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(Source: Translational Research)
Source: Translational Research - November 19, 2022 Category: Research Source Type: research
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(Source: Translational Research)
Source: Translational Research - November 19, 2022 Category: Research Source Type: research
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(Source: Translational Research)
Source: Translational Research - November 19, 2022 Category: Research Source Type: research
Contents
(Source: Translational Research)
Source: Translational Research - November 19, 2022 Category: Research Source Type: research
Risk Factors for Clonal Hematopoiesis of Indeterminate Potential and Mosaic Chromosomal Alterations
Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) of the autosomes, X, and Y chromosomes are aging-related somatic mutations detectable in peripheral blood. The presence of these acquired mutations predisposes otherwise healthy adults to increased risk of several chronic aging-related conditions including hematologic cancers, atherosclerotic cardiovascular diseases, other inflammatory conditions, and mortality. While the public health impact and disease associations of these blood-derived somatic mutations continue to expand, the inherited, behavioral/lifestyle, environmental ...
Source: Translational Research - November 19, 2022 Category: Research Authors: Yasminka A. Jakubek, Alexander P. Reiner, Michael C. Honigberg Tags: Review Article Source Type: research
Serum neurofilament light as a biomarker of vulnerability to a second mild traumatic brain injury
A second mild traumatic brain injury (mTBI) sustained prior to neuropathological recovery can lead to exacerbated effects. Without objective indicators of this neuropathology, individuals may return to activities at risk of mTBI when their brain is still vulnerable. With axonal injury recognised as a neuropathological hallmark of mTBI, we hypothesized that serum levels of neurofilament light (NfL), a highly sensitive biomarker of axonal injury, may be predictive of vulnerability to worse outcomes in the event of a second mTBI. (Source: Translational Research)
Source: Translational Research - November 16, 2022 Category: Research Authors: William T. O'Brien, David K. Wright, Ashley L.J.J. van Emmerik, Jesse Bain, Robert Brkljaca, Jennaya Christensen, Glenn R. Yamakawa, Zhibin Chen, Lauren P. Giesler, Mujun Sun, Terence J. O'Brien, Mastura Monif, Sandy R. Shultz, Stuart J. McDonald Source Type: research
Inhibition of PI3K/C/EBP β axis in tolerogenic bone marrow-derived dendritic cells of NOD mice promotes Th17 differentiation and diabetes development
Dendritic cells (DCs) are key regulators of the adaptive immune response. Tolerogenic dendritic cells play a crucial role in inducing and maintaining immune tolerance in autoimmune diseases such as type 1 diabetes in humans as well as in the NOD mouse model. We previously reported that bone marrow-derived DCs (BM.DCs) from NOD mice, generated with a low dose of GM-CSF (GM/DCs), induce Treg differentiation and are able to protect NOD mice from diabetes. We had also found that the p38 MAPK/C/EBP β axis is involved in regulating the phenotype, as well as the production of IL-10 and IL-12p70, by tolerogenic GM/DCs. (Source: T...
Source: Translational Research - November 14, 2022 Category: Research Authors: Chantal Guindi, Farhan Ullah Khan, Alexandre Cloutier, Puregmaa Khongorzul, Ahmed Aziz Raki, Simon Gaudreau, Patrick P. McDonald, Denis Gris, Abdelaziz Amrani Source Type: research
The E3 ubiquitin ligase CHIP protects against sepsis-induced myocardial dysfunction by inhibiting NF- κB-mediated inflammation via promoting ubiquitination and degradation of karyopherin-α 2
Cardiac dysfunction has been recognized as a major contributor to mortality in sepsis, which is closely associated with inflammatory reactions. The carboxy terminus of Hsc70-interacting protein (CHIP), a U-box E3 ubiquitin ligase, defends against cardiac injury caused by other factors, but its role in sepsis-induced cardiac dysfunction has yet to be determined. The present study was designed to investigate the effects of CHIP on cardiac dysfunction caused by sepsis and the molecular mechanisms underlying these processes. (Source: Translational Research)
Source: Translational Research - November 14, 2022 Category: Research Authors: Jia Liao, Xingyu Su, Miao Wang, Lucen Jiang, Xi Chen, Zixi Liu, Guoqing Tang, Li Zhou, Hongmei Li, Xiuxiu Lv, Jun Yin, Huadong Wang, Yiyang Wang Source Type: research
Inhibition of PI3K/C/EBP β axis in tolerogenic bone marrow derived dendritic cells of NOD mice promotes Th17 differentiation and diabetes development
Dendritic cells (DCs) are key regulators of the adaptive immune response. Tolerogenic dendritic cells play a crucial role in inducing and maintaining immune tolerance in autoimmune diseases such as type 1 diabetes in humans as well as in the NOD mouse model. We previously reported that bone marrow-derived DCs (BM.DCs) from NOD mice, generated with a low dose of GM-CSF (GM/DCs), induce Treg differentiation and are able to protect NOD mice from diabetes. We had also found that the p38 MAPK/C/EBP β axis is involved in regulating the phenotype, as well as the production of IL-10 and IL-12p70, by tolerogenic GM/DCs. (Source: T...
Source: Translational Research - November 14, 2022 Category: Research Authors: Chantal Guindi, Farhan Ullah Khan, Alexandre Cloutier, Puregmaa Khongorzul, Ahmed Aziz Raki, Simon Gaudreau, Patrick P McDonald, Denis Gris, Abdelaziz Amrani Source Type: research
Arsenic Trioxide Sensitizes Pancreatic Cancer Cells to Gemcitabine through downregulation of the TIMP1/PI3K/AKT/mTOR Axis.
Gemcitabine (GEM) is the first-line medication for pancreatic ductal adenocarcinoma (PDAC). However, over some treatment cycles, GEM sensitivity declines and chemotherapeutic resistance develops, resulting in tumor recurrence and metastasis. Therefore, it is critical to elucidate the mechanism of GEM chemoresistance. And a specific drug that is closely related to the mechanism is urgently required to sensitize GEM. Here, tissue inhibitor of matrix metalloproteinases 1 (TIMP1) and phosphorylated mammalian target of rapamycin (p-mTOR) were found to be substantially elevated in PDAC patients and were associated with worse ove...
Source: Translational Research - November 14, 2022 Category: Research Authors: Zhenfeng Tian, Ying Tan, Xingyi Lin, Mingxin Su, Lele Pan, Lijun Lin, Guangsheng Ou, Yinting Chen Tags: Original Research Article Source Type: research
Non-canonical NF- κB contributes to endothelial pyroptosis and atherogenesis dependent on IRF-1
This study investigated a role for the non-canonical NF-κB pathway in regulating endothelial pyroptosis as it relates to atherogenesis. (Source: Translational Research)
Source: Translational Research - November 12, 2022 Category: Research Authors: Xing Fan, Qiannan Li, Yiying Wang, Dai-Min Zhang, Jingchao Zhou, Qing Chen, Liang Sheng, Anthony G. Passerini, ChongXiu Sun Source Type: research
Antagonist of sphingosine 1-phosphate receptor 3 reduces cold injury of rat donor hearts for transplantation
Cold storage is widely used to preserve an organ for transplantation; however, a long duration of cold storage negatively impacts graft function. Unfortunately, the mechanisms underlying cold exposure remain unclear. Based on the sphingosine-1-phosphate (S1P) signal involved in cold tolerance in hibernating mammals, we hypothesized that S1P signal blockage reduces damage from cold storage. We used an in vitro cold storage and rewarming model to evaluate cold injury and investigated the relationship between cold injury and S1P signal. (Source: Translational Research)
Source: Translational Research - November 5, 2022 Category: Research Authors: Eisho Kanemitsu, Xiangdong Zhao, Keiko Iwaisako, Asuka Inoue, Akihide Takeuchi, Shintaro Yagi, Hidetoshi Masumoto, Hiroaki Ohara, Motoyasu Hosokawa, Tomonari Awaya, Junken Aoki, Etsuro Hatano, Shinji Uemoto, Masatoshi Hagiwara Source Type: research
Clonal hematopoiesis and bone marrow inflammation
Clonal hematopoiesis (CH) occurs in hematopoietic stem cells with increased risks of progressing to hematologic malignancies. CH mutations are predominantly found in aged populations and correlate with an increased incidence of cardiovascular and other diseases. Increased lines of evidence demonstrate that CH mutations are closely related to the inflammatory bone marrow microenvironment. In this review, we summarize the recent advances in this topic starting from the discovery of CH and its mutations. (Source: Translational Research)
Source: Translational Research - November 5, 2022 Category: Research Authors: Xinshu Xie, Meng Su, Kehan Ren, Xuezhen Ma, Zhiyi Lv, Zhaofeng Li, Yang Mei, Peng Ji Source Type: research
Defining the Sensitivity Landscape of EGFR Variants to Tyrosine Kinase Inhibitors
Tyrosine kinase inhibitor (TKI) is a standard treatment for patients with NSCLC harboring constitutively active epidermal growth factor receptor (EGFR) mutations. However, most rare EGFR mutations lack treatment regimens except for the well-studied ones. We constructed two EGFR variant libraries containing substitutions, deletions, or insertions using the saturation mutagenesis method. All the variants were located in the EGFR mutation hotspot (exons 18-21). The sensitivity of these variants to afatinib, erlotinib, gefitinib, icotinib, and osimertinib was systematically studied by determining their enrichment in massively ...
Source: Translational Research - November 5, 2022 Category: Research Authors: LEI AN, YUEQIANG WANG, GUANGYAO WU, ZHENXING WANG, ZEYUAN SHI, CHANG LIU, CHUNLI WANG, MING YI, CHENGUANG NIU, SHAOFENG DUAN, XIAODONG LI, WENXUE TANG, KONGMING WU, SHUQING CHEN, HONGEN XU Source Type: research
Targeting caspase-2 interactions with tau in Alzheimer's disease and related dementias
Targeting amyloid- β plaques and tau tangles has failed to provide effective treatments for Alzheimer's disease and related dementias (ADRD). A more fruitful pathway to ADRD therapeutics may be the development of therapies that target common signaling pathways that disrupt synaptic connections and impede communicatio n between neurons. In this review, we present our characterization of a signaling pathway common to several neurological diseases featuring dementia including Alzheimer's disease, frontotemporal dementia, Lewy body dementia, and Huntington's disease. (Source: Translational Research)
Source: Translational Research - November 3, 2022 Category: Research Authors: Steffen Pockes, Michael A. Walters, Karen H. Ashe Tags: Review Article Source Type: research
