoneaster. The Ulleung Island endemic, C. wilsonii, shared its most recent common ancestor with two species, C. schantungensis and C. zabelii, suggesting its potential origin from geographically close members of the subgenus Cotoneaster, section Integerrimi.