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Journals Translational Research : the J...

Translational Research : the Journal of Laboratory and Clinical Medicine

https://read.qxmd.com/read/38734064/immune-cell-distribution-and-dna-methylation-signatures-differ-between-tumor-and-stroma-enriched-compartment-in-pancreatic-ductal-adenocarcinoma
#1
JOURNAL ARTICLE
Erwin Tomasich, Jakob Mühlbacher, Katharina Wöran, Teresa Hatziioannou, Merima Herac, Markus Kleinberger, Julia Maria Berger, Lea Katharina Dibon, Luzia Berchtold, Gerwin Heller, Elisabeth Sophie Bergen, Andrea Macher-Beer, Gerald Prager, Martin Schindl, Matthias Preusser, Anna Sophie Berghoff
The presence of abundant tumor stroma is a prominent characteristic of pancreatic ductal adenocarcinomas (PDAC) that potentially influences disease progression and therapy response. This study aims to investigate immune cell infiltration and epigenetic profiles in tumor cell enriched ("Tumor") and stroma cell enriched ("Stroma") regions within human PDAC tissue samples. By comparing those regions, we identified 25,410 differentially methylated positions (DMPs) distributed across 6,963 unique genes. Pathway enrichment analysis using the top 2,000 DMPs that were either hyper- or hypomethylated indicated that immune response pathways and the estrogen receptor pathway are epigenetically dysregulated in Tumor and Stroma regions, respectively...
May 9, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38734063/counteracting-tgm2-by-a-fibroin-peptide-ameliorated-adriamycin-induced-nephropathy-via-regulation-of-lipid-metabolism-through-panx1-ppar-%C3%AE-pank1-pathway
#2
JOURNAL ARTICLE
Shan-Shan Li, Qiao-Juan Liu, Jia-Xin Bao, Meng-Ting Lu, Bing-Quan Deng, Wen-Wen Li, Chang-Chun Cao
Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence 'YEVEDYR') from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing...
May 9, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38723861/immune-checkpoint-activity-exacerbate-renal-interstitial-fibrosis-progression-by-enhancing-pd-l1-expression-in-renal-tubular-epithelial-cells
#3
JOURNAL ARTICLE
Yuting Zhang, Xue Mi, Yunchao Zhang, Jipeng Li, Yunlong Qin, Peng He, Ya Zhao, Binxiao Su, Lijie He
Renal interstitial fibrosis (RIF) is often associated with inflammatory cell infiltration and no effective therapy. Programmed death cell-1 (PD-1) and its ligand PD-L1 were playing critical roles in T cell coinhibition and exhaustion, but the role in RIF is unclear. Here the data analyses of serum from 122 IgA nephrology (IgAN) patients showed that high level of soluble PD-1(sPD-1) was an independent risk factor for RIF and renal function progression. PD-L1 was also overexpressed in renal interstitial tissues from both IgAN patients with high level of sPD-1 and the unilateral ureteral obstruction (UUO) mouse...
May 7, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38679230/early-growth-response-protein-2-promotes-partial-epithelial-mesenchymal-transition-by-phosphorylating-smad3-during-renal-fibrosis
#4
JOURNAL ARTICLE
Anni Song, Ruiwei Yan, Wei Xiong, Huiling Xiang, Jing Huang, Anni Jiang, Chun Zhang
Chronic kidney disease (CKD) is a serious health problem worldwide, which ultimately leads to end-stage renal disease (ESRD). Renal fibrosis is the common pathway and major pathological manifestation for various CKD proceeding to ESRD. However, the underlying mechanisms and effective therapies are still ambiguous. Early growth response 2 (EGR2) is reportedly involved in organ formation and cell differentiation. To determine the role of EGR2 in renal fibrosis, we respectively confirmed the increased expression of EGR2 in kidney specimens from both CKD patients and mice with location in proximal tubules...
April 26, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38670453/extra-nuclear-tert-counteracts-oxidative-stress-and-promotes-progression-in-papillary-thyroid-carcinoma
#5
JOURNAL ARTICLE
Marina Muzza, Gabriele Pogliaghi, Carla Colombo, Elisa Stellaria Grassi, Erika Carbone, Sonia Palazzo, Francesco Frattini, Giacomo Gazzano, Luca Persani, Laura Fugazzola
The reactivation of TERT is associated with poor outcome in papillary thyroid cancer (PTC). Extra-telomeric functions of TERT were reported, with a protective role against oxidative stress (OS). The aim of the present study was to explore the extra-nuclear TERT localization in PTC and its role in cancer progression. TERT nuclear export under OS were analyzed in K1 PTC cell line. We investigated the role of different TERT localizations using specific TERT constructs that limit its localization to the nucleus or to the mitochondria...
April 24, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38643868/inhibition-of-usp14-ameliorates-renal-ischemia-reperfusion-injury-by-reducing-tfap2a-stabilization-and-facilitating-mitophagy
#6
JOURNAL ARTICLE
Yang Li, Boqing Dong, Ying Wang, Huanjing Bi, Jing Zhang, Chenguang Ding, Chenge Wang, Xiaoming Ding, Wujun Xue
Mitochondrial dysfunction is recognized as a pivotal contributor to the pathogenesis of renal ischemia-reperfusion (IR) injury. Mitophagy, the process responsible for removing damaged protein aggregates, stands as a critical mechanism safeguarding cells against IR injury. Currently, the role of deubiquitination in regulating mitophagy still needs to be completely elucidated. This study aimed to evaluate the impact of ubiquitin-specific peptidase 14 (Usp14), a deubiquitinase, in IR injury by influencing mitophagy...
April 19, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38614213/targeting-the-devil-strategies-against-cancer-associated-fibroblasts-in-colorectal-cancer
#7
REVIEW
Yuting Chen, Zhiyong Liang, Maode Lai
Cancer-associated fibroblasts (CAFs), as significant constituents of the tumor microenvironment (TME), play a pivotal role in the progression of cancers, including colorectal cancer (CRC). In this comprehensive review, we presented the origin and activation mechanisms of CAFs in CRC, elaborating on how CAFs drive tumor advancement through their interactions with CRC cells, immune cells, vascular endothelial cells, and the extracellular matrix within the tumor microenvironment. We systematically outline the intricate web of interactions among CAFs, tumor cells, and other TME components, and based on this complex interplay, we summarize various therapeutic strategies designed to target CAFs in CRC...
April 11, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38608437/retraction-notice-to-transfer-of-microrna-221-from-mesenchymal-stem-cell-derived-extracellular-vesicles-inhibits-atherosclerotic-plaque-formation-transl-res-226-2020-83-95
#8
Ziyuan Guo, Zhuo Zhao, Chuang Yang, Chunli Song
No abstract text is available yet for this article.
April 11, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38604333/exosomal-tenascin-c-primes-macrophage-pyroptosis-amplifying-aberrant-inflammation-during-sepsis-induced-acute-lung-injury
#9
JOURNAL ARTICLE
Ting Gong, Xuedi Zhang, Xiaolei Liu, Yinfeng Ye, Zhiyuan Tian, Shuang Yin, Min Zhang, Jing Tang, Youtan Liu
Sepsis-induced acute lung injury (ALI) is a serious complication of sepsis and the predominant cause of death. Exosomes released by lung tissue cells critically influence the progression of ALI during sepsis by modulating the inflammatory microenvironment. However, the molecular mechanisms by which exosome-mediated intercellular signaling exacerbates ALI in septic infection remain undefined. Our study found increased levels of exosomal Tenascin-C (TNC) in the plasma of both patients and mice with ALI, showing a strong association with disease progression...
April 9, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38556110/transcriptomic-profiling-of-sciatic-nerves-and-dorsal-root-ganglia-reveals-site-specific-effects-of-prediabetic-neuropathy
#10
JOURNAL ARTICLE
Stéphanie A Eid, Sarah E Elzinga, Kai Guo, Lucy M Hinder, John M Hayes, Crystal M Pacut, Emily J Koubek, Junguk Hur, Eva L Feldman
Peripheral neuropathy (PN) is a severe and frequent complication of obesity, prediabetes, and type 2 diabetes characterized by progressive distal-to-proximal peripheral nerve degeneration. However, a comprehensive understanding of the mechanisms underlying PN, and whether these mechanisms change during PN progression, is currently lacking. Here, gene expression data were obtained from distal (sciatic nerve; SCN) and proximal (dorsal root ganglia; DRG) injury sites of a high-fat diet (HFD)-induced mouse model of obesity/prediabetes at early and late disease stages...
March 29, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38556109/sex-related-differences-in-sirt3-mediated-mitochondrial-dynamics-in-renal-ischemia-reperfusion-injury
#11
JOURNAL ARTICLE
Hanlin Yao, Hongchao Zhao, Yang Du, Ye Zhang, Yanze Li, Hengcheng Zhu
The prevalence of renal ischemia/reperfusion injury (IRI) in premenopausal women is considerably lower than that in age-matched men. This suggests that sex-related differences in mitochondrial function and homeostasis may contribute to sexual dimorphism in renal injury, though the mechanism remains unclear. Mouse model of unilateral left renal IRI with contralateral kidney enucleation, Ovariectomy in female mice, and a human embryonic kidney (HEK) cell model of hypoxia-reoxygenation were used to study how estrogen affects the sexual dimorphism of renal IRI through SIRT3 in vitro and in vivo, respectively...
March 29, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38552953/a-transcribed-ultraconserved-noncoding-rna-uc-285-promotes-colorectal-cancer-proliferation-through-dual-targeting-of-cdc42-by-directly-binding-mrna-and-protein
#12
JOURNAL ARTICLE
Sixian Chen, Qingyun Zhao, Ruirui Zhang, Jungang Liu, Wenyi Peng, Haotian Xu, Xiaofei Li, Xin Wang, Shuilian Wu, Gang Li, Aruo Nan
The transcribed ultraconserved region (T-UCR) belongs to a new type of lncRNAs that are conserved in homologous regions of the rat, mouse and human genomes. A lot of research has reported that differential expression of T-UCRs can influence the development of various cancers, revealing the ability of T-UCRs as new therapeutic targets or potential cancer biomarkers. Most studies on the molecular mechanisms of T-UCRs in cancer have focused on ceRNA regulatory networks and interactions with target proteins, but the present study reveals an innovative dual-targeted regulatory approach in which T-UCRs bind directly to mRNAs and directly to proteins...
March 27, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38548174/endothelial-elabela-improves-post-ischemic-angiogenesis-by-upregulating-vegfr2-expression
#13
JOURNAL ARTICLE
Jia-Yu Peng, Xiao Fu, Xue-Yang Luo, Fang Liu, Bing Zhang, Bin Zhou, Kun Sun, Alex F Chen
BACKGROUND: Post-ischemic angiogenesis is critical for perfusion recovery and tissue repair. ELABELA (ELA) plays an essential role in embryonic heart development and vasculogenesis. However, the mechanism of ELA on post-ischemic angiogenesis is poorly characterized. METHODS: We first assessed ELA expression after hind limb ischemia (HLI) in mice. We then established a HLI model in tamoxifen-inducible endothelial-ELA-specific knockout mice (ELAECKO ) and assessed the rate of perfusion recovery, capillary density, and VEGFR2 pathway...
March 26, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38522823/the-lps-inactivating-enzyme-acyloxyacyl-hydrolase-protects-the-brain-from-experimental-stroke
#14
JOURNAL ARTICLE
Yuanbo Zhu, Yue Hu, Zhongwang Liu, Luping Chang, Xue Geng, Xuhui Yin, Bing-Qiao Zhao, Wenying Fan
Blood-brain-barrier (BBB) disruption is a pathological hallmark of ischemic stroke, and inflammation occurring at the BBB contributes to the pathogenesis of ischemic brain injury. Lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, is elevated in patients with acute stroke. The activity of LPS is controlled by acyloxyacyl hydrolase (AOAH), a host enzyme that deacylates LPS to inactivated forms. However, whether AOAH influences the pathogenesis of ischemic stroke remain elusive. We performed in vivo experiments to explore the role and mechanism of AOAH on neutrophil extravasation, BBB disruption, and brain infarction...
March 22, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38499286/reversal-of-cisplatin-resistance-in-oral-squamous-cell-carcinoma-by-piperlongumine-loaded-smart-nanoparticles-through-inhibition-of-hippo-yap-signaling-pathway
#15
JOURNAL ARTICLE
Pratikshya Sa, Priya Singh, Sudhakar Panda, Rajeeb K Swain, Rupesh Dash, Sanjeeb Kumar Sahoo
Cisplatin alone or in combination with 5FU and docetaxel is the preferred chemotherapy regimen for advanced-stage OSCC patients. However, its use has been linked to recurrence and metastasis due to the development of drug resistance. Therefore, sensitization of cancer cells to conventional chemotherapeutics can be an effective strategy to overcome drug resistance. Piperlongumine, an alkaloid, have shown anticancer properties and sensitizes numerous neoplasms, but its effect on OSCC has not been explored. However, low aqueous solubility and poor pharmacokinetics limit its clinical application...
March 16, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38494125/genetic-and-pharmacological-targeting-of-xbp1-alleviates-hepatic-ischemia-reperfusion-injury-by-enhancing-foxo1-dependent-mitophagy
#16
JOURNAL ARTICLE
Baicheng Kuang, Mengqin Wang, Hao Yan, Qin Jiang, Zhiheng Wang, Haiqiang Ni, Shuaiheng Hou, Xuan Peng, Shiqi Gu, Yuanyuan Zhao, Tongwen Ou, Nianqiao Gong
Hepatic ischemia reperfusion (I/R) injury is a common clinical complication. X-box binding protein 1 (XBP1), as a critical regulator of the endoplasmic reticulum stress, has been implicated in a variety of diseases. In this study, we aimed to investigate the effects and the underlying mechanism of XBP1 in the progression of hepatic I/R injury. Hepatocyte-specific XBP1 knockout mice, multiple viral delivery systems and specific pharmacological inhibitors were applied in vivo in a partial hepatic I/R injury mouse model and in vitro in a cell model of hypoxia-reoxygenation (H/R) injury...
March 15, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38490536/the-pregnancy-associated-protein-glycodelin-as-a-potential-sex-specific-target-for-resistance-to-immunotherapy-in-non-small-cell-lung-cancer
#17
JOURNAL ARTICLE
Sarah Richtmann, Sebastian Marwitz, Thomas Muley, Hannu Koistinen, Petros Christopoulos, Michael Thomas, Daniel Kazdal, Michael Allgäuer, Hauke Winter, Torsten Goldmann, Michael Meister, Ursula Klingmüller, Marc A Schneider
Lung cancer has been shown to be targetable by novel immunotherapies which reactivate the immune system and enable tumor cell killing. However, treatment failure and resistance to these therapies is common. Consideration of sex as a factor influencing therapy resistance is still rare. We hypothesize that the success of the treatment is impaired by the presence of the immunosuppressive pregnancy-associated glycoprotein glycodelin that is expressed in patients with non-small-cell lung cancer (NSCLC). We demonstrate that the glycan pattern of NSCLC-derived glycodelin detected by a lectin-based enrichment assay highly resembles amniotic fluid-derived glycodelin A, which is known to have immunosuppressive properties...
March 13, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38471633/pcsk9-inhibition-protects-mice-from-food-allergy
#18
JOURNAL ARTICLE
Victoria Lorant, Martin Klein, Damien Garçon, Thibaud Sotin, Samuel Frey, Marie-Aude Cheminant, Audrey Ayer, Mikaël Croyal, Laurent Flet, Antoine Rimbert, Luc Colas, Bertrand Cariou, Grégory Bouchaud, Cédric Le May
The Proprotein Convertase Subtilisin Kexin of type 9 (PCSK9) has been identified in 2003 as the third gene involved in familial hypercholesterolemia. PCSK9 binds to the membrane low-density lipoprotein receptor (LDLR) and promotes its cellular internalization and lysosomal degradation. Beyond this canonical role, PCSK9 was recently described to be involved in several immune responses. However, to date, the contribution of PCSK9 in food allergy remains unknown. Here, we showed that Pcsk9 deficiency or pharmacological inhibition of circulating PCSK9 with a specific monoclonal antibody (m-Ab) protected mice against symptoms of gliadin-induced-food allergy, such as increased intestinal transit time and ear oedema...
March 10, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38453053/arginine-methylation-and-respiratory-disease
#19
REVIEW
Binbin Zhang, Youhong Guan, Daxiong Zeng, Ran Wang
Arginine methylation, a vital post-translational modification, plays a pivotal role in numerous cellular functions such as signal transduction, DNA damage response and repair, regulation of gene transcription, mRNA splicing, and protein interactions. Central to this modification is the role of protein arginine methyltransferases (PRMTs), which have been increasingly recognized for their involvement in the pathogenesis of various respiratory diseases. This review begins with an exploration of the biochemical underpinnings of arginine methylation, shedding light on the intricate molecular regulatory mechanisms governed by PRMTs...
March 5, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38453052/ras-protein-activator-like-2-rasal2-initiates-peritubular-capillary-rarefaction-in-hypoxic-renal-interstitial-fibrosis
#20
JOURNAL ARTICLE
Yu Zhang, Yiqiong Yang, Xiuxiu Hu, Bizhen Wei, Qian Shen, Chuanbing Shi, Pingsheng Chen
The progression of chronic kidney disease (CKD) often involves renal interstitial fibrosis (RIF) and subsequent loss of peritubular capillaries (PTCs), which enhances disease severity. Despite advancements in our understanding of fibrosis, effective interventions for reversing capillary loss remain elusive. Notably, RIF exhibits reduced capillary density, whereas renal cell carcinoma (RCC) shows robust angiogenesis under hypoxic conditions. Using RNA sequencing and bioinformatics, we identified differentially expressed genes (DEGs) in hypoxic human renal tubular epithelial cells (HK-2) and renal cancer cells (786-0)...
March 5, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
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