McGowan Institute for Regenerative Medicine
McGowan Institute for Regenerative Medicine
News Article | May 19, 2017
National Prevention Week: The Effectiveness of Worksite Programs in Reducing Opioid Abuse Dr. Joel Bennett CEO and Founder Organizational Wellness & Learning Systems, Inc. (OWLS) While the opioid and prescription drug epidemic has received considerable attention given the over 300,000 people it affects annually, relatively few realize the impact it's also having on the nation's workforce. It's become increasingly commonplace for employees to use prescription medication outside of intended use to improve job performance, overcome lack of sleep, or to alleviate pain. Although 70% of employers are negatively impacted by Rx abuse, less than 25% educate workers on prevention. Thirty percent do not provide access to alternative treatments. Says Dr. Bennett: "Employers are starting to realize the negative effects of Rx abuse on employee readiness, morale and productivity. But prevention programs can be a hard sell -- it's a challenge to demonstrate a concrete business return. Employers need to know that worksite awareness and education programs can be very effective in engaging people at the earliest stages of their Rx use and in a non-threatening way, steer them to safe alternatives. SAMHSA (Substance Abuse and Mental Health Services Administration) has laid out criteria and guidelines for evidence-based programs that produce positive outcomes; if properly implemented at the worksite, these programs have the potential to effectively educate a sizeable portion of at-risk employees who are otherwise hard to identify, let alone reach." Dr. Bennett is a widely sought-after speaker, consultant, and source on issues pertaining to evidence-based wellness. He has also published in a broad variety of academic, industry and business publications and consults internationally. ProfNet Profile: http://www.profnetconnect.com/joel_bennett Website: http://organizationalwellness.com Contact: Charles Epstein, email@example.com AI and Machine Learning in Medical Imaging Martin Hedlund Chief Technology Officer ContextVision "The concept of AI and machine learning has the potential to change the game of medical imaging. We can train neural networks with much more data than humans experience during a lifetime. This means that we can reproduce the competence of the best experts, or even outperform them! We can guarantee reproducibility in exams and diagnosis, and avoid human subjectivity and variations. With active learning models, results can continuously be improved. With better ground truth, i.e. data from different sources, time or outcome, AI can make better predictions, solve more complex tasks and make new discoveries." Based in Stockholm, Sweden, Hedlund is the chief technology officer and one of the founders of ContextVision. He finished his M.Sc. degree of Technology followed by further studies and research in image processing and GOP theory at Linköping University. He was R&D and site manager in Linköping until 1999 and has since served as CTO by focusing on strategic product and business development. Hedlund is spearheading the research and development of ContextVision's first AI-based imaging technology. By using algorithms, the product will be able to evaluate and enhance image quality automatically without the direct involvement of a clinical expert. This will improve workflow and improve diagnosis, and ultimately aid both patients and radiologists. Website: www.contextvision.com Contact: Stephanie Ross, firstname.lastname@example.org The Most Important Body Part You're Not Working Out Jonathan Jordan Personal Trainer, Nutrition Coach and Fitness Blogger Jonathan Jordan Fitness "As a successful personal trainer for Equinox in San Francisco, I've worked with hundreds of clients. They want to be lean. They want to be strong. They want to be healthy. But no one ever says, 'I want strong feet and mobile ankles.' Yet weak feet are often the biggest roadblocks to achieving their health goals. The ankle is one of our most important and commonly overlooked joints. Pain and injuries in the knees, hips and lower back can often be traced to issues at the ankle joint. Think of how often and how many ways we use our ankles: walking, running, biking, squatting, yoga, balancing, dancing -- you get the idea. If the muscles acting on your ankle are chronically tight or if the joint itself is jammed or lacks proper mobility, the impact can be painful and damaging, as the body will compensate at other joints to accommodate movement." Jordan recently wrote a blog post (see link below) that goes deep into the anatomy of the foot and includes an interview with physical therapist Dr. Sarah Jay. He has also included videos for his three favorite ankle mobility drills. He is available for interviews to help your readers, listeners, or viewers improve their ankle mobility, reduce pain and improve performance in their workouts Blog post: http://www.jj-fit.com/blog/ankle ProfNet Profile: http://www.profnetconnect.com/jonathan_jordan Website: http://www.jj-fit.com Expert Contact: email@example.com Can Stress Actually Kill You? Dr. Frieda Birnbaum Research Psychologist, Psychoanalyst Stress may take a toll on your mind, body, and heart, according to a new study from Massachusetts General Hospital and the Icahn School of Medicine at Mount Sinai. Researchers observed a strong correlation between activity in the amygdala -- the part of the brain activated by stress -- and subsequent cardiac events, such as heart attack, stroke, and angina. Says Dr. Birnbaum: "Our bodies are constantly reacting and responding to how we are thinking. If we stay locked into a state of high stress and anxiety for a prolonged period of time, our physical health will be affected for the worse. Yes, stress can kill you. However, there are many things a person can do to help manage their stress or remove it all together. One of the first things is to get to the root cause of the matter and resolve it, especially if it has something to do with guilt. Guilt is a powerful negative emotion that can prolong stress. If your boss or fellow employees have become a cause of stress, do whatever you can to be as far removed from them as possible, even if it means leaving your job. Any form or daily meditating or walking is another means of quieting your mind and opening doors of inner peace. Listening to peaceful music is also helpful. Stress is reactionary -- and you have the power to change how to react." Based in the New York metro area, Dr. Birnbaum is author of "Life Begins at 60: A New View on Motherhood, Marriage, and Reinventing Ourselves." She's an expert on depression, women's issues, and attaining happiness. Website: http://www.doctorfrieda.com Contact: Ryan McCormick, firstname.lastname@example.org Showtime's 'Billions' Predicts the Future Michael Klein, PsyD Psychologist, Principal MK Insights LLC Dr. Klein is available to speak about the relevance of the TV character Wendy Rhodes, an in-house psychiatrist in the fictitious firm of Axe Capital, as well as the history and trends behind this role. As a psychologist, he can address how personality, emotional intelligence, and motivators impact decision-making, management style, and potential "de-railing" behaviors: "It is impossible to work effectively in any job without running into roadblocks periodically. In-house psychiatrists and psychologists don't provide therapy at work but, rather, apply sound psychological insights and tools to help employees and managers be effective at work based on their own interest in achievement and managing psychological barriers." Dr. Klein is a psychologist, workplace coach, and in-house performance consultant. He is also author of "Trapped in the Family Business: A practical guide to understanding and managing this hidden dilemma." Book: www.trappedinthefamilybusiness.com Website: www.mkinsights.com Expert Contact: email@example.com Fireworks Safety Jenny Ziembicki, M.D. Medical Director, UPMC Mercy Burn Center Assistant Professor of Surgery, University of Pittsburgh School of Medicine Faculty Member, McGowan Institute for Regenerative Medicine "Each year, around 4th of July celebrations, we treat many people, especially children and teens, who have been injured by fireworks. Many of those injuries involve an amputation of a limb or loss of vision. We want to remind everyone that fireworks should only be handled by professionals and enjoyed at a safe distance." Dr. Ziembicki has a special interest in the development of the comprehensive outpatient burn therapy program at UPMC Mercy, which allows patients a more expedient return to a productive lifestyle. She also is a dedicated advocate in burn injury prevention, especially in the geriatric and pediatric population. Bio: http://www.mirm.pitt.edu/our-people/faculty-staff-bios/jenny-ziembicki-md/ Contact: Stephanie Stanley, firstname.lastname@example.org Skin Damage and Car/Home Windows Darrell Smith Executive Director International Window Film Association "Whether you're spending the summer on the road or enjoying the warm sunshine streaming through your home's windows, you may be doing serious damage to your skin without even realizing. The average window only blocks about 25% of UV rays from passing through and car windows aren't much better -- blocking about 40% of UV rays. In America, nearly 53% of skin cancer cases occur on the left, or driver's side, of the body. Why? Because, we enjoy sunshine but aren't fully protected against damaging UV rays -- and spend a lot of time in the car! Professionally installed window film can help block up to 99% of UV rays from passing through a window, ultimately protecting your skin and eyes from cumulative damage." Website: www.iwfa.com Contact: Amber Joy Dempsey, email@example.com Fabric and Clothing Tips for Summer James Pruden Senior Director Cotton Incorporated Pruden can provide expert summer safety tips when it comes to anything and everything summer clothing, including what to wear for the best UV protection; what fabrics keep you cooler during the warm summer months; and the health benefits of natural fibers vs. synthetic fibers. Says Pruden: "All apparel provides some degree of UV protection. UV protection in apparel is dependent on a variety of factors, including thickness of fabric (thicker fabrics absorb more UV rays), tightness of construction and the fabric's color (darker colors provide more UV protection)." Pruden is senior director of public relations at Cotton Incorporated, where he oversees brand image management for the not-for-profit company. Contact: Caleb Fernandez, firstname.lastname@example.org Pool Safety Tips for Parents, Children and Pets Tom Casey Vice President of Sales Anthony & Sylvan Pools Casey is available to share pool safety tips for parents, children, and pets: "Pools are fun for the whole family, and pool safety is crucial when it comes to enjoying your pool to its fullest. By following just a few safety tips, you'll be sure to keep this season fun and safe." Casey is vice president of sales for Anthony & Sylvan Pools, the leading swimming pool and spa builder in the U.S. Contact: John Reynolds, email@example.com Tips for an Injury-Free Summer Dr. Benjamin Domb "As the weather gets warmer and the days get longer, adults and kids alike love to engage in outdoor sports and fitness activities. This increase in physical activity can lead to an increased risk of injury." Through his experience working with athletes, both professional and amateur, as well as fitness enthusiasts like CrossFitters and runners, Dr. Domb is available to provide effective tips for an injury-free summer. Dr. Domb is a nationally recognized orthopedic surgeon specializing in sports medicine and arthroscopic surgery of the hip, shoulder and knee. Website: http://www.benjamindombmd.com Contact: Rachel Prude, Rachel.firstname.lastname@example.org Summer BBQ Safety Tips Peter Duncanson Director, Disaster Restoration Business Operations ServiceMaster Restore Duncanson is available for interviews on summer BBQ safety tips, including proper charcoal grill safety, how to use a gas grill wisely, and how to practice good grilling habits: "Set your grill up at a safe distance from structures and overhangs, including your main building, shed, garage, trees and other potentially flammable objects. Never use your grill inside, in a tent or under an outdoor awning or carport. Doing so can pose a serious fire hazard and potentially cause carbon monoxide poisoning if you're using a gas grill. Light your gas or charcoal grill using special long-length lighters or long matches to avoid getting burned. Keep all ignition sources out of the reach of children. Never leave an actively burning grill unattended, and let your grill fully cool before you cover or store it. Clean your grill thoroughly and often to reduce flammable buildup inside." Contact: Bristol Whitcher, email@example.com Summer Safety Jared Staver Attorney Staver Law Group. P.C. Staver is available to discuss various summer safety topics, including sun glare accidents, motorcycle safety, pool/water safety, heat exhaustion and more. On motorcycle safety: "During the summer months, drivers and motorcyclists should take extra precautions to avoid accidents. Statistics show that more than 50% of motorcycle accidents involve riders with less than five months of riding experience. To minimize the risk of accidents, motorcyclists should always wear protective gear including proper eyewear and helmets. Make sure your bike is properly maintained before taking it out for the first summer ride and keep a toolkit on your bike at all times. Mechanical defects can contribute to road crashes." Staver is a Chicago personal injury attorney and owner of Staver Law Group, P.C. His practice focuses on representing people seeking compensation after being hurt in the Chicago area, whether by a car accident, slip and fall, workplace accident, dog bite, or from an act of medical malpractice. An experienced and dedicated litigator, Jared has recovered tens of millions of dollars in settlements and verdicts for his clients. Bio: https://www.chicagolawyer.com/about-staver-law-group/jared-staver/ Website: https://www.chicagolawyer.com Contact: John Branham, firstname.lastname@example.org How to Stay Safe on the Job/Keep Employees Safe David Quezada Vice President of Loss Control EMPLOYERS "Working in hot and sunny environments or near heat sources all day can wear employees down. To help employees rest and recharge, encourage them to take regular breaks in the shade or other cool environments. Build break times into employees' schedules to help enforce the practice. Make sure employees know how to recognize the signs of heat-related illness and the immediate steps they need to take to help themselves or their co-workers. In the event of a medical emergency, contact 911 immediately, but also train employees so they can be proactive before professional help arrives. Fostering a safe and comfortable work environment is an important commitment every day of the year, but especially when new risks, such as extreme heat, are introduced." EMPLOYERS is a specialty workers' compensation insurance carrier. Website: www.employers.com Contact: Alexandra Gardell Kreuter, EmployersInsurance@allisonpr.com Managing Medications During the Summer Jon Michaeli EVP of Marketing and Business Development Medisafe Michaeli is available to discuss the importance of managing your medications during the summer months, whether it's during vacations or ensuring that your children are keeping up with their medications while they're at summer camp. Managing medications essentially helps you to manage your conditions, resulting in improved outcomes. Contact: Kendra Lee, email@example.com What to Do During a Power Outage Keith Pinkerton Owner Mr. Electric, Huntsville, Ala. Pinkerton is available to discuss weather precautions and backup generators during storm season. He can advise homeowners what to do when there is a power outage and how to ensure electrical safety around the house in general. He is the owner of the Huntsville, Ala., branch of Mr. Electric, a national brand of electrical installation and repair centers. Website: https://mrelectric.com/huntsville Contact: Elise Rose, firstname.lastname@example.org Safety When Completing House Projects J.B. Sassano President Mr. Handyman Sassano is available to discuss safety when completing house projects, such as using power washers, power drills, climbing on ladders for gutter cleaning, etc. He is president of Mr. Handyman, the nation's leading home repair and maintenance franchise. Website: https://www.mrhandyman.com Contact: Elise Rose, email@example.com Injury Trends Darshan Patel, M.D. Chief of Pediatric Emergency Medicine Maria Fareri Children's Hospital Dr. Patel can provide commentary on a wide variety of summer conditions and their recommended treatment, as well as injury trends. As Section Chief, Dr. Patel serves as head of the Pediatric Emergency Department. He and his team are the first line of care for children in needing immediate care after injuries or at the onset of illnesses. Maria Fareri Children's Hospital, a member of the Westchester Medical Center Health Network, is the Level 1 pediatric trauma center for a region with more than 3 million people. In the past, Dr. Patel has been a media resource for summer safety topics, including ATV and water safety, as well as injuries caused by trampolines and fireworks. He has also contributed to reports regarding dehydration and heat stroke. He has television, radio and print media experience, and is adept at breaking down complex medical topics for families. He is available for media interviews when requests do not interfere with patient care. Contact: Andy LaGuardia, firstname.lastname@example.org Water Safety Tips Ann Marie Buerkle Acting Chairman U.S. Consumer Product Safety Commission Buerkle is available to discuss the many steps that parents can take to improve safety in and around water. As acting chairman of the U.S. Consumer Product Safety Commission (CPSC), Buerkle offers a unique perspective into the importance of safety in and around water. One of the national public education campaigns the Chairman oversees is the Pool Safely campaign, which is aimed at reducing child drownings and non-fatal submersions, as well as entrapments in public swimming pools and spas. The campaign was launched in 2010 and has a network of over 1,000 partners that are dedicated to promoting and benefitting from the campaign. Website: https://www.poolsafely.gov Contact: Christina Saull: Christina.Saull@finnpartners.gov Following are links to job listings for staff and freelance writers, editors and producers. You can view these and more job listings on our Job Board: https://prnmedia.prnewswire.com/community/jobs/ Following are links to other news and resources we think you might find useful. If you have an item you think other reporters would be interested in and would like us to include in a future alert, please drop us a line. PROFNET is an exclusive service of PR Newswire. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/profnet-experts-available-on-summer-safety-opioid-abuse-stress-more-300460792.html
Goenka S.,University of Pittsburgh |
Sant V.,University of Pittsburgh |
Sant S.,University of Pittsburgh |
Sant S.,McGowan Institute for Regenerative Medicine
Journal of Controlled Release | Year: 2014
Nanomaterials offer interesting physicochemical and biological properties for biomedical applications due to their small size, large surface area and ability to interface/interact with the cells/tissues. Graphene-based nanomaterials are fast emerging as "two-dimensional wonder materials" due to their unique structure and excellent mechanical, optical and electrical properties and have been exploited in electronics and other fields. Emerging trends show that their exceptional properties can be exploited for biomedical applications, especially in drug delivery and tissue engineering. This article presents a comprehensive review of various types and properties of graphene family nanomaterials. We further highlight how these properties are being exploited for drug delivery and tissue engineering applications. © 2013 Elsevier B.V.
Johnson N.R.,McGowan Institute for Regenerative Medicine |
Wang Y.,McGowan Institute for Regenerative Medicine |
Wang Y.,University of Pittsburgh
Journal of Controlled Release | Year: 2013
Wound healing is a dynamic process that relies on coordinated signaling molecules to succeed. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is proven to accelerate healing, however precise control over its application is necessary to reduce side effects and achieve desired therapeutic benefit. To achieve effective growth factor delivery we designed a bioactive heparin-based coacervate. In vitro, HB-EGF released from the coacervate delivery system displayed enhanced bioactivity and promoted human keratinocyte migration while preserving cell proliferative capability. In a mouse excisional full-thickness wound model, controlled release of HB-EGF within the wound significantly accelerated wound closure more effectively than an equal dosage of free HB-EGF. Healing was induced by rapid re-epithelialization, granulation tissue formation, and accompanied by angiogenesis. Consistent with in vitro results, wounds treated with HB-EGF coacervate exhibited enhanced migration of keratinocytes with retained proliferative potential, forming a confluent layer for regained barrier function within 7 days. Collectively, these results suggest that coacervate-based controlled release of HB-EGF may serve as a new therapy to accelerate healing of cutaneous wounds. © 2012 Elsevier B.V.
Vodovotz Y.,McGowan Institute for Regenerative Medicine
Wound Repair and Regeneration | Year: 2010
Personalized medicine is a major goal for the future of healthcare, and we suggest that computational simulations are necessary in order to achieve it. Inflammatory diseases, both acute and chronic, represent an area in which personalized medicine is especially needed, given the high level of individual variability that characterizes these diseases. We have created such simulations, and have used them to gain basic insights into the inflammatory response under baseline, gene-knockout, and drug-treated experimental animals; for in silico experiments and clinical trials in sepsis, trauma, and wound healing; and to create patient-specific simulations in polytrauma, traumatic brain injury, and vocal fold inflammation. Since they include both circulating and tissue-level inflammatory mediators, these simulations transcend typical cytokine networks by associating inflammatory processes with tissue/organ damage via tissue damage/dysfunction. We suggest that computational simulations are the cornerstone of Translational Systems Biology approaches for inflammatory diseases. © 2010 by the Wound Healing Society.
Chu C.T.,McGowan Institute for Regenerative Medicine
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2010
Dysregulation of mitochondrial structure and function has emerged as a central factor in the pathogenesis of Parkinson's disease and related parkinsonian disorders (PD). Toxic and environmental injuries and risk factors perturb mitochondrial complex I function, and gene products linked to familial PD often affect mitochondrial biology. Autosomal recessive mutations in PTEN-induced kinase 1 (PINK1) cause an L-DOPA responsive parkinsonian syndrome, stimulating extensive interest in the normal neuroprotective and mitoprotective functions of PINK1. Recent data from mammalian and invertebrate model systems converge upon interactions between PINK1 and parkin, as well as DJ-1, α-synuclein and leucine rich repeat kinase 2 (LRRK2). While all studies to date support a neuroprotective role for wild type, but not mutant PINK1, there is less agreement on subcellular compartmentalization of PINK1 kinase function and whether PINK1 promotes mitochondrial fission or fusion. These controversies are reviewed in the context of the dynamic mitochondrial lifecycle, in which mitochondrial structure and function are continuously modulated not only by the fission-fusion machinery, but also by regulation of biogenesis, axonal/dendritic transport and autophagy. A working model is proposed, in which PINK1 loss-of-function results in mitochondrial reactive oxygen species (ROS), cristae/respiratory dysfunction and destabilization of calcium homeostasis, which trigger compensatory fission, autophagy and biosynthetic repair pathways that dramatically alter mitochondrial structure. Concurrent strategies to identify pathways that mediate normal PINK1 function and to identify factors that facilitate appropriate compensatory responses to its loss are both needed to halt the aging-related penetrance and incidence of familial and sporadic PD. © 2009 Elsevier B.V. All rights reserved.
Agrawal V.,McGowan Institute for Regenerative Medicine
Tissue engineering. Part A | Year: 2012
Tissue regeneration in response to injury in adult mammals is generally limited to select tissues. Nonmammalian species such as newts and axolotls undergo regeneration of complex tissues such as limbs and digits via recruitment and accumulation of local and circulating multipotent progenitors preprogrammed to recapitulate the missing tissue. Directed recruitment and activation of progenitor cells at a site of injury in adult mammals may alter the default wound-healing response from scar tissue toward regeneration. Bioactive molecules derived from proteolytic degradation of extracellular matrix (ECM) proteins have been shown to recruit a variety of progenitor cells in vitro and in vivo to the site of injury. The present study further characterized the population of cells accumulating at the site of injury after treatment with ECM degradation products in a well-established model of murine digit amputation. After a mid-second phalanx digit amputation in 6-8-week-old adult mice, treatment with ECM degradation products resulted in the accumulation of a heterogeneous population of cells, a subset of which expressed the transcription factor Sox2, a marker of pluripotent and adult progenitor cells. Sox2+ cells were localized lateral to the amputated P2 bone and coexpressed progenitor cell markers CD90 and Sca1. Transgenic Sox2 eGFP/+ and bone marrow chimeric mice showed that the bone marrow and blood circulation did not contribute to the Sox2+ cell population. The present study showed that, in addition to circulating progenitor cells, resident tissue-derived cells also populate at the site of injury after treatment with ECM degradation products. Although future work is necessary to determine the contribution of Sox2+ cells to functional tissue at the site of injury, recruitment and/or activation of local tissue-derived cells may be a viable approach to tissue engineering of more complex tissues in adult mammals.
Gilbert T.W.,McGowan Institute for Regenerative Medicine
Journal of Cellular Biochemistry | Year: 2012
Decellularized tissues have been successfully used in a variety of tissue engineering/regenerative medicine applications, and more recently decellularized organs have been utilized in the first stages of organ engineering. The protocols used to decellularize simple tissues versus intact organs differ greatly. Herein, the most commonly used decellularization methods for both surgical mesh materials and whole organs are described, with consideration given to how these different processes affect the extracellular matrix and the host response to the scaffold. © 2012 Wiley Periodicals, Inc.
Duncan A.W.,McGowan Institute for Regenerative Medicine
Seminars in Cell and Developmental Biology | Year: 2013
Polyploidy has been described in the liver for over 100 years. The frequency of polyploid hepatocytes varies by age and species, but up to 90% of mouse hepatocytes and approximately 50% of human hepatocytes are polyploid. In addition to alterations in the entire complement of chromosomes, variations in chromosome copy number have been recently described. Aneuploidy in the liver is pervasive, affecting 60% of hepatocytes in mice and 30-90% of hepatocytes in humans. Polyploidy and aneuploidy in the liver are closely linked, and the ploidy conveyor model describes this relationship. Diploid hepatocytes undergo failed cytokinesis to generate polyploid cells. Proliferating polyploid hepatocytes, which form multipolar spindles during cell division, generate reduced ploidy progeny (e.g., diploid hepatocytes from tetraploids or octaploids) and/or aneuploid daughters. New evidence suggests that random hepatic aneuploidy can promote adaptation to liver injury. For instance, in response to chronic liver damage, subsets of aneuploid hepatocytes that are differentially resistant to the injury remain healthy, regenerate the liver and restore function. Future work is required to elucidate the mechanisms regulating dynamic chromosome changes in the liver and to understand how these processes impact normal and abnormal liver function. © 2013 Elsevier Ltd.
Chu C.T.,McGowan Institute for Regenerative Medicine
Human Molecular Genetics | Year: 2010
The PTEN-induced putative kinase 1 (PINK1) is a mitochondrially targeted serine-threonine kinase, which is linked to autosomal recessive familial parkinsonism. Current literature implicates PINK1 as a pivotal regulator of mitochondrial quality control, promoting maintenance of respiring mitochondrial networks through cristae stabilization, phosphorylation of chaperones and possibly regulation of mitochondrial transport or autophagy. Pulse-chase studies indicate that PINK1 is rapidly processed into at least two shorter forms, which are distributed in both mitochondrial and cytosolic compartments. Through indirect regulation of mitochondrial proteases and Drp1, PINK1 may act to facilitate localized repair and fusion in response to minor mitochondrial stress. With severe mitochondrial damage, PINK1 facilitates aggregation and clearance of depolarized mitochondria through interactions with Parkin and possibly Beclin1. This switch in function most probably involves altered processing, post-translational modification and/or localization of PINK1, as overexpression of full-length PINK1 is required for mitochondrial Parkin recruitment. Under conditions of PINK1 deficiency, dysregulation of reactive oxygen species, electron transport chain function and calcium homeostasis trigger altered mitochondrial dynamics, indicating compromise of mitochondrial quality control mechanisms. Nevertheless, Parkin- and Beclin1-regulated mitochondrial autophagy remains effective at recycling PINK1-deficient mitochondria; failure of this final tier of mitochondrial quality control contributes to cell death. Thus, PINK1 plays a pivotal, multifactorial role in mitochondrial homeostasis. As autophagic recycling represents the final tier of mitochondrial quality control, whether PINK1 levels are enhanced or reduced, strat- egies to promote selective mitophagy and mitochondrial biogenesis may prove effective for multiple forms of Parkinson's disease. © The Author 2010. Published by Oxford University Press.
Balmert S.C.,McGowan Institute for Regenerative Medicine |
Little S.R.,McGowan Institute for Regenerative Medicine
Advanced Materials | Year: 2012
The nascent fi eld of biomimetic delivery with micro- and nanoparticles (MNP) has advanced considerably in recent years. Drawing inspiration from the ways that cells communicate in the body, several different modes of "delivery" (i.e., temporospatial presentation of biological signals) have been investigated in a number of therapeutic contexts. In particular, this review focuses on (1) controlled release formulations that deliver natural soluble factors with physiologically relevant temporal context, (2) presentation of surface-bound ligands to cells, with spatial organization of ligands ranging from isotropic to dynamically anisotropic, and (3) physical properties of particles, including size, shape and mechanical stiffness, which mimic those of natural cells. Importantly, the context provided by multimodal, or multifactor delivery represents a key element of most biomimetic MNP systems, a concept illustrated by an analogy to human interpersonal communication. Regulatory implications of increasingly sophisticated and "cell-like" biomimetic MNP systems are also discussed. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.