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Biochim Biophys Acta Mol Basis Dis 2022 May 23:166449. Epub 2022 May 23.

Division of Endocrinology, Gerontology, and Metabolism, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Stanford Diabetes Research Center, Stanford, CA, USA. Electronic address:

There is an inverse relationship between the differentiation of mesenchymal stem cells (MSCs) along either an adipocyte or osteoblast lineage, with lineage differentiation known to be mediated by transcription factors PPARγ and Runx2, respectively. Endogenous ligands for PPARγ are generated during the hydrolysis of triacylglycerols to fatty acids through the actions of lipases such as hormone sensitive lipase (HSL). To examine whether reduced production of endogenous PPARγ ligands would influence bone regeneration, we examined the effects of HSL knockout on fracture repair in mice using a tibial mono-cortical defect as a model. Read More

Biochim Biophys Acta Mol Basis Dis 2022 May 23:166452. Epub 2022 May 23.

Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi 710072, China; Department of Immunology, Fourth Military Medical University, 169 West Changle Road, Xi'an, Shaanxi 710032, China. Electronic address:

CD226 is a costimulatory molecule that regulates immune cell functions in T cells, natural killer cells, and macrophages. Because macrophage-derived foam cell formation is a crucial factor contributing to the development of atherosclerosis, we aimed to evaluate the potential roles of CD226 in the pathogenesis of atherosclerosis. The effects of CD226 on atherosclerosis were investigated in CD226 and apolipoprotein E double-knockout (CD226 ApoE) mice fed with a high-cholesterol atherogenic diet. Read More

Brain Res Bull 2022 May 23. Epub 2022 May 23.

Research Service, VA Boston Healthcare System, West Roxbury, MA, 02132 USA.

Post-traumatic stress disorder (PTSD) is a trauma-related condition that produces distressing fear memory intrusions, avoidance behaviors, hyperarousal/startle, stress responses and insomnia. This review focuses on the importance of the orexin neural system as a novel mechanism related to the pathophysiology of PTSD. Orexinergic neurons originate in the lateral hypothalamus and project widely to key neurotransmitter system neurons, autonomic neurons, the hypothalamic-pituitaryadrenal (HPA) axis, and fear-related neural circuits. Read More

Microvasc Res 2022 May 23:104384. Epub 2022 May 23.

Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China; Institute of Life Sciences, Chongqing Medical University, Chongqing, PR China; Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address:

Aims: Inflammation is a key feature of endothelial dysfunction induced by angiotensin (Ang) II. The purpose of this study was to explore the role of Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in endothelial dysfunction in Ang II-induced hypertension.

Materials And Methods: We analyzed blood pressure and vascular function of wild-type (WT) and Nlrp3 knockout (Nlrp3) mice, treated with Ang II. Read More

Brain Res 2022 May 23:147951. Epub 2022 May 23.

Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, NY, NY, 10029. Electronic address:

Carboxypeptidase E (CPE) is an essential enzyme that contributes to the biosynthesis of the vast majority of neuropeptides and peptide hormones. There are several reports claiming that small decreases in CPE activity cause physiological changes in animals and/or cultured cells, but these studies did not provide evidence that neuropeptide levels were affected by decreased CPE activity. In the present study, we tested if CPE is a rate-limiting enzyme in neuropeptide production using CpeNeo mice, which contain a neomycin cassette within the Cpe gene that eliminates enzyme expression. Read More

Epilepsy Res 2022 May 20;183:106944. Epub 2022 May 20.

Division of Brain Science, Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China. Electronic address:

Mice with inactivation of the Plppr5 gene (Plppr5-/-) had aggravated hypoxic-ischemic damage and partially weakened neuroprotection of melatonin (a mitochondrial targeted antioxidant), suggesting that abnormal mitochondrial homeostasis contributes to neurological abnormalities in these mice. We examined the hypothesis that Plppr5 inactivation disturbs mitochondrial homeostasis, which may cause long-term adverse consequences on behavior and cognition. We studied the long-term effects of Plppr5 knockout (KO) in both wild-type (WT) and Plppr5-null mice using a combination of neurobehavior, cognition, and standard cellular glutamate-induced excitotoxicity techniques. Read More

PLoS One 2022 26;17(5):e0267845. Epub 2022 May 26.

Graduation Program in Medical Science: Endocrinology, Department of Internal Medicine Faculty of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

The kallikrein-kinin system has been implicated in body weight and glucose homeostasis. Their major effectors act by binding to the kinin B2 and B1 receptors. It was assessed the role of the kinin B1 receptor in weight and glucose homeostasis in B1 receptor knockout mice (B1RKO) subjected to a cafeteria diet (CAF). Read More

Development 2022 May 26. Epub 2022 May 26.

Education Key Laboratory of Cell Proliferation & Regulation Biology, College of Life Sciences, Beijing Normal University, 100875 Beijing, China.

The perinuclear theca (PT) is a cytoskeletal element encapsulating the sperm nucleus; however, physiological roles of PT in sperm are largely uncertain. Here, we revealed that ACTRT1, ACTRT2, ACTL7A, and ACTL9 proteins interact to form a multimeric complex and localize to the subacrosomal region of spermatids. Furthermore, we engineered Actrt1-knockout (KO) mice to define the functions of ACTRT1. Read More

Mol Nutr Food Res 2022 May 26:e2100889. Epub 2022 May 26.

Department of Endocrinology and Metabolism, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, China.

Scope: Phenotypic switch of macrophage polarization in adipose tissue has been associated with obesity-induced adipose tissue inflammation (OATI). Therefore, we aimed to explore the possible mechanism of adipocytes-derived exosomes (ADEs) carrying microRNA-1224 (miR-1224) in M2 macrophage polarization of OATI.

Methods And Results: We developed miR-1224-knockout (miR-1224-KO) mice for this study, and isolated primary adipocytes from high-fat diet (HFD) or normal diet (SD)-fed mice. Read More

Adv Sci (Weinh) 2022 May 26:e2105120. Epub 2022 May 26.

Research and Development Service, VA San Diego Healthcare System, San Diego, CA, 92161, USA.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Serine-arginine rich splicing factor 3 (SRSF3) plays a critical role in hepatocyte function and its loss in mice promotes chronic liver damage and leads to HCC. Hepatocyte-specific SRSF3 knockout mice (SKO mice) also overexpress insulin-like growth factor 2 (IGF2). Read More

Oxid Med Cell Longev 2022 16;2022:8652741. Epub 2022 May 16.

Department of Neurology, Hebei Medical University, Shijiazhuang, China.

Increasing evidence shows that oxidative stress and neuroinflammation play a crucial role in the pathology of vascular dementia (VD). Previously, we have found that Dl-3-n-butylphthalide (NBP) has antioxidant and anti-inflammatory activities in VD, whereas little is known about its mechanism. Therefore, the objective of our study was to explore the contribution of nuclear factor erythroid-2 related factor 2 (Nrf2) to NBP and its effects on anti-inflammatory activity in a mouse model of VD. Read More

Front Mol Neurosci 2022 9;15:895429. Epub 2022 May 9.

Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Disruption of the blood-brain barrier (BBB) causes or contributes to neuronal dysfunction and several central nervous system (CNS) disorders. Wnt/β-catenin signaling is essential for maintaining the integrity of the adult BBB in physiological and pathological conditions, including stroke. However, how the impairment of the endothelial Wnt/β-catenin signaling results in BBB breakdown remains unclear. Read More

Lipids Health Dis 2022 May 25;21(1):46. Epub 2022 May 25.

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, USA.

Background: Hepatocyte nuclear factor 4α (HNF4α) and glucocorticoid receptor (GR), master regulators of liver metabolism, are down-regulated in fatty liver diseases. The present study aimed to elucidate the role of down-regulation of HNF4α and GR in fatty liver and hyperlipidemia.

Methods: Adult mice with liver-specific heterozygote (HET) and knockout (KO) of HNF4α or GR were fed a high-fat-high-sugar diet (HFHS) for 15 days. Read More

Nature 2022 May 25. Epub 2022 May 25.

Neurobiology, Psychiatry and Psychology Departments and Integrative Center for Learning and Memory, University of California Los Angeles, Los Angeles, CA, USA.

Real-world memories are formed in a particular context and are often not acquired or recalled in isolation. Time is a key variable in the organization of memories, as events that are experienced close in time are more likely to be meaningfully associated, whereas those that are experienced with a longer interval are not. How the brain segregates events that are temporally distinct is unclear. Read More

Biochim Biophys Acta Mol Cell Res 2022 May 22:119299. Epub 2022 May 22.

The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China; Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, No. 725 Jiangzhou Avenue, Dingshan Street, Jiangjin District, Chongqing 402260, China. Electronic address:

The membrane-bound transcription factor Nrf1 (encoded by Nfe2l1) is activated by sensing glucose deprivation, cholesterol abundance, proteasomal inhibition and oxidative stress and then mediates distinct signaling responses to maintain cellular homeostasis. Herein, we found that Nrf1 stability and transactivity are both enhanced by USP19, a ubiquitin-specific protease tail-anchored in the endoplasmic reticulum (ER) through its C-terminal transmembrane domain. Further experiments revealed that USP19 directly interacts with Nrf1 in proximity to the ER and topologically acts as a deubiquitinating enzyme to remove ubiquitin moieties from this protein, which allow it to circumvent potential proteasomal degradation. Read More

Transcription 2022 May 25:1-15. Epub 2022 May 25.

Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.

N-terminal methylation (Nα-methylation) by the methyltransferase NRMT1 is an important post-translational modification that regulates protein-DNA interactions. Accordingly, its loss impairs functions that are reliant on such interactions, including DNA repair and transcriptional regulation. The global loss of Nα-methylation results in severe developmental and premature aging phenotypes, but given over 300 predicted substrates, it is hard to discern which physiological substrates contribute to each phenotype. Read More

Gut Microbes 2022 Jan-Dec;14(1):2077602

Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Maladaptive inflammatory and immune responses are responsible for intestinal barrier integrity and function dysregulation. Proline/serine-rich coiled-coil protein 1 (PSRC1) critically contributes to the immune system, but direct data on the gut microbiota and the microbial metabolite trimethylamine N-oxide (TMAO) are lacking. Here, we investigated the impact of PSRC1 deletion on TMAO generation and atherosclerosis. Read More

Sci Adv 2022 May 25;8(21):eabn1606. Epub 2022 May 25.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

The chromatin state, which undergoes global changes during spermatogenesis, is critical to meiotic initiation and progression. However, the key regulators involved and the underlying molecular mechanisms remain to be uncovered. Here, we report that mouse BEND2 is specifically expressed in spermatogenic cells around meiotic initiation and that it plays an essential role in meiotic progression. Read More

Sci Adv 2022 May 25;8(21):eabh3568. Epub 2022 May 25.

Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, School of Medicine, Southeast University, Nanjing 210009, China.

The mammalian neocortex is a highly organized six-layered structure with four major cortical neuron subtypes: corticothalamic projection neurons (CThPNs), subcerebral projection neurons (SCPNs), deep callosal projection neurons (CPNs), and superficial CPNs. Here, careful examination of multiple conditional knockout model mouse lines showed that the transcription factor FOXG1 functions as a master regulator of postmitotic cortical neuron specification and found that mice lacking functional FOXG1 exhibited projection deficits. Before embryonic day 14. Read More

Bioengineered 2022 May;13(5):12726-12737

Department of Anesthesiology, Second Affiliated Hospital of Nanchang University, Nanchang, China.

Evidence suggests circRBMS1 regulates mRNA to mediate cell apoptosis, inflammation, and oxidative stress in different diseases. MST1 is reported to be the target and activator of apoptosis-related molecules and signaling pathways. Hence, the present study aims to investigate the role of circ-RBMS1/miR-2355-3p/MST1 in the development of I/R injury. Read More

Circ Res 2022 May 25:101161CIRCRESAHA121319976. Epub 2022 May 25.

Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (D.Z., Z.Z., J.Z., D.L., L.G., W.B.L., D.X., Z.M., P.Y., J.T., T.A.C., B.L.L., Y.W., X.-L.M.).

Background: Despite significantly reduced acute myocardial infarction (MI) mortality in recent years, ischemic heart failure continues to escalate. Therapeutic interventions effectively reversing pathological remodeling are an urgent unmet medical need. We recently demonstrated that AdipoR1 (APN [adiponectin] receptor 1) phosphorylation by GRK2 (G-protein-coupled receptor kinase 2) contributes to maladaptive remodeling in the ischemic heart. Read More

J Neurodev Disord 2022 May 24;14(1):33. Epub 2022 May 24.

Institute for Behavioral Genetics, University of Colorado Boulder, 1480 30th Street, Boulder, CO, 80309-0447, USA.

Background: Regulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer's disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Read More

Nat Commun 2022 May 24;13(1):2899. Epub 2022 May 24.

State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, 100094, Beijing, China.

Osteoclast over-activation leads to bone loss and chloride homeostasis is fundamental importance for osteoclast function. The calcium-activated chloride channel Anoctamin 1 (also known as TMEM16A) is an important chloride channel involved in many physiological processes. However, its role in osteoclast remains unresolved. Read More

Transl Res 2022 May 21. Epub 2022 May 21.

Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China; NHC Key Laboratory of Cell Translation, Harbin Medical University, Heilongjiang, 150001, China; Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University, Harbin, 150001, China; Key Laboratory of Hepatosplenic Surgery, Harbin Medical University, Ministry of Education, Harbin, 150001, China. Electronic address:

Cardiac fibrosis is a process characterized by extracellular matrix accumulation leading to myocardial dysfunction. Angiotensin II (Ang II) has been shown to play an important role in the pathogenesis of cardiac fibrosis. However, the underlying mechanisms are not well established. Read More

Biochem Biophys Res Commun 2022 May 18;615:75-80. Epub 2022 May 18.

Pharmacogenetics Section, Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA.

Nuclear receptor Pregnane X Receptor (PXR; NR1I2) has transcriptional regulation functions for energy homeostasis in the liver. Mouse PXR has a conserved phosphorylation motif at serine 347 (serine 350 in humans) within the ligand-binding domain. PXR phosphorylated at this motif is expressed in mouse livers in response to fasting. Read More

Biochem Biophys Res Commun 2022 May 17;615:109-115. Epub 2022 May 17.

State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College. Beijing, PR China. Electronic address:

Endoplasmic reticulum stress (ER stress) plays a crucial role in the process of Alzheimer's disease (AD). Activating transcription factor 6 (ATF6) is a crucial sensor of ER stress. In AD patients, the homeostasis of the endogenous signal HS produced by cystathionine γ-lyase (CTH) is in disbalance. Read More

Mol Biol Cell 2022 May 24:mbcE22030089. Epub 2022 May 24.

Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.

Primary cilia are antenna-like organelles that contain specific proteins, and are crucial for tissue morphogenesis. Anterograde and retrograde trafficking of ciliary proteins are mediated by the intraflagellar transport (IFT) machinery. BROMI/TBC1D32 interacts with CCRK/CDK20, which phosphorylates and activates the ICK/CILK1 kinase, to regulate the change in direction of the IFT machinery at the ciliary tip. Read More

Bioinformatics 2022 May 24. Epub 2022 May 24.

Department of Anesthesia, Pain and Perioperative Medicine, Stanford University School of Medicine, Stanford, CA, 94305.

Motivation: Our ability to identify causative genetic factors for mouse genetic models of human diseases and biomedical traits has been limited by the difficulties associated with identifying true causative factors, which are often obscured by the many false positive genetic associations produced by a GWAS.

Results: To accelerate the pace of genetic discovery, we developed a graph neural network (GNN)-based automated pipeline (GNNHap) that could rapidly analyze mouse genetic model data and identify high probability causal genetic factors for analyzed traits. After assessing the strength of allelic associations with the strain response pattern; this pipeline analyzes 29M published papers to assess candidate gene-phenotype relationships; and incorporates the information obtained from a protein-protein interaction network and protein sequence features into the analysis. Read More

Development 2022 May 24. Epub 2022 May 24.

Institute of Translational Medicine, Tianjin Union Medical Center, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Frontiers Science Center for Cell Responses, National Demonstration Center for Experimental Biology Education and College of Life Sciences, Nankai University, Tianjin, China.

Hbxip, also named Lamtor5, has been well characterized as a transcriptional coactivator in various cancers. However, the role of Hbxip in normal development remains unexplored. Here, we demonstrated that homozygous knockout of Hbxip leads to embryonic lethality, with retarded growth around E7. Read More

Exp Ther Med 2022 Jun 4;23(6):425. Epub 2022 May 4.

Department of Orthopedics, General Hospital of Central Theater Command (Hankou District), Wuhan, Hubei 430000, P.R. China.

In patients with diabetes, the Wnt/β-catenin pathway in vascular smooth muscle cells (VSMCs) is continuously activated by low-intensity inflammation, which leads to the osteoblastic differentiation of these cells and the deposition of calcium and phosphorus in blood vessels. The aim of the present study was to determine whether long intergenic non-coding RNA-erythroid pro-survival (lincRNA-EPS) was able to ameliorate vascular calcification (VC) associated with diabetes. VSMCs isolated from C57BL/6 mice were transfected with lincRNA-EPS overexpression vector and their osteoblastic differentiation was evaluated under high-glucose conditions. Read More