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PAI-1 induction during kidney injury promotes fibrotic epithelial dysfunction via deregulation of klotho, p53, and TGF-β1-receptor signaling.

Cody C Gifford, Fei Lian, Jiaqi Tang, Angelica Costello, Roel Goldschmeding, Rohan Samarakoon, Paul J Higgins,

Renal fibrosis leads to chronic kidney disease, which affects over 15% of the U.S. population. PAI-1 is highly upregulated in the tubulointerstitial compartment in several common nephropathies and PAI-1 global ablation affords protection from fibrogenesis in mice. The precise contribution of renal tubular PAI-1 induction to disease progression, however, is ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21725]

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Overexpression of D-dopachrome tautomerase increases ultraviolet B irradiation-induced skin tumorigenesis in mice.

Yoko Yoshihisa, Mati Ur Rehman, Tsugunobu Andoh, Yoshiaki Tabuchi, Teruhiko Makino, Tadamichi Shimizu,

Ultraviolet irradiation (UV) exposure is the leading factor underlying the development of skin malignancies. D-dopachrome tautomerase (D-DT), a functional homolog of macrophage migration inhibitory factor (MIF), has functional similarities to MIF. However, its role, unlike the role of MIF in photocarcinogenesis, is unknown. We therefore explored the role of D-DT ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21671]

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Trypanosoma cruzi Letm1 is involved in mitochondrial Ca2+ transport, and is essential for replication, differentiation, and host cell invasion.

Guilherme Rodrigo Rm Dos Santos, Ana Catarina Rezende Leite, Noelia Lander, Miguel Angel Chiurillo, Aníbal Eugênio Vercesi, Roberto Docampo,

Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1) is a mitochondrial inner membrane protein involved in Ca<sup>2+</sup> and K<sup>+</sup> homeostasis in mammalian cells. Here, we demonstrate that the Letm1 orthologue of Trypanosoma cruzi, the etiologic agent of Chagas disease, is important for mitochondrial Ca<sup>2+</sup> uptake and release. The results show that ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21685]

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A novel role of ADGRF1 (GPR110) in promoting cellular quiescence and chemoresistance in human epidermal growth factor receptor 2-positive breast cancer.

Noor Mazin Abdulkareem, Raksha Bhat, Lanfang Qin, Suhas Vasaikar, Ambily Gopinathan, Tamika Mitchell, Martin J Shea, Sarmistha Nanda, Hariprasad Thangavel, Bing Zhang, Carmine De Angelis, Rachel Schiff, Meghana V Trivedi,

While G protein-coupled receptors (GPCRs) are known to be excellent drug targets, the second largest family of adhesion-GPCRs is less explored for their role in health and disease. ADGRF1 (GPR110) is an adhesion-GPCR and has an important function in neurodevelopment and cancer. Despite serving as a poor predictor of survival, ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21719]

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Methylome profiling identifies TCHH methylation in CfDNA as a noninvasive marker of liver metastasis in colorectal cancer.

Shanwen Chen, Tao Liu, Dingfang Bu, Jing Zhu, Xin Wang, Yisheng Pan, Yucun Liu, Zhi John Lu, Pengyuan Wang,

Methylation of circulating free DNA (CfDNA) has emerged as an efficient marker of tumor screening and prognostics. However, no efficient methylation marker has been developed for monitoring liver metastasis (LM) in colorectal cancer (CRC). Utilizing methylome profiling and bisulfite sequencing polymerase chain reaction of paired primary and LM sites, significantly ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21720]

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Emodin inhibits lipid accumulation and inflammation in adipose tissue of high-fat diet-fed mice by inducing M2 polarization of adipose tissue macrophages.

Fang Yu, Nan Yu, Jie Peng, Yan Zhao, Lei Zhang, Xiaohui Wang, Xiaona Xu, Jian Zhou, Feng Wang,

Adipose tissue macrophages (ATMs) represent the most abundant leukocytes in adipose tissue (AT). An increase in number and a phenotypical switch of ATMs during the development of obesity contribute to chronic inflammation and metabolic disorders, which have been regarded as potential therapeutic targets to restore AT homeostasis. Emodin has been shown to exert strong anti-inflammatory property via acting on macrophages in a ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21730]

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CLEC14A protects against podocyte injury in mice with adriamycin nephropathy.

Zeyu Su, Yujia Li, Hang Lv, Xiaoyang Cui, Min Liu, Ziying Wang, Yan Zhang, Junhui Zhen, Wei Tang, Xiaojie Wang, Fan Yi,

Podocyte injury is a major determinant of focal segmental glomerular sclerosis (FSGS) and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance for the treatment of FSGS. CLEC14A is a single-pass transmembrane glycoprotein belonging to the vascular expressed C-type lectin family. CLEC14A is found to be ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21711]

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The miR-455-3p/HDAC2 axis plays a pivotal role in the progression and reversal of liver fibrosis and is regulated by epigenetics.

Hongmei You, Ling Wang, Fangtian Bu, Hongwu Meng, Xueyin Pan, Juanjuan Li, Yafei Zhang, Ao Wang, Nana Yin, Cheng Huang, Jun Li,

Histone deacetylases (HDACs), especially HDAC2, play a role in alleviating liver fibrosis; however, the specific upstream regulation mechanism is unknown. Herein, TargetScan was used to predict the potential upstream targets of HDAC2, and the role of miR-455-3p was explored. The dual luciferase reporter assay showed that miR-455-3p binds to the ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21700]

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A novel imidazolinone metformin-methylglyoxal metabolite promotes endothelial cell angiogenesis via the eNOS/HIF-1α pathway.

Huong Nguyen, Jia Yi Koh, Hainan Li, Argel Islas-Robles, Sai Pranathi Meda Venkata, Jie-Mei Wang, Terrence J Monks,

Peripheral arterial disease (PAD) is one of the major complications of diabetes due to an impairment in angiogenesis. Since there is currently no drug with satisfactory efficacy to enhance blood vessel formation, discovering therapies to improve angiogenesis is critical. An imidazolinone metabolite of the metformin-methylglyoxal scavenging reaction, (E)-1,1-dimethyl-2-(5-methyl-4-oxo-4,5-dihydro-1H-imidazol-2-yl) guanidine (IMZ), ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21645]

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Cooperativity between β-agonists and c-Abl inhibitors in regulating airway smooth muscle relaxation.

Ajay P Nayak, John M Lim, Eylon Arbel, Ruping Wang, Dominic R Villalba, Tahn L Nguyen, Niccole Schaible, Ramaswamy Krishnan, Dale D Tang, Raymond B Penn,

Current therapeutic approaches to avoid or reverse bronchoconstriction rely primarily on β2 adrenoceptor agonists (β-agonists) that regulate pharmacomechanical coupling/cross bridge cycling in airway smooth muscle (ASM). Targeting actin cytoskeleton polymerization in ASM represents an alternative means to regulate ASM contraction. Herein we report the cooperative effects of targeting these distinct ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21674]

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PFKFB3-dependent glucose metabolism regulates 3T3-L1 adipocyte development.

Beth A Griesel, Satoshi Matsuzaki, Albert Batushansky, Timothy M Griffin, Kenneth M Humphries, Ann Louise Olson,

Proliferation and differentiation of preadipocytes, and other cell types, is accompanied by an increase in glucose uptake. Previous work showed that a pulse of high glucose was required during the first 3 days of differentiation in vitro, but was not required after that. The specific glucose metabolism pathways required for adipocyte ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21728]

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Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis.

Xiang Xie, Jiayu Liang, Run Huang, Chuang Luo, Jiali Yang, Hongming Xing, Le Zhou, Han Qiao, Erti Ergu, Huan Chen,

Ketamine cystitis (KC) is a chronic bladder inflammation leading to urinary urgency, frequency, and pain. The pathogenesis of KC is complicated and involves multiple tissue injuries in the bladder. Recent studies indicated that urothelium disruption, lamina propria fibrosis and inflammation, microvascular injury, neuropathological alterations, and bladder smooth muscle (BSM) abnormalities ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21703]

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Quantitative proteomics of hamster lung tissues infected with SARS-CoV-2 reveal host factors having implication in the disease pathogenesis and severity.

Voddu Suresh, Varshasnata Mohanty, Kiran Avula, Arup Ghosh, Bharati Singh, Rajendra Kumar Reddy, Deepti Parida, Amol Ratnakar Suryawanshi, Sunil Kumar Raghav, Soma Chattopadhyay, Punit Prasad, Rajeeb Kumar Swain, Rupesh Dash, Ajay Parida, Gulam Hussain Syed, Shantibhusan Senapati,

Syrian golden hamsters (Mesocricetus auratus) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests lung pathology. In this study, efforts were made to check the infectivity of a local SARS-CoV-2 isolate in a self-limiting and non-lethal hamster model and evaluate the differential expression of lung proteins during acute infection ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21713]

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Copper ions impair zebrafish skeletal myofibrillogenesis via epigenetic regulation.

XiaoDong Jin, WenYe Liu, Jing Miao, ZhiPeng Tai, LingYa Li, PengPeng Guan, Jing-Xia Liu,

Unbalanced copper (Cu<sup>2+</sup> ) homeostasis is associated with the developmental defects of vertebrate myogenesis, but the underlying molecular mechanisms remain elusive. In this study, it was found that Cu<sup>2+</sup> stressed zebrafish embryos and larvae showed reduced locomotor speed as well as loose and decreased myofibrils in skeletal muscle, coupled with ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21686]

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Chemerin regulates formation and function of brown adipose tissue: Ablation results in increased insulin resistance with high fat challenge and aging.

Yiqiang Zhang, Wen-Jun Shen, Shuo Qiu, Pinglin Yang, Garrett Dempsey, Lei Zhao, Qin Zhou, Xiao Hao, Dachuan Dong, Andreas Stahl, Fredric B Kraemer, Lawrence L Leung, John Morser,

Apart from its role in inflammation and immunity, chemerin is also involved in white adipocyte biology. To study the role of chemerin in adipocyte metabolism, we examined the function of chemerin in brown adipose tissue. Brown and white adipocyte precursors were differentiated into adipocytes in the presence of Chemerin siRNA. ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21687]

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Endocrine disruption in Crohn's disease: Bisphenol A enhances systemic inflammatory response in patients with gut barrier translocation of dysbiotic microbiota products.

Raquel Linares, Mariana F Fernández, Ana Gutiérrez, Rocío García-Villalba, Beatriz Suárez, Pedro Zapater, José Alberto Martínez-Blázquez, Esther Caparrós, Francisco A Tomás-Barberán, Rubén Francés,

The relevance of environmental triggers in Crohn's disease remains poorly explored, despite the well-known association between industrialization and disease onset/progression. We have aimed at evaluating the influence of endocrine disrupting chemicals in CD patients. We performed a prospective observational study on consecutive patients diagnosed of CD. Serum levels of endocrine ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21697]

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Apical CLC-2 in retinal pigment epithelium is crucial for survival of the outer retina.

Christin Hanke-Gogokhia, Guillermo L Lehmann, Ignacio Benedicto, Erwin de la Fuente-Ortega, Vadim Y Arshavsky, Ryan Schreiner, Enrique Rodriguez-Boulan,

Knockout of the chloride channel protein 2 (CLC-2; CLCN2) results in fast progressing blindness in mice. Retinal Pigment Epithelium (RPE) and photoreceptors undergo, in parallel, rapid, and profound morphological changes and degeneration. Immunohistochemistry and electron microscopy of the outer retina and electroretinography of the CLC-2 KO mouse demonstrated normal morphology ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21689]

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Outcomes comparison of IVF/ICSI among different trigger methods for final oocyte maturation: A systematic review and meta-analysis.

Yu Zhang, Xiaoyan Guo, Linjiang Guo, Hsun-Ming Chang, Jing Shu, Peter C K Leung,

During the in vitro fertilization treatment, human chorionic gonadotrophin (hCG) is routinely used as a substitute for the natural endogenous LH surge during the final stage of oocyte maturation. However, it does not provide the FSH surge observed in the mid-cycle of the natural cycle. To date, whether the FSH ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21696]

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Asporin inhibits collagen matrix-mediated intercellular mechanocommunications between fibroblasts during keloid progression.

Longwei Liu, Hongsheng Yu, Yi Long, Zhifeng You, Rei Ogawa, Yanan Du, Chenyu Huang,

Keloids are fibrotic lesions that grow unceasingly and invasively and are driven by local mechanical stimuli. Unlike other fibrotic diseases and normal wound healing, keloids exhibit little transformation of dermal fibroblasts into α-SMA<sup>+</sup> myofibroblasts. This study showed that asporin is the most strongly expressed gene in keloids and its gene-ontology ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21705]

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Exposure of human fetal kidneys to mild analgesics interferes with early nephrogenesis.

Sabrina Leverrier-Penna, Alain Michel, Laetitia L Lecante, Nathalie Costet, Antonio Suglia, Christèle Desdoits-Lethimonier, Hugoline Boulay, Roselyne Viel, Jonathan M Chemouny, Emmanuelle Becker, Vincent Lavoué, Antoine D Rolland, Nathalie Dejucq-Rainsford, Cécile Vigneau, Séverine Mazaud-Guittot,

Acetaminophen, aspirin, and ibuprofen are mild analgesics commonly used by pregnant women, the sole current recommendation being to avoid ibuprofen from the fifth month of gestation. The nephrotoxicity of these three analgesics is well documented in adults, as is their interference with prostaglandins biosynthesis. Here we investigated the effect of ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21718]

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Regular exercise stimulates endothelium autophagy via IL-1 signaling in ApoE deficient mice.

Mitsuharu Okutsu, Mami Yamada, Ken Tokizawa, Shuri Marui, Katsuhiko Suzuki, Vitor A Lira, Kei Nagashima,

Regular exercise maintains arterial endothelial cell homeostasis and protects the arteries from vascular disease, such as peripheral artery disease and atherosclerosis. Autophagy, which is a cellular process that degrades misfolded or aggregate proteins and damaged organelles, plays an important role in maintaining organ and cellular homeostasis. However, it is unknown ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21698]

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G protein-coupled receptors can control the Hippo/YAP pathway through Gq signaling.

Diana Zindel, Patrick Mensat, Claire Vol, Zeinab Homayed, Fabienne Charrier-Savournin, Eric Trinquet, Jean-Louis Banères, Jean-Philippe Pin, Julie Pannequin, Thomas Roux, Elodie Dupuis, Laurent Prézeau,

The Hippo pathway is an evolutionarily conserved kinase cascade involved in the control of tissue homeostasis, cellular differentiation, proliferation, and organ size, and is regulated by cell-cell contact, apical cell polarity, and mechanical signals. Miss-regulation of this pathway can lead to cancer. The Hippo pathway acts through the inhibition of ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21668]

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Palmitic acid induces insulin resistance by a mechanism associated with energy metabolism and calcium entry in neuronal cells.

Karina Sánchez-Alegría, Carlos Ernesto Bastián-Eugenio, Luis Vaca, Clorinda Arias,

Palmitic acid (PA) is a saturated fatty acid whose high consumption has been largely associated with the development of different metabolic alterations, such as insulin resistance, metabolic syndrome, and type 2 diabetes. Particularly in the brain, insulin signaling disruption has been linked to cognitive decline and is considered a risk ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21712]

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The role of nuclear receptor 4A1 (NR4A1) in drug-induced gingival overgrowth.

Saki Hatano, Shinji Matsuda, Ai Okanobu, Daisuke Furutama, Takumi Memida, Mikihito Kajiya, Kazuhisa Ouhara, Tsuyoshi Fujita, Noriyoshi Mizuno, Hidemi Kurihara,

Drug-induced gingival overgrowth (DIGO) is a side effect of cyclosporine A (CsA), nifedipine (NIF), and phenytoin (PHT). Nuclear receptor 4A1 (NR4A1) plays a role in fibrosis in multiple organs. However, the relationship between NR4A1 and DIGO remains unclear. We herein investigated the involvement of NR4A1 in DIGO. In the DIGO ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(7):e21693]

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Endothelial cells from umbilical cord of women affected by gestational diabetes: A suitable in vitro model to study mechanisms of early vascular senescence in diabetes.

Pamela Di Tomo, Nicola Alessio, Stefano Falone, Laura Pietrangelo, Paola Lanuti, Valeria Cordone, Silvano Junior Santini, Nadia Di Pietrantonio, Marco Marchisio, Feliciano Protasi, Natalia Di Pietro, Gloria Formoso, Fernanda Amicarelli, Umberto Galderisi, Assunta Pandolfi,

Human umbilical cord endothelial cells (HUVECs) obtained from women affected by gestational diabetes (GD-HUVECs) display durable pro-atherogenic modifications and might be considered a valid in vitro model for studying chronic hyperglycemia effects on early endothelial senescence. Here, we demonstrated that GD- compared to C-HUVECs (controls) exhibited oxidative stress, altered both ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(6):e21662]

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