Search Our Scientific Publications & Authors

Int J Med Sci 2018 7;15(13):1423-1432. Epub 2018 Sep 7.

Department of Orthopedics, Xuanwu Hospital, Capital Medical University.

Peripheral nerve injury is known to activate the hypoxia-inducible factor-1α (HIF-1α) pathway as one of pro-regenerative transcriptional programs, which could stimulate multiple injury-induced gene expression and contribute to axon regeneration and functional recovery. However, the role of HIF-1α in peripheral nerve regeneration remains to be fully elucidated. In this study, rats were divided into three groups and treated with sham surgery, surgery with cobalt chloride (CoCl) and surgery with saline, respectively. Read More

Dev Neurobiol 2018 10 18;78(10):978-990. Epub 2018 Jul 18.

Department of Neurology & Neurosurgery, Montréal Neurological Institute, Montréal, Quebec H3A 2B4, Canada.

Neurons face a series of morphological and molecular changes following trauma and in the progression of neurodegenerative disease. In neurons capable of mounting a spontaneous regenerative response, including invertebrate neurons and mammalian neurons of the peripheral nervous system (PNS), axons regenerate from the proximal side of the injury and degenerate on the distal side. Studies of Wallerian degeneration slow (Wld /Ola) mice have revealed that a level of coordination between the processes of axon regeneration and degeneration occurs during successful repair. Read More

Elife 2018 07 3;7. Epub 2018 Jul 3.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.

Neuropathic pain resulting from nerve injury can become persistent and difficult to treat but the molecular signaling responsible for its development remains poorly described. Here, we identify the neuronal stress sensor dual leucine zipper kinase (DLK; ) as a key molecule controlling the maladaptive pathways that lead to pain following injury. Genetic or pharmacological inhibition of DLK reduces mechanical hypersensitivity in a mouse model of neuropathic pain. Read More

Mar Environ Res 2018 Aug 5;139:99-112. Epub 2018 May 5.

Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare "A. Monroy", Via Ugo La Malfa 153, 90146, Palermo, Italy. Electronic address:

Lithium (Li), Nickel (Ni), and Zinc (Zn) are metals normally present in the seawater, although they can have adverse effects on the marine ecosystem at high concentrations by interfering with many biological processes. These metals are toxic for sea urchin embryos, affecting their morphology and developmental pathways. In particular, they perturb differently the correct organization of the embryonic axes (animal-vegetal, dorso-ventral): Li is a vegetalizing agent and Ni disrupts the dorso-ventral axis, while Zn has an animalizing effect. Read More

Exp Eye Res 2018 06 8;171:54-61. Epub 2018 Mar 8.

Shiley Eye Institute, University of California, La Jolla, San Diego, CA 92037, USA. Electronic address:

Optic neuropathies such as glaucoma are characterized by the degeneration of retinal ganglion cells (RGCs) and the irreversible loss of vision. In these diseases, focal axon injury triggers a propagating axon degeneration and, eventually, cell death. Previous work by us and others identified dual leucine zipper kinase (DLK) and JUN N-terminal kinase (JNK) as key mediators of somal cell death signaling in RGCs following axonal injury. Read More

Oncotarget 2018 Jan 9;9(1):122-141. Epub 2017 Nov 9.

Hunan Normal University Medical College, Changsha, Hunan, China.

Stargardt disease-4 (STGD4) is an autosomal dominant complex, genetically heterogeneous macular degeneration/dystrophy (MD) disorder. In this paper, we used targeted next generation sequencing and multiple molecular dynamics analyses to identify and characterize a disease-causing genetic variant in four generations of a Chinese family with STGD4-like MD. We found a novel heterozygous missense mutation, c. Read More

Neuroscience 2017 Nov 19;364:107-121. Epub 2017 Sep 19.

Neurogenomics Laboratory, Multiple Sclerosis Center, Sheba Medical Center, Israel; Sackler School of Medicine, Tel-Aviv University, Israel.

Spontaneous neural repair from endogenous neural stem cells' (NSCs) niches occurs in response to central nervous system (CNS) injuries to only a limited extent. Uncovering the mechanisms that control neural repair and can be further manipulated to promote NSCs toward oligodendrocyte progenitors cells (OPCs) and myelinating oligodendrocytes is a major objective. In the current study, we describe high-throughput transcriptional changes in adult mouse subventricular zone (SVZ)-NSCs during differentiation in vitro. Read More

J Emerg Med 2017 Sep 25;53(3):369-382. Epub 2017 Aug 25.

East Orange General Hospital, East Orange, New Jersey.

Background: Traumatic lacerations to the skin represent a fairly common reason for seeking emergency department care. Although the incidence of lacerations has decreased over the past decades, traumatic cutaneous lacerations remain a common reason for patients to seek emergency department care.

Objective: Innovations in laceration management have the potential to improve patient experience with this common presentation. Read More

Invest Ophthalmol Vis Sci 2017 07;58(9):3656-3668

Department of Ophthalmology, Eye and Ear Nose Throat Hospital of Fudan University, Shanghai, China 2Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China.

Purpose: The aim of the present study was to investigate the neuroprotective effects of glucocorticoid-induced leucine zipper (GILZ) in a light-induced retinal degeneration model and to explore the underlying mechanisms.

Methods: Intravitreal injection of recombinant GILZ-overexpressing lentivirus (OE-GILZ-rLV) and short hairpin RNA targeting GILZ recombinant lentivirus (shRNA-GILZ-rLV) was performed to up- and downregulate retinal GILZ, respectively. Three days after stable transduction, rats were exposed to continuous bright light (5000 lux) for 2 days. Read More

Neuron 2017 Jun;94(6):1142-1154.e6

Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Solomon H. Snyder Department of Neuroscience, Department of Molecular Biology and Genetics, Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:

Dual leucine zipper kinase (DLK) has been implicated in cell death signaling secondary to axonal damage in retinal ganglion cells (RGCs) and other neurons. To better understand the pathway through which DLK acts, we developed enhanced functional genomic screens in primary RGCs, including use of arrayed, whole-genome, small interfering RNA libraries. Explaining why DLK inhibition is only partially protective, we identify leucine zipper kinase (LZK) as cooperating with DLK to activate downstream signaling and cell death in RGCs, including in a mouse model of optic nerve injury, and show that the same pathway is active in human stem cell-derived RGCs. Read More

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2017 May;29(5):479-480

Department of Critical Care Medicine, the 401st Hospital of PLA, Qingdao 266071, Shandong, China (Li HL, Wang HP); Division of Medical Affairs, the 401st Hospital of PLA, Qingdao 266071, Shandong, China (Lu Q, Li LJ). Corresponding author: Li Lujia, Email:

Objective: Cooling bag for heat stroke in wild field was invented in order to fulfill rapid cooling for heat stroke in field environment. The cooling bag is composed of the hood, the body cover (which is made up of the anterior portion, the linking, and the posterior portion), the fixed straps, the handles. The length is 200 cm, the regulative width is 60-70 cm, the folding volume is 26 cm × 20 cm × 9 cm, and the weight is 1. Read More

Urol Case Rep 2017 Jul 26;13:85-86. Epub 2017 Apr 26.

University of Central Florida College of Medicine, 6850 Lake Nona Boulevard, Orlando, FL 32827, USA.

Genital injury can occur at any age of life but is most common in the pediatric population. Hair-tourniquets and circumcision procedures are the most common causes of penile injury in children. Foreskin trauma, aside from zipper related injuries, is sparsely reported. Read More

Neurobiol Dis 2017 Jul 8;103:133-143. Epub 2017 Apr 8.

Departments of Anesthesiology and Physiology, Loma Linda University School of Medicine, Loma Linda, CA, USA. Electronic address:

Objective: Dual leucine zipper kinase (DLK/MA3K12) has been reported involved in apoptosis and neuronal degeneration during neural development and traumatic brain injury. This study was designed to investigate the role of DLK with its adaptor protein JNK interacting protein-3 (JIP3), and its downstream MA2K7/JNK signaling pathway in early brain injury (EBI) after subarachnoid hemorrhage (SAH) in a rat model.

Design: Controlled in vivo laboratory study. Read More

J Clin Ultrasound 2017 Nov 10;45(9):589-591. Epub 2017 Feb 10.

Mount Sinai St. Luke's Mount Sinai West Hospitals, Department of Emergency Medicine, 1000 10th Avenue, New York, NY.

Injury to the penis resulting from zipper entrapment is a painful condition that presents a unique anesthetic challenge to the emergency physician and may even require procedural sedation for removal. In this case report, we describe successful removal of zipper entrapment from the penis of a 34-year-old patient after the application of an ultrasound-guided dorsal penile nerve block. We discuss the anatomy, sonographic features, and steps required for the nerve block procedure. Read More

Pediatr Res 2017 Jun 18;81(6):926-931. Epub 2017 Jan 18.

Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.

Background: BTB and CNC homology 1 (Bach1) is a transcriptional repressor of heme oxygenase (HO)-1. The effects of Bach1 disruption on hyperoxic lung injury in newborn mice have not been determined. We aimed to investigate the role of Bach1 in the newborns exposed to hyperoxia. Read More

Ophthalmic Surg Lasers Imaging Retina 2016 12;47(12):1162-1163

Intraocular foreign bodies (IOFBs) may be associated with occult exit wounds. The authors present a case of a man who sustained a zipper-tooth IOFB through the cornea from a car tire explosion. CT showed an IOFB within the vitreous cavity, but the IOFB was not identified during vitrectomy. Read More

Am J Emerg Med 2017 05 2;35(5):783-784. Epub 2016 Nov 2.

Michigan State University, College of Human Medicine, Department of Emergency Medicine, United States; Spectrum Health, Department of Emergency Medicine, Grand Rapids, MI, United States.

PLoS One 2016 9;11(9):e0162471. Epub 2016 Sep 9.

Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, P.R. China.

Background: It is controversial whether surgical zipper technique (SZT), a non-invasive method of surgical wound closure, achieves a better outcome of incision healing than intracutaneous sutures (IS) in the surgery. This meta-analysis was performed to systematically analyze whether surgical zipper is superior to suture material for the incision closure.

Methods: Databases and reference lists were searched for randomized controlled trials (RCTs) comparing SZT with IS for the incision closure. Read More

Neuropharmacology 2016 09 13;108:316-23. Epub 2016 Apr 13.

Departments of Anesthesiology and Physiology, Loma Linda University School of Medicine, Loma Linda, CA, USA. Electronic address:

Background And Purpose: Since tozasertib is neuroprotective for injured optic nerve, this study is intended to test whether tozasertib reduces early brain injury after subarachnoid hemorrhage (SAH) in a rat model.

Methods: Two hundred sixteen (216) male Sprague-Dawley rats were randomly subjected to endovascular perforation model of SAH and sham group. SAH grade, neurological score, and brain water content were measured at 24 and 72 h after SAH. Read More

Oncotarget 2016 Apr;7(15):19272-83

Department of Cardiothoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a basic leucine zipper transcription factor that principally defends against oxidative stress and also plays a unique role in severe sepsis. However, its contribution to intestinal injury and death after burn trauma is unclear.In this study, wild-type (Nrf2+/+) and Nrf2-deficient (Nrf2-/-) mice were subjected to 15% or 30% total body surface area burn or sham injury. Read More

Neuroscience 2016 Jan 19;313:10-22. Epub 2015 Nov 19.

Department of Functional Anatomy & Neuroscience, Nagoya University, Graduate School of Medicine, 65 Tsurumaicho, Showa-ku, Nagoya 466-8550, Japan; Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency (JST), Saitama, Japan. Electronic address:

In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. Read More

Int J Nanomedicine 2015 21;10:5925-39. Epub 2015 Sep 21.

School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.

It has been reported that increased levels and activity of the heme oxygenase-1 (HO-1) protein ameliorate tissue injuries. In the present study, we investigated the effects and mechanisms of action of gold nanoparticles (AuNPs) on HO-1 protein expression in human vascular endothelial cells (ECs). The AuNPs induced HO-1 protein and mRNA expression in a concentration- and time-dependent manner. Read More

Eur J Med Res 2015 Aug 25;20:70. Epub 2015 Aug 25.

Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, Center of Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany.

Background: After severe blunt chest trauma, the development of an acute lung injury (ALI) is often associated with severe or even lethal complications. Especially in multiple injured patients after blunt chest trauma ALI/ARDS [acute respiratory distress syndrome (ARDS)] is frequent. However, in the initial posttraumatic phase, inflammatory clinical signs are often not apparent and underlying changes in gene-expression profile are unknown. Read More

PLoS One 2015 20;10(5):e0127163. Epub 2015 May 20.

Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.

Axonal regeneration after injury requires the coordinated expression of genes in injured neurons. We previously showed that either reducing expression or blocking function of the transcriptional repressor NFIL3 activates transcription of regeneration-associated genes Arg1 and Gap43 and strongly promotes axon outgrowth in vitro. Here we tested whether genetic deletion or dominant-negative inhibition of NFIL3 could promote axon regeneration and functional recovery after peripheral nerve lesion in vivo. Read More

BMJ Case Rep 2015 Jan 30;2015. Epub 2015 Jan 30.

Department of ENT, Pandit Bhagwat Dayal PGIMS, Rohtak Haryana, India.

We report a case of a 2-month-old male child who presented with sudden onset of vomiting and refusal to breast feed. Chest and abdomen examination were normal. A foreign body (zipper) was visualised in the cervical oesophagus on X-ray of the neck. Read More

Biofactors 2014 Nov-Dec;40(6):569-85. Epub 2014 Dec 20.

Division of National Research Center for Apple Engineering and Technology, Shandong Agricultural University, Tai'an, Shandong, China; Division of State Key Laboratory of Crop Biology, Shandong Agricultural University, Tai'an, Shandong, China; College of Horticulture Science and Engineering, Shandong Agricultural University, Tai'an, Shandong, China.

The endoplasmic reticulum is the cellular compartment in which secretory proteins are synthesized and folded. Perturbations of endoplasmic reticulum homeostasis lead to the accumulation of unfolded proteins. The activation of the unfolded protein response during endoplasmic reticulum stress transmits information about the status of protein folding to the cytosol and nucleus. Read More

Oncotarget 2014 Nov;5(22):11413-27

Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Plant flavonoid apigenin prevents and inhibits UVB-induced carcinogenesis in the skin and has strong anti-proliferative and anti-angiogenic properties. Here we identify mechanisms, by which apigenin controls these oncogenic events. We show that apigenin acts, at least in part, via endogenous angiogenesis inhibitor, thrombospondin-1 (TSP1). Read More

Proc Natl Acad Sci U S A 2014 Nov 27;111(45):16142-7. Epub 2014 Oct 27.

Departments of Anatomy and Cell Biology and Cameco Multiple Sclerosis Neuroscience Research Center, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5

Luman/cAMP response element binding protein 3 is an endoplasmic reticulum (ER) transmembrane basic leucine zipper transcription factor whose mRNA and protein localize to adult sensory axons, the latter with axonal ER components along the axon length. Here we show that axon-derived Luman plays an important role in relaying information about axonal injury to the neuronal cell body. Axotomy induces axonal Luman synthesis and also release from the axonal ER of Luman's transcriptionally active amino terminus, which is transported to the cell body in an importin-mediated manner. Read More

Versicherungsmedizin 2014 Sep;66(3):132-6

It is not unusual for a neurological expert to have problems defining the precise anatomical location and the required objective proof of damage, especially if the medical history and the neurological report released by the clinic prove inadequate in terms of providing a reliable assessment. This may well result from somatoform disorders, dissociation, aggravation and simulation, as well as dissimulation and complex organic diagnostic findings. A range of standardised neurophysiologic procedures is available for the objective measuring of motor, vegetative and sensory systems; a brief summary of the most frequent occurrences is given here, along with their significance for appraising damage resulting from an accident. Read More

Pharmacol Biochem Behav 2014 Nov 23;126:181-6. Epub 2014 Aug 23.

Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Nanchang Road, Lanzhou 730000, China; Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Nanchang Road, Lanzhou 730000, China. Electronic address:

Oxidative stress is one of the major mechanisms implicated in carbon ion irradiation. Curcumin is a natural phenolic compound with impressive antioxidant properties. What's more, curcumin is recently proved to exert its effects partly radioprotection. Read More

CNS Neurosci Ther 2014 Nov 21;20(11):973-81. Epub 2014 Aug 21.

IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Messina, Italy.

Aims: Spinal cord injury (SCI) occurs following damage to the spinal column. Following trauma, tissue damage is further exacerbated by a secondary damage due to a SCI-activated inflammatory process. Control of leukocytes activity is essential to therapeutic inhibition of the spinal cord damage to ameliorate the patient's conditions. Read More

J Neurosci 2014 Aug;34(32):10729-42

Department of Neurology, School of Medicine and Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, California 95817.

Motoneuron death after transection of the axons (axotomy) in neonates is believed to share the same mechanistic bases as naturally occurring programmed cell death during development. The c-Jun N-terminal kinase pathway is activated in both forms of motoneuron death, but it remains unknown to what extent these two forms of motoneuron death depend on this pathway and which upstream kinases are involved. We found that numbers of facial motoneurons are doubled in neonatal mice deficient in either ZPK/DLK (zipper protein kinase, also known as dual leucine zipper kinase), a mitogen-activated protein kinase kinase kinase, or in MKK4/MAP2K4, a mitogen-activated protein kinase kinase directly downstream of ZPK/DLK, and that the facial motoneurons in those mutant mice are completely resistant to axotomy-induced death. Read More

Mitochondrial DNA A DNA Mapp Seq Anal 2016 18;27(2):896-903. Epub 2014 Jun 18.

a Department of Pharmaceutical Sciences, University at Buffalo , The State University of New York , Buffalo , NY , USA.

Cancer patients with Down syndrome (DS) are at increased risk for anthracycline-related cardiotoxicity. Mitochondrial DNA (mtDNA) alterations in hearts with-DS may contribute to anthracycline-related cardiotoxicity. Cardiac mtDNA and the mtDNA(4977) deletion were quantitated in samples with- (n = 11) and without-DS (n = 31). Read More

Zhonghua Bing Li Xue Za Zhi 2014 Feb;43(2):123-4

J Neurochem 2014 Sep 7;130(5):612-25. Epub 2014 May 7.

Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Kashihara, Japan.

Old astrocyte specifically induced substance (OASIS), a basic leucine zipper transcription factor of the cAMP response element binding/Activating transcription factor family, is induced in reactive astrocytes in vivo and has important roles in quality control of protein synthesis at the endoplasmic reticulum. Reactive astrocytes produce a non-permissive environment for regenerating axons by up-regulating chondroitin sulfate proteoglycans (CSPGs). In this study, we focus on the potential role of OASIS in CSPG production in the adult mouse cerebral cortex. Read More

J Pediatr 2014 May 7;164(5):1152-6. Epub 2014 Feb 7.

Goldberg Center for Community Pediatric Health, Children's National Medical Center, Washington, DC; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC. Electronic address:

Objective: To assess risks involved in using wearable blankets, swaddle wraps, and swaddling.

Study Design: This was a retrospective review of incidents reported to the Consumer Product Safety Commission between 2004 and 2012.

Results: A total of 36 incidents involving wearable blankets and swaddle wraps were reviewed, including 10 deaths, 2 injuries, and 12 incidents without injury. Read More

Plant Cell Rep 2014 Jun 16;33(6):849-60. Epub 2014 Jan 16.

Department of Biological Mechanisms and Functions, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan.

Endogenous JA production is not necessary for wound-induced expression of JA-biosynthetic lipase genes such as DAD1 in Arabidopsis. However, the JA-Ile receptor COI1 is often required for their JA-independent induction. Wounding is a serious event in plants that may result from insect feeding and increase the risk of pathogen infection. Read More

Urology 2014 Feb 22;83(2):465-70. Epub 2013 Nov 22.

Detroit Medical Center, Detroit, MI.

Objective: To review our experience with severe penile trauma, mechanism of injury, and their treatment modalities in 16 children younger than 18 years. Management of penile trauma poses diverse challenges to the reconstructive urologist, as injuries vary from abrasions to total emasculation.

Methods: Analysis of 16 patients with severe penile injuries referred to us between 2002 and 2011 was undertaken. Read More

Eur J Emerg Med 2014 Aug;21(4):308-9

St Mary's Hospital Imperial College Healthcare NHS Trust, London, UK.

Zipper injuries are highly distressing to patients and often difficult to manage. Several management techniques are described in the literature. Many are complex and laborious, requiring sophisticated instruments in skilled hands, or even rely on a formal operation. Read More

Neuroscience 2013 Oct 2;250:8-19. Epub 2013 Jul 2.

Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.

Progranulin (PGRN) is known to play a role in the pathogenesis of neurodegenerative diseases. Recently, it has been demonstrated that patients with the homozygous mutation in the GRN gene present with neuronal ceroid lipofuscinosis, and there is growing evidence that PGRN is related to lysosomal function. In the present study, we investigated the possible role of PGRN in the lysosomes of activated microglia in the cerebral cortex after traumatic brain injury (TBI). Read More

J Hepatol 2013 Nov 29;59(5):1124-6. Epub 2013 May 29.

Department of Medicine II, Saarland University Medical Center, Homburg, Germany. Electronic address:

The phenotype and function of liver dendritic cells (LDCs) are poorly understood. This Snapshot summarizes our current knowledge on LDCs in the healthy and injured liver, and their role in fibrosis progression and reversal. It also draws attention to various pitfalls in the current experimental design and conclusions based on available data. Read More

Atherosclerosis 2013 May 13;228(1):90-3. Epub 2013 Mar 13.

Cardiovascular Research Center, Temple University School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, USA.

Objective: The Max-interacting protein Mnt is a transcriptional repressor that can antagonize the transcriptional and proliferation-related activities of Myc. Here, we tested the hypothesis that Mnt is a negative regulator of pathological vascular remodeling.

Methods: Adenovirus encoding Mnt or control GFP was infected to cultured rat vascular smooth muscle cells (VSMC) and carotid arteries after a balloon angioplasty. Read More

PLoS One 2013 15;8(2):e56526. Epub 2013 Feb 15.

Section of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo Japan.

Lipopolysaccharide (LPS)-induced myocardial dysfunction is caused, at least in part, by mitochondrial dysfunction. Mitochondrial dysfunction and the oxidative damage associated with it are scavenged through various cellular defense systems such as autophagy to prevent harmful effects. Our recent study has demonstrated that cobalt protoporphyrin IX (CoPPIX), a potent inducer of heme oxygenase-1 (HO-1), ameliorates septic liver injuries by enhancing mitochondrial autophagy in rats. Read More

Proc Natl Acad Sci U S A 2013 Mar 19;110(10):4039-44. Epub 2013 Feb 19.

Neurodegeneration Laboratories, Department of Neuroscience, Gentech, Inc., South San Francisco, CA 94080, USA.

The cell intrinsic factors that determine whether a neuron regenerates or undergoes apoptosis in response to axonal injury are not well defined. Here we show that the mixed-lineage dual leucine zipper kinase (DLK) is an essential upstream mediator of both of these divergent outcomes in the same cell type. Optic nerve crush injury leads to rapid elevation of DLK protein, first in the axons of retinal ganglion cells (RGCs) and then in their cell bodies. Read More

Proc Natl Acad Sci U S A 2013 Mar 19;110(10):4045-50. Epub 2013 Feb 19.

Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Glaucoma, a major cause of blindness worldwide, is a neurodegenerative optic neuropathy in which vision loss is caused by loss of retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for the development of neuroprotective drugs, we developed a high-throughput RNA interference screen with primary RGCs and used it to screen the full mouse kinome. The screen identified dual leucine zipper kinase (DLK) as a key neuroprotective target in RGCs. Read More

PLoS Biol 2012 4;10(12):e1001440. Epub 2012 Dec 4.

Department of Molecular Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.

Axonal degeneration is a hallmark of many neuropathies, neurodegenerative diseases, and injuries. Here, using a Drosophila injury model, we have identified a highly conserved E3 ubiquitin ligase, Highwire (Hiw), as an important regulator of axonal and synaptic degeneration. Mutations in hiw strongly inhibit Wallerian degeneration in multiple neuron types and developmental stages. Read More

Am J Emerg Med 2013 Feb 15;31(2):419-20. Epub 2012 Nov 15.

Eur Spine J 2012 Sep 26;21(9):1748-57. Epub 2012 Jul 26.

Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi, Hiroshima, 734-8551, Japan,

Purpose: Intervertebral disc degeneration is considered to be a major feature of low back pain. Furthermore, oxidative stress has been shown to be an important factor in degenerative diseases such as osteoarthritis and is considered a cause of intervertebral disc degeneration. The purpose of this study was to clarify the correlation between oxidative stress and intervertebral disc degeneration using Broad complex-Tramtrack-Bric-a-brac and cap'n'collar homology 1 deficient (Bach 1-/-) mice which highly express heme oxygenase-1 (HO-1). Read More

Neuron 2012 Jun;74(6):1015-22

Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Here we demonstrate that the dual leucine zipper kinase (DLK) promotes robust regeneration of peripheral axons after nerve injury in mice. Peripheral axon regeneration is accelerated by prior injury; however, DLK KO neurons do not respond to a preconditioning lesion with enhanced regeneration in vivo or in vitro. Assays for activation of transcription factors in injury-induced proregenerative pathways reveal that loss of DLK abolishes upregulation of p-STAT3 and p-cJun in the cell body after axonal injury. Read More